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The patient was a 72-year-old man who had a history of hepatic cyst, which had, however, not been followed up. It was noted that he had internal hemorrhage in the hepatic cyst as well as a contrast-enhanced tumorous lesion in the cystic wall. Further detailed examination could not rule out hepatic cystadenocarcinoma or cystadenoma, so a right hepatic lobectomy was performed. The lesion was histopathologically diagnosed as non-malignant cyst with angiogenesis simulating cavernous hemangioma and intra-cystic hemorrhage. Although this disease is difficult to diagnose, its diagnosis is not impossible as long as the disease is kept in mind.

The patient was a 68-year-old woman who had cecal cancer with para-aortic lymph node metastases. Ileocecal resection was performed palliatively. Since metastasis to cervical vertebrae was detected after the operation, she received radiation therapy of 14 Gy to improve neck pain. Chemotherapy with TS-1 (80 mg/day) was started on an outpatient basis (4 weeks administration followed by a 2-week drug-free period). After 4 courses of this chemotherapy, metastases to both para-aortic lymph nodes and cervical vertebrae were remarkably reduced on CT and PET. Throughout the period of treatment, there was no adverse effect and this treatment has been maintained. In conclusion, this case seems significant from the viewpoint of achieving a partial response to TS-1 and maintaining a high quality of life. Moreover,we identified the presence of TS and DPD using an immunohistochemical staining technique. The primary tumor was positive for DPD stain test and negative for TS stain test. It was suggested that this cancer especially would respond to TS-1 chemotherapy.

Recent studies have reported that bone marrow cells (BMCs) have the ability to generate functional hepatocytes. However, the efficiency with which BMC transplantation generates functional hepatocytes is rather low. We assumed that if BMCs accumulated directly in liver, the functional BMC-derived hepatocytes should increase more efficiently. An attempt was made to increase the accumulation of BMCs directly in liver through the interaction between hepatic asialoglycoprotein receptor (ASGPR) and galactose-exposing BMCs. Galactose-exposing BMCs that expressed green fluorescent protein (GFP) were injected into Long-Evans-Cinnamon (LEC) rats, a Wilson's disease (WD) model, via the tail vein. The WD is an autosomal-recessive disorder characterized by impaired biliary copper excretion and copper toxicosis, all due to mutations in the atp7b gene. At 5 months after transplantation, GFP-expressing hepatocyte nodules accounted for 2.4% of total liver mass, and the normal ceruloplasmin was detectable in the sera of these LEC rats. These findings suggest that the functional BMC-derived hepatocytes can be generated and the new genes derived from BMCs, such as ATP7B and GFP, can be transferred to LEC rats by the direct accumulation of BMCs in liver without hematopoietic reconstitution in need of preparative lethal irradiation.

We report a case of cervical and upper thoracic esophageal adenocarcinoma with tracheal stenosis and bilateral recurrent nerve palsy. A 64-year-old man with unresectable esophageal cancer (A3, N1, M0) was treated with concurrent chemoradiotherapy. A dose of 67.4 Gy was irradiated to the cervical and upper thoracic area where the primary tumor and lymph node metastases were located, and six courses of 5-FU (250 mg/24 h/day 1-5) and CDDP (5 mg/1 h, just before radiation/day 1-5) were delivered concurrently. The esophageal tumor showed a complete response (CR), and the paratracheal lymph node metastases showed partial responses (PR). The reason these therapies were more effective against the tumor than the lymph node metastases is uncertain. The patient is no longer required to stay in the hospital, and his QOL has been improving. His condition has been maintained for 4 months, so this type of concurrent chemoradiotherapy may be recommended for cervical and upper thoracic esophageal adenocarcinoma.

Although biliary tract surgery for cholelithiasis is performed frequently, cirrhotic patients require special consideration. The prevalence of postoperative severe complications, such as hepatic failure and biliary peritonitis caused by insufficient fistula formation after removal of the T-tube, is higher than non-cirrhotic patients. We suggest that definitive surgery can be carried out safely, in Child's A and B cirrhotic patients, either electively or as an emergency. However, a more conservative approach is advisable in Child's C patients with acute conditions and definitive surgery is recommended as an elective procedure after liver function has improved. And for the treatment of choledocholithiasis in patients with severe cirrhosis, avoiding surgical intervention through the use of such techniques as endoscopic papillotomy is recommended whenever possible.

Biliary tree of gastrectomized patients was examined with ultrasonography to investigate the factors affecting post-gastrectomy gallstone formation. Only gallbladder stone was found in 57 (18.9%). In 11 (20.0%) of 55 patients, stones had developed within 2 years after surgery, but no difference in incidence were observed by sex and age. Sixty four gastrectomized gallstone patients were examined in respect to the kind of gallstone. Patients with cholesterol gallstones were 18 (28.1%), patients with black gallstones were 29 (45.3%) and patients with calcium bilirubinate gallstones were 17 (26.6%). The incidence rate of cholesterol gallstones was lower and the rate of black gallstones and calcium bilirubinate gallstones was higher than that of non-gastrectomized patients. In conclusion, the incidence of pigment gallstones is very high in gastrectomized patients.

