J. Brantley Thrasher

Radical Cystectomy for Stages TA, TIS and T1 Transitional Cell Carcinoma of the Bladder

Between January 1969 and January 1990, 531 patients underwent bilateral pelvic lymph node dissection and radical cystectomy for the management of transitional cell carcinoma of the bladder. Of these procedures 220 were performed for clinical stage Ta (31 patients), Tis (23) or T1 (166) disease, which was either high grade or recalcitrant to transurethral resection and/or intravesical chemotherapy. This subgroup of patients was studied to evaluate the outcome of recurrent or chemotherapy resistant superficial transitional cell carcinoma of the bladder after radical cystectomy. The operative mortality rate for the group was 2.3% and the overall complication rate was 20.4%. The pelvic recurrence rate was 5.9%. The 5-year cancer-specific survival rates for patients with pathological stage Ta (11), Tis (19), T0 (43) and T1 (91) disease were 88%, 100%, 80% and 76%, respectively. The 10-year cancer-specific survival rates were 75%, 92%, 66% and 62%, respectively. A total of 74 patients received preoperative radiation therapy (2,000 rad) but they had no better 5-year cancer-specific survival rates than did nonirradiated patients. Transurethral resection and/or preoperative radiation therapy resulted in a pathological status of T0 in 43 patients but this did not confer a survival advantage. Although bladder preservation is preferable, low operative mortality and pelvic recurrence rates, as well as new methods of continent urinary diversion continue to make radical cystectomy the definitive form of therapy for patients with superficial disease recalcitrant to transurethral therapy.

MULTICENTER PATIENT SELF-REPORTING QUESTIONNAIRE ON IMPOTENCE, INCONTINENCE AND STRICTURE AFTER RADICAL PROSTATECTOMY

PURPOSE We determined the incidence of patient self-reported post-prostatectomy incontinence, impotence, bladder neck contracture and/or urethral stricture, sexual function satisfaction, quality of life and willingness to undergo treatment again in a large multicenter group of men who underwent radical prostatectomy. We also determined whether the morbidities of sexual function satisfaction, quality of life and bladder neck contracture and/or urethral stricture are predictable from demographic and postoperative prostate cancer factors. MATERIALS AND METHODS A self-reporting questionnaire was completed and returned by 1,069 of 1,396 eligible patients (77%) who underwent radical prostatectomy between 1962 and 1997. Of the respondents 868 (85.7%) underwent surgery after 1990 and in all prostatectomy had been done a minimum of 6 months previously. Questionnaire results were independently analyzed by a third party for morbidity tabulation and the association of patient reported satisfaction. RESULTS The patient self-reported incidence of any degree of post-prostatectomy incontinence, impotence and bladder neck contracture or urethral stricture was 65.6%, 88.4% and 20.5%, respectively. The incidence of incontinence requiring protection was 33% and only 2.8% of respondents had persistent bladder neck contracture or urethral stricture. Although incontinence and impotence significantly affected self-reported sexual function satisfaction, quality of life and willingness to undergo treatment again (p = 0.001), 77.5% of patients would elect surgery again. This finding remained true even after adjusting for demographic variables, and the time between surgery and the survey by multiple logistic regression. CONCLUSIONS Although radical prostatectomy morbidity is common and affects self-reported overall quality of life, most patients would elect the same treatment again. Impotence and post-prostatectomy incontinence were significantly associated with sexual function satisfaction, quality of life and willingness to undergo treatment again. Bladder neck contracture and/or urethral stricture was associated with willingness to undergo treatment again after adjusting for demographic variables and time from surgery to the survey.

Limited value of bone scintigraphy and computed tomography in assessing biochemical failure after radical prostatectomy.

OBJECTIVES To define the utility of bone scan and computed tomography (CT) in the evaluation of patients with biochemical recurrence after radical prostatectomy. METHODS A retrospective analysis of the Center for Prostate Disease Research database was undertaken to identify patients who underwent radical prostatectomy between 1989 and 1998. Patients who developed biochemical recurrence (two prostate-specific antigen [PSA] levels greater than 0.2 ng/mL) and underwent either bone scan or CT within 3 years of this recurrence were selected for analysis. The preoperative clinical parameters, pathologic findings, serum PSA levels, follow-up data, and radiographic results were reviewed. RESULTS One hundred thirty-two patients with biochemical recurrence and a bone scan or CT scan were identified. Of the 127 bone scans, 12 (9.4%) were positive. The patients with true-positive bone scans had an average PSA at the time of the bone scan of 61.3 +/- 71.2 ng/mL (range 1.3 to 123). Their PSA velocities, calculated from the PSA levels determined immediately before the radiographic studies, averaged 22.1 +/- 24.7 ng/mL/mo (range 0.14 to 60.0). Only 2 patients with a positive bone scan had a PSA velocity of less than 0.5 ng/mL/mo. Of the 86 CT scans, 12 (14.0%) were positive. On logistic regression analysis, PSA and PSA velocity predicted the bone scan result (P <0.001 each) and PSA velocity predicted the CT scan result (P = 0.047). CONCLUSIONS Patients with biochemical recurrence after radical prostatectomy have a low probability of a positive bone scan (9.4%) or a positive CT scan (14.0%) within 3 years of biochemical recurrence. Most patients with a positive bone scan have a high PSA level and a high PSA velocity (greater than 0.5 ng/mL/mo).

