Meta-analysis of prognostic factors for overall survival in patients with resected hilar cholangiocarcinoma.

BACKGROUND: Hilar cholangiocarcinoma is staged using the AJCC staging system. Numerous other prognostically important histopathological and demographic characteristics have been reported. The objective of this meta-analysis was to assess statistically the effect of postresectional tumour characteristics on overall survival of patients undergoing attempted radical curative resection for hilar cholangiocarcinoma. METHODS: Relevant studies were identified by searching the Ovid MEDLINE and PubMed databases. The search was limited to studies published between 2009 and 2017. Papers referring to intrahepatic or distal cholangiocarcinoma were excluded from review. Data extraction used standard Parmar modifications to determine pooled univariable hazard ratios (HRs). RESULTS: Twenty-four articles, containing 4599 patients, were assessed quantitatively. In pooled analyses, age (HR 1·16, 95 per cent c.i. 1·04 to 1·28), T category (HR 1·49, 1·30 to 1·70), lymph node involvement (HR 1·78, 1·65 to 1·93), microvascular invasion (HR 1·49, 1·34 to 1·68), perineural invasion (HR 1·54, 1·40 to 1·68) and tumour differentiation (HR 1·54, 1·38 to 1·72) were significant prognostic factors, with low heterogeneity. Portal vein resection (HR 1·54, 1·15 to 1·70) and resection margin status (HR 1·77, 1·57 to 1·99) had significant effects, but with high heterogeneity. Sex, tumour size and preoperative carbohydrate antigen 19-9 levels did not have a statistically significant effect on postoperative prognosis. CONCLUSION: Several tumour biological variables not included in the seventh edition of the AJCC classification affect overall survival. These require incorporation into prognostic models to ensure a personalized approach to prognostication and treatment.

Immunohistochemical hENT1 expression as a prognostic biomarker in patients with resected pancreatic ductal adenocarcinoma undergoing adjuvant gemcitabine-based chemotherapy.

BACKGROUND: Human equilibrative nucleoside transporters (hENTs) are transmembranous proteins that facilitate the uptake of nucleosides and nucleoside analogues, such as gemcitabine, into the cell. The abundance of hENT1 transporters in resected pancreatic ductal adenocarcinoma (PDAC) might make hENT1 a potential biomarker of response to adjuvant chemotherapy. The aim of this study was to see whether hENT1 expression, as determined by immunohistochemistry, was a suitable predictive marker for subsequent treatment with gemcitabine-based adjuvant chemotherapy. METHODS: A systematic review was performed, searching databases from January 1997 to January 2016. Articles pertaining to hENT1 immunohistochemical analysis in resected PDAC specimens from patients who subsequently underwent adjuvant gemcitabine-based chemotherapy were identified. Eligible studies were required to contain survival data, reporting specifically overall survival (OS) and disease-free survival (DFS) with associated hazard ratios (HRs) stratified by hENT1 status. RESULTS: Of 42 articles reviewed, eight were suitable for review, with seven selected for quantitative meta-analysis. The total number of patients included in the meta-analysis was 770 (405 hENT1-negative, 365 hENT1-positive). Immunohistochemically detected hENT1 expression was significantly associated with both prolonged DFS (HR 0·58, 95 per cent c.i. 0·42 to 0·79) and OS (HR 0·52, 0·38 to 0·72) in patients receiving adjuvant gemcitabine but not those having fluoropyrimidine-based adjuvant therapy. CONCLUSION: Expression of hENT1 is a suitable prognostic biomarker in patients undergoing adjuvant gemcitabine-based chemotherapy.