Epidermal growth factor receptor (EGFR) amplification remains a controversial therapeutic biomarker. We report outcomes of erlotinib plus bevacizumab (E + B) in patients with EGFR-amplified metastatic solid tumors. Patients with metastatic solid cancer who had progressed after standard therapies and were treated with E + B based on central molecular tumor board recommendations in the KOSMOS trial were included. Only those with an EGFR copy number ≥ 3 were selected. The primary endpoint was the clinical benefit rate (CBR), while secondary endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Between February 2021 and April 2024, 25 patients were treated with E + B (median EGFR copy 8.9; range, 3–76). Six tumor types were included, with colorectal cancer being the most prevalent (N = 14), followed by glioblastoma (N = 5), and other types (N = 6). Overall, four partial responses (PR) and seven cases of stable disease (SD) lasting over 16 weeks were observed, resulting in a CBR of 44.0

Abstract Background Following the positive results of TOPAZ-1 and KEYNOTE-966, gemcitabine plus cisplatin (GemCis) combined with durvalumab or pembrolizumab has been established as a global standard first-line regimen for advanced biliary tract cancer (BTC). Because patients treated in routine practice may differ from those enrolled in prospective trials, real-world evaluation of these regimens is warranted. Method The K-HBP Cancer Alliance comprises 11 tertiary referral hospitals in Korea. This multicenter retrospective study included patients who received first-line GemCis plus durvalumab or pembrolizumab for unresectable or metastatic BTC. Efficacy endpoints included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results Between November 2022 and May 2025, 534 patients with BTC (211 [40%] intrahepatic cholangiocarcinoma [iCCA], 212 [40%] extrahepatic cholangiocarcinoma [eCCA], and 111 [20%] gallbladder cancer [GBC]) received GemCis plus durvalumab or pembrolizumab. Median age was 67 years (range, 29-89); 58% were male; 95% had ECOG performance status 0-1; and 81o/o had recurrent or metastatic disease. Median follow-up was 12.0 months (95% Cl, 10.3-13.5). ORR was 20% (95% Cl, 17-24%). Median PFS and OS were 6.6 months (95% Cl, 6.1-7.2) and 14.3 months (95% Cl, 12.9-15.8), respectively. One-year PFS and OS rates were 26% and 58%, respectively. Primary tumor site was not associated with PFS or OS. Elevated CA 19-9 (> median) was associated with inferior PFS (HR, 1.35; 95% Cl, 1.08-1.70; p = 0.009) and OS (HR, 1.53; 95% Cl, 1.13-2.03; p = 0.006). Conclusion In this large multicenter real-world cohort, GemCis plus durvalumab or pembrolizumab demonstrated efficacy outcomes consistent with prospective trials.

Background/Objectives: Cancer cachexia is a multifactorial syndrome characterized by involuntary weight loss and muscle wasting, leading to impaired quality of life and poor clinical outcomes. Although oral nutritional supplements (ONS) are recommended to support inadequate oral intake during chemotherapy, their effects on underlying metabolic alterations and gut microbiome composition, particularly across different stages of cachexia remain unclear. This single-arm pilot study aimed to evaluate the feasibility and metabolic effects of an 8-week ONS intervention in patients with cancer cachexia undergoing chemotherapy. Methods: This study was conducted at the Chungnam National University Hospital, Daejeon, Republic of Korea between January 2023 and October 2023. The primary endpoints were feasibility outcomes, including adherence, tolerability, attrition rate, and ONS-related adverse events. Secondary outcomes included body composition, physical performance, biochemical markers, quality of life, plasma GDF-15 levels, serum metabolomics, and gut microbiome composition. Assessment of secondary outcomes and multi-omics profiling was performed at baseline and after 8 weeks. Patients were stratified into severe and non-severe cachexia groups and analyzed. Results: A total of 10 patients (median age 65 years, range 42-76) participated. Primary cancer types included cholangiocarcinoma (n = 4), colorectal (n = 4), and gallbladder cancer (n = 2). Adherence was 82%, with excellent tolerability and no ONS-related adverse events. Body composition, quality of life, and gut microbiome showed no significant changes. Hand-grip strength and walking-speed were slightly improved after 8 weeks intervention (p = 0.014 for hand-grip strength; p = 0.021 for walking-speed, Wilcoxon signed-rank test) in overall cohort. Metabolomics identified 10 metabolites, predominantly fatty acids, with significant between-group differential responses (p < 0.05, Mann-Whitney U test). Non-severe cachexia patients showed reductions in circulating fatty acids following ONS, consistent with attenuated lipolysis and reduced endogenous fat mobilization, whereas severe cachexia patients demonstrated increases, suggesting limited metabolic responsiveness to nutritional intervention. Fatty acid metabolism emerged as the predominant discriminatory pathway. Conclusions: This study showed the feasibility of integrating ONS with multi-omics profiling. Our findings suggest that metabolic alterations might precede clinically detectable changes, potentially providing a rationale for early intervention. Specifically, certain fatty acids were identified as candidate biomarkers that warrant further validation in larger cohorts.

