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: Radiotherapy is used to reduce the risk of breast cancer recurrence after surgery, but it is a potential cause of secondary cancer. We validated the risk of secondary cancer in primary breast cancer who received radiotherapy compared with those who did not from a matched cohort using a large-scale observational study of the Observational Health Data Sciences and Informatics (OHDSI) data network. Materials and Methods: A retrospective comparative cohort study using propensity score-matched cohorts was performed using two Observational Medical Outcome Partnership common data model databases, from tertiary general hospitals in South Korea. Among female patients who underwent surgery after the diagnosis of breast cancer, the risk of secondary primary malignant occurrence after 1:1 matching was analyzed. Results: Among 27,078 patients with breast cancer, there was no significant difference in the risk of secondary cancer following radiotherapy in 4,426 patients after 1:1 propensity-score matching. Further, there were no significant differences in the sensitivity analysis according to age, latency period, and number of radiation treatments. Conclusion There was no difference in the risk of secondary cancer in the patients diagnosed with breast cancer depending on whether or not radiotherapy was performed after surgery. In the future, it is necessary to analyze including data generated during cancer treatment.

Purpose: Limited treatment options exist for patients with metastatic castration-resistant prostate cancer (mCRPC) after the failure of taxane-based chemotherapy and novel hormonal therapy. Here, we report the safety and efficacy of ifosfamide and mesna in patients with mCRPC after the failure of taxane-based chemotherapy and novel hormonal therapy (NCT06236789). Materials and Methods: Patients with histologically confirmed prostate cancer who had failed taxane-based chemotherapy and novel hormonal therapy received ifosfamide 2,500 mg/m2 and mesna 1,500 mg/m2 on days 1–3, repeated every 21 days. Safety, objective response rate, disease control rate, reduction in serum prostate-specific antigen (PSA) concentration by >50% (PSA50) or >90% (PSA90), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed. Results: A total of 47 patients with mCRPC were included in the study. The median number of lines of treatment was 5 (range, 3 to 7). All patients were previously administered docetaxel and novel hormonal therapies including abiraterone (51.1%) and/or enzalutamide (61.7%). Thirty-eight patients (80.9%) were administered cabazitaxel. The objective response and disease control rates were 21.3% and 80.9%, respectively. PSA50 and PSA90 were achieved in 31.9% and 10.6%, respectively. During a median follow-up duration of 54.3 months, rPFS and OS were 5.0 and 9.0 months, respectively. All the patients experienced treatment-related adverse events of any grades; however, no new safety signs were detected. Genomic biomarker analysis revealed that alterations in the TP53 pathway were associated with inferior rPFS and OS. Conclusion Ifosfamide and mesna showed appreciable efficacy and manageable safety profiles in heavily treated patients with mCRPC.

Background: We analyzed the status of organ distribution in pediatric deceased donor liver transplantation (DDLT) in Korea. Additionally, we estimated how many pediatric patients could have avoided living donor liver transplantation (LDLT) or survived if new criteria for splittable deceased donors were adopted. Based on the findings, we advocate expanding policy to promote the universal adoption of split liver transplantation (SLT). Methods: Using the Korean Network for Organ Sharing database, we identified patients who underwent DDLT between January 2000 and December 2020. We considered “po-tential splittable donors” those with a donor-to-recipient weight ratio of ≥1.0 who met the existing SLT criteria (age 10–40 years; weight ≥50 kg). By comparing the numbersof pediatric LDLT recipients and potential splittable donors annually, we estimated how many patients might have avoided LDLT if the left lateral section of each splittable liver had been allocated to a child. Additionally, we compared the number of deaths on the DDLT waiting list with the number of potential splittable donors to estimate possibly preventable deaths. Results: Overall, we identified 640 potential splittable donors. Over the 20-year period, 1,210 pediatric patients (<19 years old) received LDLT. If potentially splittable livers had been split, this number could have been nearly halved. Furthermore, 127 patients died while on the DDLT waiting list. Using SLT with potential splittable donors, these deaths might have been prevented. Conclusions SLT could reduce avoidable deaths among pediatric patients while decreasing the economic and social burden of LDLT, without compromising survival for adult DDLT recipients.

Purpose: This study evaluated the clinical outcomes and prognostic factors in patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) treated with upfront FOLFIRINOX followed by local-regional therapy (LRT), surgical resection (SR), and radiotherapy (RT). We aimed to identify specific patient subgroups for which RT may serve as a reasonable alternative to SR for local tumor control. Methods: We retrospectively analyzed 116 patients (SR group, n= 70; RT group, n= 46) at a single center between 2015 and 2020. Survival outcomes were compared based on LRT modalities, focusing on identifying subgroups in which RT provided an efficacy comparable to that of SR. Results: Among 116 patients, the SR group achieved a significantly higher 5-year overall survival (OS) than the RT group (27.1% vs. 8.7%, P< 0.0001), despite similar progression-free survival (P= 0.23). Significant prognostic factors for OS included carbohydrate antigen 19-9 (CA19-9) response in BRPC (P= 0.02) and radiologic partial response in LAPC (P= 0.05). Subgroup analysis revealed that, while SR provided a survival advantage in CA19-9 responders, no significant difference in OS was observed between SR and RT in CA19-9 non-responders (P= 0.37). Conclusion Although surgery remains the gold standard, RT may be considered a justifiable local alternative for CA19-9 non-responders and surgically ineligible patients with LAPC, yielding comparable outcomes in these specific, biologically unfavorable subgroups.

Purpose: Hematopoietic stem cell transplantation (HSCT) has been an important method of treatment in the advance of pediatric acute lymphoblastic leukemia (ALL). The indications for HSCT are evolving and require updated establishment. In this study, we aimed to investigate the efficacy of HSCT on the treatment outcome of pediatric ALL, considering the indications for HSCT and subgroups. Materials and Methods: A retrospective analysis was conducted on ALL patients diagnosed and treated at a single center. Risk groups were categorized based on age at diagnosis, initial white blood cell count, disease lineage (B/T), and cytogenetic study results. Data on the patients’ disease status at HSCT and indications of HSCT were collected. Indications for HSCT were categorized as upfront HSCT at 1st complete remission, relapse, and refractory disease. Results: Among the 549 screened patients, a total of 418 patients were included in the study; B-cell ALL (n=379) and T-cell ALL (T-ALL) (n=39). HSCT was conducted on a total of 106 patients (25.4%), with a higher frequency as upfront HSCT in higher-risk groups and specific cytogenetics. The overall survival (OS) was significantly better when done upfront than in relapsed or refractory state in T-ALL patients (p=0.002). The KMT2A-rearranged ALL patients showed superior event-free survival (p=0.002) and OS (p=0.022) when HSCT was done as upfront treatment. Conclusion HSCT had a substantial positive effect in a specific subset of pediatric ALL. In particular, frontline HSCT for T-ALL and KMT2A-rearranged ALL offered a better prognosis than when HSCT was conducted in a relapsed or refractory setting.

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.