To study the association between pancreatic juice reflux into the biliary tract and cholangiocarcinogenesis, we used dibutyltin dichloride (DBTC) -treated rats as our model of bile duct dilatation. Moreover, we compared the DBTC-treated model with rats with bile ducts ligated near the duodenum or at the porta hepatica. The epithelium of the extra hepatic bile duct in the DBTC-treated rats and the rats with ligation near the duodenum exhibited cell proliferation and COX-2expression. Since these changes may be caused by the reflux of pancreatic juice into the biliary tract, the models seemed to closely resemble pancreaticobiliary maljunction in man. Furthermore, the increase in COX-2 expression in both models suggests that there is an association between the pancreatic juice reflux and cholangiocarcinogenesis.

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We sometimes encounter a buried gallbladder in patients with gallbladder carcinoma. If the buried gallbladder is defined as over one third of the gallbladder buried into the liver, it was found in 4 out of 6 autopsied cases and 2 of 13 extended cholecystectomized cases with gallbladder carcinoma, respectively, but not in 9 controlled cases. These buried gallbladder cases were associated with directly metastasized carcinoma to the liver which showed both tumor necrosis and fibrosis in various degrees. Fibrosis was immunopositive for α-smooth muscle actin, a marker of myofibroblasts. The elastic fiber layer of hepatic capsule was destroyed in the buried gallbladder cases, while well-preserved in the 9 controlled cases.
Tumor necrosis plays a role in decreasing tumor volume and myofibroblasts have contraction ability. Therefore, a buried gallbladder might appear after occurrence of gallbladder carcinoma.

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Various hepatic transporters such as Mrp 2 and Bsep are considered to be down-regulated in obstructive jaundice. In the present study, the biliary transport maximum (Tm) of tauroursodeoxycholate (TUDC), a Bsep substrate, BSP, an Mrp 2 substrate, and ICG was studied in bile ductligated rats for 3 days (BDL rats). In BDL rats, the Tm of TUDC and ICG was decreased to 53%and 40% of controls. The Tm of BSP was markedly decreased in BDL rats (13% of controls), and was relieved to 44% of controls by the coadministration of TUDC. The decrease of the Tm of TUDC was not as prominent as that of taurocholate, probably due to the enhancement of the vesicular targeting of Bsep to the canalicular membrane and the phosphorylation of Bsep, which are specific to TUDC. The recovery of the Tm of BSP by TUDC in BDL rats is considered to be due to the partial recovery of the Mrp 2 function by TUDC.

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Contrast-enhanced ultrasonography (CEUS), using Agent Detection Imaging (ADI), is able to detect both signals from the tissue and from contrast medium. With this mode, therefore, we can evaluate vascular and perfusion patterns more precisely. In this study, diagnostic efficacies of ADI were assessed in 25 patients with gallbladder cancer, including 12 resected cases. CEUS was evaluated on tumor vascular image (TVI), tumor perfusion image (TPI), and liver parenchymal image (LPI). TVI could offer detailed structure of vessels, comparable with power Doppler image. TPI showed various patterns of perfusion: hyper-enhanced, partially-enhanced, or less-enhanced pattern. Compared with pathological findings, papillary or tubular adenocarcinoma principally showed hyper-enhancement, although squamous cell carcinoma or mucinous carcinoma showed less-enhancement. LPI, acquired 5 minutes after contrast injection, was available for evaluating direct invasion into liver parenchyma (hinf). Compared with histology of resected specimen, diagnostic accuracy of LPI was 83% in this series. In addition, CEUS was helpful for evaluating the depth of cancer invasion, because subserosal layer was demonstrable on TPI of ADI.
In conclusion, CEUS was thought to be useful for localization and evaluation of extension of gallbladder cancer.

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Our paper describes morphological characteristics of extrahepatic bile duct cancer, using surgically resected 102 cancer cases. About 10% of the cases were early cancers, limited to bile duct mucosa or fibromuscular layer. Macroscopically, all of the early cancer cases were papillary type. Gross types of advanced cancers were classified into three groups: papillary infiltrating type (mass-forming tumor mainly in mucosa), nodular infiltrating type (mass-forming tumor mainly in bile duct wall) and flat infiltrating type (infiltrating tumor without distinct mass). The majority of advanced cancers cases were nodular infiltrating type or flat infiltrating type, while about 10%of advanced cancers were papillary infiltrating type.64% of nodular infiltrating type, as well as 97% of flat infiltrating type, showed diffusely infiltrating cancer growth in the bile duct wall, while 50% of papillary infiltrating tumor exhibited expansive cancer growth in the bile duct wall.

