Jeffrey M. Ignatoff

Molecular Detection of Prostate Epithelial Cells from the Surgical Field and Peripheral Circulation during Radical Prostatectomy

PURPOSE Prostate cancer progression despite organ confined pathological assessment has been reported in a variable number of men after radical retropubic prostatectomy. To study this phenomenon, we used the prostate specific antigen (PSA) reverse transcriptase-polymerase chain reaction assay. MATERIALS AND METHODS We prospectively assayed the peripheral venous blood before, during and after surgical manipulation as well as the intraoperative field blood for PSA reverse transcriptase-polymerase chain reaction-positive cells in 22 men undergoing radical retropubic prostatectomy. RESULTS PSA reverse transcriptase-polymerase chain reaction-positive cells were identified in 20 of the 22 operative field samples (91%) and 4 of 16 (25%) had evidence of intraoperative hematogenous dissemination (p = 0.046). No significant association was identified among Gleason score, pathological stage and the PSA reverse transcriptase-polymerase chain reaction result. CONCLUSIONS Our results suggest that tumor cell spillage and less frequently hematogenous dissemination may be associated with operative manipulation of the prostate during radical retropubic prostatectomy and may potentially represent mechanisms of failure after radical retropubic prostatectomy.

Use of Electrocoagulation in the Treatment of Vesicovaginal Fistulas

The role of electrocoagulation for the treatment of vesicovaginal fistulas has not been clearly defined. To determine the use of this therapeutic modality, 15 cases of fistulas treated with electrocoagulation were retrospectively reviewed. Fulguration represented the primary treatment in 12 patients and the secondary treatment in 3 after an initial attempt at open surgical closure failed. In all instances fistula size was estimated to be 3.5 mm. or less. A Bugbee electrode, which was inserted into the fistula either cystoscopically or vaginally, was used to destroy the epithelial lining of the fistula tract. Following the procedure the bladder was decompressed with a large indwelling Foley catheter for at least 2 weeks. Fulguration was successful as the sole treatment modality in 9 of 12 patients (75%) and as an alternative intervention after failure of an open surgical repair in 2 of 3 (66%). Therefore, 11 of the 15 women (73%) had complete resolution of the fistulas with this technique. We conclude that fulguration is usually effective in managing patients with vesicovaginal fistulas a few millimeters in size or less. This technique should be used as an initial treatment for appropriately selected patients and in women with small residual fistulas after open surgical failure.

PROSTATE SPECIFIC ANTIGEN REVERSE TRANSCRIPTASE- POLYMERASE CHAIN REACTION ASSAY IN PREOPERATIVE STAGING OF PROSTATE CANCER

PURPOSE Extracapsular extension of prostate cancer occurs in a significant number of men believed to have clinically localized disease. We report the ability of the reverse transcriptase-polymerase chain reaction (RT-PCR) assay to predict preoperatively the pathological stage of cases of clinically localized prostate cancer. MATERIALS AND METHODS Since October 1994, 82 consecutive men with clinically localized prostate cancer had a venous blood RT-PCR assessment before radical retropubic prostatectomy. The extracted ribonucleic acid was reverse transcribed, amplified and the amplicon identity confirmed by prostate specific antigen (PSA) directed probe hybridization. An additional 31 patients were enrolled to provide appropriate positive (T + Nx/1M2) and negative (human female and benign prostatic hyperplasia) controls. Histological examination of the entire prostatectomy specimen was performed. RESULTS Positive RT-PCR assay results correlated significantly with skeletal metastases and elevated levels of serum PSA but they did not significantly improve our ability to identify prospectively patients with extracapsular extension over traditional predictors (serum PSA, Gleason score). CONCLUSIONS The role of molecular techniques in prostate cancer evaluation and prognosis continues to emerge. However, in our study we demonstrate no significant advantage in preoperative staging of prostate cancer using RT-PCR assay with PSA primers.

Clear Cell Adenocarcinoma of the Urethra: Evidence for Origin within Paraurethral Ducts

We report a case of clear cell adenocarcinoma arising in a paraurethral duct treated by anterior pelvic exenteration. Immunohistochemical stains for prostate specific acid phosphatase and prostate specific antigen were positive in the primary tumor and regional metastases. Focal positive staining also was noted in normal paraurethral duct epithelium. Our observations suggest that clear cell adenocarcinoma arises from the female paraurethral ducts, rather than embryonic remnants. These ducts appear to be homologous to the prostate and in some cases may be misinterpreted as urethral diverticula.

Clinical and molecular followup after radical retropubic prostatectomy.

PURPOSE We previously reported evidence of hematogenous dissemination of prostate cells during radical retropubic prostatectomy, and we now provide clinical and molecular reverse transcriptase-polymerase chain reaction (RT-PCR) followup of that patient cohort. MATERIALS AND METHODS A total of 101 men with clinically localized prostate cancer were prospectively enrolled in the study. The prostate specific antigen (PSA) RT-PCR assay was performed on peripheral venous blood samples preoperatively in 101, during surgery in 29, during and up to 12 weeks after surgery in 50 and at least 1 year postoperatively in 65 patients. Correlation with clinical (PSA) indicators of recurrence was performed. RESULTS Of the 101 patients 9 demonstrated biochemical evidence of prostate cancer progression (median followup 22 months). Of the 50 men with perioperative molecular results the RT-PCR positive rate increased from 22% preoperatively in 11 to 48% in 24 (p = 0.02) and then decreased to 10% in 4 of 40 men at 1 year postoperatively (p = 0.07). Molecular followup at a minimum of 1 year after radical retropubic prostatectomy was obtained in 65 men, of whom the RT-PCR positive rate decreased from 23% preoperatively in 14 to 9.2% in 6 (p = 0.05). No significant correlation was observed between a persistently positive RT-PCR result and biochemical failure. CONCLUSIONS Although a significant proportion of men have molecular evidence of hematogenous prostate cell dissemination intraoperatively, longitudinal molecular and clinical followup demonstrates reconversion to a negative status as the predominant trend. At relatively short followup no significant correlation was identified between the RT-PCR result and the PSA progression-free survival.

