M. Stöckle

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.

Conservative surgery of renal cell tumors in 140 patients: 21 years of experience.

Operative method, course and complications were analyzed retrospectively in 140 patients who underwent a conservative operation for renal tumor between June 1969 and December 1990. In 53 patients (20 women and 33 men, mean age 61.2 years, range 38 to 77 years, with 49 renal cell carcinomas and 4 benign renal tumors) there was an imperative indication for an organ preserving operation because nephrectomy would have made dialysis obligatory. In 87 patients (29 women and 58 men, mean age 53.7 years, range 27 to 74 years, with 72 renal cell carcinomas and 15 benign renal tumors) the tumor was conservatively resected in the presence of a normal contralateral unit (elective indication) and 68 of these patients (78%) were symptom-free. In the imperative group 32 of 49 patients (65.3%) with renal cell carcinoma had no evidence of disease after a mean followup of 4.6 years. Known metastases were present in 4 of 7 patients who died of the tumors in this group. In 3 patients with an imperative indication for conservative surgery a second tumor occurred in the kidney: 2 were treated with further parenchyma sparing operations, while in 1 with poor physical condition no further measures were possible. Of 72 patients with renal cell carcinoma who underwent an elective operation 68 (94.4%) had no signs of tumor progression after a mean followup of 3.3 years. One patient died of tumor metastases, and 2 (2.7%) had tumor recurrence in the kidney requiring nephrectomy and enucleation, respectively. The 5-year cause-specific survival rates for the imperative and elective groups were 84% and 96%, respectively. Patients with a local stage T3 tumor were characterized by a significantly worse survival curve than those with a stage T1 or T2 tumor but no significant difference was noted among the various grades of differentiation.

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.

The Fate Of The Adult Exstrophy Patient

Between 1968 and 1993, 101 patients with bladder exstrophy or incontinent epispadias underwent surgery at our hospital. The standard procedure was ureterosigmoidostomy and additional genital reconstruction. Of the 56 patients who have reached adulthood 45 could be interviewed regarding social integration, sexuality and fertility. All patients have a functioning urinary diversion. Of the 45 patients questioned 41 have completed vocational training or are currently in training, 3 are unemployed and 1 lives at a therapeutic center. Among the patients 29 are married or have a steady partner. All women engage in sexual intercourse and 2 have delivered 3 children by cesarean section. All men achieve erection. Of the 28 men who underwent reconstruction of the external genitalia 11 have a penile deviation, which is distressing in only 2. Only 3 of the men are dissatisfied with the cosmetic result and 33% had epididymitis, necessitating 2 orchiectomies and 3 vasectomies. No patient with reconstruction of the external genitalia can ejaculate normally or has fathered children, whereas all 5 who did not undergo genital reconstruction had normal ejaculation and 2 have fathered children. Male patients with genital reconstruction and closure of the urethra have a high risk of infertility. Our patients demonstrate that the cosmetic results after genital reconstruction are satisfactory. However, in male patients, surgery is performed at the expense of fertility. Because this corrective procedure is usually performed during childhood, the parents must be informed of these consequences before surgical correction.

Prognostic value of DNA analysis in colorectal carcinoma

Background. Reported experiences regarding the prognostic significance of DNA content in colorectal carcinoma have been a matter of controversy.

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.

Social integration, sexual behaviour and fertility in patients with bladder exstrophy- a long-term follow up

After primary bladder closure or urinary diversion, other factors apart from the reconstruction itself gain importance for individuals with the exstrophy-epispadias complex: social integration and, after reaching puberty, sexuality and fertility. Between 1968 and July 1994 115 patients with bladder exstrophy or incontinent epispadias underwent surgery at our institution. A total of 104 patients could be followed, 2 of whom died in the meantime. Of the remaining 102 patients 48 attend school, 4 are in college, 40 have completed or are currently undergoing vocational training, 3 are unemployed, 1 lives in a therapeutic centre and 6 are younger than 6 years of age. A total of 95% of the patients with continent urinary diversion are continent day and night, whereas only three of five patients with a sling plasty (incontinent epispadias) or with primary bladder closure followed by a Young-Dees procedure are continent. None of the patients showed deterioration of renal function. In 25 females the external genitalia were reconstructed. Fixation of the uterus was done in 13 to correct or prevent uterine prolapse. Of the 17 women older than 18 years of age with genital reconstruction, 16 are satisfied with the cosmetic result. All adults engage in sexual intercourse. Five women have delivered seven children by Caesarean section. Of the 35 male adults 32 underwent reconstruction of the external genitalia and 34 males achieve erection. One developed necrosis of the penis early in life following primary bladder closure performed at an outside hospital. Penile deviation was present in 11 of the 32 patients with genital reconstruction, which is distressing in only 2. Thirty patients are satisfied with the cosmetic result. After genital reconstruction 9 males developed epididymitis, necessitating two orchiectomies and three vasectomies. No patient with reconstruction of the external genitalia can ejaculate normally or has fathered children, whereas ejaculation was normal in the three men who did not undergo genital reconstruction and in two patients prior to post-pubertal reconstruction. Furthermore, two of these three men have fathered four children.

Urethral Tumor Recurrences after Radical Cystoprostatectomy: The Case for Primary Cystoprostatourethrectomy?

Of 273 male patients who underwent radical cystoprostatectomy between 1967 and 1987, 22 were regarded as at risk for urethral recurrence. These patients underwent simultaneous primary urethrectomy or urethrectomy shortly after cystectomy because of the histology of the cystectomy specimen. Of the remaining 251 patients a urethral recurrence was observed in 23 (9.2%). A patient with a urethral recurrence originally had undergone an operation at another hospital. The first urethral tumor recurrence was observed in 1977 but between October 1987 and May 1988, 7 patients were treated for an initial or secondary urethral recurrence. This finding suggests that the rate of urethral recurrence increases with improved survival rates after cystoprostatectomy and longer followup of these patients. Of the 24 patients who had urethral recurrence 21 showed multifocal tumor growth in the primary cystectomy specimen and 2 had unifocal tumors. The original histological status in the patient treated elsewhere is not known. The data suggest that primary simultaneous urethrectomy should be performed in all patients undergoing cystoprostatectomy for multifocal bladder tumors. Patients who retain the urethra require regular and life-long washout cytology studies of the urethra for early diagnosis of recurrent urethral tumor.

Involvement of the chromosomal region 11q13 in renal oncocytoma: Case report and literature review

Renal oncocytomas comprise a cytogenetically heterogeneous group of tumors consisting potentially of cytogenetic distinguishable subgroups. Review of the literature revealed loss of chromosome 1 and Y as a possible anomaly for at least one subset oncocytomas. The frequent finding of rearrangements involving chromosome 11 band q13 characterizes another subset of oncocytomas. We report the cytogenetic and pathological features of a renal oncocytoma diagnosed in a 72-year-old woman and found a t(9;11)(p23;q13) as a consistent abnormality. This supports the idea that translocations involving 11q13 define a further subset of oncocytoma.