Yutaka Nakata

Prolonged decrease in hepatic connexin32 in chronic liver injury induced by carbon tetrachloride in rats

BACKGROUND/AIMS Our previous study indicated that the amount of connexin32, the major gap-junctional protein of rat liver, is transiently reduced in acute liver injury after single administration of hepatotoxic chemicals. This study was designed to examine alteration in the expression of connexin32 in chronic liver injury, unassociated with hepatocyte proliferation. METHODS Rats were injected with carbon tetrachloride (CCI4, 0.5 ml/kg) twice a week for 12 weeks. After cessation of CCI4 injection, hepatic contents of connexin32 and its mRNA levels were measured by immunoblotting as well as immunohistochemical examination and by Northern-blot analysis. RESULTS The plasma alanine-aminotransferase activity was increased from 30 U/I to about 1000 U/l after 12 weeks of CCI4 injections, but recovered nearly to normal level in 7 days after cessation of the injection. Liver specimens 12 days after the last CCI4 injection appeared cirrhotic with a marked increase in fibrosis. Connexin32 contents in these livers decreased to about 37% of controls. The significant decrease in connexin32 content was sustained for at least 30 days and recovered to the control level by 60 days. The alteration of connexin32 content in chronically injured liver was confirmed immunohistochemically. The level of connexin32-mRNA, however, was not reduced, but rather increased by chronic injection of CCI4. CONCLUSION The results suggest that intercellular communication is disturbed in chronic liver injury, lasting even after recovery from the acute phase of injury. Since the mRNA levels of connexin32 were sustained, the prolonged decrease in connexin32 contents in these livers might be due to a post-transcriptional change that causes decrease in protein synthesis or a derangement of post-translational controls.

Successful simultaneous operation of concomitant early gastric cancer, transverse colon cancer, and a common iliac artery aneurysm

In an 83-year-old Japanese man, concomitant bleeding colon cancer, early gastric cancer, and an expanding right common iliac artery aneurysm were evident. The patient underwent an artificial graft implantation, partial gastrectomy, and transverse colectomy, simultaneously. To protect against graft infection, the aneurysm was resected first, and then the retroperitoneum was tightly closed to isolate the graft from the peritoneal cavity. The postoperative course was uneventful, except for symptoms of temporary delirium. Recently, simultaneous surgery for concomitant abdominal aortic aneurysms and early gastric cancer has been commonly performed in Japan because the contamination of the peritoneal cavity during a gastrectomy is thought to be less severe than that during lower abdominal surgery. However, the positive rate for bacterial culture in colorectal resections is virtually the same as that in gastrectomies. Moreover, the incidence of graft infection is substantially lower than the positive rate for bacterial culture in surgery for aneurysms. Some surgeons object to a simultaneous resection due to fear of graft infection, but even the presence of infectious organisms does not always result in graft infection. The present case illustrates the benefits of a simultaneous operation for both an aneurysm and gastrointestinal malignancy.

Early gastric cancer associated with synchronous liver metastasis and portal tumorous embolism: Report of a case

We report herein the first known case of early gastric cancer with synchronous liver metastasis forming a portal tumorous embolism. A 62-year-old man was found to have multiple liver tumors and a portal tumorous embolism by ultrasonography. A gastroscopy subsequently showed Borrmann type III-like gastric cancer in the antrum. His carbohydrate antigen (CA) 19-9 level was elevated to 8280 U/ml, but the α-fetoprotein level was within normal limits. A laparotomy revealed multiple liver metastasis and subpyrolic lymph-node enlargement; a distal partial gastrectomy with group 1 lymph-node dissection for the gastric cancer in the antrum, and cannulation of the proper hepatic artery for postoperative chemotherapy were performed. Histopathologically, the cancer was found to be a medullary type well-differentiated adenocarcinoma. Subpyrolic lymphnode metastasis was noted, but cancer invasion was localized to only the mucosal and submucosal layers of the stomach. Thus, the patient was diagnosed as having early gastric cancer. Adjuvant chemotherapy given through the cannula suppressed further elevation of CA19-9 levels, and a total of 26 Gy irradiation to a liver tumor, which had caused ascites by pressing on the inferior vena cava, diminished the ascites. The patient was able to remain at home with treatment for 7 months after radiation therapy, but finally died of cancer with jaundice 13 months after his operation. Therefore, although adjuvant chemotherapy and radiation therapy contributed to improving his quality of life, it could not prolong survival.

Alteration of connexin 32 content in acute and chronic liver injury induced by carbon tetrachloride in rats

The change in hepatic content of connexin 32 was studied in carbon tetrachrolide (CCl4)-induced liver injury in rats. In acute liver injury caused by a single administration of CC14, the content of connexin 32 decreased transiently to 45% of control level and recovered to normal in 7 days. In chronic liver injury induced by repeated injections of CC14 for 12 weeks, in contrast, the decreased level of connexin 32 in the liver was maintained even 12th day after the last injection of CC14. These results suggest that gap junctional communication between adjacent hepatocytes was disturbed in acute and chronic liver injury.