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Tuesday, July 31, 2007

Blog Updates for July 2007

These retroactive updates to past posts are important reading for users of this web site. Rather than trickle them in one by one they are batched together and posted all at once. The text has been been included here to save the reader from having to click back to the original article.

July ?. In PSA Screening and Early Detection - Part 3. Current Environment we mention that:
  • mounting evidence suggests that PSA screening of men in their 40's can potentially be used to predict the risk of developing prostate cancer many years lter (see [link]). We also mentioned this in How Healthy Men can Reduce their Risk.
  • another debate on PSA testing is presented in the June 2007 Canadian Family Physician (see [link] with Yves Fadet presenting the Yes case (in favor of PSA screening) and Michel Labrecque, France Légaré and Michel Cauchon presenting the No case (against testing).
  • according to [PMID: 17372918] about 45% of men in the US within ages 40 - 84 had had at least one PSA test by the year 2000.

July ?. In the post on Vitamin D we rewrote the Deficiency and Toxicity section to make it clearer and to add information from Medline:

"Vitamin D deficiency can lead to osteoporosis in adults or rickets (a bone disease) in children.

Too much vitamin D can make the intestines absorb too much calcium. This may cause high levels of calcium in the blood. High blood calcium can lead to calcium deposits in soft tissues such as the heart and lungs. This can reduce their ability to function.

Kidney stones, vomiting, and muscle weakness may also occur if you have too much vitamin D."

The above quote is from the Medline page on Vitamin D.

Vitamin D deficiency can result from insufficient sunlight exposure or insufficient consumption of vitamin D in the diet, liver disease or kidney disease or genetic defects in the body's vitamin D receptors. See [Mayo clinic].

According to an article by Dr. Trump mice genetically modified to have no vitamin D receptors exhibit low blood calcium, weak bones, hairless skin, abnormal muscle development, high blood pressure, abnormal heart muscle development, increased susceptibility to infection and increased susceptibility to blod clot formation.

Toxicity does not normally occur from sunlight exposure due to self-regulatory mechanisms in the skin; however, increased sun exposure does put one at increased risk for skin cancer; although, according to this Reihold Vieth presentation sun exposure increases risk of skin cancer by 1% - 2% but reduces risk of all cancers by 10% - 20% so it reduces overall cancer risk but much more than it increases skin cancer risk.

The self-regulatory mechanisms do not appear to exist when the vitamin D is consumed as through supplements. Since Vitamin D is fat soluble rather than water soluble, in principle, it can build up in fat stores to toxic levels. In an article by Lisa Tseng: "Concurrent with this rise in vitamin D ingestion in Canada, United States, Sweden, Israel, and England were the epidemic onsets of atherosclerosis and osteoporosis, which led Moon et al. to hypothesize that chronic vitamin D excess contributes to the development of these two illnesses. Moon and colleagues supported their postulate by citing 37 studies, some dated as early as 1945, which documented cardiovascular and skeletal effects similar to atherosclerosis and osteoporosis in humans and laboratory animals after high vitamin D intake. Subsequently, Haddad et al. showed in seven healthy human volunteers that while endogenously synthesized dermal vitamin D is transported on vitamin D binding protein and causes a more sustained increase in serum 25-hydroxy vitamin D, the orally administered vitamin D is absorbed from the intestinal tract via chylomicrons and carried in the circulation by lipoproteins such as VLDL and LDL, which may end up in the artery wall. This finding supports Fraser’s earlier speculation that the toxicity of orally acquired vitamin D might be due to its unnatural route through the body and, consequently, it is less finely regulated than endogenously synthesized dermal vitamin D."
[link]. Perhaps man evolved to regulate vitamin D from the sun since early man was constantly exposed to the sun but because consumption of large amounts of vitamin D through supplements is only possible with modern technology no similar mechanism evolved to regulate that.

In [PMID: 16598750] 2 of 37 patients taking vitamin D developed kidney stones.

July ?. In the same Vitamin D post we also added a new section on Dosages:


The Canadian Cancer Society recommends that Canadians take 1000 IU per day of Vitamin D in fall and winter and those at risk of not getting sunlight in the other seasons take it all year round. The American and Canadian Cancer Societies and a number of other prominent organizations agreed at a 2006 Vitamin D conference in Toronto that 2000 IU/day was safe [link] and Reinhold Vieth has even suggested 4000 IU/day [link].

