IntroductionAlthough pathologic complete response (pCR) after neoadjuvant therapy (NAT) is associated with favourable survival in pancreatic ductal adenocarcinoma (PDAC), factors predicting its achievement remain unclear. Furthermore, the clinical implications of pCR regarding definitive cure versus recurrence risk require further investigation.Materials and MethodsWe retrospectively analysed 181 patients with PDAC who underwent NAT followed by curative-intent resection between 2019 and 2024. Predictors of pCR were identified using multivariable logistic regression, the optimal NAT duration was determined using receiver operating characteristic curve analysis, and prognostic factors for survival were identified using Cox proportional hazards models.ResultsTwenty patients (11.0 per cent) achieved pCR. The optimal cut-off NAT duration for predicting pCR was nine cycles. In multivariable analysis, the independent predictors of pCR were chemoradiotherapy, pre-NAT carbohydrate antigen 19-9 (CA19-9) level of 37 U/mL or less, and post-NAT CA19-9 normalization. Patients achieving pCR demonstrated superior 2-year overall survival compared with those who did not achieve pCR. Receipt of nine or more NAT cycles was an independent prognostic factor for improved survival; however, 20 per cent of patients with pCR experienced recurrence.DiscussionIntensive NAT strategies, including chemoradiotherapy and extended duration of nine or more cycles, are associated with higher pCR rates and improved survival. Although pCR is a strong marker of favourable tumour biology, it does not guarantee cure, underscoring the need for risk-adapted surveillance.

4221 Background: Organotypic models of patient-specific tumors are revolutionizing our understanding of cancer heterogeneity and its implications for personalized medicine. The study's aims were as follows: 1) to establish a PDAC patient-derived organoid (PDO) model obtained from various PDAC specimens. 2) to find out clinicogenomic factors affecting patients’ outcomes. Methods: The SMC PDAC Cohort Patients were prospectively enrolled and underwent EUS-guided FNB, metastatic sites (such as liver, ascites, lung, and bone), and surgical resection. PDAC PDOs were comprehensively analyzed for histology, next generation sequencing (NGS), and high-throughput screening (HTS) drug sensitivity tests. Results: The 735 PDAC patients were prospectively enrolled in this study. PDAC PDO platform has been trying to establish from the following cancer specimens: ascites, biopsies from bone, liver, lung, and pancreas, or surgical resection. The success rate was as follows according to the source of obtaining site; ascites due to peritoneal seeding (3/3: 100%), bone mets (1/1: 100%), EUS-FNB (195/183: 87.8%), liver mets (7/8: 87.5%), lung mets (1/1: 100%), surgical specimens (394/500: 78.8%) and PDO was successfully established within 8.2±2.6 days. It took approximately 3 weeks to acquire each specimen and generate sufficient PDAC PDOs for the simultaneous HTS drug sensitivity test and NGS. Whole exome or genome sequencing (WES/WGS, n = 357) showed an almost identical concordance between original PDAC tissues and matched PDOs and the increased frequency of genetic alterations in PDOs. The HTS drug sensitivity test (n = 151) revealed the clinical correlation between the PDO response and the actual chemotherapeutic response of the study patients in both palliative and adjuvant in real-world settings (ranging from 84.0~ to 91.2%). In addition, whole transcriptome sequencing (n = 373) identified nab-paclitaxel resistance-associated genes such as ITGB7, ANPEP, and ST3GAL1, and also found early recurrence-related genes including COL2A1, CALB1, and CYP24A1 in the extracellular matrix, calcium signaling, and vitamin D metabolism. Conclusions: The PDAC PDO platform may become a valuable tool for personalized medicine and may give us insights into tumor biology.

