Egbert, Lena K.

ABSTRACT Human intestinal diseases, including inflammatory bowel disease (IBD), are difficult to model because existing animal and in vitro systems do not capture the intestine’s integrated vascular, immune, and metabolic complexity. Here, we establish a custom normothermic machine perfusion platform that maintains surgically resected human intestinal tissue for up to 72 hours under near-physiological conditions. Discarded specimens from patients with nonmalignant intestinal diseases, including IBD and diverticulitis, were continuously perfused at 37°C with real-time hemodynamic and metabolic monitoring. Perfusion preserved tissue viability, mucosal architecture, epithelial integrity, oxygen consumption, metabolic activity, and vascular patency. Daily perfusate sampling enabled longitudinal profiling and experimental modulation of inflammatory mediators, revealing patient-specific immune states. This long-duration platform bridges reductionist in vitro models and clinical disease, enabling mechanistic studies of intestinal inflammation and future testing of personalized therapies in intact patient-derived tissue.

e12749 Background: Breast cancer (BC) survivors are at higher risk for recurrence or new primary disease and often require complex surveillance imaging. Use of contrast enhanced surveillance imaging modalities with contrast-enhanced digital mammography (CEM) and magnetic resonance imaging (MRI) has increased in recent years. This study evaluates characteristics of those BC survivors who receive contrast enhanced imaging and whether the addition of contrast enhanced imaging affects biopsy outcomes in BC survivors. Methods: An IRB-approved retrospective chart review identified female BC survivors who underwent breast surgery and subsequent surveillance imaging at a single academic center between 2016 and 2025. Surveillance episodes were categorized as mammography alone versus mammography with addition of CEM and/or MRI. Multivariable generalized estimating equations were used to compare patient and tumor characteristics associated with enhanced imaging modality use. Similarly rates of biopsy and cancer were evaluated with enhanced imaging use. Results: A total of 4,050 surveillance imaging episodes in 861 patients were identified and 54 resulted in biopsy-proven malignancy. Mammography alone was performed in 3,459 episodes, while enhanced imaging with CEM or MRI was used in 591 (14.6%) episodes. Use of CEM or MRI for surveillance imaging increased over time. In 2016, surveillance imaging consisted predominantly of mammography alone (93.3%) with 6.6% incorporating MRI or CEM. By 2025, mammography only surveillance decreased to 78.4% while use of MRI or CEM increased to 21.6%. Use of contrast enhanced imaging was associated with higher incidence rate ratios (IRR) for dense breast tissue [IRR 2.33; 95% CI 1.92, 2.82), p < 0.001] and less frequently used among patients aged 65–79 years [IRR 0.60, 95% CI 0.49, 0.74; p < 0.0001] and > = 80 years of age [IRR 0.40; 95% CI 0.24, 0.66; p < 0.001]. Ductal carcinoma in situ (DCIS) (IRR 3.09, p = 0.0061), and immunotherapy use (IRR 2.56, p = 0.0006) also were associated with increased use of CEM/MRI enhanced imaging. Biopsies were performed in 146 (4.2%) mammography alone episodes and 55 (9.3%) enhanced imaging episodes [IRR 2.20; 95% CI 1.63, 2.96; p < 0.001]. Surveillance with mammography yielded malignant biopsy results in 39 (1.1%) episodes, compared with 15 (2.5%) episodes using enhanced imaging [IRR 2.25; 95% CI 1.25, 4.06; p = 0.007). Conclusions: In breast cancer surveillance at our institution, the addition of contrast enhanced imaging modalities were utilized in a minority of surveillance episodes but did increase over time and were higher in patients with dense breasts. CEM or MRI usage demonstrated higher biopsy rates and increased malignancy detection compared with mammography alone, but the incidence of a positive biopsy was low. These findings suggest and are in keeping with 2023 ACR guidelines that enhanced imaging may improve cancer detection in select breast cancer survivors.

