Background: Warm ischemia is a major contributor to ischemic cholangiopathy and non-anastomotic biliary strictures (NAS) after liver transplantation, particularly in donation-after-circulatory-death grafts. However, the isolated impact of warm ischemia on peribiliary fibrosis is difficult to delineate because clinical settings involve overlapping effects of cold ischemia, reperfusion injury, and alloimmunity. This study aimed to establish a non-transplant rat model that isolates warm ischemic biliary injury and to compare the antifibrotic effects of rapamycin and tacrolimus. Methods: Warm ischemia was induced in Sprague–Dawley rats by ligating both ends of the peribiliary vascular plexus and the hepatic artery, followed by 30 minutes of portal vein clamping. Rats were randomly assigned to control, tacrolimus (1 mg/kg/day), or rapamycin (1 mg/kg/day) groups (n=15 per group). Serum alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and total bilirubin were measured serially. Hematoxylin and eosin (H&E) and Sirius red staining were performed at 1, 3, and 6 weeks. Peribiliary fibrosis was quantified using digital image analysis of collagen area fraction. Results: Warm ischemia induced acute hepatobiliary injury with transient enzyme elevations, but no significant intergroup differences were observed. Histologically, biliary epithelial proliferation and collagen deposition increased progressively and became prominent at 6 weeks. At this time point, fibrosis ratios differed significantly (overall p=0.002): controls showed the highest fibrosis (4.8%), followed by tacrolimus (2.4%) and rapamycin (1.7%). Both immunosuppressants significantly reduced fibrosis compared with controls (p<0.05), whereas the difference between tacrolimus and rapamycin was not significant. Conclusion This warm ischemia model demonstrates that isolated ischemic injury alone can induce progressive peribiliary fibrosis. Rapamycin and tacrolimus attenuated fibrosis, with rapamycin producing the lowest collagen deposition. These findings provide mechanistic insight into ischemic cholangiopathy after liver transplantation—particularly in donation after circulatory death grafts—and underscore the need for further studies using models that incorporate cold ischemia, reperfusion, and alloimmune factors.

Purpose: Weight reduction (WR) can reduce liver volume, affecting the graft-to-recipient weight ratio (GRWR). This study aimed to evaluate the decrease in liver volume after WR and analyze risk factors affecting liver volume reduction in potential liver donors with steatosis. Methods: We retrospectively reviewed data of 147 potential liver donors with steatosis who participated in a WR program prior to liver transplantation between January 2016 and December 2021. Total liver volume (TLV) was measured using CT and MRI. Risk factors for large liver volume reduction (≥10%) were analyzed using multivariate logistic regression. Results: Ninety-seven donors (66.0%) underwent donor hepatectomy after WR. Liver volumes showed a statistically significant decrease (from 1,399.6 ± 315.4 mL to 1,283.6 ± 271.2 mL, P < 0.05). Thirty-eight donors (42.7%) showed large liver volume reduction. There was a more significant reduction in weight, AST, and ALT in the large liver volume reduction group than in the small liver volume reduction group (all P < 0.05). WR percentage and ALT abnormalities were independent risk factors for large liver volume reduction (odds ratio, 1.184 [95% confidence interval, 1.054–1.329] and odds ratio, 5.502 [95% confidence interval, 1.660–18.229], respectively; all P < 0.05). Conclusion Potential liver donors with 7% or more WR or ALT abnormality require liver volume/GRWR remeasurement after WR to ensure adequate graft size and prevent small-for-size syndrome.

