Faculty Bibliography

INTRODUCTION AND OBJECTIVES/OBJECTIVE:Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease but remains widely under-recognized in primary care. The 2023 shift from "nonalcoholic fatty liver disease" to MASLD emphasized metabolic dysfunction as a driver of disease but introduced new communication and educational challenges for primary care providers (PCPs). We aimed to assess PCPs' awareness, risk assessment, and management practices related to MASLD in the four most populous U.S. cities. MATERIALS AND METHODS/METHODS:A cross-sectional online survey was conducted from 5 to 13 September 2024 among 800 primary care providers (PCPs; n = 200 per city) in New York City, Los Angeles, Chicago, and Houston. Participants included physicians, physician assistants, nurse practitioners, and other primary care professionals. The survey assessed awareness of "MASLD" and "fatty liver disease", risk assessment practices for high-risk groups, patient discussions, management strategies, and the use of patient-reported outcomes (PROs). Descriptive statistics characterized sample responses, and logistic regression models identified correlates of awareness. RESULTS:Overall, 54.7% of PCPs reported awareness of MASLD and 86.6% were aware of fatty liver disease. Awareness of MASLD was highest among physicians (81.3%) and hospital-based practitioners (odds ratio [OR] = 2.02, 95% confidence interval [CI] 1.02-4.02) and lowest among nurse practitioners (OR = 0.21, 95% CI 0.09-0.49). Awareness of fatty liver disease increased with provider age (OR = 1.04, 95% CI 1.00-1.08). Lifestyle modification was the most recommended management approach (41.3-65.5%), while referral rates to specialists and PRO use varied substantially across cities, and 48.5% were aware of the FIB-4 Index. CONCLUSIONS:Only half of PCPs recognized the term MASLD, highlighting gaps in awareness and clinical practice following the mid-2023 terminology change. Targeted educational initiatives and standardized implementation of MASLD guidelines in primary care are needed to improve timely detection and management of this highly prevalent condition.

BACKGROUND:Accurate preoperative malignancy risk assessment in intraductal papillary mucinous neoplasm (IPMN) is essential to balance timely intervention for high-grade dysplasia or invasive cancer (HGD/IC) against avoiding unnecessary or premature surgery in low-grade IPMN. This study aimed to externally validate the 2023 International Association of Pancreatology (IAP)/Kyoto guidelines and develop a combined prediction model incorporating routinely collected clinical data and laboratory parameters. METHODS:We conducted a retrospective cohort study of 194 patients who underwent resection for IPMN between 2012 and 2024. We evaluated the predictive performance of the current IAP/Kyoto criteria ("Kyoto model"), developed a clinical model using routinely available laboratory and clinical variables, and integrated both into a combined model. Model performance was assessed using discrimination and calibration metrics, with internal validation via bootstrapping and five-fold cross-validation. RESULTS:The Kyoto model demonstrated modest discrimination (AUC 0.62). The clinical model, incorporating neutrophil-to-lymphocyte ratio (NLR), smoking history, blood glucose, CA19-9, and alkaline phosphatase, achieved an optimism-corrected AUC of 0.76. Compared to the Kyoto model, the combined model (AUC 0.77) significantly improved discrimination and calibration (p < 0.001). At a predicted probability threshold of >0.75, the combined model achieved a 90% specificity and 91% positive predictive value for HGD/IC, identifying a high-risk subgroup suitable for surgical intervention. CONCLUSIONS:Integrating routinely collected clinical and laboratory parameters with guideline-based imaging features shows promise to enhance preoperative identification of high-risk IPMN in patients already being considered for surgical resection. The combined model offers a practical, high-specificity tool to support surgical decision-making in this selected population, though its performance metrics should not be extrapolated to unselected surveillance cohorts. External validation is required before broader clinical implementation.

