Bernard Lobel

Guidelines on Bladder Cancer

OBJECTIVES On behalf of the European Association of Urology (EAU) guidelines for diagnosis, therapy and follow-up of bladder cancer patients were established. Criteria for recommendations were evidence based, and included aspects of cost-effectiveness and clinical feasibility. METHOD A systematic literature research using Medline Services was conducted. References were weighted by a panel of experts. RESULTS TNM 1997 classification and WHO grading 1998 are recommended. Recommendations are developed for diagnosis for bladder cancer in general, treatment of superficial and infiltrative bladder cancer, and follow-up after different types of treatment modalities, such as intravesical instillations, radical cystectomy, urinary diversions, radiotherapy and chemotherapy.

Use of the University of California Los Angeles integrated staging system to predict survival in renal cell carcinoma: an international multicenter study.

PURPOSE To evaluate ability of the University of California Los Angeles Integrated Staging System (UISS) to stratify patients with localized and metastatic renal cell carcinoma (RCC) into risk groups in an international multicenter study. PATIENTS AND METHODS 4,202 patients from eight international academic centers were classified according to the UISS, which combines TNM stage, Fuhrman grade, and Eastern Cooperative Oncology Group performance status. Distribution of the UISS categories was assessed in the overall population and in each center. RESULTS The UISS stratified both localized and metastatic RCC into three different risk groups (P <.001). For localized RCC, the 5-year survival rates were 92%, 67%, and 44% for low-, intermediate-, and high-risk groups, respectively. A trend toward a higher risk of death was observed in all centers for increasing UISS risk category. For metastatic RCC, the 3-year survival rates were 37%, 23%, and 12% for low-, intermediate-, and high-risk groups, respectively; in 6 of 8 centers, a trend toward a higher risk of death was observed for increasing UISS risk category. A greater variability in survival rates among centers was observed for high-risk patients. CONCLUSION This study defines the general applicability of the UISS for predicting survival in patients with RCC. The UISS is an accurate predictor of survival for patients with localized RCC applicable to external databases. Although the UISS may be useful for patients with metastatic RCC, it may be less accurate in this subset of patients due to the heterogeneity of patients and treatments.

EXTRAPERITONEAL LAPAROSCOPIC PYELOPLASTY: A MULTICENTER STUDY OF 55 PROCEDURES

PURPOSE We assessed the feasibility, reproducibility and morbidity of retroperitoneal laparoscopic pyeloplasty for ureteropelvic junction obstruction. MATERIALS AND METHODS A total of 55 retroperitoneal laparoscopic pyeloplasties were performed at 3 institutions between September 1996 and May 2000 in 33 women and 21 men. Results were analyzed in regard to radiological assessment by excretory urography at 3 months, complications and hospital stay. RESULTS We performed dismembered pyeloplasty in 48 cases and Fenger plasty in 7 cases. Crossing vessels were noted in 23 patients. The conversion rate was 5.4%. Mean operative time was 185 minutes (range 100 to 260), mean hospital stay was 4.5 days (range 1 to 14) and mean followup was 14.4 months (range 6 to 43.6). The overall complication rate was 12.7%. Complications in 7 patients included hematoma in 3, urinoma in 1, severe pyelonephritis in 1 and anastomotic stricture in 2 requiring open pyeloplasty at 3 weeks and delayed balloon incision at 13 months, respectively. Excretory urography in 50 patients and ultrasound in 4 showed decreased hydronephrosis in 88.9% at 3 months. Normal physical activity and absent pain were reported by 47 patients (87%) 1 month after surgery. CONCLUSIONS Retroperitoneal laparoscopic pyeloplasty seems to be a valuable alternative to open pyeloplasty for ureteropelvic junction obstruction. The long-term outcome must be assessed before this procedure may be definitively validated.

Correlation between Symptom Graduation, Tumor Characteristics and Survival in Renal Cell Carcinoma

OBJECTIVES To compare renal tumors with respect to initial clinical presentation and assess the prognostic value of a symptom based classification. MATERIAL AND METHODS Based on symptoms at diagnosis, 388 renal tumors were stratified into three groups: (1) asymptomatic tumors; (2) tumors with local symptoms (3) tumors with systemic symptoms. The three groups were compared for usual clinical and pathological variables using chi(2)-tests and Anova regression, for qualitative and quantitative variables, respectively. Survival assessment was made with univariate and multivariate analysis using the Kaplan-Meier method and Cox regression analysis. RESULTS The three defined groups were significantly different for all analysed variables except for age, sex ratio and pathological subtype. In univariate analysis: ECOG performance status, symptom classification, tumour size, TNM stage and grade, adrenal, perinephric fat or vein invasion were significant prognostic factors (p<0.001). In multivariate analysis, symptom classification, TNM stage, Fuhrman grade and perinephric fat invasion remained independent prognostic factors (p<0.001). CONCLUSION The proposed classification merits further validation through multi-institutional studies before integrating it in further prognosis algorithms.

