Background Evaluation of indeterminate biliary strictures typically involves collection and analysis of tissue or cells. Brush cytology and intraductal biopsies that are routinely performed during ERCP to assess malignant-appearing biliary strictures are limited by relatively low sensitivity. Objective To study the comparative effectiveness of brushings for cytology and intraductal biopsies in the etiology of biliary strictures. Design Meta-analysis. Setting Referral center. Patients PUBMED and Embase databases were reviewed for studies published to April 2014 where diagnostic correlation of histology was available. Intervention Database and review of study findings. Main Outcome Measurements Sensitivity and specificity. Results The pooled sensitivity and specificity of brushings for the diagnosis of malignant biliary strictures was 45% (95% confidence interval [CI], 40%–50%) and 99% (95% CI, 98%–100%), respectively. The pooled diagnostic odds ratio to detect malignant biliary strictures was 33.43 (95% CI, 14.29–78.24). For intraductal biopsies, the pooled sensitivity and specificity were 48.1% (95% CI, 42.8%–53.4%) and 99.2% (95% CI, 97.6%–99.8%), respectively. The pooled diagnostic odds ratio to detect malignant biliary strictures was 43.18 (95% CI, 19.39–95.83). A combination of both modalities only modestly increased the sensitivity (59.4%; 95% CI, 53.7%–64.8%) with a specificity of 100% (95% CI, 98.8%–100.0%). The Begg-Mazumdar and Egger tests indicated a low potential for publication bias. Limitations Inclusion of low-quality studies. Conclusion Our study suggests that both brushings and biopsy are comparable and have limited sensitivity for the diagnosis of malignant biliary strictures. A combination of both only modestly increases the sensitivity.

§ Drs. Murphy and Parikh contributed equally and are co-senior authors Author contributions: Dr. Singal had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design (Singal and Parikh); Acquisition, analysis and interpretation of the data (all authors); Drafting of the manuscript (Singal); Critical revision of the manuscript for important intellectual content (all authors); Obtained funding (Singal, Parikh); Administrative, technical, and material support (Singal and Parikh); Study supervision (Singal) Conflicts of Interest: Amit Singal was on speakers bureau for Gilead, Bayer, and Bristol Meyers Squibb. He has served on advisory boards for Gilead, Abbvie, Bayer, Eisai, Wako Diagnostics, Roche, and Exact Sciences. He serves as a consultant to Bayer, Eisai, Roche, and Glycotest. He has received research funding from Gilead and Abbvie. Neil Mehta has received research funding from Wako Diagnostics. Anjana Pillai serves as a consultant and is on speakers bureau for Eisai and BTG. Jordan Feld has received research support from Gilead, Abbvie, Merck, and Janssen. Binu John has served on advisory boards for Eisai. Catherine Frenette is on speakers bureaus for Bayer, Bristol Meyers Squibb, Gilead, Merck, Abbvie, and Eisai. She served on advisory boards for Gilead, Eisai, and Wako. She served as a consultant for Bayer and Gilead. She received research funding from Bayer. Parvez Mantry is on speakers bureaus and served on advisory boards for Gilead, Abbvie, Bayer, BMS, Eisai, Merck, and BTG. He has received research funding from Gilead and Sirtex. Michael Leise has received research funding from Abbvie. Kalyan Ram Bhamidimarri serves as scientific advisory board member for Gilead, Merck, and Abbvie. He has received research funding from Gilead. Laura Kulik is on speakers bureau for Eisai, Gilead, and Dova. She serves as an advisory board member for BMS, Eisai, Bayer, Exelixis Reena Salgia is on speakers bureau for Bayer. She has served on advisory boards for Bayer, Eisai, and Exelixis. Sanjaya Satapathy has received research support from Gilead and Bayer.He has served on advisory boards or as a consultant for Abbvie and Gilead.

Background and Aims There are limited data on hepatocellular carcinoma (HCC) growth patterns, particularly in Western cohorts, despite implications for surveillance, prognosis, and treatment. Our study’s aim was to quantify tumor doubling time (TDT) and identify correlates associated with indolent and rapid growth. Approach and Results We performed a retrospective multicenter cohort study of patients with cirrhosis diagnosed with HCC from 2008 to 2017 at six US and European health systems with two or more contrast‐enhanced imaging studies performed ≥ 30 days apart prior to HCC treatment. Radiologists independently measured tumors in three dimensions to calculate TDT and specific growth rate (SGR). We used multivariable ordinal logistic regression to identify factors associated with indolent (TDT > 365 days) and rapid (TDT < 90 days) tumor growth. In the primary cohort (n = 242 patients from four centers), median TDT was 229 days (interquartile range [IQR], 89‐627) and median SGR was 0.3% per day (IQR, 0.1%‐0.8%). Over one‐third (38%) of HCCs had indolent growth, 36.8% intermediate growth, and 25.2% rapid growth. In multivariable analysis, indolent growth was associated with larger tumor diameter (odds ratio [OR], 1.15, 95% confidence interval [CI], 1.03–1.30) and alpha‐fetoprotein < 20 ng/mL (OR, 1.90; 95% CI, 1.12‐3.21). Indolent growth was more common in nonviral than viral cirrhosis (50.9% versus 32.1%), particularly in patients with T1 HCC (OR, 3.41; 95% CI, 1.08‐10.80). Median TDT (169 days; IQR 74‐408 days) and SGR (0.4% per day) were similar in an independent cohort (n = 176 patients from two centers). Conclusions In a large Western cohort of patients with HCC, we found heterogeneous tumor growth patterns, with one‐fourth exhibiting rapid growth and over one‐third having indolent growth. Better understanding different tumor growth patterns may facilitate a precision approach to prognostication and treatment.

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