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Background and Rationale: Immune checkpoint inhibitor (ICI) therapy is an expanding therapeutic option for hepatocellular carcinoma (HCC). Antibiotics (ATB) taken prior to or early during ICI therapy can impact immunotherapy efficacy across indications; however, the effect of ATB is undefined in HCC. Methods: In a large international cohort of 450 ICI recipients from Europe, North America, and Asia, we categorized patients according to timing of ATB focusing on exposure within −30 to +30 days from ICI (early immunotherapy period [EIOP]). EIOP was evaluated in association with overall survival (OS), progression-free survival (PFS), and best radiologic response using RECIST 1.1 criteria. Results: Our study comprised mostly cirrhotic (329, 73.3%) males (355, 79.1%) with a Child-Turcotte Pugh class of A (332, 73.9%), receiving ICI after 1 therapy line (251, 55.9%) for HCC of Barcelona clinic liver cancer stage C (325, 72.4%). EIOP (n = 170, 37.9%) was independent of baseline clinicopathologic features of HCC and correlated with longer PFS (6.1 vs. 3.7 months, log-rank p = 0.0135). EIOP+ patients had similar OS, overall response, and disease control rates (DCRs) compared to EIOP. The effect of EIOP persisted in landmark time analyses and in multivariable models, confirming the independent predictive role of EIOP in influencing PFS following adjustment for covariates reflective of tumor burden, liver function, and ICI regimen administered. In patients receiving programmed cell death-1 receptor/ligand inhibitors monotherapy, EIOP was also associated with higher DCRs (61.4% vs. 50.9%, p = 0.0494). Conclusions: Unlike other oncological indications, ATB in the 30 days before or after ICI initiation is associated with improved benefit from immunotherapy, independent of disease and treatment-related features. Evaluation of the immune microbiologic determinants of response to ICI in HCC warrants further investigation.

Diffuse echogenicity of the pancreas, a commonly discovered finding on endoscopic ultrasound (EUS), is often of undetermined significance. The goal of this study was to characterize the clinical picture and pancreatic function in patients who incidentally present with this endosonographic finding. This was a case–control study comparing consecutive adult patients with diffuse echogenicity of the pancreas found on EUS to those who did not have known pancreas disease. Demographic and clinical data were extracted from the electronic medical record. The primary endpoint was exocrine pancreatic insufficiency (EPI) defined as fecal elastase (FE-1)

The diagnosis and treatment of gastrointestinal (GI) bleeding secondary to malignancy can be challenging. Endoscopy is the gold standard to diagnose and treat gastrointestinal bleeding but clinical characteristics and outcomes of patients with malignancy-related bleeding are not well understood. This study aims to look at clinical characteristics, endoscopic findings, safety and clinical outcomes of endoscopic interventions for GI malignancy-related bleeding.We retrospectively reviewed outcomes of patients with confirmed GI malignancies who underwent endoscopy for GI bleeding at MD Anderson Cancer Center between 2010 and 2019. Cox hazard analysis was conducted to identify factors associated with survival.A total of 313 patients were included, with median age of 59 years; 74.8% were male. The stomach (30.0%) was the most common tumor location. Active bleeding was evident endoscopically in 47.3% of patients. Most patients (77.3%) did not receive endoscopic treatment. Of the patients who received endoscopic treatment, 57.7% had hemostasis. No endoscopy-related adverse events were recorded. Endoscopic treatment was associated with hemostasis (P 0.001), but not decreased recurrent bleeding or mortality. Absence of active bleeding on endoscopy, stable hemodynamic status at presentation, lower cancer stage, and surgical intervention were associated with improved survival.This study indicates that endoscopy is a safe diagnostic tool in this patient population; while endoscopic treatments may help achieve hemostasis, it may not decrease the risk of recurrent bleeding or improve survival.

