Faculty Bibliography

Partial nephrectomy has proved to be a safe and effective treatment modality, even for patients with normal contralateral kidneys. The indications for elective partial nephrectomy continue to evolve as contemporary series demonstrate low morbidity approaching that of radical nephrectomy. Furthermore, patients who undergo partial nephrectomy have a significantly decreased risk of future renal insufficiency. As such, a rationale exists for expanding indications in an era of excellent technical outcomes and increased patient longevity. Characterization of newer diagnostic (three-dimensional imaging) and treatment (laparoscopic partial nephrectomy, cryosurgery) modalities will allow continued evolution of nephron-sparing techniques

PURPOSE: The purpose is to investigate the clinical relevance of altered patterns of p27 and Skp2 expression in African-American patients with localized prostate cancer. The abundance of p27, an inhibitor of cell proliferation, is controlled by Skp2-dependent proteolysis. EXPERIMENTAL DESIGN: A well-characterized cohort of 162 African-Americans who underwent radical prostatectomy at the Veterans Affairs Medical Center of New York between 1990 and 2000 was studied. We analyzed p27 and Skp2 expression by immunohistochemistry. Altered expression of p27 (defined as <40% tumor cells expressing the protein) and Skp2 (defined as > or ==' BORDER='0'>20% tumor cells expressing the protein) were correlated with clinicopathological parameters and time to prostate-specific antigen (PSA) recurrence. RESULTS: Altered expression of p27 and Skp2 was observed in 112 of 162 (69.1%) and 93 of 162 (57.4%) cases, respectively. Inverse patterns of Skp2 and p27 protein expression were seen in 87 of 162 (53.7%) cases. A marginally significant association was found between Skp2 overexpression and extracapsular extension (P = 0.065). Moreover, patients with Skp2 overexpression had a 2.77 years decreased median time to PSA recurrence compared with patients with low Skp2 expression; however, the difference was not statistically significant. In multivariate analysis, only tumor grade and stage independently predicted PSA recurrence in this cohort. CONCLUSIONS: Our data suggest a role for Skp2 overexpression in prostate cancer pathogenesis that might not be exclusively related to p27 degradation. More studies are needed to determine the mechanistic role of Skp2 in prostate cancer

Major risk factors for developing prostate cancer, including positive family history and African-American ethnicity, can be quantified for genetic counseling. Factors increasing familial risk for prostate cancer are closer degree of kinship, number of affected relatives, and early age of onset (< 50 years) among the affected relatives. Genetic testing may be useful for modification of risk, but currently should be performed only within the context of a well-designed research study that will determine penetrance and genotype-phenotype correlation of specific mutations. Even in the absence of genetic testing, African-American men and men with a strong family history of prostate cancer may opt to initiate screening by prostate specific antigen (PSA) and digital rectal exam (DRE) screening at age 40

Anti-tubulin couplets have activity in hormone-resistant prostate cancer. This study was designed to define the dose-limiting toxicity (DLT) and recommended phase II dose (RPTD) of the unique triplet combination of paclitaxel, estramustine phosphate (EMP) and vinorelbine (Pacl-E-Vin). Patients with advanced malignancies who had failed standard therapy, ECOG performance status (PS 0-2) and adequate organ function were included. Dose of EMP was fixed at 300 mg/m /dose p.o. t.i.d. on days 1-3 and 8-10. Vinorelbine dose was 20 mg/m /day i.v. on days 3 and 10. Paclitaxel was dose escalated from 40 to 50 mg/m /day i.v. on days 3 and 10. Cycles were repeated every 3 weeks. Twelve adults (median age 72) were entered on this study. Primary tumors included prostate ( =7), cervix ( =2), melanoma ( =1), colon (1) and lung with synchronous prostate cancer ( =1). Nine patients had received no prior chemotherapy, one had received a prior regimen and two had received two or more prior regimens. Of four evaluable patients at dose level 1, one patient had grade 3 neutropenia leading to the day 10 dose being withheld. Of five evaluable patients at dose level 2, there was one DLT (febrile neutropenia) and two grade 3 neutropenias leading to the day 10 dose being withheld. One patient had a lower extremity deep vein thrombosis. Other side effects were mild and reversible. Nine patients were evaluable for efficacy: three with prostate cancer had a greater than 50% prostate-specific antigen (PSA) response, and a patient with synchronous prostate and lung cancer had a greater than 50% PSA response. We conclude that the DLT of Pacl-E-Vin is neutropenia. RPTD is vinorelbine 20 mg/m, paclitaxel 40 mg/m, both administered on days 3 and 10, and EMP 900 mg/m /day on days 1-3 and 8-10, q3w. Dose omission at day 10 followed by 20% dose reduction of paclitaxel and vinorelbine is recommended in the event of grade 3 neutropenia. Activity in hormone-refractory prostate cancer is promising and warrants phase II evaluation

