Ouki Yasui

Copper incorporation into ceruloplasmin in rat livers

Ceruloplasmin, a blue copper oxidase found in plasma, is synthesized in hepatocytes as a single polypeptide chain consisting of a 19 amino acid leader peptide plus 1046 amino acids of mature protein (132 kDa). Holoceruloplasmin is secreted into the plasma with 6-7 atoms of copper bound per molecule. In this study we identified apo- and holoceruloplasmin and examined the mechanism of copper incorporation during ceruloplasmin biosynthesis using the Long-Evans Cinnamon (LEC) rat which does not incorporate copper into newly synthesized ceruloplasmin. We followed the conversion from ceruloplasmin precursor (with little or no carbohydrate) to the larger product (after carbohydrate addition), which occurred in the secretory compartments of hepatocytes, by native gel electrophoresis. We found that copper accumulates in the hepatocellular Golgi apparatus of LEC rats due to a disorder in the process of copper incorporation. The data indicate that copper is incorporated into ceruloplasmin late in the course of its transport through the secretory compartments.

Small Bowel Perforation Caused by Metastasis from an Extra-Abdominal Malignancy: Report of Three Cases

Abstract Small bowel perforation is rarely caused by metastasis from an extra-abdominal malignancy. This report describes three cases of small bowel perforation that occurred secondary to a metastatic tumor. The first case involved a 72-year-old man with malignant lymphoma of the larynx that had been treated with chemo- and radiation therapy; the second involved a 70-year-old man with rhabdomyosarcoma of the mediastinum that had been treated with radiation therapy; and the third involved a 41-year-old man with lung carcinoma that had been treated with surgery 10 months prior to perforation. Each patient presented with acute abdominal pain, had X-ray findings of free air in the abdomen, and underwent limited emergency surgery. Wedge resection and closure of the ileum was performed for the first patient and partial bowel resection with the creation of an intestinal stoma was performed for the second and third patients. In each case, the histologic findings of the resected specimens were consistent with the extra-abdominal primary tumors. Although the patients recovered sufficiently to begin eating and moving about, all three died of cancer or cancer-related complications within 45 days of surgery. We conclude that surgeons should be aware of the poor prognosis of such patients and perform only the minimal surgery required.

Outcomes and Indications of Segmental Pancreatectomy

Background/Aim: To preserve pancreatic function, segmental pancreatectomy has been proposed for benign or low-malignancy tumors in the pancreatic body. Indications for the procedure, however, are still controversial. Methods: In this study, we investigated the advantages and disadvantages of segmental pancreatectomy compared with distal pancreatectomy and subsequently determined indications for segmental pancreatectomy. Results: The distal pancreatectomy patients had shorter operation times, lower incidence of operative complications, and shorter hospital stays compared to segmental pancreatectomy patients. Endocrine function in distal pancreatectomy patients deteriorated compared to that of segmental pancreatectomy patients. The postoperative 75-gram oral glucose tolerance test showed a diabetic pattern in 3 of 7 distal pancreatectomy patients, whereas none of the segmental pancreatectomy patients became diabetic after surgery. The relation between the length of the removed pancreas and plasma glucose at 2 h after the 75-gram glucose intake showed a significant correlation. Conclusion: According to our results, if the length of removed pancreas is longer than 12 cm, the patients will have a risk of acquiring diabetes. In those cases, the segmental pancreatectomy should be considered.

Jejunal Varix with Extrahepatic Portal Obstruction Treated by Embolization Using Interventional Radiology : Report of a Case

Abstract.We report a case of relapsing jejunal varix with extrahepatic portal obstruction, which was successfully treated by embolization using interventional radiology. A 79-year-old woman suffered repeated episodes of tarry stools 2 years after undergoing jejunal resection for a jejunal varix. The bleeding point was inferred to be in the small intestine, and abdominal angiography revealed extrahepatic portal obstruction and the development of a jejunal varix around the hepaticojejunostomy. Because surgical obliteration of the varices or a shunt operation for portal decompression may have been very invasive due to severe adhesions, the jejunal varix was embolized with anhydrous ethanol and interlocking detachable coils. There were no changes in liver enzymes, the clearance rate of indocyanine green, or portal pressure, and there has been no sign of rebleeding for 13 months. Our experience shows that hemostasis can last, as long as the embolization can be done without aggravating portal hypertension. In conclusion, embolization using interventional radiology is a safe and useful method of treating intestinal varices.

