Biomarkers in bile-complementing advanced endoscopic imaging in the diagnosis of indeterminate biliary strictures

Biliary strictures present a diagnostic challenge and a conundrum, particularly when an initial work up including abdominal imaging and endoscopic retrograde cholangiopancreatography based sampling are nondiagnostic. Advances in endoscopic imaging have helped us diagnose these strictures better. However, even with modern technology, some strictures remain a diagnostic challenge. The proximity of bile fluid to the bile duct epithelia makes it an attractive option to investigate for bio-markers, which might be representative of the functions/abnormal changes taking place in the biliary system. A number of biomarkers in bile have been discovered recently in approaching biliary strictures with their potential future diagnostic utility, further supported by the immunohistochemical analysis of the resected tissue specimens. Novel biliary biomarkers especially carcinoembryonic cell adhesion molecule 6 and neutrophil gelatinase-associated lipocalin seem promising in differentiating malignant from benign biliary strictures. Recent developments in lipidomic profiling of bile are also very promising. Biliary biomarkers appear to complement endoscopic imaging in diagnosing malignant etiologies of biliary stricture. Future studies addressing these biomarkers need to be incorporated to the current endoscopic techniques to determine the best approach in determining the etiology of biliary strictures.

Endoscopic ultrasound in the diagnosis of cholangiocarcinoma as the etiology of biliary strictures:a systematic review and meta-analysis

Background and aim:Extrahepatic cholangiocarcinoma(CCA)typically presents as biliary strictures.Endoscopic ultrasound(EUS)-fine needle aspiration(FNA)may contribute to the diagnosis of CCA as the etiology of extrahepatic biliary strictures.Our aim was to study the uselfulness of EUS-FNA in diagnosing CCA as the etiology of biliary strictures.Patients and methods:In this meta-analysis,PUBMED and EMBASE databases were examined to find studies published to April 2014 where diagnostic correlation of CCA was available.Studies reporting only‘‘positive for malignancy’’were included in our analysis.The main outcome measurements were sensitivity,specificity and likelihood ratio.Results:Six studies were included,covering 196 patients.The overall pooled sensitivity and negative likelihood ratio(LR-)of EUS-FNA for diagnosis of CCA were 66%[95%confidence interval(CI)57-74%]and 0.34(95%CI 0.26-0.43),respectively.In five studies(146 patients),where a mass lesion was detected during EUS,the pooled sensitivity and LR-of EUS-FNA for diagnosis of CCA were 80%[95%CI 72-87%]and 0.20(95%CI 0.13-0.28),respectively.In the 49 patients with a negative brush cytology,the pooled sensitivity and LR-of EUS-FNA for diagnosis of CCA were 59%[95%CI 44-73%]and 0.41(95%CI 0.27-0.56),respectively.Conclusions:Our study suggests that EUS-FNA is useful in the evaluation of CCA as the etiology of biliary strictures.EUS-FNA may improve the diagnosis of CCA in patients with negative cytology and no mass on cross-sectional imaging.

炎症性肠病患者中结直肠癌患者的切除率:基于人群的研究

背景与目的:炎症性肠病(IBD)患者结直肠癌的发生风险升高。本研究旨在分析美国IBD相关结直肠癌手术切除率的变化趋势。方法:我们收集了美国住院样本数据库1995-2012年间的相关病例资料。采用多因素Joinpoint回归模型分析年龄标化的IBD相关结直肠癌的手术切除率的时间变化趋势。主要结局指标是IBD相关结直肠癌的手术切除率。结果:共纳入1995-2012年间3,597,168例IBD出院病例,其中275,479例接受了结直肠癌切除手术。IBD人群中的结直肠癌切除率从1995年至2012年显著下降,各个年龄组的年切除例数均显著下降,18-39岁组、40-49岁组、50-74岁组和75岁以上组每100,000例IBD患者中结直肠癌年切除例数从1995年至2012年分别减少393、359、293和159例(均P<0.001);其中,近端结直肠癌年切除例数分别减少149、130、95和50例(均P<0.001),远端结直肠癌年切除例数分别减少104、123、123和82例(均P<0.001)。多因素Poisson回归分析显示,校正年龄和性别因素后,结直肠癌切除率从1995-2012年间年均下降了3.9%。结论:从1995-2012年间,IBD患者中的结直肠癌切除率逐年下降,且近端和远端结直肠癌切除率均呈现下降趋势。这一人群水平的下降趋势反应了美国IBD相关结直肠癌发病率的下降。

