Background Intraductal papillary mucinous neoplasms (IPMNs), a type of cystic pancreatic cancer (PC) precursors, are increasingly identified on cross-sectional imaging and present a significant diagnostic challenge. While surgical resection of IPMN-related advanced neoplasia, i.e., IPMN-related high-grade dysplasia or PC, is an essential early PC detection strategy, resection is not recommended for IPMN-low-grade dysplasia (LGD) due to minimal risk of carcinogenesis, and significant procedural risks. Based on their promising results in prior validation studies targeting early detection of classical PC, DNA hypermethylation-based markers may serve as a biomarker for malignant risk stratification of IPMNs. This study investigates our DNA methylation-based PC biomarker panel (ADAMTS1, BNC1, and CACNA1G genes) in differentiating IPMN-advanced neoplasia from IPMN-LGDs. Methods Our previously described genome-wide pharmaco-epigenetic method identified multiple genes as potential targets for PC detection. The combination was further optimized and validated for early detection of classical PC in previous case–control studies. These promising genes were evaluated among micro-dissected IPMN tissue (IPMN-LGD: 35, IPMN-advanced neoplasia: 35) through Methylation-Specific PCR. The discriminant capacity of individual and combination of genes were delineated through Receiver Operating Characteristics curve analysis. Results As compared to IPMN-LGDs, IPMN-advanced neoplasia had higher hypermethylation frequency of candidate genes: ADAMTS1 (60% vs. 14%), BNC1 (66% vs. 3%), and CACGNA1G (25% vs. 0%). We observed Area Under Curve (AUC) values of 0.73 for ADAMTS1, 0.81 for BNC1, and 0.63 for CACNA1G genes. The combination of the BNC1/ CACNA1G genes resulted in an AUC of 0.84, sensitivity of 71%, and specificity of 97%. Combining the methylation status of the BNC1/CACNA1G genes, blood-based CA19-9, and IPMN lesion size enhanced the AUC to 0.92. Conclusion DNA-methylation based biomarkers have shown a high diagnostic specificity and moderate sensitivity for differentiating IPMN-advanced neoplasia from LGDs. Addition of specific methylation targets can improve the accuracy of the methylation biomarker panel and enable the development of noninvasive IPMN stratification biomarkers.
To characterize outcomes in patients hospitalized with coronavirus disease 2019 (COVID-19) who present with gastrointestinal (GI) symptoms.Clinical outcomes in patients with COVID-19 associated with GI symptoms have been inconsistent in the literature.The study design is a retrospective analysis of patients, age 18 years or older, admitted to the hospital after testing positive for COVID-19. Clinical outcomes included intensive care unit requirements, rates of discharges to home, rates of discharges to outside facilities, and mortality.Seven hundred fifty patients met the inclusion criteria. Three hundred seventy three (49.7%) patients presented with at least one GI symptom and 377 (50.3%) patients presented with solely non-GI symptoms. Patients who presented with at least one GI symptom had significantly lower ICU requirements (17.4% vs 20.2%), higher rates of discharges home (77.2% vs 67.4%), lower rates of discharges to other facilities (16.4% vs 22.8%), and decreased mortality (6.4% vs 9.8%) compared with patients with non-GI symptoms. However, patients who presented with solely GI symptoms had significantly higher ICU requirements (23.8% vs 17.0%), lower rates of discharges home (52.4% vs 78.7%), higher rates of discharges to facilities (28.6% vs 15.6%), and higher mortality (19.0% vs 5.7%) compared with those with mixed GI and non-GI symptoms.Although patients with COVID-19 requiring hospitalization with GI symptoms did better than those without GI symptoms, those with isolated GI symptoms without extra-GI symptoms had worse clinical outcomes. COVID-19 should be considered in patients who present with new onset or worsening diarrhea, nausea, vomiting, and abdominal pain even without pulmonary symptoms.
Rationale: Patients with severe acute respiratory syndrome coronavirus 2 may have gastrointestinal symptoms including abdominal pain and burning. However, these symptoms may be due to functional dyspepsia (FD), a heterogeneous disorder with some documented cases being due to postinfectious sequela. Patient Concerns: We report a case of a 57-year-old female with well-controlled celiac disease and vitamin D deficiency who developed early satiety, abdominal pain, stomach fullness, postprandial burning, and weight loss after testing positive for coronavirus disease 2019. Diagnoses: Her symptoms started improving with medical treatment of FD. The timeline of symptom onset, persistence, and eventual improvement suggests she had postinfectious FD as a likely sequelae of severe acute respiratory syndrome coronavirus 2 infection. Interventions: She failed to improve with antiemetic and anti-reflux medications, and work-up revealed no endoscopic evidence of her dyspepsia. Outcomes: Her symptoms started improving with medical treatment of FD. Lessons: This case report highlights the importance of suspecting coronavirus disease 2019 as the etiology in patients who develop dyspepsia but have no endoscopic abnormalities.
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