Flow-cytometric and quantitative histologic parameters as prognostic indicators for occult retroperitoneal disease in clinical-stage-I non-seminomatous testicular germ-cell tumors

Our study was performed to clarify whether the combination of DNA flow-cytometric and quantitative histopathological parameters improves the prediction of occult metastatic disease in clinical stage-I non-seminomatous testicular germ-cell tumors (NSGCT). We used archival paraffin primary-tumor tissue of 67 clinical stage-I NSGCT patients who had undergone retroperitoneal lymph-node dissection (RPLND). According to the RPLND specimens, 24 patients were at pathological stage I and 43 at pathological stage II. Archival blocks were redissected for histological re-evaluation. In addition, 50 μm sections were prepared according to the Hedley technique in order to obtain nuclear suspensions which were processed for flow cytometry (FC). In univariate analysis, the percentage of embryonal carcinoma, the percentage of immature teratoma and vascular invasion were the most accurate predictive histopathological parameters. The percentage of aneuploid cells in S-phase was the best predictive FC parameter. In multivariate analysis, the percentage of embryonal carcinoma and the S-phase fraction of aneuploid cells were the only independent markers for occult metastatic disease. According to this statistical approach, 91.0% of pathological stage-I and stage-II cases were correctly classified. Sensitivity was 95.3% and specificity was 83.3%. Using histopathological criteria alone, only 56.7% NSGCT patients were correctly classified.     

Extended radical lymphadenectomy in patients with urothelial bladder cancer: results of a prospective multicenter study

PURPOSE: Previous studies demonstrate a positive correlation between postoperative survival and the extent of pelvic lymphadenectomies in patients with bladder cancer. However, the distribution of nodal metastases has not been examined in sufficient detail. Therefore, we conducted a comprehensive prospective analysis of lymph node metastases to obtain precise knowledge about the pattern of lymphatic tumor spread. MATERIALS AND METHODS: Between 1999 and 2002 we performed 290 radical cystectomies and extended lymphadenectomies. Cranial border of the lymphadenectomy was the level of the inferior mesenteric artery, lateral border was the genitofemoral nerve and caudal border was the pelvic floor. We made every effort to excise and examine microscopically all lymph nodes from 12 well-defined anatomical locations. RESULTS: Mean total number and standard deviation of lymph nodes removed was 43.1 +/- 16.1. Nodal metastases were present in 27.9% of patients. The percentage of metastases at different sites ranged from 14.1% (right obturator nodes) to 2.9% (right paracaval nodes above the aortic bifurcation). By studying cases of unilateral primary tumors or with only 1 metastasis we observed a preferred pattern of metastatic spread. However, there were many exceptions to the rule and we did not identify a well-defined sentinel lymph node. CONCLUSIONS: We strongly recommend extended radical lymphadenectomy to all patients undergoing radical cystectomy for bladder cancer to remove all metastatic tumor deposits completely. The operation can be conducted in routine clinical practice and our data may serve as a guideline for future standardization and quality control of the procedure.     

Refluxing ureterointestinal anastomosis for continent cutaneous urinary diversion

PURPOSE: We question the statement that anti-refluxing ureteral implantation is mandatory in low pressure, high capacity reservoirs. In a series of patients with ureteral obstruction after implantation with an anti-refluxing submucosal tunnel reimplantation was performed as a direct ureter-pouch anastomosis. The same technique was used for primary anastomosis in a later group of patients as the method of choice for ileocolic and colonic continent urinary diversion. MATERIALS AND METHODS: Direct ureteral reimplantation was performed in 10 patients in whom a total of 19 obstructed renal units were associated with an ileocolic reservoir. The retroperitoneal supracostal approach was used to avoid complications caused by repeat laparotomy. The ileocecal reservoir was opened superior and the obstructed ureter was identified and reimplanted via a buttonhole. The same technique was used for primary anastomosis in 20 patients (40 renal units), in whom the ureter was implanted in an ileocecal (10) or colonic (10) pouch. RESULTS: Postoperatively complications did not develop in any patient. Radiography of the pouch postoperatively showed renal reflux in only 1 renal unit. In the group with reimplanted ureters median followup was 81 months (range 10 to 120). Of the 19 obstructed ureters 14 returned to normal, while 5 showed persistent grade I dilatation. Median followup in patients with primary direct ureteral anastomosis was 20 months (range 2 to 36). Of the 22 preoperatively dilated systems 20 returned to normal and none of the 18 nondilated systems was obstructed. CONCLUSIONS: Direct ureter-pouch reimplantation proved to be simple and safe. When performed primarily for continent urinary diversion, the anastomosis was anti-refluxing in pouches with high capacity and low pressure. The advantage of this technique is the low risk of ureteral obstruction and subsequent deterioration in kidney function.     