Small-interfering RNA-induced androgen receptor silencing leads to apoptotic cell death in prostate cancer

Prostate cancer is the second leading cause of cancer death in the United States and, thus far, there has been no effective therapy for the treatment of hormone-refractory disease. Recently, the androgen receptor (AR) has been shown to play a critical role in the development and progression of the disease. In this report, we showed that knocking down the AR protein level by a small interfering RNA (siRNA) approach resulted in a significant apoptotic cell death as evidenced by an increased annexin V binding, reduced mitochondrial potential, caspase-3/6 activation, and DFF45 and poly(ADP-ribose) polymerase cleavage. The apoptotic response was specifically observed in those siRNA-transfected cells that harbor a native AR gene. No cell death was found in the AR-null prostate cancer cell PC-3 or its subline that has been reconstituted with an exogenous AR gene, as well as two breast cancer cell lines that are AR positive. Moreover, in parallel with the siRNA-induced AR silencing, the antiapoptotic protein Bcl-xL was significantly reduced, which might account for the apoptotic cell death because ectopic enforced expression of Bcl-xL protein partially inhibited apoptosis after AR silencing. Taken together, our data showed that knocking down the AR protein level in prostate cancer cells leads to apoptosis by disrupting the Bcl-xL–mediated survival signal downstream of AR-dependent survival pathway.

Multi-institutional experience with buccal mucosa onlay urethroplasty for bulbar urethral reconstruction.

PURPOSE Buccal mucosa has been advocated as an ideal graft material for urethral reconstruction. We report our multicenter experience with buccal mucosa ventral onlay urethroplasty for complex bulbar urethral reconstruction in adults. MATERIALS AND METHODS A retrospective analysis of patients who had undergone buccal onlay urethroplasty at 4 military medical treatment facilities participating in the Uniformed Services Urology Research Group was performed. The database generated included demographic data, genitourinary history, preoperative symptoms (American Urological Association symptom score), preoperative urinary flow rate, stricture length and operative statistics. Postoperative followup data included symptom score, flow rate, retrograde urethrogram results, and complications. RESULTS A total of 53 patients (average age 32 years, range 17 to 64) underwent buccal mucosa graft urethroplasty between January, 1996 and March, 1998 for refractory strictures. Sixteen patients had undergone an average of 2.2 prior endoscopic procedures (range 1 to 7). Average stricture length was 3.6 plus or minus standard deviation 1.8 cm. (range 2 to 7.5) as measured on preoperative retrograde urethrogram. Followup averaged 25 months (range 11 to 40 months). Average symptom scores decreased from 21.2 (range 14 to 33) preoperatively to 5.4 (range 3 to 8) postoperatively (p <0.001). Average peak urinary flow rates increased from 7.9 preoperatively to 30.1 ml. per second postoperatively (p <0.001). Postoperative retrograde urethrograms were available for 34 patients and were normal in 24. The overall complication rate was 5.4%. Three patients required endoscopic incisions. One patient has a recurrent narrowing and treatment is considered a failure. There were 4 sacculations (7.5%) and 6 narrowings, 3 of which required further treatment. Of the patients 50 required no additional procedures (94.3%). CONCLUSIONS Buccal mucosa grafts used as a ventral onlay for bulbar urethral reconstruction yield reproducibly excellent results with minimal morbidity and low complication rates. Longer followup will be required to confirm the durability of our results.

A comparison of radical retropubic with perineal prostatectomy for localized prostate cancer within the Uniformed Services Urology Research Group.

Objective To review and compare the outcome of patients undergoing radical retropubic prostatectomy (RRP) or radical perineal prostatectomy (RPP) for clinically localized prostate cancer.