BACKGROUND:Conditional survival offers dynamic, time-adjusted prognostic information but remains understudied in extrahepatic cholangiocarcinoma (EHCC). This study evaluated conditional overall survival (COS), conditional recurrence-free survival (CRFS), and conditional relative survival (CRS) after curative-intent resection for EHCC. METHODS:We conducted a retrospective cohort study of 1266 patients who underwent curative-intent resection for EHCC (hilar, n = 424; common bile duct cancer [CBDC], n = 842) at a single institution between 2005 and 2019. Conditional 5-year COS, CRFS, and CRS were calculated annually using Kaplan-Meier methods and compared across demographic, clinical, and tumor-related subgroups. RESULTS:At baseline, 5-year COS, CRFS, and CRS were 41.3 %, 29.3 %, and 47.9 %, respectively, improving to 51.9 %, 50.0 %, and 59.3 % at five years post-surgery. Stage III patients demonstrated the largest gains in COS (24.7 %-51.0 %) and CRFS (14.6 %-53.3 %). Younger patients and females consistently had superior outcomes, whereas obese patients and those receiving adjuvant therapy showed less favorable long-term trends. Conditional survival patterns were similar between hilar and CBDC. CONCLUSION:Conditional survival in EHCC improves substantially with time survived, particularly among advanced-stage, younger, and female patients. However, nearly 40 % remain at risk of recurrence even after 5 recurrence-free years. Conditional estimates provide dynamic insights to guide counseling and surveillance.

BACKGROUND:Multivisceral resection (MVR) in pancreatic ductal adenocarcinoma (PDAC) involves en bloc resection of adjacent organs due to direct invasion. Despite its clinical significance, adjacent organ invasion is not included as a determinant in the American Joint Committee on Cancer (AJCC) staging or National Comprehensive Cancer Network resectability criteria. This study aimed to evaluate the safety and efficacy of MVR vs standard resection. METHODS:This study analyzed 1222 patients who underwent surgery for PDAC at a tertiary institution between 2009 and 2019. Patients with stage IV disease, recurrent operations, incomplete data, or MVR performed for double primary malignancy were excluded. Propensity score matching (PSM) was performed at a 1:2 ratio, matching for operation type and AJCC T/N stages. Short- and long-term outcomes were compared between the 2 groups. RESULTS:Before PSM, 42 MVR cases and 1099 standard resections demonstrated similar postoperative hospital stay lengths (11.4 vs 12.6 days, respectively; P =.094), major complications (23.8% vs 19.0%, respectively; P =.566), and clinically relevant postoperative pancreatic fistula (11.9% vs 6.6%, respectively; P =.310). However, compared with standard resections, MVR showed poorer long-term outcomes, including 2-year overall survival rate (2YSR; 49.9% vs 33.3%, respectively; P =.006), 2-year disease-free survival rate (2YDFSR; 25.9% vs 11.3%, respectively; P =.018), and 2-year local recurrence rate (2YLRR; 30.9% vs 41.3%, respectively; P =.319). After PSM, both groups maintained similar short-term outcomes and showed no statistical difference in 2YSR (P =.143), 2YDFSR (P =.279), and 2YLRR (P =.362). CONCLUSION:MVR demonstrates comparable short- and long-term outcomes to standard resection and should be considered for selected patients with suspected organ invasion. Our findings reinforce current staging and resectability criteria and support surgical decision-making for PDAC.

Background Pancreaticoduodenectomy (PD) increases risk of new-onset diabetes mellitus (NODM), but early predictive markers remain poorly defined. We investigated whether immediate postoperative hyperglycemia (IPH) predicts long-term NODM development following PD, potentially enabling early risk stratification and intervention. Methods We retrospectively analyzed patients undergoing pancreaticoduodenectomy (2010–2020) without pre-existing diabetes. IPH was defined as glucose ≥200 mg/dL within 24 h postoperatively. The primary endpoint was NODM occurrence following PD > 90 days, defined by ADA criteria. Kaplan-Meier survival analysis and multivariable Cox regression models assessed the association between IPH and NODM following PD, adjusting for demographic and tumor factors. Results Among 1060 patients, 662 (62.5 %) experienced IPH. During median follow-up of 4.8 years, NODM following PD developed in 48.5 % of IPH patients versus 42.5 % of non-IPH patients. IPH patients demonstrated significantly worse diabetes-free survival (log-rank p = 0.003) and earlier onset (median 584 vs 844 days, p < 0.001). After multivariable adjustment, IPH independently predicted NODM (HR 1.28, 95 % CI 1.06–1.56, p = 0.012), along with male (HR 1.32, p = 0.004) and specific tumor types (pancreatic cancer HR 1.73, p = 0.005; duodenal cancer HR 1.85, p = 0.019). Conclusions Immediate postoperative hyperglycemia independently predicts long-term diabetes development after pancreaticoduodenectomy. Incorporating IPH into postoperative risk assessment may enable targeted surveillance and early intervention strategies.

