Exosomal glypican-1 is elevated in pancreatic cancer precursors and can signal genetic predisposition in the absence of endoscopic ultrasound abnormalities.

BACKGROUND: Individuals within specific risk groups for pancreatic ductal adenocarcinoma (PDAC) [mucinous cystic lesions (MCLs), hereditary risk (HR), and new-late onset diabetes mellitus (NLOD)] represent an opportunity for early cancer detection. Endoscopic ultrasound (EUS) is a premium image modality for PDAC screening and precursor lesion characterization. While no specific biomarker is currently clinically available for this purpose, glypican-1 (GPC1) is overexpressed in the circulating exosomes (crExos) of patients with PDAC compared with healthy subjects or those harboring benign pancreatic diseases. AIM: To evaluate the capacity of GPC1+ crExos to identify individuals at higher risk within these specific groups, all characterized by EUS. METHODS: This cross-sectional study with a prospective unicentric cohort included 88 subjects: 40 patients with MCL, 20 individuals with HR, and 20 patients with NLOD. A control group (CG) was submitted to EUS for other reasons than pancreatic pathology, with normal pancreas and absence of hereditary risk factors (n = 8). The inclusion period was between October 2016 and January 2019, and the study was approved by the Ethics Committee of Centro Hospitalar Universitário de São João, Porto, Portugal. All patients provided written informed consent. EUS and blood tests for quantification of GPC1+ crExos by flow cytometry and carbohydrate antigen 19-9 (CA 19-9) levels by ELISA were performed in all subjects. EUS-guided tissue acquisition was done whenever necessary. For statistical analysis, SPSS® 27.0 (IBM Corp., Armonk, NY, United States) version was used. All graphs were created using GraphPad Prism 7.00 (GraphPad Software, San Diego, CA, United States). RESULTS: Half of MCLs harbored worrisome features (WF) or high-risk stigmata (HRS). Pancreatic abnormalities were detected by EUS in 10.0% and 35.0% in HR and NLOD individuals, respectively, all considered non-malignant and "harmless." Median levels of GPC1+ crExos were statistically different: MCL [99.4%, interquartile range (IQR): 94.9%-99.8%], HR (82.0%, IQR: 28.9%-98.2%), NLOD (12.6%, IQR: 5.2%-63.4%), and CG (16.2%, IQR: 6.6%-20.1%) (P < 0.0001). Median levels of CA 19-9 were within the normal range in all groups (standard clinical cut-off of 37 U/mL). Within HR, individuals with a positive history of cancer had higher median levels of GPC1+ crExos (97.9%; IQR: 61.7%-99.5%), compared to those without (59.7%; IQR: 26.3%-96.4%), despite no statistical significance (P = 0.21). Pancreatic cysts with WF/HRS were statistically associated with higher median levels of GPC1+ crExos (99.6%; IQR: 97.6%-99.8%) compared to those without (96.5%; IQR: 81.3%-99.5%) (P = 0.011), presenting an area under the receiver operating characteristic curve value of 0.723 (sensitivity 75.0% and specificity 67.7%, using a cut-off of 98.5%; P = 0.012). CONCLUSION: GPC1+ crExos may act as biomarker to support the diagnosis and stratification of PDAC precursor lesions, and in signaling individuals with genetic predisposition in the absence of EUS abnormalities.

Narrow-band imaging versus white light versus mapping biopsy for gastric intestinal metaplasia: a prospective blinded trial.

BACKGROUND AND AIMS: Gastric intestinal metaplasia (GIM) is a gastric cancer precursor. Narrow-band imaging (NBI) may improve detection of GIM. We compared detection of GIM with high-definition white-light (HD-WL) endoscopy, NBI, and mapping biopsies in a population with increased gastric cancer risk. METHODS: Patients undergoing upper endoscopy had HD-WL examination by 1 endoscopist, followed by an NBI examination by a second endoscopist blinded to HD-WL findings. The location of abnormalities detected by HD-WL and NBI were recorded by a research coordinator, and targeted biopsies of abnormal areas were performed after NBI. Subsequently, 5 mapping biopsies were performed per patient. Biopsy specimens were read by a pathologist blinded to mode of acquisition. The primary outcome was the proportion of patients with GIM. RESULTS: We enrolled 112 patients: 107 (96%) were Hispanic or Asian, and 34 (30%) had GIM. Higher proportions of patients with GIM were detected by NBI (22/34 [65%]) and mapping (26/34 [76%]) versus HD-WL (10/34 [29%]) (P < .005 for both comparisons). GIM was detected by NBI in only 6 patients and only by mapping biopsy in 10 patients; no patient had GIM detected solely by HD-WL. Higher proportions of sites with GIM also were detected with NBI (30/57 [53%]) and mapping biopsies (38/57 [67%]) than HD-WL (16/57 [28%]) (P < .005 for both comparisons). The median number of biopsies per patient with mapping biopsies (5) was significantly higher than with NBI (2) or HD-WL (1). CONCLUSIONS: HD-WL endoscopy is insufficient for detection of GIM in patients at increased risk for gastric cancer. NBI-targeted biopsies plus mapping biopsies should be used. (Clinical trial registration number: NCT02197351.).

The learning curve for narrow-band imaging in the diagnosis of precancerous gastric lesions by using Web-based video.

BACKGROUND: A simplified narrow-band imaging (NBI) endoscopy classification of gastric precancerous and cancerous lesions was derived and validated in a multicenter study. This classification comes with the need for dissemination through adequate training. OBJECTIVE: To address the learning curve of this classification by endoscopists with differing expertise and to assess the feasibility of a YouTube-based learning program to disseminate it. DESIGN: Prospective study. SETTING: Five centers. PARTICIPANTS: Six gastroenterologists (3 trainees, 3 fully trained endoscopists [FTs]). INTERVENTIONS: Twenty tests provided through a Web-based program containing 10 randomly ordered NBI videos of gastric mucosa were taken. Feedback was sent 7 days after every test submission. MAIN OUTCOME MEASUREMENTS: Measures of accuracy of the NBI classification throughout the time. RESULTS: From the first to the last 50 videos, a learning curve was observed with a 10% increase in global accuracy, for both trainees (from 64% to 74%) and FTs (from 56% to 65%). After 200 videos, sensitivity and specificity of 80% and higher for intestinal metaplasia were observed in half the participants, and a specificity for dysplasia greater than 95%, along with a relevant likelihood ratio for a positive result of 7 to 28 and likelihood ratio for a negative result of 0.21 to 0.82, were achieved by all of the participants. No constant learning curve was observed for the identification of Helicobacter pylori gastritis and sensitivity to dysplasia. The trainees had better results in all of the parameters, except specificity for dysplasia, compared with the FTs. Globally, participants agreed that the program's structure was adequate, except on the feedback, which should have consisted of a more detailed explanation of each answer. LIMITATIONS: No formal sample size estimate. CONCLUSION: A Web-based learning program could be used to teach and disseminate classifications in the endoscopy field. In this study, an NBI classification for gastric mucosal features seems to be easily learned for the identification of gastric preneoplastic lesions.