Faculty Bibliography

PURPOSE OF REVIEW/UNASSIGNED:Dysphagia is a common medical condition among the geriatric population that can significantly impact a patient's quality of life. The manifestations, diagnosis, and treatment of esophageal dysphagia differ greatly based on the underlying etiology, especially in older individuals who may have accompanying complex medical comorbidities. This review explores the intricacies of esophageal dysphagia in the older population and how they are managed. RECENT FINDINGS/UNASSIGNED:Novel modalities, like the functional luminal imaging probe (FLIP) and timed barium esophagram (TBE), are now woven into our diagnostic schemas for esophageal dysphagia. Studies have also looked at the safety profile of available therapeutic interventions for older individuals. There are newer, less invasive treatment options, including radiofrequency application (RFA) and transoral incisionless fundoplication (TIF) for GERD management, that may benefit the geriatric population. SUMMARY/UNASSIGNED:In this review, we discuss the most likely etiologies of esophageal dysphagia in the elderly population. We then explore a diagnostic schema and highlight treatment choices based on diagnosis. Our review specifically explores the risks and benefits of management options in more medically complex geriatric patients.

OBJECTIVES/OBJECTIVE:Achalasia is an esophageal motility disorder that impairs quality of life and is often missed (20-50%) on endoscopy. A newly developed computer-aided detection (CAD) software has shown high accuracy for achalasia diagnosis in preclinical settings. However, its benefit in a clinical setting remains unclear. METHODS:Between February and August 2023, 83 endoscopists from 27 centers assessed 50 randomized endoscopic videos (25 achalasia, 25 nonachalasia) without and with CAD. Endoscopists assessed videos without CAD, then with CAD after 2 months. The primary end-point was improvement in sensitivity for nonexperienced endoscopists (no endoscopic experience of achalasia). Sensitivity, specificity, and accuracy with and without CAD were compared using the McNemar test. RESULTS:Sensitivity for diagnosing achalasia increased significantly with CAD, rising from 74.2% (95% confidence interval [CI] 72.2-76.0%) to 91.2% (95% CI 89.9-92.4%) for all readers, showing a difference of 17.1% (95% CI 15.1-19.0%). Specifically, sensitivity improved from 66.9% (95% CI 63.6-70.0%) to 91.9% (95% CI 89.9-93.6%) among nonexperienced endoscopists, resulting in a difference of 25.0% (95% CI 21.7-28.4%), and from 79.5% (95% CI 77.1-81.8%) to 90.8% (95% CI 89.0-92.3%) among experienced endoscopists (endoscopic experience of at least one achalasia case), with a difference of 11.3% (95% CI 8.9-13.6%). Accuracy and specificity improved significantly with CAD assistance, regardless of reader's experience. CONCLUSION/CONCLUSIONS:CAD improves achalasia detection by 17%, confirming preclinical results. The benefit was higher for nonexperienced endoscopists. CAD assistance may lead to prompt and effective treatment, minimizing the risk of false-negative diagnosis in clinical practice. TRIAL REGISTRATION/BACKGROUND:This study was registered in the University Hospital Medical Information Network Clinical Trial Registry (https://www.umin.ac.jp/ctr/) number: UMIN000053047.

PURPOSE OF REVIEW/OBJECTIVE:Colorectal cancer (CRC) is a leading cause of cancer-related mortality, with 44% of deaths occurring in individuals aged 75 years and older. With 78 million adults over 65 years projected by 2035, optimizing CRC screening and surveillance is crucial. This review examines guidelines, risks, and personalized approaches. RECENT FINDINGS/RESULTS:CRC screening reduces incidence by 17-33% and mortality by 11-53%. Colonoscopy lowers mortality by 61% but has a 6.8% complication rate in those aged 75 years and older. The risk of gastrointestinal bleeding is 8.7 per 1,000 for polypectomy, and perforation occurs in 0.6 per 1,000. Frailty indices assess suitability, but surveillance guidelines lack clear discontinuation criteria. Screening should balance risk, complications, and health status. It may be cost-effective up to age 86 years in healthy individuals, but more research is needed to refine surveillance strategies and reduce overtreatment in older adults.

IMPORTANCE/UNASSIGNED:Colorectal cancer screening is widely recommended but underused. Blood-based screening offers the potential for higher adherence compared with endoscopy or stool-based testing but must first be clinically validated in a screening population. OBJECTIVE/UNASSIGNED:To evaluate the clinical performance of an investigational blood-based circulating tumor DNA test for colorectal cancer detection in an average-risk population using colonoscopy with histopathology as the reference method. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Prospective, multicenter, cross-sectional observational study enrolling participants between May 2020 and April 2022 who were asymptomatic adults aged 45 to 85 years, at average risk of colorectal cancer, and willing to undergo a standard-of-care screening colonoscopy. Participants, staff, and pathologists were blinded to blood test results, and laboratory testing was performed blinded to colonoscopy findings. The study was conducted at 201 centers across 49 US states and the United Arab Emirates. Site-based and mobile phlebotomy were used for blood collection. EXPOSURES/UNASSIGNED:Participants were required to complete a screening colonoscopy after blood collection. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary end points were sensitivity for colorectal cancer, specificity for advanced colorectal neoplasia (colorectal cancer or advanced precancerous lesions), negative predictive value for advanced colorectal neoplasia, and positive predictive value for advanced colorectal neoplasia. The secondary end point was sensitivity for advanced precancerous lesions. RESULTS/UNASSIGNED:The median age of participants in the evaluable cohort (n = 27 010) was 57.0 years, and 55.8% were women. Sensitivity for colorectal cancer was 79.2% (57/72; 95% CI, 68.4%-86.9%) and specificity for advanced colorectal neoplasia was 91.5% (22 306/24 371; 95% CI, 91.2%-91.9%). The negative predictive value for advanced colorectal neoplasia was 90.8% (22 306/24 567; 95% CI, 90.7%-90.9%) and the positive predictive value for advanced colorectal neoplasia was 15.5% (378/2443; 95% CI, 14.2%-16.8%). All primary end points met prespecified acceptance criteria. The sensitivity for advanced precancerous lesions was 12.5% (321/2567; 95% CI, 11.3%-13.8%), which did not meet the prespecified acceptance criterion. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In an average-risk colorectal cancer screening population, a blood-based test demonstrated acceptable accuracy for colorectal cancer detection, but detection of advanced precancerous lesions remains a challenge, and ongoing efforts are needed to improve test sensitivity. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04369053.