Immune checkpoint inhibitors (ICIs), used for the treatment of solid and hematologic malignancies, come with the risk of immune-related adverse events (irAEs). Opportunistic infections (e.g., cytomegalovirus [CMV]) mimic irAE symptoms and are understudied in this population. We aimed to describe the incidence, characteristics, treatment and outcomes of CMV infection in ICI-treated patients.We conducted a single-center retrospective review of all adult patients who were CMV-positive after ICI therapy between 06/2011 and 05/2020. A CMV-positive non-ICI cohort was matched to the ICI group based on age, sex and cancer type. Variables of interest were collected through electronic medical records.The study population comprised 192 patients overall. CMV infection incidence was 7.7% in ICI patients and 12.9% in non-ICI patients (P0.001). Rates of infection clearance (83% vs. 50%, P=0.002) and recurrence (20% vs. 3%, P=0.037) were higher in ICI patients with hematologic vs. solid tumors, despite similar treatments. All-cause mortality was higher in solid rather than hematologic malignancies in ICI patients (83% vs. 54%, P=0.009); CMV-related mortality was low (3-4%) in both groups.CMV infection occurred in about 7.7% of the ICI-treated cancer population. The infection can be disseminated in multiple organs and has a wide spectrum of clinical symptoms. ICI-treated patients with a hematologic malignancy had higher viral clearance and recurrence than those with solid tumors. In this study, CMV itself did not lead to high mortality in cancer patients. Further study is needed to investigate the role of CMV infection in patients' irAEs and cancer outcome.

The availability of immune checkpoint inhibitors (ICIs) for the management of advanced hepatocellular cancer (HCC) has changed the treatment paradigm. There are emerging questions regarding the efficacy of subsequent anticancer therapies. The primary aim of this retrospective, multicenter study was to examine the types of anticancer treatment received after ICIs and to assess the impact on post-ICI survival. We established an international consortium of 11 tertiary-care referral centers located in the USA (n = 249), Europe (n = 74), and Asia (n = 97), and described patterns of care following ICI therapy. The impact of subsequent therapy on overall survival (OS) was estimated using the Kaplan–Meier method and presented with a 95% confidence interval (CI). A total of 420 patients were treated with ICIs for advanced HCC after one line of systemic therapy (n = 371, 88.8%): 31 (8.8%) had died, 152 (36.2%) received best supportive care (BSC) following ICIs, and 163 patients (38.8%) received subsequent anticancer therapy. Tyrosine kinase inhibitors (TKIs, n = 132, 80.9%), in particular sorafenib (n = 49, 30.0%), were the most common post-ICI therapy followed by external beam radiotherapy (n = 28, 17.2%), further immunotherapy (n = 21, 12.9%), locoregional therapy (n = 23, 14.1%), chemotherapy (n = 9, 5.5%), and surgery (n = 6, 3.6%). Receipt of post-ICI therapy was associated with longer median OS compared with those who had received BSC (12.1 vs. 3.3 months; hazard ratio [HR]: 0.4 (95% CI: 2.7–5.0). No difference in OS was noted in those patients who received TKI before ICIs compared with those who received ICIs followed by TKI. Conclusion: Post-ICI therapy is associated with OS in excess of 12 months, suggesting a role for therapeutic sequencing. OS from TKI therapy was similar to that reported in registration studies, suggesting preserved efficacy following ICIs.

Purpose The development of treatment-related adverse events (trAE) correlates favorably with clinical outcomes in multiple studies of patients receiving immune checkpoint inhibitors (ICI); however, this relationship is undefined in patients with hepatocellular carcinoma (HCC). Patients and methods We derived a cohort of 406 patients with unresectable/advanced HCC receiving ICI therapy as part of international clinical trials submitted to the US Food and Drug Administration (FDA) in support of marketing applications. We tested whether the development of clinically significant trAE (i.e. graded ≥2, trAE2) predicted improved overall survival (OS), progression-free survival (PFS), and objective response rates (ORR) following ICI. We established an international consortium of 10 tertiary-care referral centres located in Europe (n = 67), United States (US, n = 248) and Asia (n = 42) to validate this association. Results In the FDA dataset of 406 patients, 325 (80%) with Barcelona Clinic Liver Cancer (BCLC) stage C HCC mostly treated with ICI monotherapy (n = 258, 64%), trAE2 were reported in 228 patients (56.1%). Development of trAE2 was associated with longer OS (16.7 versus 11.2 months) and PFS (5.5 versus 2.2 months) and persisted as an independent predictor of outcome after adjusting for viral aetiology, gender, Child-Pugh class, BCLC stage, AFP levels, ECOG-PS, ICI regimen (mono/combination therapy) and receipt of corticosteroid therapy. In a multi-institutional cohort of 357 patients with similar characteristics mostly treated with ICI monotherapy (n = 304, 85%), the development of trAE2 was associated with longer OS (23.3 versus 12.1 months) and PFS (9.6 versus 3.9 months). TrAE2 were confirmed predictors of improved OS (HR 0.43; 95% CI:0.25–0.75) and PFS (HR 0.48; 95% CI: 0.31–0.75), with multivariable analyses confirming their association with outcome independent of clinicopathologic features of interest. Additional time-varying multivariable analyses also indicated that trAEs were associated with a decreased risk of progression (HR 0.56, 95% CI: 0.46–0.67) in the FDA dataset and death (HR 0.55; 95% CI: 0.32–0.95) in the multi-institutional dataset. Conclusion Development of trAE2 correlates with improved outcomes in patients with HCC receiving ICI in clinical trials and in routine practice. Prospective studies aimed at understanding the underlying immunologic foundations of such relationships are warranted to identify predictive biomarkers of toxicity and response.