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Bile duct diseases are complex; besides the malignant lesions represented by cancer and benign lesions such as bile duct stone and cholangitis, the bile duct is liable to tumor invasion or influence of inflammation from the adjacency. The diagnostic system should consist of positive utilization of US, following blood test, to detect even slightest dilatation or minute changes of the bile duct, and their close examination.
MRCP wh ich is drawing attention recently is a highly suitable examination method for bile duct diseases, and its wide-spread usage is much anticipated.
As methods for the close examination, endo scopic ultrasonography, intraductal ultrasonography and peroral/percutaneous cholangioscopy are used in addition to the direct imaging of the bile duct by ERCP or percutaneous transhepatic cholangiography.
For the diagnosis of horizontal spread which is characteristic of the bile duct cancer, cholangioscope is used for superficial spread, cholangiography and IDUS for intraductal spread. For the diagnosis of tumor invasion of the right hepatic artery which influences surgical style, IDUS is used. It is important to select and combine the imaging diagnostic methods most suitable for each lesion.

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Treatment of benign disorders of the bile duct has been diversified and specialized with the development of therapeutic techniques and instrumentations. In many centers endoscopic sphicterotomy or papillary balloon dilatation have been the treatment of choice for CBD stones. However endoscopic treatment induces some dysfunction of sphincter of Oddi and can subsequently bring about recurrence of CBD stones. Open choledocholithotomy is safe and certain modality for CBD stones but is more invasive than any other treatments. Laparoscopic management of CBD stones is ideal in terms of recurrence rate and invasiveness, but demands surgical skills. The management of Mirizzi syndrome and confluence stone has endoscopic and surgical treatments. Endoscopic treatment is effectively combined with ESWL or EHL. Pancreaticobiliary maljunction should be carefully treated after seeing whether or not the bile duct is dilated. That is because the incidences of gallbladder cancer and bile duct cancer are different between the cases with and without bile duct dilatation. Hepatolithiasis is difficult to correctly discern the pathogenesis in terms of location of the stones and existence of stenosis or cancer of bile duct. It is not only treated with surgical methods as choledochotomy with or wihtout hepatic resection but also percutaneous transhepatic cholangioscopic lithotomy.

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Surgical resection is very crucial because it has been reported to be only hope for cure in the treatment for biliary tract cancer. The surgical outcome of intrahepatic cholangiocarcinoma has been revealed to be mainly dependent on its macroscopic type, curative resection and lymph node metastases. The prognosis after surgical resection of intraductal growth type tumor is significantly better than that of other type tumors such as mass-forming and periductal infiltration types. There have been some long-term survivors who had lymph node metastases in mass-forming and periductal patients. For the treatment of hilar cholangiocarcinoma, there might have been shown to be beneficial for the improvement of surgical outcome by preoperative portal embolization, parenchymapreserving-hepatectomy and sophisticated biliary drainage techniques. Furthermore, the improved surgical skills of combined vascular resection and extended hepatectomy has brought about the beneficial effect on the surgical outcome for hilar cholangiocarcinoma.
The appropriate patient selection for surgical resection could be a useful contribution to the further improvement of the prognosis of the biliary tract cancer.

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A liver cyst was detected in a 56-year-old man by screening examination in 1998.
In August,2002, his CEA level was found to be elevated and he was admitted to our hospital because of an enlarged cyst revealed by abdominal CT and US. Abdominal CT showed a 8 cm-sized multilocular tumor in the lateral segment of the liver.
Within the cyst, a 2×1 cm-sized papillary tumor with enhancement was found. MRI showed the tumor to be of low intensity on T 1-weighted images and high intensity on T 2-weighted images. Although the papillary tumor inside was enhanced, the tumor stain and the exclusion image were not recognized by arteriography. These findings suggested a cystadenocarcinoma of the liver, and a left lobectomy was performed. Examination of the resected specimen disclosed a 8×5 cm multilocular cystic tumor with prominent papillary projections inside.
Histopathologically the tumor was diagnosed as a biliary cys tadenocarcinoma. The patient is doing well and there has been no recurrence as of two years and one month after surgery.

