Faculty Bibliography

PURPOSE: We describe the literature base pertaining to adrenalectomy at radical nephrectomy and present a pragmatic approach based on primary tumor and disease characteristics. MATERIALS AND METHODS: Literature searches were performed via the National Center for Biotechnology Information databases using various keywords. Articles that pertained to the concomitant use of adrenalectomy with radical nephrectomy were surveyed. RESULTS: The incidence of solitary, synchronous, ipsilateral adrenal involvement, ie that which is potentially curable with ipsilateral adrenalectomy along with nephrectomy, is much lower than previously thought at 1% to 5%. Evidence to date supports increased size and T stage, multifocality, upper pole location and venous thrombosis as risk factors for adrenal involvement. Cross-sectional imaging is now accurate at demonstrating the absence of adrenal involvement but still carries a significant risk of false-positives. The morbidity of adrenalectomy is minimal except in those patients with metachronous contralateral adrenal metastasis in whom the impact of adrenal insufficiency can be devastating. Disease specific and overall survival of those undergoing radical nephrectomy, with or without adrenalectomy, are similar. The survival of patients with widespread metastatic disease is historically poor regardless of whether adrenalectomy is performed. There is evidence for a survival advantage in patients with isolated adrenal metastasis, although this group comprises no more than 2% of those undergoing surgery for renal tumors. CONCLUSIONS: The apparent benefit of ipsilateral adrenalectomy does not support it as a standard practice in all patients with normal imaging. However, it should be considered in select cases in which there are risk factors for adrenal involvement

The androgen receptor (AR) directs diverse biological processes through interaction with coregulators such as AR trapped clone-27 (ART-27). Our results show that ART-27 is recruited to AR-binding sites by chromatin immunoprecipitation analysis. In addition, the effect of ART-27 on genome-wide transcription was examined. The studies indicate that loss of ART-27 enhances expression of many androgen-regulated genes, suggesting that ART-27 inhibits gene expression. Surprisingly, classes of genes that are up-regulated upon ART-27 depletion include regulators of DNA damage checkpoint and cell cycle progression, suggesting that ART-27 functions to keep expression levels of these genes low. Consistent with this idea, stable reduction of ART-27 by short-hairpin RNA enhances LNCaP cell proliferation compared with control cells. The effect of ART-27 loss was also examined in response to the antiandrogen bicalutamide. Unexpectedly, cells treated with ART-27 siRNA no longer exhibited gene repression in response to bicalutamide. To examine ART-27 loss in prostate cancer progression, immunohistochemistry was conducted on a tissue array containing samples from primary tumors of individuals who were clinically followed and later shown to have either recurrent or nonrecurrent disease. Comparison of ART-27 and AR staining indicated that nuclear ART-27 expression was lost in the majority of AR-positive recurrent prostate cancers. Our studies show that reduction of ART-27 protein levels in prostate cancer may facilitate antiandrogen-resistant disease

OBJECTIVES: To report a technique of stomal creation before abdominal wall transposition of the conduit that reduces asymmetry, retraction, and stenosis of the stoma. The ileal conduit remains the most common form of urinary diversion. Despite extensive experience with the procedure, a significant rate of stomal complications is still observed. METHODS: Unlike the traditional approach, after the segment of the distal ileum is selected and excluded from the bowel continuity, the stoma is prepared intracorporeally. The critical elements of this technique include defatting of the distal mesentery, placement of everting sutures immediately adjacent to the bowel mesentery in a diamond configuration, full-thickness locking sutures to fix the eversion, and fascial fixation sutures on abdominal wall transposition. RESULTS: The technique of early stomal maturation has been performed in 45 consecutive ileal conduit procedures. To date, early stomal retraction with poor appliance fit has been observed in 1 patient who underwent simultaneous abdominal wall reconstruction, requiring early revision of the stoma. The remaining stomas have demonstrated excellent protrusion with no requirement for revision owing to stenosis or retraction. CONCLUSIONS: To date, we have experienced excellent outcomes with the technique, independent of body habitus or mesenteric thickness. The usual tendency of the stoma to be flush at the position of the mesentery is avoided, and symmetric protrusion of the stoma appears to allow a better stomal appliance fit. The effect on long-term complication rates remains to be defined

Laparoscopic partial nephrectomy (LPN) has been underused because of its technical complexity and difficulty. We present a knotless and bolsterless technique that allows simultaneous repair of the pelvicaliceal system and compression of the parenchyma defect using a series of single-pass running sutures. We believe that this technique will simplify reconstruction and aid in popularization of LPN

PURPOSE: Because many investigators have suggested that ideal candidates for focal therapy are those with unilateral prostate cancer, we evaluated whether these men are at decreased risk for adverse pathological and oncological outcomes. MATERIALS AND METHODS: We reviewed the charts of 1,458 consecutive patients who underwent open radical prostatectomy, as performed by a single surgeon. Patients were divided into 311 with unilateral (group 1) and 1,147 with bilateral (group 2) disease on final surgical pathology. They were also substratified by clinical risk into low risk (prostate specific antigen less than 10 ng/ml, clinical stage less than T2b or Gleason score less than 7) and high risk groups. The groups were compared with respect to extracapsular extension, seminal vesical invasion, percent of tumor involvement, pathological Gleason score and biochemical recurrence. RESULTS: Compared to patients with bilateral disease those with unilateral disease had a lower rate of extracapsular extension (p = 0.004), seminal vesical invasion (p = 0.003), greater than 10% tumor involvement (p <0.001) and Gleason score 7 or greater (p <0.001). At a median followup of 36 months 8.3% and 16.7% of the men in groups 1 and 2, respectively, experienced biochemical recurrence (p = 0.001). Low risk disease was more prevalent in those with unilateral disease than in those with bilateral disease. Of men with low risk disease the risk of adverse pathological features/biochemical recurrence did not differ between groups 1 and 2. CONCLUSIONS: Although men with unilateral prostate cancer have more favorable oncological outcomes than those with bilateral prostate cancer, this appears to be due to the higher prevalence of low risk disease. While focality/laterality may direct the method of subtotal gland treatment, clinical risk features may be adequate to select candidates for focal therapy