An in vitro study was done to evaluate combination use of aspoxicillin (ASPC) with each of 3 beta-lactam preparations, ceftazidime (CAZ), cefmetazole (CMZ) and aztreonam (AZT). The results obtained are summarized as follows: 1. ASPC has strong activity against Gram-positive bacteria and anaerobic bacteria, while CMZ and CAZ have strong activity against Gram-negative bacteria. 2. Rates of beta-lactamase producing strains among the isolated bacteria (a total of 383 isolates) were 4.4% among Gram-positive bacteria, 71.6% among Gram-negative bacteria and 89.3% among anaerobic bacteria. The overall rate of beta-lactamase secreting strains among all isolates was 46.5%. 3. Efficacies of combination uses were studied using the FIC index. Combination of ASPC and CAZ was effective against 95.0% of the isolates, ASPC and AZT against 85.7%, and ASPC and CMZ against 83.5%. Combination of ASPC and CMZ showed antagonism in 12.8% of the isolates. In conclusion, combination use of ASPC with any one of CMZ, AZT or CAZ proved to be highly effective. In particular, combination of ASPC and CAZ appeared to be the best in view of complementing antibacterial spectra.

In order to investigate the pathogenesis of black gallstones associated with hemolytic disorders, experimental and clinical studies were performed. Firstly, a one-shot injection of bilirubin and hemolyzed blood, and a continuous injection of bilirubin were performed in mongrel dogs with the aim to analyze the changes of hepatic and gallbladder bile composition. Secondly, gallbladder bile obtained intraoperatively from the patients with black gallstones associated with hemolytic disease, patients with black stones not associated with hemolytic disease and patients with gallbladder polyp were analyzed in order to compare the characteristics of hemolytic patients' bile with those of the model animals. High concentration of total bilirubin and increased proportion of bilirubin monoconjugate (BMC) fraction was observed in the bile of patients with black stone associated with hemolytic disease compared with the bile of the patients of other two groups. Bile pH, total calcium concentration and ionized calcium concentration were similar in all the groups. Total bile lipid concentration of hemolytic patients was decreased but the ratio of total bile acid to total lipid was increased. Both bolus injection of bilirubin and hemolyzed blood produced an increase of total bilirubin concentration and BMC in hepatic bile. Continuous bilirubin injection for 7 days induced an increase of total bilirubin and BMC in both hepatic and gallbladder bile. These results suggest that the conjugating capacity of the hepatocyte is surpassed by the excessive amount of bilirubin produced after hemolysis, producing therefore, an increased BMC and unconjugated bilirubin content in bile. This increased content can precipitate in bile as black gallstones.

Eight livers surgically resected for intrahepatic gallstones were submitted to graphic reconstruction from serial histological sections to correlate the peculiar ductal changes with the pathogenetic aspects of this disease. Reconstruction was aided by a microcomputer system we have developed. Further, morphometric analysis was added to relate the obstruction of portal veins with parenchymal atrophy. Three-dimensionally, the ducts in these livers were strikingly transformed into a chain of ampullar dilatations interposed by either bending or strictures. Morphometrically, even a stenotic segment was wider than a corresponding normal one, showing that it was a relative stricture. The parenchymal lobule was atrophic or even completely destroyed due to the frequent thrombotic obstruction of portal veins about 0.5mm diameter. These 3-D morphology of intrahepatic bile ducts provided little evidence of congenital bile duct anomaly for the origin of intrahepatic gallstones. The basic ductal changes were dilations, alternated with "stenoses" that were more apparent than real. On the other hand, both the frequent obstruction of small portal veins and the lobular atrophy reflected a severely reduced portal blood flow. Not only the recurrent cholangitis that is apt to occur upon dilated ducts, but this functional incompetence of a stone-harboring, atrophic liver lobe strongly suggests a surgical indication for hepatic resection.

In order to establish the animal model of papillary insufficiency, 10% formalin solution (0.5-1.0 ml) was injected into duodenal papillae just after cholecystectomy in ten dogs. The bile duct pressure of the dogs was monitored by the manometer utilizing the saline perfusion system. Persistent dilatation of the bile duct was observed postoperatively. Two weeks after operation, the maximum dilatation of the bile duct was observed. The bile duct pressure of the dogs showed several characteristic changes: 1) the perfused pressure increased rapidly just after saline perfusion and then became stable, 2) the dumping time was shorter than that of the control dogs, 3) the residual pressure was lower than that of the control dogs. A metal sound, 4mm in diameter, was passed through the duodenal papillae of the dogs with ease. After injection of 10% formalin solution, macroscopic findings of the duodenal papillae revealed the diminish of their protrusions. These results demonstrated that the pathophysiology of the duodenal papillae treated with 10% formalin solution in this animal model is quite similar to that of human papillary insufficiency.

To understand the pathogenesis of cholesterol gallstones from a crystallographic point of view, we investigated gallstones and precipitates in gallbladder bile by the optical method used in crystallography. First, ground thin sections of cholesterol gallstones in 28 cases were examined by a polarizing microscope. The crystalline fragments which were peeled off from gallstones by sonication were also examined in the same manner. Secondly, the cholesterol monohydrate crystals in gallbladder bile were examined by a polarizing and phase contrast microscope. The bile samples were obtained from 15 patients with cholesterol gallstones by the needle puncture of gallbladder during surgery. The results of observation were as follows. 1) The cholesterol gallstones were composed of many small plated cholesterol monohydrate crystals aggregated radially. 2) Each small plated crystal was grown by the lateral growth mechanism in bile. Spiral growth patterns were often observed on the (001) faces. 3) The cholesterol gallstones were formed by two successive mechanisms: The aggregation of cholesterol monohydrate crystals and the lateral growth of each single crystal.