Loss of heterozygosity on chromosome 5p13-12 predicts adverse prognosis in advanced bladder cancer independent of tumor stage and grade

PURPOSE: The individual prognosis in patients with bladder cancer is only partially predicted by tumor stage and grade. Various molecular markers have been shown to correlate with disease progression and prognosis but few add some predictive capacity beyond that offered by standard clinical and pathological parameters. MATERIALS AND METHODS: A total of 191 urothelial carcinomas from 157 patients were analyzed. Paired normal and tumor cells were microdissected by manual and microbeam-microdissection of membrane mounted native tissue, and analyzed for loss of heterozygosity (LOH) at a critical region of LOH on chromosome 5p13-12 that is involved in bladder cancer progression. LOH data were correlated with progression-free and tumor specific survival by multivariate analysis. RESULTS: Informativity of the assay was 60.7%. Log rank analysis of 100 evaluable patients showed a progression-free survival benefit without LOH at 5p13-12 of more than 3 years (p <0.01). Mean followup was 36 months. Multivariate analysis revealed that this benefit was not predicted by tumor stage and grade alone in advanced disease (stages T3/4 and/or N+/M+, stages III/IV). CONCLUSIONS: LOH at the critical region on chromosome 5p13-12 is a molecular marker of adverse prognosis in advanced bladder carcinoma independent of tumor stage and grade.     

Significance of pelvic lymphadenectomy for the prognosis after radical cystectomy

OBJECTIVE: In contrast to other carcinomas such as breast or colon cancer, there are no guidelines regarding the number and location of lymph nodes to be removed during radical surgery in patients with invasive bladder carcinoma. The therapeutic effect of pelvic lymphadenectomy and its influence on tumour staging has not been documented yet. METHODS: Here we present an evaluation of pelvic lymph nodes from 484 patients who underwent radical cystectomy with curative intention between 1986 and 1999. The number of lymph nodes was correlated with the depth of invasion of the primary tumour, occurrence of nodal metastases, clinical outcome, the operating surgeon, and the pathologist. RESULTS: There were 484 patients with a mean age of 62.7 years. Clinical follow up was available from 321 patients with a mean follow up period of 35.9 months. The average number of lymph nodes removed was 14.3 (range: 1-46). The number of lymph nodes removed varied significantly between different surgeons and did not correlate with the pathologists. There was a significant correlation between the number of lymph nodes removed and the tumour-free survival in pT2 or pT3 tumours and in patients without lymph node metastases. Multivariate analysis revealed that pT-category (p < 0.01), pN-category (p < 0.01), and the total number of lymph nodes removed (p = 0.04) were the most important factors affecting survival. CONCLUSION: The more extensive lymphadenectomy significantly improved the prognosis of patients with invasive bladder cancer and therefore, represents a potentially curative procedure. The results indicate a need for a standardised lymph node dissection.     

Single potential analysis of cavernous electrical activity

Summary Recording of cavernous electric activity was performed in 178 patients with erectile dysfunction and in 37 normal patients. In 34/37 normal patients, potentials of a uniform shape were recorded during flaccidity: At cut-off frequences of 0.5–500 Hz, the length was 8–18 (mean 12.8, SD 2.8), the amplitude 250–750 (mean 444, SD 109) V, and the polyphasity 8–22 (mean 13.8, SD 3.3). In impotent patients with upper motor neuron lesions or peripheral lesions, specific types of potentials were observed. In 11/14 impotent patients with insulin-dependent diabetes for over 20 years and clinical findings of cavernous myopathy, potentials showed low amplitude, irregular shape, and slow depolarizations. In 51% of the consecutive impotent patients, abnormal findings of cavernous electric activity were recorded. Our clinical study suggests that single potential analysis of cavernous electric activity (SPACE) may be useful in the diagnosis of cavernous autonomic neuropathy and cavernous smooth muscle myopathy.This study was supported by a grant of the Deutsche Forschungsgemeinschaft (Sti 96/2-1)Part of this paper was presented at the 10th Symposium of the Association for Experimental Urology of the German Urological Society, June 21–23, 1990, Munich, FRG     

Mutations of the flavin-containing monooxygenase gene (FMO3) cause trimethylaminuria, a defect in detoxication

Individuals with the recessive condition trimethylaminuria exhibit variation in metabolic detoxication of xenobiotics by hepatic flavin- containing monooxygenases. We show here that mutations in the human flavin-containing monooxygenase isoform 3 gene ( FMO3 ) impair N - oxygenation of xenobiotics and are responsible for the trimethylaminuria phenotype. Three disease-causing mutations in nine Australian-born probands have been identified which share a particular polymorphic haplotype. Nonsense and missense mutations are associated with a severe phenotype and are also implicated in impaired metabolism of other nitrogen- and sulfur-containing substrates including biogenic amines, both clinically and when mutated proteins expressed from cDNA are studied in vitro . These findings illustrate the critical role played by human FMO3 in the metabolism of xenobiotic substrates and endogenous amines.