Urinary carcinogen [nitrosamine] production in a rat animal model for ureterosigmoidostomy

Tumor development at the site of ureterointestinal anastomosis is a recognized complication in patients undergoing ureterosigmoidostomy. In order to explore the hypothesis that carcinogens (nitrosamines) may be a factor in ureterosigmoidostomy, female Sprague-Dawley rats (n = 125) underwent urethral ligation, bladder dome resection and anastomosis of the bladder trigone to an opening in the anterior rectosigmoid wall. Biweekly nitrosamine determinations were performed on the resultant urine-feces slurry by gas chromatography up to thirty-two weeks post surgery. Nitrosamine (N,N-dimethylnitrosamine) was noted as early as two weeks after surgery in 39% (11/28) of rats. One hundred percent of animals consistently demonstrated nitrosamine by week 14 (32 rats). Nitrosamine levels increased throughout the study with a peak level after thirty-two weeks of 0.275 micrograms./ml. Only a portion (n = 40) of the total animal population was deemed suitable for pathologic examination secondary to animal demise and autolysis at autopsy related to infection and obstruction. In these animals, no adenocarcinoma was found although hyperplastic changes and metaplastic changes were demonstrable at nine days and eight weeks respectively. In one animal a grade I transitional cell papilloma was identified after eight weeks. Control animals demonstrated no nitrosamine production. In vitro combinations of rat urine and feces yielded nitrosamine after six weeks. The absence of adenocarcinoma tumor development is believed indirectly related to animal demise in that not enough time had elapsed to allow significant tumor development. This study lends support to the concept that nitrosamines may play a role in the development of hyperplasia, dysplasia and eventual neoplasia in ureterosigmoidostomy.