Tomoo Kitajima

Spontaneous perforated pyometra presenting as pneumoperitoneum.

BACKGROUND Spontaneous perforated pyometra presenting as pneumoperitoneum is extremely rare. CASE REPORT An 80-year-old Japanese female with spontaneous perforating pyometra presenting as pneumoperitoneum is reported. The patient came to our institute with severe abdominal pain. Routine abdominal examination showed muscular defense, and plain chest roentgenograms revealed infradiaphragmatic free gas. Subsequent computed tomography also demonstrated pneumoperitoneum. Laparotomy was performed on the basis of a tentative diagnosis of perforation of the gastrointestinal tract but revealed a perforated pyometra. A simple hysterectomy was performed. The histological diagnosis of the surgical specimen was acute endometritis without neoplasm. The present report is the third case of spontaneous perforated pyometra with pneumoperitoneum to date. CONCLUSION Although uterine disease presenting as pneumoperitoneum is rare in elderly patients with an acute abdomen, the possibility of a perforated pyometra should be considered in the differential diagnosis.

Chemopreventative effect of an inducible nitric oxide synthase inhibitor, ONO-1714, on inflammation-associated biliary carcinogenesis in hamsters

The present study was designed to investigate whether an inducible nitric oxide synthase (iNOS)-specific inhibitor, ONO-1714 [(1S, 5S, 6R, 7R)-7-chloro-3-imino-5-methyl-2-azabicyclo[4.1.0] heptane], could prevent inflammation-associated biliary carcinogenesis in bilioenterostomized hamsters. Syrian golden hamsters underwent choledochojejunostomy and then received subcutaneous injections of the chemical carcinogen N-nitrosobis(2-oxopropyl)amine every 2 weeks at a dose of 10 mg/kg body wt, starting 4 weeks after surgery and continuing for 18 weeks. The hamsters were divided into two groups according to their oral intake of either a standard pelleted diet containing ONO-1714 at 100 p.p.m. for 18 weeks (ONO group, n = 15) or an ordinary diet alone (control group, n = 15). The animals were killed 22 weeks after surgery, and the development of biliary tumors was examined histologically. The presence and degree of cholangitis, cell kinetic status of the biliary epithelium and iNOS expression were evaluated. Intrahepatic biliary adenomas developed in all control animals, whereas they developed in only seven (47%) hamsters treated with ONO-1714 (P < 0.05). Intrahepatic biliary carcinomas were present in 13 (87%) hamsters in the control group and in only 6 (40%) hamsters in the ONO groups (P < 0.05). Histological and immunohistochemical examinations demonstrated a significant decrease in the degree of cholangitis, biliary epithelial cell kinetics and the expression of iNOS in the biliary epithelium in the ONO group in comparison with the control (P < 0.05). These results indicate that ONO-1714 represses N-nitrosobis(2-oxopropyl)amine-induced biliary carcinogenesis in bilioenterostomized hamsters and inhibits iNOS expression in the biliary epithelium. ONO-1714 may therefore be a promising agent for the prevention of biliary carcinoma in various inflammation-associated biliary disorders.

Chemopreventative Effect of Hochu-ekki-to (TJ-41) on Chemically Induced Biliary Carcinogenesis in Hamsters

BACKGROUND Bilioenterostomy is a common surgical technique that is widely used. Recently, clinical studies have revealed that biliary carcinomas can occur after bilioenterostomy. The present study was designed to evaluate whether hochu-ekki-to (TJ-41), a Japanese herbal drug, could prevent chemically induced biliary carcinomas in bilioenterostomized hamsters. MATERIALS AND METHODS Syrian golden hamsters were subjected to choledochojejunostomy and then received subcutaneous injections of N-nitrosobis(2-oxopropyl) amine every 2 weeks at a dose of 10 mg/kg. N-nitrosobis(2-oxopropyl) amine administration was started 4 weeks after surgery. The animals were simultaneously p.o. administered TJ-41 in water every day at a dose of 1000 mg/kg (TJ-41 group). The control hamsters were administered water alone. The hamsters were sacrificed 22 weeks after surgery, and the development of biliary carcinomas, the presence and degree of cholangitis, and the cell kinetic status of the biliary epithelium were evaluated histologically. RESULTS Intrahepatic bile duct carcinomas developed in 15/17 (88%) hamsters in the control group and in only 8/17 (47%) hamsters in the TJ-41 group (P < 0.05). The degree of cholangitis was not different between the two groups. However, the proliferating cell nuclear antigen labeling index of the biliary epithelium in the TJ-41 group (6.46%) was significantly lower than the controls (9.67%) (P < 0.05). These findings indicated that TJ-41 reduced accelerated biliary epithelial cell kinetics after bilioenterostomy, resulting in the prevention of carcinogenesis. CONCLUSION TJ-41 has a preventive effect on chemically induced carcinoma of the biliary tract after bilioenterostomy.

