Yoshifumi Ogura

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.

Splenectomy does not offer immunological benefits in ABO-incompatible liver transplantation with a preoperative rituximab.

Background. Preformed anti-ABO antibodies are primarily responsible for antibody-mediated rejection (AMR) after ABO-incompatible (ABO-I) liver transplantation (LT) resulting in lethal hepatic necrosis and biliary complications. Splenectomy, an integral part of protocol for ABO-I LT, decreases anti-ABO antibodies. With the preoperative rituximab prophylaxis, role of the splenectomy for ABO-I LT is now under debate. We investigated the necessity of splenectomy by retrospective analyses of the short-term anti-ABO antibody response and long-term outcomes of ABO-I LT. Methods. Thirty-seven ABO-I LTs performed from May 2006 through July 2009, at Kyoto University Hospital, Kyoto, Japan, were retrospectively analyzed. Twenty-seven patients who underwent splenectomy (splenectomy group) received 329.6±35.8 mg rituximab 17.7±11.9 days before living donor LT. Ten patients without splenectomy (nonsplenectomy group) received 320.0±10.3 mg rituximab 26.6±21.3 days before transplantation. All patients received a posttransplant hepatic artery infusion with prostaglandin E1 and methylprednisolone. Perioperative anti-ABO immunoglobulin M and immunoglobulin G antibody titers, rejections, biliary complications, infections, and survival results were compared. Results. Preoperative rituximab with plasma exchange effectively reduced anti-ABO antibodies in both patient groups at the time of LT. There was no statistically significant difference observed in anti-ABO immunoglobulin M and immunoglobulin G antibody titers between the “splenectomy” and “nonsplenectomy” groups during the initial 8 weeks. The clinical outcomes, including AMR, biliary complications, infections, and survival, were similar in both the groups. Conclusions. Preoperative rituximab effectively decreased the anti-ABO antibodies sufficiently to prevent the AMR irrespective of splenectomy. Splenectomy does not offer any immunological benefit in ABO-I LT with preoperative rituximab.

Effect of Hepatic Invasion on the Choice of Hepatic Resection for Advanced Carcinoma of the Gallbladder: Histologic Analysis of 32 Surgical Cases

Abstract. The purpose of this study was to assess the patterns of hepatic invasion in advanced carcinoma of the gallbladder by histologically examining surgical specimens obtained in 32 cases of hepatectomy for that carcinoma. Two modes of microscopic tumor extension were observed. The expansive pattern was restricted to liver-bed carcinomas, in which the tumor extends into the liver, primarily from the liver bed. Most of the infiltrating patterns were found with hepatic-hilar carcinomas, in which the tumor invades the hepatic hilum along Glisson’s sheath, especially tumors exhibiting a discontinuous front of tumor invasion. The average width for wedge resection of the liver bed was 15.6 ± 2.9 mm, in contrast to 25.6 ± 8.1 mm for resection of segments IVa and V and 44.1 ± 10.3 mm for extensive hepatic resection (bothp < 0.01). When the hepatic invasion distance is more than 20 mm, the tumor should be selectively managed by extensive hepatic resection, such as extended right hepatic lobectomy or central bisegmentectomy. The results suggest that wedge resection of the liver bed and resection of segments IVa and V are advisable for carcinoma localized to the gallbladder alone and for liver-bed carcinoma with slight hepatic invasion and an expansive tumor growth pattern. Extensive hepatic resection, however, is recommended for carcinoma of the invasive liver-bed type and carcinoma of the hepatic-hilar type.

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.

Effect of IS-741 (a new synthetic antiinflammatory agent) on acute necrotizing pancreatitis in dogs. Significance of its inhibitory effect on cytosolic phospholipase A2.

IS-741, a new synthetic anti-inflammatory agent, is known to have some inhibitory effect on cytosolic phospholipase A2 (cPLA2), an enzyme which hydrolyzes cellular phospholipids, liberating fatty acids and lysophospholipids and providing the precursor substrates for the biosynthesis of eicosanoids and platelet-activating factor. cPLA2 is therefore an attractive target for the development of novel therapies. During infusion of lactated Ringer’s solution at a rate of 10 ml/kg/h, acute pancreatitis was induced in dogs by injecting autologous gallbladder bile into the main pancreatic duct. The dogs were then divided into two groups: group A (nontreatment), no treatment during the experiment, and group B (IS-741), intravenously injected with IS-741 at 6 and 30 h after induction of acute pancreatitis. As a result, the survival rate was significantly higher in group B than in group A. Mean arterial pressure and PaO2 were well maintained in group B as compared with group A. The NAG index, which is known to be markedly increased in renal tubular damage, was significantly lower in group B than in group A. Histological examination of the pancreas, lung, and kidney in group B showed milder changes than in group A. cPLA2 activity in the pancreas, lung and renal cortex was much lower in group B than in group A, but sPLA2 activity in these tissues did not differ significantly between the two groups. In conclusion, IS-741 exerts a potentially therapeutic effect on experimental acute pancreatitis by mitigating the degree of damage in the pancreas, lung, and kidney. The inhibitory effect of IS-741 on cPLA2 may contribute to one of the antiinflammatory mechanisms of actions of this agent.

Pathophysiological effect of hepatic ischemia and reperfusion after hepatectomy in dogs with obstructive jaundice, focusing on the effect of coenzyme Q10 and styrene-co-maleic acid superoxide dismutase.

The purpose of the present study was to elucidate the effect of hepatic reflow following ischemia on the remnant liver after hepatectomy with occluded hepatic blood inflow in dogs with obstructive jaundice. When 40% hepatectomy was performed with 10-min occlusion of hepatic blood inflow in dogs with obstructive jaundice, the lipid peroxide content in the remnant liver increased significantly, together with a reduction in superoxide dismutase (SOD)-like activity. The levels of endotoxin and β-N-acetyl hexosaminase (NAH) in peripheral blood also increased. The phagocytic index increased transiently after 30 min, followed by a marked decrease after 3h. Histologically, degeneration and necrosis of the hepatic parenchymal cells were demonstrated, and survival rate at 7 days was only 23.1%. With the administration of coenzyme Q10 (CoQ10) or styrene-co-maleic acid SOD (SM-SOD), these phenomena were significantly inhibited, and the survival rate improved. After hepatectomy, Kupffer cells in the remnant liver were activated by increased endotoxin levels in the portal vein, inducing the production of free radicals, which, in turn, damaged the Kupffer cells by reducing endotoxin clearance. Finally, the impaired functional reserve in the remnant liver provoked liver failure. The administration of CoQ10 or SM-SOD prevented the occurrence of these phenomena triggered by the free radicals generated by Kupffer cells, stimulated by endotoxin in the portal vein.

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.