Faculty Bibliography

The transcriptional activity of the androgen receptor (AR) is modulated by interactions with coregulatory molecules. It has been proposed that aberrant interactions between AR and its coregulators may contribute to diseases related to AR activity, such as prostate cancer and androgen insensitivity syndrome (AIS); however, evidence linking abnormal receptor:cofactor interactions to disease is scant. The Androgen Receptor Trapped clone-27 (ART-27) is a recently identified AR N-terminal coactivator that is associated with AR-mediated growth inhibition. Here we analyze a number of naturally occurring AR mutations identified in prostate cancer and AIS for their ability to affect AR response to ART-27. Although the vast majority of AR mutations appeared capable of increased activation in response to ART-27, an AR mutation identified in prostate cancer (AR P340L) and AIS (AR E2K) show reduced transcriptional responses to ART-27, whereas their response to the p160 class of coactivators was not diminished. Relative to the wild-type receptor, less ART-27 protein associated with the AR E2K substitution, consistent with reduced transcriptional response. Surprisingly, more ART-27 associated with AR P340L, despite the fact that the mutation decreased transcriptional activation in response to ART-27. Our findings suggest that aberrant AR-coactivator association interferes with normal ART-27 coactivator function resulting in suppression of AR activity and may contribute to the pathogenesis of diseases related to alterations in AR activity, such as prostate cancer and AIS

We describe the case of a 76-year-old man with a renal cell carcinoma thrombus extending into the right atrium, prolapsing across the tricuspid valve into the right ventricle during diastole, and producing sufficient portal venous pressure to result in intestinal venous thrombosis and necrosis of the upper gastrointestinal mucosa. The related published studies are reviewed and discussed

Overactive bladder (OAB) is a debilitating condition characterised by an urgent need to urinate (urgency), often with urinary frequency and, in some cases, urgency incontinence and nocturnal frequency. Patients often adopt complex adaptive behaviours to cope with their symptoms as OAB can compromise all dimensions of a patient's quality of life. Most OAB patients present initially to their primary care physician. Diagnosis is based on presenting symptomatology and does not require any invasive tests. Direct questioning about symptoms is important in achieving a differential diagnosis. The most common condition to be considered when working towards a differential diagnosis is a urinary tract infection (UTI). However, some physicians have expressed concerns about identifying the small number of cases where bladder cancer is a potential underlying aetiology for the symptoms of OAB. In this review, we examine the prevalence and patient profiles for these bladder conditions and their presenting symptomatology. We also review tests that may be recommended to exclude a diagnosis of UTI or bladder cancer and present a diagnostic algorithm suitable for office-based primary care practice.

OBJECTIVES: To determine whether prostate-specific antigen (PSA) velocity (PSAV), used as a selection criterion for salvage radiotherapy (RT) after radical prostatectomy (RP), predicts the likelihood of response to RT in men with biochemical relapse. METHODS: We retrospectively reviewed the records of 48 patients who had undergone salvage RT for biochemical relapse after RP. All men were followed up with serial PSA measurements for a minimum of 6 months from their initial PSA recurrence, and RT was only offered to those patients with a serum PSA level remaining at less than 1.0 ng/mL. The response to RT was defined as maintenance of a PSA level of less than 0.1 ng/mL. The pathologic and clinical parameters, including PSAV, were examined to determine their individual ability to predict the response to RT. RESULTS: Of the 48 patients, 30 had maintained a PSA level of less than 0.1 ng/mL at a median follow-up of 16 months. The PSAV was strongly predictive of the likelihood of a response to salvage RT. The median relapse-free survival time for patients with a PSAV of less than 0.035 ng/mL/mo was 28 months compared with 16 months for patients with a PSAV greater than 0.035 ng/mL/mo. All other parameters tested, including Gleason score, seminal vesicle invasion, extracapsular extension, and margin status, were not predictive of the likelihood of a response to RT. CONCLUSIONS: In the present study, PSAV accurately predicted the likelihood of response to salvage RT in men with biochemical relapse after RP. No other pathologic parameters predicted the likelihood of response to RT. Using PSAV as a sole selection criterion for salvage RT after RP may allow improvement in the historically low rates of durable response

