Yoshio Kinami

Influence of Incomplete Bile Duct Obstruction on the Occurrence of Cholangiocarcinoma Induced by Diisopropanolnitrosamine in Hamsters

This study was performed to clarify the influence of incomplete bile duct obstruction (IBDO) on the occurrence of cholangiocarcinoma, using Syrian golden hamsters. These hamsters underwent simple laparotomy (SL) or IBDO at the choledochus and received diisopropanolnitrosamine (DIPN) once weekly for 20 weeks (SL-DIPN or IBDO-DIPN groups). Histological examination in the liver showed increased bile ductules, goblet cell metaplasia of the bile duct epithelium and cholangiocarcinoma in the two groups. The occurrence rates of cholangiocarcinoma at 20 weeks were 35% in the SL-DIPN group and 89% in the IBDO-DIPN group (p less than 0.01). The mean numbers of tumors per hamster in the IBDO-DIPN group were significantly higher than those in the SL-DIPN group (p less than 0.01). Regarding the composition of bile acid in the intraductal bile, both groups revealed an increase in primary bile acid, consisting of more than 80% of cholic acid. Bacteria were detected in the group with IBDO throughout the whole course. These results suggest that IBDO has an influence as promoter on the occurrence of DIPN-induced cholangiocarcinoma.

Promoting Effects of Bile Acid Load on the Occurrence of Cholangiocarcinoma Induced by Diisopropanolnitrosamine in Hamsters

This study was performed to clarify the promoting effects of primary or secondary bile acid load on the occurrence of cholangiocarcinoma, using Syrian golden hamsters. These hamsters received subcutaneously diisopropanolnitrosamine (DIPN) once weekly for 10 weeks, and simultaneously were given a standard pellet diet (control group) containing taurocholic acid (TCA group) or deoxycholic acid (DCA group). The rates of cholangiocarcinoma at 20 weeks were 23% in the control group, 60% in the TCA group and 59% in the DCA group. There were significant differences between the control and the TCA or DCA groups (p < 0.05). The rates of proliferation of bile ductules or hyperplasia of the bile duct epithelium and the bromodeoxyuridine labeling indices of bile duct epithelial cells were high in both groups treated with bile acids, compared with those in the control group. Regarding the composition of bile acids in the intraductal bile, the TCA and DCA groups revealed a decrease in primary bile acids and an increase in DCA. These results suggest that both TCA and DCA given orally promote the occurrence of DIPN-induced cholangiocarcinoma.

Multifocal intraductal papillary adenocarcinoma of the pancreas: Report of a case

This paper descibes a case of a mucin-producing tumor of the pancreas, histologically diagnosed as multifocal intraductal papillary adenocarcinoma. The patient had a markedly dilated main pancreatic duct, detected by ultrasound (US) and computed tomography (CT), and endoscopy showed a papillary tumor projecting from the patulous orifice of the enlarged papilla of Vater. Several biopsies taken from the tumor indicated a diagnosis of papillary adenocarcinoma. Total pancreatectomy was thus performed, revealing a multifocal papillary tumor growing along the main duct in the head, body, and tail of the pancreas. Microscopically, these multiple tumors were found to be mucin-producing papillary adenocarcinoma of the main and subsidiary pancreatic ducts with nodular and microfocal periductal invasion. The surgical treatment of multifocal tumors, may therefore necessitate total pancreatectomy to achieve curative resection, in some cases.