The impact of corticosteroid therapy (CT) on efficacy of immune checkpoint inhibitors (ICI) is undefined in hepatocellular carcinoma (HCC). We evaluated whether CT administered at baseline (bCT) or concurrently with ICI (cCT) influences overall (OS), progression-free survival (PFS) and overall response rates (ORR) in 341 patients collected across 3 continents. Of 304 eligible patients, 78 (26%) received >10 mg prednisone equivalent daily either as bCT (n=14, 5%) or cCT (n=64, 21%). Indications for CT included procedure/prophylaxis (n=37, 47%), management of immune-related adverse event (n=27, 35%), cancer-related symptoms (n=8, 10%) or comorbidities (n=6, 8%). Neither overall CT, bCT nor cCT predicted for worse OS, PFS nor ORR in univariable and multivariable analyses (p>0.05). CT for cancer-related indications predicted for shorter PFS (p

BackgroundNivolumab is Food and Drug Administration approved in sorafenib-experienced, advanced hepatocellular carcinoma (HCC). Post-registration data of treatment in a real-world setting is lacking.Patients and methodsWe performed an international, multicenter observational study to confirm safety and efficacy of nivolumab in 233 patients treated outside clinical trials from eight centers in North America, Europe and Asia.ResultsPatients received nivolumab for Barcelona Clinic Liver Cancer stage C (n=191, 92.0%) and Child-Pugh (CP) A (n=158, 67.8%) or B (n=75, 32.2%) HCC as first (n=85, 36.5%) or second to fourth systemic therapy line (n=148, 63.5%). Objective response rate (ORR) was 22.4% and disease control rate was 52.1%. Median overall survival (OS) was 12.2 months (95% CI 8.4 to 16.0) and median progression-free survival was 10.1 months (95% CI 6.1 to 14.2). Treatment-related adverse events of grade >2 occurred in 26 patients (11.2%). Efficacy and safety were similar across CP classes and therapy line. OS was shorter in CP-B than A (7.3 months vs 16.3 months, p=0.05). Achievement of an objective response predicted for improved OS (25.4 months vs 13.2 months, pConclusionsThis study confirms safety and efficacy of nivolumab in advanced HCC across various lines of therapy and degrees of liver dysfunction. Despite equal ORR and toxicity to nivolumab, patients with CP-B functional class have shorter survival than the patients with CP-A.

Immune checkpoint inhibitors (ICI) have shown positive results in patients with hepatocellular carcinoma (HCC). As liver function contributes to prognosis, its precise assessment is necessary for the safe prescribing and clinical development of ICI in HCC. We tested the accuracy of the albumin-bilirubin (ALBI) grade as an alternative prognostic biomarker to the Child-Turcotte-Pugh (CTP). In a prospectively maintained multi-centre dataset of HCC patients, we assessed safety and efficacy of ICI across varying levels of liver dysfunction described by CTP (A to C) and ALBI grade and evaluated uni- and multi-variable predictors of overall (OS) and post-immunotherapy survival (PIOS). We studied 341 patients treated with programmed-death pathway inhibitors (n = 290, 85%). Pre-treatment ALBI independently predicted for OS, with median OS of 22.5, 9.6, and 4.6 months across grades (p &lt, 0.001). ALBI was superior to CTP in predicting 90-days mortality with area under the curve values of 0.65 (95% CI 0.57&ndash, 0.74) versus 0.63 (95% CI 0.54&ndash, 0.72). ALBI grade at ICI cessation independently predicted for PIOS (p &lt, 0.001). Following adjustment for ICI regimen, neither ALBI nor CTP predicted for overall response rates or treatment-emerging adverse events (p &gt, 0.05). ALBI grade identifies a subset of patients with prolonged survival prior to and after ICI therapy, lending itself as an optimal stratifying biomarker to optimise sequencing of systemic therapies in advanced HCC.

