The diagnosis and treatment of urethral recurrence after radical cystectomy.

OBJECTIVE: To illustrate the problem of urethral recurrence of transitional cell carcinoma (TCC) after radical cystectomy, and define surveillance and treatment algorithms. METHODS: There are 6 unique cases of urethral tumor recurrence presented, and current relevant literature is reviewed. Three risk groups are defined based on the likelihood of urethral recurrence. Surveillance and treatment options are delineated. RESULTS: Although the incidence of recurrent tumor in the urethra is low, the prevalence is increasing because of improvements in bladder cancer survival and the fact that the urethra is retained more often for orthotopic urinary diversion. Patients can be categorized as low, intermediate, and high risk based on the pathologic finding of degree of prostatic involvement by the initial tumor. CONCLUSION: Based on limited available literature, it appears that surveillance strategies range from observation alone to more invasive monitoring that includes urethral wash cytology and urethroscopy. Treatment options include local resection, intraurethral agents, and complete urethrectomy. A surveillance algorithm based on risk for recurrence and a treatment algorithm based on histopathologic risk factors of the recurrent tumor are proposed. This problem will assume increasing importance in the future.

Efficacy of high dose per fraction radiation for implanted human prostate cancer in a nude mouse model.

PURPOSE: SBRT is a new therapeutic paradigm using large dose per fraction treatments (aggressive hypofractionation). While SBRT has shown efficacy for treating patients with lung, liver and spine tumors, to our knowledge there have been no preclinical studies evaluating the efficacy of this treatment for prostate cancer. We investigated the dose-response characteristics of SBRT for treating human prostate cancer in a nude mouse model. MATERIALS AND METHODS: Nude mice were injected subcutaneously into the right flank with C4-2 prostate cancer cells grown in culture. A dose escalation trial was performed to assess toxicity and response. Tumor bearing animals were radiated with 3 fractions (1 per week) for a total dose of 15 Gy in 11, 22.5 Gy in 9 and 45 Gy in 10, while 8 untreated animals served as controls. The mice were weighed, and tumor volume and PSA measurements were performed at baseline and weekly until 4 weeks after treatment. RESULTS: There was no treatment related toxicity. There was a significant difference in the tumor response to higher radiation doses. In the 15 and 22.5 Gy groups mean tumor volume decreased to 58% and 90% of the original volume, respectively, but the rats experienced progressive tumor regrowth within 1 week after the completion of therapy. The 45 Gy group had a mean tumor volume and PSA decrease of greater than 90%, which was sustained 1 month after treatment in all except 2 mice. CONCLUSIONS: SBRT dose level treatments were able to significantly decrease tumor volume and PSA. However, using 15 and 22.5 Gy durable responses were not achieved except in a few mice. The 45 Gy group demonstrated sustained PSA and tumor volume decreases in most mice. These results clearly show an increasing dose-response relationship for a range of hypofractionated dose levels, as used in SBRT.

Hand-assisted laparoscopic nephrectomy for renal masses >9.5 cm: series comparison with open radical nephrectomy.

OBJECTIVE: To assess the feasibility of hand-assisted laparoscopic nephrectomy (HALN) for large renal masses (stage T2, mean size 9.7 cm) and compare outcomes with a similar cohort undergoing open radical nephrectomy (ORN). METHODS: A nonrandomized comparison of 19 consecutive patients who underwent nephrectomy for renal masses >or=7 cm was performed. The HALN group was compared to the ORN group regarding demographic parameters and perioperative data, including blood loss, operating time, narcotic usage, hematocrit change, return to standard oral intake, length of hospital stay, and complications. Data collected prospectively and statistics used 2-tailed t-test analysis. RESULTS: Patients underwent either ORN (mean tumor size 12.3 cm) or HALN (mean tumor size 9.7cm). Tumors up to 14 cm (n = 2) and pT3b, with renal vein thrombosis (n = 2), could be safely excised with HALN. There were no differences between the HALN and ORN groups regarding any demographic parameter. Blood loss, operating time, length of stay, parenteral narcotic use, and time to tolerating regular diet were all less statistically significant in the HALN group as compared to the ORN group (P < 0.05). Tumors >15 cm necessitated ORN. CONCLUSIONS: HALN is technically feasible even for tumors with mean size >9.5 cm. There is a significant advantage to HALN over ORN regarding the intraoperative and postoperative morbidity. Tumors >or=15 cm should, in most cases, be performed with an open approach.

Laparoscopic retroperitoneal lymph node dissection in the extremely obese patient: technical insight into access and port placement.

PURPOSE: We report on laparoscopic retroperitoneal lymph node dissection (RPLND) in a morbidly obese patient to discuss the associated technical steps for satisfactory completion of staging lymphadenectomy. METHODS: A laparoscopic RPLND was performed using a modified template on the left side. Initially, 4 ports were placed with the patient in the supine position. Three were placed 3 cm to the left of midline and one in the anterior axillary line, at the level of the umbilicus. During the operation, successful bowel retraction necessitated placement of 2 additional ports in the anterior axillary line (just above the pelvis and off the tip of the 12th rib). Using these 6 trocar sites, the dissection was completed, and 44 lymph nodes were obtained. RESULTS: Laparoscopic retroperitoneal lymph node dissection was accomplished in an extremely obese patient with acceptable morbidity by using prudent modification of standard techniques. CONCLUSION: If access and port placement limitations are overcome, the benefits of laparoscopy in the obese are clear. This report serves as a signpost that laparoscopic retroperitoneal lymph node dissection for testes cancer can also be accomplished using modification of standard techniques.

Heterogeneity of 5 alpha-reductase gene expression in benign prostatic hyperplasia.

PURPOSE: The search for molecular markers of benign prostatic hyperplasia in general is based on an analysis of a limited number of biopsy samples. Little is known about the homogeneity of the expression of key genes in different zones of the prostate. We studied the intraprostatic (that is within the same gland) and inter-prostatic (that is between glands) variability of 5 alpha-reductase 2 (5aR2) gene expression. MATERIALS AND METHODS: Ten tissue samples removed by open prostatectomy were the source of tissue specimens. Two frozen sections were generated from each of several random biopsies taken from each adenoma immediately after enucleation, 1 of which was used for 5aR2 gene expression analysis and 1 for morphometric analysis. Results among biopsies were compared using the 5 alpha-reductase index (ratio of 5 alpha-reductase expression to an internal standard measured as electrophoretic band intensity). Morphometric composition was determined for smooth muscle, collagen, epithelium and glandular lumens. Statistical comparisons were performed with ANOVA by pairwise multiple comparison (Dunn) and Spearman's rank correlation procedure. RESULTS: For the 71 biopsies analyzed mean 5 alpha-reductase index was 0.23 +/- 0.16 and overall tissue distribution was smooth muscle 34%, collagen 35%, epithelium 14% and glandular lumens 17%. Inter-prostate and intraprostate variability in 5 alpha-reductase index was statistically significant (p = 0.004) as was the variability in stromal-to-epithelial ratio (p = 0.012). The 5 alpha-reductase index showed strong correlation with stroma (%) and negative correlation with epithelium (%). CONCLUSIONS: Benign prostatic hyperplasia is heterogeneous in terms of tissue morphometry and expression of single important genes. This finding limits the use of single biopsy based markers to predict biological behavior, and has significant impact on the ability of distinguishing longitudinal changes in tissue composition from sampling artifacts.