Cancerfighter’s Weblog

Alternative cancer therapies and ideas

Archive for April, 2011

Rosemary, betulinic acid and cancer

Posted by Jonathan Chamberlain on April 28, 2011

If you want cancer related info then there’s a lot her so do browse – see also my two cancer books –

Rosemary, betulinic acid and cancer

Rosemary has long been one of my favourite essential oils – good for the liver. I now discover that it is a notable source for betulinic acid which has demoinstrated strong anti-tumour activity. SeeWikipedia for more details

Note: The Cancer Survivor’s Bible (2012) is now available – see

“You gave us a path when we thought all was lost.”

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Chinese herb (TCM) fights tumours (tumors)

Posted by Jonathan Chamberlain on April 28, 2011

If you are looking for cancer related information then please browse this site – this info supports and extends the info and critical discussion in my two cancer books – see

Chinese herb fights tumours

The herb, thunder god vine (lei gong teng), is a Chinese herb generally used for inflammatory conditions such as rheumatoid arthritis.  But researchers from Johns Hopkins School of Medicine have found that it can also stop tumour growth.  Its active ingredient is triptolide.  Researcher Jun Liu, professor of pharmacology and molecular sciences found that low doses of thunder god vine blocked cell growth in 60 different types of cancer, and even killed off some cancers in laboratory conditions.  (Source: Nature Chemical Biology, 2011; 7: 182).

However, Europeans may have to find sources in Asia as new laws are coming into effect the effect of which will be to reduce access to many herbs. Those interested in getting hold of this herb might wish to contact Chris Teo in Penang

Note: The Cancer Survivor’s Bible (2012) is now available – see

“The book is more precious than gold.”

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Ian Clements’ anti-cancer protocol

Posted by Jonathan Chamberlain on April 21, 2011

If you are looking for cancer information then you’ve come to the right place. There’s a lot here and in my two cancer books – see for details.

Dr Ian Clements’ Anti-Cancer CAM Regime

Ian Clements is not a medical doctor – he’s an engineer. He approaches problems in a pracgmatic but highly analytic way. This is how he approached his own diagnosis of terminal bladder cancer. He was told he had only weeks or months to live – and at one time he was admitted to a hospice with no expectation of emerging. Today, three a a half years later, he is still battling. Here is the protocol he has developed for himself. I have posted elsewhere lengthy docuuments on his own research into radical cystectomy for bladder cancer and his protocol for supporting yourself through chemotherapy

CANCER? – The Quick Start Back

DON’T PANIC! – Well, try to calm down.

You will not die overnight – cancer is not the same as a bullet or car accident. It will have been developing for months, if not years. Most people die from the side-effects of cancer, rather than the cancer directly. So you can usually take a couple of weeks to learn more before you decide anything.

The three standard orthodox treatments are surgery, chemotherapy, and radiation. All are strong assaults on the body. So it is best to prepare your body for this if you do decide to have any of these treatments.

Meanwhile, there are several proven things you can to improve your length of survival and help your body cope with any treatment:


  • Cut out sweet things[i], reduce carbohydrates (potatoes, pasta, bread, cakes) which get quickly converted to blood sugar, and alcohol
  • Go for salads, with organic produce if possible, and fresh fruit.
  • Cut out red and processed meat – sausages, bacon, steak, pork. Go for fish, white meat (chicken, turkey).
  • Drink green and/or white tea in preference to coffee or black tea (tho’ the latter is OK, just not as good as green or white).


  • Aim to do as much as you can, getting more vigorous with time. If you are not used to doing any, then build up to half-an-hour’s walk a day. Then get faster and longer as you get more able to. Aim to get an hour a day. Other forms help too: swimming, weights, jogging, etc.



  • A comprehensive multi-vitamin and mineral pill/pills[iii]
  • Vitamin C[iv]– 3gm
  • Vitamin D3[v] – 10,000IU
  • Omega 3 oil[vi] – 5 gm


CANCER? – The Quick Start Back. 1

Nutrition. 1

Exercise. 1

Supplements. 1

General Cancer Theory. 6

Things to do right away. 7

Nutrition. 7

Exercise. 7

Supplements. 7

My Various CAM Treatments. 8

Lifestyle. 8

Exercise. 8

Nutrition. 8

Weight 9

Supplements. 9

Other Treatments I use. 11

Hyperthermia. 11

Enhanced oxygen. 11

Low-Dose Naltrexone – LDN.. 12

PsychoNeuroImmunology- PNI. 13

Chemotherapy Help. 13

My Daily regime. 13

Diet/nutrition: 14

Oxygenation/Exercise: 15

Being considered. 15

Feedback. 15

Alternatives I’ve Tried and Abandoned. 16

Fiery chillies, garlic and butter. 16

Alkalizing. 17

Veganism.. 17

Juicing. 17

Budwig Diet 17

Conclusions. 18

Acknowledgements. 18

Bibliography. 19


You are probably reading this either because you have been diagnosed as having cancer, or that of a loved one who has. Please don’t panic. Cancer will not cause you or your loved one to die within days – so you have time to look at various alternative treatments:

  • the orthodox ones of surgery, chemotherapy and/or radiation;
  • and what are known as Complementary and Alternative Medicine (CAM), and to enhance survival independently of whatever you and your doctors decide is best.
  • There is a lot of information and advice available on the Internet on both orthodox treatments and CAM – sure, not all of it is good, but some is. This document will help guide you through all that.

Having been diagnosed with terminal bladder cancer in October 2007 at aged 71, and only been given a few weeks to live – (by 4 orthodox experts – the urological surgeon and three oncologists), my own experience and now extensive reading and discussions with other survivors has made me at least as expert as the medicos in many ways (but not all) in the following 3+ years (as of writing). This book is a collation of my wisdom on cancer and how to mitigate it. Given the present state of ignorance about the origination and causal chain development of cancer, no-one can be certain of how each proven anti-cancer treatment actually works – only that the evidence is that certain things actually do bring about cancer and other things cause an improvement in some or all patients. I believe that my now lengthy survival against the original prognosis is due to one or more of the various treatments I have undertaken. I offer this to others that it may help them. I am not a medical doctor; I am a retired research scientist, able to understand research reports and summarise them coherently, concisely and clearly.

Unlike some people offering anti-cancer advice or ‘cures’, I do not claim that either what I have done or my protocol will definitely increase survival time (or cure cancer – not even the orthodox medicos do that). What I am offering is evidence-based anti-cancer advice, quoting this evidence so that you can check it for yourself, that is known to generally enhance survival times for cancer patients.

Alas, there are some who proffer easy cures or help. These, I believe, are generally sincere. But (a) their own experience may have had nothing to do with their supposed treatment; (b) even if it was, it may be something that just works for them (however, if may work for you too). There are also a lot of well-documented cases of spontaneous remission – the cancers just went away, for no known reason; and so for people to whom this happened, this may lead them to think they did something to cause this.

I am not opposed to orthodox treatments – chemotherapy probably saved my life – but I do think that patients need to be well informed about them before deciding on doing one. There will always be time to do this; don’t let the doctors rush you into any particular treatment (I alas did). This will enable them to choose whichever is best for them – or non at all. From what I now know, the surgery I had to remove my tumour was unnecessary (it re-grew in 3 months; it was the chemotherapy that then drove my cancer into remission) and this surgery spread cancer cells throughout my body, reducing my survival chances significantly. I now realise what should have been obvious: the specialists are naturally committed to their speciality, often to that alone (their colleagues in ‘rival’ specialisms will often disagree with their rivals). This is not to doubt their sincerity, just their blinkered approach – which can equally be true of CAM specialists. I also now know that my continuing my complementary ‘treatments’ (supplements, exercise, nutrition) enabled the chemotherapy to work much better and reduced the severity of the side-effects.

CAM (Complementary and Alternative Medicine) is, as the name says, composed of two parts – that which helps orthodox medicine, and so is complementary to it; and that which is Alternative to standard treatment and so sometimes is opposed to it. Both are unfairly stigmatised by the orthodox medical community, who, to their shame, are usually ignorant of it. Some doctors will readily admit this, especially given that their training omits it – and refer patients to those who are expert in these areas. Others will denounce anything that they don’t themselves know, trusting that those experts who taught them, and their reading within their narrow speciality since, know all that there is to know of their area.

All of this is regrettable, because much of CAM conforms to that highest of medical standards – evidence-based, often the gold-standard of double-blind, placebo alternative research. Much of orthodox medicine is inheritance-based – passed on from predecessors without any evidence-based research behind it at all (it is claimed that 75% of patient advice and medicine is not evidence-based) this is no better than the anecdotal evidence that such practitioners denounce when used by CAM advocates. Perhaps worse, much of medical research is actually wrong[vii] (as is most expert advice[viii]). Fortunately, nowadays patients have access to a great deal of medical expertise via the Internet, including consultations with far-away orthodox specialists if they want.

One enormous advantage that much of CAM has over mainstream orthodox treatment is that much of the Alternative side is usually side-effect free and virtually of the Complementary is, unlike virtually all of traditional medicine. This is especially true of cancer treatment: surgery, chemotherapy, and radiation – all of which carry mortality risk and damage to healthy cells. But let me be clear: some Alternative treatments are invasive and need careful consideration before being undertaken – they can have serious and deleterious side-effects – such as intravenous vitamin C, and enemas. So far, none of what I have done falls in to that category.

There is much that CAM offers that supports orthodox treatment in becoming more efficacious and lowering the inevitable nasty side-effects, so it is surprising that the GPs and specialists are both ignorant of this enhancer of their treatments and preventing such treatments being more successful.

This resumé of this expertise, with references (tho’ all can easily be research and updated by Googling everything mentioned), may help others to improve their chances with both their cancer and their orthodox treatment (for instance, responses to chemo, radiation and surgery are enhanced as well as the side-effects reduced).

Complementary and Alternative Medicine covers many different treatments for the same spectrum of illnesses as that of the orthodox NHS. However, this does not mean there is not a respectable body of scientific evidence to support CAM – on the contrary, most such interventions do indeed have this. Whilst many NHS practitioners may be unfamiliar with some CAM, there are books by orthodox MDs which do report such evidence[ix].

My choosing which CAM to use is based on two principles: weight of evidence (even if anecdotal), and indications that there are no serious downsides. Note that ‘evidence’ here is exactly that – where the usage gives improvement, even if the intervening causal chain is unknown.

Within CAM there is a diverse field, only part of this relates to cancer. Within CAM cancer information, there is that which relates to prevention; other to enhancing survival (a better phrase than ‘cure’; tho’ ‘cures’ are claimed and so could be dismissed for that reason, this doesn’t mean any such CAM may not be useful); and that to supporting orthodox treatments (enhancing their efficacy or reducing the side-effects). Naturally, there is much overlap between these aspects.

To fully investigate and research both orthodox and CAM, I have of necessity spent much time and money on literature – books, membership to health newsletters, and forums. It is from all this, plus my own continuing research on the Internet, that I have evolved – and still evolve – my anti-cancer actions.  I have read much of both the orthodox approach and the many alternative cancer treatments – which I readily admit are often way to optimistic and misleading; but which, to my mind, are usually genuine (the same being applicable to orthodox medicine).

I offer this distillation of knowledge and advice. But, as always, the decision rests with you, the patient, as to what you do to optimise your own survival.

For those who wish to explore some of the Alternative medicine ideas in more depth, I recommend two books and their associated websites: “Cancer: The Complete Recovery Guide” by Jonathan Chamberlain ( and “Conventional Cancer Cures: What’s the Alternative” by Chris Woollams (

You now have to hand the most empowering tool ever available for advice on any illness: the Internet. To get up-to-date information on any proposed treatment, food, or supplement, just enter the “illness and item” into a search engine such as Google. Examples: Bladder cancer and vitamin C; Kidney disease and eggs; etc. From this you will quickly know what may help or harm your illness and treatment.

General Cancer Theory

The complete aetiology (step-by-step chain of cause and effect) of cancer is not, at present, known. This is a summary of the present state of knowledge. Robert Weinberg[x] distilled six characteristics which all cancers are found to have (and are now accepted by the cancer specialists) plus two more that are usually present:

  1. Self-sufficiency in growth signals (rather than from other body signals)
  2. Insensitivity to anti-growth signals (the body usually can signal cells to stop growing)
  3. Tissue invasion and metastasis (cells and organs remain where they are normally)
  4. Limitless replicative potential (can and do keep growing continuously)
  5. Sustained angiogenesis (keep making blood vessels to feed the tumours)
  6. Evasion of apoptosis (avoid normal cell death – all other cells, apart from nerves, die after a time)
  7. Tumour promoting inflammation (turns on the body’s inflammation all the time, instead of just when it is injured)
  8. Gene instability and mutation (all other cells replicate clones; and, when they don’t, the body recognises this and makes them die)

We attempt to control cancer by interfering with each of these factors.

For cancer to develop into a life-threatening stage, it goes through three phases: initiation, promotion, and progression. The initiation can be due to a virus, parasite, emotional shock (such as a relative suddenly dying), poor nutrition, or poor environment (such as radiation, smoking, asbestos).  For a cancer to develop, a cell has to go ‘rogue’ – its DNA has to be damaged in such a way that it proliferates outside the control of the body’s normal regulatory mechanisms. So there are three aspects to this[xi]:

  • What makes the DNA corrupt?
  • Why don’t the body’s normal immune processes recognise this and destroy it (they normally do)?
  • And how does the rogue cancer cell then grow?

The changed cell then propagates daughter cells – the tumour is promoted. If the immune system is poor, due maybe to poor nutrition and lack of exercise – then progression is likely, generally via angiogenesis (growing a blood supply for the tumour). For example, bladder cancer (mine) risk factors include smoking, obesity, working with chemicals (painters and carpenters), arsenic in the tap water, eating processed or overdone meat, and being a USA Vietnam veteran. Medical and CAM treatments along with lifestyle changes attempt to address each of these three stages: cancer cell initiation, cancer cell death, cancer cell growth.

The embryonic cancer cells generally need a blood supply (angiogenesis) for tumours to grow to life-threatening size, and this process is susceptible to nutrition, supplements and drugs (Dr William Li: Can we eat to starve cancer? [xii] and David Agus: A new strategy in the war on cancer[xiii]).Genes only predispose, and are not causative.[xiv]

Cancers need much greater than normal amounts of energy to grow, and cause inflammation to hide from the body’s immune system – so much so, it is probable that inflammation and cancer generally go hand-in-hand[xv]. Restricting the glucose that cancer cells need (all sugars, including alcohol) is therefore a good thing. This includes what may be called fast carbs – easily digested carbohydrates like white bread, potatoes, etc[xvi]. Anti-inflammation (by such supplements as curcumin and omega3 oils) will damp it down.

Orthodox medicine has three main alternatives: radiation, surgery, chemotherapy. There is a little immunotherapy (BCG[xvii]for bladder cancer is probably the only established one; there is a lot of experimental vaccines; and a new prostate cancer one, Provenge). Or (if it is thought that the cancer is too far gone or not life threatening) just let it go on until death (which may be from other causes).

Points to bear in mind:

Since about 1940 there has been a significant increasing of cancer rates in Western countries – and this is not mainly due to better screening or diagnosis (which do have an effect on the figures, but only about 30%), as this has occurred in non-screened-for cancers and in children. Even breast cancer rates, which were falling, are no longer doing so[xviii].

It is thought that this increase of cancer in general is  must mostly be due to Western lifestyles (The National Cancer Institute estimates that roughly one-third of all cancer deaths may be diet related; WHO think 70% related to lifestyle); embracing less Western ones will likely lead to fewer succumbing to cancer.[xix] Whilst there has been a reduction in cancer death rates in the last 20 years, this is probably mostly (if not entirely) due to reduced smoking, rather than improved treatments.[xx] All this evidence leads to the inevitable conclusion that cancer is a disease of modern Western civilisation and is not ‘natural’; so we must look to our lifestyle and modern environment for causation and, by extension, to reducing the enhancement of cancer once we have it. Insulin appears to be a major factor, enhanced by fast carbs[xxi].

There are some strong criticism of orthodox treatment by some members of the medical profession themselves. I think these are too strong, but it would be unfair not to air them:

  • Surgery: Prof. of Medical Physics calculated that on balance, cancer patients are likely to live four times longer if they do nothing for their cancer rather than do something.
  • Surgery enhances the chances of metastasis (spreading the cancerous cells; see Surgery Could Accelerate Tumor Growth?[xxii] “Surgery Triggers Outgrowth of Latent Distant Disease in Breast Cancer: An Inconvenient Truth?”[xxiii], & “Proof That Cancer Surgery Increases Mortality”[xxiv].)
  • Radiation: Many experts consider it useless. Radiation itself can cause cancer (tho’ there’s some evidence that light radiation is actually good[xxv]. It also adversely affects the immune system.
  • Chemotherapy: Of the 75% receiving chemo, less than 15% are ‘cured’. Only 5% of cancers treated with chemo succeed. 58 of 79 (73%) of doctors referring patients for chemo said that they themselves would not have any chemo. “The overall contribution of curative and adjuvant (helping) cytotoxic chemotherapy to 5-year survival in adults was estimated to be 2.3% in Australia and 2.1% in the USA.”[xxvi]Chemo seriously harms one’s immune system.
  • Some Cancers May Just Go Away[xxvii]

Note that the worst that can be said about CAM is that it may prevent/delay orthodox treatment – CAM itself has remarkably few other downsides.

Things to do right away

Whatever you decide to do, some things will help in various ways without interfering with whatever treatment you then undertake – in essence, optimal health things. These will fortify you for what lies ahead. For what may help with the specific treatment of chemotherapy, see here.


  • Cut out sweet things[xxviii], reduce carbohydrates (potatoes, pasta, bread, cakes) which get quickly converted to blood sugar, and alcohol
  • Go for salads, with organic produce if possible, and fresh fruit.
  • Cut out red and processed meat – sausages, bacon, steak, pork. Go for fish, white meat (chicken).
  • Drink green and/or white tea in preference to coffee or black tea (tho’ the latter is OK, just not as good as green or white).


  • Aim to do as much as you can. If you are not used to doing any, then build up to half-an-hours walk a day. Then get faster and longer as you get more able to. Aim to get an hour a day. Other forms help to: swimming, weights, jogging, etc.



  • A comprehensive multi-vitamin and mineral pill/pills[xxx]
  • Vitamin C[xxxi]– 1gm
  • Vitamin D3[xxxii] – 5,000IU
  • Omega 3 oil[xxxiii] – 1 – 5 gm

My Various CAM Treatments

This falls into three parts: lifestyle, supplements, and other treatments.


Cancer was virtually unknown in ancient times (‘Data from across the millennia has given modern society a clear message: cancer is man-made and something that we can and should address’).[xxxiv],[xxxv] Cancer rates in non-advanced societies are virtually unknown.[xxxvi] Cancer incidences in 1870’s were less than 2%; now more than 33% (p.4) and rising. Death rates are 25%, and rising.

Apart from a couple of cancers (lung, and prostate (men)/breast (women – probably due to the decline of smoking)[xxxvii], cancer incidences (diagnosis) have either not markedly declined or have increased since the 1930’s; in the EU, cases have increased 20% in the six years to 2008 (colon having increased since 1975)[xxxviii]; studies reveal substantial increases in non-melanoma skin cancers[xxxix]. Cancer death rates have slowly increased for all others. “…survival rates haven’t improved for most cancers”[xl].

This increase is not mainly due to better screening or diagnosis (which do have an effect on the figures, but only about 30%), as this has occurred in non-screened-for cancers and in children. It is thought that this increase must mostly be due to Western lifestyles (The National Cancer Institute estimates that roughly one-third of all cancer deaths may be diet related; WHO think 70% related to lifestyle); embracing less Western ones will likely lead to fewer succumbing to cancer.[xli] All this evidence leads to the inevitable conclusion that cancer is a disease of modern Western civilisation and is not ‘natural’; so we must look to our lifestyle and modern environment for causation and, by extension, to reducing the enhancement of cancer once we have it. Insulin appears to be a major factor, enhanced by fast carbs[xlii].

Most cancer patients will survive for years, but have a higher chance of dieing of something else than normal. “current recommendations for cancer survivors, which emphasize achieving and maintaining a healthy weight; encouraging regular physical activity (for adults at least 30 minutes of moderate to vigorous physical activity every day); eating a diet rich in vegetables, fruits, and whole grains; and limiting red and processed meats and alcohol consumption. Further, the current recommendations are that cancer survivors try and obtain their nutrients from foods, rather than supplements since there have been several studies that have linked supplement intake with higher cancer-specific and all-cause mortality among cancer survivors.”[xliii]

Note: nearly all cancer research money is spent on trying to find cures; very little is spent of prevention (1%?).


There is now a mass of evidence that exercise of various sorts, indeed of any sort, increases survival. I thus try various sorts – walking, jogging, and weights.[xliv] It is possible that exercise works by causing an increase in internal heat and thus is anti-cancer by the same way that hyperthermia is – cancer cells are more sensitive to heat and become apoptotic – die. My target is about one hour a day vigorous walking (defined as such that one’s heart rate exceeds 50% of one’s maximum). I check this using a wrist watch heart-rate monitor.


Whilst there is as yet no certainty about the best nutrition overall, some have been proven and others are considered prudent:

Avoiding sugar[xlv], fast carbs (maybe carbohydrates altogether – see Gary Taubes “Good Calories, Bad Calories”)

Lower/zero alcohol[xlvi]

Eat lots of cruciferous vegetables[xlvii], berries, fresh organic fruit and veggies in general[xlviii]

Avoid red meat[xlix], processed meats

Avoid pollutants – smoking, aerosols, and poor water[l] (that is, use a water filter)

Particular foods are known to retard certain cancers[li],[lii], whilst others are good against most, such as green tea, and brassicas (Brussels’ sprouts, broccoli) [liii].


Overweight/obesity is known to enhance cancer[liv], altho’ there is some counter-evidence for breast cancer[lv].  Whilst overall weight reduction is probably good (as recognised by the BMI measure), it seems that it is mainly the fat around the waist that causes the most reduction in general survival[lvi]. For this, the best measure is the ratio of the waist to maximum outer-thighs; it is good to aim for a ratio of waist to thighs of less than 0.95.

Changes in weight are predominately brought about by nutrition, not exercise (as good as this may be for other reasons – see above; my personal data over 30 years is that there is no relationship between how much I exercised and my weight, fat or muscle mass). My experience is that weight and fatness loss is brought about by one of two ways:

  • alternate day ‘fasting’ (on ‘fasting days, just eating fruit – grapefruit for breakfast, big orange for lunch, big apple for dinner)
  • cutting out all obvious carbs: no potatoes, no bread, no pasta, no cakes, no crisps, etc.


These do any of four things:

  • they drive cancer cells into apoptosis,
  • boost the immune system so that it recognises the cancer cells as in need of removal,
  • reduce inflammation (a known cancer stimulant[lvii]) and
  • they effect the tumour’s angiogenesis (grow feeding blood vessels) adversely.

There are many supplements for which there are claims that they help with cancer. I have checked a lot of them, and those that have credible evidence (often provided by orthodox medical scientists) I have tried. Here I give selected references to each supplement (sometimes the opposing views too) to give the reader some confidence in my use of these. Note too that I do not use all of these all the time. These references are generally the result of my collecting information since my diagnosis; but often also by the simple procedure of putting “X and Cancer” into Google – which I recommend doing for all of these if anyone wishes to use them, as new research appears all the time, some showing what was once thought good is now bad. Caution is the watchword; check for downsides and conflicts with any other treatment you may be having.

It is noteworthy that supplements are incredibly safe, unlike prescription drugs. For example, there was not one single death recorded in the USA in 2009 from supplements amongst the 2.5 million cases reported to the USA’s Poison Control Centres (there were 500 deaths from other causes).[lviii] There are horrendous figures for deaths due to orthodox medicine’s involvement – drug side-effects, often for drugs that are ineffective anyway; hospital-induced illnesses; medical accidents; etc. This is not to decry orthodox medicine’s undoubted successes, but just to highlight that caution is needed. However, all supplements have side-effects, albeit generally mild ones. It is prudent to check whether any you propose to take may make an existing illness (other than the cancer) worse; for example, if you have kidney problems, search for, say, “Astralagus and Kidney Disease” (in fact, Astralagus is actually good for kidneys).

I also give the daily quantities that I take.

This list is not exhaustive. Tho’ I believe all of these apply to most cancers, it is as well to check whether your particular cancer is known to be helped by those supplements you choose.

Aloe Vera[lix] – 6gm

Alpha Lipoic Acid[lx] – 300mg

Arginine[lxi] – 1gm

Astralagus[lxii] – 2 x 250mg

AveULTRA[lxiii] – 1 pack

Barley Grass[lxiv] – 1gm

Bee Propopolis[lxv] – 2 x 1gm

Beta Glucan[lxvi] – 500mg

Boswelia[lxvii] – 307mg (avoid for kidney problems)

Carnitine (as Acetyl L-Carnitine)[lxviii] – 500mg

Carnosine (as L-Carnosine)[lxix] – 2 x 250mg

Cat’s Claw 30mL[lxx] – 5 drops

Cherry Fruit Extract[lxxi] – 500mg

Chlorella[lxxii] – 1gm

Conjugated Linoleic Acid[lxxiii] – 500mg

Curcumin-0.9g + Piperene[lxxiv] – 6 x 900mg

Cysteine (as N-Acytel Cysteine)[lxxv] – 600mg

DHEA[lxxvi] – 25mg

DIM[lxxvii] – 2 x 100mg

DMAE[lxxviii] – 350mg

DMG[lxxix] – 100mg

EDTA[lxxx] – 400mg

Flora Flor Essence[lxxxi] (avoid for kidney problems)

Fucoidan[lxxxii] 2 x 300mg

Glutathione[lxxxiii] – 500mg

Graviola[lxxxiv] – 2 x 650mg

Green tea extract[lxxxv] – various, including green tea leaves

Indole-3-Carbinal[lxxxvi] – 2 x 200mg

Inositol[lxxxvii] – not taken separately (it is in some of the other supplements)

Lactoferrin + Colostrum[lxxxviii] – 960mg

Lycopene[lxxxix] – 15mg

Melatonin[xc] – 3mg

Melon – Bitter Melon Fruit[xci] – 450mg

Multi vitamin and mineral set[xcii]

Mushroom Extracts (Agaricus Blazei, Maitake, Mesima, Reishi, Shiitake)[xciii] various

Nattokinase[xciv] – 2 x 2,000FUs

Niacin[xcv] – 500mg (avoid for kidney problems)

Omega-3 DHA & EPA in various forms[xcvi] – 6mg[xcvii]

Papaya[xcviii] – 50mg

Pau d’Arco tea – 1 – 3 tea bags

PeakImmune4[xcix] – 8 x 250mg

Probiotics[c] – 2 x 16 billion various

Sterols – Phystosterol[ci] – 937mg

Proline + Lysine[cii] – 2 x 275mg each

Proteolytic Enzymes[ciii] – 3 different brands, so 3 x 500mg

Quercetin[civ] + Bromilain[cv] – 250mg + 375mg

Resveratrol[cvi] – 16mg

Rosehip[cvii] – 800mg

Saw Palmetto + Nettle[cviii] – 280mg

Seanol[cix] – 400mg

Selenium[cx] – 200mcg

Serrapeptase[cxi] – 2 x 80,000

SOD – GliSODin[cxii] – 250mg

Spirulina powder[cxiii] – 1gm

Teas – 5 – 7 teabags, of Pau d’Arco[cxiv], Tulsi[cxv], White Tea, or Green Tea (occasionally black)

Ubiquinol- Co-Enzyme Q10[cxvi] – 100mg

Vit C[cxvii] as Magnesium Ascorbate – 2gm

Vit D3[cxviii] – 5,000IU

Vit K[cxix] – 100mcg

Vit K2[cxx] – 450mcg

Wheatgrass[cxxi] – 1gm

Zinc (Gluconate)[cxxii]  – 4 x 25mg

Other Treatments I use


It is known that cancer cells are more adversely sensitive to heat than normal cells, and thus more liable to die. So raised temperature enhances the immune system to deal with the cancer, and makes any chemotherapy or ingested supplements more efficacious. There are many examples of spontaneous remission following fever, thought to be the result of the high body temperature this caused – this is the basis too of BCG for bladder cancer, and Coley’s Vaccine for cancer generally.

Therapy that raises the body’s temperature is called hyperthermia, in which a device applies heat to the patient. The hyperthermia can be administered either locally or over the whole body.

In local hyperthermia, a device is placed over the specific area of the body to be heated. For example, the doctor applies the hyperthermia device to the breast of a breast cancer patient to heat up the area. This kind of hyperthermia can take place every other day.

Whole-body hyperthermia is altogether different. The patient, wrapped in towels, lies naked on a hyperthermia bed. The patient’s body temperature is gradually raised to about 105 degrees Fahrenheit and kept at that temperature for about two hours. It’s possible to go a little higher — up to 107 degrees, which is called “extreme hyperthermia.” Unlike local hyperthermia, whole-body hyperthermia can’t be done more than once a week. (German Cancer Breakthrough, p.13)

There are three kinds of whole-body hyperthermia:

Moderate hyperthermia, in which the patient’s core temperature is raised to 101-103 degrees Fahrenheit [=38-40C] for two hours, which simulates a natural fever.

Systemic hyperthermia, which raises the core temperature to 105 degrees F. = 40.5C

Extreme hyperthermia, which goes up to 107 degrees F. = 41.5C

I use a cocoon blanket-type hyperthermia kit, priced variably from about $250 to $600. This allows a three-zone temperature infra-red setting (top, middle and bottom). I use 50C/55C/50C and lie in it for 50 minutes (on alternate days) – my arm-pit temperature rises about 3C by the end, so presumably inner core from 36.8 to 39.8C – then shower off.

Enhanced oxygen[cxxiv]

An air ionizer (or negative ion generator) is a device that uses high voltage to ionize (electrically charge) air molecules. Negative ions, or anions, are particles with one or more extra electrons, conferring a net negative charge to the particle. Cations are positive ions missing one or more electrons, resulting in a net positive charge. Most commercial air purifiers are designed to generate negative ions. Another type of air ionizer is the ESD ionizer (balanced ion generator) used to neutralize static charge.[cxxv]

Low-Dose Naltrexone – LDN[cxxvi]

LDN is a safe and inexpensive prescription drug which can be used as immunotherapy for most types of cancer and may also have direct anti-tumour activity.

Naltrexone is an opioid antagonist. It blocks the receptors that bind heroin, morphine, other narcotic drugs and the body’s own endogenous opioids like beta endorphin. In doses of 50 mg a day or more, it is used in narcotic and alcohol withdrawal.

When used in low doses (usually 4.5 mg), however, naltrexone increases the secretion of these endogenous opioids, which not only relieve pain, but also regulate the immune system. This has led to its use as a treatment for HIV/AIDS, autoimmune diseases and fibromyalgia. It is especially popular as a treatment for multiple sclerosis.

LDN’s Mode of Action in Cancer

In the 1980s, researchers like Ian S. Zagon noticed that when used in large doses, naltrexone stimulated the growth of cancer, but low doses had the opposite effect. Low dose naltrexone increases the secretion of several opioid peptides, such as beta endorphin and methionine enkephalin (also known as met enkephalin and opioid growth factor or OGF).

Beta endorphin acts as a non-specific cancer immunotherapy by boosting the action of natural killer cells (NK cells). Met enkephalin/OGF has direct anti-tumour action through opioid receptors that have been detected in many types of malignant tumours. It inhibits angiogenesis (formation of new blood vessels), without which cancer cannot grow.

LDN is not a “cure for cancer.” It does not help everyone, but in many cases it can stop the growth of tumours or even shrink them, but still the patient has to continue taking it until the rest of his life or until a more effective treatment is found.

Clinical Trials, Studies and Publications

There are dozens of lab studies which show that either OGF or low doses of naltrexone can inhibit cancer growth in the following types of cancer:

ovarian cancer

thyroid follicular cancer

head and neck cancer

pancreatic cancer

renal cell cancer (kidney cancer)


colon cancer


Additionally, receptors for OGF have been found in throat cancer, brain tumours, breast cancer, oesophageal cancer, stomach cancer, liver cancer, lung cancer, leukaemia and multiple myeloma. Beta-endorphin has been shown to suppress growth of prostate cancer.

Unfortunately, no proper clinical trials have been published on LDN. There are published case studies of impressive results with LDN in metastatic pancreatic cancer (which is one of the most notorious, if not the most notorious of all, cancers to treat) and B-cell lymphoma. In pancreatic cancer, it was combined with alpha lipoic acid, which suppresses cancer growth by inhibiting NF-kappa B.

Anecdotally, LDN has also been prescribed to help the following cancers:

bladder cancer

carcinoid tumor

uterine cancer

PsychoNeuroImmunology- PNI[cxxvii]

There is now much research proving the interrelationship between the mind and the body, including mental states affecting the outcomes of illnesses – of which the placebo effect is perhaps the most famous. This covers three main areas: hypnotherapy, cognitive behaviour therapy, and meditation. Each has been shown to have a positive outcome for cancer.

Chemotherapy Help[cxxviii]

Vit.D3  4,000IU-12,000IU daily – enhances efficacy of chemo

Magnesium 500mg daily – replaces severe depletion

Ubiquinol form of Co-enzyme Q10 – 200mg/day

glutamine powder 10 grams (3 scoops) 3 times a day to minimize the side effects of chemo including neuropathy

Vit.A – 3,000IU/850mcg

Vit.C –  5 gms/day

Curcumin + piperene – 8 – 10 gms/day – enhances chemo, especially cisplatin

Green or white tea[cxxix]

Astralagus – an immune booster[cxxx]; anti-cancer generally;

Aloe Vera – enhances chemo’s effects, enhances apoptosis, improves immune system

Milk thistle[cxxxi]

Bromelain – 500mg

Resveratrol 500mg – enhances chemo’s effect[cxxxii] – but may cause diarrhoea[cxxxiii]

Medicinal mushrooms – various

Exercise: as vigorous as possible – walking 30’ day, jogging if poss., and resistance training

Stay off sugar, sodium (salt) and fruit juices

My Daily regime

This is an example of how I implement my anti-cancer days

Each day this is made up of four components (which often overlap):

1.      General healthiness stuff:

  • Lots of fresh (raw) organic veggies and some low glycaemic fruits
  • Supplements such as vitamins & minerals, probiotics, proteolytic enzymes
  • Alkalising – lots of veggies
  • Minimise carbohydrates in general, but especially fast-carbs (sugar, bread, potatoes, pasta) & alcohol
  • Exercise – walk, about one hour daily
  • Avoid unhealthy stuff: smoking, pollutants (aerosols – air-fresheners, solvents, etc)

2.      Specific anti-cancer stuff

  • Supplements such as curcumin, Graviola, Astralagus, Bee Propolis, Vit.D3,         Co.Q10, Vit.C[cxxxiv]
  • Foods: pau d’arco & green/white tea (alternatively?), juicing & eating cruciferous veggies (such broccoli, beetroot), extra virgin olive oil[cxxxv]
  • Avoid sugar, red meat (and maybe dairy products[cxxxvi]), processed meats, fried foods – these foods promote cancer (especially sugar)
  • Oxygenate – ionisers, enhanced oxygen, vigorous exercise[cxxxvii]

3.      Specific immune boosting stuff

  • Supplements such as PeakImmune4, Beta-Glucan, AveULTRA
  • Foods such as wheat-grass & spirulina+chlorella
  • Ionised air & (enhanced air) oxygen

4.      Feedback – to let myself know how I’m going on

  • Daily: body composition: weight, muscle-mass, fat%, basal metabolic rat; urine pH.
  • Bi-monthly/quarterly cancer marker tests (NMP22, CEA, etc),
  • Less frequent inflammation checks, mineral & vitamin blood levels.


On getting up: Nattokinase, Acetyl L-Carnitine


Egg, veggie sausage, mushrooms and tomatoes;

Supplements: NutriShield[cxxxviii] package of vitamins, 2 x PeakImmune4, L-arginine 1gm, Vit.D3 2,400IU, Quercetin 800mg, L-Carnosine 250mg, fish-oil 1gm, folic acid 400mcg, flaxseed oil 1gm, CLA 500mg, Nattokinase, Vit.K 100mcg, Vit.K2, 2 x curcumin+piperene 1000mg, niacin 100mg, manganese chloride 100mg, Graviola x 2, Blue-Green algae; Cup of pau d’arco tea

Mid-morning – cup of white tea

Organic green salad, mushroom, garnished olive oil & organic apple vinegar, cinnamon, chilli pepper, and Vit.D3 (& sometimes curcumin+biopiperene powder); pau d’arco tea


Cup of white tea, with an apple and nuts


greens (broccoli, sprouts, leaves),veggie protein, fish or white meat. Berries. White tea; L-Arganine 1gm, 1gm fish oil, Graviola 500mg x 2, Green sea algae, L-Carnitine, pau d’arco tea

Before bed

Low-Dose Naltrexone 4.5mg, Nattokinase, Serrapeptase, Melatonin

I also use coconut oil. I occasionally drink organic raw cocoa powder with xylitol & coconut milk.


About one hour’s fairly vigorous walk a day. Sometimes interval aerobic jogging for about30’.

50’ of enhanced ionised oxygen (30%) daily; an all night ioniser by my bed. Filtered water.

Hyperthermia alternate days: 50′ @ about 50C

Being considered

If I detect a resurgence of my cancer, I may do one or more of the following (some of which I’ve done earlier but discontinued on the assumption either that it had done its work or was ineffective):

Mid-afternoon mashed ½ avocado & 8oz carrot juice (I did this for about a month early on).

The “How to stop cancer” protocol.[cxxxix]


Revised Budwig[cxli]: 2 teaspoons of wild salmon oil & 2 tablespoons of un-denatured whey hand mixed together and spooned in, 2-10 times a day for three days; thence once a day thereafter. But there’s some debate about this revision. For original: and

EFT, Ukrain, Intravenous Vit.C

Del-Immune, Ultra H3 Plus, lactoferrin, PectaSol, Oncovite, Flor-Essence, Coley’s vaccine cancer treatment, & Essiac – see

Mix curcumin+piperene with coconut oil before taking it

Oxygen/ozone therapy


An essential part of my cancer management is knowing how I am doing – feedback. Perhaps it is because I am an Engineer that I am more sensitive than most to this very important aspect of achieving a desired goal – encapsulated in the phrase “knowledge of results improves performance”. To this end, I measure and record all that I can on a daily basis:

  • Medical data – biochemistry, cancer markers, scans, consultations – so that I can detect any changes in my cancerousness
  • Body composition – a well-known side-effect of cancer is a rapid change in body composition; particularly of muscle-mass – cachexia[cxlii] (not to be confused with sarcopenia, muscle-loss due to ageing), which is itself enhanced by pro-inflammatory immune cells (cytokines)[cxliii]. Carnosine and Ubiquinol (enhance Co-enzyme Q10) may counteract this, as may hydrazine sulphate[cxliv].
  • Nutrition – there is an ocean of anti-cancer dietary advice, much in conflict with one another. For what it is worth, after reading a lot of this, I have come to believe that the best nutrition is one with a lot of fresh fruit and vegetables, preferably organic; as little carbs as possible (see Gary Taubes “Good Calories, Bad Calories”, and all the research that implicates blood sugar as a cancer feeder – carbs are the main source of sugar in the blood); filtered water (not osmotically derived); fish; avoid red and processed meat; little or no alcohol.
  • Medicines – I keep a note of all that I take, so that if something particularly badly effects me without any clear advantage, I can avoid it in future; and to see if, later, there’s any correlation with my other data.
  • Supplements – similar reason as for medicines
  • Exercise – to ensure I’m keeping on track to average the equivalent of one hour’s vigorous (heart-rate over 50% of max) walking a day. I have a watch heart-rate monitor that I wear most of the day. Such exercise may also counteract any tendency to cachexia.
  • Checking my urine pH – more acidic is probably not too good. As a side advantage, I collect my urine in a clear cup lately, and that has enabled me to see what I may have previously missed: blood specks/flakes/clots occasionally – to me, another ‘measure’ of my cancerousness. I also use biochemistry dipsticks, which often show out-of-normal readings. I hope to tie all these in to changes in my diet, supplements, and exercise – thus enabling me to take avoidance action. Different cancers would suggest different checks, such as the size of skin lesions and/or moles for skin cancers.

Alternatives I’ve Tried and Abandoned

Now bear with me. I’ve tried a lot of what may seem barmy treatments. Look, I have been desperate; and when the ‘experts’ (heh! why am I putting it in inverted commas? – they really are the acknowledged experts) told me I only had weeks to live, I was up for anything.

However, given the wide variance of human beings, what doesn’t work for one may work for another. For what it’s worth, I think most of those offering alternative ‘cures’ are genuine (in that they sincerely believe their treatment works) – and they may well have done so for themselves. But as there is a legion of examples of spontaneous remissions/cures, it could be that they had one of these and so were not cured by their suggested cure.

Fiery chillies, garlic and butter

Yes, I know this may sound barmy – but then so does injecting a strong poison into one’s veins and hoping it will kill all the cancer cells before it kills the rest of you (chemotherapy). There were, for me, three things that led me to try this:

  • The book “The Doctor Who Cures Cancer” by William Kelley Eidem, had impressive support – from Dr Barry Sears and Dr Atkins, both of whom I have respect for.
  • There didn’t seem to be any bad side-effects, apart from the intense ‘heat’ from the chilli and the possible adverse dietary factor of butter (which I’ve since learnt are wrongly made).
  • When I did try it, it cured one of the side-effects of my chemo: neuropathy of my inner-left thigh (deadness) – as long as I did it (or any other hot chilli intake).

So when the author, Mr Eidem, promoted a supposed cancer cure based on this book (tho’ I could never understand from my reading how he got to this cure), I tried it for a few months. Alas, during this time, my NMP-22 bladder cancer marker showed increased cancerousness. So I deemed this ‘cure’ as not one that works for me.


There is a lot of chatter on the ‘net that alkalizing one’s body, via a diet very high in vegetables and fruit plus alkaline water. Couple that with the plausible anti-cancer theory based on Nobel prize-winning Dr Warburg’s idea of increasing the body’s oxygen state, and this become a reasonable anti-cancer treatment.

I even bought an expensive water alkalizer, before I learnt that this aspect of the theory is bunk.[cxlv]

Again, I didn’t find my cancerousness fell whilst following this approach, so I did not continue. However, I feel that there’s something in it, and so still check my urine pH as a possible indicator of my general healthiness – the less acidic it is, the better I am. This is because some things in my diet that I know are bad  (alcohol, sugar, meat, etc) make my urine more acidic.


Throughout my adult life, I’ve been attracted to the supposed benefits of vegetarianism (no meat and, in the more extreme form, no fish) and veganism (no animal products whatsoever – no milk, cheese, eggs, yoghourt, etc as well as no meat or fish). So when I read “The China Study” by Dr Campbell & son with its convincing case for a vegan diet being both cancer-preventative and curative, I tried it for a couple of months. But again, my cancer marker signs increased rather than decreased, so I abandoned it.

I should add that there are good arguments against De Campbell’s views too – as there are to any anti-cancer theory. That’s why I need to weigh up as much as possible and decide for myself. A good medical doctor should support this approach; sadly, few do.


I initially juiced twice a day. This was made up of:

  • Handful/cupful of broccoli
  • Ditto of cauliflower
  • A carrot
  • Half a beetroot
  • A knob of ginger
  • Two Brussels’ sprouts
  • An apple
  • A ring of pineapple

I still think this is probably a healthy thing to do, but as my cancer regrew during the doing of this; and later my cancer marker increased (having gone down); I decided that it probably didn’t make enough difference to warrant the expense and trouble. So I stopped.

Budwig Diet

Difficult one this. I did the mix of cottage cheese and flax-seed oil for about 3 months, but my cancer tumour regrew. I tried it again later, but, as with juicing above, my cancer marker went up after having been low. Now I know that there’s more to the Budwig diet than just the cottage cheese & oil – fresh veggies and fruit, for instance; and no supplements (which I continued). So it may be that a more rigorous following of her diet may be more successful.


Cancer is NOT a trauma – you won’t die within hours/days of diagnosis. So take time to know the full range of alternatives, both orthodox and CAM, upsides and downsides. Orthodox and much CAM can generally be done in parallel, to your benefit – even tho’ the docs won’t know much, if anything, about CAM research. People generally die of the wasting away of muscles (cachexia) due to the cancer taking up most of the energy, rather than the cancer itself. So ensure you eat well and check your muscle mass.

It is probable that whatever your lifestyle was, this led to or helped the cancer (such as smoking, poor nutrition, inadequate exercise, being fat, poor water supply, working with solvents/paints, hair dyes/deodorants/aerosols/cosmetics). Therefore you need to look to changing your lifestyle (stop smoking, improve nutrition, enhance exercising, move away from pollution)[cxlvi]. Cancer is a warning sign to become more congruent within yourself and your environment.

Improving your general healthiness will probably help your body slow down the cancer

Enhancing your immune system will probably slow down the cancer’s growth and maybe even drive it into regression (make it smaller) or remission (non-detectable). Getting rid of excess body fat will help.[cxlvii]

Taking anti-cancer foods and/or supplements will possibly drive the cancer into remission, with a greater chance than any of the orthodox treatments.

Initially, it is probably best to avoid surgery, chemotherapy, and radiation whilst doing some CAM helps and seeing if this improves your healthiness.

If you do do any of the orthodox treatments, my protocol will probably both minimise the side-effects and enhance to effectiveness of the treatment. Note also that the opiates for pain relief may be cancer enhancers[cxlviii]

This is not an exhaustive exposition, for two reasons: I cannot recall all that I have done; and this is an ongoing project, changing oft times.

But this will give a fair representation of the expenditure and time I have to spend since being diagnosed with terminal bladder cancer on 15th October, 2007. I hope knowledge of my successful journey will help you.

I can be contacted at


First and foremost, my wife, children, and extended family – for their support, both emotionally and physically in looking after me.

Dr Bernardo Majalca, Preventive Medical Research, who gave me hope when the orthodox professionals gave non, and showed the way that CAM enhanced mainstream medicine.

Gene Early, who guided me to have greater congruence within myself.

Dr Huddart, of the Royal Marsden, who contradicted the first three experts by telling me that chemotherapy did indeed have a success for cases such as mine, albeit slight (5%).

Dr Marie Wilkins, the oncologist at the Royal Sussex Hospital, who tolerated my CAM support strategies whilst providing excellent chemotherapy.

Jonathan Chamberlain for his comprehensive CAM guide to effective cancer therapies

My fellow colleagues on the bladder cancer forums for their information and support (, especially Peter Granger.


As well as virtually daily trawling of the Internet and reading various newspaper articles and magazines related to cancer (all of which has led to the endnoted references below), I have read and/or referred to the following books:

“Cancer: The Complete Recovery Guide” Jonathon Chamberlain, Long Island Press, 2008

“Anti-cancer: a new way of life” Dr David ServanpSchreiber, Penguin, 2007

“Definitive Guide To Cancer” – 2nd ed. Lise Alschuler & Karolyn A Gazella, Celestial Arts, 2007 –  very good survey of orthodox and CAM (Complimentary & Alternative Medicine).

“The Cancer Directory” – Dr Rosy Daniel, Thorsons, 2005

“The Hidden Story of Cancer” – Brian Scott Peskin, self-published, 2007 – a well argued alternative approach to dealing with cancer.

“Choices in Healing” – Michael Lerner, MIT Press, 1994

“Cancer: A Second Opinion” – Joseph Issels, MD, Avery, 199

“The Truth About Your Immune System” – Havard Medical School, 2007. The orthodox view of immune enhancing (it can’t be done!).

“The Official Anti-Aging Revolution” – Ronald Klatz & Robert Goldman, Basic Health Pub, 2007. Altho’ about anti-ageing, it has much to say about cancer.

“Snake Oil” – John Diamond, Vintage UK, 2001. A trenchant argument against CAM.

“Natural Compounds in Cancer Therapy” – John Boik, Oregon Medical Press, 2001. A good listing (tho’ a bit dated) of most CAM compounds.

“Nutritional Medicine” Dr Gaby, Fritz Perlberg Pub, 2010

“Spontaneous Regression” – Donald H MacAdam, self-published, 2003. A well argued, with evidence, case for immunotherapy alone.

“Conventional Cancer Cures – What’s The Alternative” – Chris Woollams, Health Issues, 2004

“Cancer Positive” – Dr James Colthurst, Michael O’Mara Books Ltd, 2003

“Dismantling Cancer” – Francisco Contreras, Jorge Barroso-Aranda, Daniel E Kennedy, Interpacific press, 2004

“The Breuss Cancer Cure” – Rudolf Breus, Alive Books, 1995

“Alkalize of Die” – Dr Theodore A Baroody, Holographic Health Press, 2006 – a bit dubious; probably Young’s book is better, or Murray’s

“The Doctor Who Cures Cancer” – William Kelley Eidem, self publication, 1997. An interesting CAM approach, with much supportive evidence.

“The China Study” by Dr Campbell & son. A convincing case for a vegan diet being both cancer-preventative and curative. A BC survivor who gives a blow-by-blow account of his own and other’s journey and ideas on improving survival chances, with an interesting flow-chart

“The Cancer Clock” Ed. Sotiris Missailidis, Wiley, 2007

“Say No to Cancer” Patrick Holford, Piatkus, 1999


[iii] I use NutriShield daily packs, from Uni-Vite ( This is a set of 7 pills containing all the compounds that medical scientist Dr Paul Clayton recommends, being frequently updated in the light of the latest research


[vii] “’Amazingly, most medical treatment simply isn’t backed up by good, quantitative evidence’. ….. The whole point of carrying out a study was to rigorously examine a question using tools and techniques that would yield solid data. ….And yet these studies, and most types of studies Dr Ioannidis looked at, were far more often than not driving to wrong answers.  The two-out-of-three wrongness rate Ionnidis found is worse than it sounds. He had been examining only [a tiny amount] of published research in the most prestigious medical journals.  …the wrongness rate would only be worse from there [less prestigious journals].” Freedman (see below, pp. 5,6) quoting John Ionnidis, MD & research medical mathematician @ Tufts-New England Medical Center.

[viii] “Wrong: Why Experts Keep Failing Us – and How to Know When Not to Trust Them” David H Freedman 2010 Little, Brown

[ix] Dr David Servan-Schreiber in his “Anti-Cancer: a new way of life” 2008 (see

“Integrative Oncology Essentials:  A Patients’  Guide To Cancer Care And Prevention”  Brian D. Lawenda, M.D. 2010 (see [“Integrative oncology is no longer an “alternative” approach to cancer care. Increasingly, prestigious academic cancer centers (for example: Harvard, Memorial Sloan Kettering, MD Anderson, Duke, UCSF) are incorporating integrative oncology within their practice of taking care of patients living with and beyond cancer.”]

“Natural compounds in cancer therapy” John Boik, MD 2001

“Nutritional Medicine” Alan R Gaby, MD 2010

“Definitive Guide to Cancer” Alsschuler & Gazella 2007 (2nd Ed)

There are also many websites offering a collation of the best of CAM, of which the UK one of is very comprehensive and up-to-date.

[xiv] It was thought that we all have a few cells frequently turning cancerous, but that our immune system deals with this without our becoming aware of it (it is seen in autopsies). “It was claimed in the past that cancer cells were forming non-stop but the immune system destroyed them. And everything which weakens it, for instance stress, may impede fighting the intruder. “Nowadays no one holds that opinion anymore”, says dr. Pardoll. Experiments on mice devoid of immune system did not confirm saliently higher cancer morbidity. Also among people with immune disorders under the influence of drugs preventing transplant rejection or as a result of AIDS a higher cancer prevalence ratio was not found.”

[xvii] “History of Bacillus Calmette-Guerin and Bladder Cancer: An Immunotherapy Success Story”

[xx] “The Secret History of the War on Cancer” Devra Davis, Basic Books, 2007

[xxi] See: Good Calories, Bad Calories by Gary Taubs, Anchor Books, 2008


[xxx] I use NutriShield daily packs, from Uni-Vite ( This is a set of 7 pills containing all the compounds that medical scientist Dr Paul Clayton recommends, being frequently updated in the light of the latest research


[xxxvi] “Good Calories, Bad Calories” pp:89-99 Gary Taubes, Anchor Books, 2007

[xlii] See: Good Calories, Bad Calories by Gary Taubs, Anchor Books, 2008


[xlvii], and

[xlviii] For a list of foods that fight cancer:

[lviii] Via Orthomolecular Medicine News Service, January 5, 2011:

Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Giffin SL. 2009 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 27th Annual Report. Clinical Toxicology (2010). 48, 979-1178. The full text article is available for free download at  The data mentioned above are found in Table 22B, journal pages 1138-1148.

[lix] Aloe Vera:

WDDTY Vol20 No 11 p.20

Dr Al Sears Newsletter 15 Apr 2010-04-15

Lim, Beong Ou, et al. “Efficacy of Dietary Aloe Vera Supplementation on Hepatic Cholesterol and Oxidative status in Aged Rats” J-Nutr-Sci-Vitaminol-(Tokyo). 2003 Aug; 49(4): 292-6.


“Other research on alpha-lipoic acid has shown that it might: inhibit the activation of “nuclear factor kappa-B,” a protein complex involved in cancer and the progression of AIDS. (Suzuki YJ, et al., Biochemical & Biophysical Research Communications, 1992;189:1709-15).  ‘The therapeutic potential of alpha-lipoic acid is just beginning to be explored,” observed Packer, “but this compound holds great promise.'”


Excessive Dietary Fat Caused 300 Percent Increase in Metastasizing Tumor Cells In Animal Models


Supplementation with trans10cis12-conjugated linoleic acid induces hyperproinsulinaemia in obese men: close association with impaired insulin sensitivity


Serum-Solubilized Curcumin. Via Pete Granger on Bladder Cancer Web Café 15:21 16 Jul 2010 extrincurcumin_selfassembly_a_novel_approach_to_improve_curcumin_delivery_a nd_its_therapeutic_efficacy_in_prostate_cancer_cells__abstract07092010.html

WDDTY Vol 20 No 11 p.21

Cancer Research 68, 5345-5354, July 1, 2008. doi: 10.1158/0008-5472.CAN-07-6805

International Braz J Urol Vol. 35 (3): 354-361, May – June, 2009


Health Sciences Institute Special Research Alert “Cancer’s Kryptonite?”

Cell Bio Toxicol 1997 Feb; 13(2): 95-102

Radiats Biol Radioecol 1999 Sep-Oct; 39(5):572-7

Eur J Haematol 1995 Jan; 54(1): 27-33


From a Dr Al Sears email on 17 Sep 09

1 R. Chan, J. Woo, E. Suen, J. Leung, N. Tang, “Chinese tea consumption is associated with longer telomere length in elderly Chinese men” British Journal of Nutrition, Aug, 12, 2009

[xcii] I use NutriShield daily packs, from Uni-Vite ( This is a set of 7 pills containing all the compounds that medical scientist Dr Paul Clayton recommends, being frequently updated in the light of the latest research


WDDTY Vol 20 No 11 p.22

[xcvii] I prefer the purer form, without Vit.A. There is much evidence, from various sources (Rivici, Peskin, Barry Sears) that the outer membrane of the body’s cells is a key factor in treating cancer. That unless there is a relatively high intake of Omega3, the cell membrane will be compromised by other fats and hence a source of the cells’ poor performance.

[cxvi] Sakano K, Takahashi M, et al. Suppression of azoxymethane-induced colonic premalignant lesion formation by coenzyme Q10 in rats. Asian Pac J Cancer Prev. 2006 Oct; 7 (4): 599-603
Folkers K, Brown R, Judy WV, Morita M. Survival of cancer patients on therapy with coenzyme Q10. Biochem Biophys Res Commun. 1993 Apr 15;192(1): 241-5
Lockwood K, Moesgaard S, Folkers K. Partial and complete regression of breast cancer in patients in relation to dosage of coenzyme Q10. Biochem Biophys Res Commun 1994 Mar 30;199 (3):1504-8

Alternative Medicine Review Volume 12, Number 2 2007



[cxxviii] via



From a Dr Al Sears email on 17 Sep 09

1 R. Chan, J. Woo, E. Suen, J. Leung, N. Tang, “Chinese tea consumption is associated with longer telomere length in elderly Chinese men” British Journal of Nutrition, Aug, 12, 2009

[cxxxvii] seems the best made case for short, sharp vigorous exercise

[cxxxix] J Dean 2009 Nile River Publications Inc

[cxl] See “How to Meditate” Lawrence LeShan, Thorsons 1974 – a classic and still thought the best guide

[cxliii] The Anti Inflammation Zone, pp.263-269, Dr Barry Sears, Regan Books, ISBN 0-06-059546-9, 2005

[cxlv] See “DRINKING WATER AND WATER TREATMENT SCAMS” by James E. Hairston, Professor and Water Quality Coordinator, Donn Rodekohr, Agricutural Program Associate, Evaden F. Brantley, Agricultural Program Associate, Lori L. Bice, Undergraduate Student Assistant; 23 Oct 2003


[cxlvi] “Researchers from Denmark found that following recommendations on physical activity, waist circumference, smoking, alcohol and diet could reduce the risk of developing bowel cancer considerably — by 23%.”

Posted in cancer and diet, cancer suppplements, cancer survivor, Comments and Suggestions, complementary therapies | Tagged: , , | 11 Comments »

Ian Clements’ Vitamin D research

Posted by Jonathan Chamberlain on April 21, 2011

Vitamin D


YouTube presentations: 2

Vitamin D Prevents Cancer: Is It True?. 2

Gabriele Stähler on Vitamin D3. 2

Most Americans Seem to Have Healthy Levels of Vitamin D.. 3

Vitamin D Linked to Lung Cancer Survival, Study Suggests. 3

Higher Vitamin D Intake Could Cut Cancer Risk. 4

Associations of circulating and dietary vitamin D with prostate cancer risk. 4

Tanned women live longer (as long as you sunbathe sensibly), say scientists. 5

Taking Vitamin D, Calcium Supplements Not Necessary. 6

Impact of oral vitamin D supplementation on serum 25-hydroxyvitamin D levels in oncology  7

Serum vitamin D and risk of bladder cancer in smokers. 8

Insufficient Vitamin D Levels in Chronic Lymphocytic Leukemia Patients Linked to Cancer Progression and Death  9

Vit D and Bladder Cancer 11

Vitamin D Levels Confusion. 11

Vitamin D Deficiency Confirmed as Common Across a Range of Rheumatic Conditions  12

Vitamin D: With Meals, or Without?. 12

“Researchers at the Cleveland Clinic discovered that taking vitamin D with large meals boosts its absorption dramatically. 12

Vit D Research Video. 12

Vitamin D deficiency linked to more aggressive lymphoma. 12

Peter Granger’s Views. 13

Wikipedia. 14

Jan Alexander’s Views. 15

Vitamin A Reduces Vitamin D’s Effectiveness. 15

Vitamin D and Calcium Interplay Explored. 16

Recommended Level of Vit D.. 17

ask for the 25-Hydroxy Vitamin D test 18

Vitamin D Crucial to Activating Immune Defenses. 18

Chemical Reaction that Enables Activation. 19

Activating and Deactivating the Immune System.. 20

Vitamin D, Miracle Drug: Is It Science, or Just Talk?. 20

The Roles of Vitamin D Binding Protein in Human Immune Function. 23

Abstract: 23

Results: 24

Discussion: 25

Citations: 25

From: Peter Granger (pete.granger@GMAIL.COM) 26

The Anticancer Effects Of Vitamin D3. 27

Vitamin D Levels Associated With Survival in Lymphoma Patients. 27

Meta-analysis of longitudinal studies: Serum vitamin D and prostate cancer risk. 29

Aim.. 29

Conclusions. 29

Does Vitamin D Treat Cancer?. 29

It’s not that simple… 29

Summer diagnosis prolongs life. Why?. 30

Sunlight’s robust treatment effect 31

So, how much vitamin D does one need?. 31

Vitamin D’s unique behavior 32

25(OH)D level should be greater than 60 ng/mL.. 33

Little to no risk. 33

The real risk: waiting for further studies. 34

Vitamin D Can Alter Colon Cancer Cells In Many Ways, Through One Pathway. 34

Macrophage Activation May Suppress Breast Cancer Metastasis. 35

Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophage-activating factor, Gc-MAF. 36

Colon cancer: prognosis for different latitudes, age groups and seasons in Norway. 37

Circulating Vitamin D3 and 25-hydroxyvitamin D in Humans: An Important Tool to Define Adequate Nutritional Vitamin D Status. 37

Abstract 37

Introduction. 38

Materials and Methods. 38

Results. 40

Discussion. 40

References. 42

Women With Breast Cancer Have Low Vitamin D Levels. 43

Real Help for Cancer?. 44

High Levels of Vitamin D in Older People Can Reduce Heart Disease and Diabetes. 47


Inadequate Levels of Vitamin D May Significantly Increase Risk of Stroke, Heart Disease and Death  49

Heart and Bone Damage from Low Vitamin D Tied to Declines in Sex Hormones. 50

Vitamin D linked to lower heart disease risk. 52

Rheumatoid Arthritis Linked to Vitamin D Deficiency, Study Suggests. 54

Low Vitamin D Levels Associated With More Asthma Symptoms and Medication Use. 55

Researchers Recommend Pregnant Women Take 4,000 IU Vitamin D a Day. 56

Low Vitamin D Levels Are Related to MS Brain Atrophy, Cognitive Function, Studies Show   57

Vitamin D Deficiency Associated With Chronic Fatigue in Brain Injured Patients. 59

Better Vitamin D Status Could Mean Better Quality of Life for Seniors. 60

Effect of 25-hydroxyvitamin D status on serological response to influenza vaccine in prostate cancer patients  61

YouTube presentations:

Vitamin D Prevents Cancer: Is It True?[i]

Gabriele Stähler on Vitamin D3[ii]

Most Americans Seem to Have Healthy Levels of Vitamin D[iii]

WEDNESDAY, March 30 (HealthDay News) — Nearly two-thirds of U.S. residents have sufficient levels of vitamin D levels, but about a fourth of the population is at risk for vitamin D inadequacy and 8 percent are at risk for vitamin D deficiency, a new federal government study indicates.

An additional 1 percent of Americans have vitamin D levels high enough that could be harmful, according to the report, released Wednesday by researchers at the U.S. National Center for Health Statistics, part of the U.S. Centers for Disease Control and Prevention.

The body needs vitamin D to help it absorb calcium, which is a requisite for healthy bones. Muscles and nerves need vitamin D to function properly, and it helps the immune system fight off disease. Too little can lead to thin, brittle bones; extremely high levels can be toxic.

Vitamin D can be absorbed naturally from sunlight or obtained through foods or dietary supplements.

The National Institute of Medicine defines sufficient vitamin D by the amount registered in the blood: as a serum 25-hydroxyvitamin D value of 50-125 nmol/L. A value of 30-49 nmol/L is defined as inadequacy and less than 30 nmol/L is considered a deficiency.

For their report, the researchers analyzed data from 2001 to 2006 from the National Health and Nutrition Examination Survey. It included people aged 1 and older.

The analysis showed that the risk for vitamin D deficiency differed by age, sex and race or ethnicity.

