Synchronous gastric and ampullary adenocarcinomas in a hairy cell leukemia patient treated with pentostatin eight years prior.

Hairy cell leukemia patients are at increased risk for second malignancies, including both solid and lymphoid neoplasms. Along with other factors, multiple immune defects present in hairy cell leukemia likely contribute to subsequent carcinogenesis. We report herein a case of synchronous high-grade gastric and ampullary adenocarcinomas in a patient with a history of hairy cell leukemia treated eight years prior with pentostatin. We include a review of immune alterations induced by both hairy cell leukemia and its therapies, and link them with the occurrence of second cancers in these patients.

Inhibition of streptozotocin-induced islet cell tumors and N-nitrosobis(2-oxopropyl)amine-induced pancreatic exocrine tumors in Syrian hamsters by exogenous insulin.

The effects of streptozotocin (SZ) and N-nitrosobis(2-oxopropyl)amine (BOP), separately or in combination, on the pancreas, common duct, and gallbladder, all target tissues of BOP, were studied in Syrian golden hamsters. Groups of hamsters were treated with either a single dose (20 mg/kg body weight) of BOP (BOP group), or a single i.p. dose (50 mg/kg body weight) of SZ and 14 days later with a single s.c. injection of the same dose of BOP (SZ + BOP group). Another group of animals was treated similarly with BOP and SZ except that they received twice daily injections of insulin, beginning 1 day after SZ administration and for the duration of the experiment (52 weeks) (SZ + insulin + BOP group). The control group consisted of hamsters treated with a single dose of BOP and daily doses of insulin (insulin + BOP group). Hamsters treated with SZ recovered spontaneously from their diabetes, although the mortality was high (86%). BOP treatment inhibited the diabetogenic effects of SZ in both SZ + BOP and SZ + insulin + BOP groups and reduced the mortality to 43 and 74%, respectively. SZ pretreatment inhibited the incidence of BOP-induced pancreatic ductal/ductular cell carcinomas in the SZ + BOP group (P less than 0.01); this protective effect of SZ on carcinoma development was potentiated by additional treatment with insulin (SZ + insulin + BOP group, P less than 0.001). Although the frequency of BOP-induced tumors in the gallbladder (all polyps) was not altered by either SZ or insulin, the frequency of the common duct polyps was significantly lower in the SZ + insulin + BOP group than in the BOP group (P less than 0.005). Hamsters in the SZ, SZ + BOP, and SZ + insulin + BOP groups developed islet cell adenomas (insulomas). However, the SZ + insulin + BOP group had significantly fewer insulomas than in the SZ + BOP group (P less than 0.0005). The overall data confirm the inhibitory effect of SZ on BOP-induced pancreatic cancer and suggest that this effect is related to the diabetic condition of hamsters rather than insulin deficiency and that intact islets appear to be prerequisite for exocrine pancreatic cancer induction by BOP. On the other hand, the inhibitory action of insulin on insuloma induction by SZ and on ductal/ductular cancer induction by BOP seems to be related to the suppressive effect of this hormone on beta-cell and ductal/ductular cell replication, respectively.

Effect of secretin on pancreatic carcinogenesis in the hamster model.

Secretin (SEC) given s.c. to hamsters at a dose of 100 clinical units/kg body weight by 6 injections each 30 min apart, inhibited induction of pancreatic cancer when it was given prior to or simultaneously with a single dose of N-nitrosobis(2-oxopropyl)amine (BOP), but was ineffective in modifying tumor incidence when it was administered after BOP. The incidence of gall bladder and common bile tumors were not influenced, regardless of the time of SEC injections, implying that the inhibitory effect of this secretagogue is pancreas specific. However, a treatment schedule in which BOP and SEC were given weekly for 20 weeks did not alter the incidence of pancreatic tumors.

Regional lipiodolized chemotherapy for cholangiocarcinoma associated with oral contraceptives.

We describe a case of cholangiocarcinoma in a young woman, who presented with cholestatic jaundice following oral contraceptive ingestion. Following diagnostic laparotomy she received intra-arterial 'lipiodolized' chemotherapy. Intravenous mitozantrone was given for 2 years and she is asymptomatic, with computed tomographic evidence of tumour response, 27 months after diagnosis. We suggest that this form of treatment is of value for cholangiocarcinoma.

Common duct carcinoma and obstruction in female hamsters treated with N-nitrosobis(2-oxopropyl)amine and/or cholecystectomy.

Detailed histologic observations were performed on the head of the pancreas of hamsters treated with 10 mg/kg body weight N-nitrosobis(2-oxopropyl)amine (BOP) once a week for 6 weeks with or without cholecystectomy. Cholecystectomy was performed 5 weeks before starting BOP initiation. The incidence of head cancers was 100% and cholecystectomy did not affect pancreatic carcinogenesis by BOP. Common bile duct dilatation was produced by advanced pancreatic head carcinomas and microadenocarcinomas in common duct. Micro-adenocarcinomas were not macroscopically detected since the tumors were located in the lumen of common duct.

Biliary carcinoma associated with methyldopa therapy.

In a retrospective study of 82 patients with biliary carcinoma a higher than expected prevalence of methyldopa therapy was found. Carcinogenesis by electrophile reactive metabolites of methyldopa is discussed.