Purpose: Right lobe living donor liver transplantation (LDLT) with dual portal veins (PVs) remains technically challenging.This study aimed to identify independent risk factors for PV complications. Methods: We retrospectively analyzed 111 recipients of dual PV LDLT between 2011 and 2020. Recipient characteristics, anatomical geometry, and surgical factors were evaluated. Outcomes were overall PV complications and major PV complications (Clavien-Dindo grade ≥III). Logistic regression was performed. Results: PV complications developed in 41 patients (36.9%), including 16 major events (14.4%). Univariate analysis revealed associations with right posterior PV (RPPV) diameter, axial angle, and coronal angle. On multivariate analysis, larger RPPV diameter (odds ratio [OR], 1.79; P = 0.041) and wider axial angle (OR, 1.08; P = 0.015) were independent predictors of major PV complications. Reconstruction method was not significant. Patients with overall major Clavien-Dindo grade ≥IIIcomplications had inferior 100-month survival (80% vs. 100%; P = 0.014, log-rank test). Conclusion In dual PV LDLT, anatomical geometry—specifically RPPV diameter and axial angle—independently predicts major PV complications, whereas surgical technique does not. Preoperative 3-dimensional imaging and anatomical risk stratification should inform donor selection and surgical planning.

Purpose: This study aimed to assess prognostic factors associated with combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and to predict 5-year survival based on these factors. Materials and Methods: Patients who underwent definitive hepatectomy from 2006 to 2022 at a single institution was retrospectively analyzed. Inclusion criteria involved a pathologically confirmed diagnosis of cHCC-CCA. Results: A total of 80 patients with diagnosed cHCC-CCA were included in the analysis. The median progression-free survival was 15.6 months, while distant metastasis-free survival (DMFS), hepatic progression-free survival, and overall survival (OS) were 50.8, 21.5, and 85.1 months, respectively. In 52 cases of recurrence, intrahepatic recurrence was the most common initial recurrence (34/52), with distant metastasis in 17 cases. Factors associated with poor DMFS included tumor necrosis, lymphovascular invasion (LVI), perineural invasion, and histologic compact type. Postoperative carbohydrate antigen 19-9, tumor necrosis, LVI, and close/positive margin were associated with poor OS. LVI emerged as a key factor affecting both DMFS and OS, with a 5-year OS of 93.3% for patients without LVI compared to 35.8% with LVI. Based on these factors, a nomogram predicting 3-year and 5-year DMFS and OS was developed, demonstrating high concordance with actual survival in the cohort (Harrell C-index 0.809 for OS, 0.801 for DMFS, respectively). Conclusion The prognosis of cHCC-CCA is notably poor when combined with LVI. Given the significant impact of adverse features, accurate outcome prediction is crucial. Moreover, consideration of adjuvant therapy may be warranted for patients exhibiting poor survival and increased risk of local recurrence or distant metastasis.

Background/Aims: Hepatocellular carcinoma (HCC) exhibits high de novo recurrence rates post-resection. Current post-surgery recurrence prediction methods are limited, emphasizing the need for reliable biomarkers to assess recurrence risk. We aimed to develop methylation-based markers for classifying HCC patients and predicting their risk of de novo recurrence post-surgery. Methods: In this retrospective cohort study, we analyzed data from HCC patients who underwent surgical resection in Korea, excluding those with recurrence within one year post-surgery. Using the Infinium Methylation EPIC array on 140 samples in the discovery cohort, we classified patients into low- and high-risk groups based on methylation profiles. Distinctive markers were identified through random forest analysis. These markers were validated in the cancer genome atlas (n=217), Validation cohort 1 (n=63) and experimental Validation using a methylation-sensitive high-resolution melting (MS-HRM) assay in Validation cohort 1 and Validation cohort 2 (n=63). Results: The low-risk recurrence group (methylation group 1; MG1) showed a methylation average of 0.73 (95% confidence interval [CI] 0.69–0.77) with a 23.5% recurrence rate, while the high-risk group (MG2) had an average of 0.17 (95% CI 0.14–0.20) with a 44.1% recurrence rate (P<0.03). Validation confirmed the applicability of methylation markers across diverse populations, showing high accuracy in predicting the probability of HCC recurrence risk (area under the curve 96.8%). The MS-HRM assay confirmed its effectiveness in predicting de novo recurrence with 95.5% sensitivity, 89.7% specificity, and 92.2% accuracy. Conclusions Methylation markers effectively classified HCC patients by de novo recurrence risk, enhancing prediction accuracy and potentially offering personalized management strategies.