INTRODUCTION/BACKGROUND:Accurate preoperative evaluation of pancreatic cysts is essential. However, cytology and biochemical analysis are often limited by low cellularity, and risk stratification is critical for management. PancreaSeq Genomic Classifier (GC) analyzes cyst fluid for molecular alterations to aid diagnosis and risk assessment. MATERIALS AND METHODS/METHODS:We retrospectively analyzed 219 pancreatic cysts from 206 patients using PancreaSeq GC, integrating molecular findings with cytology, biochemical, imaging, surgical pathology, and follow-up. RESULTS:PancreaSeq GC successfully analyzed 216/219 cysts (99%) and detected alterations in 182 (83%). Among cases with both cytology and molecular data (n = 201), concordance was high in cytologically mucinous neoplasms (94%) and atypical cases (95%). Notably, among cases reported as negative for malignancy or nondiagnostic on cytology (n = 128), PancreaSeq GC identified mucinous neoplasms in 82 cases (64%), demonstrating added value in limited samples. Surgical pathology correlation (n = 24) showed excellent performance for distinguishing mucinous from nonmucinous cysts (area under the curve [AUC] = 0.94, P < 0.001). Risk stratification for detection of any dysplasia yielded an AUC of 0.78 (P = 0.006), and for high-grade dysplasia an AUC of 0.74 (P = 0.046). PancreaSeq GC reliably predicted neuroendocrine tumors, but the sensitivity for focal high-grade dysplasia in mucinous neoplasms and serous cystadenoma was limited. Compared with carcinoembryonic antigen (CEA), cyst fluid glucose showed higher sensitivity but lower specificity for mucinous cyst detection. CONCLUSIONS:PancreaSeq GC provides significant diagnostic and risk-stratification value that complements cytological evaluation, particularly in indeterminate or nondiagnostic cytology specimens and when biochemical data are unavailable. Integration of molecular findings improves cyst classification and dysplasia risk assessment. Multidisciplinary assessment remains essential, given the assay's limited sensitivity for focal high-grade dysplasia and serous cystadenomas.

BACKGROUND AND AIMS/OBJECTIVE:Growing evidence suggests that the gut microbiome plays a role in carcinogenesis for early-onset colorectal cancer (EOCRC). The novel Ring Finger Protein 213 (RNF213) gene has broad antimicrobial properties. Our study aimed to compare RNF213 mutation rates in EOCRC and late-onset colorectal cancer using data from the cBioPortal for Cancer Genomics. METHODS:All participants from the cBioPortal with CRC samples that profiled the RNF213 gene were included. Multivariable logistic regression was used to assess the association between EOCRC and primary tumor RNF213 mutation. Cox proportional hazards models were used to evaluate the influence of RNF213 mutation on all-cause mortality risk. All tests were two-sided. RESULTS:OR 1.61, 95% CI 0.72, 3.22). There was no significant difference in all-cause mortality risk by RNF213 mutation status. CONCLUSIONS:Primary tumor mutations in exon 29 of the RNF213 gene are associated with significantly increased odds of EOCRC diagnosis in a multicohort sample of participants with CRC. Future studies of germline and precancerous RNF213 mutations are needed to elucidate its possible role in EOCRC tumorigenesis.

OBJECTIVES/OBJECTIVE:Post-colonoscopy colorectal cancer (PCCRC) represents an important real-world colonoscopy quality indicator. Using a national database, we evaluated predictors of PCCRC in fecal immunochemical test (FIT)-positive individuals, determined the PCCRC 3-year rate (PCCRC-3y), and performed a root cause analysis (RCA). METHODS:This retrospective cohort study evaluated FIT-positive patients who underwent colonoscopy from January 2015 to July 2022. Data was collected from the Veterans Affairs (VA) national database. PCCRC was defined as CRC detected ≥6 months after colonoscopy. CRC was identified using SNOMED codes and the VA Cancer Registry. The World Endoscopy Organization methodology was used to perform the RCA and calculate the PCCRC-3y rate. RESULTS:We identified 132 PCCRCs among 52,167 FIT-positive individuals. The PCCRC-3y rate was 6.4% (95% CI, 5.0-7.7%). PCCRC locations were proximal colon (43.2%), distal colon (34.8%), and rectum (22%). Root causes were likely new CRC (17.4%), missed lesions with adequate (31.2%) or inadequate (9.8%) examination, incomplete polyp resection (22%), and detected but unresected lesions (19.7%). 16.7% of patients with PCCRC had poor bowel preparation on index colonoscopy. The cecal intubation rate was 88.6% and rectal retroflexion rate was 84.5%. In 14.4% of cases, recommended surveillance intervals did not adhere to established guidelines. Independent predictors of PCCRC were ages 70-79 (HR 7.86; 95% CI, 1.08-57.39), age ≥80 (HR 10.18; 95% CI, 1.06-97.98), tubulovillous adenoma (HR 3.98; 95% CI, 2.52-6.29), and adenoma with high-grade dysplasia (HR 10.15; 95% CI, 5.91-17.42). CONCLUSIONS:Among FIT-positive individuals, the PCCRC-3y rate was 6.4%, with missed lesions and incomplete resection as key contributors. These findings provide useful information on quality metrics in FIT-based CRC screening programs.

