Objective The role of circulating tumor DNA (ctDNA) in management of patients with colorectal cancer is evolving, however, there are no data on ctDNA monitoring in patients with resected colorectal liver metastases (CRLM) who receive adjuvant hepatic artery (HAI) chemotherapy. We report our center’s initial experience with postoperative ctDNA monitoring in patients receiving adjuvant HAI chemotherapy. Summary Background Data Adjuvant HAI chemotherapy improves survival after CRLM resection. ctDNA has been shown to predict recurrence in patients with resected CRLM, however no ctDNA data are available in patients who receive adjuvant HAI chemotherapy. Methods All patients with CRLM who underwent surgical resection and HAI pump placement at our center were included in this study. Demographic, clinicopathologic, radiographic, and ctDNA data are reported. Results From 2019-2024, 13 patients with CRLM underwent surgical resection and HAI pump placement and had ctDNA testing. With median follow-up of 2.6 years (1.14-4.15), 11 (85%) patients experienced recurrence at a median of 7.9 months (2.3-22.5). In total, 10 (77%) patients were ctDNA-positive all of whom had radiographic evidence of recurrence. Three patients have died at the time of last follow-up. Conclusions After surgical resection and HAI chemotherapy, ctDNA was detectable in most patients, and was associated with radiographic recurrence in all ctDNA-positive patients. We report a high recurrence rate in this series of heavily-pretreated patients with known risk factors for recurrence.

OBJECTIVE:NUT carcinoma (NC) is a rare epithelial malignancy caused by a rearrangement of the nuclear protein in testis gene (NUTM1), with fewer than 200 cases reported worldwide to date. The majority of cases have occurred in young patients (ie, ≤25 years of age), most commonly in the thoracic and head and neck regions. This case marks the first documented occurrence of NC in the hepatobiliary system. METHODS:A 35-year-old woman presented with abdominal pain radiating to the back that has persisted for 2 weeks. Liver tests revealed obstructive jaundice. An abdominal magnetic resonance imaging scan demonstrated diffuse intrahepatic bile duct dilatation resulting from a stricture at the biliary confluence. Subsequent endoscopic retrograde cholangiopancreatography biopsy confirmed an invasive, poorly differentiated carcinoma, and a stent was placed in the left hepatic duct. Following right portal vein embolization, the patient underwent an extended right hepatectomy. RESULTS:Pathology revealed a firm 2.5-cm gray-white mass at the hepatic duct bifurcation. The initial diagnosis was a biliary carcinoma characterized by mass formation and a periductal infiltrating pattern. The tumor exhibited distinctive features, such as nested architecture, open vesicular chromatin, focal squamous differentiation, and perineural vascular invasion. Positive immunohistochemistry for CK7, CK19, P40, P63, and NUT protein and identification on DNA sequencing of a BRD3::NUTM1 fusion led to a final diagnosis of NC. Despite adjuvant chemotherapy, the patient succumbed to recurrent disease 18 months after surgery. CONCLUSIONS:This case highlights the importance of recognizing NC in atypical locations and emphasizes the need for a thorough investigation in young patients with malignancies that display squamous differentiation. This report expands our understanding of biliary NC and underscores the challenges associated with its diagnosis and management.

