Taku Matsumoto

Frequent activation of mitogen-activated protein kinase relative to Akt in extrahepatic biliary tract cancer.

BackgroundLack of effective adjuvant therapy against advanced extrahepatic biliary tract carcinoma (BTC) requires that new therapeutic methods, such as molecular targeted therapy, be developed. The mitogen-activated protein kinase (MAPK) and Akt signaling pathways, which activate cell proliferation and suppress apoptosis, respectively, may function as important targets for such therapies. The aim of this study was to examine the expression patterns of phosphorylated MAPK (p-MAPK) and phosphorylated Akt (p-Akt) proteins in BTC cell lines and clinical specimens.MethodsExpression of p-MAPK and p-Akt proteins in four human BTC cell lines and in frozen sections of 20 advanced extrahepatic BTC specimens was analyzed by Western blotting. Thirty formalin-fixed BTC specimens were immunohistochemically stained for p-MAPK and p-Akt using labeled streptavidin–biotin conjugates.ResultsExpression of p-MAPK was observed in three of four (75%) BTC cell lines, whereas no expression of p-Akt was observed. Twenty-three of 30 formalin-fixed specimens stained positive for p-MAPK (77%), whereas only 47% stained positively for p-Akt. Expression of p-MAPK relative to that of p-Akt was also seen more frequently in the frozen specimens.ConclusionsThe results of this study suggest that MAPK is activated more frequently than Akt in extrahepatic biliary tract carcinoma.

Resection of gallbladder cancer with hepatic metastasis after chemotherapy with gemcitabine

A 69-year-old man diagnosed as having gallbladder cancer with liver invasion and metastasis to Couinauds hepatic segment 8 (S8) was referred to our hospital. Because of the presence of liver metastasis, gemcitabine administration was chosen. Although gemcitabine was effective for the liver metastasis, his serum carcinoembryonic antigen (CEA) level had gradually increased after 12 cycles of gemcitabine administration. There was no distant metastasis other than the liver metastasis (manageable with gemcitabine) on detailed radiological examination. Therefore, we performed surgery for the primary lesion, after obtaining informed consent. Pathological examination demonstrated viable cancer cells with necrosis and fibrosis in the gallbladder, and fibrosis without viable cancer cells in the induration in liver S8. Gemcitabine was re-administered as postoperative adjuvant chemotherapy. Twenty months after the surgery, there was no sign of recurrence. In selected patients, gemcitabine treatment may be effective against gallbladder cancer with metastasis.

Decreased expression of intestinal chemokine TECK/CCL25 in experimental obstructive jaundice and its reversal following internal biliary drainage

BackgroundAlthough bacterial translocation is a significant problem in patients with obstructive jaundice, how translocation is promoted in this situation is not clearly understood. We previously reported the recovery of gut mucosal T-lymphocyte numbers in jaundiced rats following internal biliary drainage. This suggests that bile in the intestinal lumen promotes T-lymphocyte redistribution into the gut mucosa. To test this hypothesis, we have examined the expression patterns of chemokines that play an important role in lymphocyte recruitment into the small intestine.MethodsFour groups of rats receiving one of the following surgical procedures were studied: a sham operation (SHAM), common bile duct ligation (CBDL), CBDL followed by external drainage, or CBDL followed by internal drainage. Expression levels of intestinal mRNAs encoding TECK, MECK, and LARC chemokines were assessed using real-time polymerase chain reaction. Distribution of chemokine mRNA in the rat ileum was examined using in situ hybridization (ISH).ResultsFollowing surgery, the expression levels of TECK mRNA decreased significantly in the CBDL group compared with in the SHAM group. While TECK expression did not recover after external drainage, it recovered to a near-normal level after internal drainage. Expression levels of MECK and LARC mRNAs were similar among all groups. ISH confirmed strong expression of TECK mRNA in the epithelial cells of the small intestine.ConclusionsThese results indicate that bile may contribute to high expression levels of TECK/CCL25 mRNA in the small intestine. Bile may also have a role in regulating the distribution of gut mucosal T lymphocytes by promoting TECK production from epithelial cells.

