G. Voges

Advanced Bladder Cancer (Stages pT3b, pT4a, pN1 and pN2): Improved Survival after Radical Cystectomy and 3 Adjuvant Cycles of Chemotherapy. Results of a Controlled Prospective Study

A total of 49 bladder cancer patients with tumor stages pT3b, pT4a and/or pelvic lymph node involvement without microscopic or macroscopic evidence of residual tumor was randomized into 2 comparative groups: the chemotherapy group was to receive 3 adjuvant cycles of methotrexate, vinblastine and cisplatin plus doxorubicin (M-VAC) or epirubicin (M-VEC) after radical cystectomy. The control group received no additional treatment. The protocol was activated in May 1987. Patient recruitment was concluded in December 1990 because an interim analysis of the 49 randomized patients revealed a significant prognostic advantage in favor of 26 patients randomized to the chemotherapy group compared to 23 in the control group (p = 0.0015, log rank test for relapse-free survival curves). Of the 26 patients randomized for adjuvant chemotherapy 18 were treated with M-VAC or M-VEC (3 cycles in 16 patients and 2 cycles in 2). Of the remaining 8 patients 7 refused chemotherapy before or during cycle 1 and 1 received chemotherapy without cisplatin because of impaired renal function. An update of the patients in August 1991 revealed a further increase in the prognostic difference between the 2 trial arms (p = 0.0012). Of 18 patients who received treatment with M-VAC or M-VEC only 3 have had tumor progression to date compared to 18 of 23 patients in the control group. Further statistical analysis of the data was performed on the basis of Coxs regression model, incorporating various criteria as explanatory variables, including patient sex and age, pT stage and number of involved lymph nodes. This multivariate analysis revealed a significant decrease in the risk of tumor recurrence (p = 0.0007, 2-sided) after adjuvant chemotherapy. The number of lymph nodes involved was also of prognostic significance (p = 0.0028, 1-sided). The results indicate that the survival time after radical cystectomy can be prolonged considerably by adjuvant polychemotherapy in cases of locally advanced bladder carcinoma. Fortunately, all of these conclusions are not affected by switching from an intent-to-treat analysis to an analysis of the therapy actually performed. The p values obtained from the latter are 0.0005 (log rank test) and 0.0001 (Cox model with the same set of additional regressors).

Adjuvant polychemotherapy of nonorgan-confined bladder cancer after radical cystectomy revisited : long-term results of a controlled prospective study and further clinical experience

A total of 83 patients with nonorgan-confined bladder cancer with or without lymph node metastases (tumor stages pT3b, pT4a and/or pN1, pN2) was evaluated in November 1993 for relapse-free and overall survival. All patients underwent radical cystectomy between 1987 and 1991, 38 underwent adjuvant polychemotherapy with methotrexate, vinblastine and cisplatin plus doxorubicin (M-VAC) or epirubicin (M-VEC). Of the 83 patients 49 had entered a prospective randomized trial comparing adjuvant to no adjuvant treatment. The protocol was activated in May 1987. Patient recruitment was concluded in December 1990 because an interim analysis of the 49 randomized patients revealed a significant prognostic advantage in favor of the 26 patients randomized to the chemotherapy group compared to 23 in the control group (p = 0.0015, log-rank test for relapse-free survival curves). Preliminary data were published in 1992. Of the 26 patients randomized for adjuvant chemotherapy 18 were treated with M-VAC or M-VEC, 7 refused chemotherapy before or during cycle 1 and 1 received chemotherapy without cisplatin because of impaired renal function. The update of patient followup obtained in November 1993 continues to demonstrate a significant improvement in progression-free survival in favor of patients randomized for adjuvant chemotherapy (p = 0.0005). Followup of patients living free of disease ranged from 38 to 78 months. In a second analysis of actual treatment, the total collective of 83 patients treated from 1987 to 1991 was reviewed: 38 who had actually undergone adjuvant M-VAC/M-VEC (18 during the prospective trial and 20 in 1991 as the routinely recommended therapy) were compared with 45 without adjuvant M-VAC/M-VEC (7 refused to participate in the adjuvant trial, 8 randomized for but did not undergo adjuvant M-VAC/M-VEC, 23 belonged to the control group of the trial, and 7 underwent cystectomy in 1991 and remained without adjuvant treatment). This analysis again revealed a significant prognostic advantage in favor of the patients treated with adjuvant M-VAC/M-VEC. We conclude that adjuvant chemotherapy with M-VAC/M-VEC leads to a significant prolongation of relapse-free survival and to an improvement of the definitive cure rates after radical cystectomy for locally advanced transitional cell carcinoma of the bladder.

