Background and Objectives: The Korean Organ Transplant Registry (KOTRY) provided data for this third official report on adult heart transplantation (HT), including information from 709 recipients. Methods: Data from HTs performed at seven major centers in Korea between March 2014 and December 2020 were analyzed, focusing on immunosuppression, acute rejection, cardiac allograft vasculopathy (CAV), post-transplant survival, and mechanical circulatory support (MCS) usage. Results: The median ages of the recipients and donors were 56.0 and 43.0 years, respectively.Cardiomyopathy and ischemic heart disease were the most common preceding conditions for HT. A significant portion of patients underwent HT at waiting list status 1 and 0. In the multivariate analysis, a predicted heart mass mismatch was associated with a higher risk of 1-year mortality. Patients over 70 years old had a significantly increased risk of 6-year mortality. The risk of CAV was higher for male donors and donors older than 45 years. Acute rejection was more likely in patients with panel reactive antibody levels above 80%, while statin use was associated with a reduced risk. The employment of left ventricular assist device as a bridge to transplantation increased from 2.17% to 22.4%. Pre-transplant extra-corporeal membrane oxygenation was associated with worse post-transplant survival. Conclusions In this third KOTRY report, we analyzed changes in the characteristics of adult HT recipients and donors and their impact on post-transplant outcomes. The most notable discovery was the increased use of MCS before HT and their impact on post-transplant outcomes.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Objective: To analyze costs and cost-effectiveness of transforaminal endoscopic thoracic discectomy (TETD) for the treatment of symptomatic thoracic disc herniation (TDH) and compare it with open microdiscectomy (MD). Methods: This retrospective cohort study included patients who underwent TETD or MD for symptomatic TDH and had a minimum follow-up of 1 year. Cost analysis included direct costs (primary and secondary hospital costs), indirect costs (lost wages due to work absence), total costs (direct + indirect), and cost-effectiveness (cost per quality-adjusted life year [QALY] and incremental cost-effectiveness ratio [ICER]). Clinical outcomes included patient-reported outcome measures (Oswestry Disability Index [ODI], 36-item Short Form health survey [SF-36]), QALY gained, and reoperation and readmission rates at 1 year. TETD and MD groups were compared for outcome measures. Results: A total of 111 patients (57 TETD, 54 MD) were included. The direct ($6,270 TETD vs. $7,410 MD, p < 0.01), indirect costs ($1,250 TETD vs. $1,450 MD, p < 0.01), total costs ($7,520 TETD vs. $8,860 MD, p < 0.01), and cost per QALY ($31,333 TETD vs. $44,300 MD, p < 0.01) were significantly lower for TETD compared to MD. ICER of TETD was found to be -$33,500. At 1 year, TETD group showed significantly greater improvement in ODI (46% vs. 36%, p < 0.01) and SF-36 (64% vs. 53%, p < 0.01) and significantly greater QALY gained (0.24 vs. 0.2, p < 0.01) compared to MD group. No significant difference was found in reoperation and readmission rates. Conclusion TETD demonstrated significantly better clinical outcomes, lower overall costs, and better cost-effectiveness than MD in appropriately selected patients of symptomatic TDH.

Purpose: Inotuzumab ozogamicin (INO) has demonstrated a safe bridging role to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). How‑ ever, hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is frequently observed. This study aimed to identify significant features of INO-associated VOD/SOS. Methods: We reviewed seven cases of hepatic VOD/SOS that developed either during INO salvage or after alloge‑ neic HSCT following INO-induced complete remission (CR). Diagnosis and severity grading of VOD/SOS were based on the revised criteria from the European Society for Blood and Marrow Transplantation. Defibrotide was used to treat severe to very severe cases. Results: Four patients developed VOD/SOS during INO salvage therapy (at 21 and 36 days post-INO1, 77 days postINO3, and 21 days post-INO5), while three were diagnosed at 2, 5, and 10 days post-HSCT following INO-induced CR.Doppler ultrasonography revealed preserved portal vein flow (range 10.2–26.0 cm/sec) and normal hepatic artery resistive index (RI, range 0.56–0.74) in all but one patient (RI 0.83). Despite this, all patients presented with massive ascites and progressively elevated total bilirubin levels. All cases were classified as severe to very severe; six were treated with defibrotide and one underwent liver transplantation. Most patients ultimately died owing to VOD/SOS progression. Conclusion Post-INO VOD/SOS manifested as two different clinical settings and was characterized by preserved portal vein flow, which complicated diagnosis. Despite timely defibrotide administration, clinical outcomes were poor.These findings emphasize the need for vigilance and potential consideration of prophylactic strategies for prevention of INO-associated VOD/SOS.