Background: Gallbladder cancer (GBC) is a highly lethal disease lacking reliable prognostic biomarkers. This study aimed to evaluate the clinical utility of artificial intelligence (AI)-powered spatial analysis of tumor-infiltrating lymphocytes (TILs) and the tumor microenvironment (TME) in resected GBC. Methods: This multicenter retrospective study analyzed a total of 225 patients with R0-resected GBC and an external validation cohort of 41 patients with GBC. Hematoxylin and eosin-stained slides were analyzed using Lunit SCOPE IO, an AI-powered whole-slide image analyzer, to map TME features. TME-related risk factors – low TIL density, low tertiary lymphoid structure count, and high fibroblast density – were identified, and their associations with overall survival (OS) and disease-free survival (DFS) were evaluated. Results: Compared with the immune-desert phenotype, both immune-inflamed and immune-excluded phenotypes were associated with longer OS ( P = 0.013). As the number of TME-related risk factors increased, OS and DFS progressively worsened. Using the group with three risk factors as the reference, adjusted hazard ratios (HRs) for OS were 0.40 (95% CI, 0.19–0.85; P = 0.017) for two risk factors, 0.34 (95% CI, 0.16–0.74; P = 0.007) for one risk factor and 0.20 (95% CI, 0.06–0.67; P = 0.009) for no risk factors. Similarly, in the analysis of DFS, with three risk factors as the reference group, the adjusted HRs were 0.37 (95% CI, 0.18–0.74; P = 0.005) for two risk factors, 0.30 (95% CI, 0.15–0.62; P = 0.001) for one risk factor, and 0.13 (95% CI, 0.04–0.41; P < 0.001) for no risk factors. External validation confirmed consistent prognostic patterns. Conclusion: We demonstrated that AI can be used to analyze TME components to predict the prognosis of resected GBC, and this tool may serve as a useful prognostic biomarker for resected GBC. Graphical abstract : http://links.lww.com/JS9/H298.

Abstract Introduction: Organotypic models of patient-specific tumors are revolutionizing our understanding of cancer heterogeneity and its implications for personalized medicine. The study's aims were as follows: 1) to establish a PDAC patient-derived organoid (PDO) model obtained from various PDAC specimens. 2) to find out clinicogenomic factors affecting patients’ outcomes. Methods: The SMC PDAC Cohort Patients were prospectively enrolled and underwent EUS-guided FNB, metastatic sites (such as liver, ascites, lung, and bone), and surgical resection. PDAC PDOs were comprehensively analyzed for histology, next generation sequencing (NGS), and high-throughput screening (HTS) drug sensitivity tests. Results: The 735 PDAC patients were prospectively enrolled in this study. PDAC PDO platform has been trying to establish from the following cancer specimens: ascites, biopsies from bone, liver, lung, and pancreas, or surgical resection. The success rate was as follows according to the source of obtaining site; ascites due to peritoneal seeding (3/3: 100%), bone mets (1/1: 100%), EUS-FNB (195/183: 87.8%), liver mets (7/8: 87.5%), lung mets (1/1: 100%), surgical specimens (394/500: 78.8%) and PDO was successfully established within 8.2±2.6 days. It took approximately 3 weeks to acquire each specimen and generate sufficient PDAC PDOs for the simultaneous HTS drug sensitivity test and NGS. Whole exome or genome sequencing (WES/WGS, n=302) showed an almost identical concordance between original PDAC tissues and matched PDOs and the increased frequency of genetic alterations in PDOs. The HTS drug sensitivity test (n=151) revealed the clinical correlation between the PDO response and the actual chemotherapeutic response of the study patients in both palliative and adjuvant in real-world settings (ranging from 84.0∼ to 91.2%). In addition, whole transcriptome sequencing (n=308) identified nab-paclitaxel resistance-associated genes such as ITGB7, ANPEP, and ST3GAL1, and also found early recurrence-related genes including COL2A1, CALB1, and CYP24A1 in the extracellular matrix, calcium signaling, and vitamin D metabolism. Conclusions: The PDAC PDO platform may become a valuable tool for personalized medicine and may give us insights into tumor biology. Citation Format: Hyemin Kim, Younghoon Choi, Eun Mi Lee, Jungmyoung Han, Se-Hoon Lee, Kwang Hyuck Lee, Jong Kyun Lee, Kyu Taek Lee, So Jeong Yoon, Hongbeom Kim, Sang Hyun Shin, Jin Seok Heo, In Woong Han, Joo Kyung Park. Next-generation cancer organoids 2.0 in precision cancer medicine: Patient-derived pancreatic ductal adenocarcinoma organoids model tells not only drug sensitivity but also complexity of tumor biology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3412.

