Vasoactive intestinal peptide (VIP) nerves in the human gallbladder with cholelithiasis were immunohistochemically assessed, and were correlated with disease (cholecystolithiasis/choledocholithiasis), the histological severity of cholecystitis, the presence or absence of symptoms, and the property of gallstone. Surgically resected specimens of the gallbladder from 46 patients with cholelithiasis (39 patients with cholecystolithiasis and 7 patients with choledocholithiasis) and 8patients with gastric or colorectal cancer, whose gallbladders were resected for lymphnode dissection or hepatic arterial catheterization, were studied. The specimens were fixed in Hollande's fixative, routinely processed and embedded in paraffin blocks. Immunohistology staining was carried out by avidin-biotin peroxidase complex technique using antibody against VIP. Adobe photoshop and NIH Image were used in the digitized morphometry for a quantitative assessment of VIP immunoreactive nerve fiber density. In the proper muscle layer of the gallbladder fundus, VIP immunoreactive nerves were significantly increased in patients with cholelithiasis, especially in those whose chronic cholecystitis were histologically severe. Although no significant difference was found between cholecystolithiasis and choledocholithiasis, VIP immunoreactive nerves in the submucosal layer of the gallbladder neck were decreased in symptomatic patients and in patients having billirubinate stones. These results suggest that the alteration in VIP plays a role in the pathological course of cholecystitis and in the development of gallstone.

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The high incidence of bile duct carcinoma in patients with anomalous pancreaticobiliary ductal junction (APBDJ) has been well documented. The altered bile composition such as elevation of secondary and free bile acids (FBA) is considered to carry a great risk for biliary carcinogenesis in patients with APBDJ. Bile from the gallbladder in 8 patients with APBDJ (APBDJ group) was analyzed and compared with that from 19 patients with gastric cancer and a normal hepatobiliary tract (Control group). The results obtained were as follows. The concentrations of total, primary and secondary bile acids were significantly lower in APBDJ group than in Control group, and FBA was not detected in both groups. The concentrations of phospholipid (PL), cholesterol and total calcium were also significantly lower in APBDJ group. But the amylase concentration was elevated significantly in APBDJ group, and lysolecithin (LL) concentration in the PL, which is produced from lecithin by activated phospholipase A2 in refluxing pancreatic juice and known to have a cancer-promoting effect, was elevated significantly in APBDJ group. These data suggested that elevated LL other than secondary bile acids and FBA would be primarily of great risk to the development of bile duct carcinoma in patients with APBDJ.

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This is a report on two cases of hepatocellular carcinoma with obstructive jaundice treated by the expandable metallic stent (EMS).
Case 1: A 44-year-old woman was admitted to our hospital because of jaundice and back pain. US and CT showed the tumor at the hilar region. ERCP demonstrated the hemobilia and the complete obstruction in the left intrahepatic bile duct. ENBD and angiography were performed to stop bleeding. After seven months, the patient was readmitted because of jaundice. ERCP demonstrated that the tumor invaded to middle bile duct. EMS was inserted through the endoscopic route.
Case 2: A 80-year-old man was admitted to our hospital because of jaundice. US and CT showed the atrophic change of left lobe of liver, and the tumor at the hilar region. PTC demonstrated hemobilia, and a tear drop shaped tumor at the hilar region. EMS was inserted through the PTCD route.

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A 48-year old female was admitted to our hospital complaining of upper abdominal fullness and abdominal mass. Abdominal US and CT revealed a mass showing extragrowth from the fundus of the gallbladder and liver metastases. Angiography showed hypervascular tumors. ERCP showed stenosis of the upper bile duct and pancreatobiliary maljunction. Biopsy specimen from the liver tumor was diagnosed histologically undifferentiated carcinoma showing immunoreactivity for NSE. Administration of cytostatics, such as CDDP (cisplatin) and VP-16 to this patient resulted in the tumor shrinkage for a while, however, the patient died 16 months after the first admission. Autopsy revealed gallbladder tumor markedly invaded to surrounding organs. Microscopic examination revealed admixed proliferation of adenocarcinoma and endocrine tumor, and the tumor was diagnosed as endocrine cell carcinoma of the gallbladder.