INTRODUCTION/UNASSIGNED:In the general population, right I-sided dysplasia presents a higher risk for colorectal cancer (CRC) and metachronous dysplasia compared to left (L)-sided dysplasia. Given that patients with inflammatory bowel disease (IBD) are at higher risk for dysplasia than the general population, we sought to assess the risk factors as well as the differences in outcomes between patients with R-sided, L-sided, and both R- and L-sided dysplasia. METHODS/UNASSIGNED:A retrospective chart review was performed on patients at NYU Langone Health who had evidence of dysplasia on a colonoscopy between 2011 and 2021. Demographics and pertinent medical history were compiled. Cohorts were based on the dysplasia location (R-sided, L-sided, or R- and L-sided) and the IBD-related outcomes were analyzed. RESULTS/UNASSIGNED:= 0.03). CONCLUSIONS/UNASSIGNED:Patients with UC had a higher risk for L-sided colonic dysplasia compared to patients with CD; however, there were no differences in the progression of dysplasia between those who had R-sided and those who had L-sided dysplasia. Larger studies are needed to assess the risk factors and outcomes related to the laterality of dysplasia and further validate these findings among patients with IBD.

BACKGROUND & AIMS/OBJECTIVE:Primary sclerosing cholangitis (PSC) is a rare, chronic liver disease. Elafibranor, a dual peroxisome proliferator-activated receptor-α/δ agonist, was investigated in the phase II ELMWOOD trial (NCT05627362). METHODS:This 12-week, double-blind trial enrolled adults with PSC and alkaline phosphatase (ALP) ≥1.5× the upper limit of normal. The primary endpoint was elafibranor safety vs. placebo. Additional endpoints included relative mean change from baseline in ALP and enhanced liver fibrosis (ELF) score. RESULTS:A total of 68 participants (male: 54.4%; mean age: 46.3 years; inflammatory bowel disease: 55.9%) were randomized to elafibranor 80 mg (n = 22), elafibranor 120 mg (n = 23), or placebo (n = 23). At baseline, 70.6% were on ursodeoxycholic acid, 48.5% had ELF scores >9.8, and the mean ALP level was 369.5 U/L. At Week 12, rates of treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation in participants on elafibranor 80 mg, 120 mg, and placebo were 68.2%, 78.3%, and 69.6%, and 4.5%, 4.3%, and 8.7%, respectively. Serious TEAEs occurred only in participants on placebo (4.3%). Participants on elafibranor 80 mg and 120 mg had reductions in ALP vs. placebo (least squares mean treatment difference [95% CI]: -35.3% [-49.2, -21.4] and -54.7% [-68.3, -41.0], respectively). ALP normalization occurred only in participants on elafibranor 80 mg (9.1%) and 120 mg (17.4%). The LS mean treatment differences (95% CI) in change from baseline in ELF scores in participants on elafibranor 80 mg and 120 mg vs. placebo were -0.19 (-0.52, +0.15) and -0.28 (-0.62, +0.06), respectively. CONCLUSIONS:Elafibranor was well tolerated in people with PSC and associated with greater biochemical improvements over 12 weeks compared with placebo. A greater magnitude of response was observed with elafibranor 120 mg compared with 80 mg. IMPACT AND IMPLICATIONS/UNASSIGNED:For people with primary sclerosing cholangitis (PSC), there is a need for a well-tolerated and effective treatment that will enhance quality of life, prevent disease progression, and improve long-term outcomes. Here, we present results from the double-blind period of the phase II ELMWOOD trial in PSC, wherein elafibranor, a peroxisome proliferator-activated receptor-α/δ agonist, demonstrated a favorable safety profile, provided greater biochemical improvements over 12 weeks compared with placebo, and appeared to stabilize markers of fibrosis and improve pruritus. These findings support larger and longer term investigations of elafibranor to explore its therapeutic potential as a treatment for people with PSC.

Description Colorectal cancer (CRC) is a leading cause of morbidity and cancer-related mortality in the US. Despite multiple screening options, adherence to CRC screening in the US remains suboptimal and there are racial, ethnic and geographic disparities in CRC screening rates and outcomes. Advances in diagnostic technology have allowed for development and validation of blood tests for CRC screening. In this clinical practice update, our aims were to review the current evidence on blood tests, and the potential implications for CRC screening. We leveraged published modelling studies to understand the optimal test performance characteristics, interval, and uptake that would be needed for blood tests to achieve comparable effectiveness to that of currently available stool tests and screening colonoscopy.