Conservative Management of Twisted Testicular Appendages

We planned non-operative treatment of a twisted intrascrotal appendage in 23 consecutive patients, ranging in age from 6 to 45 years, in whom the diagnosis could be made confidently. Only 3 patients have required subsequent removal of the infarcted appendage because of persistent or recurrent pain. The remaining patients became free of pain within a week. Prompt surgical exploration to exclude torsion of the spermatic cord remains necessary if scrotal swelling obscures the diagnosis. At operation for the latter indication 5 additional boys were found to have a twisted appendix testis during the study interval.

Urinary bladder metastases from breast carcinoma

Four patients with primary carcinoma of the breast metastatic to the urinary bladder are described. Hematuria was present in 3 of the 4 patients. Two of the 4 women had received steroidal drugs which may have a role in the development of this unusual metastasis. This complication developed no sooner than 32 months after diagnosis of malignant breast disease and occurred shortly before death in 2 of the patients. Bladder metastasis in women with a history of breast carcinoma may be more prevalent than has previously been suspected. Cancer 46:229–232, 1980.

Unsuspected Bladder Carcinoma in Patients Undergoing Radical Prostatectomy

Unsuspected synchronous transitional cell carcinoma of the bladder was discovered between January 1991 and June 1993 in 4 patients who were candidates for radical prostatectomy. Each of these patients had multiple urinalyses that did not demonstrate hematuria. During the 2 1/2-year period these patients represented 1.2% of all radical prostatectomies with cystoscopy performed preoperatively. Using the National Cancer Institute Surveillance, Epidemiology and End Results (SEER) data the expected number of bladder neoplasms was estimated. The occurrence of synchronous bladder carcinoma observed in our prostatectomy group compared with age-matched population-based SEER data demonstrates a statistically significant difference as analyzed by the chi-square test (p < 0.001). Management of these superficial bladder tumors included transurethral resection before radical prostatectomy. All patients were free of prostatic and urothelial malignancy at 6 to 24 months. The finding of an unsuspected bladder malignancy in a radical prostatectomy candidate should be addressed first and further therapy should be guided by the stage of the bladder neoplasm. Cystoscopy provides information regarding bladder pathological findings, the status and location of the ureteral orifices, preexisting urethral pathological conditions and tumor encroachment on the urethra. The ideal time to perform cystoscopy is in the office before the scheduled date of surgery. Given the low morbidity and cost, cystoscopy should be performed before radical prostatectomy.

Use of Extracorporeal Shock Wave Lithotripsy in a Solitary Kidney with Renal Artery Aneurysm

Arterial aneurysms have been among the relative contraindications cited for extracorporeal shock wave lithotripsy. We report the successful use of extracorporeal shock wave lithotripsy for treatment of renal calculi in a solitary kidney with renal artery aneurysms. Appropriate management considerations and perioperative precautions are discussed.

Phase II study of intravesical therapy with AD32 in patients with papillary urothelial carcinoma or carcinoma in situ (CIS) refractory to prior therapy with bacillus Calmette-Guerin (E3897): a trial of the Eastern Cooperative Oncology Group.

OBJECTIVE To assess the safety and effectiveness of AD32, a doxorubicin analogue with little systemic exposure when administered intravesically, in patients with recurrent or refractory superficial urothelial carcinoma (formerly called transitional cell carcinoma [TCC]), or carcinoma in situ (CIS), who have failed prior BCG-based immunotherapy. METHODS Eligible patients received six weekly doses (800 mg) of intravesical AD32 and were evaluated at 12-week intervals for 24 months or until date of worsening disease. Primary analysis was the proportion of all patients recurrence-free at 12 months. Treatment-related and GU-specific toxicities were also examined. All participating institutions submitted the protocol for Institutional Review Board (IRB) approval. RESULTS The study was halted due to unavailability of study drug after accrual of 48 of a planned 64 patients; 42 were included in the analysis. Of these, 28 (67%) were still alive after median follow-up of 61.1 months. Of 21 TCC patients, 18 (85.7%) experienced disease recurrence (median time to recurrence, 5.3 months). Of the 5 CIS patients with complete response (CR), 3 (60%) experienced disease recurrence; (median time to recurrence, 37.3 months). Recurrence-free rates at 12 and 24 months were 20% (90% CI, 7.8%, 36.1%) and 15% (90 CI, 4.9%, 30.2%), respectively, for patients with TCC and 80% (90% CI, 31.4%, 95.8%) at both intervals for CIS patients with CR. Infection was the most common treatment-related toxicity; no grade 4 or higher toxicity was observed. The most common GU-specific toxicity was increased frequency/urgency. CONCLUSIONS AD32 is safe and active for treatment of recurrent or refractory superficial bladder carcinoma. The agent awaits more complete characterization when drug production problems can be solved.