Background: s/Aims: Liver transplantation (LT) is now a critical, life-saving treatment for patients with liver cirrhosis or hepatocellular carcinoma. Despite its significant benefits, biliary complications (BCs) continue to be a major cause of postoperative morbidity.This study evaluates the fluorescence intensity (FI) of the common bile duct (CBD) utilizing near-infrared indocyanine green (ICG) imaging, and examines its association with the incidence of BCs within three months post-LT. Methods: This investigation analyzed data from nine living donor LT (LDLT) recipients who were administered 0.05 mg/kg of ICG prior to bile duct anastomosis. Real-time perfusion of the CBD was recorded for three minutes using an ICG camera, and FI was quantified using Image J (National Institutes of Health). Key parameters assessed included F max, F1/2 max, T1/2 max, and the slope (F max/ T max) to evaluate the fluorescence response. Results: BCs occurred in two out of nine patients. These two patients exhibited the longest T1/2 max values, which were linked with lower slope values, implicating a potential relationship between extended T1/2 max, reduced slope, and the occurrence of postoperative BCs. Conclusions The study indicates that ICG fluorescence imaging may serve as an effective tool for assessing bile duct perfusion in LDLT patients. While the data suggest that an extended T1/2 max and lower slope may correlate with an increased risk of BCs, further validation through larger studies is required to confirm the predictive value of ICG fluorescence imaging in this setting.

Background: s/Aims: Liver transplantation (LT) is now a critical, life-saving treatment for patients with liver cirrhosis or hepatocellular carcinoma. Despite its significant benefits, biliary complications (BCs) continue to be a major cause of postoperative morbidity.This study evaluates the fluorescence intensity (FI) of the common bile duct (CBD) utilizing near-infrared indocyanine green (ICG) imaging, and examines its association with the incidence of BCs within three months post-LT. Methods: This investigation analyzed data from nine living donor LT (LDLT) recipients who were administered 0.05 mg/kg of ICG prior to bile duct anastomosis. Real-time perfusion of the CBD was recorded for three minutes using an ICG camera, and FI was quantified using Image J (National Institutes of Health). Key parameters assessed included F max, F1/2 max, T1/2 max, and the slope (F max/ T max) to evaluate the fluorescence response. Results: BCs occurred in two out of nine patients. These two patients exhibited the longest T1/2 max values, which were linked with lower slope values, implicating a potential relationship between extended T1/2 max, reduced slope, and the occurrence of postoperative BCs. Conclusions The study indicates that ICG fluorescence imaging may serve as an effective tool for assessing bile duct perfusion in LDLT patients. While the data suggest that an extended T1/2 max and lower slope may correlate with an increased risk of BCs, further validation through larger studies is required to confirm the predictive value of ICG fluorescence imaging in this setting.

Purpose: This study aimed to assess prognostic factors associated with combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and to predict 5-year survival based on these factors. Materials and Methods: Patients who underwent definitive hepatectomy from 2006 to 2022 at a single institution was retrospectively analyzed. Inclusion criteria involved a pathologically confirmed diagnosis of cHCC-CCA. Results: A total of 80 patients with diagnosed cHCC-CCA were included in the analysis. The median progression-free survival was 15.6 months, while distant metastasis-free survival (DMFS), hepatic progression-free survival, and overall survival (OS) were 50.8, 21.5, and 85.1 months, respectively. In 52 cases of recurrence, intrahepatic recurrence was the most common initial recurrence (34/52), with distant metastasis in 17 cases. Factors associated with poor DMFS included tumor necrosis, lymphovascular invasion (LVI), perineural invasion, and histologic compact type. Postoperative carbohydrate antigen 19-9, tumor necrosis, LVI, and close/positive margin were associated with poor OS. LVI emerged as a key factor affecting both DMFS and OS, with a 5-year OS of 93.3% for patients without LVI compared to 35.8% with LVI. Based on these factors, a nomogram predicting 3-year and 5-year DMFS and OS was developed, demonstrating high concordance with actual survival in the cohort (Harrell C-index 0.809 for OS, 0.801 for DMFS, respectively). Conclusion The prognosis of cHCC-CCA is notably poor when combined with LVI. Given the significant impact of adverse features, accurate outcome prediction is crucial. Moreover, consideration of adjuvant therapy may be warranted for patients exhibiting poor survival and increased risk of local recurrence or distant metastasis.