By age, the risk for deficiency ranged from 1 percent to 8 percent among males and from 1 percent to 12 percent among females. For both sexes, the risk was lowest among children aged 1 to 8 and increased significantly until age 30 in men and age 18 in women. After that, the risk changed little as people aged, the study found.

Whites were less likely to be at risk for vitamin D deficiency than blacks or Mexican-Americans.

Among women of childbearing age, those who were pregnant or lactating were less likely to be at risk for vitamin D deficiency than those who weren’t pregnant or lactating.

Though vitamin D deficiency became more common in the United States between 1988-1994 and 2001-2002, the study found, risk for the deficiency did not change between 2001-02 and 2005-06.

About 4 percent of males 12 years and older had vitamin D levels that put them at risk for deficiency in 1988-1994, and 17 percent were at risk for inadequacy. Those numbers had risen to 7 percent and 22 percent, respectively, by 2001-2002, according to the study.

Among females 12 and older, vitamin D deficiency rose from 7 percent in 1988-1994 to 11 percent in 2001-2002. However, the proportion of females with inadequate levels of vitamin D dropped from 30 percent to 25 percent in that time.

Vitamin D Linked to Lung Cancer Survival, Study Suggests[iv]

ScienceDaily (Mar. 1, 2011) — Recent research suggests vitamin D may be able to stop or prevent cancer. Now, a new study finds an enzyme that plays a role in metabolizing vitamin D can predict lung cancer survival.

The study, from researchers at the University of Michigan Comprehensive Cancer Center, suggests that this enzyme stops the anti-cancer effects of vitamin D.

Levels of the enzyme, called CYP24A1, were elevated as much as 50 times in lung adenocarcinoma compared with normal lung tissue. The higher the level of CYP24A1, the more likely tumors were to be aggressive. About a third of lung cancer patients had high levels of the enzyme. After five years, those patients had nearly half the survival rate as patients with low levels of the enzyme.

Researchers then linked this to how CYP24A1 interacts with calcitriol, the active form of vitamin D. CYP24A1 breaks down calcitriol, which has a normal and crucial role when kept in check. But when levels of CYP24A1 climb, the enzyme begins to hinder the positive anti-cancer effects of vitamin D.

Results of the study appear in Clinical Cancer Research.

Previous studies have linked low levels of vitamin D to a higher incidence of cancer and worse survival. Researchers are looking at using vitamin D to help prevent lung cancer from returning and spreading after surgery. This new study suggests the possibility of using CYP24A1 levels to personalize this approach to those likely to benefit most.

“Half of lung cancers will recur after surgery, so it’s important to find a way to prevent or delay this recurrence. A natural compound like vitamin D is attractive because it has few side effects, but it’s even better if we can determine exactly who would benefit from receiving vitamin D,” says study author Nithya Ramnath, M.D., associate professor of internal medicine at the U-M Medical School.

Researchers also are working to identify drugs that block CYP24A1. Blocking the enzyme would reinstate the positive anti-cancer effects of vitamin D, suggesting that this inhibitor could potentially be combined with vitamin D treatments.

Note: Current recommendations call for 600-800 IU of vitamin D daily, depending on age. Studies looking at vitamin D in lung cancer are testing medically administered doses 200 times what could be taken by mouth naturally. Taking large amounts of vitamin D supplements is not currently recommended to prevent or treat lung cancer.

Lung cancer statistics: 222,520 Americans will be diagnosed with lung cancer this year and 157,300 will die from the disease, making it the biggest cancer killer, according to the American Cancer Society

Additional U-M authors: Guoan Chen, So Hee Kim, Amanda N. King, Lili Zhao, Robert U. Simpson, Paul J. Christensen, Zhuwen Wang, Dafydd G. Thomas, Thomas J. Giordano, Lin Lin, Dean E. Brenner, David G. Beer

Funding was provided by the National Institutes of Health.

Story Source: The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by University of Michigan Health System, via EurekAlert!, a service of AAAS.

Journal Reference: H. Meng, G. Chen, X. Zhang, Z. Wang, D. G. Thomas, T. J. Giordano, D. G. Beer, M. M. Wang. Stromal LRP1 in lung adenocarcinoma predicts clinical outcomeClinical Cancer Research, 2011; DOI: 10.1158/1078-0432.CCR-10-2385

Higher Vitamin D Intake Could Cut Cancer Risk[v]

SUNDAY, Feb. 27 (HealthDay News) — A new study says it takes far more vitamin D than initially thought to dramatically cut the risk of several major diseases, including breast cancer.

“We found that daily intakes of vitamin D by adults in the range of 4,000-8,000 IU are needed to maintain blood levels of vitamin D metabolites in the range needed to reduce by about half the risk of several diseases — breast cancer, colon cancer, multiple sclerosis and type 1 diabetes,” study co-author Dr. Cedric Garland, a professor of family and preventive medicine at the University of California at San Diego, said in a university news release.

Garland admitted that he was surprised that the levels required were so much higher than the 400 IU a day needed to vanquish rickets in the 20th century.

Vitamin D supplements often come in pills or capsules containing 1,000 or 2,000 international units. But 4,000 to 8,000 IU a day is still much lower than the range considered safe by the National Academy of Science’s Institute of Medicine, the researchers noted.

The study — which also involved the Creighton University School of Medicine in Omaha — was based on a survey of several thousand people who took supplements ranging from 1,000 to 10,000 IU per day. The volunteers also underwent blood tests to determine the levels of vitamin D metabolites circulating in their blood.

Some studies suggest that only 10 percent of people in the United States have the appropriate level of the vitamin D-related form in their blood to prevent disease linked to a deficiency of the vitamin. These people tend to work outdoors, where their vitamin D levels are boosted through sun exposure.

Last year, a National Academy of Sciences Institute of Medicine (IOM) committee announced that 4,000 IU a day of vitamin D appears safe for adults and kids aged 9 and up.

The IOM’s recommended minimum daily level is 600 IU, however, and the Institute noted there were preliminary signals that there might be some harms associated with consuming high levels of vitamin D daily, even at amounts under the recommended upper safe limit.

Garland and his colleagues suggested that 4,000 IU a day is a safe level.

“Now that the results of this study are in, it will become common for almost every adult to take 4000 IU/day,” Garland predicted in the news release. “This is comfortably under the 10,000 IU/day that the IOM Committee Report considers as the lower limit of risk, and the benefits are substantial.”

The findings appear in the journal Anticancer Research.

Associations of circulating and dietary vitamin D with prostate cancer risk[vi]

a systematic review and dose–response meta-analysis

Cancer Causes and Control, 01/17/2011  Evidence Based Medicine

Gilbert R et al. – Published literature provides little evidence to support a major role of vitamin D in preventing prostate cancer or its progression. Authors searched over 24,000 papers from seven electronic databases (to October 2010) for exposures related to vitamin D

Tanned women live longer (as long as you sunbathe sensibly), say scientists[vii]

By Sophie Borland
Last updated at 1:51 AM on 4th December 2010

Women who regularly sunbathe live longer, a leading cancer specialist has claimed.

Hakan Olsson says his research shows the health benefits of exposure to sunlight ‘far outweigh’ the danger of skin cancer.

He said vitamin D produced by the body when tanning gives vital protection against blood clots, diabetes and some tumours.

But the professor’s claims, based on a study of 40,000 women, sharply contradict warnings that sun exposure is behind soaring levels of skin cancer.

Dr Ollson said catching the sun had more health benefits than costs, as long as you don’t burn

Rates of malignant melanoma, the deadliest form of the disease, have quadrupled since 1980. Experts blame the rise on sunbeds and the increasing numbers of Britons going abroad on cheap package holidays.

But Professor Olsson, who works in the oncology unit at Lund University in Sweden, believes the benefits of the sun ‘far outweigh the negatives’.

He said there was overwhelming evidence that exposure to the sun helps protect against blood clots in the leg, which claim the lives of 25,000 Britons a year.

These clots, known as deep vein thromboses, have been shown to be far more prevalent in winter than summer.

Professor Olsson, who was presenting his research at the Swedish Society of Medicine, cited other studies showing that more patients are diagnosed with diabetes in the colder months, a phenomenon attributed to a lack of vitamin D.

For his study, he examined tanning habits and the incidence of illnesses such as heart disease, diabetes or malignant melanoma.

‘Our studies show that women with active sunbathing habits live longer,’ he said.

Professor Olsson also suggested that skin cancer was not caused by sunbathing alone.

‘I and many others believe that there may be factors other than the sun that influence the risk of malignant melanoma,’ he said.

‘The burning of the skin in the sun is not enough to explain this.’

But Ed Yong, of Cancer Research UK, said: ‘While some sunshine is good for us and vitamin D is important for good bone health, there’s inconclusive evidence to suggest that vitamin D protects against other disease such as cancer or heart disease.

‘Not burning is the most important thing people can do to protect themselves against developing skin cancer. Sunburn is a clear sign that skin cells have been damaged and increases the risk of the disease.

‘Everyone is different and you’re most at risk from skin cancer if you have fair skin, red hair, lots of freckles, moles, or a family history of the disease. These people should take extra care in the sun.’

Experts warn that most Britons lack vitamin D, which is found in oily fish, eggs and butter. Ninety per cent of our supply of it comes from the action of sunlight on the skin.

Taking Vitamin D, Calcium Supplements Not Necessary[viii]

Posted on: Tuesday, 30 November 2010, 09:21 CST

Most people get enough vitamin D from the sun, and there’s no evidence that taking supplements of the so-called sunshine vitamin will fight off cancer, prevent diabetes, or strengthen a person’s immune system, a panel of U.S. and Canadian doctors said on Tuesday.

The announcement comes as part of a new set of dietary intake guidelines for both calcium and vitamin D, released this week by the Institute of Medicine (IOM), an independent American health agency established in 1863.

Using expert testimony and nearly 1,000 published studies analyzing the two nutrients, the IOM discerned that most North Americans 70 years of age or under need just 600 international units (IUs) of vitamin D per day, and those over the age of 71 need 800 IUs. Calcium intake, on the other hand, can vary from 700 to 1,300 milligrams daily.

“The committee that wrote the report also reviewed hundreds of studies and reports on other possible health effects of vitamin D, such as protection against cancer, heart disease, autoimmune diseases, and diabetes,” the IOM said in a Tuesday press release. “While these studies point to possibilities that warrant further investigation, they have yielded conflicting and mixed results and do not offer the evidence needed to confirm that vitamin D has these effects.”

However, both calcium and vitamin D were proven to have positive effects when it comes to bone health and skeletal growth and maintenance, the researchers noted.

“There is abundant science to confidently state how much vitamin D and calcium people need,” Committee Chairperson Catharine Ross, a professor with the Pennsylvania State University Department of Nutritional Sciences, said in a statement. “We scrutinized the evidence, looking for indications of beneficial effects at all levels of intake.  Amounts higher than those specified in this report are not necessary to maintain bone health.”

Children between the ages of 1 and 3 should consume 700mg of calcium per day, while kids between the ages of 4 and 8 should up their intake to 1,000mg, the IOM said. Individuals between the ages of 9 and 18 need no more than 1,300mg of calcium daily, while most adults between the ages of 19 and 50 can reduce their calcium intake back down to 1,000mg. Men over the age of 50 and under the age of 71 can maintain that level, while women are advised to up their consumption to 1,200mg daily.

“The majority of Americans and Canadians are getting enough vitamin D and calcium, the committee determined from reviewing national surveys of blood levels,” the IOM reported. “Some adolescent girls may not get quite enough calcium, and there is a greater chance that elderly individuals may fall short of the necessary amounts of calcium and vitamin D.  These individuals should increase their intake of foods containing these nutrients and possibly take a supplement.”

Overdosing on either nutrient can be dangerous, the researchers reported. Consuming high levels of vitamin D (at least 10,000 IUs daily) are known to cause kidney and tissue damage, they claim, and even taking 4,000 IUs daily could be risky. In terms of calcium, the IOM says that taking more than 2,000mg each day could lead to kidney stones, especially in post-menopausal women.

Impact of oral vitamin D supplementation on serum 25-hydroxyvitamin D levels in oncology[ix]

Nutrition Journal 2010, 9:60doi:10.1186/1475-2891-9-60

Published: 23 November 2010


Serum 25-hydroxyvitamin D [25(OH)D] is the major circulating form of vitamin D and a standard indicator of vitamin D status. Emerging evidence in the literature suggests a high prevalence of suboptimal vitamin D (as defined by serum 25(OH)D levels of <32 ng/ml) as well as an association between lower serum levels and higher mortality in cancer. We investigated the effect of oral vitamin D supplementation as a means for restoring suboptimal levels to optimal levels in cancer.


This is a retrospective observational study of 2198 cancer patients who had a baseline test prior to initiation of cancer therapy at our hospital to evaluate serum 25(OH)D levels between Jan 08 and Dec 09 as part of their initial nutritional evaluation. Patients with baseline levels of <= 32 ng/ml (n=1651) were considered to have suboptimal serum 25(OH)D levels and were supplemented with 8000 IU of Vitamin D3 (four 2000 IU D3 capsules) daily as part of their nutritional care plan. The patients were retested at their first follow-up visit. Of 1651 patients, 799 were available for follow up assessment. The mean serum 25(OH)D levels were compared in these 799 patients across the 2 time points (baseline and first follow-up) using paired sample t-test. We also investigated the factors associated with response to vitamin D supplementation.


Of 2198 patients, 814 were males and 1384 females. 1051 were newly diagnosed and treated at our hospital while 1147 were diagnosed and treated elsewhere. The mean age at presentation was 55.4 years. The most common cancer types were breast (500, 22.7%), lung (328, 14.9%), pancreas (214, 9.7%), colorectal (204, 9.3%) and prostate (185, 8.4%). The mean time duration between baseline and first follow-up assessment was 14.7 weeks (median 10.9 weeks and range 4 weeks to 97.1 weeks). The mean serum 25(OH)D levels were 19.1 ng/ml (SD = 7.5) and 36.2 ng/ml (SD = 17.1) at baseline and first follow-up respectively; p <0.001. Patients with prostate and lung cancer had the highest percentage of responders (70% and 69.2% respectively) while those with colorectal and pancreas had the lowest (46.7% each). Similarly, patients with serum levels 20-32 ng/ml at baseline were most likely to attain levels >32 ng/ml compared to patients with baseline levels <20 ng/ml.


The response to supplementation from suboptimal to optimal levels was greatest in patients with prostate and lung cancer as well as those with baseline levels between 20-32 ng/ml. Characteristics of non-responders as well as those who take longer to respond to supplementation need to be further studied and defined. Additionally, the impact of improved serum 25(OH)D levels on patient survival and quality of life needs to be investigated.

Serum vitamin D and risk of bladder cancer in smokers[x]

Tuesday, 16 November 2010

Vitamin D may protect against several cancers, but data about the association between circulating vitamin D and bladder cancer are limited. Within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a randomized controlled trial conducted to determine the effects of α-tocopherol and β-carotene supplements on cancer incidence in male smokers, 250 bladder cancer cases were randomly sampled by month of blood collection. Controls were matched 1:1 to cases on age at randomization and date of blood collection. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of bladder cancer by a priori categories of baseline serum 25-hydroxyvitamin D [25(OH)D; i.e., < 25, 25 to < 37.5, 37.5 to < 50, ≥50 nmol/L] and by season-specific quartiles. After multivariable adjustment, we found that lower 25(OH)D was associated with a statistically significantly increased risk of bladder cancer (versus ≥50 nmol/L; < 25 nmol/L: OR, 1.73; 95% CI, 1.03-2.91; 25 to < 37.5 nmol/L: OR, 1.81; 95% CI, 1.05-3.14; 37.5 to < 50 nmol/L: OR, 1.76; 95% CI, 1.02-3.02; P trend = 0.04). Similarly, increased risks for the lowest vitamin D category were observed when season-specific quartiles were used (Q1 versus Q4: OR, 1.63; 95% CI, 0.96-2.75; P trend = 0.03). In this prospective study of male smokers, lower serum 25(OH)D was associated with an increased risk of bladder cancer. Future studies should examine the association in other populations, especially nonsmokers and women.

Written by: Mondul AM, Weinstein SJ, Männistö S, Snyder K, Horst RL, Virtamo J, Albanes D

Reference: Cancer Res. 2010 Oct 26. doi: 10.1158/0008-5472.CAN-10-0985

PubMed Abstract PMID: 20978193

Insufficient Vitamin D Levels in Chronic Lymphocytic Leukemia Patients Linked to Cancer Progression and Death[xi]

ScienceDaily (Nov. 4, 2010) — Researchers at Mayo Clinic have found a significant difference in cancer progression and death in chronic lymphocytic leukemia (CLL) patients who had sufficient vitamin D levels in their blood compared to those who didn’t.

In the Mayo Clinic study, published online in the journal Blood, the researchers found that patients with insufficient levels of vitamin D when their leukemia was diagnosed progressed much faster and were about twice as likely to die as were patients with adequate levels of vitamin D.

They also found solid trends: increasing vitamin D levels across patients matched longer survival times and decreasing levels matched shortening intervals between diagnosis and cancer progression. The association also remained after controlling for other prognostic factors associated with leukemia progression.

The finding is significant in a number of ways. For the first time, it potentially offers patients with this typically slower growing form of leukemia a way to slow progression, says the study’s lead author, Tait Shanafelt, M.D., a hematologist at Mayo Clinic in Rochester, Minn.

“This finding may be particularly relevant for this kind of leukemia because although we often identify it at an early stage, the standard approach is to wait until symptoms develop before treating patients with chemotherapy,” Dr. Shanafelt says. “This watch and wait approach is difficult for patients because they feel there is nothing they can do to help themselves.”

“It appears vitamin D levels may be a modifiable risk factor for leukemia progression. It is simple for patients to have their vitamin D levels checked by their physicians with a blood test,” he says. “And if they are deficient, vitamin D supplements are widely available and have minimal side effects.”

While the researchers have not yet determined if vitamin D replacement in patients with initially low levels will reverse the more rapid progression associated with insufficiency, they are planning a study to explore that hypothesis.

This research adds to the growing body of evidence that vitamin D deficiency is a risk factor for development and/or progression of a number of cancers, the researchers say. Studies have suggested that low blood vitamin D levels may be associated with increased incidence of colorectal, breast and other solid cancers. Other studies have suggested that low vitamin D levels at diagnosis may be associated with poorer outcomes in colorectal, breast, melanoma and lung cancers, as well as lymphoma.

Replacing vitamin D in some patients has proven to be beneficial, the researchers say. For example, they cite a placebo-controlled clinical trial that found women who increased their vitamin D intake reduced their risk of cancer development.

Vitamin D insufficiency, in general, is widespread, Dr. Shanafelt says. “Between one-fourth and one-half of patients seen in routine clinical practice have vitamin D levels below the optimal range, and it is estimated that up to 1 billion people worldwide have vitamin D insufficiency,” he says.

Vitamin D is obtained from skin exposure to sunlight, from certain foods (fatty fish and eggs) and from supplements.

In this study, the research team, including physicians at the University of Iowa, enrolled 390 CLL patients into a prospective, observational study. They tested the blood of these newly diagnosed patients for plasma concentration of 25-hydroxyl-vitamin D and found that 30 percent of these CLL patients were considered to have insufficient vitamin D levels, which is classified as a level less than 25 nanograms per milliliter.

After a median follow-up of three years, CLL patients deficient in vitamin D were 66 percent more likely to progress and require chemotherapy; deficient patients also had a two-fold increased risk of death.

To confirm these findings, they then studied a different group of 153 untreated CLL patients who had been followed for an average of 10 years. The researchers found that about 40 percent of these 153 CLL patients were vitamin D deficient at the time of their diagnosis. Patients with vitamin D deficiency were again significantly more likely to have had their leukemia progress and to have died, Dr. Shanafelt says.

“This tells us that vitamin D insufficiency may be the first potentially modifiable risk factor associated with prognosis in newly diagnosed CLL,” he says.

The study was funded by the National Institutes of Health (, Gabrielle’s Angel Foundation for Cancer Research, the Henry J. Predolin Foundation, Vysis, Inc., and the Mayo Hematologic Malignancies Fund. The authors declare no conflicts of interest.

Vit D and Bladder Cancer

Reported by Crilly 4 Nov ‘11

Higher vitamin D levels associated with lower risk of bladder cancer 


An article published online on October 26, 2010 in the journal Cancer

Research reveals an association between higher levels of serum vitamin D and a lower risk of bladder cancer in men. The finding adds another cancer to the list of those for which vitamin D appears to have a protective benefit.


The current study involved 500 participants in the Alpha-Tocopherol,

Beta-Carotene Cancer Prevention Study, a randomized, double-blinded trial of Finnish male smokers conducted to determine the effects of alpha-tocopherol and beta-carotene supplementation on cancer risk. Participants were cancer-free at the beginning of the study. Blood samples drawn upon enrollment between 1985 and 1988 were analyzed for serum 25-hydroxyvitamin D levels and other factors.


The National Cancer Institute researchers compared 250 subjects who were diagnosed with bladder cancer through April, 2005 and an equal number of participants who did not have the disease. Cases and controls were matched for age and date of blood draw. A low level of vitamin D was associated with a significantly greater risk of bladder cancer. Men whose vitamin D level was less than 25 nanomoles per liter experienced a 73 percent greater adjusted risk of the disease than those whose levels were at least 50 nanomoles per liter. Similar risks were observed for those whose levels fell between 25 and less than 37.5, and from 37.5 to less than 50 nanomoles per liter.


"These findings are consistent with previous cell culture, in vivo, and genetic evidence suggesting that greater exposure to vitamin D could have a role in protecting against bladder cancer," Alison M. Mondul and co-authors write. "Higher serum 25-hydroxyvitamin D may be associated with greater urinary excretion and concentration of free and conjugated vitamin D metabolites. Increased exposure of the bladder mucosa to these metabolites could promote transitional cell differentiation and apoptosis and, thus, reduce epithelial proliferation and neoplasia."


"Future studies should examine the association in other populations,

especially nonsmokers and women, and evaluate possible effect modification by season of blood draw, physical activity, and intake of other nutrients, including vitamin E," they recommend.

Vitamin D Levels Confusion

From: Crilly Butler (crilly@DCN.ORG)

Sent:  01 July 2010 01:46:54

Remember--when Vit D levels are tested, the BLOOD levels are being tested, not the fat levels.

Seems to me that the more Vit D stored in the fat, the less is available to the cells that need it as fed through the circulatory system.


Also remember that Vit D is only stored in the fat, or made available to the cells that need it, when it is absorbed during digestion.  That requires a complex interplay between GI transit time, condition of the GI tract, other foods with which the Vit D is taken, the amount of water consumed, and the interaction between Vit D, Calcium, Magnesium and probably other vitamins and minerals as well, not to mention your amount of sun exposure.


Why some people seem to absorb Vit D and/or utilize it more effectively than others is difficult to pin down.  That's why it's a good idea to slowly up your intake of the vitamin over time while regularly checking your blood levels until you reach the correct dosage.

Vitamin D Deficiency Confirmed as Common Across a Range of Rheumatic Conditions[xii]

ScienceDaily (June 19, 2010) — Two separate studies have shown that vitamin D deficiency is common in patients with a range of rheumatic diseases, with over half of all patients having below the ‘normal’ healthy levels of vitamin D (48-145 nmol/L) in their bodies. A further study assessing response to vitamin D supplementation found that taking the recommended daily dose did not normalise vitamin D levels in rheumatic disease patients.

Researchers found that, regardless of supplementation, levels of 25-hydroxyvitamin D (25(OH)D), (a standard clinical measure of vitamin D in the blood), were lower than healthy levels (<50 nmol/L) in 85% of the patients not taking a vitamin D supplement and in 60% of those taking 800 IU or more vitamin D daily as a supplement.

“The results of our study show that daily 800-1,000 IU supplementation is not sufficient to normalise vitamin D levels in patients with rheumatologic or bone conditions. What is unclear is whether a higher dose would be more effective.”

Vitamin D: With Meals, or Without?

“Researchers at the Cleveland Clinic discovered that taking vitamin D with large meals boosts its absorption dramatically.

Vit D Research Video

Vitamin D deficiency linked to more aggressive lymphoma[xiii]

(NaturalNews) Lymphoma patients with vitamin D deficiency are twice as likely to die from their cancer than patients with sufficient blood levels of the vitamin, according to a study conducted by researchers from the Mayo Clinic and presented at a meeting of the American Society of Hematology.

Researchers took blood samples from 374 patients between 2002 and 2008 who had been recently diagnosed with a cancer of the white blood cells known as diffuse large B-cell lymphoma. The average participant age was 62.

Approximately 40 percent of all lymphomas are of the diffuse large-B cell type. The disease mainly affects people over the age of 50.

The researchers found that roughly 50 percent of all participants suffered from vitamin D deficiency at the beginning of the study, defined as having blood levels below 25 nanograms per liter. Over an average of three years of follow-up, patients with vitamin D deficiency were 50 percent more likely to have their cancer worsen and twice as likely to die as patients with vitamin levels above 25 nanograms per liter.

Researchers have known for a long time that vitamin D helps regulate calcium absorption and thus plays a crucial role in bone and dental health. Recent research suggests that the vitamin may also help regulate the immune system, and that higher levels can help prevent against chronic diseases such as Alzheimer’s, cancer, diabetes and dementia. Some researchers are making the case that for these benefits, vitamin D levels must be maintained at a level closer to 40 nanograms per liter.

The Mayo Clinic researchers used the 25 nanogram per liter cutoff because that is the level at which the body begins to leach calcium from its own bones, and is therefore a well-defined deficiency threshold.

Prior research has suggested that vitamin D deficiency may worsen the prognosis for patients with breast, colon and throat cancers.

Sources for this story include:

Peter Granger’s Views

From: Peter Granger (pete.granger@GMAIL.COM) Sent: 07 April 2010 21:31:07 & 16 May 2010 00:14:44

Most people are vitamin D deficient.


I have been taking 4,000 - 8,000 IU/day (divide by 40 for conversion

to mcg) for several years now, and my vitamin D [(25(OH)D] levels are

at the maximum desirable range - which is about 56 ng/ml, or 140

nmol/L. [The recommended maximum levels vary considerably -


I wont be increasing this level, in fact, I may try and reduce it

fractionally to be on the safe side. Those taking Oncovite may have

lower vitamin D levels, and may need to increase their vitamin D

intake until it gets into the preferred range.


I am not a medical practitioner, but I believe the research is

suggesting an increased intake of vitamin D and vitamin K

(spinach, greens), in combination with modest dietary intake of

calcium (dairy foods), is a more desirable option than supplementing

with high doses of calcium.


A daily 'dose' of spinach and ricotta pie is looking more and more

attractive. Actually, to reach the calcium rda, you will need (say) 1

cup of ricotta, plus one cup of yoghurt, plus a little cheese or milk.


I have serious concerns about calcium supplementation in the absence

of adequate vitamin D and vitamin K levels. It seems much preferable

to get adequate calcium from dairy foods, and vitamin K from greens -

esp, spinach and parsely), plus some vitamin D supplementation.


I believe treating calcium, vitamin D and vitamin K as separate

entities has been a big mistake.


Time will tell.
Its unlikely you will get vitamin D toxicity unless you start getting

up to the 300 level (much less if pregnant). Nonetheless, both too

much or too little vitamin D might increase the risk of

atherosclerosis, so its better to keep vitamin D levels in moderation.

Between 40 - 100 is recommended for cancer patients. Mine are are

currently at 150 (excessive supplementation), which I am cutting back

to below 100.


'vitamin D intoxication will not occur until a person (an adult) is

taking more than 10,000 IU of vitamin D/d for more than six months'.


'my preference is to recommend that you take no more than 3,000 IU of vitamin D/d.'


You can get more detail from:

Pete (and his quote from Wikipedia below)


'A concentration of over 15 ng/ml (>37.5 nmol/L) is recommended.


Higher levels (>30 ng/ml or >75 nmol/L) are proposed by some as

desirable for achieving optimum health but there is not enough

evidence to support them.[32][33][34][35]'


'Vitamin D toxicity is usually the result of taking supplements in

excess, when toxic symptoms occur the serum 25(OH)D levels are usually found to be elevated >150 ng/mL (>375 nmol/L).


'full body exposure to sunlight (produces) approximately 250 µg

(10,000 IU) per day'.


'The U.S. Dietary Reference Intake Tolerable Upper Intake Level (upper limit) of vitamin D for children and adults is set at 50

micrograms/day (2,000 IU)'.


'prompted a researcher [82]  to suggest that 250 micrograms/day

(10,000 IU) in healthy adults should be adopted as the tolerable upper limit'


One study found a possible negative link between excessive vitamin D

supplementation and calcification/atherosclerosis, however this risk

may be confined to African-Americans (it is quite possible African

Americans require much lower levels of vitamin D, and excessive

supplementation may be harmful)  - 'dietary vitamin D may be carried

by lipoprotein particles[90]  into cells of the artery wall and

atherosclerotic plaque, where it may be converted to active form by



A 2007 study reports that vitamin D supplementation (1,100

international units (IU)/day) resulted in a 60% reduction in cancer

incidence, during a four-year clinical trial, rising to a 77%

reduction for cancers diagnosed after the first year (and therefore

excluding those cancers more likely to have originated prior to the

vitamin D intervention).


However, smokers who supplement with vitamin D may be at an additional risk of cancer.

Jan Alexander’s Views

From:   Jan Alexander (jea1013@YAHOO.COM)

Sent:  16 May 2010 00:22:21

seems like we are all different–I have to take 8000/day just to maintain my level at 70.  there is some thought that taking cod liver oil may interfere with the absorption of vit. d.  i guess there is a lot we don’t know about this.  but it is being researched more and more because it seems implicated in so many diseases, or rather, the lack of it seems implicated.

From:  Jan Alexander (jea1013@YAHOO.COM)

Sent:  29 June 2010 15:27:14

My oncologist feels that anyone with cancer needs to have Vitamin D levels definitely above 60, and closer to 80 is better.  At 50,000 IU/week my level will not budge above 60, so now I am at 72,000 IU/week, and will get my levels tested again next month.  This is VERY important, she feels, for people with cancer, to keep those levels up.  30 is considered "normal" but is NOT enough for us.  -Jan

Vitamin A Reduces Vitamin D’s Effectiveness[xv]

Posted by Dr. Mercola | March 16 2010

The British Medical Journal has published a remarkable paper confirming that low vitamin D levels obtained in the past are a risk factor for developing colon cancer in the future.

But the study contained an even more significant finding — as Dr. Cannell’s site has reported before, vitamin A, even in relatively low amounts, can thwart vitamin D’s association with reduced rates of colon cancer.

This is the largest study to date showing vitamin A blocks vitamin D’s effect.

Hidden on page eight of the paper was one sentence and a small table, showing that the benefits of vitamin D are almost entirely negated in those with the highest vitamin A (retinol) intake.

And the retinol intake did not have to be that high — only about 3,000 IU/day. Young autistic children often take 3,500 IU of retinol a day in their powdered multivitamins, which doesn’t count any additional vitamin A given in high single doses.

The finding explains some of the anomalies in other papers on vitamin D and cancer — similar studies sometimes have widely different results. This may be because the effect of vitamin A was not taken into account. In some countries, cod liver oil, which contains vitamin A, is commonly used as a vitamin D supplement, and in others it is used more rarely, causing differences in the results.


The Natural Advocate February 28, 2010

Vitamin D Council

British Medical Journal, BMJ 2010;340:b5500

Vitamin D and Calcium Interplay Explored[xvi]

ScienceDaily (Mar. 15, 2010) — Increasing calcium intake is a common — yet not always successful — strategy for reducing bone fractures. But a study supported in part by the Agricultural Research Service (ARS) underscores the importance of vitamin D and its ability to help the body utilize calcium. The study also may explain why increasing calcium alone isn’t always successful in dealing with this problem.

Currently, calcium intake recommendations are not tied to vitamin D status, which may explain why markedly different recommended calcium intakes exist among countries. In the United States, the recommended calcium intake is 1,200 milligrams (mg) daily for adults aged 50 and older.

The body’s skeleton needs adequate dietary calcium to reach its full potential in terms of bone mass. Still, many other factors affect bone mass, such as exercise, smoking and vitamin D — the latter through its effect on calcium absorption and direct effect on the skeleton.

The study involved a close look at about 10,000 men and women aged 20 and older participating in a nationally representative survey. Coauthors included nutrition specialist Bess Dawson Hughes with the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University in Boston, Mass. Dawson Hughes is director of the HNRCA Bone Metabolism Laboratory.

Blood levels of 25-hydroxyvitamin D are used as the primary indicator of vitamin D adequacy. Within the study sample of U.S. adults, a large fraction of younger and older adults were below a suggested desirable serum vitamin D concentration of at least 75 nanomoles-per-liter (nmol/L).

The study supports the idea that correcting inadequate blood levels of vitamin D is more important than increasing dietary calcium intake beyond 566 mg a day among women and 626 mg a day among men for better bone mineral density. For example, a higher calcium intake beyond 566 mg a day may only be important among women whose vitamin D concentrations are low (less than 50 nmol/L), according to authors.

Journal Reference:

1.      Heike A Bischoff-Ferrari, Douglas P Kiel, Bess Dawson-Hughes, John E Orav, Ruifeng Li, Donna Spiegelman, Thomas Dietrich, Walter C Willett. Dietary Calcium and Serum 25-Hydroxyvitamin D Status in Relation to BMD Among U.S. Adults. Journal of Bone and Mineral Research, 2009; 24 (5): 935 DOI: 10.1359/jbmr.081242

Recommended Level of Vit D

Re: [CAFE] Vitamin D and Cancer/Immune System Functioning‏

From:   Jan Alexander (jea1013@YAHOO.COM)

Sent:  09 March 2010 14:27:05


my oncologist wants me at least at 80, since i have had cancer.  she said some studies even show 100 is better.

Re: [CAFE] Vitamin D and Cancer/Immune System Functioning‏

From:   Linda Weyand (lweyand@AOL.COM)

Sent:  09 March 2010 15:19:55


Hi, Puff and All,

The lab that ran my vitamin D, 25-Hydroxy test listed the range of 32 to 100 and added a note with reference that stated "Recent studies consider the lower limit of 32.0 ng/mL to be a threshold for optimal health." This coincides with articles I have read that lists anything below 30 as being a deficiency and stresses that this level is a bare minimum. These articles recommend a level of 50 to 80. With the recent studies showing the importance of vitamin D, I am glad my primary care physician suggested I have my level checked during my annual exam, especially since my results showed a level of 8.1....a severe deficiency. 


I have been taking the 50,000 IU capsules and after the first 3 months, my level tested at 22. At that time, I expressed the desire to have my levels reach the 50 to 80 level, so my doctor told me to continue taking the 50,000 IU and we would recheck at my next annual exam. She said that she has never had any of her patients test over 80, even those that had been taking high dosages over long period of time. 


Today I read: 

"Since vitamin D is a fat-soluble vitamin and is absorbed from the intestine like a fat, vitamin D [test] is sometimes used to monitor individuals with diseases that interfere with fat absorption, such as cystic fibrosis and Chron's disease, and in patients who have had gastric bypass surgery and may not be able to absorb enough Vitamin D."


To me, this means that those of us whose ileum (small intestine) has been used to make our urinary diversions MIGHT have impaired Vitamin D absorption. It also explains why the capsules are to be taken with food. With recent research connecting vitamin D deficiency with cancer, I think all of us probably should ask that the 25-Hydroxy, Vitamin D test be included with our check-ups. 


For any of us that are taking bile sequestrants, we need to space a good bit of time between taking the bile sequestrant and the Vitamin D. The literature that came with my Vitamin D stated that it should be spaced at least 2 hours, longer if possible and suggested taking the Vit. D at bedtime if taking these other medicines (bile acid sequestrants such as cholestyramine/colestipol, mineral oil, orlistat). 


This literature also cautioned that this medication (Vit. D) "may interfere with certain laboratory tests (including cholesterol test)"  so to let all your doctors know you are taking this medication. 


My best to all,

Linda W neobladder 2/2002

ask for the 25-Hydroxy Vitamin D test

Vitamin D Crucial to Activating Immune Defenses[xvii]

ScienceDaily (Mar. 8, 2010) — Scientists at the University of Copenhagen have discovered that Vitamin D is crucial to activating our immune defenses and that without sufficient intake of the vitamin, the killer cells of the immune system — T cells — will not be able to react to and fight off serious infections in the body.

For T cells to detect and kill foreign pathogens such as clumps of bacteria or viruses, the cells must first be ‘triggered’ into action and ‘transform’ from inactive and harmless immune cells into killer cells that are primed to seek out and destroy all traces of a foreign pathogen.

The researchers found that the T cells rely on vitamin D in order to activate and they would remain dormant, ‘naïve’ to the possibility of threat if vitamin D is lacking in the blood.

When the naïve T cell recognizes foreign molecules with its T cell receptor (TCR) it sends activation signals (1) to the VDR gene. The VDR gene now starts the production of VDR (2). VDR binds vitamin D in the T cell (3) and becomes activated. Vitamin D bound to activated VDR goes back into the cell nucleus and activates the gene for PLC-gamma1 (5). PLC-gamma1 is produced (6) and the T cells can get started. (Credit: Professor of Immunology, Carsten Geisler)

Chemical Reaction that Enables Activation

In order for the specialized immune cells (T cells) to protect the body from dangerous viruses or bacteria, the T cells must first be exposed to traces of the foreign pathogen. This occurs when they are presented by other immune cells in the body (known as macrophages) with suspicious ‘cell fragments’ or ‘traces’ of the pathogen. The T cells then bind to the fragment and divide and multiply into hundreds of identical cells that are all focused on the same pathogen type. The sequence of chemical changes that the T cells undergo enables them to both be ‘sensitized to’ and able to deliver a targeted immune response.

Professor Carsten Geisler from the Department of International Health, Immunology and Microbiology explains that “when a T cell is exposed to a foreign pathogen, it extends a signaling device or ‘antenna’ known as a vitamin D receptor, with which it searches for vitamin D. This means that the T cell must have vitamin D or activation of the cell will cease. If the T cells cannot find enough vitamin D in the blood, they won’t even begin to mobilize. ”

T cells that are successfully activated transform into one of two types of immune cell. They either become killer cells that will attack and destroy all cells carrying traces of a foreign pathogen or they become helper cells that assist the immune system in acquiring “memory.” The helper cells send messages to the immune system, passing on knowledge about the pathogen so that the immune system can recognize and remember it at their next encounter. T cells form part of the adaptive immune system, which means that they function by teaching the immune system to recognize and adapt to constantly changing threats.

Activating and Deactivating the Immune System

For the research team, identifying the role of vitamin D in the activation of T cells has been a major breakthrough. “Scientists have known for a long time that vitamin D is important for calcium absorption and the vitamin has also been implicated in diseases such as cancer and multiple sclerosis, but what we didn’t realize is how crucial vitamin D is for actually activating the immune system — which we know now. ”

The discovery, the scientists believe, provides much needed information about the immune system and will help them regulate the immune response. This is important not only in fighting disease but also in dealing with anti-immune reactions of the body and the rejection of transplanted organs. Active T cells multiply at an explosive rate and can create an inflammatory environment with serious consequences for the body. After organ transplants, e.g. T cells can attack the donor organ as a “foreign invader.” In autoimmune disease, hypersensitive T cells mistake fragments of the body’s own cells for foreign pathogens, leading to the body launching an attack upon itself.

The research team was also able to track the biochemical sequence of the transformation of an inactive T cell to an active cell, and thus would be able to intervene at several points to modulate the immune response. Inactive or ‘naïve’ T cells crucially contain neither the vitamin D receptor nor a specific molecule (PLC-gamma1) that would enable the cell to deliver an antigen specific response.

The findings, continues Professor Geisler “could help us to combat infectious diseases and global epidemics. They will be of particular use when developing new vaccines, which work precisely on the basis of both training our immune systems to react and suppressing the body’s natural defenses in situations where this is important — as is the case with organ transplants and autoimmune disease.”

Most Vitamin D is produced as a natural byproduct of the skin’s exposure to sunlight. It can also be found in fish liver oil, eggs and fatty fish such as salmon, herring and mackerel or taken as a dietary supplement. No definitive studies have been carried out for the optimal daily dosage of vitamin D but as a large proportion of the population have very low concentrations of vitamin D in the blood, a number of experts recommend between 25-50mg micrograms a day.

Journal Reference:

1.      von Essen et al. Vitamin D controls T cell antigen receptor signaling and activation of human T cells. Nature Immunology, 2010; DOI: 10.1038/ni.1851

Vitamin D, Miracle Drug: Is It Science, or Just Talk?[xviii]

Stuart Bradford

Imagine a treatment that could build bones, strengthen the immune system and lower the risks of illnesses like diabetes, heart and kidney disease, high blood pressure and cancer.

Some research suggests that such a wonder treatment already exists. It’s vitamin D, a nutrient that the body makes from sunlight and that is also found in fish and fortified milk.

Yet despite the health potential of vitamin D, as many as half of all adults and children are said to have less than optimum levels and as many as 10 percent of children are highly deficient, according to a 2008 report in The American Journal of Clinical Nutrition.

As a result, doctors are increasingly testing their patients’ vitamin D levels and prescribing daily supplements to raise them. According to the lab company Quest Diagnostics, orders for vitamin D tests surged more than 50 percent in the fourth quarter of 2009, up from the same quarter a year earlier. And in 2008, consumers bought $235 million worth of vitamin D supplements, up from $40 million in 2001, according to Nutrition Business Journal.

But don’t start gobbling down vitamin D supplements just yet. The excitement about their health potential is still far ahead of the science.

Although numerous studies have been promising, there are scant data from randomized clinical trials. Little is known about what the ideal level of vitamin D really is, whether raising it can improve health, and what potential side effects are caused by high doses.

And since most of the data on vitamin D comes from observational research, it may be that high doses of the nutrient don’t really make people healthier, but that healthy people simply do the sorts of things that happen to raise vitamin D.

“Correlation does not necessarily mean a cause-and-effect relationship,” said Dr. JoAnn E. Manson, a Harvard professor who is chief of preventive medicine at Brigham and Women’s Hospital in Boston.

“People may have high vitamin D levels because they exercise a lot and are getting ultraviolet-light exposure from exercising outdoors,” Dr. Manson said. “Or they may have high vitamin D because they are health-conscious and take supplements. But they also have a healthy diet, don’t smoke and do a lot of the other things that keep you healthy.”

Dr. Manson is leading a major study over the next five years that should provide answers to these questions and more. The nationwide clinical trial is recruiting 20,000 older adults, including men 60 and older and women 65 and older, to study whether high doses of vitamin D and omega-3 fatty acids from fish-oil supplements will lower risk for heart disease and cancer. (Learn about taking part in the study at

Dr. Manson said fish-oil supplements were included in the study because they are another promising treatment that suffers from a dearth of clinical trial evidence. In addition, both vitamin D and fish oil are known to have an anti-inflammatory effect, but each works through a different pathway in the body, so there may be an added health benefit in combining them.

Study participants will be divided into four groups. One will take both vitamin D and fish oil pills. Two will take either a vitamin D or a fish-oil supplement and a placebo. The fourth will take two placebo pills.

Vitamin D is found throughout the body and acts as a signaling mechanism to turn cells on and off. Right now, the recommended dose from food and supplements is about 400 international units a day for most people, but most experts agree that is probably too low. The Institute of Medicine is reviewing guidelines for vitamin D and is expected to raise the recommended daily dose.

Study participants will take 2,000 I.U.’s of vitamin D3, believed to be the form most easily used by the body. The study will use one-gram supplements of omega-3 fish oil, about 5 to 10 times the average daily intake.

The vitamin D dose is far higher than what has been used in other studies. The well-known Women’s Health Initiative study, for instance, tracked women taking 400 units of vitamin D and 1,000 milligrams of calcium. The study found no overall benefit from the supplements, although women who consistently took their pills had a lower risk of hip fracture. Even so, many experts think 400 units is far too low for any additional health benefits.

Another study, of 1,200 women, looked at the effects of 1,500 milligrams of calcium and 1,000 units of vitamin D. Women who took both supplements showed a lower risk for breast cancer over the next four years, but the numbers of actual cases — seven breast cancers in the placebo group and four in the supplement group — were too small to draw meaningful conclusions.

Although consumers may be tempted to rush out and start taking 2,000 I.U.’s of vitamin D a day, doctors warn against it. Several recent studies of nutrients, including vitamins E and B, selenium and beta carotene, have proved disappointing — even suggesting that high doses do more harm than good, increasing risk for heart problems, diabetes and cancer, depending on the supplement.

Despite the promise of vitamin D in observational studies, research into other supplements shows it’s difficult to document a benefit in otherwise healthy people, and virtually impossible to predict potential harms, notes Dr. Eric A. Klein, chairman of the Glickman Urological and Kidney Institute at the Cleveland Clinic. Dr. Klein recently worked as national coordinator for Select, a study of vitamin E and selenium for prostate cancer. The study seemed promising, but in the end it showed no benefit from the supplements and a potentially higher risk for diabetes in selenium users.

“My sentiment is that the lesson we have learned form large trials with other vitamin supplements, including Select, is that there is no proven health or preventative benefit for dietary supplements in nutritionally replete populations, which accounts for most of the people who enter this sort of clinical trial,” Dr. Klein said. “It makes more sense to me to study dietary supplements or vitamins in populations who are deficient.”

People most at risk for vitamin D deficiency are older, have diabetes or kidney disease, stay indoors or have darker skin. African-American teenagers are at particularly high risk, possibly because in addition to their dark skin, they are less likely at that stage in life to drink milk or play outside.

The scientific community continues to debate the optimum level of vitamin D. In general, people are considered to be deficient if they have blood levels below 15 or 20 nanograms per milliliter. But many doctors now believe vitamin D levels should be above 30. The ideal level isn’t known, nor is it known at what point a person is getting too much vitamin D, which can lead to kidney stones, calcification in blood vessels and other problems.

People’s vitamin D levels are influenced by whether they have light or dark skin, where they live, how much time they spend outdoors and by fish and milk consumption. To raise vitamin D without supplements, a person could increase sun exposure for 10 to 15 minutes a day. Eating more fish can help — a 3.5-ounce serving of wild fresh salmon has 600 to 1,000 I.U.’s of vitamin D — but it would take a quart of milk a day to get the recommended dose of vitamin D.

“What we know is that there are a lot of people who are vitamin D deficient based on estimates from national surveys,” said Dr. Michal L. Melamed, assistant professor of medicine at Albert Einstein College of Medicine in the Bronx. “But we don’t know what happens when the curve shifts to the other end. There probably is a risk to having too much vitamin D in the system.”

And see

The Roles of Vitamin D Binding Protein in Human Immune Function[xix]

Sunday, January 24th, 2010 at 5:47 pm


The recent proliferation of published studies outlining the role of vitamin D in the prevention of many diseases associated with a weakened immune system has brought to light the importance of monitoring the serum levels of 25(OH) vitamin D. (1)  Specifically, the direct correlation of vitamin D levels in the human serum with increased levels of cathelicidin and the potentiating role cathelicidin plays in the immune response to infections, cancer, autoimmune disease, and especially acute viral infections. (2)  While research into vitamin D needs to continue, the importance of vitamin D binding protein (VDBP) has been demonstrated to have synergistic yet independent functions in the human immune system.(3)  This article will outline the emerging role of VDBP in the field of immunology.


A review of the scientific literature pertaining to vitamin D binding protein and its derivatives identified in human serum and produced in the laboratory.


Vitamin D binding protein, also known as Gc-protein, is a group of isoform proteins with O-linked glycans.  The dominant isoform of VDBP are non-glycosylated 656 Da proteins produced mainly in the liver.(4)  Vitamin D binding protein participates in liver cell stability and regeneration through Calcium dependent interaction with the megalin/gp330 receptor.(5)  There are 4 important roles VDBP has in humans.  It binds circulating vitamin D for transport and storage, it is the most important scavenger of extracellular G-actin, it enhances the chemotactic activity of C5a for neutrophils in inflammation, and it activates macrophages thru GaINAc-modified Gc-protein. (6)  Additionally, low levels of VDBP have been found to correlate with multiple organ failure sepsis, and non-survival in fulminant liver failure and traumatic liver failure.(7)  The non-glycosylated isoform of VDBP is able to mask the presence of endotoxins by 20%.(7)  Therapy with VDBP may increase survival in trauma, sepsis and fulminant liver failure.(7)

The function of VDBP is independent of the hormone actions of 1,25(2OH) vitamin D and it has limited impact on the extracellular pool of 1,25(OH) vitamin D.(8)  Vitamin D binding protein has virtually no impact on the distribution, uptake, activation profile, or biological potency of the hormone vitamin D.(8)  Vitamin D binding protein is not affected by race or adiposity the way vitamin D levels are affected.(9)  The serum levels of VDBP are decreased by trauma, septic infections, and chronic or acute liver diseases.(10)  The normal levels of serum VDBP are 350-50 mg/L and low levels below 80 mg/L yield a positive and negative mortality predictive value 85% and 43% respectively.(11)

While vitamin D binding protein is a primary macrophage activating factor, several glycosylated isoforms have more potent and specific macrophage activating properties.(12)  The most potent serum macrophage activation factor (MAF) is produced by a series of glycosylation reactions performed by the B-cells and T-cells.(13)  Vitamin D-MAF as a potent adjuvant activity for immunization and healthy serum levels of MAF prevent tumours from being able to transplant into mice.(14)  Other roles for VDBP derived MAF have been described, including an anti-angiogenesis function through blocking VEGF-induced angiogenesis.(15)

Laboratory derived MAF from serum VDBP has the advantage of activating macrophages and not being deglycosylated by N-acetylgalactosaminidase enzymes (NaGaLase) produced by cancer cells and infectious bacteria, viruses and fungi.(16)  The clinical dose required to have a sustained systemic activation of macrophages in 100 mcg injected weekly.(16)  A novel MAF (Gc-MAF) can be produced in the lab with cancer specific activity that targets undifferentiated cancer cells better than well differentiated cancer cells.(17)  Several prospective clinical trials of treatment of cancer and HIV with Gc-MAF have been reported and three trials with metastatic colon, breast and prostate cancer have provided 100% remission rate beyond the five years since Gc-MAF treatment.(16)(17)(18)


The scientific and clinical experience with VDBP and Gc-MAF are very encouraging.  Several clinical trials are underway in the Bahamas at the Immune Augmentation Therapy Centre to reproduce and confirm the current clinic studies, as well as to answer several clinical questions that have not yet been reported in the scientific literature about VDBP and Gc-MAF.  If you would like to enrol any clients with cancer or immune suppression in a trial with Gc-MAF, please contact the author of this review.


  1. Bikie DD, “Vitamin D and immune function: understanding common pathways” Curr Osteoporos Rep. 2009 Jul;7(2):58-63
  2. Yuk JM, Shin DM, Lee HM, Yang CS, Jin HS, Kim KK, Lee SH, Kim JM, Jo EK, “Vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin” Cell Host Microbe. 2009 Sep 17;6(3):231-43
  3. Chkri M et al, “Production of human macrophages with potent antitumoral properties (MAK) by culture of monocytes in the presence of GM-CSF and 1,25-dihydroxy vitamin D3.” Anticancer Res. 1992 Nov-Dec;12(6B):2257-60
  4. Christiansen M et al, “Protein chemical characterization of Gc-gobulin (vitamin D-binding protein) isoforms; Gc-f1, Gc-s, and Gc-2.” Biochem Biophys Acta. 2007 Apr; 1774(4):481-92
  5. Gressner OA et al, “Gc-globulin (vitamin D binding protein) is synthesized and secreted by hepatocytes and internalized by hepatic stellate cells through Ca2+ dependent interaction with megalin/gp330 receptor.” Clinica ChimiceActa 2008 Apr 390;1-2:28-37
  6. Nagasawa H et al, “Gc-protein (vitamin D-binding protein): Gc genotyping and GcMAF precursor activity.” Anticancer Res. 2005 Nov-Dec; 25(6A):3689-95
  7. Jorgensen CS et al, “Large-scale purification and characterization of non-glycosylated Gc-protein (vitamin D binding protein) from plasma fraction IV.” Biotechnol Appl Biochem. 2006 Apr;44(pt1):35-44
  8. Zella LA et al, “Vitamin D-binding protein influences total circulating levels of 1,25-dihydroxyvitamin D3 but does not directly modulate the bioactive levels of the hormone in vivo.” Endocrinology. 2008 Jul;149(7):3656-67
  9. Winters SJ et al, “Influence of obesity on vitamin D-binding protein and 25-hydroxy vitamin D levels in African and white women.” Metabolism. 2009 Apr;58(4):438-42
  10. Schiodt FV et al, “Increased turnover of Gc-protein in patients with hepatic encephalopathy.” Scand J Gastroenterol. 2001 Sep;36(9):998-1003
  11. Schiodt FV et al, “Gc-globulin and prognosis in acute liver failure.” Liver Transpl. 2005 Oct;11(10):1223-7
  12. Homma S et al, “Vitamin D-binding protein (group-specific component) is the sole serum protein required for macrophage activation after treatment of peritoneal cells with lyso-phosphatidylcholine.” Immunol Cel Biol. 1993 Aug;71(pt4):249-57
  13. Yamamoto N et al, “Conversion of vitamin D3 binding protein (group-specific component) to a macrophage activating factor by stepwise action of beta-galactosidase of B-celss and sialidase of T-cells.” J Immunol. 1993 Sep 1;151(5):2794-802
  14. Yamamoto N et al, “Structurally well-defined macrophage activating factor derived from vitamin D3-binding protein has a potent adjuvant activity for immunization.” Immunol Cell Biol. 1998 Ju;76(3):237-44
  15. Kallunte S et al, “Inhibition of angiogenesis by vitamin D-binding protein: characterization of anti-endothelial activity of DBP-MAF.”  Angiogenesis. 2005;8(4):349-60
  16. Yamamoto N et al, “Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein derived macrophage activating factor, Gc-MAF.” Cancer Immunol Immunotherapy 2008;57:1007-16
  17. Yamamoto N et al, “Immunotherapy of metastatic breast cancer patients with vitamin D-bindng protein-derived macrophage activating factor (GcMAF).” Int J Cancer. 2008;122:461-467
  18. Yamamoto N, Suyama H, Yamamoto N “Immunotherapy for prostate cancer with Gc protein-derived macrophage activating factor, GcMAF.” Transl Oncol.2008 Jul;1(2):65-72

Kevin Paul Bethel MD CM FAARM is the Research Director for the Immune Augmentation Therapy Centre (Freeport Bahamas), the Regenerative Medicine Consultant at Renaissance Medical Centre (Nassau Bahamas), and Medical Director for the Freeport Family Wellness Centre (Freeport Bahamas). Contact information:, PO Box F42689, Freeport, GBI, Bahamas. 1-242-352-7455

Article Source:

Re: [CAFE] More on Vit D & cancer‏

From: Peter Granger (pete.granger@GMAIL.COM)

Sent: 26 January 2010 02:08:07

A weakened immune response contributes to the development of
infections, cancer, autoimmune disease, and acute viral infections. A
vitamin D deficiency (in fact, reduced levels of vitamin D binding
protein (VDBP) and its derivatives such as macrophage activation
factor (MAF) contribute to a weakened immune response by lowering
cathelicidin levels.

MAF has various anti-tumor effects, including as an angiogenesis
inhibitor (hindering metastasis by preventing cancer cells forming
their own blood supply).

Cancer cells, bacteria, viruses and fungi are able to block MAP. This
unfortunately leads to harmful immunosuppression – which is also
cyclical in nature. However, not so MAF developed in the laboratory,
and injected in patients at about 100 mcg/weekly for 30-50 weeks. In
trials, these injections have proved very effective in treating
metastatic cancer and HIV.

There has been 5 year, 100% remission in three trials with metastatic
colon, breast and prostate cancer following such treatment.

Several clinical trials are underway in the Bahamas at the Immune
Augmentation Therapy Centre. Clearly, it is a very promising
treatment, especially in metastatic cancer. However, the trials are
not being held at a major cancer centre. The question is, why? The
treatment has been patented by a Japanese/American researchers
(Yamamoto, Division of Cancer Immunology and Molecular Immunology,
Socrates Institute for Therapeutic Immunology, Philadelphia) which may account for its current lack of acceptance. Presumably, the treatment is also quite expensive.
In the interim, maintaining high serum levels of vitamin D may be
beneficial in protecting against viral infections and cancer.
Other immune boosting techniques include low-dose naltrexone,
melatonin, zinc, curcumin (which is also anti-inflammatory, but works
via a different pathway), vitamin K, probiotics, omega 3, calorie
restriction, green tea, oats, garlic, mushrooms, taurine, and Coley’s


The Anticancer Effects Of Vitamin D3[xx]

ScienceDaily (July 7, 2009) — The active form of vitamin D3 seems to have anticancer effects. To try and understand the mechanisms underlying these effects, researchers previously set out to identify genes whose expression in a human colon cancer cell line was altered by the active form of vitamin D3.

One gene identified in this previous study was CST5, which is responsible for making the protein cystatin D. Now, a team of researchers, at the Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Spain, and the Universidad de Oviedo, Spain, has studied this protein in detail and determined that it has tumor suppressor activity that likely accounts for some of the anticancer effects of the active form of vitamin D3.

The team, led by Alberto Muñoz and Carlos López-Otín, initially established that the active form of vitamin D3 directly activates the CST5 gene in human colon cancer cell lines, increasing levels of cystatin D protein. Functionally, cystatin D was shown to inhibit the growth of human colon cancer cells lines in vitro and when they were xenotransplanted into mice. As knocking down expression of cystatin D in human colon cancer cell lines rendered them unresponsive to the antiproliferative effects of the active form of vitamin D3, the authors conclude that CST5 is a candidate tumor suppressor gene and that it mediates a large proportion of the anticancer effects of the active form of vitamin D3. These data provide rationale for clinical trials examining the preventive and therapeutic potential of the active form of vitamin D3 in colon cancer.

Vitamin D Levels Associated With Survival in Lymphoma Patients[xxi]

ScienceDaily (Dec. 9, 2009) — A new study has found that the amount of vitamin D in patients being treated for diffuse large B-cell lymphoma was strongly associated with cancer progression and overall survival. The results will be presented at the annual meeting of the American Society of Hematology in New Orleans.

“These are some of the strongest findings yet between vitamin D and cancer outcome,” says the study’s lead investigator, Matthew Drake, M.D., Ph.D., an endocrinologist at Mayo Clinic in Rochester. “While these findings are very provocative, they are preliminary and need to be validated in other studies. However, they raise the issue of whether vitamin D supplementation might aid in treatment for this malignancy, and thus should stimulate much more research.”

The researchers’ study of 374 newly diagnosed diffuse large B-cell lymphoma patients found that 50 percent had deficient vitamin D levels based on the commonly used clinical value of total serum 25(OH)D less than 25 ng/mL. Patients with deficient vitamin D levels had a 1.5-fold greater risk of disease progression and a twofold greater risk of dying, compared to patients with optimal vitamin D levels after accounting for other patient factors associated with worse outcomes.

The study was conducted by a team of researchers from Mayo Clinic and the University of Iowa. These researchers participate in the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE), which is funded by the National Cancer Institute. The 374 patients were enrolled in an epidemiologic study designed to identify predictors of outcomes in lymphoma. Since this was not a clinical trial, patient management and treatments were not assigned, but rather followed standard of care for clinical practice.

The findings support the growing association between vitamin D and cancer risk and outcomes, and suggest that vitamin D supplements might help even those patients already diagnosed with some forms of cancer, says Dr. Drake. “The exact roles that vitamin D might play in the initiation or progression of cancer is unknown, but we do know that the vitamin plays a role in regulation of cell growth and death, among other processes important in limiting cancer,” he says.

The findings also reinforce research in other fields that suggest vitamin D is important to general health, Dr. Drake says. “It is fairly easy to maintain vitamin D levels through inexpensive daily supplements or 15 minutes in the sun three times a week in the summer, so that levels can be stored inside body fat,” he says. Many physicians recommend 800-1,200 International Units (IU) daily, he adds.

Vitamin D is a steroid hormone obtained from sunlight and converted by the skin into its active form. It also can come from food (naturally or fortified as in milk) or from supplements. It is known best for its role of increasing the flow of calcium into the blood. Because of that role, vitamin D deficiency has long been known to be a major risk factor for bone loss and bone fractures, particularly in elderly people whose skin is less efficient at converting sunlight into vitamin D. But recent research has found that many people suffer from the deficiency, and investigators are actively looking at whether low vitamin D promotes poorer health in general.

Cancer researchers have discovered that vitamin D regulates a number of genes in various cancers, including prostate, colon and breast cancers. Recent studies have suggested that vitamin D deficiency may play a role in causing certain cancers as well as impacting the outcome once someone is diagnosed with cancer.

Researchers looked at vitamin D levels in lymphoma patients because of the observation, culled from U.S. mortality maps issued by the National Cancer Institute, that both incidence and mortality rates of this cancer increase the farther north a person lives in the United States, where sunlight is limited in the winter. Also, several recent reports have concluded that vitamin D deficiency is associated with poor outcomes in other cancers, including breast, colon and head and neck cancer. This is the first study to look at lymphoma outcome.

The study was funded by the National Cancer Institute and the Mayo Hematologic Malignancies Lymphoma Fund.

Meta-analysis of longitudinal studies: Serum vitamin D and prostate cancer risk[xxii]

Aim: To review and summarize evidence from longitudinal studies on the association between serum 25-hydroxyvitamin D (25(OH)D) and the risk of prostate cancer (PC). Methods: Relevant prospective cohort studies and nested case-control studies published until July 2009 were identified by systematically searching Ovid Medline, EMBASE, and ISI Web of Knowledge databases and by cross-referencing. The following data were extracted in a standardized manner from eligible studies: first author, publication year, country, study design, characteristics of the study population, duration of follow-up, PC incidence/PC mortality according to serum vitamin D status and the respective risk ratios, and covariates adjusted for in the analysis. Due to the heterogeneity of studies in categorizing serum vitamin D levels, all results were recalculated for an increase in serum 25(OH)D by 10ng/ml. Summary odds ratios (ORs) were calculated using meta-analysis methods. Results: Overall, eleven original articles were included, ten of which reported on the association between serum vitamin D levels and PC incidence and one article reported on the association with PC mortality. Meta-analysis of studies on PC incidence resulted in a summary OR (95% confidence interval, CI) of 1.03 (0.96–1.11) associated with an increase of 25(OH)D by 10ng/ml (P=0.362). No indication for heterogeneity and publication bias was found.

Conclusions: According to available evidence from longitudinal studies, serum 25(OH)D is not associated with PC incidence.

Does Vitamin D Treat Cancer?[xxiii]

As you may remember, the last newsletter was on preventing cancer, not treating it. Below is a small sampling of some of the questions contained in the tragic emails generated by last month’s newsletter:

Dr. Cannell, I was just diagnosed with breast cancer. How much vitamin D should I take?

My mother has colon cancer, how much vitamin D should she take?

I’ve had prostate cancer for four years, is there any reason to think vitamin D would help?

Dr. Cannell, my son has leukemia, should I give him vitamin D?