Background & Aims: The use of immune checkpoint inhibitors (ICIs) in patients with advanced hepatocellular carcinoma (HCC) has become widespread with encouraging outcomes in the neoadjuvant setting. Safety and intention-to-treat (ITT) outcomes in the peri-transplant setting are currently based on small and heterogenous single-center reports. Methods: This first multiregional US study (2016-2023) included 117 consecutive patients with HCC assessed for liver transplantation (LT) and treated preoperatively with ICIs. ITT and survival analyses were conducted with evaluation of post-LT rejection rates. Results: In total, 86 (73.5%) patients exceeded Milan criteria (MC) and 65 (75.6%) were successfully downstaged within a median of 5.6 months; 43 (36.7%) underwent transplantation, including 18 (15.4%) within MC and 23 (19.7%) who were initially beyond but were downstaged. Overall, 94% of the cohort received concurrent ICIs and locoregional therapies. No grade 4-5 adverse events occurred on the waiting list. The 3-year cumulative probability of dropout was 28% for those within MC and 48% for those beyond. Independent predictors of dropout included being beyond MC (p <0.001), alpha-fetoprotein doubling from baseline (p = 0.014) and radiographic responses (p <0.001). The 3-year ITT survival rate was 71.1% (73.5% within MC vs. 69.7% beyond MC, p = 0.329), with a 3-year post-LT survival rate of 85%. Post-LT rejection occurred in seven patients, six received their last dose of ICI less than 3 months prior to LT, resulting in one graft loss. Conclusions: The first multicenter evaluation of patients with HCC receiving ICIs pre-LT demonstrates favorable survival and safety outcomes, justifying continued utilization and further evaluation of this strategy in clinical practice. High tumor burden, doubling of alpha-fetoprotein levels, and radiographic response were identified as predictors of unfavorable oncologic outcomes. (c) 2024 Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.

698 Background: Patient communication barriers are associated with worse quality of care and clinical outcomes. However there are limited data exploring their impact on shared decision-making (SDM) in the preoperative setting, especially for pancreatic ductal adenocarcinoma (PDAC). This study investigates the impact of patient communication barriers on patient-physician communication surrounding the decision to pursue pancreatectomy. Methods: This cross-sectional study investigates the impact of communication barriers on the degree of decisional regret (DR) in patients with PDAC who have undergone curative-intent resection at least 6 months prior to study recruitment. Patients completed validated surveys assessing communication preferences, SDM participation, and DR. Health literacy was assessed by the BRIEF Health Literacy survey. Groups were stratified by presence or absence of DR, assessed by the Decisional Regret Scale (DRS). Characteristics and survey scores were compared by chi-square and independent t-test. Given significant findings, results of this interim analysis are reported below. Results: 45 patients met inclusion criteria and completed all questionnaires. 19 (42.2%) patients expressed regret about their decision to pursue surgery with 5 patients expressing moderate to severe regret (DRS ≥25). Baseline characteristics were similar between groups. There were no significant differences in neoadjuvant or adjuvant treatments, or operative characteristics. Both groups reported high participation in preoperative SDM (average score 34.47 ± 9.67 in DR group vs 36.08 ± 8.88, P=0.567). Despite similar levels of education between groups, those expressing regret had a lower level of health literacy (14.68 ± 4.10 vs 17.35 ± 2.07, P=0.016). Fewer patients also identified English as their primary language in the DR group (78.9% vs 100%, P=0.026). While most patients preferred an active role in the final decision making process, fewer patients in the DR group reported this happening in actuality (ƙ= 0.635 vs ƙ=0.934). Conclusions: Almost half of patients expressed some regret pursuing surgery for PDAC. Despite similar educational backgrounds, a higher proportion of those expressing regret did not identify English as their primary language and had lower health literacy. While there was high participation in SDM, there was greater discordance between preferred and actual roles in the final decision making process. This identifies an important disparity to address in future preoperative discussions.