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The patient was a 68-year-old male. Although he had no subjective symptoms, gallbladder abnormality was detected when he underwent a physical examination. US and CT revealed a tumor which had infiltrated from the neck of the gallbladder to the liver. ERCP revealed that the inferior bile duct bifurcated and the inner bile duct joined the pancreatic duct. The patient was diagnosed with advanced gallbladder cancer complicating double bile duct and anomalous arrangement of pancreaticobiliary ducts, based on these findings. Extended cholecystectomy was performed. Histopathological examination showed the gallbladder cancer consisted of adenoendocrine cell carcinoma. Nine cases of double bile duct complicated by anomalous arrangement of pancreaticobiliary ducts have been reported,5 of which were complicated by gallbladder cancer. The present case points to the need pay careful attention to complication by gallbladder cancer and to give consideration to performing preventive surgery if similar patients are seen.

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A 62-year-old woman, who had a chief complaint of upper abdominal discomfort, was admitted to our hospital with a diagnosis of gallbladder tumor by an abdominal ultrasonography. Upper abdominal CT revealed gallbladder tumor associated with direct invasion into the liver bed. Angiography showed tumor stain localized in the gallbladder wall. ERCP revealed pancreaticobiliary maljunction (PBM) without choledochal dilatation. Under diagnosis as gallbladder carcinoma with PBM, operation was performed.
Invasive nodular type carcinoma was identified at the neck of the bladder. Histologically, tumor consisted of round shape carcinoma cells that proliferated as a cobblestone appearance. EMA, chromogranin-A and synaptophysin were positive in cytoplasm by an immunohistochemical staining. These findings were compatible with small cell carcinoma of the gallbladder.

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A 56-year old woman was admitted because of epigastric pain. Ultrasonogram and computed tomogram of the abdomen revealed no gallbladder. ERC showed irregular common bile duct and beading irregularities in the intra-hepatic bile duct, and did not visualize a gallbladder and cystic duct. These findings suggested the possibility of congenital absence of the gallbladder complicating sclerosing cholangitis.
Laparoscopic examination showed the gallbladder was absent and no fibrous band was observed at the gallbladder fossa of the liver. Histological findings of liver biopsy showed not incompatible with sclerosing cholangitis. From these image diagnosis and laparoscopic findings, we diagnosed this case as congenital absence of the gallbladder complicating sclerosing cholangitis.

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We have experienced a case of primary early carcinoma of the cystic duct. Carcinoma of the cystic duct satisfied with Farrars' criteria is a very rare condition in biliary malignancies, only 21cases had been reported in the Japanese literatures.
A 62-year-old man was admitted to the our hospital because of rt hypochondralgia. Operation was carried out under a diagnosis of early common hepatic duct carcinoma and a resection of the bile duct with lymph node dissection was added to cholecystectomy.
A Papillary soft tumor with it protruded into the common hepatic duct measuring 4.8 X 3.2cm was observed in the cystic duct of the resected spcimen. Microscopically it was papillary adenocarcinoma confined into mucosal layer of the cystic duct.
Diagnosis of carcinoma of the cystic duct is very difficult preoperatively. Therefore, if the patient has cholecystitis and gallbladder is not visualized by cholangiography, preoperative examinations including EUS, MRCP and Angiography should be performed carefully for diagnosis of carcinoma of the cystic duct.

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Surgical resected case of early carcinoma of common bile duct was described. A 67-year-old female was admitted to our hospital with unexplained abnormal liver function tests and dilatation of biliary duct on abdominal ultrasonogram. Abdominal CT documented tumor in the lower common bile duct, and endoscopic retrograde cholangiogram was highly suggestive of malignant stricture. Several biopsy specimens were obtained from the tumor and also normally appeared mucosa using cholangioscopy inserted through the PTC route. They were reported as showing adenocarcinoma with intraepithelial spread. The depth of invasion was considered as“fm”by the estimation using EUS and IDUS.
Pancreatoduodenectomy was performed and secondary deposite was not seen in the lymph nodes during surgery. Pathological examination of resected specimen was reported as early carcinoma of the lower common bile duct with the depth of invasion confined to“fm”. Histologically, carcinoma was well-differentiated papillo-tubular type with intraepithelial spead up to the upper bile duct.
Cholangioscopy and biopsy inserted through the PTC route played an important role in determining the surgical resectionline in this case.

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