Shinsuke Matsuda

Somatostatinoma of the papilla of Vater with multiple gastrointestinal stromal tumors in a patient with von Recklinghausen's disease.

We report a case of somatostatinoma of the papilla of Vater with multiple gastrointestinal stromal tumors in a patient with von Recklinghausens disease (VRD). A 64-year-old woman who had had recurrent attacks of acute pancreatitis and cholangitis was found, on gastroduodenal endoscopy, to have a tumor of the papilla of Vater and multiple submucosal tumors of the stomach and duodenum. Numerous submucosal tumors were observed in the stomach, duodenum, and jejunum, and total excision of the papilla of Vater and resection of the duodenal and jejunal submucosal tumors was performed. The tumor of the papilla of Vater showed the histologic appearance of a dense proliferation of tumor cells in acinar form, from the duodenal mucosa to the muscle layer, and psammoma bodies were revealed within the tumor. Immunohistologically, the tumor cells were intensely positive for somatostatin. The submucosal tumors of the duodenum and jejunum were negative for smooth muscle actin, s-100, and neuron-specific enolase (NSE), and positive for CD34 and c-kit, and they were diagnosed as gastrointestinal stromal tumors (GISTs) according to the strict definition. The only 25 cases of papilla of Vater somatostatinoma associated with VRD to have been reported in the English-language literature since 1982 are reviewed, as well as our own case.

Effect of Pancreatic Juice Reflux into Biliary Tract on N-Nitrosobis(2-oxopropyl)amine (BOP)-Induced Biliary Carcinogenesis in Syrian Hamsters

To elucidate the possible role of pancreaticjuice reflux into the biliary tract in promoting thedevelopment of biliary carcinoma, Syrian hamsters weresubjected to cholecystoduodenostomy and ligation of the distal end of the common duct and thensubcutaneously injected withN-nitrosobis(2-oxopropyl)amine (BOP) (experimentalgroup). The incidences of gallbladder carcinoma andextrahepatic bile duct carcinoma in the experimental group wassignificantly higher than in the sham-operated group (P< 0.01, P < 0.05). The proliferating cell nuclearantigen (PCNA) labeling indices of both regionsgradually increased with time, and were significantlyhigher in the experimental group at weeks 9 and 16 thanin the sham-operated group at the same time. Trypsin andphospholipase A2 (PLA2) activitiesin bile and tissue levels of superoxide dismutase (SOD) inthe gallbladder and extrahepatic bile ducts were higherin the experimental group than in the sham-operatedgroup. These findings suggest that the carcinogenic effect of BOP was enhanced in biliaryepithelium that had proliferated in response to and/orhad been injured by activated pancreatic enzymesrefluxing into the biliary tract and then increased freeradical activity, leading to a high frequency ofcarcinoma development in the biliary tract.

Gastric amyloidosis with massive bleeding requiring emergency surgery

Abstract: We report a 66-year-old woman who had massive bleeding from a gastric ulcer complicating primary systemic amyloidosis, in whom emergency surgery proved lifesaving. Physical examination revealed anemia and macroglossia. Gastroscopy was performed, and an extensive, irregular, hemorrhagic ulcer was found in the gastric body. Biopsy resulted in a diagnosis of amyloidosis. On the 11th hospital day the patient went into shock as a result of a massive hemorrhage. Emergency surgery was performed, but the extent of the submucosal lesion in the stomach could not be identified, and total gastrectomy was unavoidable. Histological examination of the surgical specimen and biopsy tissue collected from other organs revealed amyloid deposition extending from the submucosa to the muscularis propria of the stomach. There was also deposition of large amounts of amyloid around the small blood vessels in the liver and under the mucosa of the small intestine. The amyloid was AA-antibody-negative and resistant to treatment with K2MO4, and a diagnosis of AL-type systemic amyloidosis was made. The patients general condition recovered after the operation, but on the 103rd hospital day, she experienced sudden onset of arrhythmia and died. Patients with amyloidosis in whom gastrointestinal surgery is performed are rare; only 41 cases, including our own, have been reported in the Japanese literature since 1972.

Central Bisegmentectomy of the Liver plus Caudate Lobectomy for Carcinoma of the Gallbladder

Central bisegmentectomy of the liver is recommended as a radical surgical procedure for patients with liver-bed gallbladder carcinoma, which tends to directly invade the hepatic parenchyma through the liver bed. In this article, we describe the indications and our surgical techniques for central bisegmentectomy of the liver plus caudate lobectomy for carcinoma of the gallbladder. We employ combined resection of the caudate lobe, because the caudate lobe often becomes involved even in patients with liver-bed carcinoma. Resection of the extrahepatic bile duct is also required to achieve complete lymphadenectomy within the hepatoduodenal ligament, because tumor invasion of the hepatoduodenal ligament is frequently found. Extensive lymphadenectomy around the head of the pancreas together with removal of the para-aortic lymph nodes should be performed in patients with extensive lymph node metastases.

