Pathological analysis

All specimens were processed and evaluated at the Institute of Pathology, University of Bern, Switzerland. Pathologists experienced in genitourinary pathology examined the cystectomy specimens and nodal tissues. No single pathologist examined all specimens but a common protocol was used. The bladder was filled with formalin and fixed at least overnight. Tumor characteristics noted were localization, size, extent of invasion, and multifocality. Sections for histology were taken from the tumor(s), including the site of deepest macroscopic invasion, the anterior, posterior and lateral walls of the bladder, the bladder neck with trigone, the dome of the bladder, and any macroscopically abnormal area of the mucosa (Fig. 1). Any residual ulcer after transurethral resection was sectioned in toto. Histologically, tumor type, tumor grade, tumor stage, the presence of vascular invasion, and carcinoma-in-situ were assessed. LNs were identified visually, by palpation, and by sectioning within each package after tissue had been degreased with acetone. All macroscopically detected LNs larger than 5 mm were cut into 2-mm to 4-mm-thick sections and completely embedded in paraffin. If no LNs could be identified, the entire tissue was embedded for histologic examination. One section per paraffin block was taken. The total number of LNs and the number bearing metastases were recorded for each site separately. Pathological staging was done according to the 1997 American Joint Committee on Cancer TNM classification.