Do Orthotopic Ileal Diversions Induce Immunological Changes in Retained Urethral Tissue?

BACKGROUND: A second primary tumors of the urethra (urethral recurrence) after radical cystectomy has been reported to be more infrequent in patients with ileal orthotopic (neobladder) compared to incontinent diversions. OBJECTIVE: To investigate whether an altered immunogenic environment of urethral tissue is induced by urethro-ileal anastomosis. METHODS: Between 10/2008 and 12/2009 urethral biopsies of 19 patients (9 neobladder patients, 10 control patients without urethra-ileal anastomosis) were evaluated by conventional histopathological examination and immunohistochemistry for T- (CD3/CD5, CD4, CD8) and B-cell markers (CD20/22, CD79a, CD138). After semi-quantitative assessment, relative cell fractions (B vs. T cells) and subclasses (T4-helper vs. T8-killer cells vs. B cell clones, plasma cells) in neobladder vs. control patients were studied. Unpaired t-test was used for statistical analysis. RESULTS: Of 19 included patients, 16 were eligible for analysis (7x neobladder, 9x controls). All neobladder patients had undergone cystectomy for UBC. Comparing relative fractions of cells positive for T- and B-cell markers in NB and CO patients, no statistical differences were observed. In 4/7 neobladder patients relative fraction of CD79a positive B-cells was higher than relative fraction of CD3/CD5 positive T-cells (B/T-ratio 1.3). B cells were predominantly CD138 positive plasma cells (5/7 NB patients). Relative B-cell fraction was lower than T-cell fraction in 7/9 control patients (B/T-ratio 0.6). Neither CD 138 positive plasma cells nor CD22 positive B cell clones were predominant. T-helper and CD8 positive T-killer cells were equally distributed in both neobladder (CD4/CD8-ratio: 2.1) and control patients (CD4/CD8-ratio: 1.9). CONCLUSIONS: Comparing neobadder and control patients the distribution of B- and T-cells was statistically not different. However, a trend towards an increased presence of B-cells in urethral tissues of NB patients that could become relevant in a larger study might be suggestive for an immunological response induced by connecting urethral and ileal tissue.