Hiroshi Isozaki

Impact of the expression of cyclin-dependent kinase inhibitor p27Kip1 and apoptosis in tumor cells on the overall survival of patients with non–Early stage gastric carcinoma

The expression of p27Kip1 and apoptosis have been implicated in tumor aggressiveness and proved to be prognostic predictors for several human malignancies. In this study, the authors sought to investigate the expression of p27Kip1 and apoptosis and their potential significance in determining the prognosis of patients with non–early stage gastric carcinoma.

Surgery for gastric cancer in patients with cirrhosis

To clarify the therapeutic strategies for gastric cancer surgery in the presence of cirrhosis, 39 patients with gastric cancer accompanied by liver cirrhosis were reviewed. Severe postoperative complications developed in 10 patients (25.6%), and there were 4 (10.3%) hospital deaths, 1 (2.6%) of which occurred within 1 month. Although extended lymph node dissection of D2 or more was adopted for low-risk patients, 3 of 19 patients who underwent such extensive operations, most of which involved complete lymph node dissection in the hepatoduodenal ligament, died. Conversely, only 1 of 20 patients who underwent limited lymph node dissection of D1 or less died. Postoperative massive ascites developed in 6 patients, 3 of whom died. The cumulative 5-year survival rate following curative resection was 63.7% for patients with early gastric cancer, and 13.9% for those with advanced gastric cancer. The most frequent cause of death was cirrhosisrelated, such as hepatic failure or hepatoma. In conclusion, extensive lymph node dissection for patients with gastric cancer accompanied by cirrhosis carried a risk of postoperative fatal massive ascites as lymphorrhea. Thus, lymph node dissection in the hepatoduodenal ligament should be avoided, except in patients with evident metastases, and as a rule, aggressive surgery should not be performed in cirrhotic patients.

Multiple early gastric carcinomas: Clinicopathologic features and histogenesis

Multiple early gastric carcinomas were found in 5–15% of patients with early gastric carcinoma. The goals of this study were to clarify the clinicopathologic features of multiple early gastric carcinomas and to investigate their histogenesis.

The protective effect of thromboxane A2 synthetase inhibitor against ischemic liver injury

To evaluate the role of thromboxane A2 (TXA2) in ischemic liver injury, the serum changes in thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-K-PGF1α) following warm ischemia of the total canine liver were examined, and the protective effect of a TXA2 synthetase inhibitor was assessed. Total liver ischemia was performed for 60 min on two groups of dogs: a control group, in which ischemia alone was performed, and an OKY-046 group, which received a TXA2 synthetase inhibitor. A temporary active portacaval shunt was used to eliminate the effects of splanchnic venous stasis during clamping of the hepatic pedicle. Postoperative changes in liver function, assessed by the transaminase enzyme levels, and in prostaglandins were recorded and the histologic liver findings of both groups 1 week after ischemia were compared. The levels of 6-K-PGF1α increased after reperfusion in both groups, while those of TXB2 increased in the control group but maintained low levels in the OKY-046 group. Liver function was better and histologic changes less marked in the OKY-046 group than in the control group, suggesting the important role of TXA2 in ischemic liver injury and the usefulness of a TXA2 synthetase inhibitor for protecting the liver against ischemic injury.

Cystic lymphoepithelial lesions of the pancreas and peripancreatic region: Report of two cases

Two cases of an extremely rare cystic lymphoepithelial lesion of a lymph node associated with the pancreas are presented herein. The first patient was a 57-year-old woman with a serous cystoadenoma who underwent resection of the body and tail of pancreas, and the other patient was a 75-year-old woman with cancer of the papilla of Vater who underwent pylorus-preserving pancreatoduodenectomy. Both lesions were incidentally found during pathologic examination of lymph nodes from the peripancreatic region. Histologically, there were many scattered nests of the lymphoepithelial lesion in the lymphoid stroma, each of which was lined with stratified squamous epithelium. The pathological structure was found to resemble the lymphoepithelial lesion of the pancreas. Although the histogenesis is unknown, we hypothesize that the lesion might have arisen from squamous metaplasia of a benign epithelial inclusion such as the pancreatic duct of an ectopic pancreas in a peripancreatic lymph node. Therefore, a cystic lesion formed as a result of keratinization of the squamous epithelium with invasion into the pancreas could become a lymphoepithelial cyst of the pancreas.

