Chemoprevention of prostate cancer with lycopene in the TRAMP model.

BACKGROUND: Dietary lycopene combined with other constituents from whole tomatoes was previously found to have greater chemopreventive effects against prostate cancer as compared to pure lycopene provided in a beadlet formulation. We hypothesized that tomato paste would have greater chemopreventive effects in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice relative to equivalent lycopene doses provided from lycopene beadlets. METHODS: Fifty-nine TRAMP mice were randomized to a control diet or to diets providing 28 mg lycopene per kg diet from tomato paste (TP) or from lycopene beadlet (LB), and sacrificed at 20 weeks. Prostate histopathology, prostate weight and serum levels of IGF-I and IGF binding protein-3 were evaluated. RESULTS: The incidence of prostate cancer was significantly decreased in the LB group relative to the control group (60% vs. 95%, respectively, P = 0.0197) whereas the difference between the TP and control groups was not statistically significant (80% vs. 95%, P = 0.34). There was no difference in prostate weights between the groups. Total lycopene levels in the serum and prostate tissue were similarly elevated in the LB and TP groups relative to the control group. The ratio of 5-cis-lycopene to trans-lycopene in the serum was significantly greater in the LB group relative to the TP group (P = 0.0001). Oxidative DNA damage was significantly reduced in the livers of mice fed LB and TP diets relative to the control group. CONCLUSIONS: This preclinical trial suggests significant chemopreventive activity with a lycopene beadlet-enriched diet. The chemopreventive effects of lycopene from beadlets versus whole tomato products requires further testing in preclinical and clinical models of prostate cancer.

Short-term perioperative outcomes of patients treated with radical cystectomy for bladder cancer included in the National Surgical Quality Improvement Program (NSQIP) database.

INTRODUCTION: We report the contemporary outcomes of radical cystectomy (RC) in patients with bladder cancer using a national, prospective perioperative database specifically developed to assess the quality of surgical care. METHODS: The National Surgical Quality Improvement Program (NSQIP) database was queried from 2006 to 2011 for RC. Data on postoperative complications, operative time, length of stay, blood transfusions, readmission, and mortality within 30 days from surgery were abstracted. RESULTS: Overall, 1094 patients undergoing RC were identified. Rates of overall complications, transfusions, prolonged length of hospitalization, readmission, and perioperative mortality were 31.1%, 34.4%, 25.9%, 20.2%, and 2.7%, respectively. Body mass index represented an independent predictor of overall complications on multivariate analysis (p = 0.04). Baseline comorbidity status was associated with increased odds of postoperative complications, prolonged operative time, transfusion, prolonged hospitalization, and perioperative mortality. In particular, patients with cardiovascular comorbidities were 2.4 times more likely to die within 30 days following cystectomy compared to their healthier counterparts (p = 0.04). Men had lower odds of prolonged operative time and blood transfusions (p ≤ 0.03). Finally, the receipt of a continent urinary diversion was the only predictor of readmission (p = 0.02). Our results are limited by their retrospective nature and by the lack of adjustment for hospital and tumour volume. CONCLUSIONS: Complications, transfusions, readmission, and perioperative mortality remain relatively common events in patients undergoing RC for bladder cancer. In an era where many advocate the need for prospective multi-institutional data collection as a means of improving quality of care, our study provides data on short-term outcomes after RC from a national quality improvement initiative.

Comparative effectiveness of robot-assisted and open radical prostatectomy in the postdissemination era.

