Parapapillary choledochoduodenal fistula associated with cholangiocarcinoma.

Parapapillary choledochoduodenal fistula is a rare disorder. We herein report a case of parapapillary choledochoduodenal fistula associated with cholangiocarcinoma. A 61-year-old woman was admitted to our hospital for further examination of a liver tumor. She had no clinical symptoms, but computed tomography scans showed an irregularly contoured liver tumor which was histologically confirmed to be adenocarcinoma, by a needle biopsy examination. Duodenal fiberscopy revealed a fistula orifice 1.0 cm proximal to the orifice of the papilla of Vater, and endoscopic retrograde cholangiography through the fistula showed a communication to the common bile duct. Hypotonic duodenography demonstrated reflux of contrast material into the choledochoduodenal fistula. The bile sample collected from the common bile duct showed extremely high levels of pancreatic enzymes, including amylase, phospholipase-A2, and elastase-I. Furthermore, Helicobacter DNA was detected in bile by polymerase chain reaction (PCR) analysis. This experience suggests to us that parapapillary choledochoduodenal fistula may be a risk factor for biliary tract carcinoma, and surgical management is the treatment of choice for this rare condition, even when the patient has no significant clinical symptoms.

Occurrence of hepatocellular and cholangiocellular carcinoma in different hepatic lobes.

Separate hepatocellular and cholangiocellular carcinoma (double cancer) in the liver are extremely rare subtypes of primary hepatic carcinomas. We report a case of double primary liver carcinomas that were surgically resected simultaneously. A 66-year-old man was admitted because of elevation of serum levels of alpha-fetoprotein. Abdominal computed tomography and angiography showed two hypervascular masses in S4 and S8 hepatic segments. With the diagnosis of multiple hepatocellular carcinomas, the tumors were surgically resected. Histological examination showed that the tumor in S4 segment was moderately differentiated cholangiocellular carcinoma, the other in S8 segment was trabecular, moderately differentiated hepatocellular carcinoma. Immunohistochemically, a positive staining in carcinoembyonic antigen and cytokeratin 7 supported the diagnosis of cholangiocellular carcinoma for the tumor in S4 segment. The frequency of double cancer in the liver is much lower than mixed or combined cancer (0.1-0.5%). The different epithelial malignant tumors of hepatocellular carcinoma and cholangiocellular carcinoma, which were located in different hepatic lobes and resected simultaneously, has been reported in only two cases including the present case.

Acceleration of spontaneous biliary carcinogenesis in hamsters by bilioenterostomy.

Biliary carcinomas can occur as a delayed complication of bilioenterostomy. The aim of this study was to determine whether bilioenterostomy influences biliary carcinogenesis in hamsters. Syrian hamsters were subjected to three different surgical procedures: simple laparotomy (SL), choledochoduodenostomy (CD) and choledochojejunostomy (CJ). They were given no carcinogens, and five to six hamsters from each group were killed every 20 weeks up to 120 weeks after surgery. Thirty-seven, 32 and 38 hamsters were sampled from the SL, CD and CJ groups, respectively. Cholangiocarcinomas developed in 5.4, 15.6 and 23.7% of hamsters in the SL, CD and CJ groups, respectively. The incidence of biliary carcinoma was significantly higher in the bilioenterostomy groups, especially CJ (P < 0.05), than in SL. The tumor latency period after surgery was 20-40 weeks shorter in the bilioenterostomy groups than in SL. Persistent cholangitis and bile stasis were frequent in the bilioenterostomy groups, and a significant correlation between cholangitis and biliary carcinogenesis was noted in the CD group. The proliferative cell nuclear antigen (PCNA) labeling index was higher in the biliary epithelium of the bilioenterostomy groups. In conclusion, persistent cholangitis after bilioenterostomy accelerates biliary carcinogenesis through activation of biliary epithelial cell kinetics.

Comparative analysis of Helicobacter DNAs and biliary pathology in patients with and without hepatobiliary cancer.

Several Helicobacter species have recently been isolated from the bile and hepatobiliary systems of murine species, and are well recognized as a pathogen of the hepatobiliary disorder. This study was planned to investigate whether Helicobacter species possess a causative potential for human hepatobiliary disease, especially for hepatobiliary carcinogenesis. Bile and hepatobiliary tissue samples from 19 patients with hepatobiliary cancer and 19 patients with benign biliary diseases were subjected to polymerase chain reaction analyses for the detection of Helicobacter DNAs. Using a proliferating cell nuclear antigen (PCNA) staining technique, we also investigated the biliary epithelial cell kinetics with special reference to the presence of Helicobacter DNAs in the hepatobiliary system. We found that Helicobacter DNAs were positive in 10 (52.6%) of the 19 patients with hepatobiliary cancer. The incidence was significantly higher than that (15.7%) in the benign cases (P = 0.03). The PCNA labeling index in the biliary epithelium in Helicobacter DNA-positive patients was statistically higher than that in Helicobacter DNA-negative ones, regardless of whether the patient was suffering from hepatobiliary cancer and/or biliary inflammation. A close correlation between the presence of Helicobacter DNAs and an elevation of the PCNA labeling index in the biliary epithelium was demonstrated by multiple regression analysis. Our findings suggest that Helicobacter species may play a role in the pathogenesis of hepatobiliary cancer through an acceleration of biliary cell kinetics.

Mode of infiltrative growth of colorectal liver metastases is a useful predictor of recurrence after hepatic resection.