BACKGROUND: Subtotal cholecystectomy is increasingly recommended as a bailout strategy for the difficult gallbladder, yet its long-term durability and the risk profile of subsequent completion cholecystectomy remain incompletely defined. STUDY DESIGN: We performed a population-based retrospective cohort study of adults undergoing laparoscopic or open subtotal cholecystectomy for acute cholecystitis from 2012 to 2021 using Healthcare Cost and Utilization Project state databases from New York and Florida. The primary endpoint was remnant cholecystitis, defined as a postoperative emergency, inpatient, or outpatient diagnosis of cholecystitis or need for subsequent cholecystectomy. Kaplan–Meier analysis estimated cumulative incidence. Secondary outcomes included completion cholecystectomy and bile duct injury requiring surgical repair. RESULTS: Among 2,682 patients (98.7% laparoscopic), the cumulative incidence of remnant cholecystitis was 13.3% during a median follow-up of 2 years (interquartile range [IQR] 0.7 to 4.1). The median time to developing remnant cholecystitis was 28 days (IQR 13 to 91), with 79.7% occurring within 6 months. Only 70 patients (2.6%) underwent completion cholecystectomy at a median of 103 days (IQR 43 to 202). Completion cholecystectomy was performed via open surgery in 47.1% of patients and was associated with a 7.1% bile duct injury rate and median length of stay of 3 days (IQR 1 to 7), compared with a 0.9% bile duct injury rate for subtotal cholecystectomy overall. CONCLUSIONS: Although remnant cholecystitis occurred in 13.3% of patients after subtotal cholecystectomy, few required completion cholecystectomy. When necessary, completion cholecystectomy was frequently open and associated with a substantially higher bile duct injury rate, supporting referral to experienced hepatobiliary centers for reoperation.

Introduction Liver acceptance patterns vary significantly between transplant centers. Data pertaining to outcomes of livers declined by local and regional centers and allocated nationally remains limited. Project aim The objective was to compare post-liver transplant outcomes between liver allografts transplanted as a result of national and local-regional allocation. Design This was a retrospective evaluation of 109 nationally allocated liver allografts used for transplant by a single center. Outcomes of nationally allocated grafts were compared to standard allocation grafts (N = 505) during the same period. Results Recipients of nationally allocated grafts had lower model for end stage liver disease scores (17 vs 22, P = .001). Nationally allocated grafts were more likely to be post-cross clamp offers (29.4% vs 13.4%, P = .001) and have longer cold ischemia times (median hours 7.8 vs 5.5, P = .001). Early allograft dysfunction was common (54.1% vs 52.5%, P = .75) and did not impact hospital length of stay (median 5 vs 6 days, P = .89). There were no differences in biliary complications ( P = .11). There were no differences in patient ( P = .88) or graft survival ( P = .35). In a multivariate model, after accounting for differences in cold ischemia time and posttransplant biliary complications, nationally allocated grafts were not associated with increased risk for graft loss (HR 0.9, 95% CI 0.4-1.8). Abnormal liver biopsy findings (33.0%) followed by donor donation after circulatory death status (22.9%) were the most common reasons for decline by local-regional centers. Conclusion Despite longer cold ischemia times, patient and graft survival outcomes remain excellent and comparable to those seen from standard allocation grafts.

AbstractBackground and ObjectivesSerum tumor markers are widely used for diagnosis, prognosis, treatment response, and surveillance. Our study evaluated cancer embryonic antigen (CEA) in patients with appendiceal adenocarcinoma.MethodsThe National Cancer Database was reviewed (2004–2011) for patients with surgical treatment for appendiceal adenocarcinoma. Patients were stratified into two groups: normal and elevated CEA. Multivariable adjusted Cox proportional hazards regression analyses were used to determine the independent effect of CEA on survival.ResultsOur study consisted of 2867 patients, 54.0% having elevated CEA. Patients with elevated CEA were more likely to have Stage IV disease, be female, and African American; all p < 0.001. Three‐year overall survival (OS) was significantly higher with normal CEA (75.5% vs. 62.8%, p < 0.001). On multivariable analysis, elevated CEA was associated with worse survival (hazard ratio 1.49, 95% confidence interval 1.23–1.80). Patients with elevated CEA had improved 3‐year OS with neo‐adjuvant compared to adjuvant chemotherapy (p = 0.004), while those with normal CEA showed no difference.ConclusionsIn patients with surgically treated appendiceal adenocarcinoma, preoperative elevation in CEA independently predicts decreased 3‐year survival and correlates with improved OS with neo‐adjuvant therapy. CEA levels should be considered in clinical decision‐making regarding neo‐adjuvant therapy in patients with appendiceal adenocarcinoma.