Tumor progression and survival in patients with T1G3 bladder tumors: multicentric retrospective study comparing 94 patients treated during 17 years

OBJECTIVES To compare tumor recurrence, progression, and patient survival in T1G3 bladder tumors treated with transurethral resection (TUR) alone, early cystectomy, or TUR with an adjuvant 6-week course of bacille Calmette-Guérin (BCG) and followed up for a minimum of 5 years. METHODS Between 1979 and 1996, 94 patients with T1G3 bladder tumors (lamina propria invasion) were treated at nine different centers. The time to tumor recurrence, tumor stage and grade progression, number of delayed cystectomies, and patient survival were analyzed retrospectively in relation to the initial treatment. RESULTS The mean follow-up was 62 months. Thirty patients were treated by TUR alone (32%), 50 patients by TUR plus BCG (53%), and 14 patients by primary cystectomy (15%). The recurrence, progression, and cystectomy rates were significantly different between patients treated by TUR alone and TUR plus BCG (Fishers exact test, P = 0.0005, P = 0.02, and P = 0.005, respectively). The disease-free survival was also significantly different when comparing TUR plus BCG with TUR alone or primary cystectomy (Kaplan-Meier analysis, log-rank test, P = 0.02). CONCLUSIONS Endoscopic resection plus BCG treatment of pT1G3 tumors allows an 80% rate of disease-free 5-year survival with bladder preservation. This conservative option has been widely accepted as first-line treatment, offering good cancer control with excellent quality of life. Very accurate surgical and pathologic evaluations before treatment and lifelong follow-up are obviously required.

Prospective study comparing two methods of anaesthesia for prostate biopsies : apex periprostatic nerve block versus intrarectal lidocaine gel : review of the literature

INTRODUCTION Studies have demonstrated the need for pain control during multiple transrectal prostate biopsies. Due to encountered published results on periprostatic nerve block, we prospectively evaluated the efficacy and safety of periprostatic local anaesthesia at the apex in comparison to intrarectal lidocaine gel. METHODS From January 2001 to January 2002 110 patients underwent prostate biopsy. Patients were randomized to receive 10 cc of either 2% lidocaine gel intrarectally (Group 1) or 10 cc of 1% lidocaine solution injected under ultrasound guidance for bilateral periprostatic nerve block at the apex (Group 2). Pain during biopsy was assessed using a 10-point linear visual analog pain scale and a 5-point digital visual pain scale (continuous variables). Statistical analysis of pain scores was performed using the Student t-test. RESULTS 96 patients fitted the inclusion and presented no exclusion criteria. 43 patients composed group 1, and 53 patients group 2. The mean pain score was 2.76+/-1.69 and 1.73+/-1.26 for group 1 and 2, respectively for the 10-point linear visual analog pain scale (p=0.001). The mean pain score was 2.26+/-0.82 and 1.62+/-0.56 for groups 1 and 2, respectively for the 5-point digital visual pain scale (p<0.001). There was no difference in mean patient age (p=0.348), prostate size (p=0.899), serum PSA (p=0.932), and complications when comparing both groups. The number of biopsies per patient was significantly higher in group 2 (p=0.006), but pain scores in each scale were significantly less. CONCLUSIONS Periprostatic nerve block at the apex is superior to intrarectal lidocaine gel for controlling pain during transrectal prostate biopsy, with no increased complications. This technique should be recommended for those patients without anal or rectal inflammatory diseases.

Intravesical Bacillus Calmette-Guerin Treatment Improves Patient Survival in T1G3 Bladder Tumours