INTRODUCTION/BACKGROUND:Idiopathic acute pancreatitis (IAP) accounts for up to 20% of acute pancreatitis cases despite thorough initial evaluation. Endoscopic ultrasound (EUS) and magnetic resonance cholangiopancreatography (MRCP) are commonly used as second-line imaging modalities when IAP etiologies are unclear, yet their comparative diagnostic performance remains uncertain. We conducted a systematic review and meta-analysis to assess the diagnostic yield of EUS versus MRCP in identifying etiologies of IAP. METHODS:A systematic search of PubMed, EMBASE, and Google Scholar (January 2000-April 2025) identified English-language studies comparing EUS and MRCP diagnostic performance in IAP. Two reviewers independently extracted data and assessed study quality using the Newcastle-Ottawa Scale. Pooled relative risks (RR) were calculated using a random-effects model, with subgroup, sensitivity, and publication bias analyses done per PRISMA 2020. Subgroup analyses assessed diagnostic yield by etiology-biliary disease (cholelithiasis, choledocholithiasis, microlithiasis, and sludge), pancreatic divisum, intraductal papillary mucinous neoplasm (IPMN), and malignancy (pancreatic adenocarcinoma and periampullary cancer). RESULTS: = 0.0%). CONCLUSION/CONCLUSIONS:EUS surpasses MRCP in diagnosing IAP biliary etiologies and has an overall higher diagnostic yield. Prior studies suggest that EUS may be oversensitive in diagnosing CP, which may be consistent with the increased rate of diagnosis by EUS in our data. There was some signal that EUS had a higher diagnostic yield for cancer, which may highlight a potential role in identifying occult malignancy in IAP evaluation. In practice, choosing EUS vs. MRCP depends on resource availability, but a patient-centered approach that integrates modality strengths with clinical profiles can improve diagnostic accuracy and prognostic outcomes.

BACKGROUND:The benefits of achieving endoscopic remission among older adults with inflammatory bowel disease (IBD) who have mild persistent disease activity are unknown. METHODS:This was a retrospective study of adults ≥ 60 with IBD who had mild or no disease activity on endoscopy from January 1, 2018-January 1, 2023. The primary outcome was a composite of major IBD-specific adverse events (hospitalizations, surgery, and prescription of corticosteroids for IBD-related symptoms) within 1 year of endoscopic assessment. Our secondary outcome was a composite of 1-year morbidity-related events (mortality, all-cause hospitalization, infection requiring antibiotics, venous thromboembolism, cardiovascular events, and osteoporotic fractures). We also assessed outcomes at 5 years. RESULTS:Among 504 patients, 192 (38.1%) had mild endoscopic disease and 312 (61.9%) were in endoscopic remission, with a median disease duration of 11 years. On multivariable analysis, mild endoscopic disease activity increased the odds of a 1-year adverse IBD-specific outcome (aOR 4.16, 95% CI 2.10-8.24), with similar results at 5 years. Furthermore, mild endoscopic disease was associated with increased odds of experiencing an adverse morbidity-related outcome within 1 year as compared to endoscopic remission (aOR 1.56, 95% CI 1.01-2.43). CONCLUSIONS:Among older adults with prevalent IBD, mild endoscopic disease activity, as compared to endoscopic remission, was associated with increased odds of adverse IBD-specific and morbidity-related outcomes at 1 year, with this risk persisting for IBD-specific outcomes at 5 years. These findings highlight the importance of achieving endoscopic remission, which may confer both short- and longer-term benefits in this population.

BACKGROUND:Individuals with inflammatory bowel disease (IBD) have an elevated risk of colorectal neoplasia (CRN), including colorectal dysplasia and cancer (CRC). Despite surveillance strategies to prevent CRC, the clinical course of dysplasia types remains poorly understood. METHODS:We conducted a nationwide cohort study using the Swedish Patient Register and the ESPRESSO histopathology cohort to identify patients diagnosed with IBD between 1969 and 2023. Patients were classified according to their first (baseline) incident episode of dysplasia (no dysplasia, ND; indefinite, IND; low-grade, LGD; high-grade, HGD). Our primary outcome was future advanced CRN (HGD or CRC) during follow-up. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CI) were estimated using Cox regression. RESULTS:We identified 54,534 patients with IBD, including 1,320 with a first (baseline) episode of dysplasia (264 IND, 1031 LGD, 25 HGD), and 53,214 with ND. Over a median follow-up of 13.3 years, 2.3% of ND patients had future advanced CRN compared to 5.3% of IND patients (aHR 1.85, 95% CI 1.09-3.15) and 8.3% of LGD patients (aHR 3.51, 95% CI 2.77-4.45). Of those with HGD, 40% developed CRC (aHR 47.88, 95% CI 25.53-89.80). Risk factors for future dysplasia included male sex, younger age at diagnosis, extensive colitis, primary sclerosing cholangitis, and histologic inflammation. CONCLUSION/CONCLUSIONS:Patients with IBD and dysplasia have a significantly increased risk of future dysplasia, particularly among patients with HGD. Personalized surveillance strategies based on risk factors are critical for preventing advanced CRN.