Bile proteomics for differentiation of malignant from benign biliary strictures:a pilot study

Background:Determining the etiology of biliary strictures is challenging,and the sensitivities of the current tests to diagnose them are low.Protein biomarkers in bile,in combination with other tests,may improve sensitivity in diagnosing biliary strictures.Objective:To analyse the differential abundance of proteins in benign and malignant biliary strictures through proteomic analysis of bile.Methods:In this prospective,cross-sectional study,bile was aspirated in 24 patients undergoing endoscopic retrograde cholangiopancreatography(ERCP)including six patients with primary sclerosing cholangitis(PSC),three with cholangiocarcinoma(CCA),ten with pancreatic cancer,and five with benign biliary conditions.Liquid chromatography/mass spectrometry was used to examine the bile for differential abundance of protein biomarkers.The relative abundance of various proteins was compared in the malignant vs.benign groups and in CCA vs.PSC.Results:The majority of the proteins identified in bile were similar to those of the plasma(plasma proteins)and certain proteins were differentially expressed among the different groups(CCA,pancreatic cancer,PSC or benign).A total of 18 proteins were identified as being more abundant in the malignant group(CCA and pancreatic cancer)than in the benign strictures group,including myeloperoxidase,complement C3,inter-alpha-trypsin inhibitor heavy chain H4,apolipoprotein B-100,and kininogen-1 isoform 2.A total of 30 proteins were identified to be less abundant in the malignant group than in the benign group,including trefoil factor 2,superoxide dismutase[Cu-Zn],kallikrein-1,carboxypeptidase B and trefoil factor 1.Conclusions:Protein biomarkers in bile may differentiate malignant from benign biliary strictures.Larger studies are warranted to validate these observations.

合并溃疡性结肠炎与合并克罗恩病的原发性硬化性胆管炎患者临床结局比较

背景:合并原发性硬化性胆管炎(PSC)的溃疡性结肠炎(UC)与克罗恩病(CD)的结局比较尚不清楚。本研究旨在对两者的临床结局进行客观比较。方法:273例合并PSC的炎性肠病患者(UC 223例,CD 50例)纳入研究。收集入组病例的临床及人口统计学资料。结果:两组病例PSC危险度评分相近。PSC-UC组和PSC-CD组患者的中位随访时间分别是12(0-38)年和14(1-36)年。中位疾病复发次数PSC-UC组多于PSC-CD组[1(0-20)vs.0(0-9);P<0.001]。出现结肠瘤变的患者比例PSC-UC组高于PSC-CD组(35.9%vs.18%;P=0.009)。结肠切除手术的比例风险模型分析显示,PSC-UC患者结肠切除手术风险较PSC-CD增高12%[风险比(HR)=0.88;95%可信区间(CI)0.51-1.51;P=0.64]。同时,针对PSC的肝移植可降低结肠切除手术风险(HR=0.57;95%CI 0.37-0.89;P=0.013);而结肠瘤变则增加该风险(HR=3.83;95%CI 2.63-5.58;P<0.001)。结肠瘤变的比例风险模型显示,PSC-UC患者结肠瘤变风险较PSC-CD患者增高56%(HR=0.44;95%CI 0.16-1.25;P=0.12)。结论:合并CD的PSC患者结肠瘤变和结肠切除手术的风险低于合并UC者。