Faculty Bibliography

OBJECTIVE: To compare the surgical outcomes of elderly patients with renal masses treated with laparoscopic partial nephrectomy (LPN) or laparoscopic cryoablation (LCA). PATIENTS AND METHODS: All 15 patients who had LCA at the authors' institution between May 2003 and July 2005 were included, and compared with a matched cohort of 15 patients selected by patient age and tumour size, from a pre-existing database of 104 patients who had LPN from July 2002 to July 2005. The two groups were compared for gender, number of comorbidities, American Society of Anesthesiologists status (ASA), body mass index (BMI), baseline renal function and haematocrit, location and size of lesion, length of stay, operative time, estimated blood loss (EBL), transfusion rate, number and type of complications, conversion rate, and postoperative renal function and haematocrit. RESULTS: The two groups were similar in age, sex, BMI, ASA, baseline renal function, haematocrit, size and side of tumour, the percentage of exophytic tumours, and the likelihood of more than one comorbidity. Surgical outcomes between the groups were also relatively similar. The length of stay, creatinine and haematocrit levels after surgery did not differ between the groups. The LPN group had a significantly longer operation (248 vs 152 min, P < 0.001) and higher EBL (222 vs 59 mL, P = 0.007) than the LCA group, but only one patient required a transfusion and there was no discernible difference in discharge haematocrit values. No recurrences were detected in either group, with a similar mean follow-up of 9.8 and 11.9 months, respectively. CONCLUSION: Although this matched-cohort comparison showed that LPN had a higher mean EBL, a longer operation and higher relative risk of open conversion, the overall clinical outcome was similar in terms of complication rates, length of stay and changes in creatinine and haematocrit after surgery. In this small retrospective evaluation, there was similar morbidity, treatment outcome and short-term efficacy with LCA and LPN. At present, although still experimental, LCA is a good choice for elderly patients with comorbidities precluding blood loss or renal ischaemia. However, in experienced hands, LPN is a preferred option for most elderly patients and should be considered when contemplating definitive treatment of renal masses

BACKGROUND: Neutral endopeptidase (NEP) is a cell-surface peptidase that can regulate the activation of Akt kinase through catalytic-dependent and independent mechanisms. NEP expression is absent in approximately 50% of prostate cancers. The authors investigated whether NEP loss in vivo would result in Akt phosphorylation and potentially contribute to prostate cancer progression by examining the interaction of NEP, Akt, and phosphatase and tensin homolog (PTEN) in a prostate xenograft model and in clinical specimens from patients with prostate cancer. METHODS: Using a tetracycline-repressible expression system to express NEP in a tumor animal xenograft model, the effects of NEP were tested on tumor growth, Akt phosphorylation, and PTEN expression. The clinical relevance of NEP, phosphorylated Akt, and PTEN protein expression also was investigated in 204 patients who had undergone radical prostatectomy. RESULTS: The results indicated that the induction of NEP expression inhibited established xenograft tumor growth, diminished Akt phosphorylation, and increased PTEN protein levels. In humans, prostate cancers with complete loss of NEP expression were significantly more likely to express phosphorylated Akt (P = .02). Moreover, patients who had prostate cancers with concomitant loss of NEP and expression of phosphorylated Akt had an increased, independent risk of prostate-specific antigen (PSA) recurrence (P = .03). In the study cohort, loss of PTEN protein expression did not correlated significantly with phosphorylated Akt or with patients' clinical outcome. CONCLUSIONS: The findings from this investigation demonstrated that NEP loss leads to Akt activation and contributes to the clinical progression of prostate cancer

OBJECTIVES: To determine whether the discrepancy in the radiologic and pathologic size of renal cell carcinoma influences the final cancer stage. METHODS: Renal masses resected from December 1999 to September 2004 were identified using a pathologic database and compared by surgical accession number to an existing clinical renal tumor database to identify those T1 and T2 tumors for which radiologic and pathologic data were available. The tumor histologic features, maximal pathologic diameter, and maximal radiologic diameter were recorded. The percentage of tumor size reduction was then calculated using these data. RESULTS: Of the 236 renal cancers evaluated, 52% had regressed in size when comparing the pathologic and radiologic sizes. When stratified by histologic subtype, clear cell tumors regressed more often and to a greater degree than those that were chromophobe or papillary. Also, 15 organ-confined tumors were downstaged when comparing the maximal radiologic diameter and the maximal pathologic diameter, and 13 of these were clear cell tumors. CONCLUSIONS: A reduction in kidney tumor size is commonly observed at surgical resection because of a loss of blood flow to the tumor. This tumor size reduction has an impact on the final pathologic stage in organ-confined tumors for which size is the only criterion. The greatest tumor size reduction, and most frequent downstaging, was observed for conventional (clear cell) tumors. We believe this may explain, in part, the worse stage-stratified outcomes for clear cell tumors compared with other tumor types. We propose that renal cancer staging should be determined from accurate measurement of the radiologic size, rather than the pathologic size