OBJECTIVE To study the clinical and pathological factors that affect recurrence, progression and survival in pT1G3 bladder tumours treated conservatively. MATERIAL AND METHODS From January 1979 to December 1996, 80 patients were conservatively treated for pT1G3 bladder tumours. All patients were studied for potential prognostic factors such as: age, sex, previous tumour recurrence, tumour size, multiple tumours, carcinoma in situ, and intravesical instillations. A longitudinal, retrospective, observational and analytical study was conducted to evaluate four different types of events: recurrence, progression, overall survival, and disease-specific survival. The chi(2) (Fischer exact test) and student t tests were used to assess the prognostic value of the qualitative and quantitative variables. Estimations of the survival distributions were calculated according to the Kaplan-Meier method and compared with the Log rank test. Multivariate analysis of the data was performed with Cox proportional hazard models. RESULTS Among the 80 patients, 67 (84%) were men and 13 (16%) were women, with median age of 65.5 years. The median tumour size was 20 mm, most had single tumour (58.8%) and carcinoma in situ was found in six patients (7.5%). Thirty patients were treated with transurethral resection (TUR) of the bladder tumour and 50 patients were treated with TUR followed by BCG. The two groups of patients were comparable and followed up during a median time of 61 and 65 months, respectively (p=0.454). Kaplan-Meier estimators and Log rank tests demonstrated that patients with TUR alone recurred (p<0.0001), progressed (p<0.040) and died (overall survival: p<0.009; disease-specific p<0.040) earlier than patients who received intravesical instillations of BCG. The results were confirmed with Cox models and odds-ratios are presented. CONCLUSION In this study, BCG adjuvant immunotherapy was the only factor affecting recurrence, progression and survival. Conservative treatment using TUR followed by BCG may improve disease-specific survival.

Bacterial hypermutation: clinical implications

Heritable hypermutation in bacteria is mainly due to alterations in the methyl-directed mismatch repair (MMR) system. MMR-deficient strains have been described from several bacterial species, and all of the strains exhibit increased mutation frequency and recombination, which are important mechanisms for acquired drug resistance in bacteria. Antibiotics select for drug-resistant strains and refine resistance determinants on plasmids, thus stimulating DNA recombination via the MMR system. Antibiotics can also act as indirect promoters of antibiotic resistance by inducing the SOS system and certain error-prone DNA polymerases. These alterations have clinical consequences in that efficacious treatment of bacterial infections requires high doses of antibiotics and/or a combination of different classes of antimicrobial agents. There are currently few new drugs with low endogenous resistance potential, and the development of such drugs merits further research.

Non-transitional cell bladder carcinomas

From a clinical perspective most NUTs are diagnosed at an advanced stage and require aggressive treatment with radical surgery combined in some cases with adjuvant or neoadjuvant chemotherapy (notably in neuroendocrine tumours, NETs). The classical distinction between superficial and infiltrating tumours and its therapeutic implications (conservative management for superficial tumours, radical surgery for infiltrating tumours) might not apply to NUTs. The clinical presentation is common to all bladder tumours (urothelial and or not) and is essentially characterized by gross haematuria and irritative voiding symptoms. There is no specific staging system for NUTs and the 1997 TNM classification is generally applied.

Real indications for adrenalectomy in renal cell carcinoma.

Objectives: We determined the incidence and characteristics of adrenal involvement in localized and advanced renal cell carcinoma, and evaluated the role of adrenalectomy as part of radical nephrectomy. Patients and Methods: From 1993 to 1999, 210 patients with renal cell carcinoma (RCC) (139 men and 71 women, mean age 60.8 years, range 12-96 years) underwent radical nephrectomy with associated adrenalectomy. Patients were divided into two subgroups of 106 with localized (stage T1-2 tumor, group 1) and 104 with advanced (stage T3-4N01M01, group 2) renal cell carcinoma. A retrospective review of preoperative computerized tomography (CT) of the abdomen was performed. Radiographic findings were subsequently compared with postoperative histopathological results to assess the predictive value of tumor characteristics and imaging in determining adrenal metastasis. Results: Of the 210 patients, 15 (7.1%) had adrenal involvement. Tumor stage correlated with probability of adrenal spread, with T3-4 and T1-2 accounting for 13.4% and 0.9% of cases, respectively ( p < 0.001). Upper pole intrarenal RCC most likely to spread was local extension to the adrenal gland, representing 53.3% of adrenal involvement. In contrast, multifocal, lower pole and mid region RCC tumors metastasized hematogenously, representing 21.4%, 7%, and 14% of adrenal metastasis, respectively. The relationship between intrarenal tumor size (mean 7.8 cm, range 4-21) and adrenal involvement was not statistically significant. Preoperative CT demonstrated 97.7% specificity, 98.4% negative predictive value, 87% sensitivity and 80% positive value for adrenal involvement by RCC. Conclusions: Ipsilateral adrenalectomy should only be performed if a lesion is seen preoperatively on CT scan or if gross disease is seen at the time of nephrectomy. The prognosis is poor for RCC with ipsilateral involvement even with complete removal. Because of this poor prognosis we believe that adrenal involvement should constitute a separate stage category.