Abstract Background/Aim This study retrospectively examined the clinical implications of monitoring JAK2V617F, with a particular focus on disease transformation, in a Korean population of patients with essential thrombocythemia (ET). Methods Medical records of patients diagnosed with ET between January 1996 and December 2021 at Chungnam National University Hospital, Daejeon, Korea, were reviewed. Both episodic changes (increase or decrease) and longitudinal patterns of change (stable, gradual increase, or gradual decrease) in JAK2V617F variant allele frequency (VAF), measured at 1-year intervals, were analyzed. Results Among the 87 patients who had JAK2V617F VAF measured at least three times, 23 (26.4%), 21 (24.1%), and 16 (18.4%) experienced increases of ≥ 25%, ≥ 50%, and ≥ 100%, respectively, while 27 (42.5%), 26 (29.9%), and 2 (2.3%) experienced decreases of ≥ 25%, ≥ 50%, and 100%, respectively. Patients with VAF increases had significantly poorer transformation-free survival than those without increases (15-year survival for ≥ 50% increase: 79.2% vs. 97.5%; p = 0.007). Regarding the longitudinal patterns, 62 (71.3%), 13 (14.9%), and 12 (13.8%) patients were classified as having stable, gradual increase, and gradual decrease patterns, respectively. Transformation-free survival was worse in patients with a gradual increase and better in those with a gradual decrease than in those with a stable pattern (20-year survival: 100% vs. 88.8% vs. 31.3%; p = 0.026). Conclusions An increasing JAK2V617F allele burden over time is associated with disease transformation in ET, supporting the need for the ongoing monitoring of JAK2V617F VAF in these patients.

BACKGROUND/AIM:This study aimed to evaluate the efficacy and safety of pemetrexed/oxaliplatin (PemOx) in patients with advanced or metastatic biliary tract cancer (aBTC) after failure of gemcitabine/cisplatin (GP)-based chemotherapy. PATIENTS AND METHODS:This investigator-initiated, multicenter trial was conducted at four tertiary referral centers in South Korea. PemOx was administered as follows: intravenous Pem 500 mg/m2 and Ox 120 mg/m2 on day 1, every three weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). Based on the Minimax two-stage design, a total of 30 patients were planned to be enrolled to detect an increase in the ORR from 5% to 20%, with two-sided α=0.05, β=0.2, and a 10% dropout rate. RESULTS:Between November 2023 and November 2024, 30 patients were enrolled. The median age of the patients was 68 years, and 70% were male. Five patients achieved a partial response, resulting in an ORR of 16.7% and a disease control rate of 76.7%. With a median follow-up duration of 11.0 months (range=6.9-15.1 months), the median PFS and OS were 3.6 months [95% confidence interval (CI)=1.9-5.3] and 9.9 months (95%CI=6.8-13.0), respectively. Dose delays or reductions were required in 13 (43.3%) and four (13.3 %) patients, respectively. Grade 3 TRAEs were reported in three patients (10%). No grade ≥4 TRAEs were reported. CONCLUSION:PemOx showed modest efficacy and manageable TRAEs in patients with aBTC after the failure of first line GP-based chemotherapy, although the primary endpoint was not met.