Be sure to review the deficiencies and toxicities section of this page and not that higher dosages should only be taken with sufficient medical monitoring. Also people with kidney, liver or heart disease may not be able to handle Vitamin D supplementation at all.

July 9. In the post on Historical Developments we have added the forecast of developments expected for the 2008 AUA meeting as written by Mitchell H. Sokoloff: "(1) definitive prospective comparison studies of cancer control and quality-of-life outcomes in open and robotic prostatectomy; (2) expanded stratification of risk among patients with localized disease; (3) improved standardization of adjuvant and salvage therapies for preventing and treating recurrent disease; and (4) results from phase 3 trials investigating new systemic therapies for prostate cancer."

July 9. In the Urinary Incontinence post we mention a review at the 2007 AUA meeting of new incontinence treatments: [link]. (Signup is required but is free.)

July 9. In the post on Pubmed Front Ends we added a section on google: Google Scholar is not a front end to PubMed but many readers may wish to try it anyways. Just plain google is also very useful. Also, if you know a Pubmed ID then just enter pubmed into google to get to pubmed and in the pubmed search bar enter something like 15313934[uid] where you replace the number with the ID of interest to you.

July 9. In PSA Screening and Early Detection Part 4 we added another sentence about the PCPT: "The Prostate Cancer Prevention Trial (PCPT) was a randomized, double-blind, placebo-controlled study of the efficacy of finasteride in preventing prostate cancer in 18,882 men aged 55 years or older."

July 15. In the post on Vitamin D and Prostate Cancer we added a reference to the Wikipedia entry on Vitamin D.

July 18. In 2007 AUA Update of Guidelines for Localized Prostate Cancer the following links were added. Readers interested in prostate cancer guidelines may also wish to look at the NCCN Guidelines. Readers interested in the AUA may also wish to look at this post on AUA 2007 Conference Summaries.

July 19. Lycopene, Selenium and Vitamin E in Combination.

Vitamin E. Although no toxicities were observed in this study,
  • a meta analysis of other studies concluded that Vitamin E increased the risk of dying by 39 in 10,000 when taken at a dosage of 400 IU/day or more; however, the conclusion seems controversial and, in particular, some of the studies used multi-vitamins, not just E. See the related articles at the bottom of [link] for discussion on this study.
  • the Womens' Health Study (WHS) concluded that cardiovascular disease increased among users of 600 IU/day of Vitamin E though the increase was not statistically significant. [link]
  • The Heart Outcomes Prevention Evaluation–The Ongoing Outcomes (HOPE-TOO) patients in the vitamin E group had a significantly increased risk for heart failure and hospitalization for heart failure in the Vitamin E group. [link]

Lycopene. High levels of lycopene may have adverse effects in smokers and certain other groups. [link].

  • Diabetes. In a 7.7 year human trial subjects who took 200 mcg/day of selenium increased their risk of developing diabetes by 50% (incidence, 12.6 cases per 1000 person-years vs. 8.4 cases per 1000 person-years for controls). See [PMID: 17620655] [Full Text]. A probability sample done in the US determined that the quartile taking the greatest amount of selenium had a 57% greater probability of developing diabetes than the quartile taking the lowest amount of selenium (however, the quartiles were not monotonically increasing). See [PMID: 17392543].
  • Toxicities not explored. In Bottom Line's "Why Doctors Don't Get Sick", Dr. Victor Herbert of the Mount Sinai School of Medicine in New York is said to have commented on the Harvard study that indicated selenium reduced the risk of advanced prostate cancer saying that the study failed to look at the incidence of other kinds of cancer, overall death and illness rates. Also there is little evidence that Americans are selenium deficient.
  • More. For more on selenium see [link].


Doubts on Lycopene Effectiveness. A recent study of 28,000 men concluded that lycopene does not prevent prostate cancer [link] [PMID: 17507623] contradicting previous studies and the FDA has concluded that there is only a limited evidence of association between eating tomatoes and decreased risk of prostate cancer [article], [link]. Giovannucci speculates in [PMID: 17623795] [Full Text] that lycopenes may have more of an effect on later stage cancers when the initial studies that showed association were prevalent but that in today's environment of PSA testing and earlier stage cancer they may be less effective. That would account for the discrepancy in results. Fleshner's study suggests that there is still the possibility that it may be effective in conjunction with other antioxidants.

