Screening for Pancreatic Cancer

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A meta-analysis of prospective cohort studies to determine the diagnostic yield and outcomes of abdominal imaging screening for asymptomatic individuals at high risk for pancreatic cancer, based on family history or genetic variants was carried out.

Through a systematic review of electronic databases and conference proceedings through July 2017, prospective cohort studies (greater than 20 patients), of asymptomatic adults with alifetime risk greater than 5%, including specificgenetic-associated conditions, who were screened by endoscopic ultrasound (EUS) and/or MRI to detect pancreatic lesions. The primary outcomewas identification of high-risk pancreatic lesions(high-grade pancreatic intraepithelial neoplasia, high-grade dysplasia, or adenocarcinoma) at initial screening and overall incidence during followup.

Summary estimates were reported as incidence rates per 100 patient-years.

A total of 19 studies were identified, comprising7085 individuals at high-risk for pancreatic cancer. Of these, 1660 patients were evaluated by EUS or MRI. A total of 59 high-risk lesionswere identified; 43 had no carcinomas; 28 duringthe initial examination and 15 during follow-up surveillance. A total of 257 patients underwent pancreatic surgery. Based on this meta-analysis, the overall diagnostic yield screening for high-riskpancreatic lesions was 0.74 per 100 patient-years,with moderate heterogeneity among studies. The number needed to screen to identify one patientwith a high-risk lesion was 135. The diagnosticyield was similar for patients with different genetic features at increased risk, and whether patients were screened by EUS or MRI.

Corral, J., Mareth, K., Riegert-Johnson, D., Daas, A., Wallace, M. “Diagnostic Yield from Screening Asymptomatic Individuals at High Risk for Pancreatic Cancer: A Meta-Analysis of Cohort Studies.” Clinical Gastroenterology and Hepatology 2019; Vol. 17, pp. 41-53.

Assessment of Fibrosis and Steatosis in NAFLD

To determine the diagnostic accuracy of vibration- controlled transient elastography (VCTE), which measures liver stiffness, a prospective study of393 adults with NAFLD was carried out within one year of liver histology analysis from 7/1/2014 through 7/31/2017.

Liver stiffness measurement (LSM) cut-off values for pairwise fibrosis stage and controlledattenuation parameter cut-off values for pairwise steatosis grade were determined using cross- validated area under the receiver operating characteristics curve (AUROC) analyses.Diagnostic statistics were computed at a sensitivity fixed at 90% and a specificity fixed at 90%.

LSM identified patients with advanced fibrosis with an AUROC of 0.83 and patients with cirrhosis with an AUROC of 0.93. At a fixed sensitivity, a cut-off LSM of 6.5 kBa excluded advancedcirrhosis with a negative predictive value of 0.99.At a fixed specificity, LSM identified patients with advanced fibrosis with a positive predictive valueof 0.71 and patients with cirrhosis with a positivepredictive value of 0.41.

Controlled attenuation parameter analysis detected steatosis with an AUROC of 0.76. In contrast, the VCTE was less accurate indistinguishing lower fibrosis stages, higher steatosis grades, or the presence of NASH.

It was concluded in a prospective study ofadults with NAFLD, VCTE was found to accurately distinguish advanced vs earlier stages of fibrosis,using liver histology as the reference standard.

Siddiqui, M., Vuppalanchi, R., Van Natta, M., et al for the NASH Clinical Research Network. “Vibration-Controlled Transient Elastography to Assess Fibrosis and Steatosis in Patients With Nonalcoholic Fatty Liver Disease.” Clinical Gastroenterology and Hepatology 2019; Vol. 17, pp. 156-163.

Transient Elastography in Apparently Healthy Individuals and Changes
in Liver Stiffness

A systematic review was carried out to determine the range of liver stiffness measurements (LSMs) examined by transient elastography in healthy individuals and individuals who are susceptible tofibrosis. Data was collected from 16,082 individuals in 26 cohorts, identified from systematic searches of MBASE, Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews for studies of liver stiffness measurements.

Studies analyzed included apparently healthy adults (normal levels of liver enzymes, low-risk alcohol use patterns, and negative for markers of viral hepatitis). The presence of diabetes, hypertension, dyslipidemia, or steatosis based on ultrasound examination was known for most participants.

Participants with a BMI less than 30 wereexamined with a medium probe and those witha BMI greater than 30 were examined with the extra-large probe. Linear regression models wereconducted after adjusting for potential confoundingfactors of LSMs. Several sensitivity analyses werecarried out.

LSM ranges for healthy individuals wereestablished, measured with both probes. They didnot change significantly in sensitivity analysesof individuals with normal platelet counts andnormal ALTs in men and women. Multivariate analysis factors that modified LSMs with statistical significance included diabetes, dyslipidemia(decrease), waist circumference, level of AST and systolic blood pressure at examination time.Significant increases in LSMs were associated witha metabolic syndrome in individuals examinedby either probe. Diabetes in obese individuals increased the risk of LSMs in range associated with advanced fibrosis.

It was concluded that a comprehensive setof LSM ranges measured by TE in large cohortsof healthy individuals and persons susceptibleto hepatic fibrosis regression analyses identified factors associated with increased LSMs obtainedby TE with the medium and extra-large probes.

Bazurbachi, F., Haffar, S., Wang, Z., et al. “Range of Normal Liver Stiffness and Factors Associated with Increased Stiffness Measurements in Apparently Healthy Individuals.” Clinical Gastroenterology and Hepatology 2019; Vol. 17, pp. 54-64.

Thermal Ablation of Endoscopic
Mucosal Resection

Endoscopic mucosal resection (EMR) is performed to remove large laterally spreading colonic lesions with a high risk of progression to CRC. Because endoscopically invisible micro-adenomas at the margins of the EMR site might contribute toadenoma recurrence that occurs at 15-30% ofpatients who undergo surveillance, determinationof the efficacy of adjuvant thermal ablation of theEMR mucosal defect margin in reducing polyp recurrence was carried out.

A prospective study of 390 patients with largelaterally spreading colonic lesions (greater than20 mm/N = 416), referred for EMR at 4 tertiarycenters in Australia was carried out. After complete excision by EMR, lesions were randomly assigned. The thermal ablation of the post-EMR mucosaldefect margin (N = 210), or no additional treatment (N = 206), surveillance colonoscopies wereperformed with standardized photo documentation and biopsies of the scar after 5 to 6 months. Patient, procedure and lesion characteristics were similar between the groups. The primary endpoint wasdetection of lesion recurrence at first surveillancecolonoscopy.

A significantly lower proportion of patientswho received thermal ablation of the post-EMR mucosal defect margin had evidence of recurrenceat first surveillance colonoscopy (10/192; 5.2% and controls 37/176; 21%). The relative risk ofrecurrence in the thermal ablation group was 0.25 compared with the control group. Rates of adverse events were similar between the groups.

In this multicenter, randomized trial, it was concluded that thermal ablation in the post-EMRmucosal defect margin significantly reduced polyp recurrence at first surveillance colonoscopy,compared with no additional treatment.

Klein, A., Tate, D., Jayasekeran, V., et al. “Thermal Ablation of Mucosal Defect Margins Reduces Adenoma Recurrence After Colonic Endoscopic Mucosal Resection.” Gastroenterology 2019; Vol. 156, pp. 604-613.