699 Background: Surgery is potentially curative for patients with localized pancreatic ductal adenocarcinoma (PDAC). Given the high rate of complications, decline in quality of life (QoL) postoperatively, and high rates of recurrence, clear preoperative communication and expectation setting is critical. This study investigates clinical outcomes that affect postoperative decisional regret (DR) in patients with PDAC. Methods: This mixed-methods study investigates the impact of clinical outcomes and QoL on the degree of DR in patients with PDAC who have undergone curative-intent resection at least 6 months prior to study recruitment. Patients completed validated surveys assessing DR and QoL by the European Organization for Research and Treatment of Cancer (EORTC). Groups are stratified by presence or absence of DR, assessed by the Decisional Regret Scale (DRS). Characteristics and survey scores were compared by chi-square, independent t-test, and median test. Narrative responses were thematically analyzed. Given significant findings, results of this interim analysis are reported below. Results: 45 patients met inclusion criteria and completed all questionnaires. 19 (42.2%) patients expressed regret about their decision to pursue curative-intent surgery, with 5 patients expressing moderate to severe regret (DRS ≥ 25). There was no significant difference in median postoperative timing of survey completion between groups (56 months in DR group vs 34 months, P=0.465). Baseline characteristics, medical treatments, and operative approaches were similar. Both groups had similar recurrence rates at time of survey completion. While 30 and 90 day readmission rates were similar, a greater proportion of the DR group had 30 day complications (42.1% vs 15.4%, P=0.045). Those expressing regret reported poorer physical functional status (mean score 79.30 ± 18.84 vs 92.31 ± 10.27, P=0.011) and greater impact on social activities (mean score 67.54 ± 33.55 vs 84.67 ± 19.19, P=0.038). Thematic analysis of narrative responses revealed that a majority of patients expressed a strong desire to have a greater focus on potential QoL changes during preoperative discussions. Conclusions: Patients expressing postoperative DR experienced more 30 day complications, and still report lasting effects on their current physical status and social activities. This emphasizes the importance of thorough preoperative counseling on surgical risks and potential changes in postoperative QoL so that patients may make the best informed decision.

Background:Patients living with human immunodeficiency virus 1 (PLWH) develop accelerated liver fibrosis, but the exact mechanism remains unknown. Activation of hepatic stellate cells (HSCs)-a cornerstone of fibrosis-is influenced by various factors, including viral infection, hepatocellular injury, chronic immune activation, gut barrier dysfunction, and microbial translocation. The role of gram-positive microbial products in human immunodeficiency virus 1 (HIV-1) infection-associated liver inflammation and fibrosis remains poorly understood. This study investigates the effect of lipoteichoic acid (LTA), a major gram-positive bacterial component, on HSCs in the context of HIV-1 infection. Methods:Human HSCs were isolated from liver tissues of both HIV-1-infected and uninfected individuals undergoing hepatic resection. Inflammatory responses of HSCs to LTA stimulation were measured ex vivo via ELISA before and after HIV-1BaL exposure. Western blotting, ChIP-qPCR and RNA-seq were used to reveal the mechanisms contributing to the IL-8 response to LTA stimulation and HIV-1BaL exposure in HSCs. Results:LTA modestly induced interleukin-8/CXCL8 (IL-8) production in HSCs, but this response was significantly heightened following HIV-1 exposure. Increased IL-8 levels were also observed in liver tissues from HIV-1-infected patients. In vitro, IL-8 treatment of HSCs elevated α-SMA and COL1A1 expression, implicating IL-8 in fibrosis progression in HIV-1 infection. Transcriptomic analysis pointed to histone acetylation as a key regulator of the IL-8 response of HSCs to LTA during HIV-1 infection. Supporting this, the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) further enhanced IL-8 expression in HIV-1-exposed HSCs. ChIP-qPCR confirmed that acetylation of histone H4K5 facilitated IL-8 promoter transactivation, sensitizing HSCs to LTA under HIV-1 influence. Conclusions:HIV-1 infection primes HSCs for an exaggerated response to LTA, driven by histone acetylation and resulting in elevated IL-8 production-potentially accelerating liver fibrosis in PLWH. Given the persistence of microbial translocation despite effective antiretroviral therapy, these findings highlight the need for targeted interventions to prevent or mitigate liver fibrosis in PLWH.

