Faculty Bibliography

PURPOSE: Intracorporeal injections have low use rates and high discontinuation rates. We examined factors associated with intracorporeal injection use, long-term satisfaction with intracorporeal injection and reasons for discontinuation in men treated with radical prostatectomy. MATERIALS AND METHODS: Between October 2000 and September 2003, 731 men who underwent open radical retropubic prostatectomy were enrolled in a prospective outcomes study. The 8-year followup evaluation included the UCLA-PCI, and a survey capturing intracorporeal injection use, satisfaction and reasons for discontinuation. Logistic regression was used to determine associations between intracorporeal injection use and preoperative variables. RESULTS: The 8-year self-assessment was completed by 368 (50.4%) men. Of these men 140 (38%) indicated prior or current intracorporeal injection use, with only 34 using intracorporeal injection at 8 years. Overall, 44% of the men were satisfied with intracorporeal injections. Reasons for discontinuation included dislike (47%), pain (33%), return of erection (19%), inefficacy (14%) and no partner (6%). Men trying intracorporeal injections had greater preoperative UCLA-PCI sexual function scores (75.2 vs 65.62, p = 0.00005) as well as greater decreases in this score at 3 months (p = 0.0002) and 2 years (p = 0.003). Higher preoperative sexual function scores were independently associated with the use of intracorporeal injections in a model adjusted for age, marital status, nerve sparing status and body mass index (OR 1.021, 95% CI 1.008-1.035). CONCLUSIONS: Men pursuing intracorporeal injections have better baseline erectile function and experience greater deterioration in erectile function during the early postoperative period. Despite the high efficacy of injections, many men discontinue intracorporeal injections due to dislike or discomfort. Satisfaction rates for intracorporeal injections indicate their long-term role in restoring sexual function in men with post-prostatectomy erectile dysfunction.

Integration of cellular signaling pathways with androgen receptor (AR) signaling can be achieved through phosphorylation of AR by cellular kinases. However, the kinases responsible for phosphorylating the AR at numerous sites and the functional consequences of AR phosphorylation are only partially understood. Bioinformatic analysis revealed AR serine 213 (S213) as a putative substrate for PIM1, a kinase overexpressed in prostate cancer. Therefore, phosphorylation of AR serine 213 by PIM1 was examined using a phosphorylation site-specific antibody. Wild-type PIM1, but not catalytically inactive PIM1, specifically phosphorylated AR but not an AR serine-to-alanine mutant (S213A). In vitro kinase assays confirmed that PIM1 can phosphorylate AR S213 in a ligand-independent manner and cell type-specific phosphorylation was observed in prostate cancer cell lines. Upon PIM1 overexpression, AR phosphorylation was observed in the absence of hormone and was further increased in the presence of hormone in LNCaP, LNCaP-abl and VCaP cells. Moreover, phosphorylation of AR was reduced in the presence of PIM kinase inhibitors. An examination of AR-mediated transcription showed that reporter gene activity was reduced in the presence of PIM1 and wild-type AR, but not S213A mutant AR. Androgen-mediated transcription of endogenous PSA, Nkx3.1 and IGFBP5 was also decreased in the presence of PIM1, whereas IL6, cyclin A1 and caveolin 2 were increased. Immunohistochemical analysis of prostate cancer tissue microarrays showed significant P-AR S213 expression that was associated with hormone refractory prostate cancers, likely identifying cells with catalytically active PIM1. In addition, prostate cancers expressing a high level of P-AR S213 were twice as likely to be from biochemically recurrent cancers. Thus, AR phosphorylation by PIM1 at S213 impacts gene transcription and is highly prevalent in aggressive prostate cancer.Oncogene advance online publication, 17 September 2012; doi:10.1038/onc.2012.412.

Epidemiologic and experimental data suggest that soy consumption may prevent prostate cancer and be beneficial for men with prostate cancer. Soy intake and risk of prostate cancer are inversely correlated; soy isoflavones inhibit growth of prostate cancer cells and reduce prostate carcinogenesis in animal models. We tested the hypothesis that soy consumption reduces biochemical recurrence after radical prostatectomy in a randomized controlled clinical trial with a soy protein supplement versus a casein-based placebo in men at increased risk for PSA failure in the first 2 years after radical prostatectomy. PSA was tested at 2-month intervals in year 1 and every 3 months in year 2. Eligibility criteria were: Gleason sum of >8, extra-capsular extension, seminal vesicle invasion, positive surgical margins, positive lymph nodes, and/or a preoperative PSA of >20 ng/ml. Biochemical recurrence was defined a priori as reaching a PSA value of alpha0.07 ng/ml, confirmed twice. A two-year PSA failure rate in eligible subjects of approximately 30% was expected, based on data from NYU and previous literature. With a planned sample size of 128 evaluable subjects per arm, the study had 80% power to detect a 50% reduction in PSA failure rate at a 2-sided significance level of 0.05. The soy protein isolate and placebo (generously provided by Solae LCC, St Louis, MO) were identical in composition, except for the protein source (19.2-19.8 g protein/day); the soy product provided daily 23.5 mg genistein and 40.9 mg total isoflavones (aglycone equivalents); the placebo was devoid of any soy-specific constituents. Accrual did not reach the intended level and 172 subjects were randomized and enrolled, of whom 142 were evaluable (completed two years on study or developed confirmed recurrence within two years). Soy protein consumption did not alter recurrence rate or time-to-recurrence (TTR). Of the 74 evaluable subjects in the soy arm 22 (30%) recurred as did 22 (32%) of the 68 subjects in the placebo arm recurred. The!