PURPOSE:While fluoropyrimidine-based chemotherapy regimens are recommended second-line treatment for patients with advanced biliary tract cancer (BTC), there have been no studies comparing different regimens head-to-head. MATERIALS AND METHODS:We performed individual patient-level meta-analysis based on data from the intention-to-treat population of the phase 2b NIFTY trial (liposomal irinotecan [nal-IRI] plus fluorouracil and leucovorin [5-FU/LV] vs. 5-FU/LV; NCT03542508) and the phase 2 FIReFOX trial (modified oxaliplatin plus 5-FU/LV [mFOLFOX] vs. modified irinotecan plus 5-FU/LV [mFOLFIRI]; NCT03464968). Pairwise log-rank tests and multivariable analysis using Cox proportional hazards modeling with shared frailty to account for the trial's effect were used to compare overall survival (OS) between regimens. RESULTS:A total of 277 patients were included. The nal-IRI plus 5-FU/LV group (n=88) showed significantly better OS compared to the mFOLFOX group (n=49, pairwise log-rank, p=0.02), and mFOLFIRI group (n=50, p=0.03). Multivariable analysis showed consistent trends in OS with adjusted hazard ratios of 1.39 (mFOLFOX vs. nal-IRI plus 5-FU/LV: 95% confidence interval [CI], 0.93 to 2.07; p=0.11) and 1.36 (mFOLFIRI vs. nal-IRI plus 5-FU/LV: 95% CI, 0.92 to 2.03; p=0.13), respectively. Compared to the 5-FU/LV group, the mFOLFOX group and the mFOLFIRI group did not show differences in terms of OS (pairwise log-rank p=0.83 and p=0.58, respectively). The nal-IRI plus 5-FU/LV group experienced more frequent diarrhea, while the mFOLFOX group experienced peripheral neuropathy. CONCLUSION:Nal-IRI plus 5-FU/LV showed favorable survival outcomes compared to mFOLFOX, mFOLFIRI, or 5-FU/LV. The safety profiles of these regimens should be considered along with efficacy.

620 Background: Cholangiocarcinoma is an aggressive malignancy with a poor prognosis. While gut microbial dysbiosis is linked to various diseases, including biliary disorders and cancer, its association with cholangiocarcinoma remains unclear. Methods: This study compared the mucosal and gut microbiomes of patients with extrahepatic cholangiocarcinoma (n = 21) to those with cholecystitis (n = 21) and healthy individuals (n = 28). Mucosal microbiomes were collected from cancer lesions and gallbladders, with fecal samples obtained from 31 participants. The 16S rRNA gene (V3 and V4 region) was sequenced using the Illumina MiSeq platform and analyzed with QIIME 2. Results: 16S rRNA sequencing revealed Proteobacteria as the dominant taxon in the cancer cohort, with Klebsiella, Aeromonas, Staphylococcus, Fusobacterium, and Haemophilus also enriched. In contrast, Firmicutes dominated in the cholecystitis and control cohorts. β-diversity analysis highlighted significant differences between cohorts. Elevated levels of bile acids, particularly chenodeoxycholic acid and ursodeoxycholic acid, were observed in the cancer cohort and positively correlated with Proteobacteria, Aeromonas, Enterobacter, and Enterococcus. Conclusions: These findings suggest that microbiome dysbiosis contributes to cholangiocarcinoma development.