Diffuse echogenicity of the pancreas, a commonly discovered finding on endoscopic ultrasound (EUS), is often of undetermined significance. The goal of this study was to characterize the clinical picture and pancreatic function in patients who incidentally present with this endosonographic finding.This was a case-control study comparing consecutive adult patients with diffuse echogenicity of the pancreas found on EUS to those who did not have known pancreas disease. Demographic and clinical data were extracted from the electronic medical record. The primary endpoint was exocrine pancreatic insufficiency (EPI) defined as fecal elastase (FE-1) 200 μg/g.A total of 166 patients were included in this study. There were 89 patients who had diffuse echogenicity of the pancreas on EUS and FE-1 testing. There were 77 control patients with chronic diarrhea who did not have known pancreas disease but did have FE-1 testing. EPI was significantly more likely in the fatty pancreas group compared to the control group (47% vs 6%, p 0.001). There was also a significantly greater proportion of smokers in the fatty pancreas group compared to the control group (42% vs 17%, p = 0.002). There were no other differences in baseline characteristics between the two groups, including prevalence of chronic pancreatitis by Rosemont classification. On multiple logistic regression analysis controlling for multiple variables, smoking (OR 2.26, 95% CI 1.15-4.43) and NAFLD (OR 3.99, 95% CI 1.09-14.70) had significant associations with EPI.This study found a significantly greater amount of patients who had diffuse echogenicity of the pancreas on EUS to also have EPI. This is compared to a control group of patients without known pancreas disease. This prevalence was found in the absence of a significant association with chronic pancreatitis on EUS based on Rosemont classification. Future controlled studies are required to further investigate this relationship.

Background: Immune checkpoint inhibition (ICI) is an expanding option in hepatocellular carcinoma (HCC). Antibiotics (ATB) have been shown to reduce response and survival after ICI in other cancers. Methods: Efficacy of ICI is described in patients (pt) from 11 centres (246 USA, 100 Asia, 68 Europe), with median overall (OS), progression-free survival (PFS) and best response (RECIST 1.1) compared between pt with and without ATB exposure in the early immunotherapy period (EIOP) of 30 days before and after ICI initiation. Results: Most of our 414 pt were cirrhotic (297, 71.7%) due to hepatitis C (162, 391.1%) with Barcelona Clinic Stage C (294, 71.0%), Child-Pugh class (CP) A (313, 76.3%) and AFP>400 IU/mL (158, 39.3%). OS was 15.4 mo (95%CI 13.1-17.7) and PFS was 5.3 months (95% CI 4.5-6.0). Most ICI was anti-PD-1 monotherapy (358, 86.5%) and given as 1st (173, 41.8%) or 2nd line (208, 50.2%). Best response to ICI was complete response in 27 pt (6.5%), partial response in 45 (10.9%), stable disease (SD) in 160 (38.6%) and progressive disease (PD) in 161 (38.9%). ATB was given to 167 pt (40.3%), prior to or early after (30 d) ICI initiation (EIOP, 157, 38.0%) or beyond 30 days (21, 5.1%), mostly as beta-lactams (27, 10.9%) or quinolones (26, 10.5%). ATB use was independent of CP class (p=0.76), ECOG performance status (p=0.58) and BCLC stage (p=0.60). mOS in the EIOP+ group was similar to the EIOP- group (13.1 vs 15.5 mo, p=0.92). mPFS in the EIOP+ group was significantly longer than the EIOP- group (7.9 vs 4.2 mo, p=0.004). Observations persisted when stratified by CP class (p=0.42) and ICI type (p=0.92). Partial response rate was higher in the EIOP+ group (17.3% vs 8.6%, p=0.01), although overall objective response and disease control rates were similar between EIOP groups (ORR: 22.7% vs 15.9%, p=0.10; DCR: 64.0% vs 56.6%, p=0.15). Pt in the EIOP+ group were not more likely to experience gastrointestinal AE (EIOP +/- 9.2%/5.4%, p=0.12) or hepatic AE (EIOP +/-, 17.9%/16.5%, p=0.92) of any grade, while severe liver AE (grade 2 or above) were less common in the EIOP+ group (EIOP+/- 2.8%/9.5%, p=0.01). Conclusions: ATB in the 30 d before or after ICI initiation in HCC is associated with prolonged PFS. This is contrary to findings in other solid tumors. Evaluation of the immune-microbiologic determinants of response to ICI in HCC a key research question. Citation Format: Petros Fessas, Muntaha Naeem, Thomas U. Marron, David Szafron, Elad Sharon, Anwar Saeed, Tomi Jun, Sirish Dharmapuri, Abdul R. Naqash, Thoetchai Peeraphatdit, Anuhya Gampa, Yinghong Wang, Uqba Khan, Mahvish Muzaffar, Musharraf Navaid, ChiehJu Lee, Pei-Chang Lee, Anushi Bulumulle, Bo Yu, Sonal Paul, Neil Nimkar, Dominik Bettinger, Hannah Hildebrand, Yehia I. Abugabal, Tiziana Pressiani, Nicola Personeni, Naoshi Nishida, Masatoshi Kudo, Ahmed Kaseb, Yi-Hsiang Huang, Celina Ang, Anjana Pillai, Lorenza Rimassa, David J. Pinato. Early antibiotic exposure delays disease progression following immune checkpoint inhibitor therapy for hepatocellular carcinoma: Evidence from an observational study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 485.