Ampulla of Vater (AoV) carcinoma is a rare malignancy arising at the junction of intestinal and pancreatobiliary epithelium. Its heterogeneous clinical behavior and histological diversity have hindered therapeutic advances, and the cellular basis of this heterogeneity remains unclear. We aimed to construct a single-cell transcriptomic atlas of AoV carcinoma, with a focus on identifying epithelial subtypes and their interactions with the tumor microenvironment (TME). We performed single-cell RNA sequencing on eight primary AoV tumors and four matched normal tissues. Comprehensive clustering and transcriptomic analyses identified cell-type composition, epithelial heterogeneity, and tumor-immune interactions. Findings were validated using deconvolution of bulk RNA-seq data from 62 AoV carcinoma patients. Results Malignant epithelial cells were categorized into four distinct subtypes: Int-Wnt, PB-KRAS, Int-Hypoxia, and Cycling stage. PB-KRAS cells exhibited stem-like transcriptional programs and high genomic instability. Deconvolution analysis of bulk RNA-seq data from the independent AoV cohort revealed that enrichment of the PB-KRAS subtype correlated with tumor recurrence and poor survival. Our immune profiling analysis discovered a significant association between PB-KRAS subtype and GZMK+ CD8+ T cells, which are in a pre-dysfunctional state, alongside SPP1+ macrophages exhibiting immunosuppressive traits. Spatial transcriptome data further supports the immunosuppressive natures of TME around PB-KRAS subtype malignant epithelial cells in AoV carcinoma. Our study presents a single-cell atlas of AoV carcinoma, highlighting the molecular diversity of malignant epithelium and its association with the immune microenvironment. The PB-KRAS subtype emerges as a stem-like, immunosuppressive tumor state associated with poor prognosis, providing insights for future therapeutic targeting.

Abstract Introduction: The prognosis of localized BTC remains poor despite surgery. The role of neoadjuvant therapy in BTC has not been well established. Methods: DEBATE is a multicenter, randomized, non-comparative phase 2 trial enrolling treatment-naïve patients (pts) with localized BTC. Pts were randomized (2:1) to receive 4 cycles of neoadjuvant D+GP or GP alone. Those undergoing surgery received 6 cycles of adjuvant durvalumab. The primary endpoint was the R0 resection rate. Biomarker analyses included single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs), and plasma proteomics (baseline and cycle 1 day 8 [C1D8]). Results: A total of 45 pts were enrolled (D+GP, n=31; GP, n=14). Surgery was performed in 64.5% vs. 42.9%, and R0 resection rates were 48.4% vs. 42.9% in the D+GP and GP arms, respectively. In the D+GP group, the objective response rate was 38.7%, median PFS 19 months (1-sided 80% CI, 15-21), and OS 28 months (24-43), versus 14.3%, 6 months (3-11), and 30 months (23-44) in the GP group. Biomarker data were available in 98% (n=44). scRNA-seq showed a significant enrichment of classical monocytes with pro-inflammatory signatures in the D+GP group, especially among responders, along with increased CXCL10 expression in both scRNA-seq and plasma proteomics. Responders in the D+GP group also exhibited increased CD8+ T cell cytotoxicity, CD4+ Terminally differentiated effector memory T (TEMRA) cells, and IL12RB2 expression. TIGIT expression in CD4+ TEMRA cells decreased from baseline to C1D8 only in responders treated with D+GP. Conclusion: Neoadjuvant D+GP was feasible and demonstrated encouraging efficacy in localized BTC. Integrated biomarker analyses suggest that enhanced monocyte activation and T cell responses contribute to the added benefit of durvalumab. Current study provide the rationale of adding anti-TIGIT to D+GP in BTC (NCT04308174). Citation Format: Changhoon Yoo, Hyung-Don Kim, Chang Yeon Kim, Joon Oh Park, Hyehyun Jeong, Kyu-Pyo Kim, Jung Yong Hong, Sang Hyun Shin, Tae Jun Song, Dongwook Oh, Woohyung Lee, Jae Hoon Lee, Dae Wook Hwang, Jeong Seok Lee. Enhanced monocyte activation and T cell cytotoxicity underlie the benefit of neoadjuvant durvalumab plus gemcitabine-cisplatin (D+GP) in localized biliary tract cancer (BTC): Phase 2 DEBATE study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6454.