The introduction of the daVinci surgical system has changed the way both surgeon and patient view radical prostatectomy. We hypothesized that the same theoretical and tangible benefits may be realized when employing the system for partial nephrectomy. This paper reviews our technique of robot-assisted laparoscopic partial nephrectomy (RALPN) utilizing the daVinci surgical system. Intraoperative hilar clamping is utilized in all cases. With the daVinci system, the tumor is excised with cold scissors, biopsies are taken from the base for frozen-section study, sutures are placed at the base, Gelfoam/fibrin glue is activated in the defect, a Surgicel bolster is laid in the defect, and mattress sutures are placed prior to releasing the clamp. After performing 12 RALPNs, it appears this technique is safe, feasible, and reproducible both for small exophytic masses and for deeper lesions involving the collecting system. A RALPN requires two surgeons, both well versed in laparoscopic and robotic techniques

PURPOSE: Ultrasensitive prostate specific antigen (PSA) assays allow a lower limit of detection (less than 0.01 ng/ml) than standard PSA assays. In this study we examined the ability of ultrasensitive PSA nadir to predict relapse after radical prostatectomy (RP). MATERIALS AND METHODS: A total of 906 men treated with RP were followed with PSA measurements at 3, 6 and 12 months, and yearly thereafter. Of the 906 men 545 (60%) with a PSA nadir of less than 0.01 ng/ml or at least 3 followup ultrasensitive PSA measurements underwent analysis and stratification by PSA nadir. Biochemical relapse was defined as 2 consecutive increasing post-nadir PSA measurements of 0.1 ng/ml or greater. The ability of ultrasensitive PSA nadir to predict relapse was assessed by univariate and multivariate analysis. RESULTS: At a mean followup of 3.1 years 54 of 545 men (9.9%) experienced biochemical relapse with a mean time to relapse of 25.2 months. Relapse rates in men with a PSA nadir of less than 0.01 (423), 0.01 (75), 0.02 (19) and 0.04 or greater ng/ml (28) were 4%, 12%, 16% and 89%, respectively. Men with a nadir of less than 0.01 ng/ml had a significantly lower relapse rate than men with a nadir of 0.01 (p <0.01), 0.02 (p <0.025) or 0.04 or greater ng/ml (p <0.01). Multivariate logistic regression analysis showed that a nadir of 0.01 (p <0.05), 0.02 (p <0.05) and 0.04 or greater ng/ml (p <0.01) independently predicted an increased risk of biochemical relapse compared to a nadir of less than 0.01 ng/ml. CONCLUSIONS: Ultrasensitive PSA nadir accurately predicts the risk of early biochemical relapse following RP. Men who achieve a nadir of less than 0.01 ng/ml have a low likelihood of early relapse. Higher nadir points may identify candidates for early adjuvant or salvage therapies

The indications for nephron-sparing surgery and for minimally invasive surgery are continually expanding. Nephron-sparing surgery, also known as partial nephrectomy, presents a challenge to the minimally invasive surgeon. Herein, we describe our technique of robot-assisted laparoscopic partial nephrectomy. This approach may have potential advantages of including easier excision and suturing. Moderate training is required

High-grade prostatic intraepithelial neoplasia (HGPIN) is a precursor to invasive prostate cancer observed as an isolated entity in a growing subset of men undergoing prostate biopsy. The presence of HGPIN predicts an increased risk of 1) coexisting occult prostate cancer at baseline and 2) delayed progression to prostate cancer. As such, men with HGPIN represent a population at high risk for the development of prostate cancer. Because the current recommended therapy is observation and delayed-interval biopsies until cancer develops, a well-tolerated therapeutic agent capable of interrupting the progression of HGPIN to cancer is highly desirable. Given the known cancer-stimulatory effects of estrogens in the prostate, the use of selective estrogen receptor modulators (SERMs) to provide an antiestrogen effect represents a novel strategy for prostate cancer prevention. Recent phase II data from trials using toremifene in the treatment of men with HGPIN validate the use of SERMs as a rational and provocative strategy for the prevention of prostate cancer