Cholangiocarcinoma coincident with schistosomiasis japonica

The relationship of parasitic liver disease to cholangiocarcinoma has long been debated, and it has been reported that cholangiocarcinoma is associated with opisthorchiasis viverrini. We report herein a rare case of cholangiocarcinoma associated with schistosomiasis japonica. A 76-year-old Japanese man with jaundice was diagnosed with cholangiocarcinoma. Radical resection was not done because of hepatic arterial and portal vein invasion. Biliary microwave tissue coagulation therapy was performed with placement of a metallic stent endoprosthesis. Twenty-two months after the treatment, however, the patient died from hematemesis. Autopsy findings revealed that there was no distant metastasis, even in the area of regional lymph node metastasis. The primary tumor in the hepatic hilar region had been replaced by necrotic debris resulting from the microwave therapy, and an expandable metallic stent was located in the center of the debris. Histological findings showed schistosome eggs, which were old and microcalcified, in veins in the colonic submucosa. Glisson’s fibrosis around the cancer lesion suggested that schistosomiasis japonica and cholangiocarcinoma can occur together with severe chronic inflammation of the portal vein.

Resection of a solitary pancreatic metastasis from renal cell carcinoma with a gallbladder carcinoma: Report of a case

Most metastatic pancreatic tumors are detected at an advanced stage and are not considered suitable for surgery; however, resection is sometimes indicated for a solitary pancreatic metastasis from renal cell carcinoma (RCC) and improves the prognosis. We report such a case, in which the hilar liver was resected with lymph node dissection and distal pancreatectomy. Histological examination revealed regional lymph node metastasis of gallbladder carcinoma (GBC), but all the surgical margins were free of cancer. Postoperative extra-beam radiation therapy was delivered to the hepatic portal lesion to prevent GBC recurrence. The patient remains disease-free 14 months after the completion of radiation therapy. Thus, if all affected areas can be resected, the prognosis associated with pancreatic metastasis from RCC may be favorable.

Prostaglandin E1 Continuous Hepatic Arterial Infusion in the Treatment of Postoperative Acute Liver Failure

Aim: In the treatment of severe liver damage, it is of greater advantage to administer prostaglandin E1 (PGE1) directly to the liver compared with systemic intravenous infusion, because of its high inactivation rate in the lungs. In comparison with intraportal infusion, hepatic arterial infusion is more advantageous because of its easier and safer accessibility. This study was designed to prove the superiority of hepatic arterial infusion to intravenous infusion. Methods: Changes in hepatic hemodynamics and oxygen delivery accompanying PGE1 infusion using both methods were investigated in pigs. In addition, continuous hepatic arterial infusion was applied in 3 cases of postoperative acute liver failure, for patients in whom other conventional treatments like plasma exchange failed to improve the functioning of the liver. Results: Hepatic arterial flow increased significantly accompanying hepatic arterial infusion of PGE1 at a rate of 0.1 μg/kg/min compared with intravenous infusion at the same rate in pigs. Such an increase resulted in elevation of total hepatic blood flow and oxygen delivery to the liver. Correspondingly, bile flow significantly increased accompanying hepatic arterial infusion of PGE1. Continuous hepatic arterial infusion was applied in 3 cases of postoperative acute liver failure. The infusion was continued for 7–9 days at a rate of 0.01 μg/kg/min without any complications through heparin-coated catheters inserted via the femoral artery. Significant increase in bile flow was observed in 2 cases in whom bile was collected, serum total bilirubin began to decrease in all these 3 cases, and the patients recovered from acute liver failure. Conclusion: Hepatic arterial infusion of PGE1 is very useful and effective in the treatment of acute liver failure.