OBJECTIVES: To present our experience with hand-assisted laparoscopy (HAL) for larger renal specimens. One of the theoretical benefits of HAL is the ability to manage large renal specimens, which we defined as tumors greater than 7 cm, and tumors in obese patients. METHODS: Between March 1998 and October 2000, 106 HAL radical nephrectomies were performed for enhancing renal masses, for which 95 patients had complete preoperative, intraoperative, and postoperative data. Of the 95 patients, 32 underwent HAL for large tumors (7 cm or greater) and 41 had a body mass index of 31 or greater. The demographic and outcome data of these two groups were compared with 63 patients who underwent HAL for tumors less than 7 cm and 54 patients with a body mass index of less than 31. RESULTS: When comparing cohorts by tumor size, the only statistically significant differences were in convalescence and specimen weight. Patients with lesions 7 cm or greater required 21 days to recover compared with 18 days for patients with lesions less than 7 cm. Obese patients had statistically significantly higher American Society of Anesthesiologists classifications, longer operative times (214 versus 176 minutes), and longer convalescences (21 versus 17.5 days) compared with nonobese patients. The estimated blood loss and conversion rate was not different between the groups. Furthermore, no difference was noted between the groups in the incidence of positive margins, local recurrence, or metastatic recurrence at a mean follow-up of 12.2 months. CONCLUSIONS: HAL provides a safe, reproducible, and minimally invasive technique to remove large renal tumors and renal tumors in the obese

The patient with hormone-refractory prostate cancer (HRPC) presents unique management challenges for both the urologist and the medical oncologist. Because of a lack of effective treatment options, the management of patients with HRPC has historically been palliative. Over the past 10 years, the advent of relatively efficacious chemotherapeutic regimens, particularly taxane-based chemotherapy, has resulted in a desire to treat patients with HRPC more aggressively. The complex needs of these patients have made a multidisciplinary approach, inclusive of specialists with expertise in disease processes directly affecting the patient, the optimal means of treating HRPC. An understanding of the natural history and complications of HRPC, combined with a systemic evaluative process, can allow the multidisciplinary team to comprehensively address the needs of the individual patient with HRPC

The patient with hormone-refractory prostate cancer (HRPC) presents unique management challenges for both the urologist and the medical oncologist. Because of a lack of effective treatment options, the management of patients with HRPC has historically been palliative. Over the past 10 years, the advent of relatively efficacious chemotherapeutic regimens, particularly taxane-based chemotherapy, has resulted in a desire to treat patients with HRPC more aggressively. The complex needs of these patients have made a multidisciplinary approach, inclusive of specialists with expertise in disease processes directly affecting the patient, the optimal means of treating HRPC. An understanding of the natural history and complications of HRPC, combined with a systemic evaluative process, can allow the multidisciplinary team to comprehensively address the needs of the individual patient with HRPC

The importance of prostate biopsy in urologic practice has been magnified by the routine use of serum prostate-specific antigen in prostate cancer screening. Given the potential impact of the procedure on both patient care and health care costs, an optimal strategy for accurate and judicious detection of early prostate cancer is imperative. Maintaining maximal sensitivity and negative predictive value are equally important to the patient. In this article, we review recent modifications in prostate biopsy indications and techniques that may allow for a systematic biopsy approach to the patient in whom prostate cancer is suspected