BACKGROUND:The accuracy of Logical Observation Identifiers Names and Codes (LOINC) mappings is reportedly low, and the LOINC codes used for research purposes in Korea have not been validated for accuracy or usability. Our study aimed to evaluate the discrepancies and similarities in interoperability using existing LOINC mappings in actual patient care settings. METHODS:We collected data on local test codes and their corresponding LOINC mappings from seven university hospitals. Our analysis focused on laboratory tests that are frequently requested, excluding clinical microbiology and molecular tests. Codes from nationwide proficiency tests served as intermediary benchmarks for comparison. A research team, comprising clinical pathologists and terminology experts, utilized the LOINC manual to reach a consensus on determining the most suitable LOINC codes. RESULTS:A total of 235 LOINC codes were designated as optimal codes for 162 frequent tests. Among these, 51 test items, including 34 urine tests, required multiple optimal LOINC codes, primarily due to unnoted properties such as whether the test was quantitative or qualitative, or differences in measurement units. We analyzed 962 LOINC codes linked to 162 tests across seven institutions, discovering that 792 (82.3%) of these codes were consistent. Inconsistencies were most common in the analyte component (38 inconsistencies, 33.3%), followed by the method (33 inconsistencies, 28.9%), and properties (13 inconsistencies, 11.4%). CONCLUSION:This study reveals a significant inconsistency rate of over 15% in LOINC mappings utilized for research purposes in university hospitals, underlining the necessity for expert verification to enhance interoperability in real patient care.

ABSTRACTBackgroundNumerous studies have explored the role of vitamin D in various cancers; however, its impact on advanced biliary tract cancers (BTC) within a prospective cohort remains to be investigated. This preplanned subgroup analysis of the NIFTY trial evaluated the prognostic implications of serum vitamin D levels in patients with advanced BTC undergoing second‐line chemotherapy.MethodsFrom the 174 patients in the NIFTY trial, a total of 173 patients (99.4%) were included in this analysis comparing a liposomal irinotecan plus 5‐FU/leucovorin group (n = 87) and a 5‐FU/leucovorin alone group (n = 86). Baseline serum 25‐hydroxyvitamin D (25(OH)D) levels, an indicator of vitamin D status, were analyzed for their association with baseline characteristics and overall survival (OS) in patients undergoing second‐line chemotherapy. Multivariable Cox proportional hazards regression and a restricted cubic spline function were used to assess the association with OS.ResultsThere were no significant associations between baseline characteristics and serum 25(OH)D levels. Baseline serum 25(OH)D levels were not associated with OS in either the multivariable Cox proportional hazard regression or restricted cubic spline analysis. In the subgroup analysis, however, higher serum 25(OH)D levels were significantly associated with poorer OS in female patients, while no significant association was observed in male patients, indicating a significant interaction by sex. Additionally, a marginally significant interaction was observed between body mass index and serum 25(OH)D levels for OS, with higher levels associated with better OS in patients who were underweight.ConclusionsOur preplanned subgroup analysis of the NIFTY trial indicates that the serum 25(OH)D levels did not have a significant effect on OS in the overall patient population with advanced BTC. However, higher serum 25(OH)D levels were associated with worse OS in female patients, underscoring the need for further investigation into the role of vitamin D in BTC.