It’s not that simple…

It’s one thing to talk about evidence that vitamin D may prevent cancer but something quite different to discuss evidence that vitamin D might help treat cancer. I used to think the answers to all the above questions were the same. Like anyone else, people with cancer should be screened for vitamin D deficiency and be treated if deficiency is present. Simple. However, it’s not that simple. The real questions are:

  • What are reasonable 25-hydroxy-vitamin D [25(OH)D] levels for someone with a life-threatening cancer?
  • How much vitamin D do they need to take to obtain such levels?
  • Is there any evidence, of any kind, that vitamin D will help treat cancer?

The risk/benefit analysis of taking vitamin D is quite different if you are in perfect health than if your life, or your child’s life, is on the line.

Remember, unlike cancer prevention, not one human randomized controlled trial exists showing vitamin D has a treatment effect on cancer. By treatment effect, I mean prolongs the lives of cancer patients. However, as I cited in my last newsletter, Dr. Philippe Autier of the International Agency for Research on Cancer, and Dr. Sara Gandini of the European Institute of Oncology, performed a meta-analysis of 14 randomized controlled trials showing even low doses of vitamin D extend life but they looked at all-cause mortality, not just cancer. Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med. 2007;167(16):1730–1737.

Summer diagnosis prolongs life. Why?

However, some epidemiological studies indirectly address the treatment issue and are quite remarkable. The first are a series of discoveries by Professor Johan Moan, Department of Physics at the University of Oslo, with Dr. Alina Porojnicu as the lead author on most of the papers. Moan J, et al. Colon cancer: Prognosis for different latitudes, age groups and seasons in Norway. J Photochem Photobiol B. 2007 Sep 19. Lagunova Z, et al. Prostate cancer survival is dependent on season of diagnosis. Prostate. 2007 Sep 1;67(12):1362–70. Porojnicu AC, et al. Changes in risk of death from breast cancer with season and latitude: sun exposure and breast cancer survival in Norway. Breast Cancer Res Treat. 2007 May;102(3):323–8. Porojnicu AC, et al. Season of diagnosis is a predictor of cancer survival. Sun-induced vitamin D may be involved: a possible role of sun-induced Vitamin D. J Steroid Biochem Mol Biol. 2007 Mar;103(3–5):675–8. Porojnicu AC, et al. Season of diagnosis is a prognostic factor in Hodgkin’s lymphoma: a possible role of sun-induced vitamin D. Br J Cancer. 2005 Sep 5;93(5):571–4. Porojnicu AC, et al. Seasonal and geographical variations in lung cancer prognosis in Norway. Does Vitamin D from the sun play a role? Lung Cancer. 2007 Mar;55(3):263–70.

What Professor Moan’s group repeatedly discovered is quite simple—whether it be cancer of the breast, colon, prostate, lung, or a lymphoma: You live longer if your cancer is diagnosed in the summer. And it is not just Moan’s group who has found this. A huge English study recently confirmed Moan’s discovery. Lim HS, et al. Cancer survival is dependent on season of diagnosis and sunlight exposure. Int J Cancer. 2006 Oct 1;119(7):1530–6.

What do these studies mean? Something about summer has a treatment effect on cancer. Whatever it is, you live longer if you are diagnosed in the summer but die sooner if you are diagnosed in the winter. What could it be about summer? Exercise? Fresh air? Melatonin? Sunlight? Pretty girls? Remember, these patients already had cancer. Whatever it is about summer, it is not a preventative effect that Professor Moan discovered, it is a treatment effect. Something about summer prolongs the life of cancer patients.

Sunlight’s robust treatment effect

Dr. Ying Zhou, a research fellow, working with Professor David Christiani at the Harvard School of Public Health, went one step further. The stuffy Harvard researchers assumed summer worked its magic, not by pretty girls, but by summer sunlight making vitamin D. So they looked at total vitamin D input, from both sun and diet, to see if high vitamin D intake improved the survival of cancer patients. Yes, indeed, remarkably. They found that early stage lung cancer patients with the highest vitamin D input (from summer season and high intake from diet) lived almost three times longer than patients with the lowest input (winter season and low intake from diet). Three times longer is a huge treatment effect, a treatment effect that most conventional cancer treatment methods would die for. Zhou W. Vitamin D is associated with improved survival in early-stage non-small cell lung cancer patients. Cancer Epidemiol Biomarkers Prev. 2005 Oct;14(10):2303–9.

And that’s not all, Marianne Berwick and her colleagues, at the New Mexico Cancer Institute, found malignant melanoma patients with evidence of continued sun exposure had a 60% mortality reduction compared to patients who did not. That implies a robust treatment effect from sunlight. Berwick M, et al. Sun exposure and mortality from melanoma. J Natl Cancer Inst. 2005 Feb 2;97(3):195–9.

I will not list the thousands of animal studies that indicate vitamin D has a treatment effect on cancer as almost all of them studied activated vitamin D or its analogs—drugs that bypass normal regulatory mechanisms, cannot get autocrine quantities of the hormone into the cell, and that often cause hypercalcemia. However, Michael Holick’s group found that simple vitamin D deficiency made cancers grow faster in mice. That is, vitamin D has a cancer treatment effect in vitamin D-deficient mice. Professor Gary Schwartz, at Wake Forest, recently reviewed the reasons to think that vitamin D may have a treatment effect in cancer. Tangpricha V, et al. Vitamin D deficiency enhances the growth of MC-26 colon cancer xenografts in Balb/c mice. J Nutr. 2005 Oct;135(10):2350–4. Schwartz GG, Skinner HG. Vitamin D status and cancer: new insights. Curr Opin Clin Nutr Metab Care. 2007 Jan;10(1):6–11.

Finally, one human interventional study exists. In 2005, in an open trial, Professor Reinhold Vieth and his colleagues found just 2,000 IU of vitamin D per day had a positive effect on PSA levels in men with prostate cancer. Woo TC, et al. Pilot study: potential role of vitamin D (Cholecalciferol) in patients with PSA relapse after definitive therapy. Nutr Cancer. 2005;51(1):32–6.

So, how much vitamin D does one need?

So we come back to the crucial question. If you have cancer, how much vitamin D should you take, or, more precisely, what 25(OH)D level should you maintain? We don’t know. You can correctly say that definitive studies have not been done and incorrectly conclude physicians treating cancer patients should do nothing. I say incorrectly because standards of medical practice have always demanded that doctors make reasonable decisions as to what is best for their patients based on what is currently known—what is called a risk/benefit analysis. If a patient has a potentially fatal cancer, the doctor cannot dismiss a relatively benign potential treatment modality just because definitive studies have not been done, passively watching his or her patient die. Standards of care require doctors perform a risk/benefit analysis and then act in the best interest of their patient.

Luckily, such doctors recently obtained some guidance. In the first study of its kind, Professor Bruce Hollis of the Medical University of South Carolina gave all of us something to think about. He asked and answered a simple question: How much vitamin D do you have to take to normalize the metabolism of vitamin D?

Vitamin D’s unique behavior

Remember, unlike other steroid hormones, vitamin D has very unusual metabolism in most modern humans, called first-order, mass-action kinetics. What this means is that the more vitamin D you take, the higher the 25(OH)D level in your blood and the higher the 25(OH)D level in your blood, the higher the levels of activated vitamin D in your tissues. No other steroid hormone in the body behaves like this. Think about it, would you like your estrogen level to be dependent on how much cholesterol you ate? Or your cortisol level? (I’d ask the same about testosterone levels but I know men well enough not to ask.) No, the body must tightly regulate powerful steroid hormones through substrate inhibition, that is, if an enzyme turns A into B, when the body has enough B, B inhibits the enzyme and so limits its own production.

Not so with vitamin D, at least at modern, human vitamin D levels. Professor Reinhold Vieth was the first to write about this and Vieth’s Chapter 61 in Feldman, Pike, and Glorieux’s wonderful textbook, entitled Vitamin D (Elsevier, 2005, second edition), is a great reason to buy the textbook or have your library do so. I’m glad to see Amazon is out of stock of the new ones—someone must be reading about vitamin D!—but you can still buy used editions.

Why would the kinetics of vitamin D be different from all other steroids? Maybe they are not, Hollis reasoned like Vieth before him. Maybe vitamin D levels are so low in modern humans that its metabolic system is on full blast all the time in an attempt to give the body all the vitamin D metabolites it craves. So Hollis asked, Is vitamin D’s metabolism different in populations in the upper end of 25(OH)D levels (a population of sun-exposed people and a group of women prescribed 7,000 IU per day)? Note: the entire Hollis study is free to download on Medline. Hollis BW, et al. Circulating vitamin D3 and 25-hydroxyvitamin D in humans: An important tool to define adequate nutritional vitamin D status. J Steroid Biochem Mol Biol. 2007 Mar;103(3–5):631–4.

If you look at the two graphs (Figures 1 and 2) of Hollis’ paper, you find vitamin D’s kinetics can be normalized, made just like all other steroid hormones in the body, but you have to get enough sunshine or take enough vitamin D to get your 25(OH)D level above 50 ng/mL—60 ng/mL would be even better. Then your body would start to store cholecalciferol without much further increase in 25(OH)D levels. The reaction becomes saturable. This is a remarkable discovery and it implies levels of 30 and 40 ng/mL are usually not sufficient. It also implies actual vitamin D levels (cholecalciferol levels), not just 25(OH)D levels, may be useful in diagnosing and treating deficiency. Note, that not all of the sun-exposed individuals or women prescribed 7,000 IU/day achieved such levels. That’s because the sun-exposed individuals were tested after an Hawaiian winter and because prescribing and taking are two different things.

25(OH)D level should be greater than 60 ng/mL

So my answer to “How much should I take if I have cancer?” is “Take enough to get your 25(OH)D level above 60 ng/mL, summer and winter.” In doing so, you will have normalized the kinetics of vitamin D and stored the parent compound, cholecalciferol, in your tissues. In the absence of sunshine, you need to take at least 5,000 IU/day to do this. And this may not be enough; cancer patients may use it up faster (increased metabolic clearance) and children may do the same due to their young and vital enzymes. Or you may need less, because you get more sun than you think, more from your diet, or because you are taking a modern medicine that interferes with the metabolism of vitamin D. An even easier way to do it is go to a sun tanning booth every day and obtain and keep a dark, full-body, tan. Then you don’t have to worry about blood levels but I’d get one anyway, just to be sure it was above 60 ng/mL.

Given what Hollis discovered, given the well-known potent anti-cancer properties of activated vitamin D, given epidemiological evidence that summer extends the life of cancer patients, given a meta-analysis of randomized controlled trials showed that vitamin D prolongs life, given animal data that simple vitamin D has a treatment effect on cancer, and given a patient with a life-threatening cancer, what would a reasonable physician do? Simply let their patient die while muttering something about the lack of randomized controlled trials?

No, they would simply check 25(OH)D levels every month and advise cancer patients to take enough vitamin D or to frequent sun tanning parlors enough to keep their level above 60 ng/mL. Toxicity does not start until levels reach 150 ng/mL but if you take more than 5,000 IU per day have your doctor order a blood calcium every month or two, along with the 25(OH)D. Both you and he will feel better and because, if you have cancer, you are probably taking lots of other drugs and little is known about how modern drugs interact with vitamin D metabolism. By getting your level above 60 ng/mL, all you are doing is getting your level to where most lifeguards’ levels are at the end of summer, to levels our ancestors had when they lived in the sun, to levels regular users of sun-tan parlors levels achieve, and most importantly, to levels where vitamin D’s pharmacokinetics are normalized.

Little to no risk

In the end, if you have cancer and your physician won’t do a risk/benefit analysis, do it yourself. The risk side of that equation is easy. Both Quest Diagnostics and Lab-Corp, the two largest reference labs in the United States, report the upper limit of 25(OH)D normal is 100 ng/mL and toxic is above 150 ng/mL, so 60 ng/mL is well below both. The reason levels up to 100 ng/mL are published normals is because there is no credible evidence in the literature that levels of 100 ng/mL do any harm and because sun worshipers often have such levels. (If you don’t believe me, go to the beach in the summer for one month, sunbath every day for 30 minutes on each side in your bathing suit, and go home and have a 25(OH)D level.) By getting your level above 60 ng/mL, all you are doing is getting your levels into the mid to upper range of laboratory reference normals. Little or no risk.

What are the potential benefits? It probably depends on a number of things. Did your cancer cells retain the enzyme that activates vitamin D? Many do. Did your cancer cells retain the vitamin D receptor? Many do. If your cancer cells get more substrate [25(OH)D], will that substrate induce the cancer cells to make more vitamin D receptors or more of the activating enzyme? Some cancer cells do both. In practical terms, vitamin D is theoretically more likely to help your cancer the earlier you start taking it. However, no one knows. Certainly there is no reason, other than bad medicine, for cancer patients to die vitamin D deficient. Unfortunately, most do. Tangpricha V, et al. Prevalence of vitamin D deficiency in patients attending an outpatient cancer care clinic in Boston. Endocr Pract. 2004 May–Jun;10(3):292–3. Plant AS, Tisman G. Frequency of combined deficiencies of vitamin D and holotranscobalamin in cancer patients. Nutr Cancer. 2006;56(2):143–8.

It is very important that readers understand I am not suggesting vitamin D cures cancer or that it should replace standard cancer treatment. Oncologists perform miracles every day so one should do what they say. The only exception is vitamin D. If your oncologist tells you not to take vitamin D, ask him three questions.

  • How do you convert ng/mL to nmol/L?
  • How many IU in a nanogram (ng)?
  • How do you spell “cholecalciferol?”

If he doesn’t know how to measure it, weigh it, or spell it, chances are he doesn’t know much about it.

The real risk: waiting for further studies

All of the epidemiological and animal studies in the literature suggest cancer patients will prolong their lives if they take vitamin D. I can’t find any studies that indicate otherwise. However, none of the suggestive studies are randomized controlled interventional trials; they are all epidemiological or animal studies, or, in the case of Vieth’s, an open human study. However, if you have cancer, or your child does, do you want to wait the decades it will take for the American Cancer Society to fund randomized controlled trials using the proper dose of vitamin D? Chances are you, or your child, will not be around to see the results.

John Jacob Cannell MD Executive Director

Vitamin D Can Alter Colon Cancer Cells In Many Ways, Through One Pathway[xxiv]

ScienceDaily (Nov. 26, 2008) — A colon cancer cell isn’t a lost cause. Vitamin D can tame the rogue cell by adjusting everything from its gene expression to its cytoskeleton. In the Nov. 17 issue of the Journal of Cell Biology, Ordóñez-Morán et al. show that one pathway governs the vitamin’s diverse effects. The results help clarify the actions of a molecule that is undergoing clinical trials as a cancer therapy.

Vitamin D stymies colon cancer cells in two ways. It switches on genes such as the one that encodes E-cadherin, a component of the adherens junctions that anchor cells in epithelial layers. The vitamin also induces effects on the cytoskeleton that are required for gene regulation and short-circuiting the Wnt/b-catenin pathway, which is overactive in most colon tumors. The net result is to curb division and prod colon cancer cells to differentiate into epithelial cells that settle down instead of spreading.

To delve into the mechanism, the team dosed colon cancer cells with calcitriol, the metabolically active version of vitamin D. Calcitriol triggered a surge of calcium into the cells and the subsequent switching on of RhoA–RhoGTPases, which have been implicated in the cytoskeletal changes induced by vitamin D. The activated RhoA in turn switched on one of its targets, the rho-associated coiled kinase (ROCK), which then roused two other kinases. Each step in this nongenomic pathway was necessary to spur the genomic responses, the researchers showed. The team also nailed down the contribution of the vitamin D receptor (VDR). The receptor was crucial at the beginning of the pathway, where it permitted the calcium influx, and at the end, where it activated and repressed genes.

The study is the first to show that vitamin D’s genomic and nongenomic effects integrate to regulate cell physiology. One question the researchers now want to pursue is whether VDR from different locations—the nucleus, the cytosol, and possibly the cell membrane—has different functions in the pathway.

Reference: Ordóñez-Morán, P., et al. 2008. J. Cell Biol. doi:10.1083/jcb.200803020.

Macrophage Activation May Suppress Breast Cancer Metastasis[xxv]

By David Douglas

NEW YORK FEB 20, 2008 (Reuters Health) – Vitamin D-binding protein-derived macrophage activating factor (Gc-MAF) appears to be an effective immunotherapeutic agent in patients with metastatic breast cancer, according to US and Japanese researchers.

“Serum vitamin D-binding protein – known as Gc protein – is the precursor of the principal macrophage activating factor,” lead investigator Dr. Nobuto Yamamoto told Reuters Health.

“Treatment of purified Gc protein with beta-galactosidase and sialidase generates Gc-MAF,” he added, “the most potent macrophage activating factor ever discovered, which produces no side effect in humans.”

Dr. Yamamoto of the Socrates Institute for Therapeutic Immunology, Philadelphia and colleagues note that in vitro studies show that macrophages treated with Gc-MAF have a highly tumoricidal effect in mammary adenocarcinomas.

To investigate whether the approach can be effective in humans, the researchers studied 16 non-anemic breast cancer patients who were given “a minute amount – 100 nanograms per week – of Gc-MAF,” Dr. Yamamoto said.

The researchers found that after 16 to 22 Gc-MAF doses, initially elevated nagalase levels, which reflect the tumor burden, fell to those found in healthy controls. Follow-up over 4 years showed that the level remained low and that there was no tumor recurrence, they report in the January 15th issue of The International Journal of Cancer.

The findings, the team concludes, clearly demonstrate “the importance of focusing cancer immunotherapy on macrophage activation.”

International Journal Cancer. 2008 Jan 15; 122(2):461-7.

Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophage-activating factor, Gc-MAF

Nobuto Yamamoto, Hirofumi Suyama, Hiroaki Nakazato, Nobuyuki Yamamoto and Yoshihiko Koga

Abstract: Serum vitamin D binding protein (Gc protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of colorectal cancer patients was lost or reduced because Gc protein is deglycosylated by serum α-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Deglycosylated Gc protein cannot be converted to MAF, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized β-galactosidase and sialidase generated the most potent macrophage-activating factor (Gc-MAF) ever discovered, but it produces no side effect in humans. Macrophages treated with Gc-MAF (100 pg/ml) develop an enormous variation of receptors and are highly tumoricidal to a variety of cancers indiscriminately. Administration of 100 nanogram (ng)/human maximally activates systemic macrophages that can kill cancerous cells. Since the half-life of the activated macrophages is approximately 6 days, 100 ng Gc-MAF was administered weekly to eight nonanemic colorectal cancer patients who had previously received tumor-resection but still carried significant amounts of metastatic tumor cells. As Gc-MAF therapy progressed, the MAF precursor activities of all patients increased and conversely their serum Nagalase activities decreased. Since serum Nagalase is proportional to tumor burden, serum Nagalase activity was used as a prognostic index for time course analysis of Gc-MAF therapy. After 32–50 weekly administrations of 100 ng Gc-MAF, all colorectal cancer patients exhibited healthy control levels of the serum Nagalase activity, indicating eradication of metastatic tumor cells. During 7 years after the completion of Gc-MAF therapy, their serum Nagalase activity did not increase, indicating no recurrence of cancer, which was also supported by the annual CT scans of these patients.

May 22, 2008

Colon cancer: prognosis for different latitudes, age groups and seasons in Norway.[xxvi]

Moan J, Porojnicu A, Lagunova Z, Berg JP, Dahlback A.

Department of Radiation Biology, Institute for Cancer Research, Montebello, 0310 Oslo, Norway.

The survival of colon cancer patients in Norway, as determined three years after diagnosis, is dependent on the season of diagnosis. This has been attributed to seasonal variations of the vitamin D status. Since solar radiation and food are the human sources of vitamin D, we divided Norway in three regions: The southeast region with a high annual dose of ultraviolet (UV) to the population, as evidenced by a high incidence rate of squamous cell carcinoma of the skin (SCC), the midwest region and the north region with low annual UV doses. The latter region is characterized by a high consumption of vitamin D, mainly through fish intake. Vacations to southern latitudes were equally frequent for all the three geographical regions. Two age groups were analyzed separately (< or =65 years and >65 years), since the photosynthesis of vitamin D(3) in skin decreases with age. In all three regions, and in both age groups, the survival was highest for summer and autumn diagnosis. The seasonal effect was slightly, but not significantly, better for the younger than for the older age group. The effect was similar for all three geographical regions, irrespective of SCC incidence.

PMID: 18029190 [PubMed – indexed for MEDLINE]

Circulating Vitamin D3 and 25-hydroxyvitamin D in Humans: An Important Tool to Define Adequate Nutritional Vitamin D Status[xxvii]

Bruce W. Hollis, Carol L. Wagner, Mark K. Drezner, and Neil C. Binkley


Circulating 25-hydroxyvitamin D [25(OH)D] is generally considered the means by which we define nutritional vitamin D status. There is much debate, however, with respect to what a healthy minimum level of circulation 25(OH)D should be. Recent data using various biomarkers such as intact parathyroid hormone (PTH), intestinal calcium absorption, and skeletal density measurements suggest this minimum level to be 80 nmol (32 ng/mL). Surprisingly, the relationship between circulating vitamin D3 and its metabolic product—25(OH)D3 has not been studied. We investigated this relationship in two separate populations: the first, individuals from Hawaii who received significant sun exposure; the second, subjects from a lactation study who received up to 6,400 IU vitamin D3/day for six months.

Results: 1) The relationship between circulating vitamin D3 and 25(OH)D in both groups was not linear, but appeared saturable and controlled; 2) Optimal nutritional vitamin D status appeared to occur when molar ratios of circulating vitamin D3 and 25(OH)D exceeded 0.3; at this point, the Vmax of the 25-hydroxylase appeared to be achieved. This was achieved when circulating 25(OH)D exceeded 100 nmol.

We hypothesize that as humans live today, the 25-hydroxylase operates well below its Vmax because of chronic substrate deficiency, namely vitamin D3. When humans are sun (or dietary) replete, the vitamin D endocrine system will function in a fashion as do these other steroid synthetic pathways, not limited by substrate. Thus, the relationship between circulating vitamin D and 25(OH)D may represent what “normal” vitamin D status should be.

Keywords: vitamin D, 25-hydroxyvitamin D, nutritional vitamin D status


What is a normal circulating level of 25(OH)D that is sufficient to meet all physiological needs, not simply skeletal requirements in humans? In the past, this was addressed by simply sampling a diverse population of subjects who were asymptomatic for disease, measuring circulating 25(OH)D, and plotting the data using a Gaussian distribution. This approach yields normative data that are used to assess circulating 25(OH)D in that population. This is how Haddad and Chyu (1) performed their assessment of 25(OH)D status more than thirty-five years ago. They referred to their normal, asymptomatic volunteers as the normal population for circulating 25(OH)D levels. Their study also presented a group of lifeguards that had circulating 25(OH)D levels 2.5 times that of the “normals.” Countless similar studies have been performed during the ensuing decades, reiterating the same conclusion. We, however, interpret the original Haddad data differently: we suggest that the 25(OH)D levels in the sun-replete lifeguards are normal and the “normals” actually exhibit varying degrees of vitamin D deficiency.

How nutritional vitamin D deficiency is defined is a key to developing a coherent supplement policy that meets the needs of all humans. Recently, inadequate circulating 25(OH)D levels have been linked to biomarkers, including skeletal density (24), intestinal calcium absorption (5), secondary hyperparathyroidism (610), insulin secretion (11, 12), and innate immune response (13). These markers all are useful in identifying nutritional vitamin D deficiency; however, the link between 25(OH)D and vitamin D—when available at adequate concentration, remains unknown and could prove to be another important piece in understanding vitamin D metabolism. We sought to investigate this question of how 25(OH)D would respond if adequate substrate, namely vitamin D3, was always present. Thus, for this project, we studied two groups of subjects, one from a sun-rich environment and the other from a high-dose vitamin D3 supplementation study, the results of which are presented here.

Materials and Methods

Part 1. Study of Sun-Exposed Subjects

Approval for this study was granted by the University of Wisconsin Health Sciences Institutional Review Board for Human Subjects and the Committee on Human Studies at the University of Hawaii at Manoa. All subjects provided written informed consent prior to the conduct of any study procedure.


Skin surface exposed to the sun in these subjects varied from almost total in surfers to head, arms and hands in skateboarders. Ninety-three subjects (63 males/30 females) participated in the study.

Entrance Criteria

Subjects from a sun-rich climate were recruited from the University of Hawaii at Manoa, and from patrons of the A’ala Park Board shop, Honolulu, Hawaii (latitude 21°N), in late March 2005. In order to participate, volunteers had to have met the entrance criteria of the following: a self-reported sun exposure time of three or more hours per day on five or more days per week for at least the preceding three months. Those who met entrance criteria were enrolled in the study following written informed consent.

Study Protocol

  1. Blood was collected for serum 25(OH)D and vitamin D3 measurement when they were interviewed.
  2. All participants completed a non-validated, self-administered questionnaire, which included questions about sun exposure, sunscreen use, and dietary vitamin D intake.
  3. To document sun exposure, skin color was measured by reflectance colorimetry (IMS SmartProbe, Millford, CT). A measurement was taken on the back of the hand and the front of the distal thigh for the darkest measurement and under the arm and at the self-reported least sun-exposed area—often the breast or buttock, to determine the lightest or natural skin color. A previously developed sun exposure index (14), which utilizes the rule of nines was used to estimate the amount and duration of skin sun exposure.
  4. Circulating 25(OH)D was measured on all 93 subjects using an RIA as previously reported (15).
  5. Data Analysis: The 10 highest and 10 lowest circulating 25(OH)D levels were selected to determine circulating vitamin D3 levels using direct ultraviolet (UV) detection following high performance liquid chromatography as previously described (16). The data were plotted using a best-fit regression analysis with vitamin D3 serving as the independent variable.

Part II. Study of High Dose Vitamin D3 Supplemented Subjects

Approval for this study was granted by the Medical University of South Carolina’s (MUSC) Institutional Review Board for Human Subjects, HR #11345 and the General Clinical Research Center (GCRC; Protocol #694). Fully lactating mothers (17) within one month postpartum were eligible for inclusion in the study if they planned to continue full breastfeeding for the next six months. The subjects were randomly divided into two groups. Exclusion criteria included preexisting type I or type II diabetes, hypertension, parathyroid disease, and uncontrolled thyroid disease. Subjects were compensated for their participation with gift cards given at the end of each visit.

Study Design

Women in the high dose supplementation group of a larger randomized, double-blind, placebo-control trial were included in this study. Following written informed consent, mothers were randomized to one of two vitamin D supplementation regimens: Group 1: 400 IU vitamin D3/day (0 IU vitamin D3—placebo and 1 prenatal vitamin containing 400 IU vitamin D3), or Group 2: 6,400 IU vitamin D3/day (6,000 IU vitamin D3 and 1 prenatal vitamin containing 400 IU vitamin D3).

Study Protocol

  1. Following written informed consent, each mother had baseline serum samples collected for measurement of circulating 25(OH)D and vitamin D3.
  2. The mothers were started on a total of 400 or 6,400 IU vitamin D3 tablets/day (Tishcon Corporation, Westberry, NY, a Good-Manufacturing-Practice (GMP) facility that met FDA production guidelines) for up to 6 months.
  3. Serum samples were collected at monthly intervals and analyzed for circulating 25(OH)D and vitamin D3 as described for the sun-rich population in Part I (Methods).
  4. Data Analysis: The data were plotted as in Part I of the study using a best-fit regression analysis with vitamin D3 serving as the independent variable.


Subjects from the sun-rich environment exhibited a wide range of circulating 25(OH)D levels (11–71 ng/mL). Similarly, the range of circulating 25(OH)D levels in women in the supplementation group was from 12–77 ng/mL. This wide range also was observed for the circulating vitamin D3 levels (<1–64 ng/mL in the sun-rich environment group and <1–75 in the supplementation group). When data from the 20 subjects in the lowest and highest quartiles, comparing circulating 25(OH)D and vitamin D3 were plotted, a significant second-order equation was generated (p<0.0001, Figure 1). Similarly, when the data from the supplementation group was plotted, a similar, significant second-order equation was observed (p<0.0001, Figure 2). These equations did not differ statistically (p>0.15).

Figure 1

Circulating 25(OH)D as a Function of Vitamin D3 Status in Subjects from a Sun-Rich Environment

Figure 2

Circulating 25(OH)D as a Function of Vitamin D3 Status in Supplemented Subjects


The question, what is a “normal” nutritional vitamin D status, is currently a hotly debated topic. Historically, a “normal” nutritional vitamin D status has been defined as just about any circulating level of 25(OH)D in asymptomatic subjects (1, 18). Recently, attempts have been made to reevaluate this “normal” circulating level of 25(OH)D using biomarkers such as parathyroid hormone (610), intestinal calcium absorption (5), skeletal density (24), glucose clearance (12), and innate immune function (13). Generally, these studies suggest that a minimum circulating level of 25(OH)D should be >80 nmol (32 ng/mL) (18).

In the present study, we sought to investigate what circulating 25(OH)D levels would result in populations exhibiting no substrate limitations to the vitamin D-25-hydroxylase. To perform this, we chose two distinct populations. The first were individuals from a year-found sunny environment who spent a good deal of time outdoors. The second were a group of lactating women receiving a substantial daily oral dose of vitamin D3. Surprisingly, a study such as this previously had not been undertaken. There are several reasons for this. First, finding a group of sun-exposed individuals is not an easy task; in fact, we had to go to Hawaii to find them. Secondly, very few studies have been performed where subjects actually received adequate vitamin D3 supplementation to make them replete. Finally, it is very difficult and costly to measure circulating vitamin D3 and relate it to circulating 25(OH)D. The results of our study are far-reaching.

At a maternal intake of 6,400 IU vitamin D3/day, circulating vitamin D3 increased dramatically. Maternal circulating 25(OH)D also increase; however, the increase appeared to be limited and controlled (Figure 2). A similar relationship was observed in the sun-exposed individuals (Figure 1). In these individuals, sun exposure was greater than fifteen hours/week—although not all had total body exposure, some only hands, arms, and head. The data from our study suggests the following: The relationship between circulating vitamin D3 and 25(OH)D is not linear in either case; rather it appears saturable and controlled. This suggest either/or product-substrate inhibition of the vitamin D-25-hydroxylase. Optimal nutritional vitamin D status may occur when approaching equimolar concentrations of circulating vitamin D3 and 25(OH)D (>100 nmol). At this point, the Vmax of the enzyme appears to be achieved. It is important to note that as humans live today, the vitamin D-25-hydroxylase operates well below its Vmax because of chronic substrate (vitamin D) deficiency. Not a single other steroidal hormone system in the body is limited in this fashion since their starting point is cholesterol. When humans are sun- (or dietary-) replete, the vitamin D endocrine system will function in a fashion as do these other steroid synthetic pathways, not limited by substrate availability.

This study also demonstrates that individuals can be vitamin D deficient with significant sun exposure if the skin area exposed is limited as was suggested several years ago (19). Finally, whether one receives their vitamin D3 orally or through UV exposure, the vitamin D-25-hydroxylase appears to handle it in an equivalent fashion with respect to maintaining circulating 25(OH)D levels. Thus, we believe that the relationship between circulating vitamin D and 25(OH)D may define adequate nutritional vitamin D status.


1. Haddad JG, Chyu K. Competitive protein-binding radioassay for 25-hydroxycholecalciferol. J Clin Endocrinal Metab. 1971;33:992–995.

2. Bischoff-Ferrari H, Dietrich T, Orav E, Dawson-Hughes B. Positive association between 25(OH)D levels and bone mineral density: A population-based study of younger and older adults. Amer J Med. 2004;116:634–639. [PubMed]

3. Fuleihan E, Nabulsi M, Tamim H, Maalouf J, Salamoun M, Khalife H, et al. Effect of vitamin D replacement on musculoskeletal parameters in school children: A randomized controlled trial. J Clin Endocrinal Metab. 2006;91:405–412.

4. Javaid M, Crozier S, Harvey N, Gale C, Dennison E, Boucher B, et al. Maternal vitamin D status during pregancy and childhood bone mass at 9 years: A longitudinal study. Lancet. 2006;367:36–43. [PubMed]

5. Heaney R, Dowell M, Hale C, Bendich A. Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Amer College Nutr. 2003;22(2):142–146.

6. Lips P, Wiersinga A, Van Ginkel FC, Jongen MJ, Netelenbos JC, Hackeng WH, et al. The effect of vitamin D supplementation on vitamin D status and parathyroid function in elderly subjects. J Clin Endocrinol Metab. 1988;67:644–650. [PubMed]

7. Gloth FM, Gundberg CM, Holllis BW, Haddad JG, Tobin JD. Vitamin D deficiency in homebound elderly persons. JAMA. 1995;274:1683–1686. [PubMed]

8. Visser M, Deeg D, Lips P. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): The longitudinal aging study Amsterdam. J Clin Endocrinal Metab. 2003;88:5766–5772.

9. Vieth R, Ladak Y, Walfish P. Age-related changes in the 25-hydroxyvitamin D versus parathyroid hormone relationship suggest a different reason why older adults require more vitamin D. J Clin Endocrinal Metab. 2003;88:185–191.

10. Chel VG, Ooms ME, Popp-Snijders C, Pavel S, Schothorst AA, Meulemans CCE, et al. Ultraviolet irradiation corrects vitamin D deficiency and suppresses secondary hyperparathyroidism in the elderly. J Bone Mineral Res. 1998;13:1238–1242.

11. Lee S, Clark S, Gill R, Christakos S. 1,25-Dihydroxyvitamin D3 and pancreatic beta-cell function: vitamin D receptors, gene expression, and insulin secretion. Endocrinology. 1994;134(4):1602–1610. [PubMed]

12. Chiu K, Chu A, Go V, Soad M. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Amer J Clin Nutr. 2004;79:820–825. [PubMed]

13. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik S, et al. Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response. Science. 2006:1770–1773. doi: 10.1126/science.1123933. [PubMed]

14. Barger-Lux MJ, Heaney RP. Effects of Above Average Summer Sun Exposure on Serum 25-Hydroxyvitamin D and Calcium Absorption. J Clin Endocrinol Metab. 2002;87(11):4952–4956. doi: 10.1210/jc2002-020636. [PubMed]

15. Hollis BW, Kamerud JQ, Selvaag SR, Lorenz JD. Determination of vitamin D status by radioimmunoassay with a 125I-labeled tracer. Clin Chem. 1993;39:529–533. [PubMed]

16. Hollis BW. Detection of vitamin D and its major metabolites. In: Feldman D, Glorieux F, Pike J, editors. Vitamin D. New York, N.Y.: Academic Press; 2005. pp. 932–950.

17. Coffin CF, Labbok MH, Belsey M. Breastfeeding definitions. Contraception. 1997;55:323–325. [PubMed]

18. Hollis BW. Circulating 25-hydroxyvitamin D levels indicative of vitamin sufficiency: Implications for establishing a new effective DRI for vitamin D. J Nutr. 2005;135:317–322. [PubMed]

19. Matsuoka LY, Wortsman J, Hollis BW. Use of topical sunscreen for the evaluation of regional synthesis of vitamin D3. J Amer Acad Dermatol. 1990;22:772–775. [PubMed]

Women With Breast Cancer Have Low Vitamin D Levels[xxviii]

ScienceDaily (Oct. 10, 2009) — Women with breast cancer should be given high doses of vitamin D because a majority of them are likely to have low levels of vitamin D, which could contribute to decreased bone mass and greater risk of fractures, according to scientists at the University of Rochester Medical Center.

In a study of 166 women undergoing treatment for breast cancer, nearly 70 percent had low levels of vitamin D in their blood, according to a study being presented Thursday, Oct. 8, at the American Society of Clinical Oncology’s Breast Cancer Symposium in San Francisco. The analysis showed women with late-stage disease and non-Caucasian women had even lower levels.

“Vitamin D is essential to maintaining bone health, and women with breast cancer have accelerated bone loss due to the nature of hormone therapy and chemotherapy. It’s important for women and their doctors to work together to boost their vitamin D intake,” said Luke Peppone, Ph.D., research assistant professor of Radiation Oncology, at Rochester’s James P. Wilmot Cancer Center. He is a member of the National Cancer Institute’s Community Clinical Oncology Program research base in Rochester.

Scientists funded by the NCI analyzed vitamin D levels in each woman, and the average level was 27 nanograms per milliliter; more than two-thirds of the women had vitamin deficiency. Weekly supplementation with high doses of vitamin D — 50,000 international units or more — improved the levels, according to Peppone’s study.

The U.S. Institute of Medicine suggests that blood levels nearing 32 nanograms per milliliter are adequate.

This problem is not unexpected, Peppone said, because previous studies have shown that nearly half of all men and women are deficient in the nutrient, with vitamin D levels below 32 nanograms per milliliter. Vitamin D, obtained from milk, fortified cereals and exposure to sunlight, is well known to play an essential role in cell growth, in boosting the body’s immune system and in strengthening bones.

Symptoms of Vitamin D deficiency include muscle pain, weak bones/fractures, low energy and fatigue, lowered immunity, symptoms of depression and mood swings, and sleep irregularities, many of which are common for women undergoing breast cancer treatment.

Adapted from materials provided by University of Rochester Medical Center.

Real Help for Cancer?

by Bill Sardi and Timothy Hubbell

The weekly injection of just 100 billionths of a gram of a harmless glyco-protein (a naturally-produced molecule with a sugar component and a protein component) activates the human immune system and cures cancer for good, according to human studies among breast cancer and colon cancer patients, producing complete remissions lasting 4 and 7 years respectively. This glyco-protein cure is totally without side effect but currently goes unused by cancer doctors.

Normal Gc protein (also called vitamin D binding protein), an abundant glyco-protein found in human blood serum, becomes the molecular switch to activate macrophages when it is converted to its active form, called Gc macrophage activating factor (Gc-MAF). Gc protein is normally activated by conversion to Gc-MAF with the help of the B and T cells (bone marrow-made and thymus gland-made white blood cells). But, as researchers explain it themselves, cancer cells secrete an enzyme known as alpha-N-acetylgalactosaminidase (also called Nagalase) that completely blocks conversion of Gc protein to Gc-MAF, preventing tumor-cell killing by the macrophages. This is the way cancer cells escape detection and destruction, by disengaging the human immune system. This also leaves cancer patients prone to infections and many then succumb to pneumonia or other infections.

The once-weekly injection of minute amounts of Gc-MAF, just 100 nanograms (billionths of a gram), activates macrophages and allows the immune system to pursue cancer cells with vigor, sufficient to produce total long-term cures in humans.

Nobuto Yamamoto, director of the Division of Cancer Immunology and Molecular Biology, Socrates Institute for Therapeutic Immunology, Philadelphia, Pennsylvania, says this is “probably the most potent macrophage activating factor ever discovered.”


Once a sufficient number of activated macrophages are produced, another Gc-MAF injection is not needed for a week because macrophages have a half-life of about six days. After 16-22 weekly doses of Gc-MAF the amount of Nagalase enzyme fell to levels found in healthy people, which serves as evidence tumors have been completely eliminated. The treatment was fool-proof – it worked in 100% of 16 breast cancer patients and there were no recurrent tumors over a period of 4 years, says a report in the January 15 issue of the International Journal of Cancer. [International Journal Cancer. 2008 January15; 122(2):461-7]

In another startling follow-up report by Dr. Yamamoto and colleagues, published in the upcoming July issue of Cancer Immunology Immunotherapy, Gc-MAF therapy totally abolished tumors in 8 colon cancer patients who had already undergone surgery but still exhibited circulating cancer cells (metastases). After 32-50 weekly injections, “all colorectal cancer patients exhibited healthy control levels of the serum Nagalase activity, indicating eradication of metastatic tumor cells,” said researchers, an effect that lasted 7 years with no indication of cancer recurrence either by enzyme activity or CT scans, said researchers. [Cancer Immunology, Immunotherapy Volume 57, Number 7 / July, 2008] Published in an early online edition of this journal, this confirming report has received no attention by the new media so far, despite its striking importance.

Gc-MAF treatment for cancer has been agonizingly slow to develop. Dr. Yamamoto first described this immuno-therapy in 1993. [The Journal of Immunology, 1993 151 (5); 2794-2802]

● Untreated mice ○ Mice given macrophage activating factor

In a similar animal experiment published in 2003, researchers in Germany, Japan and the United States collaborated to successfully demonstrate that after they had injected macrophage activating factor (Gc-MAF) into tumor-bearing mice, it totally eradicated tumors (see the above chart). [Neoplasia 2003 January; 5(1): 32–40]

In 1997 Dr. Yamamoto injected Gc-MAF protein into tumor-bearing mice, with the same startling results. A single enzyme injection doubled the survival of these mice and just four enzyme injections increased survival by 6-fold. [Cancer Research 1997 Jun 1; 57(11):2187-92]

In 1996 Dr. Yamamoto reported that all 52 cancer patients he had studied carried elevated blood plasma levels of the immune inactivating alpha-N-acetylgalactosaminidase enzyme (Nagalase), whereas healthy humans had very low levels of this enzyme. [Cancer Research 1996 Jun 15; 56(12):2827-31]

In the early 1990s Dr. Yamamoto first described how the human immune system is disengaged by enzymes secreted from cancer cells, even filing a patent on the proposed therapy. [US Patent 5326749, July 1994; Cancer Research 1996 June 15; 56: 2827-31]

Activated Gc protein has been used in humans at much higher doses without side effect. This Gc macrophage activating factor (Gc-MAF) has been shown to be effective against a variety of cancers including breast, prostate, stomach, liver, lung, uterus, ovary, brain, skin, head/neck cancer and leukemia.

Although Gc-MAF is also called vitamin D binding protein, the activation of macrophages does not require vitamin D.

It cannot be said the Gc-MAF cancer cure has gone unheralded. Reuters News covered this developing story in January. But the news story still did not receive top billing nor did it fully elucidate the importance of the discovery, actually made years ago, that the human body is capable of abolishing cancer once its immune system is properly activated.

Gc-MAF is a naturally made molecule and is not patentable, though its manufacturing process is patent protected. There is no evidence of any current effort to commercialize this therapy or put it into practice. Should such an effective treatment for cancer come into common practice, the income stream from health insurance plans for every oncology office and cancer center in the world would likely be reduced to the point of financial insolvency and hundreds of thousands of jobs would be eliminated.

The National Cancer Institute estimates cancer care in the U.S. costs ~$72 billion annually (2004). Furthermore, about $55 billion of cancer drugs are used annually, none which have not significantly improved survival rates throughout the history of their use. If a typical cancer patient had to undergo 30 Gc-MAF injections at a cost of $150 per injection, that would cost ~$4500, not counting doctor’s office visits and follow-up testing. For comparison, gene-targeted cancer drugs range from $13,000 to $100,000 in cost per year and produce only marginal improvements in survival (weeks to months). [Targeted Oncology 2007 April, 2 (2); 113-19]

Up to this point, the National Cancer Institute is totally silent on this discovery and there is no evidence the cancer care industry plans to quickly mobilize to use this otherwise harmless treatment.

Timothy Hubbell, a biochemist from Cincinnati, first called attention to this discovery and provided consultation on the biochemistry.

High Levels of Vitamin D in Older People Can Reduce Heart Disease and Diabetes[xxix]

ScienceDaily (Feb. 22, 2010) — Middle aged and elderly people with high levels of vitamin D could reduce their chances of developing heart disease or diabetes by 43%, according to researchers at the University of Warwick.

A team of researchers at Warwick Medical School carried out a systematic literature review of studies examining vitamin D and cardiometabolic disorders. Cardiometabolic disorders include cardiovascular disease, type 2 diabetes mellitus and metabolic syndrome.

Vitamin D is a fat-soluble vitamin that is naturally present in some foods and is also produced when ultraviolet rays from sunlight strike the skin and trigger vitamin D synthesis. Fish such as salmon, tuna and mackerel are good sources of vitamin D, and it is also available as a dietary supplement.

Researchers looked at 28 studies including 99,745 participants across a variety of ethnic groups including men and women. The studies revealed a significant association between high levels of vitamin D and a decreased risk of developing cardiovascular disease (33% compared to low levels of vitamin D), type 2 diabetes (55% reduction) and metabolic syndrome (51% reduction).

The literature review, published in the journal Maturitas, was led by Johanna Parker and Dr Oscar Franco, Assistant Professor in Public Health at Warwick Medical School.

Dr Franco said: “We found that high levels of vitamin D among middle age and elderly populations are associated with a substantial decrease in cardiovascular disease, type 2 diabetes and metabolic syndrome.

“Targeting vitamin D deficiency in adult populations could potentially slow the current epidemics of cardiometabolic disorders.”

All studies included were published between 1990 and 2009 with the majority published between 2004 and 2009. Half of the studies were conducted in the United States, eight were European, two studies were from Iran, three from Australasia and one from India.

Journal Reference: Parker et al. Levels of vitamin D and cardiometabolic disorders: Systematic review and meta-analysis. Maturitas, 2010; 65 (3): 225 DOI: 10.1016/j.maturitas.2009.12.013


“ …. studies have shown a link between low vitamin D status and heart disease.”[xxx]


I hope you are convinced by the information I’ve given you that Vitamin D3 is a vital part of your recovery (or prevention) regimen for cancer. It also is vital for preventing or treating virtually all other degenerative conditions. Studies have shown that over 95% of the population of all civilized countries are deficient in this vital substance.

When I interviewed Dr. William Grant a few weeks ago on my Web Talk Radio show, he stressed the importance of cancer patients taking enough of Vitamin D3. This is significant because Dr. Grant is one of the world’s most informed scientists about this subject. He has published at least three dozen studies of the effects of Vitamin D and cancer. He is a Ph.D., not a medical doctor, and this is his primary field of study.

Dr. Grant told me about a wonderful service where you can get your Vitamin D level tested every 6 months for the next 5 years for the very reasonable price of $40 every six months. This is part of a five-year study being done by Carole Baggerly, another Vitamin D expert, on the long term effects of Vitamin D on your health. When you go to the website below and sign up for this study, you’ll be asked to fill out a short health questionnaire. When you pay your $40, you’ll be sent a kit and instructions for drawing a couple of drops of blood from your finger at home. You send the packet back to them. A week or so later, you’ll receive an e-mail with your Vitamin D level. Here’s the website for getting started:

My first test came back at 94. That’s in the top 3% of all the tests they have done so far of these levels. Most cancer patients, according to Dr. Grant and others I have talked to about this, are in the low 20’s. The “healthy level” is defined as 40-60 on this test, but Dr. Grant assured me that even higher levels are healthy. Dr. Grant recommended that all cancer patients begin taking 30,000 to 40,000 I.U. of Vitamin D3 every day immediately. Then, he said you should adjust this dosage up or down after you get your test results. There is no toxicity at these levels — or much higher levels. The easy way to take this amount is to buy the 5,000 I.U gelcaps. They are very small and easy to swallow. They are also very inexpensive. I get mine at I take one or two of these a day for prevention.

Inadequate Levels of Vitamin D May Significantly Increase Risk of Stroke, Heart Disease and Death[xxxii]

ScienceDaily (Nov. 16, 2009) — While mothers have known that feeding their kids milk builds strong bones, a new study by researchers at the Heart Institute at Intermountain Medical Center in Salt Lake City suggests that Vitamin D contributes to a strong and healthy heart as well — and that inadequate levels of the vitamin may significantly increase a person’s risk of stroke, heart disease, and death, even among people who’ve never had heart disease.

For more than a year, the Intermountain Medical Center research team followed 27,686 patients who were 50 years of age or older with no prior history of cardiovascular disease. The participants had their blood Vitamin D levels tested during routine clinical care. The patients were divided into three groups based on their Vitamin D levels — normal (over 30 nanograms per milliliter), low (15-30 ng/ml), or very low (less than 15 ng/ml). The patients were then followed to see if they developed some form of heart disease.

Researchers found that patients with very low levels of Vitamin D were 77 percent more likely to die, 45 percent more likely to develop coronary artery disease, and 78 percent were more likely to have a stroke than patients with normal levels. Patients with very low levels of Vitamin D were also twice as likely to develop heart failure than those with normal Vitamin D levels.

Findings from the study will be presented at the American Heart Association’s Scientific Conference on Nov. 16 in Orlando, Florida.

“This was a unique study because the association between Vitamin D deficiency and cardiovascular disease has not been well-established,” says Brent Muhlestein, MD, director of cardiovascular research of the Heart Institute at Intermountain Medical Center and one of the authors of the new study. “Its conclusions about how we can prevent disease and provide treatment may ultimately help us save more lives.”

A wealth of research has already shown that Vitamin D is involved in the body’s regulation of calcium, which strengthens bones — and as a result, its deficiency is associated with musculoskeletal disorders. Recently, studies have also linked Vitamin D to the regulation of many other bodily functions including blood pressure, glucose control, and inflammation, all of which are important risk factors related to heart disease. From these results, scientists have postulated that Vitamin D deficiency may also be linked to heart disease itself.

“Utah’s population gave us a unique pool of patients whose health histories are different than patients in previous studies,” Dr. Muhlestein says. “For example, because of Utah’s low use of tobacco and alcohol, we were able to narrow the focus of the study to the effects of Vitamin D on the cardiovascular system.”

The results were quite surprising and very important, says Heidi May, PhD, MS, an epidemiologist with the Intermountain Medical Center research team and one of the study authors.

“We concluded that among patients 50 years of age or older, even a moderate deficiency of Vitamin D levels was associated with developing coronary artery disease, heart failure, stroke, and death,” she says. “This is important because Vitamin D deficiency is easily treated. If increasing levels of Vitamin D can decrease some risk associated with these cardiovascular diseases, it could have a significant public health impact. When you consider that cardiovascular disease is the leading cause of death in America, you understand how this research can help improve the length and quality of people’s lives.”

Because the study was only observational, definitive links between Vitamin D deficiency and heart disease could not be assigned — but the findings create an impetus for further study, says Dr. Muhlestein.

“We believe the findings are important enough to now justify randomized treatment trials of supplementation in patients with Vitamin D deficiency to determine for sure whether it can reduce the risk of heart disease,” he says.

Heart and Bone Damage from Low Vitamin D Tied to Declines in Sex Hormones[xxxiii]

ScienceDaily (Nov. 16, 2009) — Researchers at Johns Hopkins are reporting what is believed to be the first conclusive evidence in men that the long-term ill effects of vitamin D deficiency are amplified by lower levels of the key sex hormone estrogen, but not testosterone.

In a national study in 1010 men, to be presented Nov. 15 at the American Heart Association’s (AHA) annual Scientific Sessions in Orlando, researchers say the new findings build on previous studies showing that deficiencies in vitamin D and low levels of estrogen, found naturally in differing amounts in men and women, were independent risk factors for hardened and narrowed arteries and weakened bones. Vitamin D is an essential part to keeping the body healthy, and can be obtained from fortified foods, such as milk and cereals, and by exposure to sunlight.

“Our results confirm a long-suspected link and suggest that vitamin D supplements, which are already prescribed to treat osteoporosis, may also be useful in preventing heart disease,” says lead study investigator and cardiologist Erin Michos, M.D., M.H.S.

“All three steroid hormones — vitamin D, estrogen and testosterone — are produced from cholesterol, whose blood levels are known to influence arterial and bone health,” says Michos, an assistant professor at the Johns Hopkins University School of Medicine and its Heart and Vascular Institute. “Our study gives us a much better understanding of how the three work in concert to affect cardiovascular and bone health.”

Michos says the overall biological relationship continues to puzzle scientists because studies of the long-term effects of adding estrogen in the form of hormone replacement therapy in women failed to show fewer deaths from heart disease. Indeed, results showed that in some women, an actual increase in heart disease and stroke rates occurred, although, bone fractures declined.

The Hopkins team’s latest data were provided by analyzing blood samples from a subset of men participating in a study on cancer. That study was part of a larger, ongoing national health survey involving both men and women and was designed to compare the risk of diseases between those with the lowest blood levels of vitamin D to those with higher amounts. An unhealthy deficiency, experts say, is considered blood levels of 20 nanograms per milliliter or lower.

The men in the study had their hormone levels measured for both chemical forms of testosterone and estrogen found in blood, when each is either unattached or circulating freely, and when each is attached to a separate protein, known as sex hormone binding globulin, or SHBG for short.

Initial results showed no link between vitamin D deficiency and depressed blood levels of either hormone. And despite finding a harmful relationship between depressed testosterone levels and rates of heart disease, stroke, and high blood pressure, as well as osteopenia in men, researchers found that it was independent of deficiencies in vitamin D.

However, when researchers compared ratios of estrogen to SHBG levels, they found that rates of both diseases, especially osteopenia, the early stage of osteoporosis, were higher when both estrogen and vitamin D levels were depressed.

For every single unit decrease in ratios of estrogen to SHBG (both in nanomoles per liter), men low in vitamin D showed an 89 percent increase in osteopenia, but men with sufficient vitamin D levels had a less worrisome 64 percent jump.

Using the same measure of estrogen levels, men low in vitamin D were also at heightened risk of cardiovascular diseases, at 12 percent, compared to men with adequate levels of the vitamin, at 1 percent, numbers that researchers say are still statistically significant.

“These results reinforce the message of how important proper quantities of vitamin D are to good bone health, and that a man’s risk of developing osteoporosis and heart disease is heavily weighted on the complex and combined interaction of how any such vitamin deficits interact with both their sex hormones, in particular, estrogen,” Michos says.

Michos and her team next plan to analyze blood samples from women to see if the same results from men hold true.

Michos recommends that men and women boost their vitamin D levels by eating diets rich in fatty fish, such as cod, sardines and mackerel, consuming fortified dairy products, taking vitamin supplements, and in warmer weather briefly exposing skin to the sun’s vitamin-D producing ultraviolet light.

She points out that clinical trials are under way to determine whether or not vitamin D supplements can prevent incidents of or deaths from heart attack, stroke and other signs of cardiovascular disease.

The U.S. Institute of Medicine suggests that an adequate daily intake of vitamin D is between 200 and 400 international units, but Michos feels this is inadequate to achieve optimal nutrient blood levels (above 30 nanograms per milliliter). Previous results from the same nationwide survey showed that 41 percent of men and 53 percent of women are technically deficient in the nutrient, with vitamin D levels below 28 nanograms per milliliter.

Funding for this study was provided by the Hormone Demonstration Project, a part of the Maryland Cigarette Restitution Fund Research Grant Program at the Johns Hopkins University. Additional support was provided by the American College of Cardiology Foundation and a Clinician Scientist Award at the Johns Hopkins University.

Besides Michos, other researchers at Johns Hopkins involved in this study were Jared Reis, Ph.D.; and Meredith Shields and Elizabeth Platz, Ph.D., Sc.D., at the University’s School of Public Health; and Sabine Rohrmann, now at the German Cancer Research Center in Heidelberg. Another investigator in this research was Nader Rifai, Ph.D., at Children’s Hospital Boston and Harvard Medical School.

Vitamin D linked to lower heart disease risk[xxxiv]

By raising low levels of the vitamin to normal levels, patients reduce their risk of heart disease by about 30%, an observational study finds.

March 15, 2010|By Shari Roan

Raising the amount of vitamin D in the blood appears to help some people — at least those deficient in the vitamin — reduce their risk of heart disease by about 30%, researchers announced Monday. The findings, though preliminary, support further investigation of the interplay between vitamin D and heart health.

Observational studies have linked heart disease with low vitamin D levels in the blood. In recent years, studies have shown that as many as three-quarters of Americans have a concentration in their blood that is under the normal level of 30 nanograms per milliliter.

But it has been unclear if people with low vitamin D have more heart disease because of the vitamin deficiency or for other reasons, such as lack of exercise, said Dr. J. Brent Muhlestein, the lead author of the new study and director of cardiovascular research at Intermountain Medical Center Heart Institute in Salt Lake City.

He announced the findings at the American College of Cardiology annual meeting in Atlanta. “The question we looked at is, if you do something about it, like taking vitamin D supplements, does that reduce the risk?” he said.

Researchers have been uncomfortable randomizing people with low vitamin D into a group that receives supplements and a group that does not because, in theory, every vitamin D deficiency should be treated. Low vitamin D levels can contribute to weaker bones and have been associated with increased risks of several diseases, including several types of cancer.

Instead, Muhlestein’s group examined data from more than 9,000 people who had been diagnosed with low vitamin D and who had a blood sample taken at a later date.

About half of the people had normalized their vitamin D levels by the time of the second blood sample, and they showed much less heart disease compared to people whose levels were still below normal.

“What we did was observational and not definitive, but we think it adds significantly to the story,” Muhlestein said. “It’s at least a reasonable piece of evidence to add to the hypothesis that low vitamin D is causative of cardiovascular risk and treatment can reduce cardiovascular disease risk.”

It’s not clear, however, whether the people who improved their vitamin D levels did other things to benefit their health, such as lowering their cholesterol or blood pressure, that might account for the lower risk of heart disease. Moreover, the pages of science journals are littered with now-disproved studies suggesting that various nutrients, such as vitamins E, C and folic acid, might prevent or treat heart disease.

“It turned out those things didn’t help. The low levels seem to be just markers for people who are less healthy,” said Dr. Douglas Weaver, immediate past president of the American College of Cardiology and chief of cardiology at the Henry Ford Health System in Detroit. “But I think these studies that show a relationship between heart attack and vitamin D are going to provoke a lot more research to understand what is going on.”

Vitamin D is synthesized in the skin from exposure to sunlight. It’s also found in a limited number of foods, including salmon and fortified milk. Adequate levels may strengthen the immune system and reduce inflammation, Muhlestein said.


Rheumatoid Arthritis Linked to Vitamin D Deficiency, Study Suggests[xxxv]

ScienceDaily (Apr. 10, 2010) — Women living in the northeastern United States are more likely to develop rheumatoid arthritis (RA), suggesting a link between the autoimmune disease and vitamin D deficiency, says a new study led by a Boston University School of Public Health researcher.

In the paper, which appears online in the journal Environmental Health Perspectives, a spatial analysis led by Dr. Verónica Vieira, MS, DSc, associate professor of environmental health, found that women in states like Vermont, New Hampshire and southern Maine were more likely to report being diagnosed with RA.

“There’s higher risk in the northern latitudes,” Dr. Vieira said. “This might be related to the fact that there’s less sunlight in these areas, which results in a vitamin D deficiency.”

The study looked at data from the Nurses’ Health Study, a long-term cohort study of U.S. female nurses. Looking at the residential addresses, health outcomes and behavioral risk factors for participants between 1988 and 2002, researchers based their findings on 461 women who had RA, compared to a large control group of 9,220.

RA is a chronic inflammatory disease that affects the lining of the joints, mostly in the hands and knees. This chronic arthritis is characterized by swelling and redness and can wear down the cartilage between bones. RA is two to three times more common in women than in men.

Although the cause of RA is unknown, the researchers wrote, earlier studies have shown that vitamin D deficiency, which can be caused by a lack of sunlight, has already been associated with a variety of other autoimmune diseases.

“A geographic association with northern latitudes has also been observed for multiple sclerosis and Crohn’s disease, other autoimmune diseases that may be mediated by reduced vitamin D from decreased solar exposure and the immune effects of vitamin D deficiency,” the authors wrote.

The authors said further research is needed to look into the relationship between vitamin D exposure and RA.

Dr. Vieira said she and her co-authors were somewhat surprised by the findings. A previous geographic study of RA had suggested an ecologic association with air pollution, she said.

“The results were unexpected,” Dr. Vieira said. “Prior to the analysis, we were more interested in the relationship with air pollution. I hadn’t given latitudes much thought.”

In addition to the geographic variation, the study suggested that the timing of residency may influence RA risk. “Slightly higher odds ratios were observed for the 1988 analysis suggesting that long term exposure may be more important than recent exposure,” the study said.

Dr. Vieira and other BUSPH researchers previously have used innovative spatial-temporal analyses to study the incidence of breast cancer, specifically focused on Cape Cod.

In addition to Dr. Vieira, co-authors of the article are Dr. Jaime Hart, MS, ScD, research fellow, Department of Epidemiology, Harvard School of Public Health; Dr. Thomas Webster, DSc, professor and associate chair, Department of Environmental Health, Boston University School of Public Health; Dr. Janice Weinberg, ScD, MS, associate professor, Department of Biostatistics, Boston University School of Public Health; Dr. Robin Puett, PhD, MPH, research assistant professor, Environmental Health Sciences, University of South Carolina; Dr. Francine Laden, ScD, MS, associate professor, Department of Epidemiology, Harvard School of Public Health; Dr. Karen Costenbader, MD, assistant professor of medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital and Harvard Medical School; and Dr. Elizabeth Karlson, MD, associate professor of medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital and Harvard Medical School.

The research was funded by grants from the National Institutes of Health.

Journal Reference:

Vieira et al. Association between Residences in U.S. Northern Latitudes and Rheumatoid Arthritis: A Spatial Analysis of the Nurses’ Health Study. Environmental Health Perspectives, 2010; DOI: 10.1289/ehp.0901861

Low Vitamin D Levels Associated With More Asthma Symptoms and Medication Use[xxxvi]

ScienceDaily (Apr. 20, 2010) — Low levels of vitamin D are associated with lower lung function and greater medication use in children with asthma, according to researchers at National Jewish Health. In a paper published online this week in the Journal of Allergy & Clinical Immunology, Daniel Searing, MD, and his colleagues also reported that vitamin D enhances the activity of corticosteroids, the most effective controller medication for asthma.

“Asthmatic children in our study who had low levels of vitamin D were more allergic, had poorer lung function and used more medications,” said Dr. Searing. “Conversely, our findings suggest that vitamin D supplementation may help reverse steroid resistance in asthmatic children and reduce the effective dose of steroids needed for our patients.”

The researchers examined electronic medical records of 100 pediatric asthma patients referred to National Jewish Health. Overall, 47 percent of them had vitamin D levels considered insufficient, below 30 nanograms per milliliter of blood (ng/mL). Seventeen percent of the patients had levels below 20 ng/mL, which is considered deficient. These levels were similar to vitamin D levels found in the general population.

Patients low in vitamin D generally had higher levels of IgE, a marker of allergy, and responded positively to more allergens in a skin prick test. Allergies to the specific indoor allergens, dog and house dust mite, were higher in patients with low vitamin D levels. Low vitamin D also correlated with low FEV1, the amount of air a person can exhale in one second, and lower FEV1/FVC, another measure of lung function. Use of inhaled steroids, oral steroids and long-acting beta agonists were all higher in patients low in vitamin D.

“Our findings suggest two possible explanations,” said senior author Donald Leung, MD, PhD. “It could be that lower vitamin D levels contribute to increasing asthma severity, which requires more corticosteroid therapy. Or, it may be that vitamin D directly affects steroid activity, and that low levels of vitamin D make the steroids less effective, thus requiring more medication for the same effect.”

The researchers performed a series of laboratory experiments that indicated vitamin D enhances the action of corticosteroids. They cultured some immune cells with the corticosteroid dexamethasone alone and others with vitamin D first, then dexamethasone. The vitamin D significantly increased the effectiveness of dexamethasone. In one experiment vitamin D and dexamethasone together were more effective than 10 times as much dexamethasone alone.

