The Tuesday news report: January 20, 2009

Today’s inauguration day (here in the USA) news reports address:

  • Obesity and prostate cancer screening PSA levels
  • The possible association of bone mineral density with prostate cancer risk in older men
  • Soy, genistein, and the inhibition of prostaglandins
  • Pathologic prostate specimen weight and perioperative outcomes in LRP

Rundle et al. have attempted to resolve the two competing hypotheses used to explain the observed inverse association between obesity and screening PSA levels. One hypothesis is that endocrine disturbances related to abdominal obesity influence PSA production. The other proposes that increased plasma volume associated with obesity dilutes PSA. Under the endocrine disturbance hypothesis, fat mass (but not lean mass) and an abdominal distribution of fat are expected to be inversely associated with PSA levels. Under the plasma volume dilution theory, PSA levels are inversely associated with both lean and fat mass and are independent of body fat distribution patterns. The authors used data on weight, percent body fat, and waist circumference from approximately 8,000 men undergoing routine PSA screening to evaluate the potential acuracy of the two hypotheses. PSA levels were significantly inversely associated with both lean and fat mass. The authors’ results were clearly more consistent with predictions arising from the volume dilution theory than the hormone disturbance theory.

Farhat et al. have investigated the association of bone mineral density (BMD) with prostate cancer risk in older men enrolled in the Osteoporotic Fractures in Men Study. They hypothesized that men aged ≥ 65 years with higher BMD (a marker of exposure to endogenous sex hormones) would have an increased incidence of prostate cancer. The cohort included 4,597 men (89 percent White) with no prior history of prostate cancer. Baseline total body, total hip, and spine BMD were assessed. Prostate cancer was confirmed by review of medical records. Over an average follow-up of 5.2 years, 255 men (5.6 percent) developed prostate cancer. Total body BMD was inversely associated with incident prostate cancer, with a significant trend for decreasing risk with increasing BMD quartiles. Men in the highest total body BMD quartile had a 41 percent reduced risk for prostate cancer compared with men in the lowest quartile. The authors state that their results “provide support for an inverse association between BMD and [prostate cancer] risk.”

Swami et al. have studied the effects of soy and its constituent isoflavone genistein in cultured cells and in prostate cancer patients. They believe that their research reveals a novel pathway for the actions of genistein, namely the inhibition of the synthesis and biological actions of prostaglandins (PGs), which are known stimulators of prostate cancer growth. In their experiments, genistein significantly reduced the secretion of PGE(2). Secretion of EP4 and FP PG receptor mRNA were also reduced by genistein, providing an additional mechanism for the suppression of the biological effects of PG. Swami et al. also performed a pilot randomized double-blind clinical study in which placebo or soy isoflavone supplements were given to prostate cancer patients for 2 weeks before prostatectomy. Gene expression changes were measured in the prostatectomy specimens. They observed significant decreases in prostate COX-2 mRNA and increases in p21 mRNA among men ingesting isoflavones. There were significant correlations between COX-2 mRNA suppression, p21 mRNA stimulation, and serum isoflavone levels. The authors propose that the inhibition of the PG pathway contributes to the beneficial effect of soy isoflavones in prostate cancer chemoprevention and/or treatment.

The relationship between pathologic prostate specimen weight and perioperative outcomes in laparoscopic radical prostatectomy (LRP) has been analyzed in numerous small series. Levinson et al. have now analyzed data from  802 consecutive patients who underwent LRP for localized prostate cancer between April 2001 and April 2007. Complete perioperative data were available for 720 of these men (90 percent). The patients were categorized into three groups by pathologic specimen weight: < 35 g, 35-70 g, and > 70 g, and outcomes were assessed. Outcomes were also analyzed using prostate weight as a continuous variable. The mean age, body mass index (BMI), preoperative PSA level, and postoperative Gleason score were 57.6 years, 26.7 kg/m2, 5.9 ng/ml, and 6.3, respectively. The mean pathologic specimen weight was 51.3 g. When compared with lighter counterparts, patients with the heaviest glands were older, had a higher PSA level, and had a higher percentage of pathologically organ-confined disease. Increasing prostate weight was associated with longer operative times, more blood loss, longer lengths of stay, and more perioperative complications. Smaller glands showed a trend toward a higher rate of positive surgical margins overall and in pT2 disease, but there was no association between surgical margins and gland size in pT3 disease. Increasing BMI was also independently predictive of positive margins regardless of prostate size.

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