BACKGROUND & AIMS:Liposomal irinotecan (nal-IRI) combined with fluorouracil (5-FU)/leucovorin (LV) as a second-line treatment for biliary tract cancer (BTC) following progression on gemcitabine-based therapy yielded conflicting outcomes in the Korean NIFTY and German NALIRICC trials. This necessitated a comprehensive pooled analysis to evaluate its efficacy and safety. METHODS:Individual patient data were pooled from the intention-to-treat populations of the NIFTY and NALIRICC trials. The primary endpoint was progression-free survival (PFS). RESULTS:A total of 278 patients were included: 137 in the nal-IRI plus 5-FU/LV group and 141 in the 5-FU/LV group. The nal-IRI plus 5-FU/LV group showed significantly longer median PFS (3.6 months [95% CI 2.7-4.4] vs. 1.8 months [95% CI 1.5-2.6]; hazard ratio 0.65, p <0.001). Median overall survival was 8.1 months (95% CI 6.0-8.9) and 6.1 months (95% CI 5.3-7.5), respectively (hazard ratio 0.77, p = 0.051). Objective response rates were also higher in the nal-IRI plus 5-FU/LV group than in the 5-FU/LV group (17.5% vs. 2.8%; p <0.001). Post-study irinotecan-containing therapy was administered in 4 (2.9%) and 21 (15.3%) patients in the nal-IRI plus 5-FU/LV group and 5-FU/LV group, respectively. Adverse events varied by ethnicity, with gastrointestinal toxicities more common in Germans and neutropenia more prevalent in Koreans; treatment discontinuation without disease progression occurred in 31.3% vs. 8.0%, respectively. CONCLUSION:The addition of nal-IRI to 5-FU/LV significantly improved PFS and objective response rates, supporting its potential as subsequent-line therapy. Differences in safety profiles underscore the relevance of ethnicity for nal-IRI in patients with BTC. IMPACT AND IMPLICATIONS:Current standard of care for second-line therapy in patients with advanced biliary tract cancer (BTC) is FOLFOX. This study provides robust evidence supporting the potential role of adding liposomal irinotecan (nal-IRI) to fluorouracil and leucovorin (5-FU/LV) as a subsequent therapy for patients with BTC who have progressed on gemcitabine-based regimens. The findings demonstrate significant improvements in progression-free survival and objective response rates in a patient population for whom treatment options are limited. Furthermore, the study underscores the necessity of considering ethnic differences in adverse event profiles to optimize treatment administration and patient outcomes. CLINICAL TRIAL REGISTRATION NUMBER:NCT03524508 and NCT03043547.

Post-transplantation cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are common prophylactic strategies for graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Interleukin (IL)-6 is a surrogate marker for cytokine release syndrome (CRS) and acute GVHD. The clinical outcomes and complications of haplo-HSCT with PTCy plus ATG versus PTCy monotherapy were compared according to serum IL-6 levels at Chungnam National University Hospital (Daejeon, South Korea) from January 2019 to February 2023. Forty patients who underwent haplo-HSCT were analyzed. A significant difference in IL-6 levels was observed between the PTCy plus ATG and PTCy alone groups (7.47 ± 10.55 vs. 117.65 ± 127.67; p = 0.003). More patients in the PTCy plus ATG group had a CRS grade of 0 than in the PTCy alone group (p < 0.001). Serum IL-6 levels were associated with grades II–IV acute GVHD (r = 0.547, p < 0.001). The cumulative incidence (CI) of grades II–IV acute GVHD was significantly higher in the PTCy alone group (67.9