Bile Acid Load on the DNA Distribution Pattern of Bile Ductules and Cholangiocarcinoma Induced by Diisopropanolnitrosamine in Hamsters

This study evaluated the influence of bile acid load on the DNA distribution pattern of proliferated bile ductules and cholangiocarcinoma induced by diisopropanolnitrosamine. Ninety hamsters were separated into control, tauro- and deoxycholic acid (DCA) groups. The DNA distribution pattern of intrahepatic lesions at 15–25 weeks was measured by cytofluorometry and classified into three types: I (-A, -B), II and III, according to the degree of dispersion on the DNA histogram. Regarding proliferated bile ductule lesions, all groups showed an increase in cell populations, indicating the dispersion of nuclear DNA content from the 4C to 6C ranges over the course of 25 weeks, and two groups with bile acids, especially the DCA group, revealed significant high incidences of lesions with type I-B plus II compared with those in the control group (p < 0.05, 0.01). Changes in carcinoma types were similar to those of bile ductule lesions, and the tumors in the DCA group had a significant high frequency of type II plus III (p < 0.05). In addition, heterogeneity of the DNA distribution pattern was observed within individual lesions of not only carcinoma but also bile ductules. These results suggest that bile acid load, especially DCA, promotes an increase in nuclear DNA content or DNA polyploidization and enhances the distribution of the DNA pattern of proliferating bile ductules and carcinoma. Furthermore, a bile ductule-carcinoma sequence may be present in the development of cholangiocarcinoma.

Hepatic resection for primary liver malignancy

The results of hepatic resection for patients with primary liver malignancy seen at our clinic during the past 21 years are reported. Of 92 patients, 57 had cirrhosis in addition to hepatocellular carcinoma, and 49 (53 percent) underwent hepatic resection of various degrees from partial resection to trisegmentectomy. Resectability rates of the liver were 52 percent in 77 patients with hepatocellular carcinoma, including 19 in whom the tumor was less than 5 cm in diameter, and 60 percent in 15 patients with other malignant tumors; operative mortality rates were 15 percent in the former and 0 percent in the latter. Cumulative survival rates of all patients who underwent hepatic resection, excluding death within one month, were 55 percent at one year, 29 at 3 and 5 years. In patients with hepatocellularcarcinoma, survival rates of 15 those who had a curative resection of the tumor were 87 percent at one year and 47 percent at 3 or 5 years, there was a significant difference in survival curves between those with tumors less than 5 cm and more than 5 cm (p<0.05). On the other hand, survival rates of all patients with other malignant tumors were 78 percent at one year and 37 percent at 5 years. These results indicate the importance of performing hepatic resection for patients with small hepatocellular carcinoma associated with cirrhosis and those with other malignant tumors.

The Effect of Incomplete Bile Duct Obstruction on Diisopropanolnitrosamine—Induced Cholangiocarcinoma

This study was carried out to clarify the influence of incomplete bile duct obstruction (IBDO) on the occurrence and proliferation of cholangiocarcinoma and to evaluate the effect of release of IBDO at an early stage, using 175 Syrian golden hamsters. These hamsters received 500mg/kg body weight of diisopropanolnitrosamine (DIPN) once weekly for 10 weeks, and then were divided into 3 groups, consisting of the simple laparotomy group (SL group), the IBDO group and 2 week IBDO group, in which IBDO was released after 2 weeks. The occurrence rates of cholangiocarcinoma at 20 weeks were 42% in the SL group, 76% in the IBDO group and 30% in the 2 week IBDO group. The mean numbers of tumors per hamster in the IBDO group were significantly greater than those in other groups (p < 0.05). Both occurrence rates and numbers of tumors in the 2 week IBDO group were similar to those in the SL group. The proliferation of bile ductules and isolation of bacteria from bile in the IBDO group had higher rates at 15, 20 weeks than those found in the other groups. These results suggest that IBDO has an influence, as promoter, on the occurrence of cholangiocarcinoma induced by DIPN, and the disappearance of its promoting effect is caused by release of the obstruction.