PURPOSE: Given the lack of randomized trials comparing robot-assisted radical prostatectomy (RARP) and open radical prostatectomy (ORP), we sought to re-examine the outcomes of these techniques using a cohort of patients treated in the postdissemination era. PATIENTS AND METHODS: Overall, data from 5,915 patients with prostate cancer treated with RARP or ORP within the SEER-Medicare linked database diagnosed between October 2008 and December 2009 were abstracted. Postoperative complications, blood transfusions, prolonged length of stay (pLOS), readmission, additional cancer therapies, and costs of care within the first year after surgery were compared between the two surgical approaches. To decrease the effect of unmeasured confounders, instrumental variable analysis was performed. Multivariable logistic regression analyses were then performed. RESULTS: Overall, 2,439 patients (41.2%) and 3,476 patients (58.8%) underwent ORP and RARP, respectively. In multivariable analyses, patients undergoing RARP had similar odds of overall complications, readmission, and additional cancer therapies compared with patients undergoing ORP. However, RARP was associated with a higher probability of experiencing 30- and 90-day genitourinary and miscellaneous medical complications (all P ≤ .02). Additionally, RARP led to a lower risk of experiencing blood transfusion and of having a pLOS (all P < .001). Finally, first-year reimbursements were greater for patients undergoing RARP compared with ORP (P < .001). CONCLUSION: RARP and ORP have comparable rates of complications and additional cancer therapies, even in the postdissemination era. Although RARP was associated with lower risk of blood transfusions and a slightly shorter length of stay, these benefits do not translate to a decrease in expenditures.

Early detection, PSA screening, and management of overdiagnosis.

Prostate cancer diagnosis and treatment rates have increased significantly since the introduction of prostate-specific antigen (PSA) screening. Although it was initially thought that most prostate cancers would lead to death or significant morbidity, recent randomized trials have demonstrated that many patients with screening-detected cancer will not die of their disease. Modifications to PSA screening, screening guideline statements, and novel screening markers have been developed to minimize the risk and morbidity associated with overdiagnosis and overtreatment. Less aggressive management strategies such as active surveillance may lead to lower treatment rates in men who are unlikely to benefit while maintaining cure rates.

Selective suture ligation of the dorsal vein complex during robot-assisted laparoscopic radical prostatectomy.

Technique for apical dissection and control of the dorsal vein complex (DVC) during robot-assisted laparoscopic radical prostatectomy (RALP) affects blood loss, apical positive margins, and recovery of urinary control. Over the past 7 years, our technique for apical dissection has been spurred by the overarching goal of minimizing injury to the rhabdosphincter to improve urinary continence, evolving from stapling to suture ligation of the DVC before bladder neck dissection to an athermal DVC division followed by selective suture ligation (DVC-SSL) before RALP anastomosis. Assessment of patient-reported quality of life outcomes demonstrates earlier recovery of continence with DVC-SSL.

Effect of a low-fat diet combined with IGF-1 receptor blockade on 22Rv1 prostate cancer xenografts.

In preclinical models, both dietary fat reduction and insulin-like growth factor I receptor (IGF-1R) blockade individually inhibit prostate cancer xenograft growth. We hypothesized that a low-fat diet combined with IGF-1R blockade would cause additive inhibition of prostate cancer growth and offset possible untoward metabolic effects of IGF-1R blockade antibody therapy. Fifty severe combined immunodeficient mice were injected with 22Rv1 cells subcutaneously. Ten days postinjection, the animals were randomized to four groups: (i) high-fat diet + saline (HF); (ii) high-fat diet + IGF-1R blocking antibody, ganitumab (HF/Ab); (iii) low-fat diet + saline (LF); and (iv) low-fat diet + ganitumab (LF/Ab). After 19 days of treatment, the animals were euthanized, serum was collected, and tumors were weighed. Tumor Ki67, Akt and extracellular signal-regulated kinase (ERK) activation, serum insulin, IGF-I and TNF-α were measured. In vitro, ganitumab treatment inhibited growth and induced apoptosis in several prostate cancer cell lines. In vivo, tumor weights and volumes were unaffected by the different treatments. The LF/Ab therapy significantly reduced proliferation (Ki67) and ERK activation in tumors. The HF/Ab group had significantly higher serum insulin levels than the HF group. However, LF/Ab combination significantly reduced serum insulin back to normal levels as well as normalizing serum TNF-α level. Whereas the combination of low-fat diet and IGF-1R blockade did not have additive inhibitory effects on tumor weight, it led to reduced tumor cell proliferation and a reduction in serum insulin and TNF-α levels.

