Faculty Bibliography

BACKGROUND:The potential impact of treatment sequencing in chemoimmunotherapy combinations remains underexplored. We evaluated 2 alternative dosing schedules of chemotherapy (cisplatin and gemcitabine [GC]) and an immune checkpoint inhibitor (CPI; atezolizumab [A]) for metastatic urothelial carcinoma (mUC). METHODS:This multicenter phase II study randomized cisplatin-eligible patients with previously untreated mUC in a 1:1 ratio. The chemo-first schedule included 2 cycles of GC, followed by 4 cycles of GC + A and A maintenance. The CPI-first schedule originally included a two-cycle A lead-in, later amended to a one-cycle lead-in, followed by 6 cycles of GC + A and A maintenance. The primary endpoint was objective response rate after the protocol amendment. Secondary endpoints included progression-free survival, overall survival, and safety. RESULTS:Overall, 31 patients were randomized between 9/2017 and 2/2021 (chemo-first, n = 15; CPI-first, n = 16), with early discontinuation due to the evolving mUC management paradigm. Among the per-protocol evaluable patients (n = 19), ORR was 44% (95% CI, 14%-79%) in the chemo-first schedule and 40% (95% CI, 12%-74%) in the CPI-first amended schedule, with neither arm meeting the predefined efficacy threshold. Median follow-up was 60 months (95% CI 48-not reached [NR]). Median progression-free survival and overall survival (95% CI) were: chemo-first, 6.1 (4.4-NR) and 15 (10-NR) months; CPI-first original, 1.3 (1.1-NR) and 12 (8.4-NR) months; and CPI-first amended, 7.6 (2.0-NR) and 26 (3.6-NR) months. No new safety signals or treatment-related deaths occurred. CONCLUSIONS:This study evaluating the impact of chemotherapy and CPI dosing sequence in patients with mUC was limited by a small sample size and early discontinuation, with neither arm meeting the primary endpoint. Exploratory observations highlight CPI lead-in duration as a potential consideration for future trial design.

BACKGROUND AND AIMS:Stenosis after laparoscopic sleeve gastrectomy (LSG) is common. Endoscopic balloon dilation is first-line therapy but often requires multiple sessions and may fail. Surgical conversion to Roux-en-Y gastric bypass is effective but invasive. Endoscopic tunneled stricturotomy offers a less-invasive alternative. We compared clinical success, adverse events, and length of stay between endoscopic and surgical treatments for post-LSG stenosis. METHODS:This retrospective, matched cohort study included patients treated with endoscopic stricturotomy (ENDO) group or Roux-en-Y gastric bypass conversion (SURG) group, matched 1:1 by age, sex, body mass index, time from LSG, and previous treatments. The Fisher exact and t tests were used. RESULTS:In 24 patients (12/group), the rate of adverse events was lower in ENDO (0% vs 41.7%, P = .04). Length of stay was shorter in ENDO (1.21 vs 2.57 days, P = .03). Clinical success was 83.3% (ENDO) versus 100% (SURG) (P = .48). CONCLUSIONS:Endoscopic stricturotomy is a safe, effective alternative for refractory post-LSG stenosis.

BACKGROUND/UNASSIGNED:Endoscopic submucosal dissection (ESD) is an established therapy for superficial esophageal lesions. Endoscopic ultrasound (EUS) is commonly used to assess submucosal invasion (SMI) and lymphadenopathy. METHOD/UNASSIGNED:Retrospective cohort of patients with esophageal and gastroesophageal junction lesions undergoing EUS before ESD (2014-2025). EUS T stage was compared with final pathology to evaluate detection of SMI. RESULTS/UNASSIGNED: = 7). CONCLUSION/UNASSIGNED:EUS showed limited reliability for pre-ESD staging of esophageal/GEJ lesions, with suboptimal performance in detecting SMI. As depth of invasion determines therapeutic strategy, EUS should not be used in isolation but rather alongside expert endoscopic assessment and biopsy. ESD remains central by offering definitive treatment and precise histologic staging.

INTRODUCTION/BACKGROUND:We sought to perform the first validation of the American Society for Gastrointestinal Endoscopy complexity grades for esophagogastroduodenoscopy (EGD), colonoscopy, endoscopic retrograde cholangiopancreatography (ERCP), and endoscopic ultrasound (EUS). METHODS:We used Pearson correlation coefficients to measure the correlation between complexity grades and both work relative value units and malpractice relative value units (RVUs) obtained from the Centers for Medicare and Medicaid Services. RESULTS:There was moderate to strong positive correlation between complexity grades and both work relative value unit and malpractice RVU for a range of EGD, colonoscopy, and EUS procedures. This was not observed for ERCP procedures, with many RVU values remaining low for even the most complex ERCP cases. DISCUSSION/CONCLUSIONS:The American Society for Gastrointestinal Endoscopy's endoscopic complexity grading system for EGD, colonoscopy, and EUS seems to correlate reasonably well with other recognized metrics of complexity and risk. The complexity levels for ERCP may be valid, but there is poor correlation with how these procedures are valued by Medicare.