BACKGROUND:Gallbladder cancer (GBC) is an aggressive malignancy in which lymph node (LN) status is a key prognostic factor. Adequate LN retrieval is essential for accurate nodal staging. This study aimed to identify an LN threshold that reduces false node-negative (false N0) rates and to evaluate its association with overall survival (OS) as supportive evidence. METHODS:This retrospective study included 425 patients in a development cohort and 176 patients in an external validation cohort who underwent curative-intent surgery for GBC between 2008 and 2017. False N0 rates were estimated according to the number of retrieved LNs using a β-binomial model, and survival analyses were performed as complementary assessments. RESULTS:In both cohorts, retrieval of 11 LNs reduced the false N0 rate to approximately 11%-13% across T stages. Spline-based analyses demonstrated changes in survival patterns according to LN yield in the development cohort, with an inflection around 11 retrieved LNs, although dichotomized survival comparisons were not statistically significant in either cohort. CONCLUSIONS:Retrieval of at least 11 LNs was associated with a lower false N0 rate in GBC and may serve as a reference point for nodal staging. Survival analyses provided contextual support rather than evidence of a direct survival benefit.

Background: Clinically relevant postoperative pancreatic fistula (CR-POPF) remains a leading cause of morbidity after laparoscopic distal pancreatectomy (LDP), with rates plateauing at 20%–30%. Staple-line clip reinforcement is a widely used technical adjunct intended to reduce CR-POPF, but multicenter randomized evidence supporting its routine use is lacking. This study aimed to evaluate whether routine clip reinforcement reduces CR-POPF incidence and whether its effect is influenced by pancreatic texture or friability. Materials and methods: This multicenter, open-label, randomized clinical trial was conducted at three tertiary referral centers in the Republic of Korea between June 2021 and February 2025. A total of 190 adult patients undergoing elective LDP were randomized 1:1 to stapled transection with metallic clip reinforcement (clip group, n = 96) or standard stapled transection alone (no-clip group, n = 94). The primary outcome was CR-POPF incidence (ISGPS grade B or C). Prespecified subgroup analyses assessed treatment-by-subgroup interactions according to pancreatic texture, friability, body mass index, and operation time. Results: In the intention-to-treat analysis, CR-POPF occurred in 21 of 96 patients (21.9%) in the clip group and 26 of 94 patients (27.7%) in the no-clip group [risk difference, −5.8% (95% CI, −17.5%–6.0%); P = 0.45]. No grade C fistulas occurred. Per-protocol analysis yielded consistent results. No significant treatment effect modification was observed in any prespecified subgroup. Multivariable analysis identified prolonged operation time as the only independent risk factor for CR-POPF [adjusted OR, 1.012 per minute (95% CI, 1.004–1.020); P = 0.004]. Conclusion: Routine staple-line clip reinforcement during LDP did not significantly reduce CR-POPF incidence. These findings do not support its routine use in an unselected LDP population and suggest that operative efficiency may be a more relevant target for CR-POPF prevention than additional technical reinforcement.