SMALL NON-FUNCTIONING ENDOCRINE TUMOR OF PANCREAS : COMPARISON WITH SOLID CYSTIC TUMOR

Abstract: A small non-functioning islet-cell tumor of the pancreas in a 79-year-old man is reported. Ultrasonography showed a solid small mass in the body of the pancreas. All laboratory data, including serum hormones and tumor markers, were within normal limits. A distal pancreatectomy was performed. Cut sections of the specimen revealed a small, hard, solid mass measuring 2.8 × 2.2 × 2.0 cm. Histologically, the tumor consisted of large acidophilic cells with round nuclei, and these cells were similar to those normally found in solid and cystic tumors (SCT) of the pancreas. However, the tumor cells were slightly positive for somatostatin and neuron-specific enolase. Ultrastructural studies revealed clear nuclei with no zymogen but immature neurosecretory granules in the cytoplasm of the tumor cells. These findings were consistent with those of non-functioning islet-cell tumors. We describe the clinical and histological differences between non-functioning islet-cell tumors and SCT based on an analysis of the literature.

Tauroursodeoxycholate and cholestyramine enhance biliary carcinogenesis in hamsters.

The aim of this study was to examine whether tauroursodeoxycholate (TUDC) and cholestyramine resin (CR) enhance biliary carcinogenesis in the hamster model. A cholecystoduodenostomy with dissection of the extrahepatic bile duct on the distal end of the common duct was performed on Syrian hamsters. The hamsters were then divided randomly into 3 groups: control group, TUDC-treated group, and CR-treated group. All animals received N-nitrosobis(2-oxopropyl)amine (BOP) to initiate pancreaticobiliary cancer. The experiment was terminated at week 16 and the number of neoplastic lesions was counted microscopically. In the TUDC group, the intrahepatic biliary carcinogenesis was more accelerated than that observed in the control group, but no promoting effect was seen in the pancreas, gallbladder, or extrahepatic bile duct. In the CR group, both the intrahepatic biliary and the gallbladder carcinogenesis were inhibited compared with that observed in the control group and the TUDC group. TUDC enhanced the intrahepatic bile duct carcinogenesis, whereas CR inhibited both the intrahepatic bile duct and the gallbladder carcinoma. Bile acids were suggested to promote biliary carcinoma in the hamster model.

Interleukin-6 Expression on the Biliary Epithelia During Inflammation-Associated Biliary Carcinogenesis in Bilioenterostomized Hamsters

BACKGROUND Chronic inflammatory conditions of the biliary tree strongly predispose patients to biliary carcinoma. The aim of this study was to evaluate the role of interleukin-6 (IL-6) expression during biliary carcinogenesis in bilioenterostomized hamsters. MATERIALS AND METHODS Syrian hamsters were subjected to either a choledochoduodenostomy (CD, n=11) or a simple laparotomy (SL, n=10) and then received N-nitrosobis(2-oxopropyl)amine (BOP) treatment. The animals were sacrificed 20 wk after surgery and the development of biliary carcinoma, the presence and degree of cholangitis, and IL-6 expression on the biliary epithelia were examined histologically. RESULTS In the CD group, eight hamsters (73%) demonstrated persistent cholangitis and six (55%) of them developed intrahepatic biliary carcinoma, while no hamster without cholangitis showed any biliary carcinoma. In the SL group, cholangitis was recognized in four hamsters (40%) and no development of biliary carcinoma was identified. A significantly high incidence of tumor development (P=0.024) and a close correlation between the presence of cholangitis and the occurrence of biliary carcinoma (P =0.013) were thus evident in the CD group. Moreover, the degree of cholangitis was significantly higher in the CD hamsters (P=0.041) and an IL-6 overexpression was identified in five hamsters that had undergone a CD, with a scattered expression on the intra- and extrahepatic biliary epithelia. Despite the fact that the induced biliary carcinomas showed a multicentric occurrence in the liver, these tumors originated from within the restricted area where IL-6 was expressed. CONCLUSIONS A deregulated IL-6 overexpression on the biliary epithelia may therefore be involved in inflammation-associated biliary carcinogenesis in hamsters that have undergone a bilioenterostomy.