Computerized Tomography: An Unreliable Method for Accurate Staging of Bladder Tumors in Patients who are Candidates for Radical Cystectomy

A total of 164 patients with bladder tumors underwent preoperative staging by computerized tomography. All patients were previously untreated, or had undergone only transurethral biopsy or resection of the tumor before computerized tomography. The post-cystectomy histological stage was compared to the preoperative computerized tomography stage. Computerized tomography accuracy according to the tumor, nodes and metastasis classification was only 32.3%, whereas overstaging was found in 39.6% and understaging in 28.1% of the cases. In untouched tumors or after transurethral resection computerized tomography accuracy demonstrated no significant difference. Only 2 of 19 true positive lymph nodes were staged correctly. Of 10 suspicious nodes results of computerized tomography were false positive in 8. Computerized tomography is an unreliable method for accurate preoperative staging of bladder carcinoma. The indication for either an operation, chemotherapy or radiotherapy for the treatment of bladder neoplasms should not be based on computerized tomography findings.

Ureterosigmoidostomy: An Outdated Approach to Bladder Exstrophy?

Long-term results among 46 children with ureterosigmoidostomy are presented. The indication for ureterosigmoidostomy had been bladder exstrophy in 40 patients, incontinent epispadias in 5 and neurogenic bladder dysfunction in 1. Of the 40 patients with bladder exstrophy 8 had undergone ureterosigmoidostomy after failure of other types of urinary tract reconstruction (6 had upper tract dilatation before ureterosigmoidostomy). Three patients with previously damaged upper urinary tracts required early postoperative conversion because of severely increasing kidney dilatation. Three other patients required conversion after a mean of 10 years to preserve kidney function. One patient died after 16 years of a cause not related to ureterosigmoidostomy. The remaining 39 patients were alive with a functioning ureterosigmoidostomy after a mean followup of 14.7 years. The daytime continence rate was 97.4% (38 of 39 patients) and the complete continence rate was 92.3% (36 of 39). Except for 1 tubular adenoma that was removed successfully during routine colonoscopy, no bowel neoplasia has been observed. None of the 45 living patients has renal insufficiency.

Comparison of Selective Internal Iliac Pharmaco- Angiography, Penile Brachial Index and Duplex Sonography with Pulsed Doppler Analysis for the Evaluation of Vasculogenic (Arteriogenic) Impotence

Between July 1987 and February 1988 selective internal iliac angiography was performed before and after intracavernous injection of papaverine plus phentolamine in 43 patients with erectile dysfunction. In 63% of the patients stenosis or occlusion of the pudendal artery was found. The penile brachial index was calculated and duplex sonography with pulsed Doppler analysis was performed in 23 patients. Angiography and penile brachial index correlated in only 39% of the patients, whereas selective internal iliac angiography and duplex sonography correlated in 91% (21 of 23). In 2 patients duplex sonography with pulsed Doppler analysis rendered better information about penile arterial perfusion than did angiography.