The researchers also incubated immune-system cells for 72 hours with a staphylococcal toxin to induce corticosteroid resistance. Vitamin D restored the activity of dexamethasone.

“Our work suggests that vitamin D enhances the anti-inflammatory function of corticosteroids,’ said Dr. Leung. “If future studies confirm these findings vitamin D may help asthma patients achieve better control of their respiratory symptoms with less medication.”

This study comes on the heels of another paper by National Jewish Health faculty, which showed that low levels of vitamin D in adult asthma patients are associated with lower lung function and reduced responsiveness to corticosteroids.

Journal Reference: Searing et al. Decreased serum vitamin D levels in children with asthma are associated with increased corticosteroid use. The Journal of Allergy and Clinical Immunology, 2010; DOI: 10.1016/j.jaci.2010.03.008

Researchers Recommend Pregnant Women Take 4,000 IU Vitamin D a Day[xxxvii]

ScienceDaily (May 1, 2010) — Taking vitamin D supplements during pregnancy is not only safe for mother and baby, but also can prevent preterm labor/births and infections, according to results of a randomized controlled study to be presented at the Pediatric Academic Societies (PAS) annual meeting in Vancouver, British Columbia, Canada.

In the 1950s and ’60s, people were concerned that vitamin D could cause birth defects, according to Carol L. Wagner, MD, lead author of the study and a pediatric researcher at Medical University of South Carolina. It now is known that vitamin D is important for maternal and infant health, including bone health and immune function.

Recent studies have shown that vitamin D deficiency during pregnancy is a serious public health issue.

“Diet doesn’t provide enough vitamin D, and we don’t go in the sun as much as we need,” Dr. Wagner said.

Therefore, she and her colleagues, including Bruce W. Hollis, PhD, who has worked in the field of vitamin D research for the last 30 years, set out to determine the optimal dose of vitamin D supplements for pregnant women without doing harm.

Researchers randomized 494 pregnant women at 12-16 weeks’ gestation into three treatment groups. Group one received 400 International Units (IU) of vitamin D a day until delivery; group two received 2,000 IU and group three received 4,000 IU. The women were evaluated monthly to ensure safety.

“No adverse events related to vitamin D dosing were found in any of the three arms of the study,” Dr. Wagner said.

Investigators also looked at the effects of vitamin D supplementation on complications during pregnancy, including preeclampsia, gestational diabetes, infections, and preterm labor and birth.

“The spectacular part of the study was it showed women replete in vitamin D had lower rates of preterm labor and preterm birth, and lower rates of infection,” Dr. Wagner said.

The greatest effects were seen among women taking 4,000 IU of vitamin D per day. Therefore, the researchers recommend this daily regimen for all pregnant women.

Story Source: Adapted from materials provided by American Academy of Pediatrics, via EurekAlert!, a service of AAAS.

Low Vitamin D Levels Are Related to MS Brain Atrophy, Cognitive Function, Studies Show[xxxviii]

ScienceDaily (Apr. 30, 2010) — Low vitamin D levels may be associated with more advanced physical disability and cognitive impairment in persons with multiple sclerosis, studies conducted by neurologists at the University at Buffalo have shown.

Their results, reported at the American Academy of Neurology meeting, held earlier this month, indicated that:

  • The majority of MS patients and healthy controls had insufficient vitamin D levels.
  • Clinical evaluation and magnetic resonance imaging (MRI) images show low blood levels of total vitamin D and certain active vitamin D byproducts are associated with increased disability, brain atrophy and brain lesion load in MS patients.
  • A potential association exists between cognitive impairment in MS patients and low vitamin D levels.

The MRI study involved 236 MS patients — 208 diagnosed with the relapsing-remitting type and 28 with secondary progressive, a more destructive form of MS — and 22 persons without MS.

All participants provided blood serum samples, which were analyzed for total vitamin D (D2 and D3) levels as well as levels of active vitamin D byproducts. MRI scans performed within three months of blood sampling were available for 163 of the MS patients.

Results showed that only seven percent of persons with secondary-progressive MS showed sufficient vitamin D, compared to 18.3 percent of patients with the less severe relapsing-remitting type.

Higher levels of vitamin D3 and vitamin D3 metabolism byproducts (analyzed as a ratio) also were associated with better scores on disability tests, results showed, and with less brain atrophy and fewer lesions on MRI scans.

Bianca Weinstock-Guttman, MD, UB associate professor of neurology/Jacobs Neurological Institute and director of the Baird Multiple Sclerosis Center, is first author on the study. Commenting on these results, Weinstock-Guttman said: “Clinical studies are necessary to assess vitamin D supplementation and the underlying mechanism that contributes to MS disease progression.”

While lower-than-normal vitamin D status is known to be associated with a higher risk of developing MS, little is known about its relationship to cognitive impairment.

Sarah A. Morrow, MD, UB assistant research professor of neurology/Jacobs Neurological Institute and lead author on the cognitive-impairment study, compared vitamin D levels in blood samples of 136 MS patients with the results of their neuropsychological assessments that tested multiple types of cognition affected by MS.

“Results showed that MS patients who were impaired on tests of executive function — critical reasoning and abstract thinking — and the ability to plan and organize, were more likely to be deficient in vitamin D,” said Morrow.

“This relationship held true when controlling for the season during which vitamin D was measured, as well as depression, which is known to be associated with lower vitamin D levels.” Morrow noted there also was a suggestion that verbal fluency (word generation) and visual-spatial memory (learning and memory of shapes and figures) is more likely to be affected when vitamin D levels are not sufficient.

Morrow is continuing her research to clarify these relationships.

Vitamin D Deficiency Associated With Chronic Fatigue in Brain Injured Patients[xxxix]

ScienceDaily (Apr. 28, 2010) — New evidence presented at the European Congress of Endocrinology has shown that vitamin D deficiency is closely associated with the chronic fatigue that often follows post traumatic brain injury (TBI).

TBI is a major cause of death and disability worldwide. In the European Union the annual incidence of TBI hospitalizations and fatalities is estimated at 235 per 100,000 people. This means that on average a large European state such as the UK, France or Germany, will have around 140,000 new traumatic brain injuries every year (national figures vary). Around two-thirds of post TBI patients go on to suffer chronic fatigue. Now a group of researchers in the Netherlands have linked vitamin D deficiency to chronic fatigue in post-TBI sufferers.

The group, led by Dr Jessica Schnieders from Rijnstate Hospital in Arnham, The Netherlands, looked at vitamin D and hormone levels in 90 fatigued and non-fatigued subjects. They also systematically evaluated pituitary hormones and factors such as sleep, attention, emotional well-being, quality of life, coping style, and daily activity. They found that 51% of TBI patients were severely fatigued 10 years after the trauma. Vitamin D deficiency was present in 65% of post TBI patients and significantly related with fatigue (P<0.05), with patients who suffered from fatigue more likely to be vitamin D deficient. The group also found a higher incidence of growth hormone and sex hormone deficiency in the fatigued group, but they found no evidence that these deficiencies contributed to the fatigue.

This work opens the possibility that correcting the vitamin D deficiency might help to reduce some of the chronic fatigue in TBI patients. However, as vitamin D levels in the body are affected by diet and time spent in the sunshine, further studies are now needed to confirm whether low vitamin D levels are a cause of the fatigue or whether they are a consequence of altered lifestyle led due to suffering from fatigue.

Lead researcher, Dr Jessica Schnieders said: “In the Netherlands we have 30,000 people every year who suffer a traumatic brain injury and many of these go on to suffer from chronic fatigue. This is early work, so we need to confirm that vitamin D is the cause of this fatigue, and if so to see if taking vitamin D, perhaps coupled with improved sleep patterns, can alleviate some of the symptoms.

“We looked at patients around 10 years after their trauma. Fatigued post traumatic brain injury patients are less active, and generally experience a reduced quality of life. They have difficulties in maintaining relationships and keeping jobs, and are less independent than people who have not had to cope with such trauma.”

Story Source:

Adapted from materials provided by European Society of Endocrinology, via AlphaGalileo.

Better Vitamin D Status Could Mean Better Quality of Life for Seniors[xl]

ScienceDaily (Apr. 26, 2010) — According to legend, it was The Fountain of Youth that the famed Spanish explorer Ponce de Leon was seeking when he landed on the Floridian coast in 1513. It has long been said that he who drinks from the Fountain will have his youth restored. Without a doubt, the quest for eternal youth is as ancient as any pursuit. However, although we are now living longer than ever, there is now growing concern that quantity of years is not nearly as important as quality of those years. Indeed, as we experience the many joys of living longer, we also must deal with myriad consequences accompanying this aging trend.

For instance, osteoporosis, arthritis, and other serious and often painful bone and joint diseases are much more common as we get older. And, not surprisingly, seniors often struggle daily with what was once the simple task of getting around. Hence, the obvious question in today’s society concerning our longevity is “What choices can we make to help ease these inconveniences of aging?”

One area of particular interest is the role that diet plays in keeping bones and muscles strong from infancy to old age. For instance, a limited number of studies point to the possibility that optimal intake of vitamin D (the “sunshine” vitamin) might help keep our muscles strong and preserve physical function. Although there are only few longitudinal studies investigating this relationship, their findings have been mixed. To help understand this diet-health association, Dr. Denise Houston from the Sticht Center on Aging at Wake Forest University and her collaborators studied the relationship between vitamin D status and physical function in a group of relatively healthy seniors living in Memphis, TN and Pittsburgh, PA. Their results will be presented on April 25 as part of the scientific program of the American Society for Nutrition, composed of the world’s leading nutrition researchers, at the Experimental Biology 2010 meeting in Anaheim, California.

This study was part of the Health, Aging, and Body Composition (Health ABC) study initially designed to assess the associations among body composition, long-term health conditions, and mobility in older adults. For Houston’s segment of the investigation, she studied 2788 seniors (mean age: ~75 years) for 4 years. At the beginning of the study, they assessed vitamin D status by analyzing each person’s blood for 25-hydroxyvitamin D, a precursor for activated vitamin D. At baseline and then 2 and 4 years later, the research team then determined whether circulating 25-hydroxyvitamin D was related to the participants’ physical function. Specifically, they looked at how quickly each participant could walk a short distance (6 meters) and rise from a chair five times as well as maintain his or her balance in progressively more challenging positions. Each participant was also put through a battery of tests assessing endurance and strength.

When the results were tabulated, participants with the highest levels of 25-hydroxyvitamin D had better physical function. And, although physical function declined over the course of the study, it remained significantly higher among those with the highest vitamin D levels at the beginning of the study compared to those with the lowest vitamin D levels. The scientists were not surprised to learn that, in general, vitamin D consumption was very low in this group of otherwise healthy seniors. In fact, more than 90% of them consumed less vitamin D than currently recommended, and many were relying on dietary supplements.

The good news: higher circulating 25-hydroxyvitamin D is related to better physical function in seniors. But it’s impossible to tell from this type of research whether increasing vitamin D intake will actually lead to stronger muscles and preserve physical function. This is partly due to the fact that our bodies can make vitamin D if they get enough sunlight. So, it is possible that the participants with better physical function had higher vitamin D status simply because they were able to go outside more often. Indeed, the ominous “chicken-or-the-egg” question can only be answered by carefully controlled clinical intervention trials. Nonetheless, it is possible that getting more vitamin D from foods (like fortified milk and oily fish) or supplements will help maintain youth and vitality as we enjoy longer lifespans. As Houston points out: “Current dietary recommendations are based primarily on vitamin D’s effects on bone health. It is possible that higher amounts of vitamin D are needed for the preservation of muscle strength and physical function as well as other health conditions. However, clinical trials are needed to definitively determine whether increasing 25-hydroxyvitamin D concentrations through diet or supplements has an effect on these non-traditional outcomes.”

Will vitamin D research lead us to The Fountain of Youth? Probably not. But paying attention to how much vitamin D we get is likely important at every age and will help enhance the “quality” component of life as we enter our senior years.

Dr. Denise Houston (Wake Forest University, Winston Salem, NC); Dr. Janet Tooze (Wake Forest University); Rebecca Neiberg (Wake Forest University), Dr. Kyla Shea (Wake Forest University), Dr. Dorothy Hausman (University of Georgia, Athens, GA), Dr. Mary Ann Johnson (University of Georgia), Dr. Jane Cauley (University of Pittsburgh, Pittsburgh, PA), Dr. Doug Bauer (University of California, San Francisco, CA), Dr. Frances Tylavsky (University of Tennessee, Memphis, TN), Dr. Marjolein Visser (VU University, Amsterdam, Netherlands), Dr. Eleanor Simonsick (National Institute on Aging, Baltimore, MD), Dr. Tamara Harris (National Institute on Aging), and Dr. Stephen Kritchevsky (Wake Forest University) were coauthors on this paper.

Story Source:

Adapted from materials provided by Federation of American Societies for Experimental Biology, via EurekAlert!, a service of AAAS.

Effect of 25-hydroxyvitamin D status on serological response to influenza vaccine in prostate cancer patients[xli]

The Prostate, 09/08/2010

Chadha MK et al. – Epidemiologic data suggest that there is an association between vitamin D deficiency and influenza infection. The authors conducted a prospective influenza vaccination study to determine the influence of vitamin D status on serological response to influenza vaccine in prostate cancer (CaP) patients. In this study in CaP patients, a replete vitamin D status was associated with more frequent serological response to influenza vaccine.

Posted in cancer suppplements, complementary therapies, Supporting chemo, Vitamin C and cancer | 3 Comments »

Ian Clements Radical Cystectomy for Bladder Cancer Overview

Posted by Jonathan Chamberlain on April 21, 2011

Radical Cystectomy


Overview.. 3

Arguments against organ preservation in patients with muscle invasive bladder cancer 4  4

A prospective randomized trial for postoperative vs. preoperative adjuvant radiotherapy for muscle-invasive bladder cancer 5

Influence of older age on survival after radical cystectomy due to urothelial carcinoma of the bladder 5

Robotic-assisted laparoscopic radical cystectomy: Evaluation of functional and oncological results  6

Predictors of outcome of non-muscle-invasive and muscle-invasive bladder cancer 6

Do patients benefit from routine follow-up to detect recurrences after radical cystectomy and ileal orthotopic bladder substitution. 6

Invasive bladder cancer in the eighties: transurethral resection or cystectomy. 7

Maximizing cure for muscle-invasive bladder cancer: Integration of surgery and chemotherapy  7

Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer Well Tolerated Among Elderly Patients  7

Perioperative mortality is significantly greater in septuagenarian and octogenarian patients treated with radical cystectomy for urothelial carcinoma of the bladder 8

Early vs delayed radical cystectomy for ‘high-risk’ carcinoma not invading bladder muscle: Delay of cystectomy reduces cancer-specific survival 9

Trends in the use of radiotherapy and radical surgery for patients with bladder urothelial cell carcinoma in East Anglia, 1995–2006. 9

Does the greater number of lymph nodes removed during standard lymph node dissection predict better patient survival following radical cystectomy?. 9

Perioperative Mortality Is Significantly Greater in Septuagenarian and Octogenarian Patients Treated With Radical Cystectomy for Urothelial Carcinoma of the Bladder  Urology, 02/01/2011. 10

RC Mortality Stats. 10

Hospital volume and 90-day mortality risk after radical cystectomy: A population-based cohort study  10

Contemporary outcomes of 2287 patients with bladder cancer who were treated with radical cystectomy  12

Long-term complications of conduit urinary diversion. 12

Does the greater number of lymph nodes removed during standard lymph node dissection predict better patient survival following radical cystectomy. 12

Radical TURB for management of muscle invasive disease. 13

Hospital volume and 90-day mortality risk after radical Cystectomy. 13

Cisplatin-Based Induction Regimens Comparable for Invasive Bladder Cancer 14

Defining Early Morbidity of Radical Cystectomy for Patients with Bladder Cancer Using a Standardized Reporting Methodology. 15

Take Home Message. 16

Radical cystectomy for patients with pT4 urothelial carcinoma in a large population-based  17

Radical cystectomy for bladder cancer in the 70+ population: A nation-wide registry analysis of 845 patients  17

See also Memorial Sloan-Kettering Bladder Cancer Nomogram.. 18

Update on muscle-invasive and locally advanced BC.. 18

Disease progression for neo-ad chemotherapy for TCC: Who’s at risk?. 19

Cystectomy, Radical 20

Current Value of Neoadjuvant Chemotherapy Prior to Cystectomy. 24

The role of adjuvant chemotherapy in patients with locally advanced (pT3, pT4a) and/or lymph node–positive bladder cancer. 24

Use of radical cystectomy for patients with invasive bladder cancer 25

Treatment and outcome in muscle invasive bladder cancer 26

The management of BCG failure in non-muscle-invasive bladder cancer 27

Prevention and management of complications following radical cystectomy for bladder cancer 27

Radical cystectomy in patients with non-muscle invasive bladder cancer who fail BCG therapy  28

Effect of a minimum lymph node policy in radical cystectomy and pelvic lymphadenectomy on lymph node yields, lymph node positivity rates, lymph node density, and survivorship in patients with bladder cancer 29

Update of the Clinical Guidelines of the European Association of Urology on muscle-invasive and metastatic bladder carcinoma. 29

Beyond the Abstract – Risk factor analysis in a contemporary cystectomy. 30

An analysis of upper urinary tract recurrence following radical cystectomy for bladder cancer 31

Predictive factors and long term carcinogenic results of patients who no longer have residual tumors (stage pT0) on specimens of total cystectomy carried out for cancer of the bladder 31

Outcome of treatment of bladder cancer: A comparison between low-volume hospitals and an oncology centre  32

Survival after cystectomy for invasive bladder cancer 33

External stoma and peristomal complications following radical cystectomy and ileal conduit diversion  34

A phase II trial of neoadjuvant erlotinib in patients with muscle-invasive bladder cancer undergoing radical cystectomy. 34

Risk factor analysis in a contemporary cystectomy cohort using standardized reporting methodology and adverse event criteria. 35

Urinary diversion and morbidity after radical cystectomy for bladder cancer 35

Characteristics and Outcomes of Patients with Clinical T1 Grade 3 Urothelial Carcinoma Treated with Radical Cystectomy: Results from an International Cohort 36

An Updated Critical Analysis of the Treatment Strategy for Newly Diagnosed High-grade T1 (Previously T1G3) Bladder Cancer 36

Impact of comorbidity on survival of invasive bladder cancer patients, 1996-2007: A Danish population-based cohort study. 37

Robot-assisted radical cystectomy: intermediate survival results at a mean follow-up of 25 months  38

Invasive TCC in the Elderly: Radical cystectomy?. 38

Management of muscle invasive disease. 39

Bladder cancer in the elderly. 40

Complications and Mortality After Radical Cystectomy for Bladder Transitional Cell Cancer 41

Complications Following Radical Cystectomy for Bladder Cancer in the Elderly. 42

A Thorough Pelvic Lymph Node Dissection in Presence of Positive Margins Associated With Better Clinical Outcomes in Radical Cystectomy Patients. 43

Neobladder vs. Ileal Conduit 45

Analysis of Perioperative and Survival Outcome of RC.. 46

Quality of Pathologic Response and Surgery Correlate With Survival for Patients With Completely Resected Bladder Cancer After Neoadjuvant Chemotherapy. 46

A Population Based Assessment of Perioperative Mortality After Cystectomy for Bladder Cancer 49

Twenty-Year Experience of Radical Cystectomy for Bladder Cancer in a Medium-Volume Centre  50

Impact of Treatment Delay in Patients with Bladder Cancer Managed with Partial Cystectomy in Quebec  51

The Risk Factor for Urethral Recurrence after Radical Cystectomy in Patients with Transitional Cell Carcinoma of the Bladder 51

Chemo-surgery yields 92% survival in metastatic TCC‏.. 53

Superficial (pT2a) and deep (pT2b) muscle invasion in pathological staging of bladder cancer following radical cystectomy. 60

Radical cystectomy in the treatment of bladder cancer always in due time?. 61

Radical cystectomy for bladder cancer: the case for early intervention. 62

Related Articles. 62

Radical cystectomy for bladder cancer: the case for early intervention. 63

Re: [CAFE] metastatic blc/RC‏.. 69

Subject:           Re: cystectomy a guarantee??. 70

Subject:           Re: metastatic blc/RC.. 71

Re: [CAFE] cystectomy a guarantee??‏. 77

Defining Early Morbidity of Radical Cystectomy for Patients with Bladder Cancer Using a Standardized Reporting Methodology. 78

Radical cystectomy for T2 bladder cancer with failed chemo. 79

Hygiene and urinary tract infections after cystectomy in 452 Swedish survivors of bladder cancer 80


See: Improving Survival for Patients with Muscle Invasive Bladder Cancer Dr Ralph de Vere White: An overview of Chemo, RC & survival + new predictive diagnostic with an excellent presentation of the need to do chemo first, then RC with >10 node removal

This states unequivocally that Chemo should precede TURB and RC for maximum survival chance.

22% get urinary infections after RC (see Hygiene and urinary tract infections after cystectomy in 452 Swedish survivors of bladder cancer)

A major review is that of Dr Bajorin:


There’s also the problem for men of maybe (most?) have erectile disfunction afterwards (“a contemporary questionnaire-based study that reported 13% and 42% potency rate following radical surgery and nerve-sparing cystectomy, respectively”. Vs. “with trimodality treatment …. 75% were considered to have bladders with normal function” [i])

See also: Rapid metastasis to the scrotum and penis following laparoscopic radical cystoprostatectomy

Status of robot-assisted radical cystectomy – good and getting better

Confirmation that removing >10 nodes @ RC is best

The risk of an upper urinary tract recurrence following a radical cystectomy has been reported to be approximately 2 to 8%

According to European guidelines on BC, the favoured treatment of MIBC is RC with urinary diversion. However, it has been shown that only 16-35% of the patients with MIBC undergo cystectomy. Bladder-sparing treatments (TUR, interstitial readiotherapy, and external radiotherapy with or without systemic chemo) can be considered in patients not suitable for major surgery.  .. Patients with metastases can only be treated with palliative intent. Their median survival is only 6 months and can be extended to 14-15 months by systemic ploychemo.[ii] [that perhaps should be polychemo – IC]

It is important to consider trimodality treatment as an alternative to RC, research shows this gives at least equivalent survival whilst preserving the bladder. See my collation on this (RC Alternatives).

There’s another risk factor: 4.4% of RCs have recurrent cancer

The known factors that effect survival for BC RC are:

Age – older have higher mortality and less survival time

Gender – women have a higher mortality and less survival time

Experience of the surgeon – less experienced ones have poorer outcomes

Invasive bladder cancer in the eighties: Transurethral resection or cystectomy?[iii]

Tue, 29 March 2011

Department of Urology, Fundacio Puigvert, Universitat Autonoma de Barcelona, Barcelona, Spain.

Describe morbidity and survival in patients older than 80 years with muscle invasive bladder cancer (MIBC) treated with radical cystectomy (RC) or transurethral resection (TUR) in our institution.

We reviewed our database of all patients older than 80 years treated with RC and TUR for MIBC between 1993 and 2005 in our institution. Twenty-seven patients were submitted to RC, with mean age of 82 years and mean follow-up of 16.4 months. RC was carried out following diagnosis of previous MIBC in 14 cases (51.9%). The American Society of Anesthesiology (ASA) score was III or IV in 23 patients (85.1%). Seventy-two patients with a mean age of 84 years and mean follow-up of 33 months, diagnosed with MIBC, were managed by means of TUR. The ASA score was III-IV in 64 (88.8%) patients.

Pathological stage of the RC specimen was pT3 in 18 cases (66.7%). Mean hospital stay was 16 days. Early complications were assessed in 8 patients (29.6%), with an overall survival (OS) of 42.94%, and cancer-specific survival (CSS) of 60.54%. In patients submitted to TUR, clinical stage was T2 in 36 cases (50%). The mean hospital stay was 7 days, with a readmission rate (RR) of 87.5%. OS and CSS was less than 20%.

RC in octogenarian patients is a safe procedure, with complication and survival rates comparable to RC series in general population. Transurethral resection (TUR) for patients with MIBC within this age range is a much less morbid procedure, but disease specific survival is lower.

Written by:  Faba OR, Palou J, Urdaneta G, Gausa L, Villavicencio H.

Reference: Int Braz J Urol. 2011 Jan-Feb;37(1):49-56. doi: 10.1590/S1677-55382011000700007

PubMed Abstract  PMID: 21385480

Arguments against organ preservation in patients with muscle invasive bladder cancer

A prospective randomized trial for postoperative vs. preoperative adjuvant radiotherapy for muscle-invasive bladder cancer[iv]

Wed, 23 March 2011

Department of Radiation, National Cancer Institute, Cairo University, Cairo, Egypt.

Although radical cystectomy is considered to be the primary treatment for muscle-invasive bladder cancer, it is associated with unfavorable outcome. Local recurrence is still a major problem. Survival rates as well as quality of live are far from being satisfactory. Postoperative radiotherapy is considered the standard adjuvant treatment in the NCI-Egypt. This is a prospective randomized study conducted to compare preoperative with postoperative radiotherapy as regard the survival and complication rates.

In the period from May, 2004 to June 2007, 100 eligible patients were included into the study, 50 patients in each treatment arm. Pelvic irradiation was identical in both groups aiming at 50 Gy/25 Fs/5 wk. Radical cystectomy was the standard surgery. Locoregional control, survival rates, and complications rates were compared in both arms.

Patients had a median follow-up period of 32 months (range 0-69 months). Patients had an average age of 54.8 ± 9.5 years with a male/female ratio 3:1. In the present study, transitional cell carcinoma constitutes (51%), while squamous cell carcinoma was reported in 46% of cases. Grades II and III pathology were 81% and 17%, respectively. Pathological stage P(2b) was encountered in 39.5% of the patients followed by P(3)b (33.3%) and P(3)a (14.6%). For the preoperative group, the 3-year overall survival, disease-free survival, locoregional control, and metastases-free survival rates were 53.4%, 47.4%, 89.3%, and 61.5%, respectively. The corresponding figures for the postoperative group were 51.8%, 34.1%, 80.6%, and 55.7% for the postoperative group. None of the patients had serious radiation reactions.

In our study, preoperative radiotherapy was almost equivalent to postoperative radiation therapy as regard OS, DFS, as well as complication rates. Given the recent physical developments in radiation therapy techniques and the biological rationale for treating the pelvis after cystectomy, adjuvant radiotherapy should be re-evaluated world wide. Preoperative radiotherapy may re-emerge as a useful tool for adjuvant treatment.

Written by: El-Monim HA, El-Baradie MM, Younis A, Ragab Y, Labib A, El-Attar I.

Reference: Urol Oncol. 2011 Feb 24. doi: 10.1016/j.urolonc.2011.01.008

PubMed Abstract PMID: 21353794

Influence of older age on survival after radical cystectomy due to urothelial carcinoma of the bladder[v]

Survival analysis of a German multi-centre study after curative treatment of urothelial carcinoma of the bladder

Tue, 22 March 2011

Urologische Klinik, St. Elisabeth Klinikum Straubing , St. Elisabeth-Straße 23, 94315, Straubing, Deutschland.

The therapeutic gold standard of muscle-invasive tumour stages is radical cystectomy (RC), but there are still conflicting reports about associated morbidity and mortality and the oncologic benefit of RC in elderly patients. The aim of the present study was the comparison of overall (OS) and cancer-specific survival (CSS) in patients < 75 and >75 years of age (median follow-up was 42 months).

Clinical and histopathological data of 2,483 patients with urothelial carcinoma and consecutive RC were collated. The study group was dichotomized by the age of 75 years at RC. Statistical analyses comprising an assessment of postoperative mortality within 90 days, OS and CSS were assessed. Multivariate logistic regression and survival analyses were performed.

The 402 patients (16.2%) with an age of ≥75 years at RC showed a significantly higher local tumour stage (pT3/4 and/or pN+) (58 vs 51%; p=0.01), higher tumour grade (73 vs 65%; p=0.003) and higher rates of upstaging in the RC specimen (55 vs 48%; p=0.032). Elderly patients received significantly less often adjuvant chemotherapy (8 vs 15%; p< 0.001). The 90-day mortality was significantly higher in patients ≥75 years (6.2 vs 3.7%; p=0.026). When adjusted for different variables (gender, tumour stage, adjuvant chemotherapy, time period of RC), only in male patients and locally advanced tumour stages was an association with 90-day mortality noticed. The multivariate analysis showed that patients ≥75 years of age have a significantly worse OS (HR=1.42; p< 0.001) and CSS (HR=1.27; p=0.018).

An age of ≥75 years at RC is associated with a worse outcome. Prospective analyses including an assessment of the role of comorbidity and possibly age-dependent tumour biology are warranted.

Written by: May M, Fritsche HM, Gilfrich C, Brookman-May S, Burger M, Otto W, Bolenz C, Trojan L, Herrmann E, Michel MS, Wülfing C, Tiemann A, Müller SC, Ellinger J, Buchner A, Stief CG, Tilki D, Wieland WF, Höfner T, Hohenfellner M, Haferkamp A, Roigas J, Müller O, Bretschneider-Ehrenberg P, Zacharias M, Gunia S, Bastian PJ.

Reference: Urologe A. 2011 Feb 23. doi: 10.1007/s00120-011-2507-9

PubMed Abstract PMID: 21340593

Robotic-assisted laparoscopic radical cystectomy: Evaluation of functional and oncological results[vi]

Monday, 21 March 2011

Departamento de Urología Robótica, Universidad del Saarland, Homburg/ Saar, Alemania.

Radical cystectomy remains the most effective treatment for patients with localized, invasive bladder cancer and recurrent noninvasive disease. We report our experience with 84 consecutive cases of robotic assisted laparoscopic radical cystectomy with regard to perioperative results, pathological outcomes and surgical complications.

A total of 84 consecutive patients (70 male and 14 female) underwent robotic radical cystectomy and urinary diversion at our institution from January 2007 to August 2010 for clinically localized bladder cancer. Outcome measures evaluated included operative variables, hospital recovery, pathological outcomes and complication rate.

Mean age of this cohort was 65.5 years (range 28 to 82). Of the patients 62 underwent ileal conduit diversion, 22 received a neobladder. Mean operating room time for all patients was 261min. (range: 243-618min.) and mean surgical blood loss was 298ml (range: 50-2000ml). 29% of the cases were pT1 or less disease, 38% were pT2, 26% and 7% were pT3 and T4 disease respectively, 15% were node positive. Mean number of lymph nodes removed was 15 (range 1 to 33). In 2 cases (2.4%) there was a positive surgical margin. Mean days to flatus were 2.12, bowel movement 2.87 and discharge home 17.7 (range: 10-33). There were 45 postoperative complications with 11.9% having a major complication (Clavien grade 3 or higher). At a mean followup of 16.7 months 10 patients (11%) had disease recurrence and 2 died of disease.

Our experience with robotic radical cystectomy for the treatment of bladder cancer suggests that in proper hands this procedure provides acceptable surgical and pathological outcomes.

Written by: Treiyer A, Saar M, Kopper B, Kamradt J, Siemer S, Stöckle M.

Reference: Actas Urol Esp. 2011 Mar;35(3):152-157.

PubMed Abstract  PMID: 21345519

Predictors of outcome of non-muscle-invasive and muscle-invasive bladder cancer[vii]

Thursday, 17 March 2011

Bladder cancer is a major cause of morbidity and mortality. At initial diagnosis, 75% of patients present with non-muscle-invasive disease and 25% of patients have muscle-invasive or metastatic disease.Patients with noninvasive disease suffer from a high rate of recurrence and 10-30% will have disease progression. Patients with muscle-invasive disease are primarily treated with radical cystectomy, but frequently succumb to their disease despite improvements in surgical technique. In non-muscle-invasive disease, multiplicity, tumor size, and prior recurrence rates are the most important predictors for recurrence, while tumor grade, stage, and carcinoma in situ are the most important predictors for progression. The most common tool that clinicians use to predict outcomes after radical cystectomy is still the tumor-node-metastasis (TNM) staging system, with lymph node involvement representing the most important prognostic factor. However, the predictive accuracy of staging and grading systems are limited, and nomograms incorporating clinical and pathologic factors can improve prediction of bladder cancer outcomes. One limitation of current staging is the fact that tumors of a similar stage and grade can have significantly different biology. The integration of molecular markers, especially in a panel approach, has the potential to further improve the accuracy of predictive models and may also identify targets for therapeutic intervention or patients who will respond to systemic therapies.

Written by:  Youssef RF, Lotan Y.

Reference: ScientificWorldJournal. 2011 Feb 14;11:369-81.  doi: 10.1100/tsw.2011.28

PubMed Abstract  PMID: 21336453

Do patients benefit from routine follow-up to detect recurrences after radical cystectomy and ileal orthotopic bladder substitution[viii]

International Braz J Urol, 03/15/2011

Giannarini G et al. – Patients diagnosed with asymptomatic recurrences during the routine follow–up after radical cystectomy (RC) had a slightly higher survival than patients with symptomatic recurrences.

Does intubated uretero-ureterocutaneostomy provide better health-related quality of life than orthotopic neobladder in patients after radical cystectomy for invasive bladder cancer[ix]

International Urology and Nephrology, 03/15/2011

Vakalopoulos I et al. – Patients with uretero–ureterocutaneostomy (UUC) surprisingly presented at least equal quality of life than the presumably less debilitating and more recent orthotopic neobladder (ONB).

Invasive bladder cancer in the eighties: transurethral resection or cystectomy[x]

International Braz J Urol, 03/09/2011

Faba OR et al. – Radical cystectomy (RC) in octogenarian patients is a safe procedure, with complication and survival rates comparable to RC series in general population. Transurethral resection (TUR) for patients with muscle invasive bladder cancer (MIBC) within this age range is a much less morbid procedure, but disease specific survival is lower.

Maximizing cure for muscle-invasive bladder cancer: Integration of surgery and chemotherapy[xi]

Friday, 25 February 2011

Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

The optimal treatment strategy for muscle-invasive bladder cancer remains controversial.

To determine optimal combination of chemotherapy and surgery aimed at preserving survival of patients with locally advanced bladder cancer.

We performed a critical review of the published abstract and presentation literature on combined modality therapy for muscle-invasive bladder cancer. We emphasized articles of the highest scientific level, combining radical cystectomy and perioperative chemotherapy with curative intent to affect overall and disease-specific survival.

Locally invasive, regional, and occult micrometastases at the time of radical cystectomy lead to both distant and local failure, causing bladder cancer deaths. Neoadjuvant and adjuvant chemotherapy regimens have been evaluated, as well as the quality of cystectomy and pelvic lymph node dissection.

Prospective, randomized clinical trials argue strongly for neoadjuvant cisplatin-based chemotherapy followed by high-quality cystectomy performed by an experienced surgeon operating in a high-volume center. Adjuvant chemotherapy after surgery is also effective when therapeutic doses can be given in a timely fashion. Both contribute to improved overall survival; however, many patients receive only one or none of these options, and the barriers to receiving optimal, combined, systemic therapy and surgery remain to be defined. An aging, comorbid, and often unfit population increasingly affected by bladder cancer poses significant challenges in management of individual patients.

Written by:  Feifer AH, Taylor JM, Tarin TV, Herr HW.

Reference: Eur Urol. 2011 Jan 18. doi: 10.1016/j.eururo.2011.01.014

PubMed Abstract  PMID: 21257257

Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer Well Tolerated Among Elderly Patients[xii]

: Presented at ASCO-GU

By Ed Susman

ORLANDO, Fla — February 22, 2011 — About half of older patients diagnosed with muscle-invasive bladder cancer achieved at least a partial response following neoadjuvant chemotherapy with gemcitabine and cisplatin, researchers
reported here at the 2011 Genitourinary Cancers Symposium (ASCO-GU).

The treatment prior to cystectomy showed that 44.4% of the patients who were initially diagnosed with a tumour stage >T2 were downgraded to pT0 or pT1 after undergoing chemotherapy.

“Neoadjuvant chemotherapy with gemcitabine and cisplatin is feasible and well-tolerated in elderly patients with adequate renal function,” reported Dora Niederseuss-Beke, MD, Barmherzige Brüder Hospital, Vienna, Austria, in her poster presentation on February 18.

“Patients achieving a less than pT2 pathologic stage after chemotherapy remained progression-free at a median follow-up of 17 months,” she added. “Patients with muscle-invasive urothelial cancer greater than pT2 had a median
progress-free survival of 14 months. The median overall survival has not been reached.”

Among the 23 patients who received chemotherapy, no treatment-related febrile neutropenia or deaths occurred, Dr. Niederseuss-Beke observed. The most common grade 3/4 events were thrombopenia (11 patients), neutropenia (6 patients), leucopenia (3 patients), nausea (2 patients), and pulmonary emboli (2 patients). “Due to these grade 4 thromboembolic events, prophylactic anticoagulation during treatment should be considered,” she noted.

The patients, all aged older than 65 years, included 8 women and 15 men. Their median age was 72; 19 were in World Health Organization (WHO) performance status 0 and the others were in performance status 1.

The study was open to patients with muscle-invasive bladder cancer with no prior treatment. The patients were required to have adequate renal functioning defined as a creatinine clearance of >60 mL/min. They were treated with
gemcitabine 1,000 mg/m[]2[] on days 1, 8, and 15 and cisplatin 70 mg/m[]2[] on day 2 every 28 days for 3 cycles. Four weeks after completing chemotherapy, the patients’ tumours were reassessed. Radical cystectomy was then performed 6 to 8 weeks after concluding chemotherapy.

In the trial, 21 of the 23 patients were able to finish the chemotherapy regimen and 17 of the patients eventually underwent cystectomy.

Dr. Niederseuss-Beke and colleagues suggested that the gemcitabine plus cisplatin neoadjuvant therapy might be less toxic than standard methotrexate-vinblastine-doxorubicin-cisplatin combination treatment. They also noted that pathologic response appeared lower in this older cohort than in younger patients.

“Further evaluation in a prospective randomised trial is needed,” the researchers suggested.

Perioperative mortality is significantly greater in septuagenarian and octogenarian patients treated with radical cystectomy for urothelial carcinoma of the bladder[xiii]

Thursday, 24 February 2011

Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Quebec, Canada.

To revisit whether the perioperative mortality differs between septuagenarian and octogenarian patients and younger patients in a large contemporary population-based cohort. The data from tertiary care centers have suggested that perioperative mortality after radical cystectomy is not considerably different in septuagenarian or octogenarian patients compared with younger patients. However, population-based data have stated otherwise.

From 1988 to 2006, 12 722 radical cystectomies were performed for urothelial carcinoma of the urinary bladder in 17 Surveillance, Epidemiology, and End Results registries. Of those 12 722 patients, 4480 (35.2%) were aged 70-79 years and 1439 (11.3%) were aged ≥80 years. Univariate and multivariate logistic regression models tested the 90-day mortality after radical cystectomy. Covariates consisted of sex, race, year of surgery, Surveillance, Epidemiology, and End Results registry, and histologic grade and stage.

The overall 90-day mortality rate was 4% for the entire population, 2% for patients aged ≤ 69 years, 5.4% for septuagenarian patients, and 9.2% for octogenarian patients. In the multivariate logistic regression analyses, septuagenarian (odds ratio 2.80; P < .001) and octogenarian (odds ratio 5.02; P < .001) age increased the risk of 90-day mortality after radical cystectomy.

In the present population-based analysis, the perioperative mortality after radical cystectomy was three- and fivefold greater in the septuagenarian and octogenarian patients, respectively, which was greater than that in tertiary care centers. This information should be included in informed consent considerations.

Written by:  Liberman D, Lughezzani G, Sun M, Alasker A, Thuret R, Abdollah F, Budaus L, Widmer H, Graefen M, Montorsi F, Shariat SF, Perrotte P, Karakiewicz PI.

Reference: Urology. 2011 Jan 20. doi: 10.1016/j.urology.2010.07.537

PubMed Abstract  PMID: 21256568

Early vs delayed radical cystectomy for ‘high-risk’ carcinoma not invading bladder muscle: Delay of cystectomy reduces cancer-specific survival

Friday, 18 February 2011

Department of Urology, University Medical Center Mainz, Germany.

Study Type – Therapy (case series) Level of Evidence 4.

To analyze the impact of a delayed radical cystectomy (rCx) and clinical variables on cancer-specific survival (CSS) in patients presenting ‘high-risk’ carcinoma not invading bladder muscle (nmiBCA).

Between 1989 and 2006, 278 patients who presented ‘high-risk’ nmiBCA finally underwent rCx in our institution. CSS was correlated with clinical variables such as the number of transurethral resections of the bladder (TURBs), interval between first TURB and rCx, adjuvant therapies, tumour upstaging at rCx, tumour stage and lymph node (LN) status.

The overall 5- and 10-year CSS was 82% and 76%, respectively. Significant correlations were found between the 5-year CSS and categorized number of TURBs (≤ 2 vs >2: 88% vs 71%; P= 0.001), interval between first TURB and rCx (≤ 4 months vs >4 months: 86% vs 77%; P= 0.04), adjuvant therapies (no vs yes: 86% vs 66%; P= 0.001), tumour upstaging at rCx (no vs yes: 89% vs 67%; P < 0.001), tumour stage at rCx (bladder confined vs non-confined: 88% vs 56%; P < 0.001) and LN status (no vs yes: 88% vs 36%; P < 0.001). Multivariate analysis identified categorized number of TURBs (hazard ratio, HR, 0.14; 95% CI, 0.07-0.44; P < 0.001), categorized interval between first TURB and rCx (HR, 3.27; 95% CI, 1.24-8.59; P= 0.017), LN status (HR, 0.13; 95% CI, 0.06-0.26; P < 0.001) and tumour stage at rCx (HR, 0.49; 95% CI, 0.26-0.92; P= 0.03) as independent risk factors for CSS.

Delay of rCx in ‘high-risk’ nmiBCA deteriorates CSS and should be avoided. The number of TURBs and the interval between first TURB and rCx are causative factors for delayed rCx and are independently correlated with CSS.

Written by: Jäger W, Thomas C, Haag S, Hampel C, Salzer A, Thüroff JW, Wiesner C.

Reference: BJU Int. 2011 Jan 18. doi: 10.1111/j.1464-410X.2010.09980.x

PubMed Abstract PMID: 21244611

Trends in the use of radiotherapy and radical surgery for patients with bladder urothelial cell carcinoma in East Anglia, 1995–2006[xiv]

Use of radical surgery in urothelial cell carcinoma (UCC) invading bladder muscle increased and use of radiotherapy decreased during the study period, most probably reflecting the increasing availability of specialist surgical management.

Does the greater number of lymph nodes removed during standard lymph node dissection predict better patient survival following radical cystectomy?[xv]

Thursday, 17 February 2011

Department of Urology, Eulji University Hospital, Eulji University College of Medicine, Daejeon, Korea.

To determine whether the number of lymph nodes (LNs) removed during radical cystectomy (RC) and pelvic LN dissection (LND) is associated with patient survival.

Data on 450 patients who underwent RC and standard bilateral pelvic LND for urothelial bladder cancer without receiving neoadjuvant chemotherapy were reviewed. The extent of LND included common iliac artery bifurcation proximally, genitofemoral nerve laterally and the pelvic floor caudally. The impact of the number of LNs removed, analyzed as both continuous and categorical variables, on cancer-specific survival (CSS) and recurrence-free survival (RFS) was analyzed.

The median number of LNs removed was 18 (mean 19.6, range 10-94). Of total 450 patients, 129 (28.7%) had node-positive (N +) disease. For entire patients, the number of LNs removed was not associated with CSS and RFS in the analysis with continuous variable (P = 0.715; P = 0.442, respectively), quartiles (P = 0.924; P = 0.676, respectively), or < 18 versus ≥18 LNs removed (5-year CSS rates: 67.0% vs. 69.4%, P = 0.679; 5-year RFS rates = 59.4% vs. 60.6%, P = 0.725, respectively). Similarly, the number of LNs removed was not associated with CSS and RFS in both N0 and N + patients, and in each T stage. Multivariate analyses showed that T stage and lymphovascular invasion were significant predictors for survival in N0 patients, whereas adjuvant chemotherapy and LN density were predictors for survival in N + patients.

If meticulous LND was performed based on standardized LND template during RC, the number of LNs removed was not associated with patient survival.

Written by: Park J, Kim S, Jeong IG, Song C, Hong JH, Kim CS, Ahn H.

Reference: World J Urol. 2011 Jan 15. doi: 10.1007/s00345-011-0644-9

PubMed Abstract  PMID: 21240505

Perioperative Mortality Is Significantly Greater in Septuagenarian and Octogenarian Patients Treated With Radical Cystectomy for Urothelial Carcinoma of the Bladder[xvi]
Urology, 02/01/2011

Liberman D et al. – In the present population–based analysis, the perioperative mortality after radical cystectomy was three– and fivefold greater in the septuagenarian and octogenarian patients, respectively, which was greater than that in tertiary care centers.

RC Mortality Stats

Hospital volume and 90-day mortality risk after radical cystectomy: A population-based cohort study[xvii]

Tuesday, 11 January 2011

Division of Urology, VA Puget Sound Health Care System, 1660 S. Columbian Way, S-112-GU, Seattle, WA, 98108, USA.

Hospital cystectomy volume has been associated with in-hospital perioperative mortality in previous studies. In this study, we examine the relationship between hospital cystectomy volume and 90-day mortality in a population-based cohort of patients undergoing cystectomy for bladder cancer.

We performed a retrospective cohort study using population from the State of Washington Comprehensive Hospital Abstract Reporting System (CHARS) database. We examined the association between hospital cystectomy volume (categorized into volume tertiles) and cumulative 90-day mortality in patients undergoing cystectomy for bladder cancer. Multivariate regression was used to adjust for patient age, comorbid disease, year of surgery, and gender. Standard errors were clustered by discharge hospital.

We identified 823 patients who underwent cystectomy for bladder cancer at 39 unique hospitals in 2003-2007. The unadjusted cumulative 90-day cumulative mortality was 5.4, 6.9, and 8.4% for patients discharged from hospitals in the high, medium, and low volume tertiles, respectively (P = 0.35). In the multivariate analysis, the patients undergoing cystectomy who were discharged from hospitals in the highest volume tertile had a lower risk of death in the first 90 days postoperatively compared to patients discharged from hospitals in the low volume tertile, though the finding was not statistically significant (OR = 0.68, 95% CI 0.29-1.56).

Ninety-day cumulative mortality after cystectomy for bladder cancer is significant and may be associated with hospital cystectomy volume.

Written by: Porter MP, Gore JL, Wright JL.

Reference: World J Urol. 2010 Dec 5. doi: 10.1007/s00345-010-0626-3

PubMed Abstract PMID: 21132553

By DukeMD (Inspire) Posted 18 May 2010 at 6:24 pm

The mortality statistics for radical cystectomy, as for any procedure or treatment need to be taken into context to be correctly understood.

1) In-hospital mortality rate = 1-2%
2) The 30-day mortality rate = 1-2%
3) The 60-day mortality rate = 2-3%
4) The 90-day mortality rate = 3-5%

So, while a 1-2% rate is true if you are asking about the likelihood of dying within a month of surgery, it does not count those people that have events or complications later in the postoperative course.

In general, in medicine we attribute a death to a major operative procedure if it occurred within 90 days of the procedure. Is this 100% accurate? Heck no! But it does allow for counting late events (infections, heart attacks, strokes, etc…) that may not manifest themselves immediately after a procedure and may be due, in part, to the procedure.

Incidentally, the mortality rates noted above are DRAMATICALLY affected by how healthy a patient is prior to surgery. For example, an average 50 year has a 90-day mortality rate of about 1% whereas a 90 year old has a 90-day mortality rate of about 15%. In other words, what you bring to the table counts for a lot and the healthier you are prior to surgery, the lower the risk of a problem. (This applies to chemo and radiation too, by the way.)

However, another piece of research on supposedly improved RC had a mortality rate of 20% within 3 years for women

Despite bacillus Calmette-Guerin therapy and early radical cystectomy, patients with primary carcinoma in situ had a high rate of disease progression. Response to bacillus Calmette-Guerin was significantly associated with a lower rate of disease progression or early radical cystectomy.

Contemporary outcomes of 2287 patients with bladder cancer who were treated with radical cystectomy[xviii]

A Canadian multicentre experience – Abstract

Tuesday, 25 January 2011  |  John W Robertson

To evaluate data obtained from a large, multi-institutional, contemporary series of patients who underwent radical cystectomy (RC) in a universal healthcare system aiming to assess outcome and identify novel prognostic variables.

Data were collected and pooled from 2287 patients treated with RC between 1998 and 2008 by urological oncologists from eight Canadian academic centres. Collected variables included various clinicopathological parameters, recurrence and death. Survival and prognostic variables were analyzed using the Kaplan-Meier method and Cox regression analysis.

The median age of patients was 68 years with a mean (median) follow-up time of 35 (29) months. The 30, 60 and 90-day postoperative mortality rates were 1.3%, 2.6% and 3.2%, respectively. The 5-year overall, recurrence-free and cancer-specific survival was 57%, 48% and 67%, respectively, with a local recurrence rate of 6%. Pathological stage distribution was<=”” p=””>

RC performed at academic centres provides excellent local control of disease and an acceptable clinical outcome with low perioperative mortality in patients who are treated within a universal healthcare system. Smoking, pelvic lymphadenectomy and receipt of adjuvant chemotherapy are independent prognostic factors for survival. Neoadjuvant chemotherapy continues to be under-utilized in Canada.

Long-term complications of conduit urinary diversion[xix]

“We evaluated long-term surgical complications and clinical outcomes in a large group of patients treated with conduit urinary diversion.

We identified 1,057 patients who underwent radical cystectomy with conduit urinary diversion using ileum or colon at our institution from 1980 to 1998 with complete followup information. Patients were followed for long-term clinical outcomes and analyzed for the incidence of diversion specific complications.

“Conduit urinary diversion is associated with a high overall complication rate but a low reoperation rate. Long-term followup of these patients is necessary to closely monitor for potential complications from the urinary diversion that can occur decades later.

Does the greater number of lymph nodes removed during standard lymph node dissection predict better patient survival following radical cystectomy[xx]

World Journal of Urology, 01/20/2011

” If meticulous lymph nodes dissection (LND) was performed based on standardized LND template during radical cystectomy (RC), the number of LNs removed was not associated with patient survival.

Radical TURB for management of muscle invasive disease[xxi]

” Retrospective studies suggest that some patients with T2 disease who do not undergo cystectomy have long term survival suggesting TURBT alone is adequate. The challenge is to prospectively identify these patients.

This group studied invasive bladder tumors in 4 samples, based upon their depth into the bladder. Among 133 patients, they found progression in 28%, and the presence of TIS was an independent predictor for progression. A sessile tumor was also significant. At 10 years, the cause-specific survival (CSS) was 79.5 %, with 65% bladder retention. Age had a negative impact on overall survival (OS), but not CSS. This might suggest that young patients are candidates, he said. Since 30% will progress, close followup is essential, he concluded.

Treatment of muscle invasive bladder cancer: Evidence from the National Cancer Database, 2003 to 2007[xxii]

40,388 patients 18 to 99 years old diagnosed with muscle invasive (stages II to IV) bladder cancer in 2003 to 2007 from the National Cancer Database. Treatment included cystectomy, neoadjuvant and adjuvant chemotherapy, chemotherapy without surgery and radiation therapy.

“The proportion of patients treated with cystectomy (42.9%) and radiation therapy (16.6%) remained stable with time while the incidence of those who received chemotherapy increased from 27.0% in 2003 to 34.5% in 2007 due to an increase in neoadjuvant chemotherapy and chemotherapy without surgery.

“The cystectomy rate decreased with age and was lower in racial/ethnic minorities (especially black patients), uninsured or Medicaid patients, patients residing in the South and Northeast, and those treated at nonteaching/research hospitals. The partial cystectomy rate decreased and lymphadenectomy extent increased with time.

“The perioperative mortality rate was 2.6% and it was higher at low vs very high volume hospitals (OR 1.71, 95% CI 1.26-2.32).

Hospital volume and 90-day mortality risk after radical Cystectomy[xxiii]

a population-based cohort study
World Journal of Urology, 12/09/2010

Porter MP et al. – Hospital cystectomy volume has been associated with in–hospital perioperative mortality in previous studies. In this study, authors examine the relationship between hospital cystectomy volume and 90–day mortality in a population–based cohort of patients undergoing cystectomy for bladder cancer. Ninety–day cumulative mortality after cystectomy for bladder cancer is significant and may be associated with hospital cystectomy volume. [My emphasis]

Cisplatin-Based Induction Regimens Comparable for Invasive Bladder Cancer[xxiv]

By: DOUG BRUNK, Internal Medicine News Digital Network 12/03/10
Major Finding: A comparison of induction regimens shows that 87% of patients treated with paclitaxel plus cisplatin and 79% of those given 5-FU plus cisplatin were downstaged to T0, Ta, and Tcis.

Data Source: 97 patients with muscle-invading bladder cancer in a randomized multicenter, phase II trial.

Disclosures: The National Cancer Institute funded the study. Dr. Zietman said that he had no financial conflicts to disclose.

SAN DIEGO – Cisplatin plus paclitaxel and cisplatin plus 5-fluorouracil induction regimens are equally effective, and can be combined with radiation and transurethral resection in a bladder-sparing protocol, preliminary results from an ongoing, randomized, phase II trial show.

Both regimens produce significant acute toxicity, yet more than 90% of patients completed induction and more than 80% completed consolidation without deviation, Dr. Anthony L. Zietman reported at the annual meeting of the American Society for Radiation Oncology.

After a median of 3 years, 73% of patients in the paclitaxel/cisplatin arm and 69% in the 5-FU/cisplatin arm were alive with intact bladders. The difference was not statistically significant.

“Adjuvant therapy remains a challenge after both regimens, with low rates of completion,” said Dr. Zietman, professor of radiation oncology at Massachusetts General Hospital and Harvard Medical School, Boston. “This is a problem because many of these patients have occult micrometastatic disease, so we do want nontoxic adjuvant therapy.”

In the RTOG (Radiation Therapy Oncology Group) 0233 study funded by the National Cancer Institute, Dr. Zietman and his associates at 33 institutions enrolled 97 patients with muscle-invading bladder cancer.

All patients underwent a transurethral resection and then were randomized into two chemotherapy arms: paclitaxel (50 mg/m2 weekly) plus cisplatin (15 mg/m2 on 3 days per week), or 5-FU (400 mg/m2 on 3 days per week on alternate weeks) plus the same cisplatin schedule. Patients in both arms also received radiotherapy twice daily to a total of 64.3 Gy, followed by adjuvant cisplatin/gemcitabine/paclitaxel chemotherapy.

Four patients were not eligible to complete the trial, leaving 46 in the paclitaxel/cisplatin arm and 47 in the 5-FU/cisplatin arm. Median follow-up was 3 years. The median age of patients was 66 years, 84% were men, and 95% had T2 disease.

Statistically similar proportions of patients in both arms had grade 2 or 3 toxicity during chemoradiation (70% in the paclitaxel/cisplatin arm and 62% in the 5-FU/cisplatin arm). The proportion with late toxicity reaching grade 3 or higher was also similar between the two groups (6% and 4%, respectively). The only case of grade 4 toxicity occurred in the paclitaxel/cisplatin arm.

“The big problem with the trial is with the adjuvant chemotherapy,” Dr. Zietman said, noting that 86% of patients in the paclitaxel/cisplatin arm and 76% in the 5-FU/cisplatin arm had grade 3 or 4 toxicity during the later adjuvant treatment.

Dr. Zietman, the immediate past president of ASTRO, reported that 98% of patients in the paclitaxel/cisplatin arm completed induction; while 4 had grade 4 toxicity during induction, 11 had grade 4 toxicity during adjuvant therapy. Similarly, 96% of patients in the 5-FU/cisplatin arm completed induction; only 1 had grade 4 toxicity during induction, but 15 had grade 4 toxicity during adjuvant therapy.

The adjuvant cisplatin/gemcitabine/paclitaxel regimen “is standard chemotherapy given to [patients] after a cystectomy, but it really was a struggle to get them through it,” he said. “It didn’t matter which chemotherapy regimen had been used up front. The outback chemotherapy was difficult. It was toxic.”

After induction therapy, 87% of patients in the paclitaxel/cisplatin arm and 79% in the 5-FU/cisplatin arm were downstaged to T0, Ta, and Tcis bladder cancer; the difference was not statistically significant. Complete response was also statistically similar between the two arms (72% and 62%, respectively).

To date, Dr. Zietman concluded, “both regimens produce similarly high rates of tumor response and bladder preservation. I think it leaves you with a choice. Either regimen can be used.”

Dr. Zietman said that he had no financial conflicts to disclose.

Defining Early Morbidity of Radical Cystectomy for Patients with Bladder Cancer Using a Standardized Reporting Methodology[1]

Accepted 2 July 2008. published online 21 July 2008.


Reporting methodology is highly variable and nonstandardized, yet surgical outcomes are utilized in clinical trial design and evaluation of healthcare provider performance.


We sought to define the type, incidence, and severity of early postoperative morbidities following radical cystectomy (RC) using a standardized reporting methodology.

Design, setting, and participants

Between 1995 and 2005, 1142 consecutive RCs were entered into a prospective complication database and retrospectively reviewed for accuracy. All patients underwent RC/urinary diversion by high-volume fellowship-trained urologic oncologists.


All complications within 90 d of surgery were analyzed and graded according to the Memorial Sloan-Kettering Cancer Center complication grading system. Complications were defined and stratified into 11 specific categories. Univariate and multivariate regression models were used to define predictors of complications.

Results and limitations

Sixty-four percent (735/1142) of patients experienced a complication within 90 d of surgery. Among patients experiencing a complication, 67% experienced a complication during the operative hospital admission and 58% following discharge. Overall, the highest grade of complication was grade 0 in 36% (n=407), grade 1–2 in 51% (n=582), and grade 3–5 in 13% (n=153). Gastrointestinal complications were most common (29%), followed by infectious complications (25%) and wound-related complications (15%). The 30-d mortality rate was 1.5%.


Surgical morbidity following RC is significant and, when strict reporting guidelines are incorporated, higher than previously published. Accurate reporting of postoperative complications after RC is essential for counseling patients, combined modality treatment planning, clinical trial design, and assessment of surgical success.

Take Home Message

Accurate reporting of complications utilizing the 10 reporting criteria and methodology is essential for preoperative counseling, for identifying modifiable risk factors to reduce complication rates, for planning combined modality treatment, for clinical trial design, and for a more accurate assessment of surgical success.

Radical cystectomy for patients with pT4 urothelial carcinoma in a large population-based[xxv]

Tuesday, 12 October 2010

Cancer Prognostics and Health Outcomes Unit Department of Urology, University of Montreal Health Centre, Montreal, Canada.

Study Type – Therapy (cohort) Level of Evidence 2b.

To examine cancer-specific mortality (CSM) in patients with pT4N(0-3) M(0) urothelial carcinoma of the urinary bladder (UCUB) and to compare it to patients with pT3N(0-3) M(0) , in a population-based cohort treated with radical cystectomy (RC).

RCs were performed in 5625 pT3-T4bN(0-3) M(0) patients with UCUB within 17 Surveillance, Epidemiology and End Results (SEER) registries between 1988 and 2006. Univariable and multivariable models tested the effect of pT4a vs pT4b vs pT3 stages on CSM. Covariates consisted of age, gender, race, lymph node status and SEER registries. All analyses were repeated in 3635 pN(0) patients.

Of 5625 patients, 2043 (36.3%) had pT4aN(0-3) , 248 (4.4%) had pT4bN(0-3) and 3334 had pT3N(0-3) (59.3%) UCUB. The 5-year CSM was 57.6% vs 81.7% vs 53.9% for, respectively, pT4aN(0-3) vs pT4bN(0-3) vs pT3N(0-3) patients (all log-rank P= 0.008). In multivariable analyses the rate of CSM was 2.3-fold higher in pT4b vs pT3 (P < 0.001), 1.1-fold higher in pT4a vs pT3 (P= 0.002) and 2.0-fold higher in pT4a vs pT4b patients. After restriction to pN(0) stage, pT4b patients had a 2.3-fold higher rate of CSM than pT3 patients (P < 0.001) and pT4b patients had a 2.1-fold higher rate of CSM than pT4a patients (P < 0.001). The CSM rate was the same for pT4a and pT3 patients (P= 0.1).

Our findings indicate that patients with pT4a UCUB have similar CSM as those with pT3 UCUB. Consequently, RC should be given equal consideration in patients with pT3 and pT4a UCUB.

Written by: Liberman D, Alasker A, Sun M, Ismail S, Lughezzani G, Jeldres C, Budaus L, Thuret R, Shariat SF, Widmer H, Perrotte P, Graefen M, Montorsi F, Karakiewicz PI.

Reference: BJU Int. 2010 Sep 22. doi: 10.1111/j.1464-410X.2010.09590.x

PubMed Abstract PMID: 20860649

Radical cystectomy for bladder cancer in the 70+ population: A nation-wide registry analysis of 845 patients[xxvi]

Thursday, 19 August 2010

Department of Urology and Andrology, Danube Hospital, Vienna, Austria.

To analyze demographics, perioperative mortality and overall survival of radical cystectomy (RC) in patients aged 70+ years in Austria in a nation-wide registry cohort.

All patients > 69 years who underwent RC in public hospitals (covering > 95% of all surgical procedures) in Austria between 1992 and 2004 were analyzed. Data were provided by the Austrian Health Institute (OBIG).

A total of 845 patients aged 70-89 years (mean 74) entered the analysis. The annual number of cystectomies in this age group increased from 27 in 1992 to 79 (+292%) in 2004. The mean length of hospital stay declined from 37.1 days (in 1992) to 27.1 days (in 2004). The 60-day mortality of the entire cohort was 1.5% and increased to 5.2% in patients aged 80+ years. Almost 50% of patients had to be rehospitalized within 30 days. The 5-year overall survival declined from 62% in those aged 70-74 years to 61% in those aged 75-79 years to 46% in the oldest age group (80+ years).

The annual number of cystectomies in patients aged 70+ years increased substantially during the study period. These nation-wide registry data provide insights into the current status of RC in the elderly in Austria and demonstrate that cystectomy in this age cohort can be done with an acceptable perioperative mortality and overall survival.

Written by: Madersbacher S, Bauer W, Willinger M, Wehrberger C, Berger I, Brössner C.

Reference: Urol Int. 2010 Jul 23. doi: 10.1159/000316100

PubMed Abstract PMID: 20664240

[Me: This report confirms earlier info on RC.
I’m not sure whether the 5-yr survival is after allowing for otherwise rate of deaths in each age range (that is, a percentage would die of other things anyway, so maybe the 5-year survival is, in a sense, better than it looks).
It is worrying that half of all patients need rehospitilisation within a month – I would hope that increased experience would reduce this, not just the time spent in hospital.]

See also Memorial Sloan-Kettering Bladder Cancer Nomogram for RC survival prediction

Update on muscle-invasive and locally advanced BC[xxvii]

“Dr. Fuad Freiha defined this group of patients as having stage T3b-T4, N0-N1, M0 disease.