Background/Aims: Hepatocellular carcinoma (HCC) exhibits high de novo recurrence rates post-resection. Current post-surgery recurrence prediction methods are limited, emphasizing the need for reliable biomarkers to assess recurrence risk. We aimed to develop methylation-based markers for classifying HCC patients and predicting their risk of de novo recurrence post-surgery. Methods: In this retrospective cohort study, we analyzed data from HCC patients who underwent surgical resection in Korea, excluding those with recurrence within one year post-surgery. Using the Infinium Methylation EPIC array on 140 samples in the discovery cohort, we classified patients into low- and high-risk groups based on methylation profiles. Distinctive markers were identified through random forest analysis. These markers were validated in the cancer genome atlas (n=217), Validation cohort 1 (n=63) and experimental Validation using a methylation-sensitive high-resolution melting (MS-HRM) assay in Validation cohort 1 and Validation cohort 2 (n=63). Results: The low-risk recurrence group (methylation group 1; MG1) showed a methylation average of 0.73 (95% confidence interval [CI] 0.69–0.77) with a 23.5% recurrence rate, while the high-risk group (MG2) had an average of 0.17 (95% CI 0.14–0.20) with a 44.1% recurrence rate (P<0.03). Validation confirmed the applicability of methylation markers across diverse populations, showing high accuracy in predicting the probability of HCC recurrence risk (area under the curve 96.8%). The MS-HRM assay confirmed its effectiveness in predicting de novo recurrence with 95.5% sensitivity, 89.7% specificity, and 92.2% accuracy. Conclusions Methylation markers effectively classified HCC patients by de novo recurrence risk, enhancing prediction accuracy and potentially offering personalized management strategies.

Background: Postoperative pain management is challenging in patients with oral cancer, especially those undergoing reconstructive surgery. Patient-controlled analgesia (PCA) is widely used, and fentanyl (FTN) concentration adjustments may improve pain control. This study aimed to evaluate the effects of FTN PCA concentration and reconstructive surgery on postoperative pain in patients with oral cancer. Methods: This retrospective observational study analyzed 140 patients with oral cancer who underwent surgery under general anesthesia. Patients were categorized based on FTN PCA dosage (FTN 700 mcg and ketorolac 150 mg vs. FTN 1400 mcg and ketorolac 150 mg). Pain was assessed using the visual analog scale (VAS) at multiple time points postoperatively (0, 12, 24, 36, 48, 60, and 72 h). PCA usage patterns, including demand count, delivery count, and delivery/demand ratios, were compared across subgroups. Missing data were imputed using linear interpolation. Results: PCA usage and pain control were evaluated between the FTN 700 mcg (N = 40) and 1400 mcg (N = 100) groups, stratified by reconstruction status. Demographic characteristics showed no significant difference.In the reconstructive surgery subgroup, patients in the FTN 1400 mcg group showed lower PCA refill counts (1.45 ± 0.69 vs. 1.61 ± 0.58) and fewer delivery counts (17.1 ± 21.3 vs. 25.1 ± 28.5) compared to those in the FTN 700 mcg group, achieving similar or superior pain control with fewer interventions. Similarly, patients without reconstructive surgery in the FTN 1400 mcg group demonstrated lower PCA refill counts, shorter PCA usage times, and fewer delivery counts. VAS scores decreased consistently over time across all groups but remained higher in the reconstruction groups. Logistic regression analysis revealed that patients with reconstructive surgery in the FTN 1400 mcg group were more likely to achieve a VAS score of ≤ 3.0 at 72 h postoperatively (P = 0.022). These findings indicate FTN 1400 mcg’s superiority in managing postoperative pain. Conclusion Comparing FTN PCA dosages, 1400 mcg demonstrated superior pain control to 700 mcg in patients undergoing oral cancer surgery, particularly those who underwent reconstructive surgery. This finding underscores the importance of optimizing FTN dosages to enhance postoperative pain management, reduce PCA-related demands, and achieve better patient outcomes.