Insulin-like growth factor II-producing intra-abdominal hemangiopericytoma associated with hypoglycemia

We report a patient with insulin-like growth factor (IGF)-II-producing hemangiopericytoma with hypoglycemia in whom repeated intra-abdominal recurrences developed over a period of about 10 years and tumor resection was performed four times. A 67-year-old woman was admitted to our hospital in 1995 because of hypoglycemic attacks. In 1985, partial resection of the small bowel had been performed for a 17-cm abdominal tumor of the transverse mesocolon, and the pathological diagnosis was hemangiopericytoma. In 1991, left hemicolectomy had been performed for a mesosigmoidal tumor associated with hypoglycemia. In 1994, hysterectomy, bilateral adnexectomy, and resection of an intrapelvic tumor were performed. The fourth operation was performed in 1996, about 10 years after the first operation. The spleen was removed, together with more than 1500 tumors having a total weight of 1,660 g. The hypoglycemia was ameliorated after each operation. Before this operation, her serum IGF-I level was low, but her IGF-II level was within the normal range; however, the Western immunoblot method showed that most of the IGF-II was high-molecular-weight IGF-II. The tissue IGF-I level was also low, and the IGF-II level was high, suggesting an IGF-II-producing tumor. We suspect that the mechanism of the hypoglycemia in this patient was related to the high-molecular-weight IGF-II produced by the tumor. The patient died in 1997 because of tumor recurrence.

Chemoprevention of biliary carcinogenesis in Syrian hamsters by the novel carboxamide derivative IS-741 after initiation with N-nitrosobis(2-oxopropyl)amine (BOP)

To elucidate the possible inhibitory effect of a novel carboxamide derivative (IS-741) on biliary carcinogenesis, Syrian hamsters were subjected to cholecystoduodenostomy and ligation of the distal end of the common duct, and then given a regular diet (group I) or a diet containing 200 p.p.m. of IS-741 (group II). All hamsters were subcutaneously injected with N-nitrosobis(2-oxopropyl)amine until 10 weeks after surgery, and continued to feed on their respective dietary regimen until termination of the experiment at 16 weeks after surgery. Biliary adenocarcinomas were evaluated histologically. Non-cancerous and cancerous hepatobiliary tract tissues were analyzed for phospholipase A(2) (PLA(2)) activity, myeloperoxidase (MPO) activity, and the concentrations of prostaglandin (PG), i.e., prostaglandin E(2), 6-ketoprostaglandin F(1)alpha and thromboxane B(2). IS-741 significantly inhibited the development and multiplicity of hepatobiliary adenocarcinomas and reduced the proliferating cell nuclear antigen labeling indices in non-cancerous hepatobiliary tissues, compared with group I. The anti-cancerous effect of IS-741 was associated with a significant inhibition of PLA(2) and MPO levels in non-cancerous tissues of the extrahepatic biliary tract and the liver, and in cancerous tissue of the liver. Furthermore, IS-741 reduced the production of PGs in non-cancerous hepatobiliary tissues, compared with group I. Although the precise mechanism of action of IS-741 in preventing biliary tumorigenesis remains to be elucidated, it is likely to be related to modulation of arachidonic acid metabolism and/or suppression of neutrophil accumulation.

Inhibitory Effect of Loxiglumide (CR 1505), a CholecystokininReceptor Antagonist, onN-Nitrosobis(2-oxopropyl)amine-induced BiliaryCarcinogenesis in Syrian Hamsters

We evaluated the cholecystokinin (CCK)receptor antagonist loxiglumide (CR1505) for a possible inhibitoryeffect on biliary carcinogenesis in a hamster model. Experimental groupI underwent cholecystoduodenostomy and ligation of the distal end ofthe common bile duct, after which the animals were injected withN-nitrosobis(2-oxopropyl)amine (BOP) alone. Group II, afterthe same surgical procedure as in group I, were given injections of BOPand then given loxiglumide in their diet. The sham-operated groupunderwent simple laparotomy and then were given injections of BOP.Loxiglumide significantly inhibited BOP carcinogenicity in thegallbladder and extrahepatic bile duct but not in the intrahepatic bileducts or pancreas. Autoradiography showed that loxiglumidesignificantly suppressed 125I-Bolton-Hanter (BH)-CCK-8binding to CCK receptors in the gallbladder and extrahepatic bile ductbut not in the liver or pancreas, and CCK binding to its receptors wasobserved in an area identified as cancer tissue. CCK receptorantagonists have an inhibitory effect on BOP carcinogenesis in theextrahepatic biliary tract, including the gallbladder and extrahepaticbile duct, of Syrian hamsters. The difference in the inhibitory effectof loxiglumide on biliary carcinogenesis in hamsters according to sitemay be due to differences in CCK receptors or the affinity ofloxiglumide for such biliary tract organs. A difference betweencarcinogenesis in the intrahepatic bile ducts and extrahepatic biliarytract may be another reason.