The options for these patients are radical cystectomy/pelvic lymph node dissection, bladder sparing (radical TURBT + chemotherapy + radiation therapy), neoadjuvant chemotherapy and radical cystectomy/pelvic lymph node dissection, and radical cystectomy/pelvic lymph node dissection followed by adjuvant chemotherapy. [Or, as in my case, nothing; or ‘watchful waiting]

” ..radical cystectomy/pelvic lymph node dissection (with or without chemotherapy) is still the standard of care for these patients.

” [for] ..patients who refuse such surgical approach. The technique of bladder preservation has evolved over the years to include radical TURBT, external beam radiation therapy, and chemotherapy. This approach, however, is labor intensive and proper patient selection is key for its success.

[Research into chemo before or after RC gives conflicting results]:

“A review and meta-analysis studied the 16 neoadjuvant studies involving 3315 patients that showed a survival benefit of 6.5% for patients treated with neoadjuvant chemotherapy (Winquist et al. J Urol 2004).

“The 6 randomized adjuvant chemotherapy studies showed a significantly longer time to progression and significant prevention of recurrence. Two of the studies showed a survival advantage, with most of the studies being underpowered to show a significant survival benefit.

“A randomized study by Millikan et al. (J Clin Oncol, 2001) compared neoadjuvant with adjuvant cisplatin-based chemotherapy and did not find any survival difference.

“Dr. Freiha concluded that if clinical staging after TURBT shows nodal involvement or extravesical disease, then neoadjuvant chemotherapy should be given, and in the absence of these features, adjuvant chemotherapy should be given to patients with pT3b-T4 or pN+ patients after undergoing radical cystectomy and extended pelvic lymph node dissection.

“In addition, if resectable nodal disease is encountered during cystectomy, cystectomy and lymph node dissection should be completed with plans to administer postoperative chemotherapy.

Disease progression for neo-ad chemotherapy for TCC: Who’s at risk?[xxviii]

Written by David P. Wood, MD

Tuesday, 01 June 2010

SAN FRANCISCO, CA USA ( – Neoadjuvant methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) chemotherapy has previously been combined with radical cystectomy to improve survival from occult metastatic disease. Gemcitabine and Cisplastin (GC) chemotherapy is effective in metastatic bladder cancer and better tolerated. The purpose of this study was to evaluate disease progression while undergoing neoadjuvant GC in muscle-invasive TCC and identify the high risk groups. 74 patients (49 male 25 female) were administered 3-4 intravenous doses of GC at 28 day intervals. Mean age was 68 years (50-78). Group 1 had T2 muscle-invasive disease (n=38), group 2 had T2 + cis (n=29) and group 3 T3 (n=7). CT scans were repeated following chemotherapy. All 74 patients subsequently underwent radical cystectomy with lymph-node dissection and ileal conduit formation (68) or neo-bladder reconstruction (6). Median time interval between initiation of chemotherapy and surgery was19 weeks (average 14-26 weeks). The results are seen in the table below:

Group 1(T2 only) Group 2 (T2+CIS) Group 3 (T3)

Progression           10%                      24%                             57%

Regression             76%                     21%                             14%

No Change             14%                     55%                             28%

The authors conclude that there is an increased risk of development of disease progression in groups 2 (T2+CIS) and group3 (T3) while undergoing neo-adjuvant chemotherapy. Response rates to T2 disease alone are good i.e. in excess of 70%. Further studies with greater numbers of patients and survival data are required.

Cystectomy, Radical[xxix]

Author: Michael Christopher Large, MD, Resident Physician, Department of Urology, University of Chicago Hospitals
Coauthor(s): Scott E Eggener, MD, Assistant Professor of Surgery/Urology, University of Chicago Hospitals


In the United States, bladder cancer is the fifth most common cancer (following lung, colon, prostate, and breast cancers), fourth in prevalence among men and eighth among women. More than 90% of bladder cancers are transitional cell in origin, while, in countries with high endemic schistosomiasis rates (eg, Egypt), squamous cell carcinoma (SCC) of the bladder is more common.

Lesions limited to the urothelium (pCIS), mucosa (pTa), or lamina propria (pT1) represent 70%-80% of all newly diagnosed bladder cancer cases. Although prone to recurrences and, less commonly, progression to higher-stage disease, these lesions are typically managed with transurethral resection and selectively with intravesical chemotherapy, such as bacille Calmette-Guérin (BCG), mitomycin, or thiotepa. Patients with pT1 disease, particularly those with high-risk features (eg, multifocality, recurrence after intravesical therapy, extensive lamina propria invasion, concomitant carcinoma in situ [CIS]) are at considerable risk of disease progression and may benefit from early radical cystoprostatectomy.

Muscle-invasive bladder cancer, defined as tumors that invade the muscularis propria (pT2 or higher), requires more intensive therapy. To date, surgical resection via radical cystoprostatectomy (bladder and prostate) and pelvic lymph node dissection remain the criterion standard for determining accurate pathologic staging, optimizing curative potential, and minimizing the risk of tumor recurrence.

History of the Procedure

The first record of a radical cystectomy dates to the late 1800s. In 1949, Marshall and Whitmore described the basic surgical principles of radical cystoprostatectomy. In 1987, following the neuroanatomic mapping of the pelvic plexus by Schlegel and Walsh, nerve-sparing cystectomy became a surgical option that allowed for preservation of sexual function.1

For many years, radical cystectomy carried a significant perioperative mortality rate (5%-10%). However, presumably because of improvements in surgical technique, the evolution of intensive care medicine, and the availability of new antibiotics, radical cystectomy is now a common procedure in major medical centers and carries a perioperative mortality rate of approximately 1%-2%.2 At high-volume centers with postoperative pathway care programs, an ICU stay is no longer routine and the median hospital stay is approximately 7 days.


Bladder cancer can be axiomatically subdivided into non–muscle invasive and muscle-invasive disease. This article focuses primarily on the management of muscle-invasive transitional cell carcinoma (TCC) and the role of radical cystectomy. For a more in-depth review of the management of non–muscle invasive bladder cancer, see Bladder Cancer.


United States

  • More than 90% of bladder cancers are TCC.
  • Bladder cancer diagnoses increased by 36% from 1984-1993.
  • In the United States, up to 600,000 people have bladder cancer. In 2008, an estimated 68,000 new cases of bladder cancer were diagnosed, and 14,000 persons died of the disease.3
  • In 2008, the male-to-female incidence ratio was 2.9:1, and the male-to-female mortality ratio is 2.4:1.3
  • Bladder cancer is more common in whites than in African Americans.
  • The average age at diagnosis is 65 years.
  • Screening of asymptomatic individuals is not currently recommended.


  • In 1996, an estimated 310,000 new cases of bladder cancer were diagnosed worldwide.
  • The incidence rate in Western Europe and North America is higher than in East Asian countries.
  • In developing countries, many bladder cancers are SCCs caused by the parasite Schistosoma haematobium. In high-prevalence regions, SCC of the bladder has enormous health implications (eg, SCC is the most common solid tumor in Egyptian men).


Environmental risk factors

  • Tobacco use accounts for up to 50% of all bladder cancer cases; people who smoke heavily quintuple their risk. Former smokers are at less of a risk for the disease than active smokers. The risk associated with second-hand smoke is unclear.
  • Exposure to aromatic amines found in some dyes, paints, solvents, leather dust, inks, combustion products, rubbers, and textiles is a risk factor.
  • Prior radiation therapy is a risk factor. Women who have undergone pelvic radiation (eg, for cervical cancer) have a 2- to 4-fold increased incidence rate; survival rates are poorer in men who have undergone radiation for prostate cancer than in men of similar age and stage who have not undergone radiation.4
  • Treatment with cyclophosphamide (Cytoxan, Neosar) and ifosfamide (Ifex) may lead to the development of bladder cancer through their metabolite acrolein. Following high-dose cyclophosphamide treatment, the 12-year prevalence of bladder cancer is as high as 11%.
  • Low daily fluid intake may be a contributing factor; the relative risk in persons who drink 6 cups of water per day is 0.49 compared with that in persons who drink one cup of water per day.
  • Schistosomiasis caused by the parasite S haematobium can cause SCC; this is common in Egypt and the Nile River Valley.
  • Long-term phenacetin use is a risk factor; this agent is no longer approved for use in the United States.
  • Long-term placement of indwelling catheters is a risk factor; patients who have indwelling catheters for longer than 10 years should undergo bladder surveillance via cytology and cystoscopy.
  • Artificial sweeteners (saccharin, cyclamate), when administered in high doses to laboratory animals, are risk factors for bladder cancer; no similar evidence has been shown in humans.
  • The use of Aristolochia fangchi, a Chinese herb, has been implicated as a risk factor for both upper and lower tract TCC.
  • Coffee and tea are not risk factors for bladder cancer.


As with most neoplasms, bladder carcinogenesis is a complex multistep process that is not fully understood. Activation of proto-oncogenes, loss or inactivation of tumor suppressor genes, and abnormal growth factor or receptor expression have been implicated.

Multiple mutations of chromosome 9 have been identified in superficial bladder cancer cells. Increased expression of the epidermal growth factor receptor and increased mutations of tumor suppressor genes (eg, TP53 and Rb) are common in patients with advanced bladder cancer. Mutations and nuclear accumulation of TP53 have been correlated with an increased grade, stage, and recurrence risk.

The risk of progression to muscle-invasive disease is associated with tumor grade, stage (Ta vs T1), size, number of lesions (solitary vs multiple lesions), previous tumor recurrence, and presence of CIS.


Gross or microscopic hematuria is the initial presenting sign in 80%-90% of patients. Approximately 20% of patients have irritative symptoms such as urinary urgency, dysuria, or frequency. This presentation is typical in patients with diffuse CIS, which can be confused with a urinary tract infection and can result in a delayed diagnosis. With the more routine use of cross-sectional imaging, many bladder lesions are incidentally diagnosed. Patients with muscle-invasive disease can present with incidental or symptomatic obstructive hydroureteronephrosis or, less commonly, with metastatic deposits. These factors make bladder cancer a very uncommon incidental finding on autopsy.


Indications for radical cystectomy include the following:

  • Infiltrating muscle-invasive bladder cancer without evidence of metastasis or with low-volume, resectable locoregional metastases (stage T2-T3b)
  • Superficial bladder tumors characterized by any of the following:
    • Refractory to cystoscopic resection and intravesical chemotherapy or immunotherapy (Up to 71% of these patients may progress to stage T2 within 5 years of initial recurrence.5 )
    • Extensive disease not amenable to cystoscopic resection
    • Invasive prostatic urethral involvement
  • Stage-pT1, grade-3 tumors unresponsive to intravesical BCG vaccine therapy
  • CIS refractory to intravesical immunotherapy or chemotherapy
  • Palliation for pain, bleeding, or urinary frequency
  • Primary adenocarcinoma, SCC, or sarcoma

Indications for urethrectomy include the following:

  • Tumor in the anterior urethra
  • Prostatic stromal invasion that is noncontiguous with the primary
  • Positive urethral margin during radical cystectomy
  • Diffuse CIS of bladder, prostatic ducts, or prostatic urethra (a relative indication)

Rarely, radical cystoprostatectomy is indicated for salvage treatment for recurrent prostate cancer or intractable hematuria following primary therapy with radiation.

Relevant Anatomy

The bladder is an extraperitoneal muscular urine reservoir that lies behind the pubis symphysis in the pelvis. At the dome of the bladder lies the median umbilical ligament, a fibrous cord that is anchored to the umbilicus and that represents the obliterated urachus. This ligament contains vessels that must be ligated when divided. The ureters, which transport urine from kidney to bladder, approach the bladder obliquely and posterosuperiorly, entering at the trigone. The intravesical ureteral orifices are roughly 2-3 cm apart and form the superolateral borders of the trigone. The trigone consists of the area between the interureteric ridge and the bladder neck. The bladder neck serves as an internal sphincter, which is sacrificed during a radical cystectomy.

In males, the seminal vesicles, vas deferens, ureters, and rectum border the inferoposterior aspect of the bladder. Anterior to the bladder is the space of Retzius, which is composed of fibroadipose tissue and the prevesical fascia. The dome and posterior surface of the bladder are covered by parietal peritoneum, which reflects superiorly to the seminal vesicles and is continuous with the anterior rectal peritoneum. In females, the posterior peritoneal reflection is continuous with the uterus and vagina.

The vascular supply to the bladder arrives primarily via the internal iliac (hypogastric) arteries, branching into the superior, middle, and inferior vesical arteries, which are often recognizable as lateral and posterior pedicles. The arterial supply also arrives via the obturator and inferior gluteal artery and, in females, via the uterine and vaginal arteries. Bladder venous drainage is a rich network that often parallels the named arterial vessels, most of which ultimately drain into the internal iliac vein.

Recent extensive anatomic pathology studies have determined that initial lymphatic drainage from the bladder is primarily into the external iliac, obturator, internal iliac (hypogastric), and common iliac nodes. Following the drainage to these sentinel pelvic regions, spread may continue to the presacral, paracaval, interaortocaval, and paraaortic lymph node chains. For a more detailed explanation of lymphatic drainage, see Treatment.


Contraindications to radical cystectomy include (1) bleeding diathesis, (2) evidence of gross, unresectable metastatic disease (unless performed for palliation), and (3) medical comorbidities that preclude operative intervention (eg, advanced heart disease, poor pulmonary mechanics, advanced age).

Current Value of Neoadjuvant Chemotherapy Prior to Cystectomy[xxx]

Radical cystectomy with pelvic lymph node dissection remains the standard treatment for muscle–invasive bladder cancer. The quality of surgery is essential for optimal treatment results. The data from prospective randomized trials and meta–analyses provide support for preoperative application of platinum–based combination chemotherapy in all patients.

The role of adjuvant chemotherapy in patients with locally advanced (pT3, pT4a) and/or lymph node–positive bladder cancer[xxxi]

Urology – Original Paper

The role of adjuvant chemotherapy in patients with locally advanced (pT3, pT4a) and/or lymph node–positive bladder cancer


To report the long-term follow up of patients with locally advanced bladder cancer treated with either adjuvant chemotherapy with gemcitabine/cisplatin (GC) or methotrexate, vinblastine, epirubicin, and cisplatin (MVEC) or no additional treatment after radical cystectomy, to examine various survival endpoints and factors associated with long-term survival.

Patients and methods  

Seventy-eight patients undergoing radical cystectomy for pathologic stage T3, T4 or lymph node–positive (N+) bladder cancer were divided to observation group (46 patients) and adjuvant chemotherapy group (32 patients). Data were obtained for recurrence free (RFS) and overall survival (OS).


One-, 2- and 5-year RFS rates were 74, 56.8 and 51.1% for chemotherapy arm, whereas these ratios were 50.6, 31 and 27.6% for control arm, respectively (P = 0.032). RFS rates were significantly better in patients with lymph node–negative disease than in those with positive lymph nodes for control arm (P = 0.007), but for the chemotherapy arm there was no statistical difference between patients with lymph node–negative and –positive disease (P = 0.28). Mean OS and RFS times were 31.03 and 28.4 months for chemotherapy arm, while they were 22.17 and 18.09 months for control arm, respectively (P = 0.142, P = 0.196). On multivariate analysis, lymph node metastasis and adjuvant chemotherapy remained significant independent prognostic factors for cancer-specific survival.


Bladder cancer is chemosensitive, and using adjuvant chemotherapy is likely to improve the outcome of local treatment and to decrease the rates of distant metastases.

Use of radical cystectomy for patients with invasive bladder cancer


Wednesday, 21 April 2010

Evidence-based guidelines recommend radical cystectomy for patients with muscle-invasive bladder cancer. However, many patients receive alternate therapies, such as chemotherapy or radiation. We examined factors that are associated with the use of radical cystectomy for invasive bladder cancer and compared the survival outcomes of patients with invasive bladder cancer by the treatment they received.

From linked Surveillance, Epidemiology, and End Results-Medicare data, we identified a cohort of 3262 Medicare beneficiaries aged 66 years or older at diagnosis with stage II muscle-invasive bladder cancer from January 1, 1992, through December 31, 2002. We examined the use of radical cystectomy with multilevel multivariable models and survival after diagnosis with the use of instrumental variable analyses. All statistical tests were two-sided.

A total of 21% of the study subjects underwent radical cystectomy. Older age at diagnosis and higher comorbidity were associated with decreased odds of receiving cystectomy (for those >/=80 vs 66-69 years old, odds ratio [OR] = 0.10, 95% confidence interval [CI] = 0.07 to 0.14; for Charlson comorbidity index of 3 vs 0-1, OR = 0.25, 95% CI = 0.14 to 0.45). Long travel distance to an available surgeon was associated with decreased odds of receiving cystectomy (for >50 vs 0-4 miles travel distance to an available surgeon, OR = 0.60, 95% CI = 0.37 to 0.98). Overall survival was better for those who underwent cystectomy compared with those who underwent alternative treatments (for chemotherapy and/or radiation vs cystectomy, hazard ratio of death = 1.5, 95% CI = 1.3 to 1.8; for surveillance vs cystectomy, hazard ratio of death = 1.9, 95% CI = 1.6 to 2.3; 5-year adjusted survival: 42.2% [95% CI = 39.1% to 45.4%] for cystectomy; 20.7% [95% CI = 18.7% to 22.8%] for chemotherapy and/or radiation; 14.5% [95% CI = 13.0% to 16.2%] for surveillance).

Guideline-recommended care with radical cystectomy is underused for patients with muscle-invasive bladder cancer. Many bladder cancer patients whose survival outcomes might benefit with surgery are receiving alternative less salubrious treatments.

Written by: Gore JL, Litwin MS, Lai J, Yano EM, Madison R, Setodji C, Adams JL, Saigal CS; the Urologic Diseases in America Project.

Reference: J Natl Cancer Inst. 2010 Apr 16. doi: 10.1093/jnci/djq121

PubMed Abstract PMID: 20400716

Treatment and outcome in muscle invasive bladder cancer[xxxiii]

A population-based survey
Tuesday, 20 April 2010

Department of Urology, University Medical Center Groningen, Hanzeplein 1, P.O. box 30.001, 9700 RB, Groningen, The Netherlands.

To assess treatments and survival of patients with muscle invasive bladder cancer (MIBC) in the Comprehensive Cancer Center Northern Netherlands (CCCN) region.

Retrospective cohort analysis. Data of 548 patients with MIBC diagnosed between 1997 and 2002 were collected from the CCCN cancer registry. All had a follow-up of at least 5 years. Logistic regression analysis on treatments as well as survival analysis was performed.

The treatments were radical cystectomy in 205/548 (37.5%) patients. TUR plus radiotherapy in 246 (44.9%) and palliation in 97 (17.7%). Multivariate analysis identified TNM stage (P < 0.0001) and age (P < 0.0001) as independent variables for cystectomy. Hospital type and year of diagnosis were not significant different between patients treated by cystectomy versus other type of treatment. TNM stage (P < 0.0001), age (P = 0.0043), and comorbidity (P = 0.0028) were independent variables for disease-specific survival (DSS) after cystectomy.

In the CCCN region, only 1/3 of patients with MIBC were treated with radical cystectomy. TNM stage and age were identified as main variables for the choice for cystectomy. TNM stage, age, and comorbidity were independent variables for disease-specific survival after cystectomy.

Written by: Leliveld AM, Doornweerd BH, Bastiaannet E, Schaapveld M, de Jong IJ.

Reference: World J Urol. 2010 Apr 10. doi:10.1007/s00345-010-0546-2

PubMed Abstract PMID: 20383640

The management of BCG failure in non-muscle-invasive bladder cancer[xxxiv]

“A major dilemma among patients with non-muscle-invasive bladder cancer (NMIBC) and their physicians is the choice of an appropriate course of action following failure of intravesical bacillus Calmette-Guerin (BCG). Although classified the same, NMIBC actually consists of 2 biologically different diseases,

1. low-grade NMBIC who are likely to recur but rarely progress and,

2. high-risk T1 bladder cancer and/or carcinoma in situ (CIS or TIS) which often progresses to an aggressive muscle-invasive life threatening disease.

“While guidelines provide a good definition of BCG failure, unfortunately BCG failure cannot be accurately predicted on an individual basis. Nevertheless, with clinical and histologic parameters, risk groups should be identified because the window of curability in patients with BCG failure is narrow in the case of tumour progression to muscle-invasive cancer. Such window should be immediately targeted if possible for optimal outcome, either with conservative treatments with immunotherapy or with cystectomy. Immunotherapy agents include agents such as Urocidin, interferon-α and Vicinium. Risk factors include presence of CIS, early recurrence, recurrent vs. progressive tumor, T1 substage and gender. For patients with CIS or high-risk tumors failing BCG, the guidelines recommend cystectomy as the treatment of choice. However, cystectomies are often associated with impaired quality of life compared with conservative therapy. Thus, it remains necessary for the clinical research community to identify new methods where patients are able to keep their bladders while simultaneously keeping their tumors under control.

Prevention and management of complications following radical cystectomy for bladder cancer[xxxv]

Wednesday, 24 March 2010

Division of Urology, Department of Surgical Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Canada.

This review focuses on the prevention and management of complications following radical cystectomy (RC) for bladder cancer (BCa).

We review the current literature and perform an analysis of the frequency, treatment, and prevention of complications related to RC for BCa.

A Medline search was conducted to identify original articles, reviews, and editorials addressing the relationship between RC and short- and long-term complications. Series examined were published within the past decade. Large series reported on multiple occasions (Lee [1], Meyer [2], and Chang and Cookson [3]) with the same cohorts are recorded only once. Quality of life (QoL) and sexual function were excluded.

The literature regarding prophylaxis, prevention, and treatment of complications of RC in general is retrospective, not standardised. In general, it is of poor quality when it comes to evidence and is thus difficult to synthesise.

Progress has been made in reducing mortality and preventing complications of RC. Postoperative morbidity remains high, partly because of the complexity of the procedures. The issues of surgical volume and standardised prospective reporting of RC morbidity to create evidence-based guidelines are essential for further reducing morbidity and improving patients’ QoL.

Written by: Lawrentschuk N, Colombo R, Hakenberg OW, Lerner SP, Månsson W, Sagalowsky A, Wirth MP.

Reference: Eur Urol. 2010 Feb 26. doi:10.1016/j.eururo.2010.02.024

PubMed Abstract PMID:20227172

Radical cystectomy in patients with non-muscle invasive bladder cancer who fail BCG therapy[xxxvi]

Monday, 22 March 2010

Servicio de Urología, Fundación Puigvert, Barcelona, España.

To assess the characteristics and outcomes of patients with non-muscle invasive bladder cancer (NMIBC) undergoing radical cystectomy (RC) due to BCG failure.

Ninety-five (11%) of the 864 patients undergoing radical cystectomy (RC) at our center from 1989 to 2002 had received prior treatment with BCG. Of these, 62 (65.2%) underwent RC due to relapsing, high-risk NMIBC or CIS despite BCG therapy. A stage >/= pT2 tumor was reported in the cystectomy specimen in 17 (27%) of these patients, who were considered to have been understaged. RC was performed for clinical progression in 33 patients (34.7%). Their last transurethral resection before RC showed invasive disease. A retrospective analysis was made of the outcomes of patients who underwent RC for BCG failure and the clinical and pathological differences between understaged patients and those with clinical progression.

Five-year CSS was 90% in 45 patients with clinical and pathological NMIBC and 50.6% in 50 patients with progression to muscle-infiltrating disease (clinical progression and understaged) (p < 0,05). There were no differences in survival in patients with clinical progression as compared to understaged patients. Median time from tumor diagnosis to tumor progression was 24 months (10th-90th percentile, 6-98 months). Patients with clinical progression had significantly more T1 tumors (p = 0.015) in TUR before progression and more pT3 tumors (p < 0.01) in the RC specimen. Understaged patients more often had pathological pT4 stages (p < 0.02).

In patients with high-risk NMIBCs who fail BCG therapy, RC should be performed before progression because survival is decreased when the RC specimen shows muscle-invasive disease. High-grade T1 tumors are responsible for most early clinical progressions. Patients with NMIBC may have subclinical progression, mainly within the prostate.

Written by: Huguet J, Gaya JM, Sabaté S, Palou J, Villavicencio H.

Reference: Actas Urol Esp. 2010 Jan;34(1):63-70.

PubMed Abstract PMID:20223134

Effect of a minimum lymph node policy in radical cystectomy and pelvic lymphadenectomy on lymph node yields, lymph node positivity rates, lymph node density, and survivorship in patients with bladder cancer[xxxvii]


Extended pelvic lymphadenectomy (PLND) during radical cystectomy (RC) reportedly improves bladder cancer-specific survival.


Patients undergoing RC and PLND for invasive bladder cancer between March 2000 and February 2008 were retrospectively reviewed at the study institution. Beginning March 1, 2004, a policy was established that at least 16 lymph nodes had to be examined. Specimens with <16 lymph nodes were resubmitted (including any fat) to detect additional lymph nodes. Lymph node yields, lymph node positivity, lymph node density (LND), and survivorship before and after policy implementation were compared.

“increase in median lymph node yield, decreased mortality risk by 30%

Update of the Clinical Guidelines of the European Association of Urology on muscle-invasive and metastatic bladder carcinoma[xxxviii]

INTRODUCTION: New data regarding diagnosis and treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC.

OBJECTIVE: To review the new EAU guidelines for MiM-BC.

Evidence acquisition: A comprehensive workup of the literature obtained from Medline, the Cochrane central register of systematic reviews, and reference lists in publications and review articles was developed and screened by a group of urologists, oncologists, and radiologist appointed by the EAU Guideline Committee. Previous recommendations based on the older literature on this subject were taken into account. Levels of evidence and grade of guideline recommendations were added, modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence.

Evidence synthesis: The diagnosis of muscle-invasive bladder cancer (BCa) is made by transurethral resection (TUR) and following histopathologic evaluation. Patients with confirmed muscle-invasive BCa should be staged by computed tomography (CT) scans of the chest, abdomen, and pelvis, if available.

Adjuvant chemotherapy is currently only advised within clinical trials.

Radical cystectomy (RC) is the treatment of choice for both sexes, and lymph node dissection should be an integral part of cystectomy.

An orthotopic bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection.

Multimodality bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomy is not considered for clinical or personal reasons.

An appropriate schedule for disease monitoring should be based on: a) natural timing of recurrence; b) probability of disease recurrence; c) functional deterioration at particular sites; and d) consideration of treatment of a recurrence. In metastatic disease, the first-line treatment for patients fit enough to sustain cisplatin is cisplatin-containing combination chemotherapy.

Presently, there is no standard second-line chemotherapy.

CONCLUSIONS: These EAU guidelines are a short, comprehensive overview of the updated guidelines of (MiM-BC) as recently published in the EAU guidelines and also available in the National Guideline Clearinghouse.

PMID: 20223133 [PubMed – as supplied by publisher]

Beyond the Abstract – Risk factor analysis in a contemporary cystectomy[xxxix]

BERKELEY, CA ( – Despite significant improvements in surgical technique, preoperative preparation and perioperative care since the inception of radical cystectomy (RC), the complication rate associated with this operation remains high [My emphasis]. Patients requiring RC are elderly with considerable associated comorbidities due to the strong association of cigarette smoking and urothelial bladder carcinoma. Diverse adverse event (AE) rates after RC for urothelial bladder carcinoma range from 25% to 64% and this variability is partly due to classification errors and under reporting and/or nonstandardized reporting of AEs in published series. Standardized reporting methods are essential to characterize RC outcomes to reliably compare complication rates and severity among institutions and surgical techniques.

In this study, we defined the frequency and severity of complications after RC in patients with urothelial bladder carcinoma using standard reporting methods and AE criteria. We also explored associations between important risk factors and various specific complications to better individualize perioperative risk assessment.

We observed at least 1 adverse event in 54.0% of patients and a grade 3–4 adverse event in 40.3%.[My emphasis] The most common grade 4 AEs were myocardial infarction in 3.5% of cases, septic shock in 2.8% and pulmonary embolism in 1.8%. An association between body mass index, and any major adverse events was found after adjusting for confounding variables. Because of the large number of multiple comparisons made, we corrected our accepted p-value to avoid false-positive conclusions. Although not significant by this corrected p-value, we also observed an association between increasing age with ileus requiring total parenteral nutrition and new onset arrhythmia. These findings may warrant consideration of specific postoperative treatment and monitoring in older patients. Such measures may include pretreatment procedural patient selection, multimodal anti-ileus therapy, and prolonged postoperative telemetry in older patients.

An analysis of upper urinary tract recurrence following radical cystectomy for bladder cancer[xl]

Transitional cell carcinoma of the urothelium is often multifocal, and subsequent tumors may occur anywhere in the urinary tract afer treating the initial carcinoma. The risk of an upper urinary tract recurrence following a radical cystectomy has been reported to be approximately 2 to 8%, but there are few reports with regard to the pattern and predictive factors of upper tract recurrence. We report here the incidence and pattern of upper tract recurrence following a radical cystectomy. Of the 166 patients 5 (3%) had upper tract recurrence. The prognosis of upper urinary tract recurrence is significantly better than other site of recurrence.

Article in Japanese.

Written by: Sugi M, Fukui K, Yoshida K, Inui H, Kawakita S, Murota T, Kinoshita H, Matsuda T.

Reference: Hinyokika Kiyo. 2010 Feb;56(2):87-90.

PubMed Abstract PMID:20185992

Predictive factors and long term carcinogenic results of patients who no longer have residual tumors (stage pT0) on specimens of total cystectomy carried out for cancer of the bladder[xli]

Monday, 15 February 2010

Service d’urologie, clinique urologique, CHU Hôtel-Dieu, 1, place Alexis-Ricordeau, 44000 Nantes, France.

The aim of our study was to evaluate predictive factors and long-term carcinogenic results for patients who had had a total cystectomy for cancer of the bladder and whose final histological results did not show evidence of a residual tumor.

From 1988 to 2002, 192 patients had a total cystectomy for a bladder tumor. No residual tumor (pT0) was evident in the specimens of cystectomy of 22 patients (11.5%). None of the patients had distant metastasis or ganglions at the time of the initial examination.

Predictive factors for having no residual tumors based on the specimen of cystectomy (pT0) were an antecedent of neo-adjuvant chemotherapy (p=0.0079), an interval between the resection of the bladder and the cystectomy of more than 12 weeks (p=0.0014) and a resection of the initial bladder considered complete (p=0.0036). The average treatment of these 22 patients was 70+/-46 months. During treatment, two patients (9%) had a recurrence in the pelvis and 10 patients died including one from the development of his cancer of the bladder. Global, specific and non-recurrence survival at five years were 75%, 100% and 94%, respectively. We revealed better specific survival (p=0.0007) and without relapse (p< 0.0001) in patients who no longer had a tumor on the specimen of cystectomy (pT0) compared with patients who had a residual tumor (pT+) but with no difference in global survival (p=0.0574).

The absence of residual tumors (pT0) on a specimen of total cystectomy for cancer of the bladder was a good factor for prognosis regarding long-term survival even if tumor development was observed. Complete resection and neo-adjuvant chemotherapy probably played a beneficial role in the future of these patients.

Written by: Hitier M, Marconnet L, Luyckx F, Branchereau J, Braud G, Karam G, Bouchot O, Rigaud J.

Reference: Prog Urol. 2010 Feb;20(2):130-137. doi:10.1016/j.purol.2009.07.004

PubMed Abstract PMID:20142054

Outcome of treatment of bladder cancer: A comparison between low-volume hospitals and an oncology centre[xlii]

Thursday, 11 February 2010

Department of Urology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.

To evaluate the effect of volume of cystectomies in the Greater Amsterdam region on postoperative outcomes.

All primary bladder tumours diagnosed between 1989 and 2003 were selected from the Amsterdam Cancer Registry, a population-based cancer registry (population 3.0 million). For all patients who underwent cystectomy during 1989-2003 at 20 participating hospitals, medical records were reviewed for information on postoperative mortality, locoregional recurrences and relative risk of death. To assess the effect of volume, outcomes at an oncology centre and low-volume hospitals were compared.

During 1989-2003 a total of 1,185 cystectomies were performed in 20 hospitals of the Greater Amsterdam region. Postoperative mortality was 3.2%. During 1989-1997, 8% of cystectomies were performed at the oncology centre, increasing to 30% in 1998-2003. Although postoperative mortality at this centre decreased from 4.0% in 1989-1997 to 1.1% in 1998-2003, the latter percentage was not statistically significantly different from the other hospitals during 1998-2003 (OR 0.3; P = 0.09). No statistically significant difference in locoregional recurrence rate and in the relative risk of death was observed between the oncology centre and all other hospitals combined.

We observed a lower postoperative mortality rate in the oncology centre compared to the low-volume hospitals; however, this difference did not reach statistical significance. We could neither prove a statistically significant relation between hospital volume, local recurrence rate and survival after cystectomy. To answer the question if centralisation of cystectomies is beneficial more procedures have to be compared.

Written by: de Vries RR, Visser O, Nieuwenhuijzen JA, Horenblas S.

Reference: World J Urol. 2010 Feb 4.

PubMed Abstract PMID:20130885

Survival after cystectomy for invasive bladder cancer[xliii]

Wednesday, 03 February 2010

Department of Urology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.

To determine the difference in survival after cystectomy between patients presenting with primary muscle infiltrating bladder cancer and patients with progression to muscle infiltration after treatment for initial non-muscle-invasive bladder cancer (NMIBC).

We retrospectively analyzed the files of 188 patients who underwent cystectomy for transitional cell carcinoma between 1987 and 2005. Two groups were defined: patients presenting with muscle-invasive tumours and those progressing to muscle invasion after initial treatment. This second group was further divided into low-intermediate and high risk according to the EAU grouping for NMIBC.

The 5-year disease specific survival (95% confidence intervals) for all patients was 50%(42-59%); 49%(40-60%) in the primary muscle infiltrating group and 52%(37-74%) in the progressive group (p = ns). The 5-year disease specific survival in the progressive group according to EAU risk groups was 75%(58-97%) for the initially diagnosed low-intermediate risk tumours and 35%(17-71%) for the initially diagnosed high-risk tumours (p = 0.015). The percentage of patients with non-locally confined tumours (pT3/4-N0//any pT-N+) was 31%//45% and 24%//46% in the primary muscle infiltrating and progressive group, respectively.

Despite close observation of patients treated for non-muscle-invasive bladder cancer, the survival of patients who progress to muscle invasion is not better than survival of patients presenting with primary muscle infiltrating cancer. Patients with high-risk non-invasive tumours (EAU risk-categories) who progress to muscle-invasive disease have a worse prognosis compared to patients with low or intermediate risk tumours.

Written by: de Vries RR, Nieuwenhuijzen JA, Vincent A, van Tinteren H, Horenblas S.

Reference: Eur J Surg Oncol. 2010 Jan 22. doi:10.1016/j.ejso.2009.11.012

PubMed Abstract PMID:20097512

External stoma and peristomal complications following radical cystectomy and ileal conduit diversion[xliv]

“An ileal conduit is the most common urinary diversion following radical cystectomy for invasive bladder cancer. Unlike internal complications commonly described in urological literature, reports about the incidence of external complications are sparse.

A Medline database review (1996-2008) of English-language literature was conducted to: 1) describe and compare external stoma and peristomal complications and complication rates among outpatients with ileal conduit diversion following radical cystectomy, and 2) summarize commonly used prevention and management strategies. Fourteen publications (mostly retrospective, single-center studies) met inclusion criteria.

The reported incidence of complications ranged from 15% to 65%.

Divided according to pathogenesis, the most commonly reported complications are 1) stoma or abdominal wall-related changes – parastomal hernia, stoma prolapse, stenosis, and retraction; and 2) peristomal skin changes – chemical injury: irritant contact dermatitis, pseudoverrucous lesions, and alkaline crustations; mechanical injury: pressure ulcers, skin stripping injuries, mucocutaneous separation; infection: candidiasis, folliculitis; immunologic disorders: allergic contact dermatitis; and disease-related lesions: varices, pyoderma gangrenosum, malignancy. Peristomal complications also appear to be under-recognized and under-reported.

Research to establish the validity and reliability of assessment tools and long-term follow-up studies are needed to improve the evidence-base of prevention and care.

A phase II trial of neoadjuvant erlotinib in patients with muscle-invasive bladder cancer undergoing radical cystectomy[xlv]

“To evaluate the clinicopathological efficacy of neoadjuvant erlotinib (an epidermal growth factor receptor, EGFR, inhibitor) for invasive bladder cancer in patients undergoing radical cystectomy (RC) as despite definitive surgical therapy, only half of patients undergoing RC will have long-term disease-free survival, and effective adjunctive therapies, especially using agents with lower toxicity, would be a significant advance in the treatment of invasive bladder cancer.

“The EGFR inhibitor erlotinib, when administered in the neoadjuvant setting, can have beneficial effects in terms of surgical pathology and short-term clinical outcomes in patients undergoing RC for invasive bladder cancer.

Risk factor analysis in a contemporary cystectomy cohort using standardized reporting methodology and adverse event criteria[xlvi]

Thursday, 28 January 2010

Department of Urology, University of Texas M. D. Anderson Cancer Center, Houston, Texas.

Adverse event reporting is poorly classified and nonstandardized in the urological literature. We report adverse event data and associated risk factors using standardized reporting methods and Common Terminology Criteria for Adverse Events, version 3.0 to minimize interpretation bias and allow reliable comparisons with other populations.

We retrospectively reviewed consecutive radical cystectomies done for urothelial bladder carcinoma at our institution between January 2004 and September 2006. Adverse events within 90 days postoperatively were recorded. We explored the association of important risk factors with the overall complication rate and specific complications.

A total of 283 patients were included in the study. Complete 90-day followup data were available on 90% of patients. Median age was 70 years (IQR 62-75). Median body mass index was 26.8 kg/m(2) (IQR 24.4-31.0). At least 1 adverse event was observed in 152 patients (54.0%) and a grade 3-4 adverse event was observed in 40.3%. The most common grade 4 adverse events were myocardial infarction in 3.5% of cases, septic shock in 2.8% and pulmonary embolism in 1.8%. No patient died during followup. An association between body mass index, and any and major adverse events was found after adjusting for confounding variables.

More than 50% of patients experience an adverse event after radical cystectomy and 40% are major. Body mass index is independently associated with adverse events in these patients. These findings are important for individualized risk assessment, patient counseling and uniform assessment of quality care.

Written by: Svatek RS, Fisher MB, Matin SF, Kamat AM, Grossman HB, Nogueras-González GM, Urbauer DL, Kennedy KA, Dinney CP.

Reference: J Urol. 2010 Jan 16. doi:10.1016/j.juro.2009.11.038

PubMed Abstract PMID:20083264

Urinary diversion and morbidity after radical cystectomy for bladder cancer[xlvii]

Adjusting for case-mix differences between reconstructive groups, continent diversions conferred a lower risk of medical, surgical, and disposition-related complications that was statistically significant for bowel (3.1% lower risk; 95% confidence interval [95% CI], -6.8% to -0.1%), urinary (1.2% lower risk; 95% CI, -2.3%, to -0.4%), and other surgical complications (3.0% lower risk; 95% CI, -6.2% to -0.4%), and discharge other than home (8.2% lower risk; 95% CI, -12.1% to -4.6%) compared with ileal conduit subjects. Older age and certain comorbid conditions, including congestive heart failure and preoperative weight loss, were associated with significantly increased odds of postoperative medical and surgical complications in all subjects. CONCLUSIONS: Mode of urinary diversion after radical cystectomy for bladder cancer is not associated with increased risk of immediate postoperative complications. These results may encourage broader consideration of continent urinary diversion without concern for increased complication rates. Cancer 2010. © 2010 American Cancer Society.

Characteristics and Outcomes of Patients with Clinical T1 Grade 3 Urothelial Carcinoma Treated with Radical Cystectomy: Results from an International Cohort[xlviii]

Approximately half of the patients treated with RC without neoadjuvant chemotherapy for clinical T1G3 UCB are upstaged to muscle–invasive UCB. These rates support the inadequacy of clinical decision making based on current treatment paradigms and staging tools. Therefore, identification of patients with clinical T1G3 disease at high risk of disease progression is of the utmost importance, as these patients are likely to benefit from early RC

An Updated Critical Analysis of the Treatment Strategy for Newly Diagnosed High-grade T1 (Previously T1G3) Bladder Cancer[xlix]


High-grade T1 (formerly T1G3) bladder cancer (BCa) has a high propensity to recur and progress. As a result, decisions pertaining to its treatment are difficult. Treatment with bacillus Calmette-Guérin (BCG) risks progression and metastases but may preserve the bladder. Cystectomy may offer the best opportunity for cure but is associated with morbidity and a risk of mortality, and it may constitute potential overtreatment for many cases of T1G3 tumours. For purposes of this review, we continue to refer to high-grade T1 lesions as “T1G3.”


To review the current literature on the management of T1G3 BCa and to provide recommendations for its treatment.

Evidence acquisition

A National Center for Biotechnology Information (NCBI) PubMed search for relevant articles published between 1996 and 9 January 2009 was performed using the Medical Subject Headings “T1G3” or “T1” and “Bladder cancer.” Articles relevant to the treatment of T1G3 BCa were retained.

Evidence synthesis

The diagnosis of T1G3 disease is difficult because pathologic staging is often unreliable and because of the risk of significant understaging at initial transurethral resection (TUR) of bladder tumour. A secondary restaging TUR is recommended for all cases of T1G3. A single dose of immediate post-TUR chemotherapy is recommended. For a bladder-sparing approach, intravesical BCG should be given as induction with maintenance dosing. Immediate or early radical cystectomy (RC) should be offered to all patients with recurrent or multifocal T1G3 disease, those who are at high risk of progression, and those failing BCG treatment.


Both bladder preservation and RC are appropriate options for T1G3 BCa. Risk stratification of patients based on pathologic features at initial TUR or at recurrence can select those most appropriate for bladder preservation compared to those for whom cystectomy should be strongly considered.

Take Home Message

High-grade T1 bladder cancer has a high propensity to recur and progress. Risk stratification based on pathologic features at initial transurethral resection or at recurrence can select those most appropriate for bladder preservation compared to those for whom cystectomy should be strongly considered.

Impact of comorbidity on survival of invasive bladder cancer patients, 1996-2007: A Danish population-based cohort study[l]

Friday, 27 November 2009

Department of Urology, Viborg Hospital 8800, Viborg, Denmark; Center for Health Services Research, Vanderbilt University Medical Center, Nashville, Tennessee.

To examine (i) the prevalence of comorbidity among invasive bladder cancer (IBC) patients, and (ii) the effect of comorbidity on IBC survival and mortality in Northern Denmark. Comorbidity has shown to be associated with treatment selection and survival in patients who undergo radical cystectomy for IBC.

Patients with a diagnosis of IBC from Danish hospitals between 1996 and 2007 within a population of 1.6 million were identified through the Danish National Patient Registry. From hospital diagnosis data, we computed Charlson Comorbidity Index scores (0, 1-2, 3+) for IBC patients and computed absolute survival and relative mortality estimates according to comorbidity level.

We identified 3997 patients with IBC among whom 1715 (43%) had comorbidities. The prevalence of comorbidity tended to increase during the study period with those having scores 3+ increasing from 8%-12%. Three- and 5-year mortality rates were higher for patients with comorbidity, with mortality rates more than 2-fold higher among those with scores of 3+ and 1.5-fold higher among those with scores of 1-2 compared with no comorbidity. Generally, the same pattern was seen for 1-year relative survival rates.

Comorbidity was seen among 43% of IBC patients and severe comorbidity was a predictor of poorer survival.

Written by: Lund L, Jacobsen J, Clark P, Borre M, Nørgaard M.

Reference: Urology. 2009 Nov 13 doi:10.1016/j.urology.2009.07.1320

PubMed Abstract PMID:19914698

Robot-assisted radical cystectomy: intermediate survival results at a mean follow-up of 25 months

Tuesday, 17 November 2009

Pathology, Mayo Clinic, Phoenix, AZ.

To assess the overall and disease-specific survival rates of patients undergoing robot-assisted radical cystectomy (RARC) compared with historical open cystectomy.

Survival, pathological and demographic data were collected on all patients undergoing RARC for bladder cancer from both Tulane University Medical Center and Mayo Clinic Arizona. Of a total of 80 RARCs we only included those with a follow-up of >/=6 months from surgery. Survival curves were compared with those from historical series of open cystectomy.

Of the 80 patients 59 were identified as having a follow-up of >/=6 months from the date of surgery. The mean (range) follow-up was 25 (6-49) months. Overall survival rates at 12 and 36 months were 82% and 69%, respectively, and disease-specific survival rates were 82% and 72% at 12 and 36 months, respectively. These results are comparable to survival rates from open cystectomy. As expected, patients with lymph node-positive disease fared worse than those with lymph node-negative disease. Patients with extravesical lymph node-negative disease (pT3, pT4) fared worse than patients with organ-confined lymph node-negative disease. Also, patients with lymph node-positive disease fared worse than those with extravesical lymph node-negative disease, which is consistent with historical results of open cystectomy.

RARC has a comparable survival rate to open cystectomy in the intermediate follow-up. Further study with a longer follow-up and more patients is necessary to determine any long-term survival benefits.

Written by: Martin AD, Nunez RN, Pacelli A, Woods ME, Davis R, Thomas R, Andrews PE, Castle EP.

Reference: BJU Int. 2009 Nov 9 doi:10.1111/j.1464-410X.2009.09042.x

PubMed Abstract PMID:19903170

Invasive TCC in the Elderly: Radical cystectomy?[li]

Friday, 28 August 2009

PORT DOUGLAS, AUSTRALIA ( – To reduce morbidity in the elderly patient, conservative multimodal therapy concepts for invasive bladder cancer are emerging as an alternative to radical cystectomy. It was the aim of the study to report on our recent experience with peri- and postoperative morbidity of radical cystectomy in patients 75 years and older compared to younger patients.

Medical records of 326 consecutive patients undergoing radical cystectomy in our institution from May 2004 through April 2008 were reviewed. Intra- and perioperative parameters have been analyzed to assess perioperative morbidity and mortality of radical cystectomy in these patients.

Eighty-five of 326 patients (26%) were ≥75 years (75 – 95) old. ASA-score was equal 3 or greater in 51% of patients ≥75 years and 32% of patients <75 years. Ileal conduit was performed in 83% of patients ≥75, 16% received an ileal neobladder compared to 46% and 51%, respectively, in patients <75. A total of 33 patients (39%) in the older patient group received blood transfusions intraoperatively compared to 76 patients (32 %) in the younger age group. In 6 patients ≥75 years (7.1%) and 17 patients < 75 (7.1%) open surgical revision was necessary, perioperative complication rate was 22% and 21%, respectively. The most common complications were wound dehiscence (5.9% vs. 7.5%), infections (4.7% vs. 4.6%), and pulmonary embolism (3.5% vs. 2.1%). Perioperative mortality was 1.2% (1 patient) in the elderly versus 0.4% (1 patient) in the younger age group.

Our data show that radical cystectomy can be offered to the elderly patient with acceptable morbidity. Because of higher comorbidity rate in elderly patients compared to younger patients, therapeutic decision for radical cystectomy in the elderly patient should be made carefully and individually. Nevertheless our results demonstrate that age itself is not a main criterion which has to be considered strongly in the decision-making for radical cystectomy.
Written by: Tilki D, Zaak D, Gerwens N, Seitz M, Stief C, and Reich O
Department of Urology, Ludwig-Maximilians-University, Munich, Germany
For presentation at the 25th Annual Meeting of the Urological Research Society (URS), August 10 – 14, 2009, Thala Beach, North Queensland, Australia

Management of muscle invasive disease[lii]

Written by David P. Wood, MD    Tuesday, 18 August 2009

RIO DE JANEIRO, BRAZIL ( – Transurethral resection alone can be effective in muscle invasive tumors. 20% of patients will have no cancer on re-resection and 15% will have Ta or T1 disease. Patients with no tumor on re-resection do very well, but those with any residual cancer have a significantly worse survival rate.

It is worthwhile to perform a repeat TURBT in patients with muscle invasive disease. If T0, consider observation, perhaps with BCG therapy. If any residual disease is found on the repeat TURBT then chemotherapy and radiation or cystectomy is recommended. Neo adjuvant chemotherapy has been shown to provide a 5% absolute survival benefit for patients undergoing a radical cystectomy. Some experts suggest that this difference is too small to recommend for patients with cT2 disease, but randomized trials show that even in this group, neoadjuvant chemotherapy is beneficial. Most experts recommend neoadjuvant chemotherapy for patients with hydronephrosis or with cT3-cT4 disease. Chemotherapy can be effective even in unresectable tumors with 30% of eligible patients having no tumor in the radical cystectomy specimen and a 50% two-year survival rate. It is critical to have complete resolution of nodal disease and the examination under anesthesia must reveal a respectable bladder after chemotherapy before proceeding with radical cystectomy. Gemcitabine and Cisplatin is the best regimen and should provide a 30% complete response rate. Using a standardized preoperative, operative, and postoperative pathway will improve the results after radical cystectomy. Key new changes include:

no bowel prep except nothing by mouth (NPO) after midnight
no nasogastric tube
limit intravenous fluids during surgery
24 hours of antibiotics only
start Heparin 5,000 units subcutaneous day of surgery
use ketoralac for postoperative pain relief with patient controlled morphine anesthesia
early ambulation on post-operative day (POD) #1
start clear liquids of POD # 2 and soft diet on POD #3

The main problem with radical cystectomy in the elderly is the urinary diversion. Most elderly patients should receive an ileal conduit (unless their creatinine is < 2mg/dl), if they have good bowel function, are able to perform chronic intermittent catheterization, and have good liver function. Most elderly patients lack the desire to perform intermittent catheterization and thus ileal conduit is the preferred diversion in the elderly. The following table shows an appropriate follow-up schedule after radical cystectomy.

Presented by David P. Wood, MD; Khaled Hafez, MD; Carlos Jose Andrade, MD; and Charles Rosser, MD at the VI Maratona Urológica do Rio de Janeiro – August 14 – 15, 2009.

Bladder cancer in the elderly[liii]

Tuesday, 18 August 2009

RIO DE JANEIRO, BRAZIL ( – A recent study from Vanderbilt University detailed the outcomes of 382 patients undergoing radical cystectomy of whom 44 were 75 years of age or older.

This group reported a 26% complication rate; 22% minor and 4% major complications. The mean hospital stay was 7 days. Unfortunately, only 29% were alive at 2 years with 91% disease-free survival rate. Elderly patients undergoing a palliative cystectomy have a much higher complication rate and poor two-year survival thus palliative cystectomy should be done only in extreme conditions. The performance status of the elderly patient is the most important determinant of long-term outcome after radical cystectomy. ECOG >1 portends a poor outcome. Use of the Pre-operative assessment of Co-morbidity evaluation (PACE) is very accurate at determining hospital outcomes. Chemo-radiation therapy should be considered for elderly patients, especially those with a poor performance status. Complete transurethral resection is appropriate if there is no tumor in a repeat transurethral resection. If there is residual cancer, then chemo-radiation or surgery is required. Radical cystectomy is difficult to tolerate in the elderly and many require short-term recovery in a rehabilitation institute.

Presented by Charles Rosser, MD at the VI Maratona Urológica do Rio de Janeiro – August 14 – 15, 2009.

Complications and Mortality After Radical Cystectomy for Bladder Transitional Cell Cancer[liv]

Giacomo Novara, Vincenzo De Marco, Maurizio Aragona, Rafael Boscolo-Berto, Stefano Cavalleri, Walter Artibani, Vincenzo Ficarra: Department of Oncological and Surgical Sciences, Urology Clinic, University of Padua, Padua, Italy

We evaluated early postoperative complications and 3-month mortality after radical cystectomy using a standardized method to report complications.

Materials and Methods

We retrospectively collected data on all 358 consecutive patients who underwent radical cystectomy for nonmetastatic bladder transitional cell carcinoma at a tertiary academic referral center from January 2002 to December 2006. The Martin criteria were used to report complications, which were graded according to a 5-grade modification of the Clavien system.


A total of 231 complications occurred in 174 patients (49%), of which 13% were grades 3 to 5. The 3-month mortality rate was 3%. After evaluating the whole patient cohort American Society of Anesthesiologists score was the only covariate significantly associated with grade 3 to 5 complications on univariate analysis. Subgroup analysis limited to patients with an orthotopic ileal neobladder showed that female gender (HR 0.204, p = 0.017) and American Society of Anesthesiologists score (HR 2.851, p = 0.013) were independent predictors of grade 3 to 5 complications on multivariate analysis.


When applying a standardized methodology to report early morbidity, about 50% of patients undergoing radical cystectomy had complications within 3 months of surgery. Although most complications were minor, about 13% of patients experienced grade 3 to 5 events, resulting in a 3-month mortality rate of 3%. American Society of Anesthesiologists score was significantly associated with major complications, while on subgroup analysis in patients who received an orthotopic ileal neobladder female gender was also an independent predictor of major complications.

Complications Following Radical Cystectomy for Bladder Cancer in the Elderly[lv]


The incidence of bladder cancer increases with advancing age. Considering the increasing life expectancy and the increasing proportion of elderly people in the general population, radical cystectomy will be considered for a growing number of elderly patients who suffer from muscle-invasive or recurrent bladder cancer.

Evidence synthesis

Perioperative morbidity and mortality are increased and continence rates after orthotopic urinary diversion are impaired in elderly patients undergoing radical cystectomy. Complications are frequent in this population, particularly when an extended postoperative period (90 d instead of 30 d) is considered.

Take Home Message

Elderly patients receiving radical cystectomy and urinary diversion are at a high risk of perioperative complications. Careful perioperative management and surveillance in experienced and properly staffed centers may improve outcome in this population.


The following article seems to be saying:

Positive surgical margins means that there are positive signs of cancer still remaining at the margins of the surgically removed area; negative that there are none – the patient is effectively clear of the cancer. (Note that for prostate cancer argues that +ve margins does not necessary mean that cancer is still there).

So this article is saying that 88.4% had no observable cancer after surgery, 11.6% did have.  The former had poorer outcomes – 9% survived overall and 18% had disease specific survival (presumably meaning that 9% died of something else?). From an analysis of the data, the authors conclude (without seemingly giving any data on this) that these patients (those with some cancer left in them) would be better off having “meticulous pelvic lymph node dissection”.

However, 48% those who appeared clear (negative surgical margins) survived 5 years; and of the 52% who didn’t, 17% (difference between the 48% and the 68% who didn’t die of cancer) died of something else – so 35% died of their cancer returning.

From this I deduce a couple of things.

First, as we know, RC gives a relatively high chance of survival, some research quoting the surgery made a critical difference to the overall survival – 44% over half of those who had RC died, whether they were initially declared clear or not.

Second. Those who did have negative margins (that is, detectable cancer adjacent to the surgical action) had a significant extra chance of dying – about 5 times on these figures.

A Thorough Pelvic Lymph Node Dissection in Presence of Positive Margins Associated With Better Clinical Outcomes in Radical Cystectomy Patients[lvi]

Daniel Cantera Corresponding Author (Department of Surgery, Division of Urology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania), Thomas J. Guzzoa, Matthew J. Resnicka, Meredith R. Bergeyb, Seema S. Sonnadb, John Tomaszewskic, Keith VanArsdalena, S. Bruce Malkowicza


To evaluate the effect of positive surgical margins in patients with muscle-invasive transitional cell carcinoma of the bladder on survival.


A retrospective evaluation of a prospectively maintained radical cystectomy database consisting of the data from 344 patients was performed. Cox regression analysis was done, and Kaplan-Meier tables were developed to evaluate the contribution of this finding to clinical outcomes.


A total of 304 (88.4%) patients had negative surgical margins in the radical cystectomy specimen, and 40 (11.6%) had positive surgical margins. On univariate analysis, positive surgical margins conferred a significant risk of poorer clinical outcomes. The 5-year overall (OS) and disease-specific survival (DSS) rate was 9% and 18% for patients with positive margins compared with 48% and 65% for patients with negative margins, respectively. The multivariate analysis demonstrated a significant independent risk of decreased recurrence-free survival, DSS, and OS for patients with positive surgical margins. The corresponding hazard ratios were 2.29 (95% confidence interval 1.54-3.41, P < .001), 1.71 (95% confidence interval 1.15-2.56, P < .009), and 1.70 (95% confidence interval 1.23-2.34, P < .001). Despite these findings, patients with positive margins and node-negative disease experienced improved DSS and recurrence-free survival (P = .001 P and = .009, respectively) if >15 lymph nodes were removed during surgery.


The presence of positive surgical margins in the pathologic specimen confers a significant independent risk of reduced recurrence-free survival, DSS, and overall survival. Nevertheless, patients with positive surgical margins will still benefit from a meticulous pelvic lymph node dissection.A Comparison of Postoperative Complications in Open versus Robotic Cystectomy[lvii]

Monday, 20 July 2009

Weill Cornell Medical College, Department of Urology, New York, NY, USA.


Robotic cystectomy is an emerging alternative for treatment of invasive bladder cancer (BCa). However, reduction in postoperative morbidity relative to the open approach has not been demonstrated. OBJECTIVE: To compare complication rates in patients undergoing robotic versus open radical cystectomy (RC).

A prospective cohort study of 187 consecutive patients undergoing RC at our institution-104 open RC, 83 robotic RC.

Intervention: Open or robotic RC with urinary diversion.

Demographic, perioperative, and complication data were recorded prospectively. Thirty-day and 90-d complication rates were assessed using the modified Clavien complication scale. Data were evaluated using chi(2) and multivariate logistic regression analyses.

At 30 d, the open group demonstrated a higher overall complication rate (59% vs 41%; p=0.04) as well as more major complications (30% vs 10%; p=0.007). At 90 d, the overall complication rate was greater in the open group, but this was not statistically significant (62% vs 48%; p=0.07). However, there was a significantly higher major complication rate in the open cohort (31% vs 17%; p=0.03). When subjected to logistic regression analysis, robotic cystectomy was an independent predictor of fewer overall and major complications at 30 and 90 d. High American Society of Anesthesiologists (ASA) score (3-4) and longer surgical time were independent predictors of major complications. Though this is one of the largest published RC series, the sample size is relatively small. Moreover, despite the two patient cohorts being similarly matched, the study was not performed in a randomized fashion.

Patients undergoing robotic cystectomy experienced fewer postoperative complications than those undergoing open cystectomy. Robotic cystectomy is an independent predictor of fewer overall and major complications. Until long-term oncologic results are available, robotic cystectomy should still be considered investigational.

Written by: Ng CK, Kauffman EC, Lee MM, Otto BJ, Portnoff A, Ehrlich JR, Schwartz MJ, Wang GJ, Scherr DS.

Reference: Eur Urol. 2009 Jun 10. doi:10.1016/j.eururo.2009.06.001

PubMed Abstract PMID:19560255

Neobladder vs. Ileal Conduit[lviii]

Orthotopic Neobladder Versus Ileal Conduit Urinary Diversion After Cystectomy – A Quality-Of-Life Based Comparison

Friday, 17 July 2009

Radical cystectomy remains the gold standard in treatment of muscle invasive bladder cancer.

Evolution of pathological guidelines has empowered centres to offer orthotopic substitution (OBS) to patients undergoing radical cystectomy. We compared health-related quality of life (HRQoL) between patients who underwent OBS or ileal conduit urinary diversion(ICD) following radical cystectomy.

A total of 57 patients who underwent cystectomy were assessed pre-operatively using Karnofsky performancescale (KPS). Of these, 52 patients (28 OBS and 24 ICD) who responded to a postal questionnaire consisting of SF-36 and a functional index questionnaire were included.

Median age of patients was 70 years. Pre-operative KPS scores were similar. All eight HRQoL scales were favourable in both groups. OBS patients had significantly better physical functioning. In the cohort, 42% of men with OBS and 25% of diversions could maintain an erection to varying degrees. Of the OBS patients, 85% were continent with two patients reporting reduced QoL with pad usage. Of ICD patients, 63% felt less complete and 42% were embarrassed due to the stoma, with58% apprehensive of stomal leakage. Of OBS patients, 96% had significant relationships and a more active life-style.

In a similar age-group population, there was no significant difference in most QoL indices but body image issues persist in ICD patients. OBS patients had significantly better physical function, continuing to have a more active lifestyle. They attained urethral voiding with good continence. A detailed discussion of long-term functional outcome would engender a realistic expectation allowing better adaptation.

Written by: Philip J, Manikandan R, Venugopal S, Desouza J, Javlé PM.

Reference: Ann R Coll Surg Engl. 2009 Jun 25. doi:10.1308/003588409X432293

PubMed Abstract  PMID:19558757

This research gives some hope to those with non-muscle invasive BC who defer/refuse/cannot have RC.

Between 1996 and 2002, 1,133 patients were treated with single stage radical cystectomy as monotherapy for invasive bladder cancer. A randomly selected 776 cases (70%) were used as a reference series. The remaining 357 cases (test series) were used for external validation. Survival estimates were analyzed using univariate and then multivariate appraisal. The results of multivariate analysis were used for risk group stratification and construction of a nomogram, whereas all studied variables were entered directly into the artificial neural networks.

Overall 5-year disease-free survival was 64.5% with no statistical difference between the reference and test series.


Analysis of Perioperative and Survival Outcome of RC[lix]

Friday, 03 July 2009

Department of Urology, Miller School of Medicine, University of Miami, Miami, FL, USA.

To review the outcomes in a large group of patients treated with radical cystectomy (RC) for urothelial cancer (UC) of the bladder, by one surgical team.

In all, 504 patients had RC for UC of the bladder between 1992 and 2007; 432 met the inclusion criteria and were analysed for survival and disease recurrence.

Of the 432 patients, (mean age 69 years; mean follow-up 38 months, range 1-172), 240 (56%) and 179 (41%) had an ileal conduit and orthotopic neobladder for urinary diversion, respectively. The mortality rate within 30 days of RC was 2%; 105 (24%) patients developed local and/or distant recurrence with a mean interval of 13.6 months. The overall survival, recurrence-free survival (RFS) and disease-specific survival (DSS) at 5 years was 58%, 64% and 74%, respectively, and 43%, 62% and 68% at 10 years. The 5-year RFS and DSS for those with organ-confined, node-negative tumours was 81% and 91%, compared to 46% and 56% in those with extravesical extension and lymph node-negative tumours. The RFS and DSS of patients with lymph node metastasis at 5 years was 29% and 40%, respectively.

Our study reaffirms that RC with bilateral pelvic lymph node dissection offers a reasonable possibility of disease control at 5 years, with a DSS of 74%. However, there is a need for an earlier diagnosis and effective systemic therapy if additional gains in survival are to be delivered.

Written by: Manoharan M, Ayyathurai R, Soloway MS

Reference: BJU Int. 2009 Jun 10. Epub ahead of print.

PubMed Abstract PMID:19519764

Quality of Pathologic Response and Surgery Correlate With Survival for Patients With Completely Resected Bladder Cancer After Neoadjuvant Chemotherapy[lx]

Thursday, 02 July 2009

Department of Medicine, Section of Medical Oncology, Baylor College of Medicine, Houston, Texas.


In a retrospective study of Southwestern Oncology Group (SWOG)-S8710/INT-0080 (radical cystectomy [RC] alone vs 3 cycles of neoadjuvant chemotherapy [NC] with methotrexate, vinblastine, doxorubicin, and cisplatin before RC for bladder cancer), factors found to be associated with improved overall survival (OS) included pathologic complete response, defined as P0; treatment with NC; completion of RC with negative surgical margins; and >/=10 pelvic lymph nodes (LNs) removed.

