Background: We developed a simplified variant of the ADV score, the AFP-PIVKAII (AP) score for post-transplant hepatocellular carcinoma (HCC) prognosis, which considers only AFP and PIVKA-II levels excluding morphometric tumor size information from the ADV score. This study investigated the prognostic performance of the AP score in predicting HCC recurrence and overall survival (OS) after living donor liver transplantation (LDLT). Methods: We analyzed 843 patients with HCC who underwent LDLT between 2006 and 2015, assessing HCC recurrence and OS in relation to AP score. Results: The median pretransplant AFP and PIVKA-II levels were 12.8 ng/mL and 27 mAU/mL, respectively. The median and mean AP scores were 2.6 log (range: 0.6–9.2 log) and 2.9±1.1 log, respectively. The 5-year time-dependent area under the receiver operating characteristic curve for the AP score in predicting post-transplant HCC recurrence was 0.672 (p<0.001). HCC recurrence and OS curves along AP score intervals of 1.0 log showed statistical differences in accordance with the AP scores (both p<0.001). Using a Youden index J-derived AP score cutoff of 4.0 log, two-tiered groups (ADV <4.0 log vs. ADV ≥4.0 log) showed statistically significant differences in HCC recurrence and OS (both p<0.001). Harrell’s c-indices for AP score with cutoff of 4.0 log and ADV scores with cutoff of 5.0 log regarding HCC recurrence and OS were similar. Conclusion The AP score functions as an integrated surrogate marker for predicting post-transplant outcomes in patients with HCC undergoing LDLT. It may serve as a simplified alternative to the ADV score, particularly in patients with small HCCs.

Background/Aims: The absence of standardized clinical minimum inhibitory concentration (MIC) breakpoints for Helicobacter pylori infection has resulted in inconsistent resistance definitions, even within the same research group in Korea. Therefore, establishing epidemiological cutoff values (ECOFFs) is essential for standardization. Methods: The MIC distributions for antibiotics commonly used against H. pylori infection in South Korea were analyzed from 2015 to 2023. A total of 5,925 primary H. pylori isolates were collected from five data sources, and MIC values were determined using the serial 2-fold agar dilution method. The ECOFFinder program was used to establish ECOFFs for six antibiotics. Results: The tentative ECOFFs for amoxicillin and clarithromycin were 0.125 μg/mL. The ECOFFs for levofloxacin, metronidazole, and tetracycline were 0.5, 8.0, and 0.25 μg/mL, respec-tively. The ECOFF for rifabutin could not be determined due to insufficient data. On the basis of these ECOFFs, the resistance rate was 17.9% for amoxicillin, 31.9% for clarithromycin, 40.9% for levofloxacin, 24.7% for metronidazole, and 11.5% for tetracycline. Conclusions This comprehensive analysis defined regional antibiotic resistance patterns and established Korea-specific ECOFFs, providing a foundation for determining clinical breakpoints and optimizing H. pylori eradication strategies.

Background: Studies on whether donor-to-recipient sex match status affects long-term survival after liver transplantation (LT) have yielded contradictory results. This study evaluated whether donor-to-recipient sex match status influenced long-term survival after living donor liver transplantation (LDLT) or deceased donor liver transplantation (DDLT) at a high-volume center. Methods: The study included 6,664 patients who underwent primary LT between January 2000 and December 2022 at our institution. Patients were divided into four groups according to donor-to-recipient sex match status: male-to-male (n=3,427 [51.4%]), male-to-female (n=1,152 [17.3%]), female-to-male (n=1,385 [20.8%]), and female-to-female (n=700 [10.5%]). Results: Regarding clinical characteristics, the four groups differed significantly regarding background liver disease (P<0.001), model for end-stage liver disease score (P<0.001), serum protein induced by vitamin K absence or antagonist II level (P=0.003), presence of concurrent hepatocellular carcinoma (HCC; P<0.001), and type of LT (P=0.003). Overall survival (OS) of all LT recipients did not differ significantly among the groups (P=0.377). Donor-to-recipient sex match status did not affect long-term OS in either LDLT (P=0.176) or DDLT (P=0.220) groups. In addition, sex match status did not significantly influence posttransplant OS among patients who underwent LDLT without HCC (P=0.464), LDLT with HCC (P=0.236), DDLT without HCC (P=0.338), or DDLT with HCC (P=0.818). Conclusions Donor-to-recipient sex match status does not significantly affect posttransplant patient survival or HCC prognosis after LDLT or DDLT.