Purpose: Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC. Materials and Methods: Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed. Results: In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT. Conclusion Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.

Purpose: The metabolism of tamoxifen is influenced by various cytochrome p450 enzymes, including CYP2D6 and CYP2C19, leading to variations in the levels of endoxifen, even with the same tamoxifen dose. However, the clinical significance of endoxifen for the prognosis of breast cancer patients remains controversial. This study aimed to elucidate the relevance of endoxifen level to recurrence-free survival censored with tamoxifen discontinuation (RFSt), representing the RFS for tamoxifen itself, of breast cancer patients and determine a suitable cutoff for prognostication. Materials and Methods: The study included 478 breast cancer patients. Tamoxifen and its metabolites, including endoxifen, were measured using liquid chromatography-tandem mass spectrometry. An optimal cutoff was determined with maximally selected rank statistics. Survival analysis and Cox regression were conducted based on this cutoff. Results: An endoxifen level of 21.00 ng/mL was the optimal cutoff for prognostication. Survival analysis revealed a statistically significant difference in RFSt between the low endoxifen group (≤ 21.00 ng/mL) and the high endoxifen group (> 21.00 ng/mL) (log-rank test, p=0.032). The 10-year probability of RFSt was 83.2% (95% confidence interval [CI], 77.0 to 89.9) and 88.3% (95% CI, 83.3 to 93.5) in the low and high endoxifen groups, respectively. Multivariable Cox proportional hazards regression indicated endoxifen concentration as a significant factor associated with prognosis. Conclusion Endoxifen could serve as a marker for appropriate tamoxifen treatment with a cutoff of 21.00 ng/mL. Based on this cutoff, therapeutic drug monitoring would benefit patients displaying suboptimal endoxifen concentrations.

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 diseasefree 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.

Objective: To analyze costs and cost-effectiveness of transforaminal endoscopic thoracic discectomy (TETD) for the treatment of symptomatic thoracic disc herniation (TDH) and compare it with open microdiscectomy (MD). Methods: This retrospective cohort study included patients who underwent TETD or MD for symptomatic TDH and had a minimum follow-up of 1 year. Cost analysis included direct costs (primary and secondary hospital costs), indirect costs (lost wages due to work absence), total costs (direct + indirect), and cost-effectiveness (cost per quality-adjusted life year [QALY] and incremental cost-effectiveness ratio [ICER]). Clinical outcomes included patient-reported outcome measures (Oswestry Disability Index [ODI], 36-item Short Form health survey [SF-36]), QALY gained, and reoperation and readmission rates at 1 year. TETD and MD groups were compared for outcome measures. Results: A total of 111 patients (57 TETD, 54 MD) were included. The direct ($6,270 TETD vs. $7,410 MD, p < 0.01), indirect costs ($1,250 TETD vs. $1,450 MD, p < 0.01), total costs ($7,520 TETD vs. $8,860 MD, p < 0.01), and cost per QALY ($31,333 TETD vs. $44,300 MD, p < 0.01) were significantly lower for TETD compared to MD. ICER of TETD was found to be -$33,500. At 1 year, TETD group showed significantly greater improvement in ODI (46% vs. 36%, p < 0.01) and SF-36 (64% vs. 53%, p < 0.01) and significantly greater QALY gained (0.24 vs. 0.2, p < 0.01) compared to MD group. No significant difference was found in reoperation and readmission rates. Conclusion TETD demonstrated significantly better clinical outcomes, lower overall costs, and better cost-effectiveness than MD in appropriately selected patients of symptomatic TDH.