Intrahepatic segmental primary sclerosing cholangitis: report of a case.

A 67-year-old woman was referred to our hospital for investigation of epigastric discomfort. Computed tomography (CT) showed dilatation of the intrahepatic bile duct in the left lobe of the liver, endoscopic cholangiography showed complete stenosis of the left main branch of intrahepatic bile duct, and CT during angiography showed decreased portal blood flow to segment 3 of the liver. Based on these findings, we suspected intrahepatic cholangiocarcinoma and performed left lobectomy of the liver. However, pathological examination revealed fibrosis and infiltration of inflammatory lymphoid cells around the stenotic bile duct and periportal area, without any evidence of malignancy. Since these findings were compatible with sclerosing cholangitis and the patient did not have a disorder that would cause secondary sclerosing cholangitis, the final diagnosis was primary sclerosing cholangitis (PSC). It is difficult to distinguish segmental PSC from cholangiocarcinoma; thus we think surgical resection is an appropriate therapeutic and diagnostic procedure for segmental intrahepatic bile duct stenosis.

Preoperative Cholangitis Affects Survival Outcome in Patients with Extrahepatic Bile Duct Cancer

BackgroundIt remains controversial whether preoperative cholangitis affects long-term outcomes after resection in patients with extrahepatic bile duct cancer.MethodsA total of 107 patients with extrahepatic bile duct cancer who underwent resection with curative intent from 2008 to 2014 were retrospectively reviewed. Patients were categorized into two groups according to the presence or absence of preoperative cholangitis. Clinicopathological variables and long-term outcomes were compared in the two groups.ResultsIn the preoperative cholangitis group, the rate of preoperative biliary drainage, the number of tube changes and/or additions, and the rate of lymph node metastasis were higher compared to the no-cholangitis group. Overall survival and disease-free survival were significantly worse in the cholangitis group compared to the no-cholangitis group (p = 0.022, p = 0.007). A poorer prognosis was not observed with an increasing grade of cholangitis in Tokyo Guidelines 2013 (p = 0.09). A multivariate logistic regression analysis revealed that the preoperative cholangitis was an independent prognostic factor for extrahepatic bile duct cancer.ConclusionPreoperative cholangitis is an independent prognostic factor in patients with extrahepatic bile duct cancer regardless of the severity of the cholangitis.

Gallbladder bed pocket score as a preoperative measure for assessing the difficulty of laparoscopic cholecystectomy

Laparoscopic cholecystectomy (Lap‐C) is a standard surgery for symptomatic gallbladder stones and acute or chronic cholecystitis. Resident surgeons often perform this operation early in their training, but they sometimes encounter difficulties for various technical reasons. Although encountering a gallbladder buried deep within the gallbladder bed is a common operative difficulty, literature on the subject scarcely exists.

Surgical resection for liver metastases developing 10 and 21 years after primary surgery for mucinous colon adenocarcinoma: A Case Report

Abstract Introduction Optimal management for liver metastases from colorectal mucinous adenocarcinoma is still controversial. Here, we report such a case of liver metastases which developed twice with 10 year intervals after curative resection. Case presentation An 84-year-old man had undergone a radical left hemicolectomy for descending colon cancer at 63 years of age. The histopathological diagnosis was mucinous adenocarcinoma. Ten years later, he was found to have a cystic tumor in liver and underwent partial hepatectomy of segment 5. Moreover, eleven years later of hepatic resection, CT showed low density tumor with calcification in remnant liver and partial hepatectomy of segment 8 was performed. Histopathological and immunohistochemical findings of each liver tumor indicated metastasis from primary colon mucinous adenocarcinoma. It is rare that colorectal mucinous adenocarcinoma recurs twice after long intervals of 10 years. However, also in a patient with a history of colorectal mucinous adenocarci...

Clinical significance of bile reflux into the pancreatic duct without pancreaticobiliary maljunction assessed by intraoperative cholangiography

Bile reflux into the pancreatic duct (BRPD) is sometimes demonstrated during intraoperative cholangiography (IOC) even in patients without pancreaticobiliary maljunction. However, the clinical significance of this finding in laparoscopic and open cholecystectomy is unclear.