BACKGROUND AND AIMS/OBJECTIVE:) imaging to quantify mucosal perfusion and its association with ulcer healing. METHODS:values were compared across regions and between healed and non-healed ulcers. RESULTS:. CONCLUSION/CONCLUSIONS:thresholds and define its role in clinical decision-making after RYGB.

The liver plays an important role in cardiovascular disease by amplifying systemic inflammation, while the underlying mechanisms remain to be defined. Soluble epoxide hydrolase (sEH) is a pro-inflammatory enzyme, and pharmacological inhibition of sEH was shown to protect against various inflammatory diseases. In this study, we have identified a novel role of the liver, through expression of sEH, in the pathogenesis of abdominal aortic aneurysm (AAA). sEH expression and activity were markedly higher in mouse liver compared with aorta and further increased in the context of AAA. Pharmacological inhibition or hepatocyte-specific disruption of sEH prevented AAA formation in two animal models of AAA (angiotensin II infusion and aortic calcium chloride application in male mice), concomitant with reduced expression of complement C3 and serum amyloid A, liver-derived inflammatory factors causally linked to AAA formation. Interestingly, data from co-incubation of liver ex vivo with aorta identified galectin-3 secreted from the aneurysm-prone aorta that activates sEH in the liver. We also determined 12,13-dihydroxyoctadecenoic acid (DiHOME) and various circulating pro-inflammatory cytokines as a downstream mechanism potentially associated with hepatic sEH in the context of AAA. These novel findings provide direct evidence that bidirectional crosstalk between aorta and liver contributes to AAA via hepatic sEH.

BACKGROUND:Fewer than 20% of donated lungs are transplanted. We examined the impacts of donor management and recovery at an in-hospital donor care unit (DCU) established in 2021 versus the donor hospital (DH). METHODS:(P/F ratio) were examined as a hypothesized effect modifier. We projected the national impact of improved utilization on lung transplant volume. RESULTS:After adjusting for donor differences, lung utilization was 88% higher (aRR: 1.88; 95% CI: 1.40, 2.53) in the DCU versus DH setting. Median P/F ratio increased from 275 to 348 mmHg (p<0.0001) in the DCU and explained approximately 38% of the improvement in lung utilization. Non-lung organ utilization was either improved or non-inferior in the DCU. Lung graft survival and pulmonary function were similar for recipients of DCU versus DH-managed donors. Nationally, an 88% improvement in lung utilization among donors not currently transferred to a DCU could theoretically result in ≥300 more lung transplants per year. CONCLUSIONS:Lung transplantation can be nearly doubled through lung-centric donor management in a DCU, without sacrificing recipient outcomes nor the utilization of other organs. Donor management practices to optimize lung utilization should be proliferated by establishing more DCUs and, where feasible, applying lung-centric protocols in donor hospitals.

Metastatic androgen pathway modulation-resistant (mAPMR) prostate cancer subtypes harboring androgen receptor (AR) alterations have distinct AR biology that may impact response to therapy. We hypothesized that patients harboring AR T878A would have superior responses to AR pathway inhibitor (ARPI) therapy based on prior preclinical data. We utilized a large genomic-clinical database to identify mAPMR patients with AR T878A, AR L702H and AR amplification and performed a matched assessment of ARPI treatment outcomes using real-world surrogate endpoints for treatment response. Among AR T878A patients treated with enzalutamide, time to treatment discontinuation (TTD) was longer relative to patients with AR L702H (8 mo (95% CI 4.6-44 mo) vs. 3.5 mo (95% CI 2.3-5.5 mo) log-rank p < 0.0001) or AR amplification (7.7 mo (95% CI 4.7-15.8 mo) vs. 4.8 mo (95% CI 4-5.1 mo) (log-rank p = 0.0034). Among the AR T878A patients treated with abiraterone, TTD was not significantly different relative to patients with AR L702H, but longer relative to patients with AR amplification (7.1 mo (95% CI 5-8.5 mo) vs. 4.2 mo (95% CI 3.5-5.4 mo) (log-rank p = 0.037). This study provides hypothesis generating evidence that outcomes for patients with AR LBD mutations may differ by mutation subtype. AR T878A may be relatively more sensitive to ARPI treatment than AR L702H or amplified AR.