Importance:Limited prospective data exist on the role of adding taxane to standard chemotherapy in the first-line treatment of advanced biliary tract cancers, especially in the Asian population, where biliary tract cancers are most prevalent. Objective:To assess the efficacy and safety of polyethoxylated castor oil-free polymeric micelle formulation of paclitaxel (hereafter, polymeric micellar paclitaxel), in combination with gemcitabine and cisplatin in patients with untreated advanced biliary tract cancers. Design, Setting, and Participants:This open-label, phase 3 randomized clinical trial was conducted across 7 centers in South Korea from September 1, 2019, to October 31, 2022. Patients were eligible if they had previously untreated, locally advanced unresectable, recurrent, or metastatic adenocarcinoma of the bile duct, were aged 19 to 79 years, had an Eastern Cooperative Oncology Group Performance Status of 0 to 2, and had measurable or evaluable lesions according to Response Evaluation Criteria in Solid Tumorsversion 1.1. Interventions:Patients were randomized to receive either polymeric micellar paclitaxel, 100 mg/m2; gemcitabine, 800 mg/m2; and cisplatin, 25 mg/m2; on days 1 and 8 or gemcitabine, 1000 mg/m2, and cisplatin, 25 mg/m2, on days 1 and 8 every 21 days. A total of 9 cycles were planned for both groups. Main Outcomes and Measures:The primary end point was overall survival. Secondary end points included investigator-assessed and blinded independent central review-assessed progression-free survival, objective response rate, and safety. Results:A total of 150 patients (median [range] age, 65 [41-79] years; 87 [58%] male) were randomly assigned to the study (74 in the gemcitabine and cisplatin combined with polymeric micellar paclitaxel group and 76 in the gemcitabine and cisplatin group). The study was prematurely terminated due to slow patient accrual. The median (IQR) follow-up duration was 10.4 (6.5-16.7) months. The median overall survival was 12.0 (95% CI, 9.9-15.8) months in the gemcitabine and cisplatin combined with polymeric micellar paclitaxel group and 11.1 (95% CI, 9.7-13.5) months in the gemcitabine and cisplatin group (hazard ratio, 0.94; 95% CI, 0.63-1.41; P = .76). Both blinded independent central review-assessed and investigator-assessed progression-free survival as well as the objective response rates did not differ significantly between the 2 groups. No unanticipated safety signals were observed. Conclusions and Relevance:In this randomized clinical trial, gemcitabine and cisplatin combined with polymeric micellar paclitaxel did not improve survival compared with gemcitabine and cisplatin combined in patients with previously untreated advanced biliary tract cancer. This study provides further evidence regarding the limitations of intensified chemotherapy with the addition of taxanes in advanced biliary tract cancer. Trial Registration:cris.nih.go.kr identifier: KCT0003726.

Abstract Background Next-generation sequencing (NGS) has been introduced to many Korean institutions to support molecular diagnostics in cancer since 2017, when it became eligible for reimbursement by the National Health Insurance Service. However, the uptake of molecularly guided treatment (MGT) based on NGS results has been limited because of stringent regulations regarding prescriptions outside of approved indications, a lack of clinical trial opportunities, and limited access to molecular tumor boards (MTB) at most institutions. The KOSMOS-II study was designed to demonstrate the feasibility and effectiveness of MGT, informed by MTBs, using a nationwide precision medicine platform. Methods The KOSMOS-II trial is a large-scale nationwide master observational study. It involves a framework for screening patients with metastatic solid tumors for actionable genetic alterations based on local NGS testing. It recommends MGT through a remote and centralized MTB meeting held biweekly. MGT can include one of the following options: Tier 1, the therapeutic use of investigational drugs targeting genetic alterations such as ALK, EGFR, ERBB2, BRAF, FH, ROS1, and RET, or those with high tumor mutational burden; Tier 2, comprising drugs with approved indications or those permitted for treatment outside of the indications approved by the Health Insurance Review and Assessment Service of Korea; Tier 3, involving clinical trials matching the genetic alterations recommended by the MTB. Given the anticipated proportion of patients receiving MGT in the range of 50% ± 3.25%, this study aims to enroll 1,000 patients. Patients must have progressed to one or more lines of therapy and undergone NGS before enrollment. Discussion This pragmatic master protocol provides a mass-screening platform for rare genetic alterations and high-quality real-world data. Collateral clinical trials, translational studies, and clinico-genomic databases will contribute to generating evidence for drug repositioning and the development of new biomarkers. Trial registration NCT05525858.

