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Impact of radiation dose in postoperative radiotherapy after R1 resection for extrahepatic bile duct cancer: long term results from a single institution.

ABSTRACT: This study was conducted to evaluate the impact of radiation dose after margin involved resection in patients with extrahepatic bile duct cancer.Among the 251 patients who underwent curative resection followed by adjuvant chemoradiotherapy, 86 patients had either invasive carcinoma (n = 63) or carcinoma in situ (n = 23) at the resected margin. Among them, 54 patients received conventional radiation dose (40-50.4 Gy) and 32 patients received escalated radiation dose (54-56 Gy).Escalated radiation dose was associated with improved locoregional control (5yr rate, 73.8% vs. 47.1%, p = 0.069), but not disease-free survival (5yr rate, 43.4% vs. 32.6%, p = 0.490) and overall survival (5yr rate, 40.6% vs. 29.6%, p = 0.348). In multivariate analysis for locoregional control, invasive carcinoma at the margin (HR 2.957, p = 0.032) and escalated radiation dose (HR 0.394, p = 0.047) were independent prognostic factors. No additional gastrointestinal toxicity was observed in escalated dose group.Delivery of radiation dose ? 54 Gy was well tolerated and associated with improved locoregional control, but not with overall survival after margin involved resection. Further validation study is warranted.

SUBMITTER: Kim BH

PROVIDER: S-EPMC5652838 | biostudies-other | 2017 Sep

REPOSITORIES: biostudies-other

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Impact of radiation dose in postoperative radiotherapy after R1 resection for extrahepatic bile duct cancer: long term results from a single institution.

Kim Byoung Hyuck BH Chie Eui Kyu EK Kim Kyubo K Jang Jin-Young JY Kim Sun Whe SW Oh Do-Youn DY Bang Yung-Jue YJ Ha Sung W SW

Oncotarget 20170421 44

<h4>Purpose</h4>This study was conducted to evaluate the impact of radiation dose after margin involved resection in patients with extrahepatic bile duct cancer.<h4>Methods</h4>Among the 251 patients who underwent curative resection followed by adjuvant chemoradiotherapy, 86 patients had either invasive carcinoma (<i>n</i> = 63) or carcinoma in situ (<i>n</i> = 23) at the resected margin. Among them, 54 patients received conventional radiation dose (40-50.4 Gy) and 32 patients received escalated ...[more]

PMID: 29100449

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Project description:Background & aimsThe extrahepatic bile duct is the primary tissue initially affected by biliary atresia. Biliary atresia is a cholangiopathy which exclusively affects neonates. Current animal models suggest that the developing bile duct is uniquely susceptible to damage. In this study, we aimed to define the anatomical and functional differences between the neonatal and adult mouse extrahepatic bile ducts.MethodsWe studied mouse passaged cholangiocytes, mouse BALB/c neonatal and adult primary cholangiocytes, as well as isolated extrahepatic bile ducts, and a collagen reporter mouse. The methods used included transmission electron microscopy, lectin staining, immunostaining, rhodamine uptake assays, bile acid toxicity assays, and in vitro modeling of the matrix.ResultsThe cholangiocyte monolayer of the neonatal extrahepatic bile duct was immature, lacking the uniform apical glycocalyx and mature cell-cell junctions typical of adult cholangiocytes. Functional studies showed that the glycocalyx protected against bile acid injury and that neonatal cholangiocyte monolayers were more permeable than adult monolayers. In adult ducts, the submucosal space was filled with collagen I, elastin, hyaluronic acid, and proteoglycans. In contrast, the neonatal submucosa had little collagen I and elastin, although both increased rapidly after birth. In vitro modeling of the matrix suggested that the composition of the neonatal submucosa relative to the adult submucosa led to increased diffusion of bile. A Col-GFP reporter mouse showed that cells in the neonatal but not adult submucosa were actively producing collagen.ConclusionWe identified 4 key differences between the neonatal and adult extrahepatic bile duct. We showed that these features may have functional implications, suggesting the neonatal extrahepatic bile ducts are particularly susceptible to injury and fibrosis.Lay summaryBiliary atresia is a disease that affects newborns and is characterized by extrahepatic bile duct injury and obstruction, resulting in liver injury. We identify 4 key differences between the epithelial and submucosal layers of the neonatal and adult extrahepatic bile duct and show that these may render the neonatal duct particularly susceptible to injury.

Dataset Information

Impact of radiation dose in postoperative radiotherapy after R1 resection for extrahepatic bile duct cancer: long term results from a single institution.

Publications

Impact of radiation dose in postoperative radiotherapy after R1 resection for extrahepatic bile duct cancer: long term results from a single institution.

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