Purpose:Neoadjuvant treatment (NAT) is now the standard for borderline resectable pancreatic cancer (RPC) and is being considered for RPC. Early recurrence after curative surgery in RPC is often seen as a treatment failure, prompting considerations for NAT. Our goal was to develop an artificial intelligence (AI)-based predictive model utilizing preoperatively available factors to forecast early recurrences of resected RPC. Methods:This study included 469 patients who underwent surgery for RPC between 2011 and 2019. Clinicopathologic and oncologic data were retrospectively reviewed. Preoperative variables, including laboratory data and imaging findings, were collected. Early recurrence was defined as recurrence occurring within a year after surgery. Deep neural networks were then used to select variables by assessing their importance. A new model predicting early recurrence of RPC was subsequently developed. Results:Of the patients evaluated, 199 (42.4%) experienced early recurrence. The predictive model included 14 preoperative variables: CA 19-9, preoperative pancreatitis, serum albumin, platelet count, lymphocyte count, the American Society of Anesthesiologists physical status classification, tumor size, monocyte count, age, body mass index, CRP, hemoglobin, WBC count, and CEA. The area under the curve for the model was 0.786 in the training set and 0.734 in the test set. Conclusion:We developed an AI-based model to predict the early recurrence of RPC using preoperative parameters. By identifying patients at risk of early recurrence, optimal individualized treatments such as NAT can be considered. Future prospective studies are crucial to establish clear indications for NAT in RPC.

BACKGROUND:Familial pancreatic cancer (FPC), defined as kindreds with at least two first-degree relatives affected by pancreatic cancer (PC), represents a high-risk subgroup. However, data on its incidence and clinical characteristics in Korea remain limited. This study evaluated the incidence, clinicopathologic features, and prognostic impact of FPC at a tertiary referral center. METHODS:We retrospectively analyzed 5 858 patients diagnosed with pancreatic ductal adenocarcinoma between 2008 and 2019. FPC was defined as at least one pair of first-degree relatives with PC. Clinicopathologic characteristics and overall survival (OS) were compared between FPC and non-FPC groups. Propensity score matching (PSM) was performed using age, sex, and clinical stage. Survival was assessed using Kaplan-Meier analysis and Cox regression. RESULTS:FPC was identified in 208 patients (3.55%) and in 5.0% of those undergoing curative-intent surgery (1 536 patients). Before PSM, FPC patients were less likely to present with metastatic disease and more likely to receive surgery and chemotherapy. After PSM, differences were not significant. OS was comparable between FPC and non-FPC groups, and FPC was not an independent prognostic factor. CONCLUSIONS:In this large Korean cohort, FPC incidence and survival outcomes were comparable to those of non-FPC cases.

e16474 Background: Ampulla of Vater carcinoma (AVC) is a rare gastrointestinal tumor that is associated with a high mortality rate and it’s often diagnosed at later stages due to lack of clinical symptoms. Elucidating complex ecosystems and molecular features of AVC is pivotal to proactive cancer prevention and optimal therapeutic intervention. Methods: We performed single-cell RNA sequencing (scRNA-seq) of treatment-naïve AVC biopsies (N = 8), and bulk RNA sequencing of surgically resected tissues (N = 62) to investigate the transcriptomic signature in tumor microenvironment (TME) of AVC. Results: We analyzed the single-cell transcriptome of 34,672 cells and epithelial cells were classified into 4 subtypes by consensus non-negative matrix factorization (cNMF) based on their gene expression profiles. Among them, the KRAS high subtype showed more increased copy number variation than other subtypes and was less differentiated with a high stemness score. Moreover, the KRAS high subtype was reversely related to overall survival (OS) and enriched with granzyme K + CD8 T cells. Deconvolution of bulk RNA-seq data validated the poor OS and progression-free survival (PFS) in the AVC patients with the KRAS high subtype. Also, it was revealed that this subtype was associated with early tumor recurrence in AVC. Conclusions: We understood the heterogenous TME of AVC and found the prognostic biomarker to predict postoperative recurrence and survival in AVC.