PURPOSE: Advances in laparoscopy have made laparoscopic partial nephrectomy a technically feasible procedure but it remains challenging to even experienced laparoscopists. We hypothesized that robotic assisted laparoscopic partial nephrectomy may make this procedure more efficacious than the standard laparoscopic approach. MATERIALS AND METHODS: Ten patients with a mean age of 58 years and mean tumor size of 2.0 cm underwent robotic assisted laparoscopic partial nephrectomy and another 10 with a mean age of 61 years and mean tumor size of 2.18 cm underwent laparoscopic partial nephrectomy, as performed by a team of 2 surgeons (MS and ST) between May 2002 and January 2004. Demographic data, intraoperative parameters and postoperative data were compared between the 2 groups. RESULTS: There were no significant differences in patient demographics between the 2 groups. Intraoperative data and postoperative outcomes were statistically similar. In the 10 patients who underwent robotic assisted laparoscopic partial nephrectomy there were 2 intraoperative complications. There was 1 conversion in the laparoscopic partial nephrectomy group. CONCLUSIONS: Robotic assisted laparoscopic partial nephrectomy is a safe and feasible procedure in patients with small exophytic masses. The robotic approach to laparoscopic partial nephrectomy does not offer any clinical advantage over conventional laparoscopic nephrectomy

The relationship between obesity and prostate cancer is currently a hotly debated topic, but despite the number of publications devoted to the topic, the actual nature of the relationship remains uncertain. Obesity has been shown to have a direct relationship with the incidence of prostate cancer in a number of studies but an equal number of studies have shown no association. The relationship is further obscured with recent findings that obesity in younger obese men may actually be protective against prostate cancer. Confounding factors include the lack of correlation of body mass index (BMI) as a measure of central obesity and the lack of consistency in timing of BMI measurements, i.e. before or after diagnosis and in young or advanced adulthood. Evidence for increased BMI as a risk factor for prostate cancer is unclear, but less ambiguous is the mounting substantiation that obesity is associated with prognostically worse disease, poorer post-surgical outcomes and increased prostate cancer mortality, irregardless of margin status. From a biologic perspective, one can put forth a number of potential mechanisms by which obesity might promote prostate cancer and/or prostate cancer progression including; low levels of testosterone, increased levels of estrogen, co-existing diabetes or metabolic syndrome, increased circulating insulin-growth factor-one (IGF-1), increased levels of leptin, decreased levels of adiponectin and increased dietary saturated fats. Evidence for the association of these factors with prostate cancer are examined herein. The timing of serum measurements is crucial in elucidating whether these factors have causative influence on prostate cancer or rather are produced by the prostate cancer cells and are better understood as markers of disease. The interaction between obesity and prostate cancer is important to clarify because it will have impact on the prevention, prognostication and treatment of prostate cancer. Future study with careful attention to avoid the methodological pitfalls of the past need be accomplished to bear out the nature of the interaction of obesity and prostate cancer

Deregulation of the estrogen axis in humans prompts a series of tissue-specific events. In the breast and prostate, alterations in estrogen signalling lead to genotypic and phenotypic molecular alterations that result in dysplastic cellular appearance, deregulated cell growth and carcinoma. In bone, decreased estrogen leads to increased osteoclastogenesis and bone resorption, decreased bone mineral density and a significant fracture risk. Toremifene is a selective estrogen receptor modulator that exerts pharmacological activity in the breast, bone and prostate. An intense interest in developing this agent for prostate cancer chemoprevention is based on the reduction of premalignant and malignant prostate lesions in a transgenic model of prostate cancer. Biological and clinical activity was demonstrated in Phase II trials by the prevention of progression to prostate cancer in men with high-grade prostate intraepithelial neoplasia and through suppression of bone turnover biomarkers and increased bone mineral density in men on androgen deprivation therapy for prostate cancer