Needle-based Confocal Laser Endomicroscopy (nCLE) for Evaluation of Pancreatic Cystic Lesions: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Given the variable diagnostic yield of endoscopic ultrasound and endoscopic ultrasound-guided fine-needle aspiration for pancreatic cystic lesions (PCLs), novel imaging techniques including needle-based confocal laser endomicroscopy (nCLE) have been devised. The aim of this study was to perform a structured systematic review and meta-analysis to evaluate the diagnostic performance and safety of nCLE for the diagnosis of PCLs. METHODS: Individualized search strategies were developed in accordance with PRISMA and MOOSE guidelines and meta-analysis analyzed according to the Cochrane Diagnostic Test Accuracy working group methodology. Measured outcomes included diagnostic characteristics and procedure-associated adverse events. A bivariate model was used to compute combined weighted sensitivity, specificity, positive/negative likelihood ratio (LR), diagnostic odds ratio, and summary receiver operating characteristic curve with corresponding 95% confidence intervals (CIs). RESULTS: Seven studies (n=324; mean age: 63.99±5.36 y; 52.47% female) were included. The pooled sensitivity, specificity, positive LR, and negative LR of nCLE was 85% (95% CI, 71-93; I2=74.20%), 99% (95% CI, 90-100; I2=72.60%), 78.66 (95% CI, 7.99-774.68; I2=26.86%), and 0.15 (95% CI, 0.07-0.31; I2=75.84%), respectively. Diagnostic accuracy as measured by summary receiver operating characteristic curve was 99% (95% CI, 98-100). The pooled diagnostic odds ratio was 534 (95% CI, 50-5664; I2=58.00%). Postprocedure pancreatitis developed in 1% (95% CI, 0-3; I2=5.64%) of cases. CONCLUSIONS: On the basis of this meta-analysis, nCLE appears to be an effective and safe technique for the diagnostic evaluation of PCLs. Although moderate-to-high amounts of heterogeneity were present, our results demonstrated that nCLE has a diagnostic accuracy of 99% with a low rate of adverse events.

Hepatocellular Carcinoma Demonstrates Heterogeneous Growth Patterns in a Multicenter Cohort of Patients With Cirrhosis.

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.

Direct-Acting Antiviral Therapy Not Associated With Recurrence of Hepatocellular Carcinoma in a Multicenter North American Cohort Study.

BACKGROUND & AIMS: There is controversy over the effects of direct-acting antiviral (DAA) therapies for hepatitis C virus (HCV) infection on hepatocellular carcinoma (HCC) recurrence and tumor aggressiveness. We compared HCC recurrence patterns between DAA-treated and untreated HCV-infected patients who had achieved a complete response to HCC treatment in a North American cohort. METHODS: We conducted a retrospective cohort study of patients with HCV-related HCC with a complete response to resection, local ablation, transarterial chemo- or radioembolization, or radiation therapy from January 2013 through December 2017 at 31 health systems throughout the United States and Canada. Cox regression was used to examine the association between DAA therapy and time to recurrence after a complete response, with DAA therapy analyzed as a time-varying exposure. We also estimated the association between DAA therapy and risk of early HCC recurrence (defined as 365 days after complete response). RESULTS: Of 793 patients with HCV-associated HCC, 304 (38.3%) received DAA therapy and 489 (61.7%) were untreated. HCC recurred in 128 DAA-treated patients (42.1%; early recurrence in 52 patients) and 288 untreated patients (58.9%; early recurrence in 227 patients). DAA therapy was not associated with HCC recurrence (hazard ratio 0.90, 95% confidence interval 0.70-1.16) or early HCC recurrence (hazard ratio 0.96, 95% confidence interval 0.70-1.34) after we adjusted for study site, age, sex, Child-Pugh score, α-fetoprotein level, tumor burden, and HCC treatment modality. In DAA-treated and untreated patients, most recurrences were within the Milan criteria (74.2% vs 78.8%; P = .23). A larger proportion of DAA-treated than untreated patients received potentially curative HCC therapy for recurrent HCC (32.0% vs 24.6%) and achieved a complete or partial response (45.3% vs 41.0%) but this did not achieve statistical significance. CONCLUSION: In a large cohort of North American patients with complete response to HCC treatment, DAA therapy was not associated with increased overall or early HCC recurrence. HCC recurrence patterns, including treatment response, were similar in DAA-treated and untreated patients.