Curative-intent pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) carries high rates of morbidity and recurrence. Patients with operable PDAC face a complex decision of whether to pursue resection. Factors impacting the decision-making process and decisional regret (DR) are relatively unexplored. Patients with PDAC who underwent curative-intent pancreatectomy at least 6 months prior to study recruitment completed validated surveys assessing DR, health literacy, shared decision-making, and quality of life. Overall, 60 patients (48

Multiplex immunostaining analysis remains fragmented, underperforming and labour intensive despite tissue proteomic methodologies achieving ever-increasing marker complexity. Here we propose an open-source, user-guided automated pipeline that streamlines start-to-finish, single-cell resolution analysis of whole-slide tissue, named multiplex-imaging analysis, registration, quantification and overlaying (MARQO). MARQO integrates elastic image registration, iterative nuclear segmentation, unsupervised clustering with mini-batch k-means and user-guided cell classification through a graphical interface. We compare and validate MARQO using multiplexed immunohistochemical consecutive staining on a single slide using human tumour and adjacent normal tissue samples. Performance is compared with manually curated pathologist determinations and quantification of multiple markers. We optimize MARQO to analyse diverse tissue sizes from whole tissue, biopsy, and tissue microarray and staining approaches, such as singleplex immunohistochemistry and 20-colour multiplex immunofluorescence, to determine marker co-expression patterns in multiple human solid cancer types. Lastly, we validate CD8+ T cell enrichment in hepatocellular carcinoma responders to neoadjuvant cemiplimab in a phase 2 clinical trial, further showing the ability of MARQO to identify spatially resolved in situ mechanisms by providing multiplex whole-slide single-cell resolution data.

Hepatic resection has long been considered the preferred treatment for hepatocellular carcinoma (HCC) when feasible, but its role, as well as the outcomes is evolving rapidly. This article explores the impact of the changing demographics of HCC, reviews current criteria for resection, considers the roles of liver transplantation and nonsurgical locoregional therapies vis-a-vis resection, highlights the potential of new systemic therapies (particularly immune checkpoint inhibitors) to improve outcomes, details the common complications associated with resection, and discusses recurrence of HCC after resection and its management.

e16320 Background: Immunotherapy has markedly improved the survival of patients with advanced hepatocellular carcinoma (HCC). Early-stage HCC is potentially curable through surgical resection, though recurrence is seen in up to 70% of patients. Neoadjuvant immunotherapy may reduce the risk of local and distal recurrences and is currently being studied in several early-phase clinical trials. Here we review our single-institution experience of neoadjuvant immunotherapy in 66 patients with resectable HCC. Methods: We identified 17 patients from NCT04123379 (nivolumab alone or in combination with BMS-813160 or BMS-986253), 41 patients from NCT03916627 (cemiplimab alone or cemiplimab plus radiation), and 8 patients who received neoadjuvant nivolumab off protocol. The primary efficacy outcomes include the overall response rate (ORR) as determined by RECIST 1.1, significant tumor necrosis (STN), defined as 70% or more necrosis in resected tumors on pathological examination, and relapse-free survival (RFS). Safety and feasibility were assessed as well; delay of surgery and treatment-related adverse events (TRAE) were tabulated. Data were analyzed using R version 4.4.1. Results: Among 66 patients, 35 patients (53%) received single-agent anti-PD-1 (nivolumab or cemiplimab), 11 patients (17%) received combination immunotherapy, and 20 patients (30%) received radiation with immunotherapy. 52 patients (79%) had viral etiology. 63 (95%) patients received up to 2 doses of pre-operative immunotherapy, and 60 (91%) patients completed surgery as planned, with one patient experiencing delay to surgery due to treatment-related adverse events (defined as surgery more than 4 weeks from the last dose of immunotherapy). 53 out of 60 patients received adjuvant immunotherapy following surgery. 6 patients did not undergo resection for reasons including metastatic diseases (N = 2), inadequate liver remnant (N = 1), progression of disease (N = 2), and severe COPD (N = 1). The ORR by RECIST 1.1 was 15% (N = 10, all partial responses). Of 60 patients who underwent surgery, 10 patients (15%) achieved STN, including 7 patients with complete pathological responses (pCR); 16 patients (24%) had ≥50% tumor necrosis. For patients who underwent resection, the 1-year RFS was 79.2% (95% CI: 69.3% to 90.4%), and the 2-year RFS was 62.7% (95% CI: 50.8% to 77.3%). Three patients experienced serious treatment-related adverse events (TRAEs), including grade 3 hepatitis (N = 1) and pneumonitis (N = 2). Conclusions: Neoadjuvant immunotherapy with anti-PD-1 in patients with resectable HCC appears to be feasible with a generally acceptable safety profile. Further studies are needed to identify optimal immunotherapy regimens to be used in the neoadjuvant setting as well as optimal duration, and larger cohorts are needed to validate the correlation of pathological response with recurrence and survival.