Phase II prospective randomized trial of a low-fat diet with fish oil supplementation in men undergoing radical prostatectomy.

Preclinical studies suggest lowering dietary fat and decreasing the ratio of omega-6 to omega-3 polyunsaturated fatty acids decreases the risk of prostate cancer development and progression. We conducted a phase II randomized trial to test the effect of decreasing dietary fat combined with decreasing the dietary omega-6:omega-3 ratio on biomarkers related to prostate cancer development and progression. Patients undergoing radical prostatectomy were randomly assigned to receive a low-fat diet with 5 grams of fish oil daily (dietary omega-6:omega-3 ratio of 2:1) or a control Western diet (omega-6:omega-3 ratio of 15:1) for four to six weeks prior to surgery. The primary endpoint was change in serum insulin-like growth factor I (IGF-1) between arms. Secondary endpoints were serum IGFBP-1, prostate prostaglandin E2 levels, omega-6:omega-3 fatty acid ratios, COX-2, and markers of proliferation and apoptosis. Fifty-five patients were randomized and 48 completed the trial. There was no treatment difference in the primary outcome. Positive secondary outcomes in the low-fat fish oil versus Western group were reduced benign and malignant prostate tissue omega-6:omega-3 ratios, reduced proliferation (Ki-67 index), and reduced proliferation in an ex vivo bioassay when patient sera was applied to prostate cancer cells in vitro. In summary, four to six weeks of a low-fat diet and fish oil capsules to achieve an omega-6:omega-3 fatty acid ratio of 2:1 had no effect on serum IGF-1 levels, though in secondary analyses, the intervention resulted in decreased prostate cancer proliferation and decreased prostate tissue omega-6:omega-3 ratios. These results support further studies evaluating reduction of dietary fat with fish oil supplementation on modulating prostate cancer biology.

Placenta percreta and the urologist.

Placenta percreta, the rarest and most severe form of placenta accreta, can involve the urinary bladder. Because of its propensity for severe hemorrhage, it is a potentially life-threatening condition. Although commonly discovered at the time of delivery, antenatal diagnosis may be achieved with ultrasound, magnetic resonance imaging, and/or cystoscopy. Every attempt should be made to minimize potential for blood loss by avoiding removal of the placenta at the time of delivery and either performing a hysterectomy or using methotrexate therapy to ablate the residual placenta in the postpartum period. If hemorrhage does occur during delivery, immediate surgical removal of the uterus should be considered and, depending on the severity of the hemorrhage and the depth of invasion of the placenta into the bladder, excision and/or reconstruction of the bladder may be necessary.

Myelomeningocele information on the internet is accessible and of variable quality, and requires a high reading level.

PURPOSE: We assessed the accessibility, readability and quality of myelomeningocele information on the Internet. MATERIALS AND METHODS: We entered the term "spina bifida" into the Google, Yahoo! and Microsoft Network search engines, and stored the first 100 links from each Web site. A total of 164 unique Web sites remained for analysis, of which 159 were classified as relevant. Relevant Web sites were considered to have relevant content if more than 50% of the text was directly relevant to the disease, and to have relevant educational content if more than 50% of the text was aimed at relaying educational information. Readability was assessed using the Flesch-Kincaid Grade Level scale. The quality of the 159 Web sites with relevant content was assessed using American Public Health Association Criteria for Assessing Health Information on the Internet. Six criteria were assessed, namely credibility, content, links, design, interactivity and caveats. Web sites were analyzed by 2 separate medical doctors, with each reviewer blinded to the findings of the other. A weighted kappa statistic was used to calculate interrater reliability. RESULTS: Of 159 relevant sites 146 (91.8%) had relevant content and 122 (76.7%) had relevant educational content. The average Flesch-Kincaid reading level was 10.9 (range 6 to 12). Quality was assessed on a 3-point scale, with 1 denoting poor quality, 2 fair and 3 good. Average scores were 1.92 for credibility, 1.88 for content, 2.29 for links, 2.53 for design, 1.99 for interactivity and 2.90 for caveats. The weighted kappa statistic for interrater reliability was 0.83. CONCLUSIONS: Myelomeningocele information on the Internet is relatively accessible, requires a high reading level for comprehension and is of variable quality.