Radiofrequency ablation (RFA) is a minimally invasive treatment modality used as an alternative to surgery in patients with benign thyroid nodules, recurrent thyroid cancers (RTCs), and primary thyroid microcarcinomas. The Korean Society of Thyroid Radiology (KSThR) initially developed recommendations for the optimal use of RFA for thyroid tumors in 2009 and revised them in 2012 and 2017. As new meaningful evidence has accumulated since 2017 and in response to a growing global interest in the use of RFA for treating malignant thyroid lesions, the task force committee members of the KSThR decided to update the guidelines on the use of RFA for the management of RTCs based on a comprehensive analysis of current literature and expert consensus.

Purpose: In this study, we investigated the effect of bisphenol-A (BPA) and its major analogs, bisphenol-F (BPF), and bisphenol-S (BPS), on spermatogonial stem cells (SSCs) populations using in vitro SSC culture and in vivo transplantation models. Materials and Methods: SSCs enriched from 6- to 8-day-old C57BL/6-eGFP+ male mice testes were treated with varying concentrations of bisphenols for 7 days to examine bisphenol-derived cytotoxicity and changes in SSC characteristics. We utilized flow cytometry, immunocytochemistry, real-time quantitative reverse transcription-PCR, and western blot analysis. The functional alteration of SSCs was further investigated by examining donor SSC-derived spermatogenesis evaluation through in vivo transplantation and subsequent testis analysis. Results: BPF exhibited a similar inhibitory effect on SSCs as BPA, demonstrating a significant decrease in SSC survival, inhibition of proliferation, and induction of apoptosis. On the other hand, while BPS was comparatively weaker than BPA and BPF, it still showed significant SSC cytotoxicity. Importantly, SSCs exposed to BPA, BPF, and BPS exhibited a significant reduction in donor SSC-derived germ cell colonies per total number of cultured cells, indicating that, like BPA, BPF, and BPS can induce a comparable reduction in functional SSCs in the recipient animals. However, the progress of spermatogenesis, as evidenced by histochemistry and the expressions of PCNA and SSC specific markers, collectively indicates that BPA, BPF, and BPS may not adversely affect the spermatogenesis. Conclusions Our findings indicate that the major BPA substitutes, BPF and BPS, have significant cytotoxic effects on SSCs, similar to BPA. These effects may lead to a reduction in the functional self-renewal stem cell population and potential impacts on male fertility.