IntroductionRoutine blood tests are prognostic tests for patients with cholangiocarcinoma. New drug regimens may produce a median overall survival of 2 years or more.MethodsThis single practice, IRB-approved, phase II trial examines prognostic tests, Kaplan-Meier survival, and univariate Cox regression analyses. Eligibility requires: intent-to-treat; signed consent; advanced measurable intrahepatic cholangiocarcinoma, with or without resistance to the test drugs; any adult age; performance status 0–2; and expected survival of ≥ 6 weeks. Biweekly treatment, with 1/3 of standard dosages in mg/M2, includes: Gemcitabine 500; 5-Fluorouracil 1200 over 24 hours; Leucovorin 180; Irinotecan 80; and on day 2, Oxaliplatin 40. On progression, drugs are added on day 2: first, Docetaxel 25 precedes Oxaliplatin, with or without Mitomycin C 6 after Oxaliplatin. The next sequential additions are day 1, Cetuximab 400 total mg, then 200 mg weekly, and then Bevacizumab 10 mg/kg is substituted for Cetuximab (FDA IND# 119005).ResultsFor 35 patients, 19 with 1–2 lines of prior therapy, resistant tumors, and 16 no prior therapy, survival at 24-months is ≥ 72 and ≥ 58%, respectively. For 14 patients aged ≥ 70 years, ≥ 63% survive 24 months, P = 0.28. Validated tests that predict ≤ 6-month survivals find median survival times of 17-months through > 2-years when compared to patients with favorable tests: Neutrophils lymphocyte ratio > 3.0, HR = 6.54, P < 6.4x10–3; absolute neutrophil count > 8000/μl, HR = 4.95, P < 6.5x10–3; serum albumin < 3.5 g/dl, HR = 4.10, P < 0.03; and lymphocyte monocyte ratio< 2.1, HR = 1.6, P = 0.50. Overall, the 76 (60–90)% of patients with 0–2 out of 4 high risk tests survive ≥ 24 months, (P = 7.1x10–3). Treatments produce neither hospitalization, neutropenic fever, severe enteritis, nor severe neuropathies.ConclusionTwo-year survival is replicable and predictable. Findings warrant phase III validation tests of sequential regimens, re-challenge with recombination, low dosages, and blood tests that are associated with lethal mechanisms that impair response and survival.

Hepatocellular carcinoma (HCC) mortality rates continue to increase faster than those of other cancer types due to high heterogeneity, which limits diagnosis and treatment. Pathological and molecular subtyping have identified that HCC tumors with poor outcomes are characterized by intratumoral collagenous accumulation. However, the translational and post-translational regulation of tumor collagen, which is critical to the outcome, remains largely unknown. Here, we investigate the spatial extracellular proteome to understand the differences associated with HCC tumors defined by Hoshida transcriptomic subtypes of poor outcome (Subtype 1; S1; n = 12) and better outcome (Subtype 3; S3; n = 24) that show differential stroma-regulated pathways. Collagen-targeted mass spectrometry imaging (MSI) with the same-tissue reference libraries, built from untargeted and targeted LC-MS/MS was used to spatially define the extracellular microenvironment from clinically-characterized, formalin-fixed, paraffin-embedded tissue sections. Collagen α-1(I) chain domains for discoidin-domain receptor and integrin binding showed distinctive spatial distribution within the tumor microenvironment. Hydroxylated proline (HYP)-containing peptides from the triple helical regions of fibrillar collagens distinguished S1 from S3 tumors. Exploratory machine learning on multiple peptides extracted from the tumor regions could distinguish S1 and S3 tumors (with an area under the receiver operating curve of ≥0.98; 95% confidence intervals between 0.976 and 1.00; and accuracies above 94%). An overall finding was that the extracellular microenvironment has a high potential to predict clinically relevant outcomes in HCC.

