Ultrastructural localization of blood group antigen A in normal and neoplastic urothelium

The subcellular distribution of the blood group antigen A in the transitional epithelium of the urinary tract and its neoplastic growths was studied using transmission immuno-electronmicroscopy. Sixty-five tissue specimens from 50 blood group A1 patients were processed according to an immunogold procedure which was optimized for preservation of both antigen and ultrastructure. The reactions were stronger in the glycocalyx of the luminal surfaces and at the interdigitating cytoplasmic processes of the cells. In the intracellular compartment the reactions were associated with tubulovesicular membrane-bound structures and with the Golgi complexes. Secretory products, intra- or extra-cellular, were also positive. The greatest variability was noted in the cell surface reactions, which were positive in 88% of normal but only 41% of neoplastic urothelial specimens. An inverse correlation was found between malignant behaviour and cell surface, but not intracellular, reactions. We conclude that, in transitional cell carcinomas, there is a quantitative defect in the processing of substance A which affects predominantly the cell surface component and may involve either the transport-insertion steps, the plasma membrane-associated glycosyltransferases or internalization of blood group antigen A.     

Further experience with seromuscular colocystoplasty lined with urothelium

PURPOSE: We report our continuing experience with seromuscular colocystoplasty lined with urothelium. This procedure is designed to preserve the urothelium and potentially decrease the incidence of complications associated with standard bladder augmentation. MATERIALS AND METHODS: We retrospectively reviewed the charts of 32 patients who underwent seromuscular colocystoplasty lined with urothelium between April 1994 and July 1999. Data were collected on patient demographics, surgical indications, previous and adjunctive surgical procedures, preoperative and postoperative urinary continence, upper urinary tract changes, urodynamic parameters, surgical complications and histological findings. RESULTS: Mean patient age at surgery plus or minus standard deviation was 11.1 +/- 4.8 years. Mean followup was 1.6 +/- 1 years. A mean of 1.5 +/- 0.9 years postoperatively urodynamic studies available in 28 cases showed that total and safe bladder capacity increased by 1.8 and 2.4-fold, respectively. Continence was achieved in 71% of patients after the initial procedure, increasing to 81% after secondary procedures. Hourglass deformity developed in 7 cases (22%), augmentation failed in 4 (12.5%) and there were bladder calculi in 2 (6%). New onset or increased hydronephrosis and reflux were present in 6 of 62 (10%) and 9 of 60 (15%) evaluated renal units, respectively. Of the 7 interpretable biopsies 5 revealed various degrees of repeat colonic mucosal growth. There was no bladder perforation or metabolic abnormalities, and mucous production was not clinically significant. CONCLUSIONS: Seromuscular colocystoplasty lined with urothelium is a viable alternative to standard bladder augmentation. The 2 procedures have a similar overall complication rate. Comparatively there appears to be a low incidence of bladder calculi, mucous production has not been clinically significant, metabolic disturbances have not developed and perforation has not occurred during short-term followup. We are enthusiastic about this technique and continue to apply it in select patients.     

治疗晚期或转移性尿路上皮癌的抗体偶联药物:enfortumab vedotin

enfortumab vedotin为一种抗体偶联药物,可与nectin-4结合释放出小分子细胞毒药物单甲基奥瑞他汀E。单甲基奥瑞他汀E具有抗有丝分裂的作用,能作用于微管蛋白抑制肿瘤生长。enfortumab vedotin可用于治疗晚期或转移性尿路上皮癌。常见不良反应有疲劳、外周神经病变、食欲下降、皮疹等。     

Therapeutic targets for overactive bladder other than smooth muscle

Introduction: For a long time, our concepts of regulation of urinary bladder function in health and disease as well as of the target structures of therapeutics have focused on detrusor smooth muscle cells. However, other structures including urothelium, afferent nerves and bladder blood vessels may also be important in pathophysiology and its treatment.

Areas covered: Based on a selective review of literature, we discuss the role of urothelium, afferent nerve fibers and bladder blood vessels in bladder pathophysiology and as targets for treatment.

Expert opinion: There is solid evidence now that multiple anatomical structures within the urinary bladder contribute to the regulation of its function and hence may be targets for established and emerging drugs. However, most previous studies have looked at the various target structures in isolation. In contrast, we propose that they should be seen as a network sensing and responding to alterations in the cellular environment or to xenobiotics. Studies are emerging in which the interaction of two of these structures is explored. Major advances in our understanding of bladder function are expected to result from studies integrating multiple such structures but these may be technically challenging and difficult to perform and interpret.