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Objectives Data from the International Cancer of the Pancreas Screening Consortium studies have demonstrated that screening for pancreatic ductal adenocarcinoma can be effective and that surveillance improves survival in high-risk individuals. Endoscopic ultrasound (EUS) and cross-sectional imaging are both used, although there is some suggestion that EUS is superior. Demonstration of the cost-effectiveness of screening is important to implement screening in high-risk groups. Methods Results from centers with EUS-predominant screening were pooled to evaluate efficacy of index EUS in screening. A decision analysis model simulated the outcome of high-risk patients who undergo screening and evaluated the parameters that would make screening cost-effective at a US $100,000 per quality-adjusted life-year willingness to pay. Results One-time index EUS has a sensitivity of 71.25% and specificity of 99.82% to detection to detect high-risk lesions. Screening with index EUS was cost-effective, particularly at lifetime pancreatic cancer probabilities of greater than 10.8%, or at lower probabilities if life expectancy after resection of a lesion that was at least 16 years, and if missed, lesion rates on index EUS are 5% or less. Conclusions Pancreatic cancer screening can be cost-effective through index EUS, particularly for those individuals at high-lifetime risk of cancer.

BACKGROUND The incidence and mortality of colorectal cancer (CRC) are increasing in adults under 50 years. Risk factors associated with early-onset colorectal neoplasia (CRN) are uncertain. We aimed to identify clinical predictors associated with the presence of CRN detected by diagnostic colonoscopy in symptomatic individuals under 50 years of age. METHODS We used a single-center endoscopy database to identify symptomatic patients 18-49 years of age who underwent ambulatory colonoscopy between 2007 and 2017. Pathology reports identified CRN as adenomas, advanced adenomas (based on size or histology), or adenocarcinomas. Multivariable analysis was used to determine factors associated with CRN. RESULTS We identified 4333 eligible patients of whom 363 (8.4%) had any CRN and 48 (1.1%) had advanced neoplasia (advanced adenoma or adenocarcinoma). Factors associated with any CRN on multivariable analysis included male sex [odds ratio (OR) 1.50 (1.19-1.88)], older age group [compared to 18-29 years, OR for 30-39: 3.12 (1.93-5.04); OR for 40-49: 4.68 (2.97-7.36)], obesity [OR for BMI 30-34.9 compared to 18-24.9: 1.44 (1.04-2.01)], and any tobacco use [OR 1.63 (1.18-2.23)]. Anemia was associated with advanced neoplasia [OR 3.11 (1.32-7.34)]. Of the advanced neoplastic lesions, 38 of 48 (79.2%) were located in the distal colon. CONCLUSIONS In the largest study to date of symptomatic individuals under 50 years of age undergoing colonoscopy in the USA, advanced CRN was most often detected in the distal colon and was associated with anemia, but not with abnormal bowel habits or abdominal pain. We also found that patients with CRN under 50 years of age were more likely to be male, smokers, and obese. These findings should prompt further investigation of these risk factors alone and in combination.

To the Editor: We are indebted to Dr Babu (1) for his thorough assessment of our article (2). Although we appreciate his concerns, we are limited in our ability to provide the positive predictive value of the Colorectal Cancer (CRC) Risk Assessment Tool as this performance measure depends on the prevalence of Lynch syndrome and the related, defining clinical criteria (as pointed out by Dr Babu). As noted in the Discussion section, our goal was not to identify gene mutation carriers as defined by mutation analysis but to provide a simple means by which health-care providers, primarily gastroenterologists performing colonoscopy, can readily and more accurately assess the risk of Lynch syndrome on the basis of personal or family history of cancer or polyps. Determining the true prevalence of mutation carriers in the population studied would be prohibitively expensive and not valuable for the vast majority of patients in the population studied, and be associated with ethical and social implications for many patients.