The authors used stratified Cox regression to retrospectively study the association of quality of pathologic response after RC with OS in the subset of S8710 patients who received NC and RC with negative surgical margins.

Of 154 patients who received NC, 68 (44.2%) were < P2 (P0, Pa, P1, or carcinoma in situ [CIS]) at RC, 46 (29.9%) were P0, and the remainder had P2+ disease or did not undergo RC. In 115 patients who had RC with negative surgical margins, compared with P0 patients, those with residual Pa, P1, or CIS appeared to have worse OS (P = .054); OS was significantly worse for patients with residual P2+ disease (P = .0006). LN-positive (LN+) disease was found to be associated with worse OS than LN-negative (LN-) disease (P = .0005). Patients with LN- disease (ie, those with < 10 LNs removed) appeared to have inferior OS compared with those with 10+ LNs removed (P = .079). The combination of pre-NC clinical stage and post-RC pathologic stage was found to be predictive of OS (P < .0001).

NC and RC with negative surgical margins for bladder cancer followed by pathologic P0 and LN- disease were found to correlate with improved OS. A combination of baseline clinical stage and post-RC pathologic stage may better predict OS.

Written by: Sonpavde G, Goldman BH, Speights VO, Lerner SP, Wood DP, Vogelzang NJ, Trump DL, Natale RB, Grossman HB, Crawford ED.

Reference: Cancer. 2009 Jun 10. Epub ahead of print. doi:10.1002/cncr.24466

PubMed Abstract PMID:19517476


26/06/2009 23:32

Hi Linda,

Many thanks for that advice and the refs – very useful addition to my ‘library’ if and when I decide to attempt to go down the RC route.

However, the research since then does paint a more positive picture for retaining the bladder until there’s a noticeable resurgence.

So with that, plus improved procedures, increased evidence of effective CAM (I’m particularly struck by J Dean 2009 Nile River Publications Inc, which has confirmatory orthodox research to support it), gives me hope that I can keep going with my bladder (which I’ve got attached to ….. haha).

But I also take note, as you emphasise, that the UK docs are opposed to RC for metastasised BC on the basis, presumably, that once the seeding has started then it is too late (which is probably based on the idea that any seeds have found fertile ‘soil’ – itself now a dubious concept). I think this is wrong; I’ve come round to thinking the USA idea that the cancerous bladder continues to be a source of seeding and would need to be removed. I also agree that there would need to be a 10+ removal of infected/suspect nodes for it to have the most chance of being effective.

Kind regards, Ian


From: Linda Weyand (lweyand@AOL.COM) Sent: 26 June 2009 20:22:32

Hi, Ian,
Several years ago when research reports showing neoadjuvant chemotherapy being advantageous were first published, Dr. Herr gave a presentation about good surgery after neoadjuvant chemotherapy having as much or more to due with long-term survival than the neoadjuvant chemo itself. If I am rememberting right, his position was that whether the patient had good surgery after the chemotherapy might be making the difference in the survival rates. He stated that all patients that had a complete response to the chemotherapy and refused cystectomy had relapsed and died. Remembering this statement and others that he made during this presentation is why I was so pushy about your needing a cystectomy when you first wrote the List. Also, since I know how “normal” life can be without a bladder, I just felt and still feel that adding cystectomy surgery to your fight against bladder cancer would be for the best. When you first joined the List, I looked on the Internet for this presentation of Herr’s without luck, but it just occurred to me to check the List archives for the link that I posted at the time. Fortunately, I found it and it still works! You can view it as a slide show with audio or as a transcript with small pictures of the slides. Here it is:
‘Surgical Variables Impact Bladder Cancer Outcomes”

One of the aspects of good surgery that Herr discusses in the above presentation is the extent of lymph node removal. On slide 11, he said, “And the patients who had more nodes retrieved, more nodes dissected and found by the pathologist survived better regardless of pathologic stage [nodes status] than those patients who had fewer in this case, than 10 nodes.” This shows the importance of having extended lymph node dissection when having a radical cystectomy, especially for those whose blc is locally advanced with a high probabilty of (or known to have) metastases. I think this presentation is good for all people to read before having cystectomy because it does stress the need to have a surgeon highly experienced in radical cystectomy surgery and discusses what comprises good surgery. I know some that have requested an extended lymph node resection and their surgeon only performed a limited one. Which just means it is hard to convince some doctors to change their normal way of doing things. But, armed with information such as this presentation gives you, I cannot help but think it would help convince the surgeon of the seriousness of your request.

The full text article of the Southweat Oncology Groups reasearch paper that Herr references in his presentation can be found:

Neoadjuvant Chemotherapy plus Cystectomy Compared with Cystectomy Alone for Locally Advanced Bladder Cancer[lxi]

I realize that cystectomy for metastatic bladder cancer is not the usual course of action in England. However, I do not understand their stance on this for those that have a complete response to chemotherapy.

Hope this helps,
Linda W
P. S. Another aspect of good surgery that Herr mentions is clean margins. I think it would be advisable for all scheduling a radical cystectomy to discuss with their doctor the possibility of not being able to achieve clean margins and what the options would be if this is the case. When clean margins cannot be obtained in this surgery, it is usually in the area of the ureters or the urethra. When it is the urethra, the remedy is urethra removal and a diversion other than a neobladder. However, when it is the ureter, its removal also means the loss of the kidney it connects to which is a serious decision. Personally, I would want the surgeon to know that I wanted to be completely free of cancer even if it meant the loss of a kidney. I would not want to go through this complicated of a surgery only to have to still have cancer that had to be treated or removed along with the kidney at a later date. With all the miraculous feats the medical profession performs, I do not know why there is not a substitute for a ureter. Do any of you know why it is always necessary to take the kidney when the ureter needs to be removed?

A Population Based Assessment of Perioperative Mortality After Cystectomy for Bladder Cancer[lxii]

Wednesday, 10 June 2009

Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Quebec, Canada.

Martini-Clinic, Prostate Cancer Center Hamburg-Eppendorf, Hamburg, Germany.

Large variability exists in the rates of perioperative mortality after cystectomy. Contemporary estimates range from 0.7% to 5.6%. We tested several predictors of perioperative mortality and devised a model for individual perioperative mortality prediction.

We relied on life tables to quantify 30, 60 and 90-day mortality rates according to age, gender, stage (localized vs regional), grade, type of surgery (partial vs radical cystectomy), year of cystectomy and histological bladder cancer subtype. We fitted univariable and multivariable logistic regression models using 5,510 patients diagnosed with bladder cancer and treated with partial or radical cystectomy within 4 SEER (Surveillance, Epidemiology, and End Results) registries between 1984 and 2004. We then externally validated the model on 5,471 similar patients from 5 other SEER registries.

At 30, 60 and 90 days the perioperative mortality rates were 1.1%, 2.4% and 3.9%, respectively. Age, stage and histological subtype represented statistically significant and independent predictors of 90-day mortality. The combined use of these 3 variables and of tumor grade resulted in the most accurate model (70.1%) for prediction of individual probability of 90-day mortality after cystectomy.

The accuracy of our model could potentially be improved with the consideration of additional parameters such as surgical and hospital volume or comorbidity. While better models are being developed and tested we suggest the use of the current model in individual decision making and in informed consent considerations because it provides accurate predictions in 7 of 10 patients.

Written by: Isbarn H, Jeldres C, Zini L, Perrotte P, Baillargeon-Gagne S, Capitanio U, Shariat SF, Arjane P, Saad F, McCormack M, Valiquette L, Peloquin F, Duclos A, Montorsi F, Graefen M, Karakiewicz PI.

Reference: J Urol. 2009 May 16. Epub ahead of print. doi:10.1016/j.juro.2009.02.120

PubMed Abstract PMID:19447427

Twenty-Year Experience of Radical Cystectomy for Bladder Cancer in a Medium-Volume Centre[lxiii]

Friday, 05 June 2009

To evaluate long-term survival after radical cystectomy (RC) for bladder cancer (BC) and to define risk factors for BC-specific death.

Patients having RC for BC with curative intent in Turku University Hospital 1986-2005 were assessed. Survival results were recorded and 10 risk factors for BC-specific death were analysed.

In total, 248 patients with a median age of 64 years were included in the study. Sixty-four per cent of the tumours were intravesical and the lymph-node metastasis rate was 9%. Disease recurrence was observed in 90 patients (36%). Median time for local recurrence and distant metastasis after RC was 9 and 12 months, respectively. The mortality rate for both local recurrence and distant metastasis was 93%. Upper urinary tract and urethral recurrences were less common (3% and 5%, respectively) and occurred later (median time to recurrence 26 and 18 months, respectively). The 5-, 10-, and 15-year BC-specific survival was 69%, 67% and 66%, respectively. Extravesical tumour status, high tumour grade, positive node status and no history of intravesical therapy before RC were significant risk factors for BC-specific death. Other variables (neoadjuvant radiation, lymphadenectomy, age, time period, gender, smoking) did not affect the risk.

The survival results are comparable with those of high-volume centres and demonstrate the possibility of excellent local control in all cases and a high rate of cure in tumours confined to the bladder. Extravesical tumour growth, high grade and lymph-node metastasis are the most important risk factors for BC-specific mortality.

Written by: Bostrom PJ, Mirtti T, Kossi J, Laato M, Nurmi M.

Reference: Scand J Urol Nephrol. 2009 May 8:1-8. Epub ahead of print.

PubMed Abstract PMID:19424935

Impact of Treatment Delay in Patients with Bladder Cancer Managed with Partial Cystectomy in Quebec[lxiv]

Thursday, 04 June 2009

Department of Surgery (Urology), McGill University, Montréal, Que.

Treatment delays have been associated with adverse outcomes in patients with bladder cancer treated with radical cystectomy (RC). We sought to evaluate the impact of treatment delay on disease recurrence and survival in patients with bladder cancer treated with partial cystectomy (PC) in Quebec.

We reviewed and obtained billing records for all patients who underwent PC and/or RC for bladder cancer in Quebec between 1983 and 2005. Analysis included age, sex, year of surgery, surgeon’s age, hospital type, preoperative and postoperative visits with accompanying diagnoses and dates of death.

A total of 714 patients underwent PC. The median patient age was 70 years. Two-hundred nineteen (30.7%) patients experienced recurrence; of these, 52 (23.7%) required salvage RC. Five-year overall and recurrence-free survival for patients who underwent PC were 49.8% and 40.3%, respectively. Patients delayed more than 12 weeks from transurethral resection of bladder tumours (TURBT) to PC were at significantly increased risk of requiring salvage RC compared with those delayed 12 weeks or less (hazard ratio [HR] 3.0, p < 0.001). Patients who underwent salvage RC had worse survival than patients who had upfront RC (HR 1.5, p = 0.006). Variables including age, sex, presence of hematuria, intravesical therapy, surgeon age, hospital PC volume, surgeon PC volume, type of hospital (academic v. nonacademic) or year of surgery were not significantly associated with PC treatment delay.

Treatment delay in patients with bladder cancer managed with PC was associated with increased risk of salvage RC. Patients with bladder cancer who underwent salvage RC had worse outcomes than those who had upfront cystectomy.

Written by: Fahmy N, Aprikian A, Al-Otaibi M, Tanguay S, Steinberg J, Jeyaganth S, Amin M, Kassouf W.

Reference:  Can Urol Assoc J. 2009 Apr;3(2):131-5.

PubMed Abstract PMID:19424467

The Risk Factor for Urethral Recurrence after Radical Cystectomy in Patients with Transitional Cell Carcinoma of the Bladder

Kang Su Choa, Joo Wan Seoa, Sung Jin Parka, Young Hoon Leea, Young Deuk Choia, Nam Hoon Chob, Seung Choul Yanga, Sung Joon Honga

aDepartment of Urology and Urological Science Institute, and
bDepartment of Pathology, Yonsei University College of Medicine, Seoul, Korea

Address of Corresponding Author

Urol Int 2009;82:306-311 (DOI: 10.1159/000209363)

Purpose: We evaluated the incidence and risk factors for urethral recurrence following radical cystectomy and urinary diversion in transitional cell carcinoma. Patients and Methods: A retrospective review was performed of the 412 consecutive patients who underwent radical cystectomy and urinary diversion for transitional cell carcinoma of the bladder between 1986 and 2004. A total of 294 patients were enrolled in this study. We investigated the impact of various clinical and pathological features on urethral recurrence by univariate and multivariate analysis. Results: Urethral recurrence developed in 13 patients (4.4%) and the 5-year urethral recurrence-free probability was 94.9%. On univariate analysis, positive urethral margin, prostatic stromal invasion, and prostatic urethral involvement had a significant influence on urethral recurrence (p < 0.05). The other clinical and pathological features were not significantly associated with urethral recurrence (p > 0.05). A multivariate Cox proportional hazard model revealed that a positive urethral margin (hazards ratio (HR) = 18.33, p < 0.001), prostatic urethral involvement (HR = 7.95, p < 0.001), and prostatic stromal invasion (HR = 5.80, p = 0.018) were independent risk factors for urethral recurrence. Conclusion: A positive urethral margin is considered an absolute indication for prophylactic urethrectomy. In addition, more careful patient selection is necessary for orthotopic urinary diversion in patients with prostatic urethral involvement and prostatic stromal invasion.

Copyright © 2009 S. Karger AG, Basel

Sung Joon Hong, MD, PhD
Department of Urology
Yonsei University College of Medicine
134 Shinchon-dong, Seodaemun-gu, Seoul (Korea)
Tel. +82 2 2228 2315, Fax +82 2 312 2538, E-Mail


05/04/2009 18:49

Hi Wendy,

Thanks for all that info and your concern – as always, much appreciated. Oh, and I don’t mind your bluntness at all.

Perhaps I should clear one or two things up. When I said I’d not had my bladder out ‘cos there was no point, I was quoting four oncologists and a urological surgeon – and, at the time, this seemed reasonable. It was only when I read that so many of the USA patients still had RC that I realised this may not necessarily be the right thing; hence my queries/contributions. I am now seriously considering it.

However, there are several cautionary factors. Let me share them:

1. It is not certain how much mets I have – initially I wasn’t thought to have any; then, only in the lymph nodes (and one contributor here implied that wasn’t the most serious mets).

2. Cisplatin based chemo seems relatively new, and seems to work much better than the older MVAC; indeed, maybe the MVAC didn’t enhance longevity at all.

3. All my 5 tumour marker tests have come back within the normal range so far.

4. The research you quote is based on only 14 patients, and only half of those who had primary bladder tumours (mine), one of which died. There’s no mention of any who didn’t have RC as a comparison, unlike the other research I was pointed to by Linda (where 40% who didn’t have RC survived 5 years).

5. My nodes seem all to be quiescent now.

6. Things are improving all the time, and indeed may already be much better but we won’t know for years – the UK’s top expert had said (18 months ago) that I had a 5% chance of remission with chemo; now the figures are up to 40% +.

7. If (I know, a big IF, but not unreasonable) improvements continue with such treatments, and with adjuvant CAM, I have a fair basis of hope.

8. Bear in mind that 2.2% die having the surgery, and 30% suffer painful complications.

So I appreciate your strong recommendation for RC, and acknowledge that it there is supportive evidence – but not, to my mind, overwhelming (given what I say above).

Hence I will continue my wait and see policy.

At the moment, I am symptom free; returned to apparent good health (doing my exercises – walking, jogging, weights; weight and muscle-mass OK; etc).

But I will continue my research; be diligent; listen to others’ experience.

Kind regards, Ian


Chemo-surgery yields 92% survival in metastatic TCC‏

From:    Wendy Ramsay (ramsaycafe@COMCAST.NET)

Sent: 05 April 2009 16:54:17



I can't find the working link to this article so here is a copy

(below). Hopefully now you know now that the opinions of your doctor "I've not had my bladder out, 'cos I was told there was no point - being diagnosed as metastatic, the cancer had already spread and so there was no point." Are wrong. That statement is very disturbing.


Here is an article that you may want to consider. After reading this

article, I flew to MDAnderson and spoke with Randall Millikan about this procedure for myself. Dr. Millikan was the point person for their study, very intelligent and agressive if the patient is willing and able. I send this to you because you said you have remnants of a lymph node that did not completely respond..."I don't really want to wait until there's a clear symptom of the recurrence - at present the only ones suggested is a noticable enlargement of my supraclavicular lymph node or repeated CT scans (which I've declined 'cos of the heavy X-Ray loading)." I considered this surgery for myself to remove a supraclavicular node(s) on my collarbone.

Because I responded completely to chemo and the node(s) disappeared, I was not a candidate for this surgery.


I hate to say this, but if you have an untreated met, I don't think

you should be worrying about x-ray loading. The met will kill you - not the x-ray(s). You seem very intelligent but to be more worried about x-rays than an existing met is dumbfounding.


Please forgive me - I don't mean to be rude - but as much as I respect the rights of people to choose what they want, your reasoning seems like a death sentence to me. I'm sorry for the bluntness but something's not right.

I hope I am as wrong as wrong can be.


Good luck, Ian.



Chemo-surgery yields 92% survival in metastatic TCC "Homburg, Germany-A combined approach of chemotherapy and surgical resection is not only feasible, it may be preferable to chemotherapy alone in some patients with advanced urothelial cancer, German researchers report.


The dual-modality treatment yielded a 3-year tumor-specific survival

rate of 92% and an overall survival rate of 85% in a cohort of 14 patients.


"We found that, if we treat patients with distant lymph node

metastasis with inductive chemotherapy and see a response, then often these lesions are resectable," said Marcus Hack, MD, a urologic fellow working with Michael Stöckle, MD, at Saarland University Hospital in Homburg. "These patients had a very good prognosis after surgical resection of their metastasis-better than treatment with just chemotherapy."


The caveat, Dr. Hack said, is that the treatment is probably suited

only for certain types of patients, and selection criteria have yet to be developed.


"It's difficult to say which patients would benefit most from this

approach, but I suspect that it may be patients with sole metastasis and small-volume metastasis who would show good response to the inductive chemotherapy," Dr. Hack said.


'New approach in urology' The 14 patients in the study were evenly

divided between those with primary bladder tumors and those with

upper-urinary-tract tumors. All but two underwent resection of their primary tumor before diagnosis of distant metastasis. The others had concurrent metastasectomy with cystectomy.


The site of metastasis was the distant lymph nodes in 11 patients and

the lungs in three others, while one patient also had metastatic disease in an adrenal gland.


Five patients received gemcitabine-based chemotherapy (Gemzar) to

optimal response as pre-emptive treatment before metastasectomy. The other nine had received adjuvant chemotherapy for their resected primary tumors, and seven underwent additional chemotherapy after metastasectomy.


Tumor recurrence was observed in three of the 14 patients at mean

follow-up of 19 months, starting from the time of diagnosis of metastatic disease. Chemotherapy and surgery were reapplied in one of those patients and were well tolerated.


In all, three patients died during the course of the study. One death

was tumor-related, while two died of other causes.


"This is a new approach in urology," Dr. Hack said at the AUA annual

meeting. "If you have metastasis, normally you would use palliative

chemotherapy and then stop treatment. Now some groups are trying to resect this metastasis in patients who respond to inductive chemotherapy."


One such group is at the University of Texas M.D. Anderson Cancer

Center in Houston. Researchers there examined 31 patients with metastatic urothelial cancer who underwent surgery after undergoing chemotherapy. They found that the median survival from time of metastasectomy was 23 months, and the 5-year survival rate was 33%, suggesting that resection may contribute to long-term disease control when integrated with chemotherapy."


Wendy Ramsay



22/03/2009 17:51

Thanks to Linda leading me to a superb summary of the recent (2008) research into muscle-invasive bladder cancer and the various ways of treating it, I’ve got a better handle on the various options and likely success outcomes. Here is my take on that work (please correct me if I’ve got it wrong).


Linda (and others) was quite right: it is better to have RC.


However, there are a few caveats:


1. there is a risk of the surgery itself: 2.2% die;


2. a third who have RC have bad post-surgery complications


3. neo-adjuvant chemo (must be cisplatin based) should be done (that is, first) – it’s not nearly as effective if done afterwards (adjuvant); those with low BRCA1 genes have less response to chemo.


4. for best results, more than 10 nodes should be taken out too


5. even when the neo-adjuvant chemo appears to have led to a cure (no clinical signs of cancer), subsequent pathological checks show that actuall about a third did indeed have cancer still


6. However, IF there is no apparent cancer (cytoscopy, etc), or ureteral obstruction, there had been a small solitary tumour, the sugery had apparently removed all the cancerousness, and no sign of cancer in the prostate, then it isn’t too unreasonably to hold off doing an RC.


7. There’s some confusion (for me), but it appears that those who have chemo, RC & radiation have 66% complete remission; 5-year Survival whether RC or not, is 53%; and keeping the bladder (non-RC) 43%. That seems to me to mean that having chemo, RC & radiation gives a 50% improved survival (66% vs. 43%) over non-RC. But the reporter emphasised that this distinction is not as clear as it looks – perhaps ‘cos neo-adjuvant cisplatin is too new to have enough data yet. He says that retention of one’s bladder is a viable option.


8. If the bladder is to remain, then there must be a complete removal of the tumour, followed by chemo, and then radiation. And be prepared to go to RC if there’s any sign of resurgence.




21/03/2009 22:28

Hi Linda,


Nope, not mind at all.


Don’t worry; I’ll not be pushed.


Re T4 + seemingly complete remission giving a possible viable option for retaining one’s bladder: The theory seems to be simple:  mets is treated differently to non-mets – by systemic chemo; so maybe there’s no more cancer; if it has previously escaped, it’s now gone; if it hasn’t, then it’s as liable to pop up anywhere as in the bladder; so keep watch and deal with whatever pops up – which may not be in the bladder any more.


However, for less serous cancer, there seems to be evidence that it’s still lurking in the lining of the bladder; systemic chemo hasn’t been used.


And anyway, I’m only quoting what the video said. Presumably the presenter knew what he was talking about. So if we take his comments on the other stuff, it seems reasonable to take it on this too.


There’s the added complication in the UK, in that this RC + neo-bladder is less common; so less experienced surgeons avaible to do it. Surgery itself carries a 2% risk of death. Add all that up, and it is less a straight choice that it is in the USA.


But I fully take on board your emphasis on insisting on the best surgeon available in the UK, etc.


Thanks again for your good wishes. I in my turn hope things continue to go well with you.


Kind regards, Ian



Sent: 21 March 2009 21:47:21

To:    ianclements@HOTMAIL.COM

Hi, Ian,
Hope you do not mind my writing directly to you instead of through the List. I am glad that you found the ASCO articles either interesting or informative. Also, I am hoping that you do not feel that I am pushing you in one direction or the other. I really meant it when I said that I do not expect you to see things as I do or make the decisions that I would make and that I respect the challenges and decisions you are facing.

In your most recent post, you said, “Whilst this generally supports that view that for most, an RC is best, one point at the end stands out: if there are a lot of favourable conditions, that saving the bladder is a viable option – just needs lots of monitoring.”

I realize this may be the position taken in the presentation, but it just does not make any logical sense to me that if for muscle invasive T2 , T3, and local N+(after neoadjuvant chemo) RC/urinary diversion is either the standard of care or has proven to provide better long-term results, then with complete response to chemotherapy for T4N+M+, how could saving the bladder ever be a viable option, no matter how much monitoring. If you have been so fortunate to have eliminated the mets why wouldn’t it be best to remove the original source of those mets. I am not saying that I know the experts are wrong, just that it makes absolutely no sense to me.

In one of your previous post on March 16th in reply to a post from Wendy R. you wrote:
=0 A”I’m just quite apprehensive about having RC, with or without the neobladder that seems the best, along with probably losing my sex life.” I hope you do not mind my addressing the sexual effects of radical cystectomy that men have to come to terms with when deciding to have an RC. Sometimes, but far from usually, surgeons are able to perform nerve sparing surgery which offers a better chance, but not a guarantee, that erections will still be possible. When successful, it usually takes a good bit of time for everything to return to normal/almost normal working order and sometimes requires an ED drug such as viagra. However, with your hope of the surgery giving you a cure and depending on where your tumors were/are located, nerve sparing may not be advisable. I should note that the removal of pelvic lymph nodes are reported to have nothing to do with these sexual after effects, it is just the RC itself. However, something that I was surprised to learn and most men do not realize unless a doctor is kind enough to point it out early in the cystectomy discussion, radical cystectomy does NOT affect the ability to have an orgasm, even though, without nerve sparing, it does affect the ability to have an erection. There are methods that men can then use that makes it possible to have sexual intercourse without natural erections such as penile injections or penile implants. Men on our List have reported good results with these methods, some referring one method, others another method. Apparently, different nerves are involved in orgasms than in erections, but I never knew this until being taught differently. Since some of the men on our List were glad to learn this, I thought I would pass it on just in case your doctor has yet to discuss this with you.

I also want you know that my life with a neobladder is no different than my life before. I can lift extremely heavy objects, take part in any sport if I chose to, travel to anywhere I please, etc. My urinary diversion imposes no physical limitations on my life. I do have to get up in the middle of the night to void, but I did that before the surgery, too. It really seems that it makes no difference which of the diversions a person choses because they soon adapt to their new normal. Now, people appear to be more satisfied with the internal catherizable pouch or the neobladder, but there are plenty of people living a wonderful life with ileal conduits(stoma/outside bag–these bags have an opening that fits over a stoma on the abdomen and do not attach to the thigh like Foley catheters do).

As I pointed out to Jan in a recent post, GOOD surgery can make all the difference in the outcome for people with bladder cancer, especially those with T3 and T4 disease. Dr. Herr gave a presentation at ASCO several annual meeting ago where he took the position that some of the good results of neoadjuvant chemo/cystectomy that M. D. Anderson was touting were from the patients having had good surgery=2 0at the time of cystectomy just as much as it could be attributed to the neoadjuvant chemo. If I were you and decided to opt for RC  then I would try my hardest to make sure the surgeon understands that I was seeking a cure (no matter how unlikely the medical proffession thought that to be) and that I wanted extremely GOOD, very thorough surgery with extended lymph node dissection.
I would keep Karen Greene’s and Hildegard’s stories foremost in my mind and strive for the same results.

I hope you soon recover from you chest infection and wish you peace of mind in whatever decision you make.

My best to you,
Linda W. neobladder 2/2002


21/03/2009 19:24

Hi Linda,


Thanks for taking the trouble to help me to get to grip with whether to have an RC or not. I’ve spent a good chunk of today viewing the three references – alas, only the last one was on target, tho’ the other two were of interest.


Your ref, specifically the third one ( does address my concerns explicitly – so for that an even greater thank you.


Whilst this generally supports that view that for most, an RC is best, one point at the end stands out: if there are a lot of favourable conditions, that saving the bladder is a viable option – just needs lots of monitoring.


I’ll be sending this to my oncologists – after I’ve viewed it again a couple of times and summarised it (and get over what I hope is just a nasty chest infection).


I do not expect anyone or set of figures to decide for me, but it helps my decision if I have figures relating to similar actions.


As far as I can see, many of the figures being used on this site, without, often, any references (so making it hard to follow up) relate to those who did not have mets – and so these do not help me.


The few figures I had managed to dig up, for those with mets and who have RC, are seemingly in conflict. So your one helps a bunch.


Kind regards, Ian


Date:               Sat, 21 Mar 2009 00:45:00 -0400

From:             Linda Weyand <lweyand@AOL.COM>

Subject:   Re: Ian/articles

Hi, Ian, I doubt that you will ever find any research that will tell you to have the RC because you will be guaranteed to live longer if you do. However, I have read enough to believe that if I had metastatic bladder cancer my chances of living longer would be increased by having a radical cystectomy and extended lymphadectomy. This increase is not guaranteed and it is not by a huge percentage, but it sure looks better to me than not having it done. I realize that some of this is based on the reports that show surgery after chemo, even with a complete response, is necessary for long-term survival in advanced N+M0 cancer

Since the present standard of care for metastatic bladder cancer has a prognosis that is very unfavorable, I would be wanting to go beyond the standard of care. And, if I had a complete response to chemo like you appear to have had, I would be looking for all the avenues that might defy the standard of care prognosis. Whether it be another chemo regimen or RC with extended lymph node dissection, or any other medical treatment that a doctor here or in Europe or Asia or elsewhere was using to try to improve survival. I would attack the cancer from every front possible, using Wendy Ramsay as my role model.

Please understand, this is just the way I would feel about it, and I do not expect you to feel the same way. I have deep respect for the challenges you are facing and the decisions that you are having to wrestle with.Â

Today I f ound a series of presentations at the 2008 ASCO Annual Meeting (American Society of Clinical Oncology). These presentations are available as video and slides. The video will both show and explain the slides so that is what I recommend anyone interested to view. The three presentations are: 1) Novel agents and strategies: What does the future hold?  by Cora M. Sternberg, MD 2) Lessons learned from studies of chemotherapy in advanced TCC  by Christopher Sweeney, MBBS 3) What is state of the art for surgery and peri-operative chemotherapy? by Dean F. Bajorin, MD

Wishing you the best, Linda W. neobladder 2/2002

Date:               Fri, 20 Mar 2009 21:53:32 -0400

From:              Ruth Mary Pollack <rmpollack@COMCAST.NET>

Subject:   Re: RC or not RC

Linda W

I want to compliment and underscore the two detailed and informative emails that you have contributed. If anything, it has been my experience these last 6 or so years on the BLC Cafe that people try and tend to be conservative in their advice, never interfering with medical opinions but educating and sharing when appropriate. My assessment is that overall there is sometimes too much encouragement and not enough hard ball. Bladder Cancer is a dangerous and deadly disease. Medical science is trying to find ways to cope and cure but still, too many people lose the battle.

Recently I had an appointment with a urology specialist at Yale assessing my yearly CT scan results. My RC took place five years ago. During our conversation, he made some stunning comments that I will share. Since I had gone through a year or so of BCG treatments, surgical removal of tumors and every three month close watching by the surgeon, this urologist asked me what precipitated my choice to have an RC. His comment was sad. He said the hardest part of his job is to convince people when the time has come, that their bladder needed to go. Then he gave me statistics: Non invasive, with an RC we have an 85% chance of being around five years later. With muscle invasion, he said our chances drop to 50%, and with lymph involvement down to 20%. Then he concluded: People hang on to their bladders too long.

Ruth Mary

Hi Linda,

Thanks for all those references.

Maybe I haven’t read them right, but when I looked at all of the articles, non of them seemed to have any evidence that doing RC was better than not doing it.

One was just assertive, not evidence based.

The others were investigating what happened to those who had RC, not comparing them with those who didn’t have it.

If I’ve misunderstood, my apologies. Maybe I was wrong to expect something different, along the lines that of comparing two similar groups, one had RC and the other didn’t – and the one that had RC lived longer.



Superficial (pT2a) and deep (pT2b) muscle invasion in pathological staging of bladder cancer following radical cystectomy.[lxv]

Yu RJ, Stein JP, Cai J, Miranda G, Groshen S, Skinner DG.

Department of Urology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, USA.

PURPOSE: We compared and evaluated clinical outcomes in patients with pathological superficial (pT2a) and deep (pT2b) invasion of bladder muscle with transitional cell carcinoma following radical cystectomy and urinary diversion. MATERIALS AND METHODS: From 1971 to 2001, 311 of 1,359 patients (23%), including 244 males (78%) and 67 females, were found to have pathological muscle invasive (pT2) bladder cancer following radical cystectomy. Of this group 147 patients (47%) had pT2a (superficial) and 164 (53%) had pT2b (deep) muscle invasive tumors. Overall 242 patients had no evidence of lymph node metastasis, including 127 with pT2a (86%) and 115 with pT2b (70%). A total of 69 patients (22%) had lymph node involvement, including 20 with pT2a (14%) and 49 with pT2b (30%). At a median followup of 14.3 years (range 0 to 30.1) clinical outcomes were determined, including recurrence-free and overall survival, and local vs distant recurrence. RESULTS: In the 311 patients with pT2 tumors 10-year recurrence-free and overall survival rates were 72% and 47%, respectively. There was a significantly higher risk of node positive disease with pT2b vs pT2a tumors (30% vs 14%, p <0.001). No significant difference was observed in 10-year recurrence-free survival in patients with pT2a node negative vs pT2b node negative tumors (84% vs 72%, p = 0.091). When comparing pT2a node positive vs pT2b node positive tumors, no significant difference was observed in 10-year recurrence-free survival (50% vs 48%, p = 0.84). Recurrence-free survival was significantly higher in patients with pT2 lymph node negative tumors than in those with pT2 lymph node positive tumors (79% vs 49%, p <0.001). Furthermore, these differences remained significant when stratified by pT2a and pT2b node negative vs positive disease. Local pelvic recurrence developed in 10 of 311 patients (3%) with pT2 disease, while 69 (22%) had distant metastatic disease. In patients with recurrence the local or distant recurrence site was not associated with tumor stage (pT2a vs pT2b p = 0.24) or lymph node status (node negative vs positive p = 0.37). CONCLUSIONS: In muscle invasive (pT2) bladder cancer treated with radical cystectomy there is a higher risk of lymph node positive disease in deep muscle (pT2b) vs superficial (pT2a) invasion. However, no apparent difference was observed in recurrence-free survival between pT2a (superficial) vs pT2b (deep) muscle invasive tumors when controlling for lymph node status. Recurrence-free survival is significantly improved in patients with pT2 lymph node negative tumors compared to survival in those with pT2 lymph node positive tumors. Patients with muscle invasive (pT2), lymph node negative tumors have excellent clinical outcomes following cystectomy, while those with muscle invasive (pT2), lymph node positive tumors have higher recurrence rates and should be considered for adjuvant treatment protocols.

(I.C.: This does not compare those who had RC with those who hadn’t)

PMID: 16813876 [PubMed – indexed for MEDLINE]

Radical cystectomy in the treatment of bladder cancer always in due time?[lxvi]


May M, Braun KP, Richter W, Helke C, Vogler H, Hoschke B, Siegsmund M.

Urologische Klinik, Carl-Thiem-Klinikum Cottbus, Lehrkrankenhaus der Universitätsklinik Charité zu Berlin, 03048, Cottbus.

INTRODUCTION: The aim of this study was to examine how the survival rates for patients with muscle-invasive bladder carcinoma are influenced by the tumor stage at initial presentation. PATIENTS AND METHODS: This study examined the clinical course of 452 patients who underwent radical cystectomy for bladder carcinoma from 1992 to 2004. The patients were divided into three groups according to the histological results of the initial and final transurethral tumor resection (TURB). In group 1 (n=114) patients who presented with a superficial bladder carcinoma which had a high likelihood of progressing underwent radical cystectomy. Group 2 included (n=92) patients who displayed a superficial tumor stage when they first presented and developed progressive muscle-invasive bladder carcinoma under conservative treatment. Group 3 (n=246) comprised patients who were already at the muscle-invasive tumor stage in the course of primary TURB. The histopathological characteristics of all transurethral tumor resections and radical cystectomy were recorded. Progression-free survival rates and overall survival rates in the three groups were then compared. RESULTS: The average patient age at cystectomy was 64.3 (35-80) years, and the average follow-up period was 49 months. Progression-free survival and overall survival of all 452 patients were 56.1 and 53.6%, respectively, after 5 years. The best outcome was a progression-free 5-year survival rate of 78.4% with organ-confined, lymph node-negative tumors (n=213). This result was statistically significant (p<0.01) compared with the progression-free 5-year survival rate of 42.3% for non-organ-confined, lymph node-negative tumors (n=112). Lymph node-positive patients (n=127) achieved a progression-free 5-year survival rate of 29.0% regardless of the tumor infiltration. Group 1 patients achieved a progression-free survival rate of 71.3% and an overall survival rate of 69.1% after 5 years. Group 2 patients achieved a progression-free survival rate of 52.9% and an overall survival rate of 51.4% after 5 years. Group 3 patients achieved a progression-free survival and overall survival of 50.2% and 47.1%, respectively, after 5 years. There was no significant difference between groups 2 and 3 with regard to their progression-free or overall survival rates (p>0.45). However, both groups displayed significantly poorer progression-free and overall survival rates compared with group 1 (p<0.01). CONCLUSION: Our results show that patients with superficial bladder carcinoma with tumor progression to muscle invasion do not have a better prognosis after radical cystectomy than patients presenting initially with muscle-invasive bladder carcinoma. Survival rates in this group can only be improved by singling out patients on the basis of risk factors at an earlier stage and carrying out cystectomy. Due to these results we must expect that waiting for a muscle invasion in patients with superficial bladder carcinoma with a high risk profile results in a significant impairment of prognosis.

PMID: 17676301 [PubMed – indexed for MEDLINE]

(I.C. There is no comparison with a similar group who did not have RD, so of little use)

Radical cystectomy for bladder cancer: the case for early intervention.[lxvii]

Chang SS, Cookson MS.

Department of Urologic Surgery, Vanderbilt University Medical Center, A-1302 Medical Center North, Nashville, TN 37232-2765, USA.

There are no prospective studies comparing early cystectomy versus cystectomy after failed conservative management in patients with high-risk superficial bladder cancer. In the absence of clinically proven biomarkers for predicting tumor biology and the response to therapy, the treatment decision must be individualized based on the high-risk features outlined herein. Assuming that all patients can be treated effectively with bladder-sparing regimens and safely salvaged at the time of failure or progression is dangerous. Data support the negative impact of a delay in cystectomy and argue for improvements in the timing of cystectomy despite the clinical absence of muscle invasion. Accordingly, high-risk patients with non-muscle invasive disease require vigilant follow-up and should be informed from the onset of the risk for progression and the possible need for cystectomy. Repeat resection before intravesical therapy in the patient with T1 tumor is advised and should help to improve, but will not completely eliminate, the problem of clinical under-staging. Among patients with CIS and recurrent high-grade non-muscle invasive tumors, repeat biopsies following intravesical therapy are encouraged to ensure treatment response. Although there is debate regarding the timing of early cystectomy for patients with high-risk non-muscle invasive bladder cancer, there is little doubt that, for muscle invasive disease, prompt cystectomy influences the effectiveness of this therapy choice. An unnecessary delay in the performance of radical cystectomy in patients with organ-confined bladder cancer compromises outcomes and risks potentially avoidable deaths from disease.

(I.C.: This is just assertion, not evidence. Phrases like “little doubt” begs the question)

PMID: 15862612 [PubMed – indexed for MEDLINE]

Related Articles


Radical cystectomy for bladder cancer: the case for early intervention.

Urol Clin North Am 2005 May;32(2):147-55

“…. Assuming that all patients can be treated effectively with bladder-sparing regimens and safely salvaged at the time of failure or progression is dangerous. Data support the negative impact of a delay in cystectomy and argue for improvements in the timing of cystectomy despite the clinical absence of muscle invasion. …. Although there is debate regarding the timing of early cystectomy for patients with high-risk non-muscle invasive bladder cancer, there is little doubt that, for muscle invasive disease, prompt cystectomy influences the effectiveness of this therapy choice. An unnecessary delay in the performance of radical cystectomy in patients with organ-confined bladder cancer compromises outcomes and risks potentially avoidable deaths from disease.” ?

The following paper is listed as a comment and you really need to have the full text for the full review. This comment is by the late John Stein one of the most repected and exceptional bladder cancer surgeon we?have ever had?in the United States. I hold much faith in his opinions as well as his data supported research. Please note that unlike the way we normally view invasive as meaning into the muscle, this article refers to invasive T1 because it has invaded the lamina propria. I have read other papers where the authors felt that invasion into the lamina propria meant that T1 should be categorized with invasive disease, not superficial. ? Invasive T1 bladder cancer: indications and rationale for radical cystectomy. BJU Int. 2008 Aug;102(3):270-5. Epub 2008 May 20

“Invasive T1 bladder cancers are potentially lethal tumours with varying degrees of aggressiveness and progression. The management of invasive tumours can be very difficult and includes bladder-sparing with transurethral resection and intravesical therapy, or a more aggressive approach with radical cystectomy. Certain clinical and pathological factors might provide some risk stratification for invasive T1 tumours, and might better direct the physician towards an earlier cystectomy for some patients. This review provides a rationale for a radical cystectomy in patients with high-risk, invasive T1 bladder cancer.”

Drs. Herr, Donat, and Dalbagni?at MSKC have an article that you might find informative since your restaging TURB showed no cancer cells: Can restaging transurethral resection of T1 bladder cancer select patients for immediate cystectomy? J Urol. 2007 Jul;178(1):352.[comment] ?and 2007 Jan;177(1):75-9; discussion 79.[for the review]

“PURPOSE: We determined whether pathological findings on restaging transurethral resection predict early stage progression of T1 bladder cancer. MATERIALS AND METHODS: A cohort of 352 patients presenting with T1 bladder cancer on initial transurethral resection was evaluated by second or restaging transurethral resection. All patients received bacillus Calmette-Guerin therapy and 88% were followed for 5 years. Pathological findings on restaging transurethral resection were correlated with tumor features, stage progression frequency and progression-free survival. RESULTS: Of the 352 patients with T1 tumors 203 (58%) had residual tumor on restaging transurethral resection, including 92 (26%) with residual nonmuscle invasive (T1) cancer. During 5 years 66% of cases recurred and 35% progressed in stage. Of the 92 patients with residual T1 cancer 75 (82%) progressed to muscle invasion within 5 years compared to 49 of 260 (19%) who had no or nonT1 tumor detected on restaging transurethral resection. CONCLUSIONS: Restaging transurethral resection identifies patients with T1 bladder cancer who are at high risk for early tumor progression, justifying immediate cystectomy.”

Although I do not have the articles available to link to you, I know that Dr. Montie at University of Michigan has also written papers concerning surveillance and early cystectomy.

I got the above articles from at the following link, and the site is well worth searching if you have interest in the latest research: ===========================================================

20/03/2009 15:40

Hi Dave,

Seems we agree re medical help in differing countries after all.

The case for RC is muddier than I thought and than the initial contributions showed.

Clearly many who write have lived quite a while with their RC and so are not unreasonably in favour. Alas, these are the survivors – not much better than anecdotal evidence (not to dismiss that – such evidence is a necessary preliminary to doing deeper research) – and we don’t know what percentage that is of all those who’ve had it.

Dave’s high quote of 86% survival (vs. 35% not having RC) may relate to those with low grade tumours, but nothing in the research I’ve seen so far supports that. I fear it may be an over-exuberant consultant trying to convince a nervous patient (no doubt sincerely, perhaps believing it him/herself).

At 72 myself, I perhaps ought to be more relaxed that my end may be nigh, but you won’t be surprised to hear that I’m not.

Yes, the group is good. I’ve been following it for a while (I was diagnosed about 17 months ago), but only recently joined in – partly ‘cos I couldn’t get the forum to work for me, partly ‘cos I was just hesitant.

Kind regards, Ian

David Simms (


20 March 2009 15:25:55

By the way, I was T1G3+CIS when after eight years of dealing with
superficial high grade disease, I decided to have Cystectomy. At 52 years
old now, two years out from Cystectomy (with neo bladder), life is pretty
much normal for me.

As a result of where I live, I self referred myself to UCSF, where I was
fortunate enough to come under the care of Dr. Konety. A Google search will
reveal more about him. I like the fact that he was so knowledgeable of all
aspects of the disease and knew the percentages of success and lack of for
all of my questions.


19/03/2009 14:04

To RC or not to RC?

Following up Karen’s very helpful listing of the research that implied having RC after successful chemo helped long-term survival, I’ve now spent a bit of time analysing that summary – and am confused by the actual data reported – admittedly only a summary. This confusion has been added to by a later report (see later) which appears to contradict it. Perhaps colleagues here can help me?

In the 2001 research into post-chemo (cisplatin) metastatic patients (such as myself), there were 207 initially.

80 had RC afterwards.

24 of these seemed clear of cancer (as I do).

14 of these ‘survived’ 9 months to 5 years after the RC – so did 10 die before that? And none after 5 years?

Of those 49 who had some evidence of cancer still, and also had the RC, 20 ‘survived’ – more than 5 years? So did 29 die in less than 5 years?

The authors then say that “only 1 of the 12 patients who refused surgery remains alive” – presumably after more than 5 years. But where did that 12 come from? It must have been from the 127 who didn’t have surgery. But why report on only 12 of those? What about the other 115 of the 127 who didn’t have RC?

And of the 80, it seems the 7 (80 less the 24 + 49) who had no response to chemo died early.

There’s no report on the survival of the 127 really apart from the 12 who refused RC. Perhaps they survived at a similar rate.

Of the 80, 34 at most survived more than 9 months; perhaps few survived more than 5 years.

So if the authors use living 9 months or more as success, I wonder how many of the 127 who didn’t have RC lived 9 months and thus did as well?

Have I read all that right?

Now, perhaps contrary to this, there’s a report this year ( which implies that RC for T4 is not effective: the authors, having surveyed all stages of bladder cancer, conclude “earlier cystectomy or other aggressive therapy can save the lives of some patients with nonmuscle-invasive disease.” – implying that this isn’t true for muscle-invasive bladder cancer. All this implies to me that the case for RC for metastatic bladder cancer is still not proven as being an advantage. Or have I misunderstood?


18/03/2009 15:13Thanks for those suggestions Karen, but I hope you will forgive me if I don’t read those. I too agree on the mind-body interconnection, and have done NLP and PNI, aromatherapy and EFT. I think they’ve helped.

Perhaps because I’m scientific/engineering oriented, I have also do a lot of supplements and nutritional stuff, plus exercise and oxygenation.

For me, the best books I came across (of many that impressed) are those of Jonathan Chamberlain:

“Cancer: The Complete Recover Guide”, and his shorter

“Cancer Recovery Guide – 15 alternative and complementary strategies for restoring health”.

Chris Woolams “The Rainbow Diet and how it can help you beat cancer” & “Everything You Need to Know to Help You Beat Cancer” give supportive info.

There’s so much out there (including Borks 2001 “Natural Compounds in Cancer Therapy” and Alschuler & Gazella’s “Definitive Guide to Cancer”).

So I’ve read myself to a stop on books just now, having ploughed through another dozen or so on top of those. Nowadays, it is mainly the ‘net & analysing my own data (I measure everything I do – weight, exercise, etc).

As well as all the pills I take, I’ve re-oriented my nutrition to drive my body’s pH (as reflected in my urine) to be more alkaline. I’m not too sure of the soundness of the underlying theory, but what it does do is guide me to eat far more veggies and fresh fruit and less carbohydrates (plus no sugar or alcohol).

Kind regards, Ian

RE: THE article‏

From:    Karen Greene (

Sent: 18 March 2009 14:55:47

To:    Ian Clements (

Despite all that I have written, I am a firm believer in the mind-body connection, and did a lot of alternate /complimentary stuff along with my medical treatment. I wanted to do everything medically, but also got my brain engaged.


Check out the following books:


L. LeShan Cancer as a Turning Point Carl Simonton et al, Getting well Again Hirshberg & Barasch Remarkable Recovery Fanning Visualizations for Change [the section on immune diseases]

J. Borysenko - Power of the Mind to Heal and Full catastrophe Living-- along with J. Kabatt-Zinn


Let me know what you think. K

18/03/2009 14:08

Thanks for that Karen.

What is slowly dawning on me is that really not much is known about how metastatis happens.

There is the view, clearly prevalent here in the UK, that once the cancer cells have started wandering, they are then self-perpetuating at whatever site they alight.

However, the implication of the USA practice of removing the bladder (and being successful) is that this would otherwise remain a source of triggering of the metastatic cells’ growth, despite their having gotten out there – not something I’d considered before (and which, I suspect, will be at odds with the UK guys ideas).

A support to the USA idea is that it is not clear why different initial cancer sites give rise to differing metastatic daughter sites (such as bladder going to the supraclavicular lymph node, liver, and lungs – rather than, say, the prostate, stomach, and heart). So with so much ignorance about how metastasis happens, one goes with the evidence, not the theory. RC =  longer survival, never mind why.

Kind regards, Ian

RE: THE article‏

From:    Karen Greene (

Sent: 18 March 2009 13:10:30

To:    Ian Clements (

Hi Ian-- it is a tough call. The thing we have to be aware of is that

all mets start as cancer cells [microscopic level] wandering through the body and nesting somewhere. And it only takes one or two to start the cascade of tumor development somewhere else. Also-- re the recurrence issue, the same conditions which were the occasion for the development of the original cancer may still pertain [genetics, environmental stress, etc]. Obviously, the stats are not 100%-- so there is always the chance of being in long term remission-- but the odds are not in your favor. Aggressive monitoring is helpful, but ultimately the decision is yours. There is life after the RC-- as you have heard from everyone who weighed in on this-- but even this is not 100% as we have lost a few people even after the RC. Go with your gut and do your part to have a healthy life, and keep reading so you are informed. If you can get to a medical library, do a search for other articles by those authors-- they are all prolific researchers and doing good research into bladder cancer survival. Karen


17/03/2009 22:35

Many thanks Karen.

Whilst it is a bit disheartening to me, as I have the fond illusion that if I’m in remission and all my cancer markers remain within normal + my scans don’t show anything, then I’m OK. Repeating this every few months, and finding the same, then I can slowly resume a ‘normal’ life – albeit now on a different nutritional regime (which I give some credit to to having come through this, as well as the major reason being the chemo).

I’ll have to stew on this; talk it over with my oncologist. As you won’t be surprised to hear, I really don’t want to do the RC, but, as you and others point out, if it is fairly certain that not doing it is a death sentence and doing it gives a good % chance of survival, then it’s a no-brainer.

Kind regards, Ian

From:    Karen Greene (

Sent: 17 March 2009 18:21:23


Hi Ian,

I finally found it-- the reference and abstract are below. My memory of the numbers was wrong-- but having the cystectomy after chemo significantly improved survival. 


On the personal note-- my mets was in the nodes way up into my trunk, not limited to around the bladder or pelvis-- and remission of the mets was shown on the progressive CTS. My surgeon [Donat above] reported an 80+% recurrence rate if the bladder remained; the guy at Columbia I went to for a second opinion state that there was a 100% rate of recurrence. So I went ahead and here I am 9 + years later. Hope this helps and that you can find a talented surgeon! Karen




Herr HW. Donat SM. Bajorin DF. Post-chemotherapy surgery in patients with unresectable or regionally metastatic bladder cancer. Journal of Urology. 165(3):811-4, 2001 Mar. 

Click the "Ovid Full Text" link. 

UI: 11176475 PURPOSE: We update our experience with post-chemotherapy surgery in patients with unresectable or lymph node positive bladder cancer. METHODS: Of 207 patients with unresectable or regionally metastatic bladder cancer 80 (39%) underwent post-chemotherapy surgery after treatment with a cisplatin based chemotherapy regimen. We assessed the impact of surgery on achieving a complete response to chemotherapy and on relapse-free survival. RESULTS: No viable cancer was present at post-chemotherapy surgery in 24 of the 80 cases (30%), pathologically confirming a complete response to chemotherapy. Of the 24 patients 14 (58%) survived 9 months to 5 years. Residual viable cancer was completely resected in 49 patients (61%), resulting in a complete response to chemotherapy plus surgery, and 20 (41%) survived. Post-chemotherapy surgery did not benefit those who failed to achieve a major complete or partial response to chemotherapy. Only 1 of the 12 patients (8%) who refused surgery remains alive. CONCLUSIONS: Post-chemotherapy surgical resection of residual cancer may result in disease-free survival in some patients who would otherwise die of disease. Optimal candidates include those in whom the pre-chemotherapy sites of disease are restricted to the bladder and pelvis or regional lymph nodes, and who have a major response to chemotherapy.


17/03/2009 14:53

Thanks Roni.

However, I am still totally bewildered by the BCC navigation. I haven’t been able to use the Webcafe’s home page. There seemed to be three different entry points, one of which (if my memory is right) which was defunct; the other confused me; and now I get all this via – it always work, so I’m (lazily) just using that.

But enough. I must sort this out!


Re: [CAFE] metastatic blc/RC‏


Sent: 17 March 2009 14:43:21

To:    ianclements@HOTMAIL.COM

Hi again Ian,

Yesterday I sent an article on urinary diversion options to you.  RC is understandably a daunting procedure.

If you go to Webcafe’s home page – upper right corner, click on Resources.  It will take you to Resources USA.  Then  scroll way down to Recommended Reading, you’ll find my book, “A Guide to Bladder Cancer, Urostomy and Impotence.”  Wendy and Joris have made it available in pdf format. You can either read it online or print anything of interest.   It covers most everything related to bladder cancer, and has 2 chapters on impotence and penile prostheses.  Ben has had an inflatable prosthesis since 1985 – comfortable, unobtrusive, easy to use and works great!  Hopefully you won’t need to know any of it and will qualify for nerve-sparing.

Also, happy to answer questions e-mail or phone.


Roni      ===========================================================17/03/2009 14:31

Thanks Wendy. That improves the picture for me.

On reflection, my oncologist did mention that things had moved on in the last few years, especially re chemo.

It may be that I need to watch the various cancer markers before deciding anything, along with the scans.

I also recall that RC was originally ruled out ‘cos the lymph nodes either side of my bladder were so enlarged and pressing on nerves that it would be difficult/impossible to remove them. Having said that, I suspect they’ve now reduced to normal.


Date:               Tue, 17 Mar 2009 15:16:04 +0100

From:              Wendy Sheridan <wendy@BLCWEBCAFE.ORG>

Subject:          Re: cystectomy a guarantee??

There is a small but real chance of a recurrence post-cystectomy of cancer elsewhere but the stats say that risk is low, about 10%. There seems to be increased risk with CIS and, logically, the recur rate increases with stage and grade of the Cx specimen.

Some experts absolutely feel the need to remove the bladder post-chemo if response was good, some obviously not.

Neoadjuvant chemo seems to becoming more and more popular in the literature and clinical trials but other experts will say that post-op is just as helpful and only use it in case of extravesical spread.

There’s also a bit of a difference between Europe or the UK and the US, with the opinion leaning to: “America doctors are more aggressive in just about every way” (not a direct quote but something I have gleaned from numerous urology conferences in Europe). Which may explain Ian’s doctor’s recommendations.

I doubt a doctor would knowing operate if there is obvious nodal involvement but it can happen that this is only discovered perioperatively. In which case it is something a person should discuss before the operation. How much spread is too much, according to the doctor, to finish the operation? Ideally spread is limited to a node, or a couple…and surgery is completed.

The stats for those who have aborted cystectomies and given chemo and no more surgery are pretty dismal.

The opinion of late seems to be toward chemo for all invasive blc, while ten years ago that was not the case, we saw many more stage IIIA and IIIB-ers having no chemo. I know a few who did fine, too, no recurs and ten years down the road!

I heard two esteemed experts dispute the famous USC/Stein paper Dan Martin mentions recommending extended lymph node removal. The debate was enlightening, basically the “con” side (delived by a UK expert, with the ‘pro’ side coming from a German expert) said that the patient population used in that paper was rather skewed, using many Pa and P1 specimens giving it all a brighter outcome than most situations would stand to gain.

Please note I’m not arguing with USC and Stein’s approach of removing many nodes-it seems too successful for me to argue! Just that there are many differences of opinion between experts, though guidelines are finally being established between the AUA and the EUA these days…However, the guidelines do not recommend 65 nodes-I think it’s more in the neighborhood of 10!

The option of surgery post-chemo might also depend on other factors, such as extent of original spread, area of spread, health of the person and personal choice. If a doctor is following standard procedure he can’t be blamed but the guidelines are flexible and ideally a doctor should be, too (not to mention the insurance involved).



Date:               Tue, 17 Mar 2009 08:44:11 -0400

From:             H Mayer <hildegard_mayer@HOTMAIL.COM>

Subject:          Re: metastatic blc/RC

Here is my bl.c. history: Diagnosed in 1999: A large through-the-bladder-wall tumor blocked the ureter which damaged my kidney severely. After 3 Taxol and Carboplatin chemo treatments, I learned during a consultation at a TX cancer center that my tumor did not shrink. Had a RC with ileal conduit 5+ months after my diagnosis (4 of 8 checked lymph nodes were cancerous). A PET scan found numerous new cancerous nodes in 2000, some in inoperable places. A MSKCC expert recommended to my small town oncologist (then my 4th) for me: Gemzar and Adriamycin chemos. A PET scan showed after 2 or 3 treatments the shrinkage of the nodes and after 4 or 5 no more cancer, but I finished all 6 treatments. It was not an easy journey (misdiagnosed for a long time; later was told: 6 to 11 or 12 months with or without RC or chemos, even “Go home and do what you still want to do.” A lot of luck was on my side: a surgeon who still did the RC; a PET scan that found during an unrelated hospital stay the metastasized nodes while a CT scan report from that month mentioned no new cancer; my last oncologist; the MSKCC doctor for the perfect for me chemo recommendation; last, but not least – this great support group. I did not even know that bladder cancer existed when I was diagnosed. The information and support I received from many list members was priceless. Please keep in mind that the treatments that I received may or may not work for others with advanced bl. c., since we are all different. I agree with Linda: A PET scan can be very helpful for us with advanced bladder cancer. My surgeon said that he wished that I would have had a PET scan before the RC. Medicare and some insurance companies do not pay for a PET scan for even advanced bladder cancer patients without a bladder. I heard of a very recent study by MSKCC, but did not see it in print, about PET scan and bladder cancer. Did someone? The suggestion to see the best expert is good, but my insurance would only pay for in-state consultation, treatment or surgery, even that there were only 3 (to 5) female RCs done in the whole small state in a year. A 2nd and 3rd opinion doctor visit was important to me for my treatment decision. How I wish that all of you can in 10 years and in good health write their follow-up note to the group. Good luck, Hildegard P.S.: Congratulations to all that had recently a “milestone”. ==========================================================

17/03/2009 13:04

Thanks Mike; that gives me some comfort and confidence to explore this alterantive.


Date:               Tue, 17 Mar 2009 08:30:45 -0400

Ian –

Whatever you decided to do there are now nerve sparing surgery techniques that can spare the sex life. I fully understand your concern, I had the same and it had prompted me give the CM a try.

Another factor for me was that I had once had a several week impotence problem brought on by medication. I knew from that experience that not having the ability had absolutely no effect on the desire.

Good luck on finding a surgeon that can spare your necessary nerves.



17/03/2009 09:31

Thanks for that elaboration Wendy. Not only am I not fatalistic (well,most of the time – I do have my dark moments), but fortunately neither is my wife. So I think I can give it a good shot.

I’m just quite apprehensive about having RC, with or without the neobladder that seems the best, along with probably loosing my sex life.

But the great support and info from this forum is helping me no end.


Date:               Mon, 16 Mar 2009 17:59:13 -0700

Ian, I’m not sure how your medical system differs but I searched hard before my RC not only to find the best surgeons, but equally important was to find doctors that were willing to fight with me. A mutual understanding of how I wanted to approach my treatment (in my case, the most aggressive approach) was necessary. There are great differences in attitude amongst doctors. Fortunately, I found one in particular (Dr. Kaplan) that was willing to give it his all right along side me. I consulted with others that advised me on the most aggressive approaches possible in my case….all in the ‘chance’ and ‘hope’ for cure and against the odds. People do survive.

I couldn’t afford a fatalistic attitude and I couldn’t afford any of my medical team to have one. Can you consult with other doctors? Maybe there is someone willing to help you that can show some optimism. Hope is tangible and affects our recovery.

Wendy Ramsay

Voiding with a neobladder…6 hours..Wow! A normal night for me is 1 and a half to 2 and a half hours before having to void…I am up 3 to 5 times a night. Dr. Grossman at M.D. Anderson told me that I need to set the clock for every two hours. Sometimes I do and sometimes I don’t..and sometimes I am really glad that someone invented Adult Depends, because I hit the snooze button and doze back off. I think that some folks have the neobladder done with the large intestine and some with small intestines…don’t know that for a fact but could be. But, those of us who can go for 6 hours must have a larger capacity than I do, that’s for sure. I have tried a couple of alternative devices but they tend to slide off while I am sleeping, so I have opted, for the moment, just to use Depends (and hope they don’t leak…and they do sometimes, too) Just sleep with a pad under me, and do the best that I can.

Bill Pullen Houston, Tx.

Date:               Mon, 16 Mar 2009 17:07:58 -0700

Dr. Stein removed my stage III bladder along with 65 nodes in January 2006. He found no evidence that it had spread to the nodes, but since cells can sometimes remain undetected, I go in for my check ups every 6 months. Diana =============================================================

16/03/2009 23:46

Great Dan; that looks really convincing – just hope (a) it works on my oncologists; (b) I can suss out an experienced urological surgeon in the specialism. I fear that, given my oncologists opinions, that there may not be too many in the UK doing such work.

Kind regards, Ian

Date:             Mon, 16 Mar 2009 19:37:03 -0400

Linda and Ian and Robert…

The ‘classic’ USC Norris journal article (by Stein and Skinner…) of 1,054 bladder cancer patients included 244 patients that had lymph node positive disease. 209 had more than 15 nodes removed and 35 had less than 15 nodes removed.

Recurrence-free survival was about 45% for the group that had more lymph nodes removed and about 20% for the group that had fewer nodes removed. See figure 6. I’m happy to send the article to anyone who wants it.

Equally important, these patients were followed for up to 15 years and the data clearly shows that the ‘C’ word (cure) can be used after about 4 or 5 years (unlike bladder sparing therapies where recurrence continues over time – this is not an anecdotal (one person hey look at me) but a statistically valid conclusion based on a large population of patients).

This shows that even for those patients whose cancer has metastasized, RC with extended lymph node removal can be a worthwhile option.

I was one of those who travelled a significant distance (350 miles) for my RC (65 nodes removed); almost 5 years later I would take the same approach, absolutely no second thoughts.

And even if my blc were to recur, at least I’d bite the big one knowing that I took my best shot.

So for those who have high-grade cancer, I agree with Silverman that a proactive and aggressive approach can save your hiney (at least until the Grim Reaper comes by for that last visit).

Dan ===========================================================

16/03/2009 23:41

Thanks Roni for that full description of the alternatives. This will help me if I decide I need to go down that route.

Alas, it still doesn’t sound too good – but as someone said, it beats the alternative.

Kind regards, Ian

Urinary diversion options‏


Sent: 16 March 2009 23:22:22

To:    ianclements@HOTMAIL.COM

Hi Ian,

In response to your inquiry about urinary diversions – all are workable/doable – and all better than the alternative.  My article on urinary diversion options follows:

Best of luck and big hugs,



16/03/2009 23:30

OK; will do. But the info you’ve given me is probably enough for now. This certainly makes me less worried about having RC.


Date:               Mon, 16 Mar 2009 19:01:47 -0400

please read about the alternatives– there is a link on the site. There are 3 options– the external appliance– on the abdomen rather than the leg– that is for immediately aftr surgery. Then there is the catheterizable internal continent reservoir which I have, and then the neobladder– which is a bladder replacement constructive of bowel tissue and which is connected to your original issue urethra. Karen =============================================================16/03/2009 23:26

Much appreciated Karen. I hope you can find it.