Treatment for postoperative liver failure after major hepatectomy under hepatic total vascular exclusion

Abstract Hepatic total vascular exclusion (HTVE) with clamping of the portal triad and the inferior vena cava below and above the liver is a useful technique in the resection of major hepatic lesions situated close to the hepatic veins and inferior vena cava. From 1996 to 2000, five patients underwent major hepatectomy under HTVE; among these, liver failure occurred in two patients because of liver cirrhosis or hepatic artery interruption. In the former case, apheresis therapy (plasma exchange: 9 times), continuous prostaglandin E1 (PGE1) infusion via the hepatic artery (0.01 μg/kg/min) for 7 days, and hyperbaric oxygen therapy (3 times: 2 ATA, 60 min) were applied. In the latter case, apheresis therapy (plasma exchange: 9 times, continuous hemodiafiltration: 12 days) and continuous PGE1 infusion via the superior mesenteric artery for 7 days were applied. With these treatment modalities, both cases were cured of postoperative liver failure.

Acute Emphysematous Cholecystitis Preceded by Symptoms of Ileus: Report of a Case

Abstract We herein describe a case of acute emphysematous cholecystitis in which the patient presented with symptoms of ileus. The patient was a 72-year-old man with no history of diabetes mellitus. He presented with epigastric pain, vomiting, and low-grade fever. Plain abdominal radiography showed some intestinal gas and niveau, and he was admitted to our hospital with a diagnosis of ileus. The next day, the abdominal pain increased and was accompanied by muscular defense. Plain radiography and computed tomography of the abdomen were carried out, and an emergency laparotomy was performed under a diagnosis of panperitonitis due to a perforation of the gallbladder caused by acute emphysematous cholecystitis. The patient made favorable progress after the operation and was discharged on postoperative day 14. Percutaneous transhepatic gallbladder drainage has been increasingly performed for the treatment of acute emphysematous cholecystitis, but when a perforation of the gallbladder is suspected, a laparotomy first should be considered.

Enhanced proliferation of hepatic progenitor cells in rats after portal branch occlusion

It is known that hepatic progenitor cells increase in number after liver injury caused by carcinogens, but this injury cannot be reproduced in humans. In order to create a practical source of hepatic progenitor cells, changes in the number of liver epithelial cells (LECs), a type of hepatic progenitor cell, were examined following partial interruption of the portal flow. Efficiency in this isolation procedure was investigated, and isolated LECs were transplanted into livers to demonstrate their differentiation into hepatocytes in vivo.A volume of 70% of Sprague‐Dawley rats livers was exposed to portal vein ligation. LECs, identified as alpha‐fetoprotein (AFP)‐positive and albumin‐negative cells, were counted and LECs isolated from the portal vein ligated‐lobe were characterized by immunostaining and Western blotting. Isolated cells were subjected to a 1‐week‐culture, and the number of colonies formed on dishes was counted. The cells were then transplanted to the livers of genetic analbuminemic rats and identified by immunohistochemistry. The number of LECs in the portal ligated‐lobes on day 7 was 14.7 ± 6.5 cells/1,000 hepatocytes: 18 times higher than numbers in a normal liver. A significant increase was noted from day 3 until day 28. Isolated LECs were AFP‐positive, albumin‐negative, and cytokeratin‐19–positive cells. The number of colonies on the 7th day following portal vein ligation was 42 times higher than in a normal liver. After transplantation of the LECs to the analbuminemic rat, a cluster of albumin‐producing cells was present until day 56, suggesting that they differentiate into hepatocytes. We conclude that after portal vein occlusion, the liver can be a good source of hepatic progenitor cell. These results open up the possibility of cellular transplantation for liver functional support in clinical settings. (Liver Transpl 2004;10:748–754.)