OBJECTIVES/GOALS: To quantify changing trends in hepatocellular carcinoma (HCC) etiologies, mainly hepatitis C related HCC (HCV-HCC), nonalcoholic fatty liver disease related HCC (NAFLD-HCC), and alcoholic liver disease related HCC (ALD-HCC), at a single center as well as compared to large national databases. METHODS/STUDY POPULATION: This is a retrospective longitudinal study using a single-center database of patients presenting with HCC from January 1995 to September 2023. Etiologies were confirmed through patient history, clinical exam, and viral serologies. Trends in rate of etiology were analyzed using linear regression. Further investigation will include survival analysis. To improve generalizability, the single-center data were supplemented with national cross-sectional data from the NHANES database on liver disease prevalence from March 1999 to August 2023. Data were provided through questionnaire, clinical exam, and viral serologies. Trends in rates will be analyzed using linear regression. RESULTS/ANTICIPATED RESULTS: Among the single center cohort, NAFLD-HCC increased at an average rate of 1.3% per year (95% Confidence Interval (CI) = 1.1% to 1.4%) and HCV-HCC decreased at an average rate of -0.56% per year (95% CI = -0.83% to -0.29%). Projecting the linear models for the past ten years forward, HCV-HCC is predicted to take up a lower proportion than NASH-HCC by 2026 and lower proportion than ALD-HCC by 2028. Future results will include analysis of the changing proportions of etiologies for liver transplant and survival analysis for HCC by etiology from the single center cohort. Additionally, national trends in HCC etiologies will be provided from the NHANES database. The trends from liver transplant etiology and NHANES are expected to parallel the preliminary results. DISCUSSION/SIGNIFICANCE: As the prevalence of NAFLD increases in the general population, more cases of NAFLD-HCC will be seen in the future. Understanding the changing trends can guide surveillance recommendations, shape treatment algorithms, and frame research priorities.

AimAssess impact of direct-acting antivirals introduction on outcomes after liver resection for hepatocellular carcinoma.Methods391 patients (1991-2021) treated with resection for hepatocellular carcinoma on Hepatitis C background were divided according to receiving Hepatitis C treatment, treatment type, achievement of sustained virological response (SVR), time of resection pre- (Era 1, 1991-2011) and post-direct acting antivirals introduction (Era 2, 2012-2021). Survival was estimated with Kaplan-Meier curves, Cox regression analysis performed to identify survival predictors.ResultsMajority of patients had single lesion (67.8%), diameter >2cm in 60.6%, no evidence of macroscopic vascular invasion on imaging. Pathology showed vascular invasion in 69.6% of patients, 76.5% microvascular. Recurrence developed in 247 patients (63.2%). 194 patients (49.6%) achieved SVR. Overall survival at 1-, 3-, 5-years was 94.6%, 85.7%, 78.8% for patients who achieved SVR, 80.1%, 48.1%, 29.9% in those who did not (p<0.001). 220 patients (56.3%) were in Era 1, 171 (43.7%) in Era 2. Survival at 1-, 3-, 5-years was 76.1%, 49%, 36% in Era 1, 94.5%, 82.5%, 70.3% in Era 2 (p<0.001). SVR was an independent predictor of survival on multiple Cox Regression analysis.DiscussionWhile many aspects of HCC management have evolved, SVR following direct-acting antivirals independently improves HCC resection outcomes.

