Anomalous junction of the pancreaticobiliary duct accompanied by gallbladder cancer and obstructive jaundice in a patient with high serum and bile cytokine levels

Abstract

We report a case of anomalous junction of the pancreaticobiliary duct (AJPBD) associated with gallbladder cancer and obstructive jaundice in a patient with high serum and bile cytokine levels. The patient was a 63-year-old woman who complained of right hypochondralgia. Ultrasound, computed tomography, percutaneous transhepatic cholangiography, and endoscopic retrograde cholangio-pancreatatography revealed dilation of the bile ducts, an elevated lesion of the gallbladder, and AJPBD. She underwent percutaneous transhepatic cholangio-drainage (PTCD) for obstructive jaundice. However, the total bilirubin concentration remained high 7 days after PTCD. Her serum interleukin 6 level was 57,359 pg/ml before PTCD, and gradually decreased to 10 pg/ml after PTCD. Bile interleukin 6 level was 10 pg/ml before PTCD, 8997 pg/ ml 3 h after PTCD and gradually decreased there after. Serum and bile levels of tumor necrosis factor alpha and hepatocyte growth factor were high before and after PTCD. The patient underwent an extended cholecystectomy and resection of the extrahepatic bile duct. The resected specimen showed two elevated lesions of the gallbladder which, microscopically, revealed moderately differentiated tubular adenocarcinoma. These findings suggest that pre-existing inconspicuous inflammation of the biliary tract due to reflux of pancreatic juice is involved in elevation of serum and bile cytokines, and that cytokines may participate in gallbladder carcinogenesis associated with AJPBD.

Carcinogenesis in the biliary system associated with APDJ

“…Recently, Akiyama et al49 reported that a patient with gallbladder carcinoma, obstructive jaundice, and APDJ had high levels of serum interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), hepatocyte growth factor, and bile TNF‐α before percutaneous drainage of the bile duct. This patient had high levels of bile IL‐6 and TNF‐α after biliary drainage.…”

Molecular mechanisms of cholangiocarcinoma

“…IL6 content is increased in the course of chronic inflammation and the neoplastic processes in biliary ducts. It is also found at increased levels in bile and serum of CC affected patients [33] . This cytokine stimulates cell proliferation by an autocrine/paracrine mechanism [34] and specifically promotes the activation of p44/p42 and p38 mitogenactivated protein kinase (MAPK) pathways [35] which, in turn, decrease the expression of p21 (WAF1/CIP1), a cell cycle controller protein [36] .…”

Pancreaticobiliary maljunction: pathophysiological and clinical aspects and the impact on biliary carcinogenesis

“…Tokiwa et al [21] also reported elevated cellular proliferative activity of the gallbladder in PBM children. Several growth factors recently reported to be induced by PBM may promote the proliferation of gallbladder mucosa with PBM, such as the overexpression of transforming growth factor-α [28].…”