Transurethral prostatectomy : A long-term follow-up study of 166 patients over 80 years of age

OBJECTIVES AND METHODS In a retrospective analysis, the medical records of 166 patients over 80 years of age (80-99 years, mean age 82 years) who underwent transurethral prostatectomy (TURP) for clinically benign prostatic hyperplasia (BPH) were reviewed in order to evaluate the morbidity and mortality rates in this special group of patients. The mean follow-up was 60 months (6-85 months). RESULTS According to the American Society of Anesthesiologists operative risk classification, 147 (88.5%) patients were found to be of groups ASA III and IV. All patients had at least one serious associated medical disease. Early complications occurred in 25.9% (n = 43) of patients. Late significant urology complications were noted in 13.2% (n = 22) of patients. Reoperation was carried out in 4.2% (n = 7) of cases. Two patients died within 30 days after the operation (1.2%). During the period of follow-up 43 patients died. Comparing the survival curve (according to the Kaplan-Meier analysis) of our group with the expected survival rate of the age-matched overall population, no statistical difference could be observed. CONCLUSION Being aware of the limits of a retrospective study, we believe that TURP as a treatment for BPH in patients over the age of 80 years has a satisfactory outcome with an acceptable morbidity and mortality rate.

PHEOCHROMOCYTOMA IN THE PEDIATRIC AGE GROUP : THE PROSTATE : AN UNUSUAL LOCATION

Pheochromocytomas of the prostate are rare, with only 3 cases in adults reported in the literature. We present the case of an 8-year-old boy with a pheochromocytoma of the prostate and a second tumor in the region of the left internal iliac artery.

Characterization of conservatively resected renal tumors using automated image analysis DNA cytometry

The DNA histograms of 57 conservatively resected renal tumors were studied using automated image analysis DNA cytometry (Leytas II). Forty‐nine of the analyzed tumors were renal cell carcinomas, six were oncocytomas, one was an angiomyolipoma, and one was a renal cell adenoma. On the basis of their DNA histograms, diploid, tetraploid, and aneuploid tumors could be distinguished. Aneuploid tumors could be subtyped further according to the DNA content of the stem cell line as hyperdiploid, hypertriploid, or hypertetraploid. Eight of the tumors were characterized by a combination of diploid and hypertriploid stem cell lines. During a mean follow‐up of 5 years, only the two patients with a pure hypertriploid tumor died of distant metastases. These results indicate that automated DNA image analysis cytometry is able to differentiate among several types of renal tumors with obviously different prognoses.

Tunica vaginalis Free Grafts for Closure of Urethrocutaneous Fistulas

In 32 patients a tunica vaginalis free graft was used for closure of urethrocutaneous fistulas (n = 26) or complicated hypospadias repair (n = 6). All patients had at least one operation (average 3.9) for urethral reconstruction prior to this procedure. 12 patients had recurrent fistulas (average 2.2). The technique proved to be very successful. Only 2 patients had to undergo subsequent reoperation for recurrent fistulas. The use of a free tunica vaginalis graft interposed between skin and urethra is our method of choice in the repair of recurrent or complicated urethrocutaneous fistulas.

Local shock-wave lithotripsy of distal ureteral calculi.

Since the initiation of the clinical trial utilizing a second-generation lithotripor (Lithostar, Siemens, Erlangen, FRG), 96 patients with distal ureteral calculi (i.e. calculi below the pelvic brim) underwent local shock-wave lithotripsy. Routine treatment was conducted under intravenous sedation and light analgesia only. Complete stone disintegration was achieved in 84 patients (87.5%), 11 requiring two sessions and 1 patient, three. In 7 patients ureteroscopy became necessary after unsuccessful local shock-wave treatment. In 2 of these patients a 9-french flexible ureteroscope and the Storz Q-switched neodymium-YAG laser was used for stone disintegration. In 3 cases loop extraction and in 2 cases open surgery had to be performed for definitive stone removal. All pre- and postoperative manipulations (except open surgery) were done on the Lithostar. Local shock-wave lithotripsy is a highly successful, noninvasive, time-saving and easily applicable technique. It has become our primary approach in the treatment of distal ureteral calculi.