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A 60-year-old woman was admitted to Gifu Red Cross Hospital because of the right upper abdominal pain with vomiting. Abdominal CT showed pneumobilia in the intrahepatic bile duct and a stone-like mass in the ileum. DIC-CT suspected pneumobilia in the gallbladder. A diagnosis of gallstone ileus was made, but all the symptoms disappeared after the treatment with long tube. ERCP revealed cholecystoduodenal fistula and a small filling defect in the common bile duct. Exploration of the abdomen showed atrophic gallbladder and cholecystoduodenal fistula. Cholecystectomy revealed no stones, but a small tumor in the common bile duct. Frozen section of the tumor revealed no atypical findings. Cholecystectomy, closure of the cholecystofistula, excision of the tumor and the external biliary drainage were carried out. The histology of permanent specimen of the tumor revealed hyperplastic polyp of the common bile duct. To our knowledge, no other case of hyperplastic polyp of the common bile duct with cholecystoduodenal fistula has been reported.

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A 76-year-old woman was admitted for the purpose of treatment of cholecystolithiasis. CA 199 level in blood was elevated to 837.4 U/ml. Abdominal CT revealed irregular low density area with inadequate enhancement at the lateral segment of the liver, and calcification in a part of the area. Swelling of No.3 and 8 a lymph node was recognized, too. Moreover calcification in the gallbladder was found. Under the diagnosis of intrahepatic cholangiocarcinoma and cholecystolithiasis, operation was performed. At laparotomy, the tumor was recognized at the lateral and medial segment of the liver with swelling of No.3 and 8 a lymph node. After dissection of lymph node in the hepatoduodenal ligament, around common hepatic artery and celiac axis, and along lesser curve of the stomach, the left lobe and left caudate lobe was resected. The resected specimen was grayish solid tumor about 5.3×3.0 cm in diameter with a part of mucinous lesion. Pathological findings revealed this tumor consisted of mainly poorly differentiated adenocarcinoma and a part of the tumor consisted of mucinous carcinoma. Moreover lymph node metastasis to the both area of hepatic hilus and lesser curve of the stomach. This case has now been followed for 5 years and 7 months with no evidence of recurrence.

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Case 1, a 62-year-old man had the reiterative elevation of serum biliary enzyme levels and mild jaundice at a clinic. Ultrasonography revealed the biliary dilatation. The dilatation of the left intrahepatic bile duct was detected on CT, and mucin outflow from the left bile duct was observed on ERCP. We diagnosed the mucin-producing neoplasm in the left bile duct, and performed left hepatectomy. The pathological diagnosis was papillary adenocarcinoma with adenoma component, which resembled intraductal papillary mucinous neoplasm of the pancreas (IPMN), limited to mucosal layer of the bile duct.
Case 2, a 52-year-old wo man had mild liver dysfunction, and the left intrahepatic biliary dilatation was revealed. After admission to our hospital, she was diagnosed with papillary neoplasm in the left bile duct, and then underwent left hepatectomy. The pathological diagnosis was well differentiated mucinous adenocarcinoma invading the subserosal layer and liver tissue.
Above two cases maybe apply to “intraductal papillary neoplasm of the liver (IPN-L)” which Chen designated as.

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A 69-year-old man presented with jaundice on October 2002. He had undergone thoracic esophagectomy for early stage esophageal cancer (sm, N₁) with gastric tube reconstruction on August 2001. After precise examinations, he was diagnosed ampullary cancer. He underwent gastric tube preserving pancreatoduodenectomy on November 2002.
It is essential to preserve both the gastrodudenal artery-right gastroepiploic artery and right gastroepiploic vein-gastrocolic trunk, which are the feeding and draining vessels for the gastric tube.

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A 70-year-old man was admitted to our hospital for liver dysfunction and acute cholecystitis. Abdominal X-ray and computed tomography revealed wall thickness of the gallbladder and hypoplasia of medial segment of the liver associated with Chilaiditi syndrome. In order to improve the patient-condition, PTGBD was performed at the back of the patient via intercostal approach, because of his anatomical location of the gallbladder. After four days of antibiotics-prescribing, laparoscopic cholecystectomy was successfully performed by choosing the adequated site of working ports.

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