16 March 2009 23:14:48


I will look some more tomorrow-- I recall the name of one of the

authors-- H. Herr, but the other authors were surgeons or fellows at

Sloan Kettering and it was a major journal. Will look some more. I

recall it convinced me I made the right decision so it must have been

after 2000. Karen


16/03/2009 23:07

Thanks for that illumination Mitch; that sounds much more aesthetically acceptable.

Regards, Ian

Mon, 16 Mar 2009 22:59:26 +0000


A neobladder is an internal bladder made from some part of your small or large intestine.  The ureters and urethra are attached to the bladder.  You pretty much void the same way, through the same plumbing, but bear down to empty the bladder.  Think of what you did as a kid when you wanted to ‘pee fast”.

I’ve had a neobladder since May 2004 with no major problems.  I’m fully continent during the day, 99% continent at night, and had a surgeon skilled in nerve sparing techniques.  Its a good option for those who are eligible for it.


16/03/2009 23:03


I agree about Linda’s good info. And others. It is making me do a re-think about RC.

However, I was just saying that the link you gave  me isn’t relevant to my case – I’m collating as much info as I can to share with my oncologists with a view to seeing what is available here (probably meaning I’ll have to make a strong case, given what appears to be the standard view that RC is of no use at my state of cancer).

Thanks again,


16 March 2009 22:55:14


Ian --


Linda sent good info to you. My husband also was node positive but we

didn't find that out until surgery. He is now 7-1/2 yrs. from neobladder surgery which was followed w/4 cyles of MVAC chemo. His surgeon also removed numerous lymph nodes and pathology confirmed one node was positive for TCC. At the time, his prognosis for survival was 25% without chemo and 50/50 if he had chemo so we feel very fortunate. Also, life with a neobladder is about like normal with the exception of having to get up at least once during the night to void.


Good luck with your decision --



[CAFE] metastatic blc/RC‏

From: The Bladder Cancer Support and Information eCommunity ( on behalf of Linda Weyand (lweyand@AOL.COM)
Sent: 16 March 2009 22:05:08

Hi, Ian and Robert,
I know of two members of our List that had metastatic bladder cancer, had neoadjuvant chemotherapy, and subsequently had their bladders removed. Both have enjoyed long-term survival. One is Karen and her story can be found here:,english/

The other is Hildegard and you could find info about her story by searching the bladder cancer cafe archives. If I remember correctly, most doctors had a fatalistic attitude toward her situation, and she had to fight like crazy to get the treatment that she wanted and needed.  After receiving the treatment she sought, her fatal prognosis became long-term survival…hooray! I think anyone considering an RC knowing they have/had node positive bladder cancer should have a pet scan immediately prior to surgery so that any lymph nodes that “light” up can be removed along with the bladder. In fact, I would want to go with USC’s protocol and have extensive lymph nodes resection. USC often removes 65+ nodes during RC whereas most surgeons elsewhere remove approx. 10-20.

Karen and Hildegard have remarkable and miraculous stories that may be of benefit to you.  (Hildegard: If I have misrepresented your story in anyway, I apologize….my memory is not what it use to be!)

Personally, if I had node positive bladder cancer and had received successful chemo, I would want an RC/urinary diversion with extensive lymph node resection. I would consult with one of the highly reputed bladder cancer surgeons even if it meant having to travel a great distance for the appointment. Although I think that your doctors are probably following the accepted standard of practice, in your situation I would want to go far beyond the accepted standard and take any logical step available in hopes of acheiving a long-term survival result….with our courageous Wendy R. as my role model. Many people and doctors think having your bladder removed is a last resort that needs to be avoided if at all possible, and it has been common practice to not remove the bladder in metastatic cases. I guess having had such a good life since my bladder was removed makes me see this is a completely different light. I do not have any research on hand that recommends RC with nodal involvement, so please remember this is just my gut feeling on this subject.n I am looking forward to reading Wendy R.’s take on this issue.

Hope this helps,
Linda W.

From:    The Bladder Cancer Support and Information eCommunity ( on behalf of Linda Weyand (lweyand@AOL.COM)

Sent: 16 March 2009 20:36:49


Hi, Lorraine,
People who receive neoadjuvant chemo prior to having their RC often have a complete response from the chemo treatment with no evidence of disease. These are the people Karen is writing about….they had neoadjuvant chemo, but no radiation.  In one research series that I am aware of, there was a 100% recurrence/fatality rate among those that opted to keep their bladders after the neoadjuvant chemo. I do not remember the statistics of those that had the RC after the chemo, but there was a much higher survival rate.

In no way does this relates to your situation because you had combined modalities (CM) not just neoadjuvant chemo. CM includes both radiation and chemo and is intended to result in the patient keeping their bladder. Of course, if a recurrence occurs after the CM treatment is completed, RC/urinary diversion is the next step to hopefully assure long-term survival. Recently, you mentioned that you had polyps removed….were these checked by pathology to determine if they were benign, atypical, or cancerous cells?

Hope this helps,
Linda W. neobladder 2/202

The Bladder Cancer Support and Information eCommunity ( on behalf of Shawhouse (shawhouse@EARTHLINK.NET)


16 March 2009 19:08:26



USC doctors have the philosophy that the more nodes that are removed

during cysectory, the less likely there will be a spread to other areas outside of the urinary tract.


Re: [CAFE] cystectomy a guarantee??‏

From:    The Bladder Cancer Support and Information eCommunity ( on behalf of Karen Greene (greenegoddess1@JUNO.COM)

Sent: 16 March 2009 19:01:01


Hi Ian- when I was diagnosed and treated 9 years ago - was told by 2 different docs at different hospitals that even tho I apparently had a complete response to the chemo, the bladder had to go since there is such a high rate of recurrence. There was an article which came out of MSKCC which showed that of a number of post chemo, none of those who refused the RC survived. Not all who had the RC didN but none of those who refused it. I can try to locate the reference if you like. Karen

Defining Early Morbidity of Radical Cystectomy for Patients with Bladder Cancer Using a Standardized Reporting Methodology[lxviii]

Accepted 2 July 2008. published online 21 July 2008.


Reporting methodology is highly variable and nonstandardized, yet surgical outcomes are utilized in clinical trial design and evaluation of healthcare provider performance.


We sought to define the type, incidence, and severity of early postoperative morbidities following radical cystectomy (RC) using a standardized reporting methodology.

Design, setting, and participants

Between 1995 and 2005, 1142 consecutive RCs were entered into a prospective complication database and retrospectively reviewed for accuracy. All patients underwent RC/urinary diversion by high-volume fellowship-trained urologic oncologists.


All complications within 90 d of surgery were analyzed and graded according to the Memorial Sloan-Kettering Cancer Center complication grading system. Complications were defined and stratified into 11 specific categories. Univariate and multivariate regression models were used to define predictors of complications.

Results and limitations

Sixty-four percent (735/1142) of patients experienced a complication within 90 d of surgery. Among patients experiencing a complication, 67% experienced a complication during the operative hospital admission and 58% following discharge. Overall, the highest grade of complication was grade 0 in 36% (n=407), grade 1–2 in 51% (n=582), and grade 3–5 in 13% (n=153). Gastrointestinal complications were most common (29%), followed by infectious complications (25%) and wound-related complications (15%). The 30-d mortality rate was 1.5%.


Surgical morbidity following RC is significant and, when strict reporting guidelines are incorporated, higher than previously published. Accurate reporting of postoperative complications after RC is essential for counseling patients, combined modality treatment planning, clinical trial design, and assessment of surgical success.

Take Home Message

Accurate reporting of complications utilizing the 10 reporting criteria and methodology is essential for preoperative counseling, for identifying modifiable risk factors to reduce complication rates, for planning combined modality treatment, for clinical trial design, and for a more accurate assessment of surgical success.

Radical cystectomy for T2 bladder cancer with failed chemo[lxix][lxx]

Outcome after radical cystectomy in patients with clinical T2 bladder cancer in whom neoadjuvant chemotherapy has failed


To analyse the outcome after radical cystectomy (RC) in patients with clinical T2 bladder cancer not responding to neoadjuvant chemotherapy (NAC).


In a retrospective analysis, study patients received NAC for clinical T2 disease before RC and a control group had RC for clinical T2 disease with no NAC. Patients treated with NAC were further grouped based on the pathological response; failure to respond was defined as ‘no change in T stage or a higher T stage in the RC specimen (≥pT2)’, and the relevant clinical and pathological data were analysed.


In all, 53 patients satisfied the inclusion criteria for the study group and 200 for the control group. In the study group 18 (34%) responded to NAC (group 1) of whom 11 (61%) were pT0 and seven (39%) pT1, and among the non-responders (group 2) 19 (54%) were pT3/pT4 and 16 (46%) were pT2; 16 (46%) patients in group 2 had lymph node metastasis. The mean follow-up was 26 months. In group 2, local recurrence occurred in six (17%) vs none in group 1. Seven patients (20%) in group 2 developed metastases, vs one (5%) in group 1 (P = 0.01). The 5-year disease-free survival was significantly lower for group 2 (40%) than group 1 (91%, P = 0.007) and the control group (67%, P = 0.04). There were 14 deaths from bladder cancer in group 2, vs one in group I (P = 0.01). The 5-year disease-specific survival was significantly lower for group 2 (52%) than group 1 (83%, P = 0.008) and the control group (70%, P = 0.001).


A lack of response to NAC is associated with a significantly higher local and distant recurrence, and with lower survival.

Hygiene and urinary tract infections after cystectomy in 452 Swedish survivors of bladder cancer

Tuesday, 10 November 2009
Division of Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.

To determine whether or not an improved hygiene can lessen the incidence of symptomatic urinary tract infections (UTIs) in patients treated by cystectomy for urinary bladder cancer.

We attempted to contact during their follow-up all men and women aged 30-80 years who had undergone cystectomy and urinary diversion at seven Swedish hospitals. During a qualitative phase we identified hygienic measures and included them in a study-specific questionnaire. The patients completed the questionnaire at home. Outcome variables were dichotomized and the results presented as relative risks (RR) with 95% confidence interval.

We received the questionnaire from 452 (92%) of 491 identified patients. The proportion of patients who had a symptomatic UTI in the previous year was 22% for orthotopic neobladder and cutaneous continent reservoir, and 23% for non-continent urostomy diversion. The RR for a UTI was 1.1 (0.5-2.5) for ‘never washing hands’ before handling with catheters or ostomy material. Patients with diabetes mellitus had a RR of 2.1 (1.4-3.2) for having a symptomatic UTI.

We could not confirm lack of hygiene measures as a cause of UTI for men and women who had a cystectomy with urinary diversion. Patients with diabetes mellitus have a greater risk of contracting a UTI.

Written by: Thulin H, Steineck G, Kreicbergs U, Onelöv E, Ahlstrand C, Carringer M, Holmäng S, Ljungberg B, Malmström PU, Robinsson D, Wijkström H, Wiklund NP, Henningsohn L.

Reference: BJU Int. 2009 Oct 23 doi:10.1111/j.1464-410X.2009.08909.x

PubMed Abstract PMID:19863516

Radical Cystectomy versus Radical Radiotherapy[lxxi]

A study of the morbidity, mortality and long-term survival following radical cystectomy and radical radiotherapy in the treatment of invasive bladder cancer in Yorkshire.

Chahal R, Sundaram SK, Iddenden R, Forman DF, Weston PM, Harrison SC.

Department of Urology, Orchard House, Pinderfields and Pontefract NHS Trust,

Wakefield, West Yorkshire WF1 4DG, UK


OBJECTIVES: To study the morbidity of radical cystectomy and radical

radiotherapy in the treatment of patients with invasive carcinoma of the bladder and to report the long-term survival following these treatments.

PATIENT AND METHODS: 398 patients with invasive carcinoma of the bladder treated between 1993 and 1996 in the Yorkshire region were studied. Of 398 patients studied, 302 patients received radical radiotherapy and 96 underwent radical cystectomy. A retrospective review of patients' case notes was performed to construct a highly detailed database. Crude estimates of survival differences were derived using Kaplan-Meier methods. Log-rank tests (or, where appropriate, Wilcoxon tests) were used to test for the equality

of these survivor functions. These functions were produced as all-cause survival. The proportional hazards regression modelling was used to assess the impact of definitive treatment on survival. A backwards-stepwise approach was used to derive a final predictive model of survival, with likelihood ratio tests to assess the statistical significance of variables to be included in the model.


CONCLUSIONS: This retrospective regional study shows that there is no

significant difference in the 5-year survival of patients with invasive bladder cancer treated with either radical radiotherapy or radical cystectomy. All forms of radical treatment for bladder cancer are associated with a significant treatment-associated morbidity and mortality.

Gastrointestinal complications were responsible for the majority of

complications. The clinical T stage, the sex and the ASA grade of the

patient were the only independent predictors of survival. The data in this series suggests that radical radiotherapy and radical cystectomy should be both considered as valid primary treatment options for the management of invasive bladder cancer.

Copyright 2003 Elsevier Science B.V

[ii]From the associated article for this abstract:

[lxx] Murugesan Manoharan, Devendar Katkoori, Thekke A. Kishore, Bruce Kava, Rakesh Singal* and Mark S. Soloway; Departments of Urology and  *Medicine, Miller School of Medicine, University of Miami, Miami, FL, USA

[lxxi] Eur Urol. 2003 Mar;43(3):246-57.

Posted in Cancer Perspectives, cancer treatment, surgery | 8 Comments »

Ian Clements: ‘radical cystectomy alternatives’ research – for bladder cancer

Posted by Jonathan Chamberlain on April 21, 2011

See also my two cancer books – for details

Ian Clements ‘ Radical Cystectomy Alternatives’ Research

RC Alternatives


Arguments against organ preservation in patients with muscle invasive bladder cancer. 2

Trimodality treatment for bladder cancer: Does modern radiotherapy improve the end results?. 2

Drug May Be an Alternative to Cystectomy for BCG Failures. 3

Phase II Study Of Conformal Hypofractionated Radiotherapy With Concurrent Gemcitabine In Muscle-Invasive Bladder Cancer. 3

Radiation plus gemcitabine might be as good as surgery for bladder cancer. 4

Improved method for RC?. 5

Update of clinical trial data for trimodality therapy. 5

Surgery not always necessary for bladder cancer patients. 6

Long-term outcomes of a randomized controlled trial comparing thermochemotherapy with mitomycin-C alone as adjuvant treatment for non-muscle-invasive bladder cancer (NMIBC). 6

Response and progression-free survival in T2 to T4 bladder tumors treated with trimodality therapy with bladder preservation. 7

Robotic cystectomy: Is it ready for prime time?. 7

RC versus Alternatives. 8

Outcome of patients who refuse cystectomy after receiving neoadjuvant chemotherapy for muscle-invasive bladder cancer. 8

Updated results of bladder-sparing trimodality approach for invasive bladder cancer, 9

Gemcitabine sensitizes invasive bladder tumors to radiation. 10

Quality of life assessment after concurrent chemoradiation for invasive bladder cancer. 10

Failure of bacille Calmette-Guérin in patients with high risk non-muscle-invasive bladder cancer unsuitable for radical cystectomy. 11

Organ-sparing strategies in the management of invasive bladder cancer. 12

Bladder Preservation in Octogenarians With Invasive Bladder Cancer. 12

Long-Term Follow-Up of Cisplatin Combination Chemotherapy in Patients With Disseminated Nonseminomatous Germ Cell Tumors. 13

Total Cystectomy Versus Bladder Preservation Therapy for Locally Invasive Bladder Cancer. 14

Bladder-Sparing Therapy a Good Alternative. 14

An Alternative to Radical Cystectomy. 16

Conservative treatment of invasive bladder cancer. 16

A 10-year retrospective review of a nonrandomized cohort of 458 patients undergoing radical radiotherapy or cystectomy in Yorkshire, UK. 17

Radiochemotherapy for bladder cancer. 18

Safety of active surveillance program for recurrent nonmuscle-invasive bladder carcinoma. 18

What happens to the patients with muscle-invasive bladder cancer who refuse cystectomy after neoadjuvant chemotherapy?. 19

Radical Cystectomy versus Radical Radiotherapy. 21

Arguments against organ preservation in patients with muscle invasive bladder cancer

Trimodality treatment for bladder cancer: Does modern radiotherapy improve the end results?[i]

by Mohamed S. Zaghloul, MD Tue, 05 April 2011

BERKELEY, CA ( – Recent trimodality organ-preservation strategies combine maximal transurethral resection of bladder tumour (TURB), chemotherapy and radiation.

The rationale for performing TURB and radiation is to achieve local tumour control. Application of systemic chemotherapy, most commonly as cisplatin-based regimen, aims at the eradication of micro-metastasis and to act as radio-sensitizers. This role has been established in many diseases and several studies. Cisplatin-based chemotherapy in combination with radiotherapy, following TURB, results in a complete response rate of 50-81%.It is recommended and stressed upon that early cystectomy is performed in individuals who do not achieve a complete response following combination therapy. This will allow about 42-78% of patients to survive with an intact bladder at 3-5 years. A comparable long-term survival rate of 50-60% at 5 years’ follow-up is reported by both multimodality bladder-preserving trials and cystectomy series. Trimodality therapy has the advantage that about half of patients expected to survive with their native bladder intact. However, both therapeutic approaches have never been directly compared. It is worth noting that bladder-preserving multimodality strategy requires very close multidisciplinary co-operation and a high level of patient compliance. Even if a patient has shown a complete response to a multimodality bladder-preserving strategy, the bladder remains a potential source of recurrence, or new tumour appearance. Pathological complete remission at repeat TUR after the initial transurethral resection of the primary tumour, followed by chemotherapy in combination with radiotherapy, was identified as a prognostically important variable. However, even the latter patients are at a life-long risk of developing intravesical tumour recurrences with the need for meticulous surveillance. Despite the absence of such direct randomized trials comparing both modalities, trimodality treatment comprising maximal TURBT followed by different regimens of combined radiochemotherapy achieved comparable results to radical cystectomy in many trials.

With the application of modern radiotherapy, it is possible to safely deliver a high radiation dose, with the sensitizing effect of the concomitant chemotherapeutic agents. These variable regimens of radiochemotherapy were successful in achieving the goal of improved survival rates, with preservation of the native bladder. The clinical target volume (CTV) for irradiating the bladder should encompass the entire outer circumference of the bladder, any extravesical disease spread and any region deemed to be at risk of microscopic disease spread. It has also been extended to include the prostate and prostatic urethra in males or upper vagina in females. The pelvic nodal CTVs extend around external and internal iliac vessels. The external iliac CTV extends anteriorly to include the lateral external iliac nodes. The internal iliac CTV extends laterally to the pelvic sidewall. The contours around the external and internal iliac vessels are joined to create a single volume on each side of the pelvis, including the obturator nodes. The pre-sacral CTV extends anteriorly to the first and second sacral prominence. The planning tumor volume (PTV) margins are 5–10 mm according to the institutional policy of creating CTV–PTV margins. Partial bladder irradiation (bladder tumor with safety margin) may be used as a boost – either through intensity-modulated radiotherapy (IMRT) external beam or via brachytherapy. The partial bladder approach permitted the delivery of a considerably higher dose without increased toxicity. It is estimated that the tolerance of part of the bladder volume is higher than that of the organ as a whole, with tolerance doses estimated at 80 Gy for two-thirds of the bladder compared with 65 Gy for the whole organ.

Radiation uncertainties include set-up errors, patient movement, internal organ movement, and volume changes due to continuous bladder filling (both inter- and intrafraction). The advancement in treatment verification procedures in modern radiotherapy and the use of fiducial markers applied during TUR, reduces set-up errors, while adaptive radiotherapy could decrease the unnecessary irradiation of normal tissues by tracking bladder volume changes. In addition, new radiotherapeutic techniques, such as IMRT and volume-modulated radiotherapy (VMAT), permit dose escalation to the target without increasing the dose to the surrounding normal tissues. The value of this trimodality treatment depends upon the extent and adequacy of TURBT, the use of effective chemotherapeutic agents both as sensitizing and adjuvant agents for radiotherapy, and more importantly, upon the precise technique of irradiation to achieve the desired results. Ensuring target coverage may improve the tumor control probability by ensuring the target receives the intended dose, while reducing dose to critical normal tissues.

Urodynamic tests and quality of life (QoL) studies for long-term survivors treated with trimodality treatment showed that 75% were considered to have bladders with normal function. Furthermore, a questionnaire study revealed that 78.8% were ‘delighted’ or ‘pleased’ in terms of urinary function after trimodality conservative therapy. More than half of men had erections hard enough for intercourse and around 59% were satisfied with their sex life after conservative therapy. Sexual function was reported in 50% of men and 71% of women following bladder preservation. These rates compare favorably with a contemporary questionnaire-based study that reported 13% and 42% potency rate following radical surgery and nerve-sparing cystectomy, respectively.

Drug May Be an Alternative to Cystectomy for BCG Failures[ii]

Jody A. Charnow March 21, 2011

VIENNA—Mycobacterial cell wall DNA complex (MCC) may provide an alternative to cystectomy for patients with non-muscle invasive bladder cancer refractory to bacillus Calmette-Guérin (BCG) treatment, according to preliminary study findings.

Alvaro Morales, MD, of Queen’s University in Kingston, Ontario, Canada, and colleagues tested MCC in 129 Caucasian patients with non-muscle invasive bladder cancer who failed to respond to one or more courses of BCG. The treatment consisted of six weekly intravesical instillations of 8 mg MCC (induction), followed by three once-weekly instillations at three, six, 12, 18, and 24 months (maintenance). MCC has two modes of action: immune stimulation and direct anticancer activity.

Of the 129 patients, 95 (73.6%) were male. At study entry, 91 (70.5%) had carcinoma in situ and 38 (29.5%) had papillary tumors.

The overall one-year disease-free survival (DFS) rate was 25%, the researchers reported at the 26th Annual Congress of the European Association of Urology. The one-year DFS rate was 21.0% for patients with CIS tumors and 35.1% for those with papillary tumors. The treatment was well tolerated, and most adverse events were mild to moderate in intensity and few led to treatment discontinuation.

Dr. Morales’ group explained that patients with tumors refractory to BCG generally have a poor response to second-line therapies. Radical cystectomy, they noted, is the standard of care following BCG failure, but some patients refuse surgery or are not good surgical candidates.

The drug, which has the trademark name Urocidin, is being developed by Endo Pharmaceuticals, of Chadds Ford, Pa., and Bioniche Life Sciences, of Belleville, Ontario.

Phase II Study Of Conformal Hypofractionated Radiotherapy With Concurrent Gemcitabine In Muscle-Invasive Bladder Cancer[iii]

Written by Lynda Coghlan    Monday, 07 February 2011 09:03

The Christie NHS Foundation Trust, Manchester, United Kingdom. The Royal Preston Hospital, Preston; Leicester Royal Infirmary, Leicester; and The Gray Institute for Radiation Oncology and Biology, Oxford, United Kingdom.

The aim of this prospective, phase II trial was to determine the response of muscle-invasive bladder cancer (MIBC) to concurrent chemoradiotherapy of weekly gemcitabine with 4 weeks of radiotherapy (RT; GemX).

Fifty patients with transitional cell carcinoma, stage T2-3, N0, M0 after transurethral resection and magnetic resonance imaging, were recruited. Gemcitabine was given intravenously at 100 mg/m(2) on days 1, 8, 15, and 22 of a 28-day RT schedule that delivered 52.5 Gy in 20 fractions. Chemotherapy was stopped for Radiation Therapy Oncology Group (RTOG) grade 3 bladder or bowel toxicity. The primary end points were tumor response, toxicity, and survival.

All patients completed RT; 46 tolerated all four cycles of gemcitabine. Two patients stopped after two cycles, and two stopped after three cycles, because of bowel toxicity. Forty-seven patients had a post-treatment cystoscopy; 44 (88%) achieved a complete endoscopic response. At a median follow-up of 36 months (range, 15 to 62 months), 36 patients were alive, and 32 of these had a functional and intact bladder. Fourteen patients died; seven died as a result of metastatic MIBC, five died as a result of intercurrent disease, and two died as a result of treatment-associated deaths. Four patients underwent cystectomy; three because of recurrent disease and one because of toxicity. One patient required a bowel resection for late toxicity. By using Kaplan-Meier analyses, 3-year cancer-specific survival was 82%, and overall survival was 75%.

Concurrent gemcitabine-based chemoradiotherapy (ie, GemX) produces a high response rate in MIBC and has durable local control and acceptable toxicity, which allows patients to preserve their own bladder. This treatment modality warrants additional investigation in a phase III setting.

Written by: Choudhury A, Swindell R, Logue JP, Elliott PA, Livsey JE, Wise M, Symonds P, Wylie JP, Ramani V, Sangar V, Lyons J, Bottomley I, McCaul D, Clarke NW, Kiltie AE, Cowan RA.

Reference: J Clin Oncol. 2011 Jan 4. Epub ahead of print. doi: 10.1200/JCO.2010.31.5721

PubMed Abstract PMID: 21205754

Radiation plus gemcitabine might be as good as surgery for bladder cancer[iv]

Radiation plus gemcitabine may be as good as cystectomy for muscle-invasive bladder cancer, a phase II study suggests.

“After radiotherapy and four cycles of gemcitabine, three-year cancer-specific survival was 82% and overall survival was 75%, the study investigators reported online January 4th in the Journal of Clinical Oncology.

“These results with gemcitabine and radiotherapy are as good as the best reported results of cystectomy, although ours is only a small group of selected patients,” said Dr. Richard Cowan, a consultant in Clinical Oncology at Christie Hospital in Manchester, England

Improved method for RC?[v]

“Hybrid laparoscopic endoscopic single-site surgery for radical cystoprostatectomy and orthotopic ileal neobladder: An initial experience of 12 cases

“Laparoscopic endoscopic single-site surgery (LESS) has recently emerged as an attempt to enhance cosmetic benefits and reduce morbidity; however, LESS for radical cystectomy is still not well established. Here we describe the technique of hybrid LESS for radical cystoprostatectomy and orthotopic ileal neobladder (RC-OIN), and evaluate its feasibility and safety.

“All operations were performed successfully without conversion to conventional laparoscopic radical cystectomy or open surgery. There was no perioperative mortality or port-related complications. The median operative time was 383 minutes. Median blood loss was 150 mL. A median of 25 lymph nodes were removed. Surgical margins were tumor free in all cases.

Hybrid LESS for RC-OIN is technically feasible with effects similar to those of conventional laparoscopic procedures. Further instrument and technique improvement are necessary to shorten operative time and reduce intraoperative difficulties.

 Update of clinical trial data for trimodality therapy[vi]

Written by Christopher P. Evans, MD

Monday, 13 December 2010

BETHESDA, MD USA ( – Tridmodel therapy includes maximal TURBT followed by XRET (40Gy) with chemotherapy, next is cystoscopic response evaluation, and if good response, then XRT for 24 Gy more.

In 348 patients treated at the Massachusetts General Hospital (where Dr. Efstathiou is a radiation oncologist) between 1986-2002, 10-year overall survival (OS) was 35% and disease-specific survival (DSS) was 59%. Ultimately cystectomy was necessary in 29%. There were very few cancer events after 5 years. Use of neoadjuvant chemotherapy did not impart any DSS or OS benefit. Their data showed that complete TURBT is essential to the outcome.

A trial called SPARE in the UK to compare surgery to trimodal therapy closed due to poor accrual. A UK trial comparing XRT alone vs. XRT plus MMC and 5-FU was recently reported. Early on there was no survival benefit, but for local-regional DFS there was benefit to the addition of chemo at 3 years. He touched on biomarkers predicting response, and Her-2 is one such that is stratifying patients for the addition of Herceptin. Another is MRE11 that predicts for CSS following radical radiotherapy for muscle invasive bladder cancer. QOL after XRT is critical and 78% have compliant bladders and 50% of men have maintained erectile function. Overall about 70% of trimodal patients retain their native bladder.

Surgery not always necessary for bladder cancer patients[vii]

October 05, 2010 / TAMPA, Fla. / Bladder cancer is the fifth most common cancer in the United States says Dr. Randy Heysek, founder of the Central Florida Cancer Institute. He says approximately 50,000 people are diagnosed with bladder malignancies each year. As a staff member at H.L. Moffitt Cancer Center and Research Institute, Dr. Heysek has the opportunity to teach resident physicians about treatment options for a variety of cancers, as he did before a group of radiation oncology residents about bladder cancer.

“I take my role at Moffitt seriously,” says Dr. Heysek. “I want to give cancer patients the best care and treatment possible. I also want to make sure the resident physicians learn as much as they can about the techniques and procedures being used.”

Currently, radical cystectomy is the common treatment for bladder cancer. The procedure removes the entire bladder, nearby lymph nodes, part of the urethra and nearby organs that may contain cancer cells. However, the surgery can reduce a patient’s sexual function. Dr. Heysek, a board-certified radiation oncologist, says there is a non-surgical alternative.

“Patients can receive a carefully administered radiation therapy with concomitant chemotherapy given daily over a seven week period,” he says. “The long term results reveal a very satisfactory bladder function following radiation and chemotherapy. A majority of patients are able to keep their own bladders, rather than having them removed or having an artificial bladder constructed.”

Dr. Heysek adds the use of this bladder conserving treatment requires close collaboration between the urologist, medical oncologist and radiation oncologist. He says this ensures perfect integration and timing.

Long-term outcomes of a randomized controlled trial comparing thermochemotherapy with mitomycin-C alone as adjuvant treatment for non-muscle-invasive bladder cancer (NMIBC)[viii]

BJU International, 10/05/2010  Clinical Article

Colombo R et al. – The authors present long–term efficacy data of intravesical thermochemotherapy vs chemotherapy alone with mitomycin–C (MMC) randomly administered to patients with non–muscle–invasive bladder cancer (NMIBC) as an adjuvant treatment after complete transurethral resection. This is the first analysis of long–term follow–up of patients treated with intravesical thermochemotherapy. The high rate of patients who were tumour–free 10 years after treatment completion as well as the high rate of bladder preservation, confirms the efficacy of this adjuvant approach for NMIBC at long–term follow–up, even in patients with multiple tumours.

Response and progression-free survival in T2 to T4 bladder tumors treated with trimodality therapy with bladder preservation[ix]

Monday, 04 October 2010

Departamento de Urología, Clínica Universidad de Navarra, Navarra, España.

To evaluate the response and the free-survival progression in patients diagnosed of invasive bladder cancer who have been treated with transurethral resection, chemotherapy and radiotherapy. This multimodal treatment is compared with a not random serie of patients treated by radical cistectomy.

Retrospective analysis of 43 cases of invasive bladder cancer treated with two schemes of bladder preservation between 1994-2007. They are compared with 145 cases treated with radical cistectomy in the same period of time. Pronostic variables included in the study are clinical stage, grade of differentiation, presence of ureteral obstruction, chemotherapy modality, radiotherapy doses and p53 and ki-67 expression.

Mean and median time are 51 and 39 months in patients with multimodal treatment. Complete response is achieved in 72% of cases treated with bladder preservation. Ureteral obstruction is a prognostic factor (OR: 7,3;p:0,02). 72% patients with complete response mantain it at the end of the study. None of analyzed variables are predictors of maintenance of the response. Survival rates with a intact bladder were 69±7% and 61±7% at three and five years. Radiotherapy doses greater than 60Gy (OR: 6,1; p<0,001) and the absence of ureteral obstruction (OR: 7,5; p<0,002) were pronostic variables. Free-survival in patients with complete response was 80±7% and 58±10% at three and five years. At the end of the study, 53,5% of patients had a intact bladder and free-disease.In the same period of time, 145 radical cistectomies were performed due to muscle invasive bladder cancer. Mean and median time in this group were 29 and 18 months respectively. Stadistical analysis reveals a worse clinical stage in the group of patients treated with multimodal treatment (p:0.01). Free-survival was 72±5% and 63±7% at 3 and 5 years in the group of radical cistectomies. There was not statistical significant differences between cistectomies and bladder preservation.

Patients treated with bladder preservation have a free-survival similar to those treated with radical cistectomy. Radiotherapy doses greater than 60Gy and absence of ureteral obstruction were free-survival prognostic variables.

Written by: Rincón Mayans A, Rosell Costa D, Zudaire Bergera JJ, Rioja Zuazu J, Barba Abad J, Tolosa Eizaguirre E, Romero Vargas L, Pascual Piedrola I.

Reference: Actas Urol Esp. 2010 Oct;34(9):775-80.

PubMed Abstract PMID: 20843454

Robotic cystectomy: Is it ready for prime time?[x]

Slide Presentation

RC versus Alternatives

Date: Mon, 13 Sep 2010 07:57:37 -0400
From: jmikemann@COMCAST.NET
Subject: Re: [CAFE] MIBC treated with TURB, Chemo & Radiation instead of RC
Ian –

Many doctors have been working with this for years and have published the results.

I read reports over ten years ago from Dr. Shipley of Harvard Medical School, and Mass General were reporting approximately equal
results from RC or multimodality.  This was my reasoning to go that route rather than an RC.

Note that my Uro who had recommended an RC disagrees with me.  He has only recently moved me to yearly checkups previously insisting on every six months for eleven years.  He told his assistant at my last check that “I had dodged a bullet” but (I?) disagree.  At the time I made the decision the long term statistics for the two approaches were similar and it has seemed to work out for me.

07:22 AM 9/13/2010, Ian Clements wrote:
This seemingly good outcome seems to me to have been prematurely assessed – only 4 weeks later. As there’s a lot of evidence of recurrence long after this period, it would be nice to see this being compared with RC for similar patients over a longer period.

Bladder preservation multimodality therapy as an alternative to radical cystectomy for treatment of muscle invasive bladder cancer[xi]
BJU International, 09/13/2010

Maarouf AM et al. ­ In this prospective study, the authors includded 33 patients with transitional cell carcinoma (TCC) (T2 and T3, Nx, M0) who were amenable to complete transurethral resection. These patients refused radical cystectomy as their first treatment option. After maximum transurethral resection of bladder tumour (TURBT), all patients received three cycles of adjuvant chemotherapy in the form of methotrexate, vinblastin, adriamycin and cisplatin (MVAC) followed by radical radiotherapy. Four weeks later, all cases had radiological and cystoscopical re­eevaluation. Complete responders were considered to be those patients who had no evidence of residual tumour.

Outcome of patients who refuse cystectomy after receiving neoadjuvant chemotherapy for muscle-invasive bladder cancer[xii]

Between 1995 and 2001, 63 patients were evaluated who declined to undergo a planned cystectomy, because they achieved a complete clinical response to neoadjuvant cisplatin-based chemotherapy.Forty patients (64%) survived, with 54% of them having an intact functioning bladder. The number and size of invasive tumors were strongly associated with overall survival.

Of 23 patients (36%) who subsequently died of disease, 19 (30%) relapsed with invasive cancer in the bladder. Over 90% of surviving patients had solitary, small, and low-stage invasive tumors completely resected, and 83% survived without relapses in the bladder.

Editorial Comment

In Northern America neoadjuvant chemotherapy before radical cystectomy became standard few years ago. What happens if patients (or their doctors, the medical oncologists who deliver chemotherapy) refuse radical cystectomy if a complete response is found in the bladder? This paper gives some very important answers.

The study group was well chosen with only patients having residual muscle-invasive tumors receiving neoadjuvant chemotherapy. After at least 85% of the planned four cycles of cisplatinum-based chemotherapy, complete clinical response and negative transurethral resection (TUR) of the primary tumor site, these patients were deemed complete responders and were evaluable for follow-up in this group.

The good news is that 64% of these patients survived at least 5 years and 54% of them with functioning bladders. The bad news is that 36% died of bladder cancer after a mean of 32 months. The survivors could be identified by their good prognostic factors, namely single (p < 0.001), or small tumor (p < 0.01), complete restaging TUR (p = 0.02), and noninvasive stage after relapse (p = 0.05). Thus patients with worse tumor features, despite responding completely to chemotherapy, should be strongly advised to undergo radical cystectomy at the earliest convenience.

Updated results of bladder-sparing trimodality approach for invasive bladder cancer[xiii],[xiv]

Received 15 December 2008;  revised 21 January 2009;  accepted 22 January 2009.


To update long-term results with selective organ preservation in invasive bladder cancer using aggressive transurethral resection of bladder tumor (TURBT) and radiochemotherapy (RCT) and to identify treatment factors that may predict overall survival (OS).

Materials and methods

Between 1990 and 2007, a total of 74 patients with T2-T4 bladder cancer were enrolled in 2 sequential bladder-sparing protocols including aggressive TURB and RCT. From 1990 to 1999, 41 patients were included in protocol no. 1 (P1) that consisted of three cycles of neoadjuvant methotrexate, cisplatin, and vinblastine (MCV) chemotherapy prior to re-evaluation and followed by radiotherapy (RT) 60 Gy in complete responders. Between 2000 and 2007, 33 patients were entered in protocol no. 2 (P2) that consisted of concurrent RCT 64, 8 Gy with weekly cisplatin. In case of invasive residual tumor or recurrence, salvage cystectomy was recommended. Primary endpoints were OS, overall survival with bladder preservation (OSB), and late toxicity.


The mean follow-up for the whole series was 54 months (range 9–156), 69 months for patients in P1 and 36 months for patients in P2. The actuarial 5-year OS and OSB for all series were 72% and 60%, respectively. Distant metastases were diagnosed in 11 (15%) patients. Grade 3 late genitourinary (GU) and intestinal (GI) complications were 5% and 1.3%, respectively. There were no significant differences in the incidence of superficial recurrences (P = 0.080), muscle-invasive relapses (P = 0.722), distant metastasis (P = 0.744), grade ≥2 late complications (P = 0.217 for GU and P = 0.400 for GI), and death among the 2 protocols (P value for OS = 0.643; P value for OSB = 0.532).


These data confirm that trimodality therapy with bladder preservation represents a real alternative to radical cystectomy in selected patients, resulting in an acceptable rate of the long-term survivors retaining functional bladders.

Gemcitabine sensitizes invasive bladder tumors to radiation[xv]

“Adding gemcitabine (Gemzar) to concurrent radiotherapy and cisplatinum in invasive bladder cancer could preserve the organ even when the tumor has invaded the muscle, according to French researchers. In their pilot study, they sought to determine the maximum tolerated dose of gemcitabine to use with the gold standard of cisplatinum + radiotherapy.

“The patients in the study received a diagnosis of urothelial invasive bladder cancer but without hydronephrosis or diffuse carcinoma in situ. The cancer stage was T2-T4a with negative nodes and no metastasis.

“…..  cystectomy is the gold standard for treatment of invasive bladder cancer, but because of a high morbidity rate, patients often opt for bladder preservation. With standard bladder preservation treatments, about 50% of patients have a functioning bladder at five years

“Seven of the nine patients who completed the experimental regimen were cancer-free with intact bladders at a median follow up of 24 months.

Quality of life assessment after concurrent chemoradiation for invasive bladder cancer[xvi]

To evaluate bladder preservation and functional quality after concurrent chemoradiotherapy for muscle-invasive cancer in 53 patients included in a Phase II trial.

Pelvic irradiation delivered 45Gy, followed by an 18-Gy boost. Concurrent chemotherapy with cisplatin and 5-fluorouracil by continuous infusion was performed at Weeks 1, 4, and 7 during radiotherapy. Patients initially suitable for surgery were evaluated with macroscopically complete transurethral resection after 45Gy, followed by radical cystectomy in case of incomplete response. The European Organization for Research and Treatment of Cancer quality of life questionnaire QLQ-C30, specific items on bladder function, and the Late Effects in Normal Tissues-Subjective, Objective, Management, and Analytic (LENT-SOMA) symptoms scale were used to evaluate quality of life before treatment and 6, 12, 24, and 36 months after treatment.

Median age was 68 years for 51 evaluable patients. Thirty-two percent of patients had T2a tumors, 46% T2b, 16% T3, and 6% T4. A visibly complete transurethral resection was possible in 66%. Median follow-up was 8 years. Bladder was preserved in 67% (95% confidence interval, 52-79%) of patients. Overall survival was 36% (95% confidence interval, 23-49%) at 8 years for all patients, and 45% (28-61%) for the 36 patients suitable for surgery. Satisfactory bladder function, according to LENT-SOMA, was reported for 100% of patients with preserved bladder and locally controlled disease 6-36 months after the beginning of treatment. Satisfactory bladder function was reported for 35% of patients before treatment and for 43%, 57%, and 29%, respectively, at 6, 18, and 36 months.

Concurrent chemoradiation therapy allowed bladder preservation with tumor control for 67% patients at 8 years. Quality of life and quality of bladder function were satisfactory for 67% of patients.

Written by: Lagrange JL, Bascoul-Mollevi C, Geoffrois L, Beckendorf V, Ferrero JM, Joly F, Allouache N, Bachaud JM, Chevreau C, Kramar A, Chauvet B.

Reference: Int J Radiat Oncol Biol Phys. 2010 Apr 10. doi: 10.1016/j.ijrobp.2009.10.038

PubMed Abstract PMID: 20385453

Failure of bacille Calmette-Guérin in patients with high risk non-muscle-invasive bladder cancer unsuitable for radical cystectomy[xvii]

An update of available treatment options

Tuesday, 16 March 2010

Department of Urology, Royal Hallamshire Hospital, Sheffield, South Yorks, UK.

Academic Department of Urology of la Pitié-Salpêtrière, Assistance Publique – Hôpitaux de Paris, University Paris VI, Faculte de medicine Pierre et Marie Curie and Centre d’Etudes et de Recherche sur les pathologies prostatiques, France.

Although the accepted standard upon failing intravesical bacille Calmette-Guérin (BCG) in patients with high-risk non-muscle-invasive bladder cancer (NMIBC) is radical cystectomy, there are some patients for whom this is not an option. We critically reviewed previous reports on the treatment possibilities available in such a clinical scenario. The options available can be categorized as chemotherapy, immunotherapy, device-assisted therapy and combined therapy. Combining new with established intravesical treatments seems to hold the most promise. Maintenance thermo-chemotherapy gives a reported 2-year disease-free survival rate of 50% and in small early-phase studies of intravesical gemcitabine administered in combination with mitomycin-C, tolerance and efficacy data would suggest the need for larger trials, given the early encouraging results. Electromotive mitomycin-C given sequentially with BCG might not only reduce the recurrence rate but also reduce progression and disease-specific mortality, although currently there is no trial in a specific population with ‘BCG failure’.

Written by:  Yates DR, Rouprêt M.

Reference: BJU Int. 2010 Mar 1. doi:10.1111/j.1464-410X.2010.09272.x

PubMed Abstract PMID:20201829

Organ-sparing strategies in the management of invasive bladder cancer[xviii]

Bladder cancer is the second most common genitourinary malignancy. Radical cystectomy and pelvic lymphadenectomy is the standard of care in the management of muscle-invasive bladder cancer. However, recently, bladder-preservation trials conducted by both single- and multi-institutional groups have gained momentum because of comparable survival and recurrence rates in select patients. While single-modality therapies have failed to provide adequate results, multimodal combination therapies consisting of a thorough transurethral resection with radiotherapy and concomitant chemotherapy have been promising. Careful patient selection, maximum transurethral resection of bladder tumor, cystoscopic evaluation of response with prompt salvage cystectomy for nonresponders and strict long-term follow-up for complete responders constitute the hallmarks of optimal bladder-preservation protocols. Advances in molecular-targeted therapy, chemotherapy and radiotherapy hold promise to improve survival and local control and decrease side effects and toxicity.

Bladder Preservation in Octogenarians With Invasive Bladder Cancer[xix]

Received 26 July 2009; accepted 15 October 2009. published online 17 December 2009.


To analyze mortality and morbidity of octogenarians with newly diagnosed invasive transitional cell cancer (TCC) of the bladder who were managed without cystectomy.


Retrospective chart review of all patients with newly diagnosed invasive TCC (≥pT1) in the period of 1997-2007, who were 80 years or older at diagnosis.


A total of 71 patients (86 + 4 years, mean + standard deviation [SD], pT1: n = 29; >pT2: n = 42) entered this analysis. In this geriatric population, treatment regimens were highly individualized. After transurethral resection, 61% of pT1-patients received bacillus Calmette-Guerin and 62% of those with >pT2-tumors external beam radiation. Mean overall survival (OS) of the entire cohort (n = 71) was 22 + 26 months for pT1-patients 34 + 33 versus 14 + 15 months for those with ≥pT2-tumors (P = .001). Mean cancer-specific survival was 58 months for pT1-patients and 11 months for ≥pT2-patients (P <.001). OS was correlated to tumor stage and the degree of mobility, to a lesser extent to the American Society of Anesthesiologists (ASA) score, and only marginally to chronologic age. Satisfactorily bladder function was preserved in 73%. pT1-patients spent 16% of their remaining life-span in the hospital compared with 23% for patients with >pT2-tumors.


OS in TCC is dependent on tumor stage, age, mobility, and comorbidities, and a risk-stratified management is necessary. Patients with pT1G3 tumor and low ASA score have satisfying OS with bladder preservation, but in patients with ≥pT2 and ASA 3-4 the prognosis is very bad. It remains questionable whether patients with tumor stages ≥pT2 and ASA 1-2 despite high age would benefit from radical cystectomy.

Long-Term Follow-Up of Cisplatin Combination Chemotherapy in Patients With Disseminated Nonseminomatous Germ Cell Tumors[xx]

Is a Postchemotherapy Retroperitoneal Lymph Node Dissection Needed After Complete Remission?


Purpose Controversy arises regarding the optimal management of patients with nonseminomatous germ cell tumor (NSGCT) who achieve a serologic and radiographic complete remission (CR) to systemic chemotherapy. Some authors recommend postchemotherapy retroperitoneal lymph node dissection (PC-RPLND), whereas others omit surgery and observe these patients. In an attempt to address this question, we report the long-term follow-up of patients treated at Indiana University who were observed without PC-RPLND.

Patients and Methods This is a retrospective analysis of patients with NSGCT who achieved a CR to first-line chemotherapy and were monitored without further therapy. CR was defined as normalization of serum tumor markers and resolution of radiographic disease (residual mass < 1 cm).

Results One hundred forty-one patients were identified. Five patients (4%) had less than 2 years of follow-up. After a median follow-up of 15.5 years, 12 patients (9%) experienced relapse. Of these 12 patients, eight patients currently have no evidence of disease (NED), and four patients died of disease. The estimated 15-year recurrence-free survival (RFS) and cancer-specific survival rates were 90% and 97%, respectively. The estimated 15-year RFS for good-risk patients (n = 109) versus intermediate- or poor-risk patients (n = 32) was 95% and 73% (P = .001), respectively. Six patients (4%) experienced recurrence in the retroperitoneum, of whom two patients died of disease. Five patients had late relapse (range, 3 to 13 years), including two patients in the retroperitoneum. All five patients currently have NED.

Conclusion Patients obtaining a CR after first-line chemotherapy can be safely observed without PC-RPLND. Relapses are rare and potentially curable with further treatment.

Total Cystectomy Versus Bladder Preservation Therapy for Locally Invasive Bladder Cancer[xxi]

Effect of Combined Therapy Using Balloon-Occluded Arterial Infusion of Anticancer Agent and Hemodialysis With Concurrent Radiation

Objectives: We tested the usefulness of balloon-occluded arterial infusion (BOAI) of anticancer agent (cisplatin/gemcitabine), concomitant with hemodialysis, which delivers an extremely high concentration of anticancer agent to the site of a tumor without systemic adverse effects, along with concurrent radiation [Osaka-Medical College (OMC)-regimen] in patients with locally advanced bladder cancer. The results were compared with those of cystectomy.

Methods: One hundred twenty-four patients were assigned to receive cystectomy (Gp1, n = 62) or OMC-regimen (Gp2, n = 62). In Gp2, patients besides undergoing complete response subsequently received secondary-BOAI with gemcitabine (1600 mg).

Results: In Gp1, 27 of 62 patients (43.5%) suffered disease recurrence, and more than half died within 1 year; the remainder died thereafter. The overall 5-, 10-, and 15-year survival rates were 53.8%, 46.0%, and 40.0%, respectively. In contrast, in Gp2, >70% of patients (44 of 62), especially >95% of patients with locally invasive tumors achieved complete response with no evidence of recurrent disease or metastasis after a mean follow-up of 163 (range, 32-736) weeks. At 14 years, overall survival was significantly improved at 79.7% (P = 0.015 vs. Gp1). Moreover, salvage therapy for secondary-BOAI with gemcitabine was effective in all 3 patients with T4 tumors or lymph node involvement, who showed stable disease (SD) after primary therapy with CDDP. No patients suffered Grade III or more severe toxicities.

Conclusion: OMC-regimen, a new strategy for patients with locally-invasive bladder cancer, can be curative not only in patients for whom cystectomy is indicated, but also in patients whose condition is not amenable to curative treatment and for whom merely palliative treatment would otherwise seem the only option.

Bladder-Sparing Therapy a Good Alternative[xxii]

By Charles Bankhead, Staff Writer, MedPage Today
Published: November 05, 2009
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

CHICAGO — Organ-sparing multimodal therapy for invasive bladder cancer achieves survival comparable to that of radical cystectomy, but with better quality of life, according to a study reported here.

The combination of transurethral tumor resection, radiation therapy, and chemotherapy led to complete responses in 72% of patients. Disease-specific and overall survival at five, 10, and 15 years compared favorably with results from contemporary patient series of radical cystectomy.

“The results support the acceptance of modern bladder-sparing trimodality therapy for selected patients as a proven alternative to cystectomy,” Jason Efstathiou, MD, PhD, of Massachusetts General Hospital in Boston, said at the American Society of Radiation Oncology.

Action Points

  • Explain to patients that a bladder-preserving therapy for invasive bladder cancer appears to attain results similar to those of radical surgery in selected patients.
  • Note that the findings came from a retrospective review of data from a single institution.
  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.

“The optimal regimen of combined chemoradiation, as well as the addition of rational molecular targeted therapy, continues to be investigated.”

The findings came from an analysis of long-term follow-up data in 343 patients with muscle-invasive bladder cancer treated with trimodal therapy. The patients were treated from 1986 to 2002.

Treatment began with a 40-Gy dose of radiotherapy, followed by repeat biopsy and urinary cytology. Patients who achieved a complete response or who were not candidates for cystectomy received boost chemoradiation to 64 or 65 Gy.

Subsequently, 102 patients underwent radical cystectomy, 60 of whom did not have a complete response and 42 because of tumor recurrence.

The patients had a five-year overall survival of 52% and disease-specific survival of 64%. The rates at 10 years were 35% and 59% for overall and disease-specific survival, respectively, and 22% and 57% at 15 years.

“Eighty percent of patients who were alive at five years still had their native bladders,” said Efstathiou.

Among patients who had cystectomy, five-year overall survival was 29%. Survival was similar in patients who underwent immediate or delayed cystectomy.

The completeness of transurethral resection of the bladder tumor significantly influenced the likelihood of response and patient survival.

The 227 patients who underwent complete tumor resection had a complete response rate of 79%, decreasing to 57% for patients with incomplete resection (P<0.001). Overall survival at five years was 57% with complete resection and 43% without (P=0.003).

Disease-specific survival was 68% with complete tumor resection and 56% without (P=0.03).

In multivariate analyses, independent predictors of survival were complete response to induction therapy (HR 0.62, P=0.013) and low clinical T stage (HR 0.66, P=0.018).

For comparison, Efstathiou reviewed five- and 10-year overall survival with cystectomy reported from the University of Southern California in Los Angeles, Memorial Sloan-Kettering Cancer Center in New York, and the Southwest Oncology Group.

Five-year survival ranged between 36% and 49%, while 10-year survival was 27% to 32%. The five-year results at Massachusetts General were slightly better but still consistent with data from other studies of chemoradiation therapy for invasive bladder cancer.

As previously reported, a subset of 221 patients had urodynamics evaluations and completed a quality-of-life questionnaire. The results showed that 78% of the patients had compliant bladders with normal capacity and flow parameters, 85% had occasional or no urinary urgency, and 50% of the male patients reported normal erectile function (J Urol 2003; 170: 1772-76).

Data on a subset of 157 patients with bladder preservation who were followed for a median 5.2 years showed a 22% incidence of grade 1 late pelvic toxicity, 10% grade 2, and 7% grade 3 (J Clin Oncol 2009; 27: 4055-61).

Efstathiou had no disclosures.

Primary source: American Society for Radiation Oncology
Source reference:
Efstathiou J, et al “15-year outcomes of selective bladder preservation by combined-modality therapy for invasive bladder cancer: the long-term MGH experience” ASTRO 2009; Abstract 21

An Alternative to Radical Cystectomy[xxiii]

September 18, 2009

Bladder-sparing treatment in which brachytherapy is added to external beam radiotherapy (EBRT) may be a valuable alternative for bladder cancer patients who refuse radical cystectomy or who are poor candidates for major surgery, according to researchers.

J.L.H. Ruud Bosch, MD, of University Medical Center Utrecht in the Netherlands, and colleagues reviewed data from 111 patients with solitary T1-T2 bladder tumors (5 cm or less in size). After undergoing transurethral resection of the tumors, patients were treated first with EBRT and then brachytherapy with iridium-192 at a dose of 40 Gy. A partial cystectomy was performed in nine patients, of whom five had a T3 tumor.

The study population had a mean follow-up of 6.2 years.

At the last follow-up, 75 patients were alive without evidence of disease and 17 had died without evidence of disease, the investigators reported in European Urology (2009;56:113-122). Nineteen patients died of bladder cancer after a mean follow-up of 2.9 years.

Overall survival rates at five, 10, and 15 years were 70%, 55%, and 51%, respectively. Disease-specific survival rates were 82%, 73%, and 73%, respectively. Disease-free survival rates were 60%, 47%, and 23%. Patients with T3 tumors had a nearly 20-fold increased risk of dying from bladder cancer. Additionally, 27% of patients experienced local recurrence and 9% underwent salvage cystectomy. Bladder function was preserved in 99 patients (89%).

From the September 2009 Issue of Renal And Urology News

Conservative treatment of invasive bladder cancer[xxiv]

Tuesday, 01 September 2009

Department of Radiation Oncology, McGill University Health Centre, Montreal, QC.

The concept of organ-preserving therapies is a trend in modern oncology, and several tumour types are now treated in this fashion. Trimodality therapy consisting of as thorough a transurethral resection of the bladder tumour as is judged safe, followed by concomitant chemoradiation therapy, is emerging as an attractive alternative for bladder preservation in selected patients with muscle-invasive bladder cancer. Long-term data from multiple institutional and cooperative group studies have shown that this approach is safe and effective and that it provides patients with the opportunity to maintain an intact and functional bladder with a survival rate similar to that for modern radical cystectomy.

Written by: Rene NJ, Cury FB, Souhami L.

Reference: Curr Oncol. 2009 Aug;16(4):36-47.

PubMed Abstract PMID:19672423

A 10-year retrospective review of a nonrandomized cohort of 458 patients undergoing radical radiotherapy or cystectomy in Yorkshire, UK[xxv]

Monday, 31 August 2009

Department of Urology, Mid Yorkshire NHS Trust, Pinderfields Hospital, Aberford Road, Wakefield.

We have previously reported on the mortality, morbidity, and 5-year survival of 458 patients who underwent radical radiotherapy or surgery for invasive bladder cancer in Yorkshire from 1993 to 1996. We aim to present the 10-year outcomes of these patients and to reassess factors predicting survival.

The Northern and Yorkshire Cancer Registry identified 458 patients whose cases were subjected to Kaplan-Meier all-cause survival analyses, and a retrospective casenote analysis was undertaken on 398 (87%) for univariate and multivariate Cox proportional hazards modeling. Additional proportional hazards regression modeling was used to assess the statistical significance of variables on overall survival.

The ratio of radiotherapy to cystectomy was 3:1. There was no significant difference in overall 10-year survival between those who underwent radiotherapy (22%) and radical cystectomy (24%). Univariate analyses suggested that female sex, performance status, hydronephrosis and clinical T stage, were associated with an inferior outcome at 10 years. Patient age, tumor grade, treatment delay, and caseload factors were not significant. Multivariate analysis models were created for 0-2 and 2-10 years after treatment. There were no significant differences in treatment for 0-2 years; however, after 2 years follow-up there was some evidence of increased survival for patients receiving surgery compared with radiotherapy (hazard ratio 0.66, 95% confidence interval: 0.44-1.01, p = 0.06).

A 10-year minimum follow-up has rarely been reported after radical treatment for invasive bladder cancer. At 10 years, there was no statistical difference in all-cause survival between surgery and radiotherapy treatment modalities.

Written by: Munro NP, Sundaram SK, Weston PM, Fairley L, Harrison SC, Forman D, Chahal R.

Reference:  Int J Radiat Oncol Biol Phys. 2009 Aug 6. doi:10.1016/j.ijrobp.2009.04.050

PubMed Abstract  PMID:19665319

See also:

Conclusion: Our results indicate that a smaller dose of anticancer drugs should be infused from the bilateral internal iliac arteries for safer pelvic BOAI.

These results demonstrate that BOAI therapy is effective for the treatment of progressive cervical carcinoma by increasing intratumoral concentrations of the drugs.

CONCLUSION: In patients diagnosed as stage T2 and T3a, or stage T1 with multiple large tumours difficult to be treat by transurethral resection, BOAI should be considered as the first choice to decrease the stage or to confirm the pathological staging.

Radiochemotherapy for bladder cancer[xxvi]

Wednesday, 22 July 2009

Department of Radiation Oncology, University Hospitals, Erlangen, Germany.

Standard treatment for muscle-invasive bladder cancer is cystectomy. Multimodality treatment, including transurethral resection of the bladder tumour, radiation therapy, chemotherapy and deep regional hyperthermia, has been shown to produce survival rates comparable with those of cystectomy. With these programmes, cystectomy has been reserved for patients with incomplete response or local relapse. During the past two decades, organ preservation by multimodality treatment has been investigated in prospective series from single centres and co-operative groups, with more than 1000 patients included. Five-year overall survival rates in the range of 50-60% have been reported, and about three-quarters of the surviving patients maintained their bladder.

Clinical criteria helpful in determining patients for bladder preservation include such variables as small tumour size (< 5cm), early tumour stage, a visibly and microscopically complete transurethral resection, absence of ureteral obstruction, and no evidence of pelvic lymph node metastases. On multivariate analysis, the completeness of transurethral resection of a bladder tumour was found to be one of the strongest prognostic factors for overall survival. Patients at greater risk of new tumour development after initial complete response are those with multifocal disease and extensive associated carcinoma in situ at presentation. Close co-ordination among all disciplines is required to achieve optimal results. Future investigations will focus on optimising radiation techniques, including all possibilities of radiosensitisation (e.g. concurrent radiochemotherapy, deep regional hyperthermia), and incorporating more effective systemic chemotherapy, and the proper selection of patients based on predictive molecular makers.

Written by: Ott OJ, Rödel C, Weiss C, Wittlinger M, Krause FS, Dunst J, Fietkau R, Sauer R.

Reference: Clin Oncol (R Coll Radiol). 2009 Jun 27. doi:10.1016/j.clon.2009.05.005

PubMed Abstract PMID:19564101

Safety of active surveillance program for recurrent nonmuscle-invasive bladder carcinoma[xxvii]

Urology, 07/07/09

In a study to explore the experience with a group of pts with low-risk tumors included in an observation and monitoring program after diagnosis of recurrence, it was found that pts with recurrent, small (<1 cm), nonmuscle-invasive bladder tumors can be safely offered monitoring under an active surveillance protocol, with minimal risk of progression in either grade or stage, thus reducing the amount of surgical intervention pts might undergo.


  • A prospective cohort study was done in pts diagnosed with recurrent, nonmuscle-invasive bladder cancer maintained under an active surveillance protocol.
  • Inclusion criteria were papillary tumors with negative cytology findings, previous nonmuscle-invasive tumor (Stage pTa, pT1a), grade 1-2, size <1 cm, and number of tumors <5.
  • No symptomatic pts or those with carcinoma in situ or grade 3 tumors were included.
  • A retrospective analysis of a control group of pts with clinical characteristics similar to those of pts on active surveillance, but who underwent transurethral resection immediately after recurrence was diagnosed was also performed.


  • Data from 64 pts (70 observation events) were analyzed.
  • Mean pt age was 66.7 yrs.
  • Median follow-up was 38.6 mos.
  • Median time pts remained in observation was 10.3 mos.
  • Tumor histologic features before observation were Stage pTa in 77.1%, Stage pT1a in 22.9%, grade 1 in 67.1%, and grade 2 in 23%.
  • After 10.3 mos, 93.5% of pts had not progressed in stage and 83.8% had not progressed in grade.
  • None of the pts experienced progression to muscle-invasive disease.
  • Comparison between rates of progression and control groups showed no statistically significant difference.

What happens to the patients with muscle-invasive bladder cancer who refuse cystectomy after neoadjuvant chemotherapy?[xxviii]

Ruchir Maheshwari, Aneesh Srivastava
Department of Urology and Renal Transplantation, SGPGIMS, Raibareilly Road, Lucknow-226 014, India

Date of Web Publication24-Jun-2009


This is a prospective study carried out to determine the outcome of patients who refuse cystectomy after receiving neoadjuvant chemotherapy for muscle-invasive bladder cancer. Sixty-three patients were evaluated between 1995 and 2001 who declined to undergo a planned cystectomy because they achieved a complete clinical response to neoadjuvant cisplatin-based chemotherapy. Herr assessed patient, tumor and treatment features for a median follow- up of 86 months, all patients being followed-up for more than 5 years. Forty patients (64%) survived, with 54% of them having an intact functioning bladder. The number and size of invasive tumors were strongly associated with the overall survival. The most significant treatment variable predicting better survival was complete resection of the invasive tumor on restaging transurethral resection (TUR) before starting chemotherapy. Of 23 patients (36%) who subsequently died of disease, 19 (30%) relapsed with invasive cancer in the bladder. Over 90% of the surviving patients had solitary, small and low-stage invasive tumors completely resected and 83% survived without relapses in the bladder. [1]


Radical cystectomy and pelvic lymph node dissection is an excellent treatment for organ-confined disease. Many patients with extravesical or lymph node-positive bladder cancer will develop recurrent disease, often with distant metastases, and will ultimately die of their disease. Given the lethality of muscle-invasive bladder cancer, there is a definite need for effective systemic chemotherapy. Neoadjuvant chemotherapy has been extensively investigated in muscle-invasive bladder cancer. When taken together, the randomized controlled trials of neoadjuvant cisplatin-based combination chemotherapy demonstrate an improved survival over cystectomy alone. In addition, neoadjuvant chemotherapy can result in downstaging of primary tumors. [2]

The Advanced Bladder Cancer Metaanalysis Collaboration concluded that platinum-based combination neoadjuvant chemotherapy and cystectomy continues to show a clear and modest benefit for survival and disease-free survival of patients with muscle-invasive bladder cancer over radical surgery alone. [3] Downstaging after neoadjuvant chemotherapy was associated with improved survival in patients with muscle-invasive, extravesical (T > 3a) disease at presentation. Chemotherapy aims to treat undetected metastasis and radical cystectomy provides the best control of the primary tumor. Most survivors achieve major response to chemotherapy and have an increased likelihood of having no residual tumor (pT0) in the cystectomy specimen. [4] The author has analyzed whether patients who have pathological pT0 tumors after chemotherapy would have survived without subsequent cystectomy.