Many studies have been conducted to determine prognosis on the basis of the characteristics of metastatic liver tumor from colorectal cancer. The present study was carried out to determine whether the pathological mode of infiltrative growth (INF) of a metastatic liver nodule is useful in predicting recurrence in the remnant liver after hepatic resection. A total of 42 curative hepatic resections were performed for 37 patients with isolated liver metastases from colorectal cancer. Multivariate analysis (n = 42) showed that number, INF type, and size of liver metastases were statistically significant as independent risk factors. Of these, 28 resected liver metastases (smaller than 6 cm in size or containing fewer than 4 nodules) were classified pathologically into INF alpha or beta types (INF a b; n = 14) and gamma type (INFg; n = 14). Disease-free survival at 5 years was 64% for patients with INF a b type, and 14% for those with the INF g type of liver metastases. Of these, recurrent disease of the liver after hepatic resection was found in 2 (14%) and 11 (79%) patients with INF a b and INF g types, respectively. From these observations, we concluded that pathological infiltrative growth of liver metastases is an informative predictor of disease-free survival and especially of recurrence in the remnant liver.

Helicobacter pylori accelerates the biliary epithelial cell proliferation activity in hepatolithiasis.

BACKGROUND/AIMS: Several authors have reported the presence of H. pylori in the human biliary tract. The aim of this study was to investigate the influence of the presence of H. pylori on the epithelial cell proliferation activity in the biliary tract with hepatolithiasis. METHODOLOGY: A histopathological examination and polymerase chain reaction were used to detect the presence of H. pylori from fourteen patients with hepatolithiasis. The cell proliferation activity in the biliary epithelia was determined using proliferating cell nuclear antigen staining. RESULTS: A histopathological examination and polymerase chain reaction analysis demonstrated H. pylori to be detected in 5 (37%) and 4 (29%) out of 14 patients, respectively. The proliferating cell nuclear antigen labeling index was significantly higher in the H. pylori-positive patients (28.3%) than in the H. pylori-negative individuals (4.9%). CONCLUSIONS: H. pylori is present in the biliary tract of patients with hepatolithiasis, while H. pylori promotes the formation of stones in the biliary tract. The development of intrahepatic cholangiocarcinoma might therefore be linked to the presence of H. pylori because of the accelerated activity of cell kinetics in the epithelium of the biliary tract.

Pre- and intraoperative evaluation of biliary system for successful laparoscopic cholecystectomy in porcelain gallbladder patients.

BACKGROUND/AIMS: A porcelain gallbladder is generally thought to be a relative contraindication for laparoscopic cholecystectomy because of the difficulties in grasping the calcified wall of the gallbladder with forceps and making a retraction which would create a good operation field. The aim of this study was to define the clinical criteria for safe laparoscopic cholecystectomy in the treatment of porcelain gallbladders. METHODOLOGY: Between January 1993 and December 2000, 4 patients with porcelain gallbladders underwent laparoscopic cholecystectomy in our department. The significant features of the biliary system which contributed to the surgical results were investigated in these patients. RESULTS: All 4 patients were successfully treated by means of laparoscopic cholecystectomy. The confluence of the cystic duct was clearly demonstrated on the preoperative cholangiogram in all patients. Furthermore, the neck portion of the gallbladder wall, revealed no calcification on the CT scans of 3 patients, although the whole wall of the gallbladder, including the neck portion, showed a circumferential calcification in the remaining patient. Laparoscopic exposure and dissection of the Calot's triangle was relatively easy to perform in the former and was difficult in the latter, and thus, an anterograde laparoscopic cholecystectomy was the procedure of choice. Intraoperative cholangiography clearly demonstrated the confluence of the cystic duct in all of the patients. CONCLUSIONS: Porcelain gallbladder is an indication for laparoscopic cholecystectomy, especially in cases of a patent cystic duct and an uncalcified wall in the neck portion of the gallbladder. Laparoscopic cholecystectomy might be an indication for selected patients with porcelain gallbladder when an uncalcified and patent cystic duct are evident in pre- and intraoperative cholangiograms.

Elevated IL-8 levels in the drainage vein of resectable Dukes' C colorectal cancer indicate high risk for developing hepatic metastasis.

To investigate the relationship between tumor angiogenesis and hematogenous metastasis in colorectal cancer, an immunohistochemical analysis using antibody against factor VIII was carried out on archival specimens of 35 primary tumors. In addition, we also evaluated the levels of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8), by an enzyme-linked immunosorbent assay (ELISA), in tumor specimens and the serum in the drainage venous blood. The levels of VEGF showed no correlation with the microvessel density and also did not increase significantly in patients with hepatic metastasis. On the other hand, the IL-8 levels in the tumor tissue (r=0.45) and the serum IL-8 levels (r=0.49) showed a significant correlation with the microvessel density. The serum IL-8 levels in patients with Dukes' C colorectal cancer and hepatic metastasis were significantly higher than in those without hepatic metastasis (p<0.05). In addition, the serum levels of IL-8 in patients with Dukes' C cancer without hepatic metastasis and those with Dukes' A and B cancer were also closely similar. These results suggest that IL-8 is associated with the microvessel density in primary tumors and thus play an important role in the occurrence of hepatic metastasis in patients with colorectal cancer. As a result, elevated levels of IL-8 in the drainage vein are considered to be a useful predictor for developing hepatic metastasis in patients with resectable colorectal cancer.