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Patterns of failure after resection of extrahepatic bile duct cancer: implications for adjuvant radiotherapy indication and treatment volumes.

ABSTRACT: BACKGROUNDThe role of adjuvant radiotherapy (RT) and setting proper RT target volumes have not been clearly demonstrated for extrahepatic bile duct (EHBD) cancer, due to the rarity of the disease and the lack of randomized trials. This study was conducted to evaluate the indication and treatment volume for adjuvant RT in EHBD cancer patients by identifying the prognostic factors for loco-regional (LR) failure, and analyze the patterns of LR failure.METHODSNinety-three patients with EHBD cancer, who underwent resection without adjuvant RT, at 2 medical centers, between 2001 and 2016, were analyzed retrospectively. Univariable and multivariable analyses were performed to find the prognostic factors for LR recurrence. The initial patterns of failure were recorded, especially those of LR recurrence, and categorized according to the Japanese classification.RESULTSThe median follow-up duration was 30 months, and 38 (40.9%) patients experienced LR recurrence during this period. With regards to LR recurrence, close or positive resection margin (RM) status (p?CONCLUSIONSA close or positive RM status may be suggestive of high LR recurrence rates. In such cases, adjuvant RT may improve outcomes. When adjuvant RT is performed, the treatment volume should be well-designed so as to encompass the tumor bed, as well as LN stations No. 8, No. 9, No. 12, No. 14, and No. 16.

SUBMITTER: Choi HS

PROVIDER: S-EPMC5941763 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Patterns of failure after resection of extrahepatic bile duct cancer: implications for adjuvant radiotherapy indication and treatment volumes.

Choi Hoon Sik HS Kang Ki Mun KM Jeong Bae Kwon BK Jeong Hojin H Lee Yun Hee YH Ha In Bong IB Kim Tae Gyu TG Song Jin Ho JH

Radiation oncology (London, England) 20180508 1

<h4>Background</h4>The role of adjuvant radiotherapy (RT) and setting proper RT target volumes have not been clearly demonstrated for extrahepatic bile duct (EHBD) cancer, due to the rarity of the disease and the lack of randomized trials. This study was conducted to evaluate the indication and treatment volume for adjuvant RT in EHBD cancer patients by identifying the prognostic factors for loco-regional (LR) failure, and analyze the patterns of LR failure.<h4>Methods</h4>Ninety-three patients ...[more]

PMID: 29739420

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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.

Project description:BackgroundMargin status is one of the most significant prognostic factors after curative surgery for middle bile duct (MBD) cancer. Bile duct resection (BDR) is commonly converted to pancreaticoduodenectomy (PD) to achieve R0 resection. Additionally, adjuvant treatment is actively performed after surgery to improve survival. However, the wider the range of surgery, the higher the chance of complications; this, in turn, makes adjuvant treatment impossible. Nevertheless, no definitive surgical strategy considers the possible complication rates and subsequent adjuvant treatment. We aimed to investigate the appropriate surgical type considering the margin status, complications, and adjuvant treatment in MBD cancer.Materials and methodsFrom 2008 to 2017, 520 patients diagnosed with MBD cancer at the Samsung Medical Center were analyzed retrospectively according to the operation type, margin status, complications, and adjuvant treatment. The R1 group was defined as having a carcinoma margin.ResultsThe 5-year survival rate for patients who underwent R0 and R1 resection was 54.4% and 33.3%, respectively (p = 0.131). Prognostic factors affecting the overall survival were the age, preoperative CA19-9 level, T stage, and N stage, but not the operation type, margin status, complications, or adjuvant treatment. The complication rates were 11.5% and 29.8% in the BDR and PD groups, respectively (p < 0.001). We observed no significant difference in the adjuvant treatment ratio according to complications (p = 0.675). Patients with PD who underwent R0 resection and could not undergo chemotherapy because of complications reported better survival rates than those with BDR who underwent R1 resection after adjuvant treatment (p = 0.003).ConclusionThe survival outcome of patients with R1 margins who underwent BDR did not match those with R0 margins after PD, even after adjuvant treatment. Due to improvements in surgical techniques and the ability to resolve complications, surgical complications exert a marginal effect on survival. Therefore, surgeons should secure R0 margins to achieve the best survival outcomes.

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Patterns of failure after resection of extrahepatic bile duct cancer: implications for adjuvant radiotherapy indication and treatment volumes.

Publications

Patterns of failure after resection of extrahepatic bile duct cancer: implications for adjuvant radiotherapy indication and treatment volumes.

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