Retraction of the bowels during abdominal surgery is generally facilitated by the use of a combination of various retractors along with surgical towels or sponges. The use of surgical towels and sponges may lead to retained foreign bodies or adhesions. In addition, these towels and sponges often require manipulation during long surgical procedures. The ideal way to avoid these problems in abdominal surgery is to develop a technique for retraction of the abdominal contents that eliminates the requirement for these foreign bodies. This article presents the results of a small trial for Lap Pak (Seguro Surgical, Columbia, MD), a disposable radio-opaque device that is made of silicone and retracts the bowels in a cephalad orientation without the need for towels or sponges.

Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Some studies have evaluated preoperative and intraoperative examination for inguinal hernias and their repair, noting a decrease in the rate of post-prostatectomy hernias. However, this did not eradicate post-prostatectomy hernias, indicating that this method probably missed subclinical hernias. Other studies looked at prophylactic procedures to prevent the formation of inguinal hernias at the time of prostatectomy and showed a decrease in the rate of postoperative hernias. To our knowledge this is the only series evaluating a multi-modal approach with magnetic resonance imaging, ultrasonography and examination to identify all clinical and subclinical hernias and repair them at the time of prostatectomy. This approach only subjects those patients at risk for symptomatic hernias to an additional procedure and decreases the post-prostatectomy hernia rate to <1%. OBJECTIVE: * To assess if a comprehensive evaluation to diagnose clinical and subclinical hernias and repair of these hernias at the time of open radical retropubic prostatectomy (ORRP) decreases the incidence of clinical inguinal hernias (IHs) after ORRP. PATIENTS AND METHODS: * Between 1 July 2007 and 31 July 2010, 281 consecutive men underwent ORRP by a single surgeon. * Of these men, 207 (74%) underwent comprehensive preoperative screening for IH, which included physical examination, upstanding ultrasonography and magnetic resonance imaging. * Between 12 and 24 months after ORRP, 178 (86%) of these men completed a questionnaire designed to capture development of clinical IHs. RESULTS: * Of the 178 evaluable patients, 92 (52%) were diagnosed preoperatively with IH by at least one diagnostic modality. * Forty-one and 51 of the men had bilateral or unilateral IHs, respectively for a total of 133 IHs. * No preoperative factor was significantly associated with the presence of an IH before prostatectomy. * No groin subjected to IH repair (IHR) at the time of ORRP developed a clinical IH compared with four of the 21 patients with postoperative IHs who did not undergo repair of their preoperatively diagnosed IH at the time of ORRP (P= 0.024). * Only one (0.4%) clinical IH developed in a groin that had no evidence of IH by physical examination, upstanding ultrasonography and magnetic resonance imaging before prostatectomy. CONCLUSIONS: * Our comprehensive evaluation increases the detection of IHs before ORRP. * Repair of these IHs at the time of ORRP significantly decreases the risk of developing post-prostatectomy clinical IHs.

The most recent guidelines on prostate cancer screening from the American Urological Association (2009), the National Comprehensive Cancer Network (2011), and the European Association of Urology (2011), as well as treatment and advances in disease monitoring, have increased the androgen deprivation therapy (ADT) population and the duration of ADT usage as the first-line treatment for metastatic prostate cancer. According to the European Association of Urology, gonadotropin-releasing hormone (GnRH) agonists have become the leading therapeutic option for ADT because they avoid the physical and psychological discomforts associated with orchiectomy. However, GnRH agonists display several shortcomings, including testosterone (T) surge ("clinical flare") and microsurges. T surge delays the intended serologic endpoint of T suppression and may exacerbate clinical symptoms. Furthermore, ADT manifests an adverse-event spectrum that can impact quality of life with its attendant well-documented morbidities. Strategies to improve ADT tolerability include a holistic management approach, improved diet and exercise, and more specific monitoring to detect and prevent T depletion toxicities. Intermittent ADT, which allows hormonal recovery between treatment periods, has become increasingly utilized as a methodology for improving quality of life while not diminishing chronic ADT efficacy, and may also provide healthcare cost savings. This review assesses the present and potential future role of GnRH agonists in prostate cancer and explores strategies to minimize the adverse-event profile for patients receiving ADT.