Background and Objectives: Early allograft dysfunction (EAD) is considered a surrogate marker for adverse post-liver transplant (LT) outcomes. With the increasing use of nonconventional donors, EAD has become a more frequent occurrence. Given this background, we aimed to assess the prevalence and impact of EAD in an updated cohort inclusive of both conventional and nonconventional liver allografts. Materials and Methods: Perioperative and one-year outcomes were assessed for a total of 611 LT recipients with and without EAD from Mayo Clinic Arizona. EAD was defined as the presence of one or more of the following: bilirubin > 10 mg/dL on day 7, INR > 1.6 on day 7, or ALT and/or AST > 2000 IU/L within the first 7 days of LT. Results: Within this cohort, 31.8% of grafts (n = 194) came from donation after circulatory death (DCD) donors, 17.7% (n = 108) were nationally shared, 16.4% (n = 100) were allocated as post-cross clamp, and 8.7% contained moderate steatosis. EAD was observed in 52.2% (n = 321) of grafts in the study cohort (79% in DCD grafts and 40% in DBD grafts). EAD grafts had higher donor risk index (DRI) scores (1.9 vs. 1.6, p < 0.0001), were more likely to come from DCD donors (48% vs. 13.8%, p < 0.0001), were regionally allocated (p = 0.003), and had higher cold ischemia times (median 6.0 vs. 5.5 h, p = 0.001). Primary nonfunction events were rare in both groups (1.3% vs. 0.3%, p = 0.22). Post-LT acute kidney injury occurred at a similar frequency in recipients with and without EAD (43.6% vs. 30.3%, p = 0.41), and there were no differences in ICU (median 2 vs. 1 day, p = 0.60) or hospital (6 vs. 5 days, p = 0.24) length of stay. For DCD grafts, the rate of ischemic cholangiopathy was similar in the two groups (14.9% EAD vs. 17.5% no EAD, p = 0.69). One-year patient survival for grafts with and without EAD was 96.0% and 94.1% (HR 1.2, 95% CI 0.7–1.8; p = 0.54); one-year graft survival was 92.5% and 92.1% (HR 1.0, 95% CI 0.7–1.5; p = 0.88). Conclusions: In this cohort, EAD occurred in 52% of grafts. The occurrence of EAD, however, did not portend inferior outcomes. Compared to those without EAD, recipients with EAD had similar post-operative outcomes, as well as one-year patient and graft survival. EAD should be managed supportively and should not be viewed as a deterrent to utilization of non-ideal grafts.

Public trust in physicians has declined over the last 50 years. Future physicians will need to mend the patient–physician trust relationship. In conjunction with the American Medical Association’s Accelerating Change in Medical Education initiative, the Mayo Clinic Alix School of Medicine implemented the Science of Health Care Delivery (SHCD) curriculum—a 4-year curriculum that emphasizes interdisciplinary training across population-centered care; person-centered care; team-based care; high-value care; leadership; and health policy, economics, and technology—in 2015. In this medical student perspective, the authors highlight how the SHCD curriculum has the potential to address issues that have eroded patient–physician trust. The curriculum reaches this aim through didactic and/or experiential teachings in health equity, cultural humility and competence, shared decision making, patient advocacy, and safety and quality of care. It is the authors’ hope that novel medical education programs such as the SHCD curriculum will allow the nation’s future physicians to own their role in rebuilding and fostering public trust in physicians and the health care system.