3134 Background: Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has single agent clinical activity in HER2 mutated cancer. This open-label single arm phase 2 trial investigated the efficacy and safety of the dual anti-HER2 therapy, neratinib plus trastuzumab in heavily pretreated patients with HER2 mutated solid tumors excluding HER2 amplifications. Methods: Neratinib was administered 240mg p.o. daily with trastuzumab biosimilar (Herzuma) every 3 weeks. The primary endpoint was objective response rate (ORR) by RECIST v1.1. Secondary endpoints were duration of response (DoR), progression free survival (PFS), and safety. An exploratory biomarker study was also conducted. Results: Forty patients were enrolled with a median follow-up of 11.08 months (range, 0.39-21.63 months) and a median of 3 (range 1-9) lines of prior systemic therapy. Tumor types included lung (42.5%), colorectal (20%) biliary (12.5%), and breast (7.5%). Sixty percent (60%) of patients (n=24) had HER2 mutation in the kinase domain. Among evaluable patients (n=39), the ORR was 23.1% (CR=0, PR=9) with a median DoR of 11.18 months (95% CI 0-22.63). Median PFS was 3.42 months (95% CI 1.57-5.27) and median overall survival was 9.47 months (95% CI 2.93-16.01). Grade ≥3 adverse events (AEs) occurred in 47.5% of patients (n=19) and diarrhea was the most frequently reported AE (n=10; 25%) followed by bilirubin elevation (n=2; 5%), and anemia (n=2; 5%). Conclusions: In heavily pretreated patients with HER2 mutated solid tumors, neratinib plus trastuzumab showed a moderate response rate, with a durable duration of response. Most AEs were manageable, highlighting the need for prophylactic diarrhea management. Exploratory biomarker results will be presented at the upcoming meeting. Clinical trial information: NCT06083662 .

BACKGROUND:Chronic biliary disease, including cholangitis and cholecystitis, is attributed to ascending infection by intestinal bacteria. Development of a mouse model for bile duct inflammation is imperative for the advancement of novel therapeutic approaches. Current models fail to replicate the harmful bacterial influx to the biliary tract observed in humans and spread of inflammation to the liver. Therefore, we aimed to establish an animal model of biliary disease that faithfully replicates the mechanisms of human diseases. AIM:To establish a cholecystoduodenal anastomosis model capable of mimicking the mechanisms of ascending infection and inflammation observed in human biliary diseases. METHODS:We established a mouse biliary disease model by directly connecting the gallbladder and duodenum, enabling ascending infection into the biliary tract without traversing the sphincter of Oddi. RESULTS:In the cholecystoduodenal anastomosis mouse model, we observed impaired epithelial structure, wall thickening, and macrophage recruitment in the gallbladder. Despite the absence of postoperative antibiotics, we detected no changes in serum proinflammatory cytokine levels, indicating no systemic inflammation. Moreover, patency between the gallbladder and duodenum was confirmed via common bile duct ligation. Injection of patient-derived pathogenic bacteria into bile duct-ligated mice led to ascending infection, which significantly increased proinflammatory cytokine mRNA expression in the liver, duodenum, and ileum. These results indicate that our mouse model exhibited a direct connection between the gallbladder and duodenum, leading to ascending infection and closely mimicking the clinical features of biliary diseases observed in humans. CONCLUSION:The cholecystoduodenal anastomosis mouse model is an effective chronic biliary disease model with significant relevance in the development of microbiome-based therapies for the prevention and treatment of biliary disease.

Patients with cancer experience physical, mental, and social pain that affects themselves and their families. The increasing cancer incidence and advances in treatment have increased the number of cancer survivors in Korea, and there is an influx of patients in Seoul and other metropolitan areas, leading to shortages of continuous care and comprehensive life support facilities. Patients must travel long distances for treatment, which poses logistical and quality-of-life challenges. This prospective cohort study targets patients with incurable cancer (n = 720) and their families (n = 288) from ten regional cancer centers and two affiliated hospitals in Korea. The sub-cohorts are based on treatment refusal, spinal metastasis with symptoms, catheter-related symptoms, and skeletal-related events. Medical records and patient-reported outcomes will be collected every three months and for up to three years, with surveys for guardians conducted for one-year post-patient demise. The dynamic nature of cancer significantly affects patients and their caregivers. It is necessary to identify the factors that affect their quality of life to integrate them into society. The findings of this study will inform the establishment of a regional cancer center consortium. This will address the unmet needs of local cancer patients and their families, enhance their overall quality of life, and contribute to the well-being of the local community. KCT0009177 (registered at https//cris.nih.go.kr/ on 2024/02/16).