Purpose: In this study, we investigated the effect of bisphenol-A (BPA) and its major analogs, bisphenol-F (BPF), and bisphenol-S (BPS), on spermatogonial stem cells (SSCs) populations using in vitro SSC culture and in vivo transplantation models. Materials and Methods: SSCs enriched from 6- to 8-day-old C57BL/6-eGFP+ male mice testes were treated with varying concentrations of bisphenols for 7 days to examine bisphenol-derived cytotoxicity and changes in SSC characteristics. We utilized flow cytometry, immunocytochemistry, real-time quantitative reverse transcription-PCR, and western blot analysis. The functional alteration of SSCs was further investigated by examining donor SSC-derived spermatogenesis evaluation through in vivo transplantation and subsequent testis analysis. Results: BPF exhibited a similar inhibitory effect on SSCs as BPA, demonstrating a significant decrease in SSC survival, inhibition of proliferation, and induction of apoptosis. On the other hand, while BPS was comparatively weaker than BPA and BPF, it still showed significant SSC cytotoxicity. Importantly, SSCs exposed to BPA, BPF, and BPS exhibited a significant reduction in donor SSC-derived germ cell colonies per total number of cultured cells, indicating that, like BPA, BPF, and BPS can induce a comparable reduction in functional SSCs in the recipient animals. However, the progress of spermatogenesis, as evidenced by histochemistry and the expressions of PCNA and SSC specific markers, collectively indicates that BPA, BPF, and BPS may not adversely affect the spermatogenesis. Conclusions Our findings indicate that the major BPA substitutes, BPF and BPS, have significant cytotoxic effects on SSCs, similar to BPA. These effects may lead to a reduction in the functional self-renewal stem cell population and potential impacts on male fertility.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Purpose: The Korean Cancer Study Group (KCSG) is a nationwide cancer clinical trial group dedicated to advancing investigator-initiated trials (IITs) by conducting and supporting clinical trials. This study aims to review IITs conducted by KCSG and quantitatively evaluate the survival and financial benefits of IITs for patients. Materials and Methods: We reviewed IITs conducted by KCSG from 1998 to 2023, analyzing progression-free survival (PFS) and overall survival (OS) gains for participants. PFS and OS benefits were calculated as the difference in median survival times between the intervention and control groups, multiplied by the number of patients in the intervention group. Financial benefits were assessed based on the cost of investigational products provided. Results: From 1998 to 2023, KCSG conducted 310 IITs, with 133 completed and published. Of these, 21 were included in the survival analysis. The analysis revealed that 1,951 patients in the intervention groups gained a total of 2,558.4 months (213.2 years) of PFS and 2,501.6 months (208.5 years) of OS, with median gains of 1.31 months in PFS and 1.58 months in OS per patient. When analyzing only statistically significant results, PFS and OS gain per patients was 1.69 months and 3.02 months, respectively. Investigational drug cost analysis from six available IITs indicated that investigational products provided to 252 patients were valued at 10,400,077,294 won (approximately 8,046,481 US dollars), averaging about 41,270,148 won (approximately 31,930 US dollars) per patient. Conclusion Our findings, based on analysis of published research, suggest that IITs conducted by KCSG led to survival benefits for participants and, in some studies, may have provided financial benefits by providing investment drugs.

Background: The World Health Organization has declared the end of the coronavirus disease 2019 (COVID-19) public health emergency. However, this did not indicate the end of COVID-19. Several months after the infection, numerous patients complain of respiratory or nonspecific symptoms; this condition is called long COVID. Even patients with mild COVID-19 can experience long COVID, thus the burden of long COVID remains considerable. Therefore, we conducted this study to comprehensively analyze the effects of long COVID using multi-faceted assessments. Materials and Methods: We conducted a prospective cohort study involving patients diagnosed with COVID-19 between February 2020 and September 2021 in six tertiary hospitals in Korea. Patients were followed up at 1, 3, 6, 12, 18, and 24 months after discharge. Long COVID was defined as the persistence of three or more COVID-19-related symptoms. The primary outcome of this study was the prevalence of long COVID after the period of COVID-19. Results: During the study period, 290 patients were enrolled. Among them, 54.5 and 34.6% experienced long COVID within 6 months and after more than 18 months, respectively. Several patients showed abnormal results when tested for post-traumatic stress disorder (17.4%) and anxiety (31.9%) after 18 months. In patients who underwent follow-up chest computed tomography 18 months after COVID-19, abnormal findings remained at 51.9%. Males (odds ratio [OR], 0.17; 95% confidence interval [CI], 0.05–0.53; P=0.004) and elderly (OR, 1.04; 95% CI, 1.00–1.09; P=0.04) showed a significant association with long COVID after 12–18 months in a multivariable logistic regression analysis. Conclusion Many patients still showed long COVID after 18 months post SARS-CoV-2 infection. When managing these patients, the assessment of multiple aspects is necessary.