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Saturday, September 27, 2008

Blog Updates for September 2008

Sep 27. In PSA Screening and Early Detection Part 2 we add that the particular PSA Assay can affect the results of a PSA test: Standard PSA tests are usually standardized to the WHO 90:10 standard or standardized to the original Hybritech(R) standard. [PMID: 18801532]. If ones switches among tests using different standards then a significant difference may appear even if there is no real difference in the underlying PSA. The situation with ultrasensitive tests is even worse since there is no real harmonization at all among such tests.

Sep 27. On the Calculators page added: Mortality from Common Diseases. Four charts giving the mortality from vascular disease, cancer, infection, lung disease, accidents and all causes combined given age, sex and smoking status. There are 2 simple charts: one for men and one for women and two more detailed charts again one for men and one for women. The charts are available [here] as supplements to this paper: [PMID: 18544745]. There is further discussion in [PMID: 18544738] [full text].

Sep 26. In PSA Screening and Early Detection - Part 3. Current Environment we add the following: On the other hand, in a 15 year followup of Seattle vs. Connecticut prostate cancer mortality showed no difference even though Seattle had more intensive screening and treatment than Connecticut. [PMID: 18795372]. This study focused on men over 65.

Sep 23. On the Calculators page and also on the Radiation risks associated with Prostate Cancer page we add: "Some patients with nonmalignant systemic diseases, like collagen vascular disease (CVD), hypertension, diabetes mellitus, and inflammatory bowel disease (IBD), tolerate radiation therapy poorly. Although the mechanisms of each of these disease processes are different, they share a common microvessel pathology that is potentially exacerbated by radiotherapy." [PMID: 11961197] [Full Text].

Sep 21. On the Calculators page and also on the Radiation risks associated with Prostate Cancer page we add: The radiation dosage calculator will estimate your lifetime radiation exposure in mSv given the types and numbers of exposures. There is a separate post on radiation risks which has more information on this area.

Sep 18. On the Community Resources we added Masschussets Prostate Cancer Coalition: MA +.

Sep 17. On the Calculators page we add: Regarding Gleason Score upgrading, note this 2008 paper on factors making Gleason Score upgrade more likely here: [PMID: 18207180] which finds that "A total of 134 patients (50%) were upgraded postoperatively to Gleason score 7 or higher. Preoperative prostate specific antigen greater than 5.0 ng/ml (p = 0.036), prostate weight 60 gm or less (p = 0.004) and more cancer volume at biopsy, defined by cancer involving greater than 5% of the biopsy tissue (p = 0.002), greater than 1 biopsy core (p <0.001) or greater than 10% of any core (p = 0.014), were associated with pathological upgrading. Upgraded patients were more likely to have extraprostatic extension and positive surgical margins at radical prostatectomy (p <0.001 and 0.001, respectively". A second 2008 paper [PMID: 18782303] concluded that "Men with a higher PSA level, perineural invasion and high-volume cancer at biopsy are most likely to be upgraded, while men with a large prostate volume and low-volume cancer at biopsy are more likely to be downgraded. These findings have implications for men with prostate cancer managed without confirmation by RP of their true GS.". Also [PMID: 18778348] concludes that " risk of upgrading is a function of two opposing contributions: (i) a more aggressive phenotype in smaller prostates and thus increased risk of upgrading; and (ii) more thorough sampling in smaller prostates and thus decreased risk of upgrading. When sampled more thoroughly, the phenotype association dominates and smaller prostates are linked with an increased risk of upgrading. In less thoroughly sampled prostates, these opposing factors nullify, resulting in no association between prostate size and risk of upgrading. These findings help to explain previously published disparate results of the importance of prostate size as a predictor of Gleason upgrading.")

Sep 17. In Testosterone Metabolism and Prostate Cancer we add: Recently it was discovered that high blood calcium levels increase the risk of fatal prostate cancer; however, this refers to calcium in the prostate cancer cells and not the blood. [PMID: 18768497] [WebMD]. Also see [Urotoday] where hypotheses related to PTH and calcium are discussed.

Sep 16. In NIH Funded Research to be Open Access: Open access to NIH funded research appears to be in danger with bill HR 6845 being introduced to Congress by Congressmen John Conyers of Michigan and Howard Berman of California. This law, if enacted, would overturn the gains that open access has achieved under recently introduced US law (as described in this post below). See [link] for more info on this new threat.

Sep 16. In How Healthy Men Can Reduce Their Risk we add: A German company, Diapat, claims to have a urine test which is more accurate than the PSA test with a sensivitiy of 90% (i.e. of 100 patients with prostate cancer it would correctly identify 90) and a specificity of 60% (i.e. of 100 patients without prostate cancer it would correctly categorize 60). It is based on applying mass spectroscopy to the detection of various protein patterns that are present in the initial portion of a urine stream but absent in midstream. The underlying technology is claimed to be applicable not only to prostate cancer but also to cardiovascular disease, identifying 7 chronic renal diseases, early detection of diabetic renal failure, bladder cancer and is currently being further investigated for the possibility of using it as a diagnostic for Alzheimer's disease, pancreatic cancer, renal cancer and heart failure. See the Diapat web page, this company video, this [2008 paper - Abstract] [Full Text] and this [list of references].