Relationship between pancreatic enzymes and pathological changes in the pancreas in acute pancreatitis

SummaryTo clarify the relationship between changes in serum pancreatic enzymes and pathological changes in pancreatic parenchyma, this study was performed by using rat models with acute pancreatitis. The models were rats with edematous and necrotizing pancreatitis. Amylase, lipase, ribonuclease (RNase), and deoxyribonuclease (DNase I, II) in the serum were determined for 48 h after the development of pancreatitis. Amylase and lipase levels rose directly in both pancreatitis groups. These enzymes in the necrotizing pancreatitis group were higher than those in the edematous pancreatitis group, but there was no significant difference. RNase levels also rose markedly, but there was no obvious difference between either of the pancreatitis groups. On the other hand, DNase levels were high in the necrotizing pancreatitis group but low in the edematous pancreatitis group, with significant differences between the two groups, especially in the DNase II levels over a 36-h period (p< 0.05-0.01). Therefore, these results suggest that serum DNase levels reveal the necrotizing changes in pancreatic parenchyma.

Operative Results of Side-To-Side Choledochoduodenostomy for Cholelithiasis

To clarify the clinical problems of side-to-side choledochoduodenostomy as an adjunct to surgical management of cholelithiasis, the operative results of 82 patients treated in our clinic during the past 10 years were studied. There were 73 patients with extrahepatic bile duct stone and 9 with intra- and extrahepatic bile duct stone. Their mean age was 64 years, and the ratio of males to females was 1.2:1. The operative mortality rate was 4.9%; early complications developed in 7% of the patients. Of all patients who were discharged, 32% developed late complications, and 22%, including 3 patients with sump syndrome, revealed ascending cholangitis. During follow-up, 13 patients died, 6 of them of cholangitis. A relationship between the occurrence of cholangitis and the size of anastomosis was investigated, but there was no obvious connection between them. Six (7.3%) patients underwent reoperations caused by cholangitis, residual or recurrent stones and stenosis of anastomosis. Good to excellent long-term results were seen in 78% of all patients, while fair to poor results were observed in the rest. Especially, results in patients with intra- and extrahepatic bile duct stones were poor. These results suggest that it is necessary to carefully consider the indication of this procedure for patients with cholelithiasis.

Pancreatic exocrine enzymes and intrapancreatic protein synthesis in acute oedematous pancreatitis.

Changes in serum and intrapancreatic enzyme content and protein synthesis in pancreas were studied in acute oedematous pancreatitis (AOP). Male Wistar rats (n = 111) were divided into 2 groups, controls with a sham operation and those with AOP. Serum amylase levels rose immediately after the procedure causing AOP and then fell gradually, while serum lipase and ribonuclease levels remained higher than control values over 48h. (p < 0.05, 0.01). Serum deoxyribonuclease (DNase) II levels were unchanged. Intrapancreatic enzyme levels were scarcely affected by AOP. 3H-leucine uptake into pancreatic tissue of rats with AOP was decreased throughout the study (p < 0.001), but some protein synthesis continued. Intrapancreatic enzyme contents are maintained despite diffusion into the blood because the pancreas retain its ability to synthesize enzymes.

The influence of cutting the pancreatic nerve plexus on exocrine function in the pancreas of rats

SummaryThis study was performed to clarify changes in protein synthesis and exocrine enzymes of the pancreas after cutting the pancreatic nerve plexus of Wistar rats. The rats were divided into two groups, consisting of a group that underwent cutting of the pancreatic nerve plexus (neurotomy group) and a group that underwent a sham operation (control group).3H-leucine uptake in the pancreatic protein fraction of the neurotomy group at 3, 5 and 7 days after the operation was significantly lower than that of the control group (P<0.05-0.01), and this low uptake returned to the normal range at 14 days. Amylase, lipase and trypsin values in pancreatic tissue of the neurotomy group decreased during the period of from 1 to 7 days, and there were significant differences in the values of the respective enzymes at 5 or 7 days between the neurotomy and the control group (P<0.05). Thereafter, all enzyme values increased to within the normal range. Upon examination of pancreatic blood flow using a microsphere, the neurotomy group showed a significant reduction at 7 days compared with the control group (P<0.05), and thereafter exhibited recovery of blood flow. These results indicate that after cutting the pancreatic nerve plexus, exocrine function in the pancreas is reduced immediately but recovers within a short period of time, and that these changes in exocrine function are affected by blood flow in the pancreas.