A 73-year-old man with a history of heart failure and hypertension presented with a several-week history of generalised weakness, anorexia, 5 kg weight loss, intermittent small volume hematochezia and right upper quadrant abdominal pain. He denied fever, chills, dysphagia, nausea, vomiting, diarrhoea and constipation. He had no previous endoscopy or colorectal cancer screening. His admission vital signs were normal. He was anaemic (haemoglobin 8.6 g/dL reference 12–18 g/dL), with mean corpuscular volume 83 (81–100 fL/cell), ferritin 321.9 (11–336 ng/mL), alkaline phosphatase 174 (38–127 IU/L), albumin 2.4 (3.5–4.9 g/dL), total bilirubin 0.8 (0.2–1.2 mg/dL) and aspartate aminotransferase/alanine aminotransferase 28/21 (10–40 U/L, 7–56 U/L). Serological tests for hepatitis and HIV were negative. RPR was negative 1 month previously. CT imaging with intravenous contrast (figure 1) revealed six target-like liver lesions (0.7 to 1 cm) with peripheral arterial enhancement and several enlarged coeliac lymph nodes (largest 0.8 cm). Due to anaemia/hematochezia, upper and lower endoscopy were performed. His oesophagogastroduodenoscopy showed …

e16677 Background: Nivo is FDA-approved in sorafenib-experienced, advanced HCC. Post-registration data to portray treatment in a real-world setting is lacking. Methods: We describe safety and efficacy of nivo in patients (pts) from 8 centres (USA n = 181, Asia n = 47, Europe n = 5), documenting overall (OS), progression-free survival (PFS), overall response (ORR) and disease control rates (DCR) (RECIST). Results: We analysed 233 pts, mostly cirrhotic (n = 176, 75%) due to hepatitis C (n = 95, 54.0%) with Barcelona Clinic Stage (BCLC) C HCC (n = 178, 76.4%), Child-Pugh class (CP) A (n = 158, 67.8%) or B (n = 75, 32.2%), and AFP > 400 IU/mL (n = 132, 56.7%). Nivo was given as first (1L, n = 85, 36.5%), second line (2L, n = 130, 55.8%) or > 2L (n = 18, 7.7%), after local (n = 191, 82%) and systemic therapy (n = 148, 63.5%), mostly sorafenib (n = 142, 60.9%). Median duration of nivo was 6.0 months (mo, interquartile range [IQR] 2.6-11.9) and stopped due to progression (n = 109, 46.8%) or toxicity (n = 8, 3.4%). After median follow up of 7 mo (IQR 3.0-12.3), ORR was 22.4% and DCR was 52.1%. Best responses (n = 219, 94%) included complete and partial responses in 18 (7.7%) and 31 (13.3%) pts respectively, stable disease in 65 (27.9%) and progressive disease in 105 (45.1%), not dissimilar by CP (p = 0.26). Median OS was 12.2 mo (95%CI 8.4-16.0) and predicted by CP (CPA 16.3 mo 95%CI 11.7-20.8; CPB 7.3 mo 95%CI 4.2-10.4; hazard ratio [HR] 1.9, p = 0.01), nivo line (1L 16.3 mo 95%CI 8.0-24.5; > 1L 10.4 mo 95%CI 7.4-13.5; HR 0.68, p = 0.05), and PVT (PVT- 13.8 mo 95%CI 11.7-16.0; PVT+ 10.4 mo 95%CI 7.8-13.0; HR 1.8, p = 0.015) but not cirrhosis, AFP, BCLC or steroid use (p > 0.05). Median PFS was 10.1 mo (95%CI 6.1-14.2), predicted by BCLC (A-B 19.0 mo 95%CI 7.1-30.8; C 8.2 mo 95%CI 4.9-11.4; HR 2.8, p = 0.002) and line (1L 18.2 mo 95%CI 10.4-25.9; > 1L 8.2 mo 95% CI 6.2-10.2; HR 0.60, p = 0.021), but not cirrhosis, AFP, or steroid use (p > 0.05). 26 pts (11.2%) suffered > = Grade 2 toxicities, most commonly fatigue (n = 29, 24.7%). Conclusions: Real-world use of nivo in advanced HCC across line of therapy suggests reproducible clinical efficacy and safety compared to prospective trials.