Increased intestinal permeability can occur in patients with diabetes mellitus. Previous studies demonstrated a correlation between impaired intestinal barrier function, elevated blood glucose levels, and diminished protective capacity of intestinal epithelial cells. However, few studies have explored gut-barrier disruption using three-dimensional (3D) in vitro models. In this study, we developed and optimized a 3D intestinal organoid model that mimics diabetic conditions by exposing the organoids to high glucose (HG) and palmitic acid (PA) levels. Human intestinal organoids derived from samples of both healthy individuals and patients with diabetes mellitus were analyzed. We evaluated the transcript levels of tight junction proteins and inflammation-related genes in ex vivo mouse intestinal organoids cultured under HG and PA conditions for 48 h. Human intestinal organoids from patients with diabetes mellitus exhibited reduced expression of genes associated with intestinal function and barrier integrity compared with those from healthy individuals. In mouse intestinal organoids, PA treatment induced cytotoxicity and significantly reduced the expression of intestinal stem cells and tight junction proteins, including zonula occludens-1 and occludin, compared with the control and HG-treated groups. Furthermore, treatment with HG and PA resulted in increased levels of inflammatory factors compared with those in the control group. Our in vitro model using 3D intestinal organoids can be used to investigate the impact of diabetic conditions and provide insights into gut barrier disruption.

4137 Background: Gallbladder cancer (GBC) is a highly lethal disease with a lack of reliable biomarkers. The tumor microenvironment (TME) is closely associated with prognosis, but its clinical application as a prognostic marker is limited by evaluation challenges. This study assessed the prognostic significance of AI-powered TME analysis in resected GBC patients. Methods: A total of 225 GBC patients with an R0 resection were enrolled, and their hematoxylin & eosin (H&E)-stained GBC sections were analyzed using Lunit SCOPE IO, an artificial intelligence (AI)-powered whole-slide image (WSI) analyze, to evaluate TME-related features, including tumor-infiltrating lymphocyte (TIL) density, fibroblast (FB) density, and tertiary lymphoid structure (TLS) counts. Risk stratification was based on TME-related risk factors (low TIL, high FB, low TLS), and survival outcomes were assessed. External validation was conducted using 146 biliary tract cancer patients. Results: Overall survival (OS) and disease-free survival (DFS) declined as the number of TME-related risk factors increased. Patients with three risk factors had the poorest outcomes (median OS: 17.7 months [reference]; median DFS: 12.7 months [reference]), followed by those with two risk factors (median OS: 115.9 months, HR = 0.40, 95% CI: 0.19–0.85; median DFS: 57.8 months, HR = 0.37, 95% CI: 0.18–0.74) and one risk factor (median OS: 126.5 months, HR = 0.34, 95% CI: 0.16–0.74; median DFS: 117.2 months, HR = 0.30, 95% CI: 0.15–0.62). Patients with no risk factors had the best survival (median OS: not reached, HR = 0.20, 95% CI: 0.06–0.67; median DFS: not reached, HR = 0.13, 95% CI: 0.04–0.41). External validation confirmed consistent trends across all risk groups. Conclusions: AI-powered TME analysis shows promise as a practical tool for identifying TME-related risk factors using H&E-stained WSI, providing valuable prognostic information for resected GBC patients.

Purpose:Pancreatic cancer has a poor prognosis; however, the implementation of neoadjuvant treatment enables borderline resectable cases to undergo curative resection and improves the overall survival rate. Attempts have been made to expand the eligibility criteria for neoadjuvant treatment, even in resectable cases. Some studies have suggested a correlation between vein abutment and poor prognosis or that the abutment angle may affect prognosis. This study investigated the anatomical factors affecting the vessel abutment angle and its prognostic value in pancreatic cancer. Methods:Patients with pancreatic ductal adenocarcinoma who underwent surgery between 2012 and 2017 were included in this study. Patients who underwent neoadjuvant treatment were excluded. Data from only the intent-to-treat pancreaticoduodenectomy group were included in the analysis. Clinicopathological characteristics; preoperative factors such as CA 19-9, preoperative biliary drainage, American Society of Anesthesiologists physical status classification, portal vein/superior mesenteric vein contact angle measured via CT scan; and intraoperative factors were collected for analysis. Results:A total of 365 patients were included in this study, and the abutment group included 92 patients (25.2%). The abutment and no-contact groups did not show any significant differences in terms of the overall survival or disease-free survival rate. Among the abutment groups, patients with less than 90° and 90°-180° did not show any significant differences. In the multivariate analysis, the only preoperative factor that had a prognostic effect was CA 19-9, a biological factor. Conclusion:When there is no vessel invasion in the abutment group, upfront surgery should be considered because the angle does not affect the overall prognosis.