Principles of Surgical Treatment

Curative treatment of gastric cancer requires complete elimination of all cancer cells. Surgery is the only treatment method that can fully and demonstrably achieve this goal. However, in the clinical setting, the most appropriate procedure for each case must be selected, based on a full grasp and understanding of various local and systemic conditions.

Evaluation of Treatment Strategies for Gastric Cancer in the Elderly According to the Number of Abnormal Parameters on Preoperative Examination

The treatment strategies in patients with gastric cancer aged 80 years or older have not yet been well defined. We examined the incidence of postoperative complications and hospital mortality regarding the preoperative condition of such patients. A preoperative examination included evaluations of the cardiac, pulmonary, renal, and hepatic functions, the presence or absence of anemia, nutritional status, and blood sugar content. The incidence of postoperative complications and hospital mortality were then studied in relation to the number of preoperative abnormal parameters. The incidence of postoperative complications was 37.0%. The rate of hospital mortality was 11.1%. Among the patients with abnormalities in five or more items, the incidence of complications was 76.9% and the rate of hospital mortality was 23.1%. In the patients with an operative time of 4h or longer, the same incidence was 71.4%. Among the patients who underwent a curative resection, the 5-year survival rate was 92.3%. For elderly gastric cancer patients with abnormalities in five or more items during a preoperative examination and for those showing a poor level of daily life activity, a less invasive treatment modality should be planned. Patients with abnormalities of four or fewer items at a preoperative examination appear to be good candidates for curative resection.

Proximal subtotal gastrectomy for the treatment of carcinoma of the upper third of the stomach: Its indications based on lymph node metastasis and perigastric lymphatic flow

To clarify the indications for a proximal subtotal gastrectomy in the treatment of carcinoma in the upper third of the stomach based on lymph node metastases, 1055 patients in whom either a D2 or greater lymph node removal was performed were reviewed. In the patients in which the lesion was confined to the upper stomach and did not invade beyond the muscularis propria of the stomach wall, no metastases to either the lymph nodes above and below the pylorus or the lymph nodes along the greater curvature were observed. A lymphatic flow study revealed a minimal flow to these nodes from the upper stomach in patients without lymph node metastasis, but in cases with lymph node metastases the lymphatic flow changed. The indications for a proximal subtotal gastrectomy for a carcinoma of upper third of the stomach therefore must fulfill the following two conditions: (1) The deepest layer of cancerous invasion does not extend beyond the muscularis propria of the stomach wall, and (2) No macroscopic evidence of lymph node metastasis can be detected during surgery.

Surgery for cholelithiasis in cirrhotic patients

Although biliary tract surgery for cholelithiasis is performed frequently in Japan, cirrhotic patients require special consideration. Postoperative complications after biliary tract surgery were studied in 23 patients with liver cirrhosis and associated cholelithiasis, 9 of whom had no complications, 8 had minor complications, and 6 had severe complications. Concerning the relation between Childs classification and postoperative complications, no complications were seen in four Childs type A patients, but seven of ten (70%) Childs type B patients and seven of nine (78%) Childs type C patients developed complications. Two (20%) of the Childs type B patients and four (44%) of the Childs type C were severe, and three of the latter group died. Regarding the preoperative laboratory findings, significant differences were seen between the patients without complications and those with severe complications in serum bilirubin, albumin, and ICG R15 values. Of the six patients with severe complications, five had choledocholithiasis, three of whom died of liver failure, while two developed biliary peritonitis caused by insufficient fistula formation after removal of the T-tube. Thus, for the treatment of choledocholithiasis in patients with severe cirrhosis, avoiding surgical invasion through the use of such techniques as endoscopic papillotomy is recommended whenever possible.

Proliferating cell nuclear antigen expression in the gallbladder with pancreaticobiliary maljunction

Background and Objective: To clarify the histogenesis of cancer of the gallbladder of the patients with pancreaticobiliary maljunction (PBMJ), the proliferating cell activity of the epithelium of gallbladder was examined.