Another Combo Study. Another animal study found positive effects from a combination of broccoli and tomatoes. In that study rats were fed the equivalent of 1.4 cups of raw broccoli and 2.5 cups of fresh tomato per day which had the effect of reducing tumor weight by about half relative to controls. 1 cup of tomato sauce or 1/2 cup of tomato paste would presumably be equivalent to the fresh tomato. See [article] and [PMID: 17213256].

SELECT. There is a large scale 7-12 year cancer prevention study underway on Selenium and Vitamin E called SELECT that enrolled subjects between 2001-2004. See [link] and the references at the bottom of that page. It is expected that better information will become available with it.

In Case Histories added some additional info on Rudi Giuliani. In his 2002 book entitled "Leadership" Rudi Giuliani (pictured below) discusses his decision process in choosing among treatment options. Giuliani is the former mayor of New York City and is currently seeking the Republican nomination for President of the United States. He is an advocate of cancer screening [link].

In the post on RP vs. LRP vs. RLRP. Part 3 Robotic Surgery we added information from the AUA 2007 meeting regardling robotic surgery. Unsubstantiated Claims. Dr. Wayne Hellstrom, summarizing presentations made at the 2007 AUA meeting writes in [link]: "Nearly half of radical prostatectomies performed in the United States were robotic-assisted radical prostatectomy (RARP). Marketing of this technique has focused on decreased pain, improved cancer control, and recovery (despite there being no published comparative analysis data on outcomes related to erectile function). One group of investigators reviewed hospital Web pages for claims relating to RARP. Of the 116 sites reviewed, 75 had information on the DaVinci system, surgical technique, and outcomes.[2] Of these sites, 78% (half university and half community hospitals) stated that RARP yielded better erectile function outcomes than open prostatectomy. Only 7 sites (15%) provided any data on postoperative erectile function, and only 2 offered their own data on this subject. The authors concluded that the claims for better erectile function outcomes are misleading and give patients choosing RARP unrealistic expectations and postoperative disappointment.

July 26, 2007. In Choosing a Surgeon - Part I. Considerations we added information from a just published paper: "This figure from the July 2007 JNCI [Fulltext] covering 7765 cancer patients and 72 surgeons shows freedom from biochemical recurrence curves for surgeons of varying experience. Note how the curve associated with surgeons having done more than 999 surgeries lies above all the others showing that their patients had the fewest recurrences of cancer. There were some limitations to the study: "Differences in case mix among surgeons may have contributed to residual confounding. Patient follow-up differed among institutions and surgeons. Accordingly, surgeon experience could not definitively be linked causally to patient outcome in this observational study. Biochemical recurrence is of uncertain clinical relevance to patients." [link].

July 28, 2007. In the post on the AUA 2007 guidelines we mention an article in the July 2007 US Too HotSheet [link] that reviews the guidelines. Also we point out that for advanced hormone sensitive cancer ASCO has guidelines [here].

July 28, 2007. Under Links to the right we added a new line, Guidelines, with links to the
NCCN AUA localized cancer and ASCO advanced cancer guidelines.

July 29, 2007. In Choosing a Surgeon - Part I. Considerations we note that there are large variations in the quality of care in the US. Discussing cancer, in general, (not specifically prostate cancer) in a July 27, 2007 New York Times article Dr. Stephen B. Edge, the chariman of surgery at the Roswell Park Cancer Institute in Buffalo says: "It’s quite surprising, but the quality of cancer care in America varies dramatically ... It’s scary how much variation there is."

July 29, 2007. In Holick's July 2007 NEJM Paper on Vitamin D my comment: perhaps one might be able to increase the Vitamin D they get from the sun by applying lanolin to the skin prior to exposure?

Dr. Richard Lehman had these thoughts on the paper: "You are vitamin D deficient, very probably, and this is making your muscles ache, slowing you brain, thinning your bones and making you more likely to get cancer and heart disease. The secret of the Mediterranean is not its food but its sunshine. Or both. Go on, take your clothes off, get outside, and eat lots of oily fish, cheese, wild fungi and eggs. Abandon your miserable existence in the dark North and start living before it is too late. Alternatively, get a sunbed and take large daily supplements of vitamin D. It’s the elixir of life, according to this very thorough and plausible review."

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