PROSTATE CANCER IN MEN AGE 50 YEARS OR YOUNGER:: A REVIEW OF THE DEPARTMENT OF DEFENSE CENTER FOR PROSTATE DISEASE RESEARCH MULTICENTER PROSTATE CANCER DATABASE

PURPOSE Prostate cancer in men age 50 years or younger traditionally has accounted for approximately 1% of those diagnosed with prostate cancer. Prior studies of prostate cancer in men of this age led many clinicians to believe that they have a less favorable outcome than older men. Most of these studies were conducted before the advent of prostate specific antigen (PSA) screening programs. We evaluated a surgically treated cohort of men age 50 years or younger to determine whether disease recurred more frequently among them than in those 51 to 69 years old in the PSA era. MATERIALS AND METHODS We reviewed the medical records of 477 men who underwent radical prostatectomy between 1988 and 1997. Age, ethnicity, preoperative PSA, clinical and pathological stage, margin and seminal vesicle involvement, and recurrence were compared between 79 men age 50 years or younger (study group) and 398, 51 to 69 years old (comparison group). Disease-free survival rates were compared using Kaplan-Meier and Cox regression techniques. RESULTS There were 6 (7.6%) recurrences in the study group (79) and 107 (26.9%) in the comparison group (398). The disease-free survival curves were significantly different (log-rank p = 0.010). Age remained a significant prognostic factor (Wald p = 0.033) in multivariate Cox regression analyses that controlled for race, clinical and pathological stage, and pretreatment PSA. Similar results were found when the comparison group was limited to 116 patients 51 to 59 years old (log-rank p = 0.034, Wald p = 0.069). CONCLUSIONS These data suggest that patients in the PSA era who underwent radical prostatectomy and were age 50 years or younger have a more favorable disease-free outcome compared to older men.

Extra Vesical versus Leadbetter-Politano Ureteroneocystostomy: A Comparison of Urological Complications in 320 Renal Transplants

The urological complications of 320 consecutive renal transplants performed at our institution between October 17, 1985 and November 10, 1989 are reviewed. The Leadbetter-Politano technique of ureteroneocystostomy was used in the first 160 patients (group 1) and an anterior extravesical technique modified from the methods of Witzel, Sampson and Lich was performed in the second 160 patients (group 2). Urological complications occurred in 15 patients (9.4%) in group 1 and 6 (3.7%) in group 2 (p = 0.04). Ureterovesical junction obstruction occurred in 6 patients (3.7%) in group 1 and 1 (0.6%) in group 2 (p = 0.05). Complications of leakage, ureteral necrosis and ureteral stricture were comparable in the 2 groups. Therefore, we advocate the use of the anterior extravesical technique over Leadbetter-Politano ureteral reimplantation based on the lower incidence of urological complications and various technical advantages, including less operative time, avoidance of a separate cystotomy, less hematuria and ability to use short donor ureters.

Long-term complications related to the modified Indiana pouch.

OBJECTIVES To describe a single-institution, single-surgeon experience with 125 modified Indiana pouches performed during a period of 14 years and their long-term complications. The modified Indiana pouch is a widely accepted and often used form of continent urinary diversion. Few studies have established the long-term complication rates associated with the procedure. METHODS A retrospective chart review of 129 modified Indiana pouches constructed from March 1985 to August 1998 was performed, and the long-term complications and reoperation rates were tabulated. RESULTS Complete information was obtained for 125 of the 129 charts, with a mean follow-up of 41.1 months (range 3 to 127). Complications occurred in 112 patients (89.6%; several patients had more than one complication), with a mean onset of 20.4 months (range 1 to 125) postoperatively. Seventy-three complications (58.4%) were due to the efferent limb, of which incontinence (defined as any leakage) was the most common (35 [28.0%]), followed by stomal stenosis in 19 (15.2%) and difficult catheterization in 12 (9.6%). Of the 26 pouch-related problems (21.8%) that occurred, the most common were stones in 13 (10.4%), perioperative leaks in 5 (4.0%), and perforations in 4 (3.2%). Ureteral anastomotic strictures were seen in 9 (7.2%). Other complications included gallstones in 32 (25.6%), kidney stones in 8 (6.4%), and small bowel obstruction in 6 (4.8%). Reoperation was performed in 65 patients (52.0%; several patients with more than one reoperation). Twenty-six (20.8%) of the patients required an open operation, and 39 (31.2%) received minimally invasive (percutaneous, endoscopic, extracorporeal shock wave lithotripsy) procedures. Sixty percent of the reoperations were minimally invasive. Reoperation was due to stomal stenosis in 18 (14.4%), pouch stones in 13 (10.4%), ureteral strictures in 9 (7.2%), and parastomal hernias in 6 (4.8%). Small bowel obstruction required reoperation in 5 patients (4.0%). CONCLUSIONS In our experience, long-term complications of the modified Indiana pouch were mostly related to the efferent limb, and reoperations were usually due to stomal stenosis. Our data suggest that with longer follow-up, the complication and reoperation rates of the modified Indiana pouch appear to be higher than previously reported.

Clinical variables which serve as predictors of cancer-specific survival among patients treated with radical cystectomy for transitional cell carcinoma of the bladder and prostate

Background. Studies have demonstrated conclusively that the stage and grade of transitional cell tumors at presentation are major determinants of survival for those with the disease in the bladder and prostate. The authors initiated a review of 531 patients with transitional cell carcinoma of the bladder and prostate treated with radical cystectomy between 1969 and 1990 to identify other clinical features predictive of cancer‐specific survival.