10074 Background: Cancer cachexia is a complex syndrome characterized by significant weight loss and depletion of skeletal muscle mass. Despite its profound impact on the well-being of cancer patients, the effective management of cancer cachexia remains a challenging and underexplored aspect of oncology. This study aims to investigate the potential benefits of oral nutritional supplements (ONS) to cancer patients undergoing chemotherapy. Methods: This is single-arm, prospective pilot study. Patients with cancer cachexia undergoing chemotherapy were included. Patients received ONS twice a day for 8 weeks. The ONS contained 200 kcal, 22.5 gram of carbohydrates, 7.5 gram of fat, and 12.5 gram of protein per 200 mL. Primary endpoints were improvements of lean body mass and physical performance. The secondary endpoints were changes of health-care related quality-of-life (HRQoL), nutritional status, and gut microbiomes profiles. EORTC-QLQ-C30 questionnaire, body composition analysis, 4-meter-walk test, hand grip strength test, and fecal microbiome analysis were conducted at baseline and after 8 weeks. The bacterial 16S rRNA gene (V3 and V4 region) was amplified using PCR and sequenced on the Illumina MiSeq platform. The QIIME 2 pipelines were used to analyze the raw data. Results: From January 2023 to October 2023, total of 10 patients were included. There were no significant differences of the mean daily energy intake (p=0.62) and calf-circumferences (p=0.2) between baseline and after 8 weeks. However, participants exhibited a statistically significant improvement in hand-grip strength (p=0.002) and 4-meter walk test (p=0.021) after 8 weeks. In the body composition analysis using dual-energy X-ray absorptiometry, no differences were observed in body weight (p=0.43), fat mass (p=0.62), fat-free mass (p=0.27), and fat-free mass index (p=0.38). Also, no significant differences were detected in the results of HRQoL survey (p=0.85). In the microbiome analysis, no differences of microbiome composition at phylum and genus levels, α-diversity, and β-diversity were observed between baseline and after 8 weeks. Conclusions: While ONS have shown potential in enhancing physical functions of patients with cancer cachexia undergoing chemotherapy, this did not correlate with the anticipated microbiome changes or improvements in body composition. The absence of expected microbiome alterations, despite enriched protein and dietary fiber, underscores the complexity of cachexia and indicates that its management may extend beyond nutritional supplementation alone. Further research should explore the broader context of cachexia, including nutrition, metabolic processes, and the impact of chemotherapy.

Ewing sarcoma is a rare and highly aggressive malignant tumour. The incidence is higher in bone tissue than in soft tissue. In this report, we described an extremely rare case of extraskeletal congenital Ewing's sarcoma in a male fetus, delivered at 22 weeks of gestation. A 30-year-old primigravida woman was referred for evaluation at 20 weeks of gestation due to the presence of a tumour in the fetal left chest wall. Sonographic examination revealed fetal hydrops with a 6 cm hyperechoic mass at the left chest wall accompanied by pleural effusion. Amniocentesis confirmed normal karyotype and chromosomal microarray (CMA) analyses. Subsequent pelvic magnetic resonance imaging (MRI) indicated the presence of a 6.3 cm tumour in the left chest wall, pleural effusion, and fetal hydrops. Based on these findings, the tumour was suspected to be a rare malignancy, such as Ewing sarcoma, Askin tumour, or malignant germ cell tumour. A follow-up ultrasound 10 days later showed a 7.2 cm mass, and the fetus was dead in the uterus. A male fetus, weighing 504g, was delivered by hysterotomy after an unsuccessful attempt at labour induction. The left arm was detached during delivery due to severe necrosis of the chest wall. The autopsy revealed a small round cell tumour sized 10 cm, which was located in the anterior mediastinum that invaded the chest wall. The CD99 immunohistochemistry test suggested Ewing sarcoma as the most likely diagnosis. However, since 95% of the mass was necrotic, the confirmation of Ewing sarcoma via gene testing was not possible. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.