Here I summarize progress in research concerning diagnostic modalities for the biliary tract carcinoma to which I personally contributed. In 1981, I reported the first correct preoperative diagnosis of longitudinal extension using percutaneous transhepatic cholangioscopy (PTCS). I also reported diagnosis of biliary strictures by quantitative assessment using a derived hemoglobin index. Our group demonstrated usefulness of intraductal ultrasonography (IDUS) in 1989, and 3-dimensional IDUS in 1997, for precise diagnosis of cancer extension. In the early of 1980,s, I developed percutaneous transhepatic cholecystoscopy as an extension of PTCS. In 1992, I participated in the first trial of endoscopic magnetic resonance imaging (MRI). Improved, endoscopic MRI was able to depict the laminar structure of the gallbladder wall, and comparison could be made with diagnostic images obtained using endoscopic ultrasonography. We investigated the differential diagnosis of polypoid gallbladder lesions using contrast-enhanced ultrasonography beginning in 2001, and ongoing refinement of this modality is expected. Despite these various techniques, however, early diagnosis of biliary tract carcinoma remains insufficiently frequent, and further efforts are necessary.

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We described the cut of edge in diagnosing biliary tract diseases. In addition to fundamental US and EUS, contrast enhanced US and EUS using Levovist or Sonazoid, have been tried to conduct for differential diagnosis of biliary tract diseases. In MDCT, multiplanar reformation image and 3D-CT angiography are very useful for decision of a progress level of biliary tract cancer. Also, in MRI, advanced MRCP imaging, SPIO MRI, and DWIBS can give us important information in diagnosis not only for primary lesion but also distant metastasis in patients with biliary tract diseases. Several investigators have reported that FDG-PET is more sensitive than CT and MRI for diagnosis of bile duct cancer.
In ERCP-related procedures in diagnosing biliary tract cancers, cytology by using endoscopic naso-gallbladder drainage tube is relatively high accuracy for diagnosis of gallbladder cancers although procedure success rate is a little low. Recent developed peroral cholangioscopy (POCS) can provide a better and fine imaging comparing conventional fibroptic cholangioscopy. Furthermore, POCS using narrow-band imaging will give us more detailed information in the bile duct.

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The requirements of biliary stenting for unresectable biliary malignancies are to be low invasive, low incidence of complications, and long patency. For the distally obstructed cases, covered metallic stent (CMS) should be selected firstly because of long patency and removability. The incidence of cholecystitis, pancreatitis, migration, and kinking tend to be higher in CMS placed cases and to establish the prevention strategies of these complications is important. On the other hand, for the hilar obstructed cases, there is very few evidence of placement manner. While there are controversial points as to approach route (endoscopic or percutaneous), type of stent (plastic stent or metallic stent), and drainage area (unilateral or bilateral), the recent consensus is endoscopic unilateral MS placement. Other important point of metallic stenting is to consider the axial force (AF; force makes stent straightened). MS with strong AF causes bile duct kinking and migrations. MS with weak AF should be selected in order to prevent complications for the cases with severe vending bile duct.

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Endoscopic microwave coagulation therapy (EMCT) was applied to three patients (bile duct cancer: 2 cases, pancreas cancer: 1 case) with re-obstructive jaundice after expandable metallic stent (EMS) therapy due to unresectable malignant biliary obstruction. Bile duct re-endoprosthesis was difficult after EMS therapy and the period of patency after re-endoprosthesis was short about 2-3 months, EMCT was carried out for local control. One patient is alive for 20 months and obstructive jaundice has not been occurred for 11 months after EMCT, and other 2 patients died 7 months, 5 months later after EMCT by liver metastasis and peritoneal dissemination but patency was reserved. Endoprosthesis was performed by EMCT with safe and this therapy was an effective therapy for patients with re-obstructive jaundice after EMS.

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Aim: To clarify the adequate surgical procedure, in patients with ampullary cancer. Patients and Methods: Between 1990 and 2007, twenty-five patients with ampullary cancer underwent surgical resection. The survival rate with respect to clinicopathological factors were analyzed. Results: The overall incidence of lymph node metastases was 36%. The patients without lymph node metastasis showed significantly better outcome than those with lymph node metastasis. When the tumor was limited in the mucosal layer, lymph node metastasis was absent. However, when the tumor invaded the sphincter of Oddi and the tumor invasion exceeded the sphincter of Oddi, lymph node metastasis was present in 25% (1/4) and 47% (8/17), respectively. The 3-year and 5-year survival rates of the patients whose cancer was limited to the mucosal layer or the sphincter of Oddi were both 100%, while these invaded over the sphincter of Oddi were 45% and 41%, respectively. Conclusions: When the tumor is limited in the mucosal layer, ampullectomy can be applied. Pancreaticoduodenectomy with lymph nodes dissection is necessary when cancer invades to or over the sphincter of Oddi.