BACKGROUND & AIMS:Hepatocellular carcinoma (HCC) risk stratification is an urgent unmet need for cost-effective HCC screening and early detection in patients with cirrhosis to improve poor HCC prognosis. METHODS:Molecular (prognostic liver secretome signature with α-fetoprotein) and clinical (aMAP [age, male sex, albumin-bilirubin, and platelets] score) variable-based scores were integrated into PAaM (prognostic liver secretome signature with α-fetoprotein plus age, male sex, albumin-bilirubin, and platelets), which was subsequently validated in 2 phase 3 biomarker validation studies: the statewide Texas HCC Consortium and nationwide HCC Early Detection Strategy prospective cohorts, following the prospective specimen collection, retrospective blinded evaluation design. The associations between baseline PAaM and incident HCC were assessed using Fine-Gray regression, with overall death and liver transplantation as competing events. RESULTS:Of 2156 patients with cirrhosis in the Texas HCC Consortium, PAaM identified 404 (19%) high-risk, 903 (42%) intermediate-risk, and 849 (39%) low-risk patients with annual HCC incidence rates of 5.3%, 2.7%, and 0.6%, respectively. Compared with low-risk patients, high- and intermediate-risk groups had sub-distribution hazard ratios for incident HCC of 7.51 (95% CI, 4.42-12.8) and 4.20 (95% CI, 2.52-7.01), respectively. Of 1328 patients with cirrhosis in the HCC early detection strategy, PAaM identified 201 high-risk (15%), 540 intermediate-risk (41%), and 587 low-risk (44%) patients, with annual HCC incidence rates of 6.2%, 1.8%, and 0.8%, respectively. High- and intermediate-risk groups were associated with sub-distribution hazard ratios for incident HCC of 6.54 (95% CI, 3.85-11.1) and 1.77 (95% CI, 1.02-3.08), respectively. Subgroup analysis showed robust risk stratification across HCC etiologies, including metabolic dysfunction-associated steatotic liver disease and cured hepatitis C infection. CONCLUSIONS:PAaM enables accurate HCC risk stratification in patients with cirrhosis from contemporary etiologies.

Zhong-Qi FAN, Xing LV, Ming-Da WANG, Xiao XU, Ya-Hao ZHOU, Xian-Ming WANG, Ting-Hao CHEN, Jie LI, Cheng-Wu ZHANG, Hong WANG, Yao-Ming ZHANG, Yong-Kang DIAO, Lan-Qing YAO, Chao LI, Wei QIU, Xiao-Dong SUN, Guo-Yue LV, Tian YANG*. Ann Hepatobiliary Pancreat Surg 2023;27:S44. https://doi.org/10.14701/ahbps.2023S1.PL-4

BACKGROUND:Recurrence of intrahepatic cholangiocarcinoma (ICC) after liver resection (LR) remains high, and optimal therapy for recurrent ICC is challenging. Herein, we assess the outcomes of patients undergoing repeat resection for recurrent ICC in a large, international multicenter cohort. PATIENTS AND METHODS:Outcomes of adults from six large hepatobiliary centers in North America, Europe, and Asia with recurrent ICC following primary LR between 2001 and 2015 were analyzed. Cox models determined predictors of post-recurrence survival. RESULTS:Of patients undergoing LR for ICC, 499 developed recurrence. The median time to recurrence was 10 months, and 47% were intrahepatic. Overall 3-year post-recurrence survival rate was 28.6%. In total, 121 patients (25%) underwent repeat resection, including 74 (61%) repeat LRs. Surgically treated patients were more likely to have solitary intrahepatic recurrences and significantly prolonged survival compared with those receiving locoregional or systemic therapy alone with a 3-year post-recurrence survival rate of 47%. Independent predictors of post-recurrence death included time to recurrence < 1 year [HR 1.66 (1.32-2.10), p < 0.001], site of recurrence [HR 1.74 (1.28-2.38), p < 0.001], macrovascular invasion [HR 1.43 (1.05-1.95), p = 0.024], and size of recurrence > 3 cm [HR 1.68 (1.24-2.29), p = 0.001]. Repeat resection was independently associated with decreased post-recurrence death [HR 0.58 0.43-0.78), p < 0.001]. CONCLUSIONS:Repeat resection for recurrent ICC in select patients can result in extended survival. Thus, challenging the paradigm of offering these patients locoregional or chemo/palliative therapy alone as the mainstay of treatment.