Citations

Background: Pancreatic adenocarcinoma (PC) is a highly lethal malignancy with a survival rate of only 12%. Surveillance is recommended for high-risk individuals (HRIs), but it is not widely adopted. To address this unmet clinical need and drive early diagnosis research, we established the Pancreatic Cancer Early Detection (PRECEDE) Consortium. Methods: PRECEDE is a multi-institutional international collaboration that has undertaken an observational prospective cohort study. Individuals (aged 18–90 years) are enrolled into 1 of 7 cohorts based on family history and pathogenic germline variant (PGV) status. From April 1, 2020, to November 21, 2022, a total of 3,402 participants were enrolled in 1 of 7 study cohorts, with 1,759 (51.7%) meeting criteria for the highest-risk cohort (Cohort 1). Cohort 1 HRIs underwent germline testing and pancreas imaging by MRI/MR-cholangiopancreatography or endoscopic ultrasound. Results: A total of 1,400 participants in Cohort 1 (79.6%) had completed baseline imaging and were subclassified into 3 groups based on familial PC (FPC; n=670), a PGV and FPC (PGV+/FPC+; n=115), and a PGV with a pedigree that does not meet FPC criteria (PGV+/FPC–; n=615). One HRI was diagnosed with stage IIB PC on study entry, and 35.1% of HRIs harbored pancreatic cysts. Increasing age (odds ratio, 1.05; P <.001) and FPC group assignment (odds ratio, 1.57; P <.001; relative to PGV+/FPC–) were independent predictors of harboring a pancreatic cyst. Conclusions: PRECEDE provides infrastructure support to increase access to clinical surveillance for HRIs worldwide, while aiming to drive early PC detection advancements through longitudinal standardized clinical data, imaging, and biospecimen captures. Increased cyst prevalence in HRIs with FPC suggests that FPC may infer distinct biological processes. To enable the development of PC surveillance approaches better tailored to risk category, we recommend adoption of subclassification of HRIs into FPC, PGV+/FPC+, and PGV+/FPC– risk groups by surveillance protocols.

PURPOSE Guidelines recommend germline genetic testing (GT) for patients with pancreatic ductal adenocarcinoma (PDAC). This study aims to evaluate the utilization and outcomes of multigene panel GT in patients with PDAC. METHODS This retrospective, multisite study included patients with PDAC diagnosed between May 2018 and August 2020 at Mayo Clinic Arizona, Florida, and Minnesota. Discussion, uptake, and outcomes of GT were compared before (May 1, 2018-May 1, 2019) and after (August 1, 2019-August 1, 2020) the guideline update, accounting for a transition period. RESULTS The study identified 533 patients with PDAC, with 321 (60.2%) preguideline and 212 (39.8%) postguideline. Patient characteristics did not differ between the preguideline and postguideline periods. GT was discussed in 34.3% (110 of 321) of preguideline and 39.6% (84 of 212) of postguideline patients (odds ratio [OR], 1.26 [95% CI, 0.88 to 1.80]) and subsequently performed in 80.9% (89 of 110) of preguideline and 75.0% (63 of 84) of postguideline patients (OR, 1.10 [95% CI, 0.75 to 1.61]). Of 152 tested patients, 26 (17.1%) had a pathogenic variant (PV), of whom 17 (11.2%; 17 of 152) were PDAC-associated. Over the entire study period, GT was more likely in younger patients (65 v 70 years; P < .001), those seen by a medical oncologist (82.9% v 69.0%; P < .001), and those surviving more than 12 months from diagnosis (70.4% v 43.4%; P < .001). Demographics and personal/family cancer history were comparable between patients with and without a PDAC PV. CONCLUSION GT remains underutilized despite National Comprehensive Cancer Network guideline recommendations. Given the poor prognosis of PDAC and potential implications of GT, efforts to increase utilization are needed to provide surveillance and support to both patients with PDAC and at-risk family members.

Background: Diagnosis of gastroesophageal reflux disease (GERD) relies on recognizing symptoms of reflux and mucosal changes during esophagogastroduodenoscopy. The desired response to acid suppression therapy is reliable resolution of GERD symptoms; however, these are not always reliable, hence the need for pH testing in unclear cases. Our objective was to identify potential predictors of a high DeMeester score among patients with potential GERD symptoms to identify patients most likely to have pathological GERD. Methods: We conducted a retrospective case-control study on patients who underwent wireless pH monitoring from January 2020 to April 2022. Cases were patients with a high DeMeester score (more than 14.7), indicating pathological reflux, and controls were those without. We collected clinical and demographic data, including age, sex, body mass index (BMI), smoking status, non-steroidal anti-inflammatory drugs (NSAIDs) use, and presence of atypical symptoms. Results: 86 patients were enrolled in the study. 46 patients with high DeMeester scores were considered cases, and 40 patients with DeMeester scores less than 14.7 were considered controls. Esophagitis (grade A) was found in 41.1% of the cases and in 22.5% of the control group. In our study, age of more than 50 years compared with age of 20-29 years and being overweight appeared to be predictors of true pathological reflux among patients with reflux symptoms who underwent wireless pH monitoring. Conclusion: Age above 50 years compared with age between 20-29 years and being overweight appeared to be predictors of true pathological reflux among patients with reflux symptoms who underwent wireless oesophageal pH monitoring. The presence of oesophagitis was approximately four times more likely to be associated with true pathological reflux.

22 Background: Glycosylation plays a pivotal role in host immune response during cancer development. Recently, we have reported specific changes in blood-based glycoforms for the early detection of advanced adenomas (AAs) and colorectal cancer (CRC). This study aims to identify glycoproteomic biomarkers associated with various polyp types, as glycosylation abnormalities are linked to neoplastic transformation, and CRC risk varies by polyp histology. Methods: Samples from an observational study (NCT05445570) were used to identify three distinct histologic polyp groups: adenomatous (AP), hyperplastic (HP), or serrated (SP). Combining liquid-chromatography/mass-spectrometry and artificial-intelligence powered data processing, our glycoproteomic profiling platform assessed glycopeptide (GP) and non-glycosylated peptide quantification transitions from the serum samples. We used multi-nominal response logit models to examine the relationship between polyp types and biomarkers. An a priori biomarker panel was interjected as exposures in the model. Each marker is assessed independently for inclusion into our final model. The final model utilized biomarkers found to have a significant association with the presence of AP, SP, or HPs along with age, sex, and BMI. Results: We identified 1,035 subjects with distinct polyp histologies and 1,300 polyp-free controls. We found a significant increase in relative risk (RR) for polyp presence in patients who were: >60 years (AP RR 1.40), male (AP RR 1.74), or had a BMI> 25. From the GP biomarker panel, 15 GPs were associated with risk of polyp presence; however, only 7 GP markers were significantly associated after adjusting for age, sex, and BMI. Two biomarkers were found to have a protective effect for the risk of an adenomatous polyp (RR 0.37; RR 0.39). Three biomarkers increased the risk of an adenomatous polyp (RR 1.31; RR 1.42; RR 1.98). One biomarker was found to increase the risk of a hyperplastic polyp (RR 1.42). Two biomarkers were found to increase the risk of serrated polyps (RR 1.67; RR 2.08) and one biomarker was found to decrease the risk of serrated polyps (RR 0.77). Conclusions: This is a novel exploratory study using GP biomarkers as it relates to risk of polyp presence by distinct histology. The use of these biomarkers allows us to harness the power of glycobiology in the liquid biopsy domain for AAs/CRC detection. The exact function of these GP markers during the development of different polyp types needs to be further explored through future studies.