Background: The incidence of portal vein/superior mesenteric vein (PV/SMV) resection during pancreatoduodenectomy is increasing in clinical practice. This study investigated the clinical significance of preoperative PV/SMV assessment and intraoperative resection and their correlation with pathological results and long-term survival outcomes. Methods: We analyzed 443 patients undergoing pancreatoduodenectomy at a tertiary center from 2012 to 2017 based on PV/SMV resection. Subgroup analyses were performed based on preoperative PV/SMV involvement, resection, and margin status. Results: Total of 441 patients were analyzed; 175 had PV/SMV involvement on preoperative radiological assessments and 128 underwent PV/SMV resection. True pathological invasion was observed in 78 patients (60.9%), with 34.3% showing no invasion and negative margins. The positive predictive value for preoperative PV/SMV involvement was 61.7%, with a false-negative value of 28.9%. Overall survival of patients who underwent PV/SMV resection was worse than those who did not (2-year survival rate, 38.1% vs 54.9%, P < 0.001). Patients without PV/SMV resection with an rR1/R1 margin showed no decrease in survival compared to those with PV/SMV resection and R0 margins (54.9% vs 40.3%, P = 0.029). Prognostic factors included hypertension, PV/SMV resection, PV/SMV R2 margin, T stage, N stage, cell differentiation, adjuvant treatment, and recurrence. Conclusion: PV/SMV resection could ensure R0 resection but may lead to unnecessary resection. Careful consideration is essential in determining the need for PV/SMV resection. Poor survival in such patients highlights the need for tailored treatments, including neoadjuvant therapy, for those who are expected to undergo PV/SMV resections.

Cancer-related distress is associated with low quality of life and oncologic outcomes in cancer patients. At present, there are limited data regarding the clinical implications of distress in patients with pancreatic cancer. The present study aimed to investigate the association between distress at diagnosis and the surgical outcomes of patients with curative-intent surgery for pancreatic cancer. Since 2014, distress thermometer (DT) surveys have been distributed to all patients with presumed cancer in the outpatient clinic of Samsung Medical Center. We retrospectively reviewed the clinicopathological data of patients who underwent curative-intent surgery for pancreatic cancer between 2014 and 2021. The survival of the patients according to DT score was analyzed using Kaplan-Meier graph and z-test. Risk factor analysis was performed to identify the impact of distress on postoperative complications. Among 1,050 patients with pancreatectomy, 130 patients responded to a DT survey. Thirty-three (25.4

Purpose:Neoadjuvant therapy (NAT) followed by surgical resection is the standard treatment for borderline resectable pancreatic cancer. The optimal timing for surgery after NAT, however, is unclear. Methods:This study retrospectively analyzed 83 patients who underwent NAT followed by resection between January 2018 and December 2021. Results:Before NAT, 22.9% of patients had resectable disease, 57.8% had borderline resectable disease, and 19.3% had locally advanced disease. After NAT, 26.5% of patients showed a downstaging of their clinical stage. After NAT, median CA 19-9 levels decreased from 148.0 to 31.7, mean tumor size from 3.1 to 2.3 cm, and the mean PET-CT maximum standardized uptake value from 6.3 to 3.6. Three-year overall survival (OS) and recurrence-free survival (RFS) were 46.7% and 22.6%, respectively. RFS and OS were significantly associated with CA 19-9 levels, lymph node metastasis, and postsurgical pathological stage, while OS was also significantly associated with tumor size and NAT. Patients with elevated CA 19-9 (> 37) which normalized after NAT showed a 3-year RFS of 32.5% compared to 0.0% in those who did not. In patients with elevated CA 19-9, OSs were 58.3% and 25.0% for those with a post-NAT decrease of ≥70% vs. those with no decrease, respectively, while RFSs were 22.6% and 0%. Conclusion:Timing of surgery after NAT should be decided considering post-NAT tumor size and CA 19-9 levels.