Enhancement of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide-induced carcinogenesis by urinary tract infection in rats.

Epidemiological studies suggest that urinary tract infection is an important risk factor in the development of bladder cancer. Chronic urinary tract infection in rats is associated with urothelial hyperplasia and papillomatosis. In the Sprague-Dawley strain, exposure to the 5-nitrofuran, N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT), is associated in particular with the development of renal pelvic tumors. The present study was designed to evaluate whether chronic urinary tract infection could enhance tumor development in FANFT-induced urinary tract carcinogenesis. One hundred forty-four female Sprague-Dawley rats were divided into the following groups. Group 1 received 0.2% FANFT in the diet for 7 wk followed by control diet. Group 2 received 0.2% FANFT in the diet for 7 wk followed by control diet. One wk after completion of FANFT administration, the suspension of 0.5 ml of Escherichia coli (06K13H1) was injected into the bladder through the urethra. Group 3 received 0.2% FANFT in the diet for 7 wk followed by control diet. One wk after completion of FANFT administration, a suspension of heat-killed E. coli (06K13H1) was injected into the bladder through the urethra. Group 4 received a suspension of 0.5 ml of E. coli (06K13H1) through the urethra and received control diet throughout the experiment. Group 5 was fed control diet only. The experiment continued for 104 wk. A significantly higher number of urinary tract tumors, particularly of the renal pelvis, was recorded in Group 2 compared to Groups 1, 3, 4, and 5. The majority of the rats in Groups 2 and 4 had morphological signs of urinary tract infections, particularly pyelitis and/or pyelonephritis. Thus, a single injection of E. coli (06K13H1) into the bladder results in an enhancement of FANFT-induced urinary tract carcinogenesis in the Sprague-Dawley rat, especially for renal pelvic tumors. The formation of dimethylnitrosamine or other nitroso compounds from nitrates in the urine or increased cell proliferation due to chronic inflammation or both may be important pathogenetic factors in the tumor development.

Primary adenocarcinoma of the urinary bladder. A clinicopathologic and prognostic study.

The study is a clinicopathologic report on 64 patients with primary adenocarcinoma of the urinary bladder and urachus, with particular reference to important prognostic and therapeutic factors. All tumors exhibited adenocarcinomatous features in at least two thirds of the examined tumor area. Pure forms of the different histological patterns were seen in 50% of the cases and in the remaining tumors a mixture was recorded. Poorly differentiated tumors were found in 41 cases. All tumors were invasive and in 40 cases the tumors penetrated through the bladder wall. The pattern and frequency of metastasis was similar to that of conventional bladder tumors of high stage. The prognosis for patients with primary adenocarcinoma of the bladder was poor and the 5-year survival rate in this study was 18%. Important prognostic factors were tumor stage, size and grade and treatment. The location of the tumor seemed less important and tumors located in the dome or anterior wall did not indicate a poorer prognosis. The adenocarcinomas of the urinary bladder were predominantly solitary tumors. They were poorly differentiated, deeply invasive large tumors associated with an exceedingly poor prognosis. Partial bladder resection appears to be adequate therapy only in patients with moderately well differentiated small tumors. In other cases more radical therapy must be considered.

The influence of phenacetin or mechanical perforation on the development of renal pelvic and urinary bladder tumors in FANFT-induced urinary tract carcinogenesis.

The influence of 0.535% phenacetin in the diet or mechanical perforation of the renal pelvis and urinary bladder of male Sprague-Dawley rats in FANFT-induced urinary tract carcinogenesis was studied. The 151 rats were divided into 5 experimental and one control group. The rats were followed for up to 80 weeks. FANFT administered at 0.2% in the diet for 11 weeks resulted in a high incidence of urinary tract tumors particularly of the renal pelvis. Similar results were obtained by administration of 0.2% FANFT for 6 weeks followed by 0.535% phenacetin while FANFT for 6 weeks preceded or followed by mechanical perforation of the renal pelvis resulted in a significantly lower incidence of renal pelvic tumors. Phenacetin appeared to enhance the development of renal pelvic tumors in FANFT-induced urinary tract carcinogenesis. In contrast no effect of phenacetin on the urinary bladder could be detected.