Analysis of the Outcomes in Central Venous Access Port Implantation Performed by Residents via the Internal Jugular Vein and Subclavian Vein

OBJECTIVE The central venous access port (CVAP) has played an important role in the safe administration of chemotherapy and parenteral nutrition. The aim of the present study was to clarify the optimal access vein for CVAP implantation when performed by residents rather than attending surgeons. METHODS A consecutive cases of CVAP implantation via the subclavian vein (SV) using a landmark-guided technique or via the internal jugular vein (JV) using an ultrasound-guided technique were divided into 2 groups according to whether the intervention was performed by a resident or an attending surgeon. Early and late complications were compared retrospectively between the 2 groups, and the outcomes of the CVAPs were compared between those implanted via the SV and those implanted via the JV in resident group. RESULTS A total of 207 cases of CVAP implantation were performed. Overall, 114 implantations were performed by residents, and another 93 implantations were performed by attending surgeons. Early complications were seen more frequently in the resident group (6.1%) than in the attending-surgeon group (1.1%), but the difference was not significant. No differences in operating time or late complications were observed between the 2 groups. In the resident group, CVAP implantations via the JV using the ultrasound-guided technique were associated with a shorter operating time compared with the SV approach. CONCLUSIONS Residents can perform CVAP implantations safely using both the SV and JV approaches. However, the JV approach using an ultrasound-guided technique can be performed in less time than the SV approach.

Chemoprevention of Biliary Carcinogenesis

This study was conducted to find out if etodolac, a cyclooxgenase-2 (COX-2)specific inhibitor, could prevent chemically induced biliary carcinogenesis in bilioenterostomized hamsters. Syrian golden hamsters were subjected to choledochojejunostomy and then given subcutaneous injections of N-nitrosobis (2-oxopropyl)amine (BOP) 10 mg/kg body weight every 2 weeks. BOP was started 4 weeks after surgery, and continued for 18 weeks. The animals were simultaneously given etodolac 10 mg/kg body weight in 0.5% methylcellulose solution orally three times per week (etodolac group). The control hamsters were administered methylcellulose solution alone. The hamsters were killed 22 weeks after surgery, and the biliary carcinomas were examined histologically. The presence and degree of cholangitis and the cell kinetic status of the biliary epithelium were also evaluated with special reference to biliary carcinogenesis. Intrahepatic bile duct carcinomas developed in 15 (88%) of 17 hamsters in the control group, but in only 6 (33%) of 18 hamsters in the etodolac group (P < 0.01). The incidence and number of developing biliary carcinomas correlated well with the degree of cholangitis, and severe cholangitis was evident in the controls. The cell kinetic study demonstrated that the proliferating cell nuclear antigen-labeling index of the biliary epithelium was 9.67% in the control group and 5.14% in the etodolac group (P < 0.05). The mean levels of prostaglandin E2 (PGE2) products in the liver tissue were 14.14 ± 3.31 pg/total protein (TP) mg in the control group, and 7.46 ± 2.34 pg/TP mg in the etodolac group (P < 0.05). These findings indicated that etodolac inhibited the occurrence of severe cholangitis and the acceleration of biliary epithelial cell kinetics after bilioenterostomy, thereby preventing BOP-induced biliary carcinogenesis in hamsters. In conclusion, the COX-2-specific inhibitor, etodolac, could be used to prevent not only reflux cholangitis, but also biliary carcinoma after bilioenterostomy.

Biliary Inflammation and Biliary Carcinogenesis

Biliary carcinoma has been reported as a late complication of bilioenterostomy. The present study was designed to find out if bilioenterostomy promotes biliary carcinogenesis, and to clarify the relationship between biliary inflammation and biliary carcinogenesis in hamsters. Syrian hamsters were subjected to simple laparotomy (SL), choledochoduodenostomy (CD), or choledochojejunostomy (CJ). All hamsters received subcutaneous injections of the chemical carcinogen, N-nitrosobis(2-oxopropyl)amine (BOP), and were killed 20 weeks after surgery. Neoplastic lesions in the biliary tree were examined histologically, and the presence and degree of cholangitis was evaluated with special reference to the biliary carcinogenesis. The incidence of bile duct carcinoma did not differ significantly among the three groups. However, numerous bile duct carcinomas were recognized in the bilioenterostomized animals, especially in the CJ group. Moreover, there was a significant correlation between biliary carcinogenesis and the presence of cholangitis in the CD and CJ groups, but not in the SL control group. Severe cholangitis was evident in the CJ group, and the number of biliary carcinomas was well correlated with the degree of cholangitis. These findings suggest that the risk of carcinoma in the biliary tract is increased when cholangitis persists after biliary reconstruction.