Background The USA is a low-incidence country for gastric cancer and screening is not performed. The use of diagnostic endoscopy (EGD) is not well standardized. As a result, patients most commonly have advanced-stage disease at diagnosis. Patients and Methods All patients with gastric cancer treated at a single center over the past 10 years were identified, and demographics, presenting symptoms, diagnostic evaluations, stage at diagnosis, and outcomes were analyzed. Results A total of 249 patients with gastroesophageal junction (GEJ) or gastric or GEJ adenocarcinoma were identified. The presence of gastrointestinal (GI)-related symptoms at diagnosis was associated with more advanced disease (p < 0.001), but 73% of stage I patients were symptomatic. The median self-reported duration of symptoms prior to first EGD was 2 months (range 0-35 months), but nearly 50% of patients with stage IV were diagnosed by cross-sectional imaging before performance of EGD. In addition, 182 patients (73%) were participating in colon cancer screening. The median overall survival (OS) of the entire cohort was 23.0 months (95% CI 14.4-31.6) and was not reached for stage I patients, 47 months (95% CI 24.3-69.7) for stage II, 23.0 months (95% CI 19.9-26.3) for stage III, and 11.0 months (95% CI 6.6-15.4) for stage IV (p < 0.001). Non-EGD method of original diagnosis was an independent predictor of poorer survival, regardless of stage (HR 1.46, 95% CI 1.03-2.09; p = 0.036). Conclusions Diagnostic EGD is underutilized in symptomatic patients, particularly those with dyspepsia, while most patients were participating in colon cancer screening. Novel protocols to standardize the use of diagnostic EGD should be investigated in the USA.

AbstractPurposeIncidental detection of pancreas lesions (IPLs) is common and creates an opportunity to intercept pancreatic ductal adenocarcinoma (PDAC). However, identifying patients at risk for progression who can benefit from surgical resection remains challenging. The current role of blood tests for risk stratification in patients with IPLs is limited.MethodsWe evaluated the performance of circulating glycoproteins (CA19-9, CEA and CA125), plasma DNA fragmentation analysis, and their combination, in 99 asymptomatic patients with IPLs, for detection of advanced pathology (high-grade dysplasia or invasive carcinoma). Plasma DNA fragmentation was analyzed using a machine learning model, adapted to detect PDAC in 242 patients with cancer and 300 healthy individuals.ResultsDuring 18.8 months of median follow-up by a multidisciplinary clinical team, 11 of 99 patients with IPLs were diagnosed with advanced pathology. We observed area under the receiver operating characteristic curves (AUROCs) of 0.78, 0.63, 0.54 and 0.74 using CA19-9, CEA, CA125 and plasma DNA fragmentation, respectively. Combined analysis of CA19-9, CA125 and plasma DNA fragmentation showed an AUROC of 0.93, with 91% sensitivity and 53% positive predictive value (PPV) at 90% specificity. In a subset of 25 patients with histologically confirmed diagnoses, AUROC improved to 0.96 and PPV improved to 91%. In one patient with an equivocal initial endoscopy, multi-analyte blood analysis predicted cancer 3 months before diagnosis of stage IA cancer.ConclusionOur results demonstrate a multianalyte blood test combining glycoprotein biomarkers with plasma DNA fragmentation could complement current clinical workflows for cancer detection in patients with IPLs.

BACKGROUND AND AIMS:Main pancreatic duct (MPD) dilatation of unclear etiology presents a diagnostic challenge because the management of neoplastic and non-neoplastic causes differs significantly. We aimed to assess the clinical utility of next-generation sequencing (NGS) in the management of MPD dilatation. METHODS:We retrospectively identified patients with dilated MPD (≥6 mm) of unclear etiology who underwent NGS at 2 academic institutions. The primary outcome was any change to management influenced by NGS compared with previous standard of practice. Adverse event rates of EUS fine-needle aspiration and ERCP were compared. RESULTS:A total of 62 patients with dilated MPD were identified; they had a mean age of 71.5 ± 12.1 years, and 53.2% were men. The majority had chronic pancreatitis (54.8%). The average MPD diameter was 8.6 ± 2.3 mm. MPD aspiration was performed by EUS fine-needle aspiration in 33 patients (53.2%) and ERCP in 29 patients (46.8%). The adverse event rate was 8.1%, with no difference between aspiration techniques observed. NGS mutations were present in 40 (64.5%) patients. The identification of mutations suggesting a neoplastic cause of MPD dilatation resulted in surgical management for 11 patients with no previous indication. In 6 cases with MPD ≥10 mm, dilatation was attributed to chronic pancreatitis and surgery was deferred despite previous practice of recommending surgery. Overall, management was changed in 17 (27.4%) patients. CONCLUSIONS:In a multicenter cohort of patients with MPD dilatation, NGS of MPD aspirates was safe and changed surgical management for more than one-quarter of patients. Providers should consider MPD sampling with NGS as an ancillary diagnostic modality for patients presenting with MPD dilatation of unclear etiology.