Patterns of recurrence and surveillance strategies for renal cell carcinoma following surgical resection.

Renal cell carcinoma (RCC) remains one of the most lethal urologic malignancies, with up to 40% of patients eventually dying of cancer progression. Despite advances in the diagnosis, staging and treatment of patients with RCC, approximately a third of patients who undergo surgery for clinically localized RCC will suffer a recurrence. Timely identification of recurrences following surgical extirpation is imperative in the treatment of these patients. RCC is known to metastasize through hematogenous routes of spread to distant organ sites and via lymphatic channels to regional lymph nodes. The path of tumor escape is associated with diverse clinical outcomes and a unique tumor biology. A consensus on surveillance regimens for patients following surgical resection of localized disease is lacking. The most extensively used system for providing prognostic information regarding survival and recurrence of disease has historically been the tumor-node-metastasis (TNM) classification system. As a result, most contemporary surveillance protocols have tailored follow-up regimens according to stage-based stratifications. Numerous studies have recently demonstrated that certain clinical and histopathological factors can improve the prediction of tumor recurrence. The incorporation of these prognostic factors into stage-based stratification models should be better than stage alone in attempting to provide a rational approach to identifying treatable recurrences while minimizing unnecessary exams and tests, as well as patient anxiety. Advances in the understanding of the pathogenesis, behavior and molecular biology of RCC have paved the way for developments that may enhance early diagnosis and prognostication, and improve survival for patients. Lastly, molecular markers should, in the future, revolutionize surveillance protocols for RCC by tailoring follow-up to specific molecular classifications.

Steroid receptors and mammalian penile development: an unexpected role for progesterone receptor?

PURPOSE: We investigated the role of steroid receptors in normal and abnormal genital tubercle development in males and females. We hypothesized that progesterone receptor expression might be involved in abnormal development in both sexes. MATERIALS AND METHODS: We examined the effects of medroxyprogesterone acetate on steroid receptor mRNA expression and assessed the involvement of androgen receptor in the action of medroxyprogesterone acetate on genital tubercle development using androgen receptor deficient (Tfm) mice. RESULTS: Quantitative reverse transcriptase polymerase chain reaction and morphological results demonstrated a pattern of virilized females and feminized males in medroxyprogesterone acetate exposed embryos. Progesterone receptor was the only steroid receptor examined that did not differ between medroxyprogesterone acetate treated males and vehicle treated females. At the morphological level in utero exposure to medroxyprogesterone acetate from gestational days 12 to 17 feminized male genital tubercles, producing a more proximal urethral opening. Female fetuses exposed for the same period exhibited virilized genitalia, with a more distal urethral opening. We also exposed Tfm mice to medroxyprogesterone acetate to assess the role of androgen receptor in the activity of medroxyprogesterone acetate. These medroxyprogesterone acetate exposed mice did not differ morphologically from vehicle treated Tfm mice, indicating that medroxyprogesterone acetate requires androgen receptor to elicit genital tubercle abnormalities. CONCLUSIONS: The increase of progesterone receptor mRNA expression in males and the decrease in females as a result of exposure to medroxyprogesterone acetate, which also causes urethral abnormalities in both sexes, suggests a previously unidentified role for progesterone receptor, possibly interacting with androgen receptor, in anomalous genital tubercle development.