OBJECTIVES: To develop a logistic regression-based model to predict prostate cancer biopsy at, and compare its performance to the risk calculator developed by the Prostate Cancer Prevention Trial (PCPT), which was based on age, race, prostate-specific antigen (PSA) level, a digital rectal examination (DRE), family history, and history of a previous negative biopsy, and to PSA level alone. PATIENTS AND METHODS: We retrospectively analysed the data of 1280 men who had a biopsy while enrolled in a prospective, multicentre clinical trial. Of these, 1108 had all relevant clinical and pathological data available, and no previous diagnosis of prostate cancer. Using the PCPT risk calculator, we calculated the risks of prostate cancer and of high-grade disease (Gleason score > or =7) for each man. Receiver operating characteristic (ROC) curves for the risk calculator, PSA level and the novel regression-based model were compared. RESULTS: Prostate cancer was detected in 394 (35.6%) men, and 155 (14.0%) had Gleason > or =7 disease. For cancer prediction, the area under the ROC curve (AUC) for the risk calculator was 66.7%, statistically greater than the AUC for PSA level of 61.9% (P < 0.001). For predicting high-grade disease, the AUCs were 74.1% and 70.7% for the risk calculator and PSA level, respectively (P = 0.024). The AUCs increased to 71.2% (P < 0.001) and 78.7% (P = 0.001) for detection and high-grade disease, respectively, with our novel regression-based models. CONCLUSIONS: ROC analyses show that the PCPT risk calculator modestly improves the performance of PSA level alone in predicting an individual's risk of prostate cancer or high-grade disease on biopsy. This predictive tool might be enhanced by including percentage free PSA and the number of biopsy cores

OBJECTIVES: To assess the prevalence and pathologic features of men with unilateral prostate cancer at radical prostatectomy (RP), because it has recently been proposed that men with small-volume, well-differentiated, unilateral prostate cancer can be treated with focal therapy. METHODS: The records of 1467 consecutive men who underwent open RP by a single surgeon from January 2000 to June 2007 were reviewed after institutional review board approval. The RP pathologic reports were analyzed to determine the frequency of unilateral or bilateral disease, surgical margin status, presence of extracapsular extension, seminal vesicle invasion, Gleason score, percentage of tumor involvement (PTI), prostate-specific antigen (PSA) level, and prostate volume. Logistic regression analysis was performed to analyze the relationship between these factors and the detection of unilateral disease. RESULTS: Unilateral cancer was identified in 313 of 1467 patients (21.3%). Of these patients, 206 had a PTI of < or = 5%, 40 had a PTI of 5%-10%, 8 had a PTI of 10%-15%, and 40 had a PTI > 15%. The factors significantly associated with unilateral disease on univariate analysis were PTI, PSA level, pathologic Gleason score, seminal vesicle invasion, and extracapsular extension. The PSA level and seminal vesicle invasion remained significant predictors on multivariate analysis. Overall, 163 men (11.1%) had unilateral, low-risk disease (defined as a PSA level < 10 ng/mL, Gleason score < 7, and PTI < 10%). CONCLUSIONS: Although candidates for focal therapy exist among men undergoing RP within a contemporary cohort, they represent a small minority. Before proceeding with focal therapy, the urology community must identify accurate methods of candidate selection

OBJECTIVES: To summarize the debate regarding use of intermittent androgen suppression therapy in the treatment of prostate cancer originally presented at the 2007 Spring Meeting of the Society of Urologic Oncology. METHODS: The debate was framed within the context of known toxicities of therapy and impact on quality of life. Arguments for and against IAS were summarized. RESULTS: IAS appears to be a reasonable treatment approach for men with advanced prostate cancer except those with high risk features including PSA > 20, or bone metastatic disease. Men with TxN1-3M0 who are sexually active, compliant to close follow-up, or who do not tolerate the side effects of androgen ablation can be considered for IAS as long as they realize it is investigational. There is not a clear consensus upon duration of treatment, interval between treatment cycles, or appropriate PSA nadir, but it does appear that PSA nadir > 4 ng/ml may predict a poor outcome. Based on time to PSA nadir and changes in expression of proliferation markers staining, treatment duration of 6 to 9 months is recommended prior to stopping therapy. Trigger points for restarting therapy are individualized, and factors that are considered include pretreatment PSA levels, stage, PSA velocity, presence of symptoms, and tolerance of androgen ablation therapy. CONCLUSIONS: IAS should be considered in the management of men with advanced prostate cancer and no evidence of bone metastases. While intermittent therapy is feasible and offers potential improvement in quality of life, it is not yet shown that it reverses the long-term side effects of androgen suppression