Comparison of the Clinicopathological Features and Survival in Small Bile Duct Type and Bile Ductular Type Intrahepatic Cholangiocarcinoma

AbstractChromosomal translocations involving fibroblast growth factor receptor 2 (FGFR2) gene at the breakpoints are common genetic lesions in intrahepatic cholangiocarcinoma (ICC) and the resultant fusion protein products have emerged as promising druggable targets. However, predicting the sensitivity of FGFR2 fusions to FGFR kinase inhibitors is crucial to the prognosis of the ICC-targeted therapy. Here, we report identification of nine FGFR2 translocations out of 173 (5.2%) ICC tumors. Although clinicopathologically these FGFR2 translocation bearing ICC tumors are indistinguishable from the rest of the cohort, they are invariably of the mass-forming type originated from the small bile duct. We show that the protein products of FGFR2 fusions can be classified into three subtypes based on the breaking positions of the fusion partners: the classical fusions that retain the tyrosine kinase (TK) and the Immunoglobulin (Ig)-like domains (n = 6); the sub-classical fusions that retain only the TK domain without the Ig-like domain (n = 1); and the non-classical fusions that lack both the TK and Ig-like domains (n = 2). We demonstrate that cholangiocarcinoma cells engineered to express the classical and sub-classical fusions show sensitivity to FGFR-specific kinase inhibitors as evident by the suppression of MAPK/ERK and AKT/PI3K activities following the inhibitor treatment. Furthermore, the kinase-deficient mutant of the sub-classical fusion also lost its sensitivity to the FGFR-specific inhibitors. Taken together, our study suggests that it is essential to determine the breakpoint and type of FGFR2 fusions in the small bile duct subtype of ICC for the targeted treatment.

Download Full-text

Detection of Small Bile Duct Stones by Intraductal US in Patients with Highly Suspected Choledocholithiasis Showing No Filling Defect on ERCP

Gastrointestinal Endoscopy ◽

10.1016/s0016-5107(04)00911-3 ◽

2004 ◽

Vol 59 (5) ◽

pp. P196 ◽

Cited By ~ 1

Author(s):

Jong Ho Moon ◽

Sang Woo Cha ◽

Young Koog Cheon ◽

Young Seok Kim ◽

Young Deok Cho ◽

...

Keyword(s):

Bile Duct ◽

Filling Defect ◽

Bile Duct Stones ◽

Small Bile Duct

Download Full-text

Increased cd1d expression on small bile duct epithelium and epithelioid granuloma in livers in primary biliary cirrhosis

Hepatology ◽

10.1002/hep.510280303 ◽

1998 ◽

Vol 28 (3) ◽

pp. 620-623 ◽

Cited By ~ 79

Author(s):

Koichi Tsuneyama ◽

Mitsue Yasoshima ◽

Kenichi Harada ◽

Katsushi Hiramatsu ◽

M. Eric Gershwin ◽

...

Keyword(s):

Bile Duct ◽

Primary Biliary Cirrhosis ◽

Biliary Cirrhosis ◽

Epithelioid Granuloma ◽

Duct Epithelium ◽

Small Bile Duct ◽

Bile Duct Epithelium

Download Full-text

Mdr 2 knockout mice link biliary phospholipid deficiency with small bile duct destruction Smit JJM, Schinkel AH, Oude Elferink RPJ, Groen AK, Wagenaar B., von Deemter L, Mol CAAM, et al. Homozygous disruption of the murine mdr2 p-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease. Cell 1993; 75: 451–462

Hepatology ◽

10.1016/0270-9139(94)90252-6 ◽

1994 ◽

Vol 19 (6) ◽

pp. 1528-1531

Author(s):

C Leveille-Webster

Keyword(s):

Liver Disease ◽

Bile Duct ◽

Knockout Mice ◽

Glycoprotein Gene ◽

P Glycoprotein ◽

Small Bile Duct ◽

Disease Cell

Download Full-text

Three Thousand Consecutive Pancreaticoduodenectomies in a Tertiary Cancer Center: A Retrospective Observational Study

Journal of Clinical Medicine ◽

10.3390/jcm9082558 ◽

2020 ◽

Vol 9 (8) ◽

pp. 2558

Author(s):

Ji Hye Jung ◽

Dong Wook Choi ◽

Sokyung Yoon ◽

So Jeong Yoon ◽

In Woong Han ◽

...

Keyword(s):

Overall Survival ◽

Survival Analysis ◽

Bile Duct ◽

Postoperative Pancreatic Fistula ◽

Clinicopathological Features ◽

Cancer Center ◽

The Past ◽

Improved Outcomes ◽

Drain Amylase ◽

Tertiary Cancer Center

(1) Aim: To evaluate clinicopathological features and postoperative outcomes including survival in patients who underwent pancreaticoduodenectomy (PD) for periampullary diseases. (2) Methods: We retrospectively reviewed 3078 cases of PD performed in our center for 25 years. Periampullary diseases were divided into benign and malignancy groups. All cases were also classified by location. The time of 25 years was divided to different periods (5 years per period) to compare outcomes. Overall survival was compared between subdivided periods. (3) Results: Hospitalization became significantly shorter from 28.0 days in the 1st period to 13.8 days in the 5th period. Overall complication rate was significantly increased since the 3rd period. The rate without postoperative pancreatic fistula (POPF) was high at 98.7% in the 1st period. This might be because drain amylase on the 3rd day after PD was not routinely checked in the past. Thus, POPF was not detected. In survival analysis of adenocarcinoma of pancreas, bile duct, and ampulla, overall survival was found to be improved significantly in recent years. (4) Conclusions: Our study revealed that outcomes were improved with increasing number of PDs performed. Although POPF and overall complications showed increases more recently, those were detected and managed, resulting in shorter hospitalization and improved outcomes.

Download Full-text