Chronic pancreatitis frequently generates complications through involvement of adjacent organs. Distal common bile duct stenosis and segmental duodenal stenosis, the most frequent complications, are usually treated by resection or bypass procedures. This study presents experience with duodenum-preserving resection of the head of the pancreas in the treatment of patients with chronic pancreatitis with predominant involvement of the pancreatic head and coexisting complications involving adjacent organs. This procedure preserves the structure and function of the bile duct and duodenum. Sixty-six patients with severe chronic pancreatitis underwent duodenum-preserving resection of the head of the pancreas. Thirty-eight had associated complications of neighbouring organs: 37 had distal common bile duct stenosis, seven had duodenal stenosis, ten had evidence of segmental portal hypertension and one suffered from a pancreatopleural fistula. Details of all patients were documented prospectively; mean follow-up was 4.2 years. The complications of adjacent organs were permanently eradicated in 36 of 38 patients. Two patients required endoscopic stenting for persisting bile duct obstruction. There was substantial or complete relief of all symptoms in 35 patients. Duodenum-preserving resection of the head of the pancreas is effective in the treatment of severe chronic pancreatitis with predominant involvement of the pancreatic head and provides definitive management of associated complications of adjacent organs.

Summary Epidemiological and experimental studies suggest that androgens influence colonic carcinogenesis. We investigated the effects of hormonal manipulations (surgical and chemical castration, hormone substitution) on colonic tumour development, tumour and mucosal histopathology, and epithelial proliferation in macroscopically normal colonic mucosa in male rats, after induction of chemical colon carcinogenesis by subcutaneous injections of azoxymethane (AOM). Chemical castration with cyproterone acetate, but not surgical castration, resulted in increased colonic tumorigenesis, which was accompanied by decreased crypt length, decreased number of cells per crypt, and increased crypt epithelial mitotic index in the right colon. Chemically castrated rats also had crypt hyperplasia and increased numbers of dysplastic foci in the left colon which were not seen with surgical castration. By contrast, rats given testosterone after surgical castration showed decreased colonic tumorigenesis with an increased proportion of tumours in the left colon and lower percentage of tumours with invasion. The grossly normal mucosa of the testosterone-substituted castrated rats showed decreased crypt length in the right colon similar to the other groups of castrated rats, but no significant increase in mitotic index. Our results suggest that the anti-androgenic progestin cyproterone is a potent enhancer of colonic tumorigenesis and epithelial proliferative abnormalities after AOM administration. Exogenous testosterone after castration alters tumour distribution and characteristics and suppresses epithelial proliferative abnormalities. Finally, androgen effects on the colonic mucosa are more prominent in the right than in the left colon, suggesting different influences of hormones on the epithelium of these anatomical sites.An important role for androgens in colonic carcinogenesis in humans has been suggested on the basis of detection of specific receptor proteins in human colorectal tissue (Odagiri et al., 1984, Jacobson 1984. Chemically induced colonic carcinogenesis models in rats have been used to study modulators of colonic carcinogenesis (Autrup & Williams, 1983). Some authors reported specific androgen receptor proteins in chemically induced colonic tumours (Mehta et al., 1980;Krelenbaum et al., 1984;Jacobson, 1984). In addition, hormonal manipulations have been reported to influence tumour yield (Balish et al., 1977;Moon & Fricks, 1977;Mehta et al., 1978;Izbicki et al., 1983). These findings seemed to support a possible role of androgens in colonic carcinogenesis.Recently, we reported the effects of hormonal manipulations on chemically induced colonic carcinogenesis and androgen receptors in macroscopically normal mucosa and colonic tumours (Izbicki et al., 1986). In the present publication we present our evaluation of the mechanisms of the observed effects. Materials and methods Experimental protocolTwo hundred 8-week-old male Sprague-Dawley rats weighing 230-275 g (Wiga, Sulzfeld, FRG) were randomly allocated to five groups ...

The rat model of azoxymethane-induced colonic carcinogenesis was evaluated for the occurrence of an adenoma-carcinoma sequence analogous to that in human beings. Male 10-week-old Fischer 344 rats were given 10 weekly subcutaneous injections of azoxymethane at a dose of 15 mg/kg. Every 2 weeks after the first dose, 5 animals were necropsied. A colon tumor was identified first at week 10. At week 16, at least 60% of the rats generally had a colon tumor. The mean size of the tumors tended to increase progressively during the study. Histopathologic examination showed invasion of the muscularis mucosae or deeper layers of the colonic wall in 74% of the tumors. Invasion was unrelated to the size of the tumors, being identified in even the smallest tumors of 1–2 mm of diameter. Invasion was also unrelated to the severity of dysplasia in the tumors, occurring in 83 % of the tumors with low-grade dysplasia, but in 69% of the tumors with high-grade dysplasia. No tumor showed the histopathologic features of an adenoma giving rise to an invasive carcinoma. The findings indicate that an adenoma-carcinoma sequence analogous to that in human beings does not occur in the rat model of azoxymethane-induced colonic carcinogenesis.

The rat model of azoxymethane (AOM) induced colonic carcinogenesis was evaluated for preneoplastic changes in epithelial DNA synthesis and histopathologic characteristics analogous to those observed in human beings at high risk for colonic carcinoma. 10-week-old male Fischer 344 rats were given 10 weekly subcutaneous injections of AOM at a dose of 15 mg/kg. Every 2 weeks after the first carcinogen dose, 5 animals were sacrificed 1 h after an intraperitoneal injection of methyl-³thymidine, 0.5 mCi/kg body weight. The experiment was terminated 25 weeks after the first AOM injection. By autoradiography, the labelling index (LI) of the ascending colon (AC) was 8.6 ± 0.5 % for AOM-treated animals and 4.7 ± 0.94% for controls (p < 0.05). In the descending colon (DLC) the LI was 10.3 ± 0.9% for AOM-treated animals as compared to 6.8 ± 1.4% for controls (p < 0.01). In the AC the main zone of DNA synthesis shifted from the lower third to the middle third of the crypt in AOM-treated rats, while in the DLC the zone remained in the basal third. No crypt epithelial hyperplasia was found with carcinogen treatment. Crypt elongation, crypt dilatation, and mucosal edema formation were associated with the course of AOM administration and appeared to be toxic effects. In contrast, the mucus content of the crypt epithelium showed a biphasic decrease over the entire time course of the study. Dysplastic crypts appeared earlier in the AC, however, and the early appearance was associated with persistently elevated labelling indices and shift in the main zone of DNA synthesis. We conclude that in experimental colonic carcinogenesis, preneoplastic changes in cell proliferation (‘stage I’ and ‘stage IF abnormalities) similar to those in human beings at high risk can be observed. Thus, despite the absence of an adenoma-carcinoma sequence, experimental colonic carcinogenesis provides an important model to study modulators of preneoplastic changes and their impact on malignant transformation of colonic mucosa.