Sep 14. After Newly Diagnosed added direct links to [surgery check list] and [waiting].

Sep 13. In RP vs LRP vs RLRP. Part 3 we add: that disappointment with robotic surgery is discussed in [PMID: 18585849] [Full Text] where the authors found that the likelihood of satisfaction among patients with open surgery was higher than patients with robotic surgery. They hypothesized that the reason was not due to actual outcomes but due to having been oversold on robotic surgery resulting in expectations were too high relative to the likely outcome whereas those who had open surgery had more realistic expectations.

Sep 13. In Biochemical PSA Recurrence we added: In [PMID: 18603352] [Full Text] the authors indicate that of those with biochemical recurrence, "25% progress to distant metastases and 11% die of prostate cancer". This same reference also contains information on predicting biochemical recurrence. Several claculators on the Calculators page also can be used to estimate the risk of biochemical recurrence.

Sep 12. In Advice to the Newly Diagnosed we added: An August 2008 paper found that obesity was associated with PSA failure after surgery and external radiation but not after brachytherapy (seeds) suggesting that brachytherapy may be more advantageous for the obese. See [PMID: 18262732]

Sep 12. In Advice to the Newly Diagnosed we added this reference to a critique of the Merglen paper: [PMID: 18775078] [Full Text].

Sep 10. In How Healthy Men Can Reduce Their Risk we add: Based on recommendations by Stephen Strum (papers) published in: PCRI Insights AUGUST 2008 VOL 11: NO 3, when having your PSA tested you should try to use the same assay at the same lab and always get tested at the same time of day (morning or afternoon, say), restrain from ejaculation in the 48 hours prior to testing avoid any examination of the prostate or athletic activity which exerts pressure on the prostate area such as bicycle riding. (There is some debate on the recommendation of avoiding prostatic examination and athletic activity.) These steps will reduce but not eliminate the random variation that occurs from one PSA test to the next. (A more comprehensive list of factors affecting PSA can be found in the Factors Affecting PSA section of PSA Screening and Early Detection Part 2 and the results of an experiment showing the natural vartiation of PSA is discussed here.)

Sep 6. In the right margin under Links on the Medical/Uro line after Pubmed we add (tags) which links to a list of tags that can be used in Pubmed queries.

Sep 6. In NIH Funded Research to be Open Access: Note that both US Presidential candidates have pledged to double NIH funding (see McCain Obama) and since all NIH funded research is now open access this promises to sharply increase the amount of research that patients have access to.

Sep 1. In Testosterone Metabolism we add

Although this result, i.e. testosterone fuels prostate cancer, is appealing in its simplicity unfortunately there is experimental evidence that seem inconsistent with it. In particular, [PMID: 18692874] found that men with lower levels of testosterone had higher grade, i.e. more aggressive, tumors. If testosterone fuels prostate cancer one would have thought that those with the highest testosterone would have the least aggressive tumors. This suggests that there must be more to the model than just testosterone.

Although removal of T kills most cancer cells, consistent with the model, Friedman points out that this destruction of the cancer cells occurs through calcium influx, i.e. calcium entering, the cells. If calcium is prevented from entering the cancer cells then 70% of the cancer cells survive even in the presence of low T. Thus it seems clear that cancer cells can very well exist without T which again seems contrary to the model. See [PMID: 2235727].

Another result that contradicts the above model is the observation, albeit in a small sample study, that the 15 year survival of prostate cancer patients who had higher DHT at diagnosis tend to survive longer than ones with lower DHT at diagnosis. If DHT were truly the key critical step then one would have expected the reverse. See [PMID: 18462534] [Full Text]

One study found that 65% of patients with androgen independent prostate cancer exhibited high levels of bcl-2. [PMID: 8996359].

We also elaborate on the results of Dambaki who showed that the mAR increase as cancer progresses: Since T interacts with mAR to increase bcl-2 while interacting with iAR to decrease bcl-2, at early stages when there is less mAR the effect of T is anti-cancer but as the ratio of mAR to iAR increases over time the balance tips and the net effect of T becomes pro-cancer.

Sep 1/08. In Pubmed Front Ends we added:

Every paper in Pubmed is assigned a pubmed id which can be used to retrieve the abstract:


Papers reporting on research that is funded by the US National Institute of Health not only appear in abstract form on Pubmed but their full text also appears in Pubmed Central and a link from the abstract to the full free text is given. (Papers that appear in Pubmed Central have both a Pubmed Id and a Pubmed Central Id. There exists a page that gives one id if you know the other [here].)

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