531 Background: The impact of corticosteroid treatment (CT) on the efficacy of immune checkpoint inhibitors (ICI) in hepatocellular carcinoma (HCC) is undefined. We evaluated whether CT administered at baseline (bCT) or concurrently to ICI (cCT) influences clinical outcomes of HCC patients treated with ICI. Methods: This retrospective, multi-center observational study was conducted across 9 tertiary academic referral centers collected 341 HCC patients who received ICI across 3 continents between January 1, 2016 and April 1, 2019. Outcome measures included overall (OS) and progression-free survival (PFS) calculated from time of ICI commencement and overall response rates (ORR) defined by Response Evaluation Criteria in Solid Tumors (v1.1) on 6-8 weekly periodic restaging. Results: Of 331 eligible patients, 254 (76%) had BCLC-C stage HCC and received mostly PD(L)-1 ICI monotherapy (n=250, 85%). Median OS was 12.1 months (95%CI 9.2-15.0 months) and median PFS was 8.1 months (95%CI 6.3-10 months). In total 81 patients (24%) received >10 mg prednisone equivalent daily either as bCT (n=15, 4%) or cCT (n=66, 20%). Indications for CT included procedure/prophylaxis (n=37, 45%), management of irAE (n=31, 37%), cancer-related symptoms (n=5, 2%) or comorbidities (n=8, 3%). Neither overall CT, bCT nor cCT predicted for worse OS, PFS nor ORR in uni- and multi-variable analyses (p>0.05). CT for cancer-related indications predicted for shorter PFS (2.4 vs. 11.3 months, p=0.01), OS (4.5 vs. 12.8 months, p=0.05) and reduced ORR (p=0.03) compared to cancer-unrelated indications. Conclusions: This is the first study to demonstrate that neither bCT nor cCT appear to influence response and OS following ICI in HCC. Worse survival and ORR in CT recipients for cancer-related indications appears driven by the poor prognosis associated with symptomatic HCC.

Injury occurring on the surface of the rectal mucosal lining that causes defects in barrier function may result in increased risk for transmission of infection by HIV and other pathogens. Such injury could occur from microbicidal or other topical agents, mechanical trauma during consensual or nonconsensual intercourse, or inflammatory conditions. Tools for evaluation of rectal mucosal barrier function for assessing the mucosa under these conditions are lacking, particularly those that can provide in vivo structural and functional barrier integrity assessment and are adaptable to longitudinal imaging. We investigated confocal endomicroscopy (CE) as a means for in vivo imaging of the rectal epithelial barrier in the ovine model following spatially confined injury to the surface at a controlled site using a topical application of the microbicide test agent benzalkonium chloride. Topical and intravenous (i.v.) fluorescent probes were used with CE to provide subcellular resolution imaging of the mucosal surface and assessment of barrier function loss. A 3-point CE grading system based on cellular structure integrity and leakage of dye through the mucosa showed significant differences in score between untreated (1.19 ± 0.53) and treated (2.55 ± 0.75) tissue ( P < 0.0001). Histological grading confirmed findings of barrier compromise. The results indicate that CE is an effective means for detecting epithelial injury and barrier loss following localized trauma in a large-animal model. CE is promising for real-time rectal mucosal evaluation after injury or trauma or topical application of emerging biomedical prevention strategies designed to combat HIV.