In the present study, 64% of the patients survived, with 54% of them having an intact functional bladder (35% of total cohort). Relapse occurred in the majority of the patients (64%), resulting in an additional disease-related mortality of 30%. The patients most likely to relapse had multiple or large tumors that were not clinically confined to the bladder. Delayed cystectomy salvaged fewer than half of the patients relapsing with persistent or new invasive bladder cancers.

Few other studies have dealt on conservative, bladder- sparing management of muscle-invasive transitional cell carcinoma (TCC) bladder using multimodality treatment. [5] These authors have used chemoradiotherapy for tumor control. Perdonà et al., have reported 121 patients with T2, T3 or T4 bladder cancer who underwent induction by TUR of the tumor and received two cycles of neoadjuvant chemotherapy followed by radiotherapy (RT) or radiochemotherapy (RCT). Six weeks after RT or RCT, responses were evaluated by restaging TUR. Patients who achieved a complete response were observed at regular intervals. In patients who had persistent or recurrent invasive tumor, further treatment was recommended. Treatment modality, tumor classification and resection status after initial TUR had an impact on survival rates (P = 0.04, 0.02 and 0.02, respectively).

These studies highlight the fact that patients refusing cystectomy after chemotherapy are at high risk for disease-related mortality. At the same time, patients with small, clinically confined single tumors, which can be visibly and microscopically completely resected before neoadjuvant chemotherapy, are most likely to survive without cystectomy. They need a close follow-up as they remain at risk for new tumors in the bladder.


1.Herr HW. Outcome of Patients Who Refuse Cystectomy after Receiving Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer. Eur Urol 2008;54:126-32.

2.Vaughn DJ, Malkowicz SB. Neoadjuvant Chemotherapy in Patients with Invasive Bladder Cancer. Urol Clin N Am 2005;32:231-7.

3.Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: Update of a systemic review and meta-analysis of individual patient data. Eur Urol 2005;48:202-6.

4.Schultz PK, Herr HW, Zhang ZF, Bajorin DF, Seidman A, Sarkis A, et al . Neoadjuvant chemotherapy for invasive bladder cancer: Prognostic factors for survival of patients treated with M-VAC with 5-year follow- up. J Clin Oncol 1994;12:1394-401.

5.Perdonà S, Autorino R, Damiano R, De Sio M, Morrica B, Gallo L, et al . Bladder-sparing, combined-modality approach for muscle-invasive bladder cancer: A multi-institutional, long-term experience. Cancer 2008;112:75-83.

Radical Cystectomy versus Radical Radiotherapy[xxix]

A study of the morbidity, mortality and long-term survival following radical cystectomy and radical radiotherapy in the treatment of invasive bladder cancer in Yorkshire.

Chahal R, Sundaram SK, Iddenden R, Forman DF, Weston PM, Harrison SC.

Department of Urology, Orchard House, Pinderfields and Pontefract NHS Trust,

Wakefield, West Yorkshire WF1 4DG, UK


OBJECTIVES: To study the morbidity of radical cystectomy and radical

radiotherapy in the treatment of patients with invasive carcinoma of the bladder and to report the long-term survival following these treatments.

PATIENT AND METHODS: 398 patients with invasive carcinoma of the bladder treated between 1993 and 1996 in the Yorkshire region were studied. Of 398 patients studied, 302 patients received radical radiotherapy and 96 underwent radical cystectomy. A retrospective review of patients' case notes was performed to construct a highly detailed database. Crude estimates of survival differences were derived using Kaplan-Meier methods. Log-rank tests (or, where appropriate, Wilcoxon tests) were used to test for the equality

of these survivor functions. These functions were produced as all-cause survival. The proportional hazards regression modelling was used to assess the impact of definitive treatment on survival. A backwards-stepwise approach was used to derive a final predictive model of survival, with likelihood ratio tests to assess the statistical significance of variables to be included in the model.


CONCLUSIONS: This retrospective regional study shows that there is no

significant difference in the 5-year survival of patients with invasive bladder cancer treated with either radical radiotherapy or radical cystectomy. All forms of radical treatment for bladder cancer are associated with a significant treatment-associated morbidity and mortality.

Gastrointestinal complications were responsible for the majority of

complications. The clinical T stage, the sex and the ASA grade of the

patient were the only independent predictors of survival. The data in this series suggests that radical radiotherapy and radical cystectomy should be both considered as valid primary treatment options for the management of invasive bladder cancer.

Copyright 2003 Elsevier Science B.V

[xiv] Almudena Zapatero M.D., Ph.D.a, Carmen Martin de Vidales M.D., Ph.D.a, Ramón Arellano M.D.b, Gloria Bocardo M.D.b, Mar Pérez M.D.c and Patricia Ríos M.D.a (aDepartment of Radiation Oncology, Hospital Universitario de la Princesa, Madrid, Spain; bDepartment of Urology, Hospital Universitario de la Princesa, Madrid, Spain; cDepartment of Medical Oncology, Hospital Universitario de la Princesa, Madrid, Spain)

[xxix] Eur Urol. 2003 Mar;43(3):246-57.

Posted in Cancer Perspectives, Comments and Suggestions, surgery | 1 Comment »

Ian Clements’ ‘Chemotherapy Help’ document

Posted by Jonathan Chamberlain on April 21, 2011

See also my two cancer books –

Chemotherapy Help – Alternative ways you can support yourself while undergoing chemotherapy


Summary. 2

Major Component in Turmeric Enhance Effect of Chemotherapy Drug in Head and Neck Cancer. 2

Advice from Cancer Active. 4

1. Clean Your Liver. 4

2. Prepare Yourself. 4

4. Certain Supplements Improve Treatment Success. 5

Antioxidants and Chemotherapy – Findings. 5

Supplements during gem/cis Yes or No ?. 6

1,25D3 [Vitamin D3] Enhances antitumor activity of gemcitabine and cisplatin in human bladder cancer models  6

Pete Granger’s Comments on Vit. D3 research above. 7

Milk thistle herb protects liver from damage caused by chemotherapy. 7

Neuropathy & Glutamine. 8

Glutamine for neuropathy and other chemo supplements‏. 8

New Way To Fight Cancer: Protect Healthy Cells With The Silver Shield. 10

The diet that won’t just help you lose weight, you’ll live longer and be brainier!. 13

Exercise May Keep Cancer Patients Healthier During, After Treatment. 15

New exercise guidelines for cancer survivors. 17

How to Take Care of Yourself During Chemotherapy. 17

Recommendations – Supplements To Take With Specific Chemotherapy Drugs. 18

Chemo, Tinnitus‏ & Hearing Loss. 19

Cold Caps Prevent Hair Loss. 19

Fruit, etc Help, but No Sugar or Fruit Juices. 21


Vit.D3  4,000IU-12,000IU daily – enhances efficacy of chemo[i]

Magnesium 500mg daily – replaces severe depletion

10 grams (3 scoops) of glutamine powder 3 times a day to minimize the side effects of chemo including neuropathy


Vit.C – 1 – 5 gms/day

Curcumin + piperene – up to 10 gms/day – enhances chemo, especially cisplatin, and reduces chemo damage[ii]

Co-Enzyme Q10 100mg/day – chemo harms the heart; Co-Q10 helps it[iii]

Omega 3 oil 5gms EPA – helps preserve muscle in cancer patients on chemo[iv]

Green or white tea

Astralagus – an immune booster[v]; anti-cancer generally;

Aloe Vera – enhances chemo’s effects, enhances apoptosis, improves immune system

Milk thistle


Resveratrol – enhances chemo’s effect[vi]

Medicinal mushrooms

Stay off sugar, sodium (salt) and fruit juices

Exercise: as vigorous as possible – walking 30’ day, jogging if poss., and resistance training

Immune-Boost Treatment Might Help Some With Advanced Colon Cancer[vii]

But whether the approach beats chemo-plus-Avastin/Erbitux remains unanswered, experts say

Posted: April 6, 2011 By Amanda Gardner HealthDay Reporter

WEDNESDAY, April 6 (HealthDay News) — By giving more intensive chemotherapy along with drugs designed to boost the body’s own immune system, researchers were able to roughly double survival time for patients with advanced, metastatic colorectal cancer compared to patients receiving standard chemotherapy alone.

In fact, the trial, results of which are being presented at the annual meeting of the American Association for Cancer Research in Orlando, was stopped early because of the promising findings.

“With this study, we have produced for the first time strong proof-of-concept that chemo-immunotherapy may be active and more efficacious than standard [chemotherapy] in metastatic colon cancer patients,” said study lead author Dr. Pierpaolo Correale, an oncologist with Siena University School of Medicine in Siena, Italy.

The standard of care right now for patients with colorectal cancer that’s spread to other regions is to use one of two dual-drug combinations of chemotherapy alone, or use them alongside a newly developed monoclonal antibody treatment such as Avastin (bevacizumab) or Erbitux (cetuximab). These approaches can boost overall survival to about 20 to 22 months.

For this study, the research team randomized 130 patients to receive either chemotherapy alone (with a regimen known as FOLFOX) or to receive FOLFOX plus drugs to ramp up the immune system (this regimen is known as GOLFIG).

The chemo/immune boost approach involves first giving patients gemcitabine plus standard FOLFOX chemotherapy (oxaliplatin, levofolinic acid and 5-FU/GOLF) that targets and kills the cancer cells in a number of ways — all the while sending off signals alerting the immune system to the cancer.

This is then followed up with the administration of signaling molecules called cytokines that spur key immune cells into action. Another immune-boosting cancer drug, called aldesleukine, is also given to help boost the population of immune cells targeted against tumor cells.

At the time of data collection, the patients treated with this approach have survived an average 16.5 months without a relapse, compared with just 7.5 months in the chemo-only group.

But the study began in 2005, before the advent of drugs like Avastin or Erbitux, meaning that investigators do not yet know if GOLFIG would outperform regimens that include those medications. This needs to be looked at, said Correale.

On the other hand, many patients do not see a benefit from biological agents such as Erbitux or Avastin because they have the wrong genetic profile, noted one outside expert.

“Essentially, we have a very problematic subset of patients with metastatic colorectal cancer which are limited to two lines of chemotherapy and [perhaps] one biological agent,” said Dr. Igor Astsaturov, assistant professor of medical oncology at the Fox Chase Cancer Center in Philadelphia.

“For those patients, which are about one-third of the overall patient population, this [new finding] will be particularly welcome news,” Astsaturov said, while adding the caution that the results are still preliminary.

However, clinical use of the protocol may be delayed further by the fact that “there is no direct commercial interest of pharmaceutical companies,” noted Correale, who is nevertheless planning larger trials.

The costs associated with GOLFIG, he added, are “four-to-five times lower than that produced by the current use of Avastin or Erbitux with apparently similar therapeutic results.”

Because this study was presented at a medical meeting, the findings should be viewed as preliminary until they are published in a peer-reviewed journal.

Curcumin and Resveratrol – Chemoresistance[viii]

The following studies suggest growth factor IGF-1 is involved in the late stage invasiveness of various cancers, including bladder and colon cancers, and inhibition of IGF-1 may minimise this effect. Curcumin and resveratrol – especially in combination, block IGF-1
expression. They also appear to enhance the efect of chemotherapy.


‘In this study, the researchers looked at the role of the protein receptor for the growth factor IGF-I, an important modulator of cell proliferation in bladder cancer cells. They found that although activation of IGF-IR did not affect growth of bladder cancer cells, it did promote the migration and invasion of these cells’.

‘IGF-IR activated other molecules in cancer-promoting pathways (Akt and MAPK) that allow cancer cells to break its bond with other cells in a tumor in order to travel to others sites in the body.

“These data seem to indicate that this protein receptor (IGF-IR) may play a more prominent role in later stages of bladder cancer, not in the initiation of the cancer,” said Dr. Morrione’.

‘Curcumin (diferuloylmethane), which has no discernible toxicity, inhibits initiation, promotion and progression of carcinogenesis. 5-Fluorouracil (5-FU) or 5-FU plus oxaliplatin (FOLFOX) remains the backbone of colorectal cancer chemotherapeutics, but produces an
incomplete response resulting in survival of cells (chemo-surviving cells) that may lead to cancer recurrence. The present investigation was, therefore, undertaken to examine whether addition of curcumin to FOLFOX is a superior therapeutic strategy for chemo-surviving cells

‘Our data suggest that inclusion of curcumin in conventional chemotherapeutic regimens could be an effective strategy to prevent the emergence of chemoresistant colon cancer cells’.

‘more recently we have demonstrated that curcumin not only inhibits the activation of EGFR and family members, but also IGF-IR in colon cancer HCT-116 cells’

‘The combination of resveratrol and curcumin causes a significantly greater inhibition of growth of tumors than either agent alone’.

Major Component in Turmeric Enhance Effect of Chemotherapy Drug in Head and Neck Cancer[ix]

ScienceDaily (Oct. 24, 2010) — Curcumin, the major component in the spice turmeric, when combined with the drug cisplatin enhances the chemotherapy’s suppression of head and neck cancer cell growth, researchers with UCLA’s Jonsson Cancer Center have found.

A naturally occurring spice widely used in South Asian and Middle Eastern cooking, Turmeric has long been known to have medicinal properties, attributed to its anti-inflammatory effects. Previous studies have shown it can suppress the growth of certain cancers, said Dr. Marilene Wang, a professor of head and neck surgery, lead author of the study and a Jonsson Cancer Center researcher.

“Head and neck cancers, particularly cases diagnosed in a later stage, are terrible cancers that often require very radical surgeries and chemotherapy and radiation,” Wang said. “They often don’t present until late, and the structures in the head and neck are so vital that our treatments often cause disfigurement and severe loss of function. So using non-toxic curcumin as a treatment was a very appealing idea.”

The study, done in cells in Petri dishes and then in mouse models, appears in the October issue of the journal Molecular Cancer Therapeutics.

In India, women for years have been using turmeric for medicinal purposes, as an anti-aging agent rubbed into their ski, to treat cramps during menstruation, as a poultice on the skin to promote wound healing and as an additive in cosmetics, said scientist Eri Srivatsan, an adjunct professor of surgery and a Jonsson Cancer Center researcher who, along with Wang, has been studying curcumin and its anti-cancer properties for six years.

A 2005 study by Wang and Srivatsan first showed that curcumin suppressed the growth of head and neck cancer cells, first in cells and then in mouse models. In the animal studies, the curcumin was applied directly onto the tumors in paste form because it did not dissolve in saline, which would have allowed it to be injected.

In need of a better way to deliver the curcumin, the team collaborated with Dr. Kapil Mehta of M.D. Anderson Cancer Center and found that encapsulating the tumor in a liposome, an artificially prepared vehicle that enclosed the spice component within its membrane, made the treatment injectable. The curcumin was injected into the tail vein of a mouse, where it circulated into the blood stream, slowing down and eventually stopping the cancer growth, a study in 2008 found.

“This was a very positive finding, developing an efficient way to deliver the treatment,” Wang said. “Our study also showed that the curcumin was very well tolerated.”

In this study, the team wanted to combine the curcumin with the chemotherapeutic drug cisplatin, which is very toxic at the doses needed to fight head and neck cancers, damaging kidneys, the ears and the bone marrow. They hoped that if they added curcumin to the mix, they might be able to lower the cisplatin dose and cause less organ damage. Their finding, that the curcumin made the cisplatin work better, was very promising, Wang said.

“We knew that both the curcumin and the cisplatin, when given alone, had an effect against head and neck cancers,” Wang said. “This finding that curcumin enhances cisplatin means that, in the future, we may be able to give this chemotherapy in lower doses.”

The study noted that “the mechanisms of the two agents through different growth signaling pathways suggest potential for the clinical use of sub-therapeutic doses of cisplatin in combination with curcumin, which will allow effective suppression of tumor growth while minimizing the toxic side effects.”

The study found that curcumin suppressed head and neck cancer growth by regulating cell cycling, Srivatsan said. It binds to an enzyme and prevents the enzyme IKK, an inhibitor of kappa B kinase, from activating a transcription factor called nuclear factor kappa B (NFκB), which promotes cancer growth. Cisplatin’s suppressive action involves a different pathway through the tumor suppressor proteins p16 and p53, both proteins that again inhibit the activity of cancer growth promoter NFκB.

“We needed to know the mechanism to help us translate this from the lab into the clinic,” Wang said. “That information will help us make better decisions on how to design therapies.”

The next step in the clinical setting is to give patients oral curcumin prior to surgery and, after surgery, study the excised tumors to determine curcumin’s effect on tumor markers, specifically whether there is reduced expression of markers such as growth promoting NFκB. They also will be monitoring to determine if the curcumin results in any side effects. After that, the team would give curcumin to patients also getting chemotherapy and radiation to see if the tumor suppression found in the cells lines and mouse models can be replicated in humans.

Although turmeric is used in cooking, the amount of curcumin needed to produce a clinical response is much larger, about 500 milligrams. Expecting a positive effect through eating foods spiced with turmeric is not realistic, the researchers said.

Curcumin also has a suppressive effect on other cancers, Wang said, including breast, colon and pancreatic cancers. However, the mechanism of suppression in those cancers has not yet been uncovered. It also may be effective against Alzheimer’s and aging, Wang said.

Advice from Cancer Active[x]

So let us try to build up a plan, based on science, to give patients a strong route forward.

1. Clean Your Liver

Before and after chemotherapy, clean out the fats, the gallstones, the dead cells, the lactic acid build up. For if the liver is inefficient the whole immune system is affected. Take milk thistle, boldo tea, dandelion or a proprietary detox. Add turmeric to some meals, drink two litres of clean filtered water a day (not from tap or plastic bottles). Think about a serious liver flush and coffee enemas to remove gallstones and clean out some of the dead cells and fats. Click here for info on  the liver flush.

2. Prepare Yourself

a) Boost your immune system:  Anti-cancer herbs like Astragalus, Cat´s Claw, and echinacea are extremely effective. Add curcumin, total vitamin E and Chlorella plus probiotics and you really will target an improvement in your weeakened immune system. You can read about all of these on our web site, but most impressive is astragalus. All have all been shown to be excellent immune boosters but astragalus has been shown by the University of Texas Cancer Center in Houston to be an excellent anti-cancer agent lighting up the cancer cells to be ´spotted´ by the immune system..

Cut sodium from your diet

b) Cut sodium from your diet. Increase potassium and magnesium. Sodium displaces potassium in the power stations of your cells, making them more toxic and more acidic. Cancer thrives in acid bodies. Cut sodium foods like salt, soy sauce, gravy granules, hams, cooked meats, salami, turkey roast slices, sliced bread, breakfast cereals, sausages, bacon, processed food, prepared meals and Chinese meals. Consume high potassium and magnesium foods like fresh nuts in moderation, jacket potatoes, whole grains, green leaf vegetables, carrots, fresh apples, bananas, whole brown rice, broad beans, peas and pulses. A little rice milk or soya milk is acceptable.

Take a good, ideally liquid vitamin and mineral supplement, plus the anti-oxidants beta-carotene (use chlorella, which is natural, rather than the synthetic high street form, which anyway is not advisable if you have lung cancer), natural vitamin C with bioflavenoids and natural total vitamin E, zinc, selenium and co-enzyme Q10 (if you are over 30). A good B complex vitamin containing choline and inositol (also in soy lecithin), biotin and folic acid would be very protective prior to chemotherapy and radiotherapy.

Take long chain omega 3. For example, a good source would be Seven Seas Pure Cod Liver Oil. We have known since 1982, and a Nobel Prize by Sir John Vane, about the positive benefits of omega 3 in the cancer process. Omega 3 can also be found from a flaxseed source in Dr Joanna Budwig´s anti-cancer diet. Omega 3, garlic, ginger, salicylic acid (in Aloe Vera) and curcumin can all reduce inflammation and agressive eicosanoids, both of which stimulate cancers.

4. Certain Supplements Improve Treatment Success

Up front it needs to be said that there has long been a debate over whether cancer patients having chemo should take antioxidants. We have reviewed the argument several times on this web site. The Truth is that various expert cancer centres like MD Anderson and UCLA have stated that antioxidants can actually improve the success of chemotherapy, rather than hinder it as some people claim. MD Anderson have actually conducted several clinical trials (covered in Cancer Watch) showing vitamin E enhances the action of specific chemotherapy drugs.

But this argument is also a bit of a red herring.

Elsewhere on this site you will find articles on:

* vitamin D

* Medicinal Mushrooms

* Green Tea

* Astragalus

* Selenium

Each and all of these have been shown in expert research to decrease tumour size and/or improve survival when taken on their own or in conjunction with chemotherapy.

Furthermore Selenium (Brazil nuts, pumpkin and sunflower seeds, oily fish), and/or soya/fruit isoflavones and/or curcumin and/or astragalus have been shown to improve the action of radiotherapy.

MGN-3 (Biobran) reduced side effects of chemotherapy and radiotherapy in Japanese Clinical Trials. It is a rice bran and Japanese medicinal mushroom formula. The same trials show improved survival rates.

The various orthodox treatments leave an imbalance of flora in the intestine. You should take a multi-strain probiotic daily (Neways Advanced Probiotic, or Probiota 8) and try to keep yeasts in check. A teaspoon of sodium bicarbonate in warm water first thing in the morning, Pau D´arco supplement, oregano and wormwood will do this.

Antioxidants and Chemotherapy – Findings[xi]

  • All of the studies that included survival data showed similar or better survival rates for the antioxidant group than the control group.
  • None of the trials supported the theory that antioxidant supplements diminish the effectiveness of chemotherapy treatments.
  • All but one of the studies that reported treatment response showed similar or better response in the antioxidant group than in the control group.
  • 15 of 17 trials that assessed chemotherapy toxicities, including diarrhea, weight loss, nerve damage and low blood counts, concluded that the antioxidant group suffered similar or lower rates of these side effects than the control group.

Supplements during gem/cis Yes or No ?[xii]

cisplatin beats the magnesium out of your blood… i take 500mg magnesium daily…over the counter…doctors orders and nulasta 24hrs after last chemo treatment…..have good insurance….$3000 a shot can be overwhelming, unless it is covered in a clinical trial – daveyo

1,25D3 [Vitamin D3] Enhances antitumor activity of gemcitabine and cisplatin in human bladder cancer models[xiii]


1,25 dihydroxyvitamin D3 (1,25D3) potentiates the cytotoxic effects of several common chemotherapeutic agents. The combination of gemcitabine and cisplatin is a current standard chemotherapy regimen for bladder cancer. The authors investigated whether 1,25D3 could enhance the antitumor activity of gemcitabine and cisplatin in bladder cancer model systems.

Human bladder cancer T24 and UMUC3 cells were pretreated with 1,25D3 followed by gemcitabine and cisplatin. Apoptosis was assessed by annexin V staining. Caspase activation was examined by immunoblot analysis and substrate-based caspase activity assay. The cytotoxic effects were examined by using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and in vitro clonogenic assay. p73 protein levels were assessed by immunoblot analysis. Knockdown of p73 was achieved by siRNA. The in vivo antitumor activity was assessed by in vivo excision clonogenic assay and tumor regrowth delay in the T24 xenograft model.

1,25D3 pretreatment enhanced gemcitabine and cisplatin-induced apoptosis and the activities of caspases 8, 9, and 3 in T24 and UMUC3 cells. 1,25D3 synergistically reduced gemcitabine and cisplatin-suppressed surviving fraction in T24 cells. 1,25D3, gemcitabine, or cisplatin induced p73 accumulation, which was enhanced by gemcitabine and cisplatin or 1,25D3 and gemcitabine and cisplatin. p73 expression was lower in human primary bladder tumor tissue compared with adjacent normal tissue. Knockdown of p73 increased clonogenic capacity of T24 cells treated with 1,25D3, gemcitabine and cisplatin, or 1,25D3 and gemcitabine and cisplatin. 1,25D3 and gemcitabine and cisplatin combination enhanced tumor regression compared with 1,25D3 or gemcitabine and cisplatin alone.

1,25D3 potentiates gemcitabine and cisplatin-mediated growth inhibition in human bladder cancer models in vitro and in vivo, which involves p73 induction and apoptosis. Cancer 2010. © 2010 American Cancer Society.

Yingyu Ma, MD, PhD 1, Wei-Dong Yu, MD 1, Donald L. Trump, MD 2, Candace S. Johnson, PhD 1


Pete Granger’s Comments on Vit. D3 research above

From:   Peter Granger (pete.granger@GMAIL.COM) 30 April 2010 22:01:57

This lab research suggests taking vitamin D3 with chemo (gemcitabine
and cisplatin) reduces bladder cancer progression. This does not
necessarily mean it will work with all chemo, but it might be worth a
try. Apparently, vitamin D3 induces expression of the p73 gene – a
gene with close similarities to the p53 gene. P53 senses DNA damage,
and places cell cycle on hold while enzymes restore the damaged DNA.
If the damage is irreparable, p53 commits the cell to
self-destruction. In cancer, including bladder cancer, the p53 gene is
often damaged (mutated) so it is incapable of carrying out this
critical function. Incidentally, there are some nutrients which assist
in carrying out similar functions to p53 via alternate pathways.
However, the role of p73 is far from clear. Unlike p53, p73 mutations
are rare in cancer. Moreover, p73 does not directly repair DNA itself,
and mutations do not necessarily directly cause cancer. It is more
likely p73 mutations interact with p53 mutations, compounding the
negative effect of the latter – perhaps via the immune system or some
other pathway.

One possibility is that vitamin-d-induces an enhanced immune response
to the chemo, or it mitigates against some of the negative,
deleterious effects of chemo – which is after all, a very blunt

Expressed another way, vitamin D3 may help correct the negative
influence of (rare) p73 mutations on (common) p53 mutations.


Milk thistle herb protects liver from damage caused by chemotherapy[xiv]

(NaturalNews) The herbal supplement milk thistle may prevent liver damage in people undergoing chemotherapy, according to a new study conducted by researchers from Columbia University Medical Center and published in the journal Cancer.

Researchers conducted the study on 50 children undergoing a “maintenance” round of chemotherapy for acute lymphoblastic leukemia (ALL), a type of blood cancer. Approximately two-thirds of all children undergoing treatment for ALL usually develop liver toxicity during their treatment, presenting doctors with the choice between scaling back the treatment and risking a resurgence of the cancer, or continuing with treatment unaltered and risking permanent liver damage and lifelong health complications. There is currently no known way of preventing liver toxicity in chemotherapy patients.

Study participants were assigned to take either a milk thistle pill or a placebo capsule for one month. At the start of the study, all 50 children were suffering from liver inflammation due to prior rounds of chemotherapy. By the end, children taking milk thistle had significantly lower levels of two liver inflammation markers than children taking a placebo.

Milk thistle has been used for more than 2,000 years as an herbal treatment for liver and gallbladder problems. Although researchers have looked for evidence that the herb might help prevent or even treat liver damage in people with hepatitis or cirrhosis, results have been inconclusive.

However, recent studies suggest that milk thistle contains an active antioxidant known as silybin that might help block toxins from breaching cell walls.

Milk thistle supplements are already sold over the counter. Striking a cautionary note, however, senior researcher Kara M. Kelley noted that further research is needed before the plant can be recommended as a treatment. She advised against patients self-medicating with milk thistle, noting that all patients undergoing treatment for cancer should always check with their doctors before taking any new kinds of supplements.

Neuropathy & Glutamine

From:   Nancy Neuman (neuman.nancy@GMAIL.COM)

Sent:  09 June 2010 21:16:35

Every time a friend has started chemo, no matter what their cancer is, I
tell them to ask their oncologist about neuropathy. I am stunned that the
patient still has to take charge of this issue in too many cases. I was
lucky that my oncologist asked me early on if I felt any numbness in my feet and when I said I thought so he immediately prescribed Glutamine (at the natural food store) and Vitamin B6. It seems to have done the trick.
Glutamine is expensive so he cut the dose in half and it still worked. It is not to be confused with Glucosamine.


Glutamine for neuropathy and other chemo supplements‏

From:   Wendy Ramsay (ramsaycafe@COMCAST.NET)

Sent:  12 March 2010 20:47:17

Hi Robert.
In 2006 I had a lot of strong chemo (gemzar/cisplatin, adriamycin/taxol, MVAC). My doc prescribed me 10 grams (3 scoops) of glutamine powder 3 times a day to minimize the side effects of chemo including neuropathy. I was told to start the day before chemo and continue for 5 days after. Since I had chemo once a week I was taking this supplement 6 days/week 3 x’s a day. I can personally attest to it’s effectiveness. I have no neuropathy even after all that chemo.

During chemo I slacked off a bit and began taking glutamine only twice a day. I noticed numbing in my feet and hands. As soon as I got back on track with taking the supplement 3 times a day, the numbing went away. I think it’s important to prevent neuropathy but I also think it can be reversed (or lessened) at some point before it becomes too severe.

Also, below is an old post (2006) of the supplements I took during chemo and some reasons why they were prescribed to me:

Fruit, etc Help, but No Sugar or Fruit Juices

From: Wendy Ramsay
Sent: Saturday, May 27, 2006 7:25 AM
Subject: [CAFE] chemo and supplements

Hi Anne,
I know this is a late reply, but there are supplements that work in conjuction with specific chemotherapies. You would need to hook up with a naturopath working in the field of cancer and/or bladder cancer. I have been taking supplements to aid, specifically, my gemzar/cisplatin treatments. Different chemos affect the body in different ways. The oncologist that is treating me doesn’t necessarily ‘believe’ in them either. I do need to take the time to print out the research supporting the supplements so that he can have it and hopefully bridge the gap a bit. In addition to supplements which I will list below, I was told adamantly to stay away from sugar except for the day I am receiving chemo. On that day, I should eat some sugar. I should not drink fruit juices but whole fruit is OK (there are differing opinions on staying away from fruit altogether). Two cups of coffee on the day of chemo was also recommended (he said I could still drink coffee the rest of the time but limit to 16 oz/day).  Soy every day. Also wild salmon, olive oil, 6 brazil nuts/day, sesame tahini (1 tablespoon/day), and lots of green tea. Below are the supplements prescribed to me. Several related specifically to decreasing metastases by binding the connectors of the cancer cells preventing them from taking hold and seeding (quercitin, fractionated fruit pectin, great tonifying formula herbal packets). Others support increased immune support or response to the chemo (melatonin, Coriolis mushroom, curcumin).

melatonin (20mg/ once before bed)
multi nutrients V (2 caps – 2x’s/day)
cal/mag    (500g 2x’s/day)
vit c    (1000 – 1x/day)
green tea (3 to 5 cups/day)

Greens First powder juice mix (1 scoop/day)     contains: barley grass juice powder, chlorella, spirulina, carrot juice powder, broccoli juice powder, cauliflower juice powder, spinach jjice powder, parsley juice powder, kale juice powder, green tea extract (decaf) blueberry, plum, grape seed extract, cranberry, rasberry, tart cherry, pine bark extract, bussel sprout, natural flavors, stevia, citric acid.

Whey protein (2 tsp – 1x/day)
cod liver oil (2 tsp/day)
curcumin (4 caps – 2 x’s/day take only the 3 days prior to chemo and not on day of chemo)
Coriolis mush (2 caps in am/ 3 caps in pm)

great tonifying extract powder formula (2 cups tea/day)    contains:   ginseng, angelica sinensis, peony root, atractylodes rhizome, hoelen, cinnamon bark, astragalus root, cnidium rhizome, licorice, tehmannia root)

quercitin (500 – 2 x’s/day)
fractionated pectin (1 scoop 2x’s/day)

Other supplements are prescribed for me depending on my individual labs etc as needed but these are the basics for my chemo regiment. The naturopath I see is Paul Reilly from Seattle Cancer Treatment and Wellness Center (Cancer Treatment Centers of America). His book (How to Prevent and Treat Cancer with Natural Medicine) does reference studies supporting various supplements to treatment.

Wendy Ramsay
Diagnosed 1994. Neobladder 2004. Right nephrectomy/chemo 2006. Upper tract chemo 2007/08. Left nephrectomy 2008. Home dialysis 6-7 x’s/week.

New Way To Fight Cancer: Protect Healthy Cells With The Silver Shield[xv]

ScienceDaily (Apr. 1, 2008) — A unique study proposes a new paradigm in cancer treatment: instead of selectively attacking cancer cells, protect all the healthy cells. Animal studies and in vitro human cell studies show that a short fast protects healthy cells against chemotherapy, while tumor cells remain sensitive to the drugs.

Fasting for two days protects healthy cells against chemotherapy, according to a study appearing online the week of Mar. 31 in PNAS Early Edition. Mice given a high dose of chemotherapy after fasting continued to thrive. The same dose killed half the normally fed mice and caused lasting weight and energy loss in the survivors.

The chemotherapy worked as intended on cancer, extending the lifespan of mice injected with aggressive human tumors, reported a group led by Valter Longo of the University of Southern California. Test tube experiments with human cells confirmed the differential resistance of normal and cancer cells to chemotherapy after a short period of starvation.

Making chemotherapy more selective has been a top cancer research goal for decades. Oncologists could control cancers much better, and even cure some, if chemotherapy were not so toxic to the rest of the body.

Experts described the study as one of a kind.

“This is a very important paper. It defines a novel concept in cancer biology,” said cancer researcher Pinchas Cohen, professor and chief of pediatric endocrinology at the University of California, Los Angeles.

“In theory, it opens up new treatment approaches that will allow higher doses of chemotherapy. It’s a direction that’s worth pursuing in clinical trials in humans.”

Felipe Sierra, director of the Biology of Aging Program at the National Institute on Aging, said: “This is not just one more anti-cancer treatment that attacks the cancer cells. To me, that’s an important conceptual difference.”

Sierra was referring to decades of efforts by thousands of researchers working on “targeted delivery” of drugs to cancer cells. Study leader Longo focused instead on protecting all the other cells.

Sierra added that progress in cancer care has made patients more resilient and able to tolerate fasting, should clinical trials confirm its usefulness.

“We have passed the stage where patients arrive at the clinic in an emaciated state. Not eating for two days is not the end of the world,” Sierra said.

“This could have applicability in maybe a majority of patients,” said David Quinn, a practicing oncologist and medical director of USC Norris Hospital and Clinics. He predicted that many oncology groups would be eager to test the Longo group’s findings, and advised patients to look for a clinical trial near home.

Longo, an anti-aging researcher who holds joint appointments in gerontology and biological sciences at USC, said that the idea of protecting healthy cells from chemotherapy may have seemed impractical to cancer researchers, because the body has many different cells that respond differently to many drugs.

“It was almost like an idea that was not even worth pursuing. In fact it had to come from the anti-aging field, because that’s what we focus on: protecting all cells at once,” Longo said.

“What really was missing was a perspective of someone from the aging field to give this field a boost,” UCLA’s Cohen said.

The idea for the study came from the Longo group’s previous research on aging in cellular systems, primarily lowly baker’s yeast.

About five years ago, Longo was thinking about the genetic pathways involved both in the starvation response and in mammalian tumors.

When the pathways are silenced, starved cells go into what Longo calls a maintenance mode characterized by extreme resistance to stresses. In essence the cells are waiting out the lean period, much like hibernating animals.

But tumors by definition disobey orders to stop growing because the same genetic pathways are stuck in an “on” mode.

That could mean, Longo realized, that the starvation response might differentiate normal and cancer cells by their stress resistance, and that healthy cells might withstand much more chemotherapy than cancer cells.

The shield for healthy cells does not need to be perfect, Longo said. What matters is the difference in stress resistance between healthy and cancerous cells.

During the study, conducted both at USC and in the laboratory of Lizzia Raffaghello at Gaslini Children’s Hospital in Genoa, Italy, the researchers found that current chemotherapy drugs kill as many healthy mammalian cells as cancer cells.

“(But) we reached a two to five-fold difference between normal and cancer cells, including human cells in culture. More importantly, we consistently showed that mice were highly protected while cancer cells remained sensitive,” Longo said.

If healthy human cells were just twice as resistant as cancer cells, oncologists could increase the dose or frequency of chemotherapy.

“We were able to reach a 1,000-fold differential resistance using a tumor model in baker’s yeast. If we get to just a 10-20 fold differential toxicity with human metastatic cancers, all of a sudden it’s a completely different game against cancer,” Longo said.

“Now we need to spend a lot of time talking to clinical oncologists to decide how to best proceed in the human studies.”

Edith Gralla, a research professor of chemistry at UCLA, said: “It is the sort of opposite of the magic bullet. It’s the magic shield.”

Funding from the study came from NIA (part of the National Institutes on Health), the USC Norris Cancer Center and the Associazione Italiana per la Lotta al Neuroblastoma.

USC graduate student Changhan Lee and Gaslini’s Raffaghello performed key experiments. The other authors were Fernando Safdie, Min Wei and Federica Madia of USC, and Giovanna Bianchi of Gaslini.

Longo has been studying aging at the cellular level for 15 years, and has published in the nation’s leading scientific journals. He is the Albert L. and Madelyne G. Hanson Family Trust Associate Professor in the USC Leonard Davis School of Gerontology with joint appointments as associate professor of biological sciences in the USC College of Letters, Arts and Sciences, and in the Norris Cancer Center.

For clinicians and patients

Fasting before chemotherapy has unknown risks and benefits for humans, Longo cautioned. Only clinical trials can establish the effectiveness and safety of fasting before chemotherapy.

“Don’t try and do this at home. We need to do the studies,” said Quinn, the USC Norris oncologist.

Adapted from materials provided by University of Southern California.

The diet that won’t just help you lose weight, you’ll live longer and be brainier! [xvi]

“But there’s now an effective weight-loss regimen that is not only simple, it promises significant health benefits – from easing asthma symptoms and reducing blood sugar levels, to fending off heart disease and breast cancer and protecting brain cells. Apparently, you’ll also live longer.

The diet goes under various names – The Alternate-Day Diet, Intermittent Fasting or The Longevity Diet – but the principle is the same: eat very little one day (50 per cent of your normal intake) and as much as you like the next.

This appears to trigger a ‘skinny’ gene that encourages the body to burn fat.

The Alternate-Day diet triggers a skinny gene that encourages the body to burn fat

Researchers first discovered the benefits of low-calorie eating in the Thirties. They found that putting a rat – or a worm, or a fruit fly or just about any animal, as it turned out – on a permanent very low calorie diet helped the animal live about 30 per cent longer than normal.

The animal had clearer arteries, lower levels of inflammation, better blood sugar control and its brain cells were less likely to get damaged. Meanwhile, rates of diseases linked to ageing all dropped.

But while scientists have known for years that animals on a low-calorie diet were healthier, no human – except a few iron-willed fanatics – could permanently stick to this regime.

The big breakthrough came in 2003 when Dr Mark Mattson, an American neuroscientist, discovered rats still enjoyed all those health benefits even when their calories were cut only on alternate days.

In other words, you don’t have to starve yourself all the time.

This was a crucial discovery, because the diet suddenly became a realistic option. In particular, it is far more palatable for the obese. The standard diet for them involves a daily intake of between 20 per cent and 40 per cent of what they would normally have.

‘These are very hard diets to follow,’ says Krista Varady, assistant professor of kinesiology and nutrition at the University of Illinois, Chicago.

You are constantly hungry. The eat-every-other-day-diet seems to offer an easier and more effective option.’

She’s just published the results of a ten-week trial of 16 patients, all weighing more than 14st.

They ate 20 per cent of their normal intake one day and a regular, healthy diet the next. Each lost between 10lb and 30lb; much more than the 5lb or 6lb expected.

‘It takes about two weeks to adjust to the diet and, after that, people don’t feel hungry on the fast days,’ says Varady.

Weight watching: Dieters should only consume around 500 calories on fasting days

Dr James Johnson, author of The Alternate-Day Diet, and a lecturer in plastic surgery, has now been doing the diet for five years.

‘I’ve always been a bit overweight. When I first started, I lost 35lb in 11 weeks.

‘Now I use the diet to keep my weight stable. If it starts going up, I’ll just go back on it for a few weeks. The evidence says this is about the most healthy thing you can do for yourself.’

One specific health benefit is relieving the symptoms of asthma – and that’s not just because the patients have lost weight.

A small study of ten obese asthmatics found that after eight weeks they’d lost eight per cent of their body weight; their symptoms of the disease had also greatly improved.

The study, conducted by Dr Johnson with scientists from the National Institute on Ageing ( including Dr Mattson) and Stamford University, showed patients had less inflammation in their lungs, making it easier for them to breathe.

They also had lower levels of damaging free radicals – the substances we produce simply by eating and breathing – which have been linked with heart disease and cancer.

‘The level of inflammation was down by 70 per cent and the level of free radicals by 90 per cent,’ says Dr Johnson. ‘No other dietary approach to asthma has recorded anything like that benefit.’

About two weeks after coming off the diet the patients’ symptoms began to return.

Meanwhile, British researchers are now looking at the benefits of the diet in preventing breast cancer in highrisk patients.

‘We’ve found a very low 800 calories-a- day diet dramatically lowers the enzymes that metabolise fat and glucose in breast tissue,’ says Dr Michelle Harvie, of the Genesis Breast Cancer Prevention Centre in Manchester. ‘These enzymes are always raised in breast cancer patients.’

When Dr Matteson made his discovery, it wasn’t clear exactly why very low calorie diets had such an effect on health and lifespan.

But in the past couple of years it’s emerged that a specific gene – SIRT1 – might explain the diet’s success; it seems the sudden, sharp stress of a big drop in food intake triggers this ‘skinny’ gene. ‘This then blocks another gene involved in storing fat,’ explains Dr Johnson.

‘The body starts using up more of the fat stores. As a result you lose more weight than you would from just eating fewer calories.’

The SIRT1 gene also seems to be responsible for all the benefits of semi-starvation found in animals – the drop in inflammation, lower blood sugar levels – as Dr Mattson and others reported this year in the journal Brain Research Reviews.

Perhaps not surprisingly, drug companies are working hard to develop medicines that imitate some of the diet’s effects by targeting the SIRT1 gene.

The weight-loss benefit could also be due to the way the diet tricks your body’s metabolism.

The problem with most diets is that after 48-to-72 hours this slows to compensate for the drop in food.

When you stop the diet and eat normally, the weight goes back on faster, as you’re eating more than your body thinks it needs to function.

The alternate day diet seems to get round that because it allows normal eating as well.

‘We’ve run trials that haven’t found any reduction in metabolic rate when people are on the alternate day diet,’ says Dr Johnson.

Enjoy: You can eat as much as you want on alternate days

How it works doesn’t matter to many people – the internet is already buzzing with those who claim dieting on alternate days has made weight loss easier.

One woman writing on a U.S-based website found that very little of the weight she’d lost went back on.

‘At the end of 2008 I lost 15lb and then I stopped the diet. Nine months later, in October, I’d only put on 2lb.

‘By the end of that month I’d lost what I’d gained and another 7.5lb. It is gone forever! Woohoo.’

Another described how the not eating days – described as ‘down’ days – are actually the easiest ones to manage.

‘It’s strangely true, but down days are a lot easier to stick to than the up days. I haven’t cheated on them once.

‘It really does work knowing you can “have it” tomorrow. It’s the eating days you have to be careful with as it would be quite easy to go over the top.’

Yet some British experts are concerned about the approach. ‘We advise anyone trying to lose weight should follow a healthy balanced diet,’ said a spokesperson for the Food Standards Agency.

‘It may not be possible to achieve this with very low calorie diets.’

However, Catherine Collins, spokesperson for the British Dietetic Association, was more enthusiastic about the weightloss benefits.

‘It sounds absolutely fine,’ she says ‘It would certainly make it easier to stick to a weight-loss programme, although I’d want to be sure people got enough fibre and protein and that they didn’t starve and binge in a fanatical way.’

However, she is sceptical about the health benefits being triggered by the SIRT1 gene.

‘We know weight loss has all sorts of metabolic benefits,’ she says.

‘That is probably what is going on rather than one gene being responsible.’

The big question now is to find the best schedule of eating and fasting that will bring the benefits and be the easiest to stick to. Alternate-day dieting has made the breakthrough, but it is only one option.

‘At the moment we are studying the benefits of having just two fasting days a week when you have very few calories, then eating normally for the rest of the week,’ says Dr Harvie.

‘Some form of fasting regime is definitely the way to go to get big health benefits. It just needs more research.’

• For more, visit: http://www.johnson 


  • For the first fortnight Dr Johnson suggests you stick to just 500 calories on the fasting days to make sure you trigger the skinny gene (to make certain of your intake, try pre-packaged shakes or meal replacements).
  • After that, you can eat regular food on the fasting days. How much depends on your goal. Up to 35 per cent of your recommended daily intake will help you lose weight. Eating 50 or 60 per cent should allow you to maintain your weight.
  • You can eat as much as you want on the alternate days, but don’t binge. Make sure you have fruit and vegetables. It’s important to enjoy these days to avoid getting fed up with being on a diet.
  • Drink plenty of water and exercise regularly, especially on the eating days. Weigh yourself only once a week, on the morning after a fasting day, so you won’t become frustrated by normal weight variations.

Exercise May Keep Cancer Patients Healthier During, After Treatment[xvii]

ScienceDaily (May 20, 2010) — Breast and prostate cancer patients who regularly exercise during and after cancer treatment report having a better quality of life and being less fatigued, according to researchers at Henry Ford Hospital in Detroit.

“Using exercise as an approach to cancer care has the potential to benefit patients both physically and psychologically, as well as mitigate treatment side effects,” says study lead author Eleanor M. Walker, M.D., division director of breast services in the Department of Radiation Oncology at Henry Ford Hospital.

“Plus, exercise is a great alternative to patients combating fatigue and nausea who are considering using supplements which may interfere with medications and chemotherapy they’re taking during cancer treatment.”

Dr. Walker will present a poster with the study’s design and intervention methods June 7 at the 2010 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. The abstract is now available online at

To study how exercise impacts cancer patients, Dr. Walker and her colleagues at Henry Ford’s Josephine Ford Cancer Center and the Henry Ford Heart & Vascular Institute developed a unique program called ExCITE (Exercise and Cancer Integrative Therapies and Education).

ExCITE works with patients who are receiving cancer treatment to create individualized exercise programs. Some patients come into one of Henry Ford’s fitness centers to workout, while others have plans that allow them to exercise at home during various stages of their care.

The study group thus far includes 30 female breast cancer patients and 20 prostate cancer patients, all ranging in age from 35 to 80. All were newly diagnosed when they began ExCITE. The study followed the patients during treatment and for one-year following completion of cancer treatment.

Before beginning the exercise program, Henry Ford’s Preventative Cardiology Division measured the patients’ exercise capacity, skeletal muscle strength and endurance. General blood work, metabolic screens, bone density and inflammatory biomarkers also were obtained at the start of the program.

Exercise and diet recommendation for each patient were based on their baseline exercise tolerances, weight, overall health, and type of cancer treatment they would receive. Acupuncture was used for patients who experienced hot flashes, pain, nausea/vomiting, insomnia and neuropathy as the result of cancer treatment.

Cheryl Fallen of Gross Pointe Park, Mich., was undergoing chemotherapy for breast cancer while she took part in the ExCITE program. Through a mix of exercise, acupuncture and good nutrition, she didn’t experiencing some of the more common side-effects from treatment — nausea, fatigue and trouble with memory.

“ExCITE offers cancer patients a way to holistically approach their cancer care by tailoring a specific exercise routine to fit the needs of the patient, whether it’s rehabilitation after surgery, or to enhance circulation or improve the immune system prior to chemotherapy or radiation,” says Fallen.

When her white blood cell count fell during chemotherapy, Fallen would work out at home using an exercise band or by walking outdoors. When she was well enough to return to the gym, her workouts consisted of using the exercise ball and treadmill, and doing other strength-training exercises.

“Overall, the program makes you feel better about yourself. It’s a positive support for cancer patients, and I really think it’s allowed me to be more productive during my treatment,” says Fallen.

Study of the ExCITE program is ongoing, with Dr. Walker and her colleagues continuing to investigate the potential benefits of exercise for cancer patients.

Study funding: Josephine Ford Cancer Center, part of the Henry Ford Health System, and Mothers, Daughters, Sisters & Friends, a group dedicated to raising funds for breast cancer care and research at Henry Ford.

Story Source:

Adapted from materials provided by Henry Ford Health System, via EurekAlert!, a service of AAAS.

See Also:

New exercise guidelines for cancer survivors

The first and most important guideline, Schmitz said, is that patients and survivors must avoid inactivity. They must continue their normal activities during and after treatment, and resume daily life as soon as possible after surgery. Other specific recommendations include:

> Over the course of one month, it’s safe to build sedentary patients up to 150 minutes of moderate-intensity aerobic exercise per week
> It’s safe for patients undergoing stem cell transplant to exercise every day, but these patients should reduce intensity and progression of intensity because of the effects on the immune system
> For patients suffering from weight loss, resistance training can help build strength
> For those with prostate, hematologic, and colon cancers, twice-weekly resistance training is recommended: one exercise for each major muscle group for eight to 10 repetitions, and one to three sets per exercise
> Women with breast and gynecologic cancers should start with a supervised resistance training program given the risk for lymphedema
> Given side effects such as incontinence and sexual dysfunction, floor exercises should be added to an exercise routine for men with prostate cancer
> Colon cancer patients with an ostomy should avoid excessive intra-abdominal pressures

How to Take Care of Yourself During Chemotherapy[xviii]

Continue all of the recommendations for what to do in preparation for chemotherapy, and increase protein powder supplementation to twice a day. If you are still experiencing some nausea, try these strategies:

  • Eat smaller, more frequent meals. Five or 6 snack-type meals a day can reduce some of the stress on your digestive tract. Smoothies make a perfect meal.
  • Do not lie down after eating. Allow yourself an hour or more to digest. Try a short walk after meals or, if you need to rest, sit with your legs stretched out and your head propped up with pillows.
  • Do not drink liquids with your meals. This keeps your digestive juices at full strength, promoting complete digestion and reducing indigestion.
  • Drink plenty of liquids between meals (at least 1 hour before or after meals). Ginger tea and peppermint time have anti-nausea/stomach settling properties. Drink them warm or iced, as you prefer. Also include vegetable and fruit juices (fresh squeezed for the highest nutrient content, if possible) and clear broths. Avoid sugar as it can increase your risk for intestinal candida infection that is very common at this vulnerable time. If you must use a sweetener, use a grain-derived sweetener like rice syrup or barley malt.
  • Avoid all fatty foods. Focus your diet on fresh fruits, steamed or boiled vegetables, light grains and proteins.
  • If you are experiencing vomiting and severe diarrhea, include sea salted vegetable broths or miso broth. These salty additions will help to keep your electrolytes balanced and can revive you when you are feeling faint. (Miso is a salty paste made from soybeans and can be found in health food stores, Asian food markets and some supermarkets).

Recommendations – Supplements To Take With Specific Chemotherapy Drugs
The side effects of chemotherapy can be reduced by decreasing the toxicity of the chemotherapy medication. Contrary to what one might expect, this does not make the chemotherapy any less effective at doing its job —killing cancer cells. More often than not, decreasing its toxicity increases a drug’s effectiveness. Supplements known to decrease various chemotherapy drugs’ toxicity are listed below. Also listed are substances known to increase the effectiveness of certain drugs.

Drug Substances That Decrease Toxicity Substances That Increase Effectiveness
Adriamycin CoQ10, Vitamin E, Riboflavin, NAC (N-Acetylcysteine), Vitamin C, Antioxidants Vitamin E, Green Tea, Vitamin A
CIS Platinum Recancostat*, Glutathione IV*, Ginkgo biloba, Milk Thistle, Selenium, Magnesium Recancostat* Vitamin C, Vitamin A
Neosar Ashwaganda herb* Aloe Vera Extract, Bu Zhong Yi Qi Wan*, Vitamin A
5 FU Vitamin B6, CoQ10, Chamomile mouthwash, Glutamine mouthwash Vitamin A, L-cysteine, Vitamin E, Aloe Vera, Calcium Butyrate
Methotrexate Glutamine Vitamin A, Glutamine, Proteolytic enzymes/Wobenzyme
Taxol Vitamin C
Tamoxifen Soy isoflavones, natural progesterone, Remifemin Melatonin
Vincristine Vitamin C Vitamin A

Chemo, Tinnitus‏ & Hearing Loss

From:   S. Norbash (sidnorbash@SBCGLOBAL.NET)

Sent:  10 June 2010 11:45:00
My husband has had transitional cell carcinoma and is followed every 6 months at MD Anderson. (left kidney, ureter and bladder “cuff” removed, BCG, etc….)  I “lurk” here to try to keep up with the latest and read the recent posts about tinnitus.  I am an audiologist and have monitored hearing in cancer patients for clinical trials, etc… It always pains me to know the likely consequences as far as hearing, but usually there is no choice.  my husband had gemzar and cisplatin chemo and now wears hearing aids.  the full effects of the chemo on hearing will often not show up for months after treatment is concluded.  His tinnitus is not severe, but he has mild to moderate hearing loss.  He had “no choice” since hearing aids are what I do,   🙂 but he does get great benefit from them and I would encourage you to see what’s out there, especially a new device that is an advanced digital hearing aid AND a tinnitus masker in one.  I have heard of
good success with it.  If you are interested, I would suggest contacting a local audiologist and asking about it.  The name is ReSound Live TS.  Most audiologists offer a trial period where you could see if it is helpful or not.

Cold Caps Prevent Hair Loss

From:  clozie@COMCAST.NET
> Subject: [CAFE] Glutamine to prevent neuropathy, and “cold cap” to prevent hair loss
> To: BLADDER-CANCER-CAFE@LISTSERV.ACOR.ORG Date: Thu, 9 Sep 2010 16:58:12 -0400

Nancy and Wendy,

I totally agree with both you.  Though I am not surprise, I find it revolting that so many oncologist won’t even “mention” Glutamine as well as other things that might be outside the “mainstream” of current oncology but which, nonetheless, “might” or are even “very likely” to help palliate some of the terrible side-effects of the “mainstream” pharmaceutical drugs that they recommend without any hesitation.

Here is another example which I want to pass along:  in my current chemo, I have been using a “cold cap” — a cap, made of cold-gel packs, which I keep over my head 15 minutes before, during and for another hour or so after the infusion;  and, after 10 infusions of Andriamycin, I still have all the hair on my head!  I am totally hairless everywhere else in my body (nice, actually — I have not needed to shave since March!), EXCEPT on my head — so, there is no question whatsoever that the “cold cap” is what prevented me from losing my hair.  And even though hair loss is, as Nancy pointed out, a “temporary” side-effect, it is still one of the most annoying ones.  I lost my hair in each one of the 4 chemos that I did before this one — that got really old!

Just like with Glutamine to preven neuropathy, why don’t oncologist doctors and nurses at least “mention” cold caps as a “possible” way to prevent hair loss??

I can understand that some would hesitate to “recommend” such things based on the common (and I think truthful, in many cases) allegation that “not enough studies have been done about it to *proof* anything scientifically”.  However, they must know, or at least should know that not enough studies will *EVER* be done about some of these things, NOT because they don’t make sense logically/theoretically or because they are not worth-studying, but because obviously these things are not patentable, therefore no profit-seeking corporation will ever dump the necessary millions or billions of dollars that are usually needed to do repeated studies in order to “proof” anything scientifically.

However, though in comparatively limited numbers and with less “rigor” (scientific rigor usually requires more money), both in the case of Glutamine as well as for the “cold caps” there HAVE been studies done — I don’t have the reference handy but I have read a couple of them by searching the net or Pubmed.  And they HAVE “demonstrated” that they worked for at least a great number of the patients in these particular studies!  I am quoting this “by memory”, so I might not get the figures right, but in the case of “cold caps” the study that I read demonstrated that it had prevented hair loss in more than 85% of the cases — that is a HUGE percentage, given that most of the toxic chemos that oncologists recommend, particularly in the metastatic stage, only work for much less than that!  I was once recommended a chemo that it is “proven” to work for only about 13% of the cases!  And although the numbers are a lot more promising in the first line treatments — as you all know, fortunately many people ARE cured by the first and only chemo that they ever take! — I believe that in the metastatic stage, unfortunately, the average response rates are around 15-30% at best.

Given that Glutamine and “cold caps” don’t seem to have any “toxic” side effects — from what I read, EVEN if they don’t work, they at least are not likely to cause any serious damage —  it is really revolting that we, the patients, are not at least “told” about the “possibility” of using these things to palliate these two very bad potential side effects of chemo.

In any event, now that I am sure it has worked for me, I am telling everybody I know to Google “cold cap chemo” before their first infusion to judge for themselves whether they should give it a try and perhaps save their hair.  I was told about this by a friend of mine and I did not have time to purchase the commercially available caps, so my husband made one for me using those “blue” cold gel packs that are used for sore muscles and that he bought, cheaply, at our local CVS pharmacy.  Once I have more time, he and I are planning on writing about it in more details for people that don’t want or can not afford the commercial caps.

As to Glutamine, I learned about it a couple of years ago right here at the WebCafe, probably thru one of your emails, Wendy — thanks for sharing your experience always so generously!  Unfortunately, that was not in time for my cysplatin chemo, and obviously I wish my doctor had told me about it.  I have used it during other chemos ever since, and I have been telling every patient I know about it.

I hope this long email helps save someone’s hair one day :)!!



Fruit, etc Help, but No Sugar or Fruit Juices

From: Wendy Ramsay
Sent: Saturday, May 27, 2006 7:25 AM
Subject: [CAFE] chemo and supplements

Hi Anne,
I know this is a late reply, but there are supplements that work in conjuction with specific chemotherapies. You would need to hook up with a naturopath working in the field of cancer and/or bladder cancer. I have been taking supplements to aid, specifically, my gemzar/cisplatin treatments. Different chemos affect the body in different ways. The oncologist that is treating me doesn’t necessarily ‘believe’ in them either. I do need to take the time to print out the research supporting the supplements so that he can have it and hopefully bridge the gap a bit. In addition to supplements which I will list below, I was told adamantly to stay away from sugar except for the day I am receiving chemo. On that day, I should eat some sugar. I should not drink fruit juices but whole fruit is OK (there are differing opinions on staying away from fruit altogether). Two cups of coffee on the day of chemo was also recommended (he said I could still drink coffee the rest of the time but limit to 16 oz/day).  Soy every day. Also wild salmon, olive oil, 6 brazil nuts/day, sesame tahini (1 tablespoon/day), and lots of green tea. Below are the supplements prescribed to me. Several related specifically to decreasing metastases by binding the connectors of the cancer cells preventing them from taking hold and seeding (quercitin, fractionated fruit pectin, great tonifying formula herbal packets). Others support increased immune support or response to the chemo (melatonin, Coriolis mushroom, curcumin).

melatonin (20mg/ once before bed)
multi nutrients V (2 caps – 2x’s/day)
cal/mag    (500g 2x’s/day)
vit c    (1000 – 1x/day)
green tea (3 to 5 cups/day)

Greens First powder juice mix (1 scoop/day)     contains: barley grass juice powder, chlorella, spirulina, carrot juice powder, broccoli juice powder, cauliflower juice powder, spinach jjice powder, parsley juice powder, kale juice powder, green tea extract (decaf) blueberry, plum, grape seed extract, cranberry, rasberry, tart cherry, pine bark extract, bussel sprout, natural flavors, stevia, citric acid.

Whey protein (2 tsp – 1x/day)
cod liver oil (2 tsp/day)
curcumin (4 caps – 2 x’s/day take only the 3 days prior to chemo and not on day of chemo)
Coriolis mush (2 caps in am/ 3 caps in pm)

great tonifying extract powder formula (2 cups tea/day)    contains:   ginseng, angelica sinensis, peony root, atractylodes rhizome, hoelen, cinnamon bark, astragalus root, cnidium rhizome, licorice, tehmannia root)

quercitin (500 – 2 x’s/day)
fractionated pectin (1 scoop 2x’s/day)

Other supplements are prescribed for me depending on my individual labs etc as needed but these are the basics for my chemo regiment. The naturopath I see is Paul Reilly from Seattle Cancer Treatment and Wellness Center (Cancer Treatment Centers of America). His book (How to Prevent and Treat Cancer with Natural Medicine) does reference studies supporting various supplements to treatment.

Wendy Ramsay
Diagnosed 1994. Neobladder 2004. Right nephrectomy/chemo 2006. Upper tract chemo 2007/08. Left nephrectomy 2008. Home dialysis 6-7 x’s/week.

[viii] Date: Sun, 6 Feb 2011 09:12:26 +1100 From: pete.granger@GMAIL.COM Subject: [CAFE] Curcumin and Resveratrol – Chemoresistance To: BLADDER-CANCER-CAFE@LISTSERV.ACOR.ORG


NOTE: The 2012 edition of The Cancer Survivor’s Bible is now available – see for details

“The section on conventional treatment was riveting.”


Posted in Cancer Perspectives, Comments and Suggestions, Supporting chemo | Tagged: , , , | 7 Comments »

The Strawberry Cure for Cancer?

Posted by Jonathan Chamberlain on April 20, 2011

If you’re seriously looking for cancer related information then this is the place – do browse – the infor here supports and extends the info in my cancer books – see

The Strawberry Cure for Cancer?

Strawberries may not be a cure but they certainly do something very measurably good – particularly for esophageal cancers but very likely for other cancers too. And you don’t have to eat loads to get the impact (though maybe this is a case of the more the better) For more information go to the link below – and note their cautions on organic being preferable.

While this news results from the publication of a particular study in China, strawberries have long been associated with anti-cancer effects as we can see here

Posted in cancer and diet | Tagged: , , | Leave a Comment »

Anti-radioactivity Foods

Posted by Jonathan Chamberlain on April 16, 2011

If you’re looking for cancer related info – then browse this site. Also read my two cancer books 0 see for details

Anti-radioactivity foods

The continuing crisis in Fukushima and the certainty that radiation levels worldwide will be impacted (bringing in its wake increases in thyroid cancer and leukemia)  leads to the obvious question of how we can protect ourselves.

The first answer is to take potassium iodide everyday 4-12mg – you can get this as a liquid called Lugol’s solution or as pills under the brand name Iodoral. I anddition you need to soak all your vegetables in water and throw the water away. Finally here is a list of foods that will be part of the optimal diet. This was prepared by Russian scientists based on their experience of Chernobyl

1.      Brown rice

2.      Seaweed

3.      Kelp

4.      Miso

5.      Pumpkin

6.      Spirulina (& Chlorella)

7.      Bee pollen

8.      Wheat grass

9.      Rosemary

10.  Blue-green algae

11.  Beets

12.  Garlic

13.  Ginger

14.  Alfalfa sprouts

15.  Broccoli

16.  Onions

17.  Olive oil

18.  Leafy greens

Apples and other sources of pectin

Note: The Cancer Survivor’s Bible (2012 edition) is now available – see

“This book tells me everything. Why didn’t my doctors tell me this?”

Posted in cancer and diet, Comments and Suggestions, Health Issues | Tagged: | Leave a Comment »

Lyme disease symptoms

Posted by Jonathan Chamberlain on April 14, 2011

Most of the info on this site is cancer related – supporting my two books. See for details

Lyme disease symptoms

Lyme disease was once associated only with the ticks on Rhode Island but seems to be spreading. Latest reports are of 3,000 victims in UK. Here is a list of the symptoms

Posted in Other Health Conditions | Leave a Comment »