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Intrahepatic gallstone disease (hepatolithiasis) is commonly described as oriental cholangiohepatitis, a problem seen frequently in East Asia Although relative incidence seems to be decreasing, it continues to be a serious health care problem in Japan, for its intractable nature and later development of bile duct cancer. The Study Group of Hepatolithiasis in Japan (Granted by Ministry of Health, Labour and Welfare) conducted nationwide epidemiologic survey for 5 times in the past (1977, 1984, 1988, 1992, and 1995). The similar epidemiology survey was conducted last year. It is also not well known how the disease and its treatment relate to the prognosis, recurrence of stone, and cancer development. A cohort of 473 patients in 1995 study was followed up last year. A total of 2592 hospitals in Japan were surveyed, and 331 cases were collected. Proportion of hepatolithiasis in all gallstone diseases were calculated 0.6% in this study, which compared less to previous studies (cf. 1977 4.1%, 1998 1.7%). Mean age of the patients was 63 years old, same as in the 1998 study. Male/female ratio continued to be 1: 1.2. Residual stone after initial treatment was found in 18.6% of patients, and recurrence rate remains unchanged despite for the modern imaging modalities and progress in treatment (cf. 1977 23.5%, 1998 18.4%). Concurrent cholangiocarcinoma was identified in 5.4% of patients. Parasitic disease seemed no relevance to hepatolithiasis. One hundred ninty-two cases (62.5%) had a history of previous biliary disease, cholecystlithiasis in 58 and CBD stone in 117. In addition to biliary neoplasia, it was notable that neoplasia in other organs were frequent (n=20, 7.5%). Surgical treatment was performed in 189 cases, predominantly hepatectomy of the affected lobe. Also medical treatment was performed in 145 cases and endoscopic stone removal (either PTCSL or ERCP) was the mainstay. A cohort study was analyzed as a proportional hazard model. Five year survival rate was 85.2%, and 10years rate was 78.6%. Jaundice and bile duct neoplasia significantly relate to patient's death and cholecystectomy and cholangitis related cholangiocarcinoma development. Cholangitis was found to significantly relate to stone recurrence and administration of UDCA had no relevance. Patients with hepatolithiasis are decreasing but the refractory nature of the disease is unchanged. Cancer development both in the biliary system and in other organs continues issue of concern.

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A 74-year-old female with a complaint of palpable mass of right hypochondrium was admitted to our hospital. Abdominal US and CT revealed a giant gallbladder tumor with liver invasion and intrahepatic bile duct dilatation. The tumor spread to the cystic duct and protruded into the common bile duct with portal invasion. Further, ERCP showed mucin pooling and multple stones in the inferior bile duct. We performed endoscopic mechanical lithotripsy, biopsy of the tumor (moderately differentiated tubular adenocarcinoma), and bile cytology (class V). Gallstone composition analysis revealed that the retrieved stones were pure cholesterol gallstones. The diagnosis of mucin-producing carcinoma of the gallbladder (Stage IVa) was made, and thereafter endoscopic placement of an expandable metallic stent was performed.

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A 68-year-old woman was admitted to our hospital with acute cholangitis. Duodenoscopy demonstrated bulla like bulging of the oral side protrusion of the papilla of Vater. Endoscopic retrograde cholangiopancreatography (ERCP) revealed intermittent cystic dilatation and contraction of the terminal bile duct as well as irregularity of the wall from the lower to the upper portion of the bile duct. A diagnosis of choledochocele associated with superficial spreading cancer of the bile duct was made based on findings of peroral cholangioscopy (POCS) and transpapillary biopsy under direct vision and fluoroscopic guidance. The amylase level in bile sampled in the upper bile duct was 2217 IU/l. There is a possibility that reflux of pancreatic juice into the bile duct influenced the development of bile duct cancer.

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A 69-year-old man who complaind of epigastric pain and jaundice came to our hospital, and the patiant underwent endoscopic sphincterotomy. We performed percutaneous transhepatic gallbladder drainage by diagnosis of choledocholithiasis with obstructive jaundice and cholangitis. After 19 days of the hospitalization, we performed laparoscopic side-to-side choledochoduodenostomy using abdominal wall lifting. The incision of the common bile duct and the duodenum using ultrasonic nife reduced bleeding and improved the bad sight of the anastomosis site. We made a 2.5 cm-longitudinal incision in the common bile duct and made horizontal incision in the duodenum, and performed side-to-side anastomosis. Progress of the operation was well, and after 15 days of the operation, the patiant left the hospital. Using abdominal wall lifting, taking forceps in and out, washing and aspiration were easy for nothing anxiety about gas leakage, and we performed smoothly to take the stones and anastomosis. As a treatment for reccurent choledocholithiasis after endoscopic sphincterotomy, laparoscopic side-to-side choledochoduodenostomy using abdominal wall lifting may be considered as a method.

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Operative indications can now be decided by MD-CT. Local invasiveness is a factor of those tumor's prognosis. EUS can reveal high resolution imaging, so preoperative diagnosis of tumor Objective is to evaluate US and EUS for preoperative diagnosis of the middle and lower bile duct carcinoma. 18 resected bile duct carcinomas were studied. Only 2 tumors were visualized by US, but all of bile duct dilatation of those could be. So the sites of obstruction were suspicious of middle or low bile duct. All tumors were visualized by EUS. In the diagnosis of depth invasion of those tumors and in pancreatic invasion, 70% and 83% were correctly diagnosed. In lymph node involvement diagnosis, and in major portal vessel involvement diagnosis could'nt be assessed, because of any PV had been resected. CONCLUSION: US should be the first imaging modality of choice in evaluation of biliary obstruction, and EUS for local extention of tumors.

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As the progress of Multidetector row CT (MDCT) drastically improve the time and spatial resolution, CT has a major role in the staging of middle and lower bile duct cancer. Performing the thin slice CT with multiphase dynamic study before bile drainage and estimating the acquired CT images on the monitor by paging very carefully, the extension of the tumor can be revealed on the accuracy of the pathological findings. However, MDCT has the limitations such as difficulty of estimating the surface spread of the tumor, which is the frequent spread form of the middle and lower bile duct cancer, IDUS or Cholangioscopy is often required to estimate the surface spread of the tumor.
For the systematic diagnosis of the middle and lower bile duct cancer, we need to familiar with expert knowledge about not only MDCT but also various examination, the characteristics of bile duct cancer and the surgery.

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