Background/Aims: Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC. Methods: We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data. Results: Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data. Conclusions Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.

Background: The tibiofibular syndesmosis is essential for preserving the stability of the ankle. Acute syndesmotic injuries with evident or latent instability usually warrant surgical interventions. This cadaveric study examines and compares biomechanical characteristics between the following treatments for syndesmosis injuries: suture-button fixation plus syndesmotic repair and screw fixation. Methods: The lower extremities of 10 cadavers disarticulated at the knee joints were used, yielding 20 feet. Ten feet underwent surgery using the suture-button fixation with syndesmotic repair, while the remaining 10 feet underwent surgery using screw fixation. Before surgical treatment of syndesmosis injuries, each cadaveric lower limb underwent preliminary physiological cyclic loading, which was followed by a series of postfixation cyclic loading tests after the surgical procedure. Results: Our principal finding is that suture-button fixation with syndesmotic repair provided torsional strength comparable to that of screw fixation. The mean failure torque did not differ between the 2 groups, but the rotational stiffness was significantly lower in the suture-button fixation/augmentation group. Conclusions Suture-button fixation/augmentation facilitates flexible (physiological) syndesmosis movement and may be a useful alternative treatment for ankle syndesmosis injury.

Background: Sarcopenia, a multifactorial disorder involving metabolic disturbance, suggests potential for metabolite biomarkers. Carnitine (CN), essential for skeletal muscle energy metabolism, may be a candidate biomarker. We investigated whether CN metabolites are biomarkers for sarcopenia. Methods: Associations between the CN metabolites identified from an animal model of sarcopenia and muscle cells and sarcopenia status were evaluated in men from an age-matched discovery (72 cases, 72 controls) and a validation (21 cases, 47 controls) cohort. Results: An association between CN metabolites and sarcopenia showed in mouse and cell studies. In the discovery cohort, plasma C5-CN levels were lower in sarcopenic men (P=0.005). C5-CN levels in men tended to be associated with handgrip strength (HGS) (P=0.098) and were significantly associated with skeletal muscle mass (P=0.003). Each standard deviation increase in C5-CN levels reduced the odds of low muscle mass (odd ratio, 0.61; 95% confidence interval [CI], 0.42 to 0.89). The area under the receiver operating characteristic curve (AUROC) of CN score using a regression equation of C5-CN levels, for sarcopenia was 0.635 (95% CI, 0.544 to 0.726). In the discovery cohort, addition of CN score to HGS significantly improved AUROC from 0.646 (95% CI, 0.575 to 0.717; HGS only) to 0.727 (95% CI, 0.643 to 0.810; P=0.006; HGS+CN score). The improvement was confirmed in the validation cohort (AUROC=0.563; 95% CI, 0.470 to 0.656 for HGS; and AUROC=0.712; 95% CI, 0.569 to 0.855 for HGS+CN score; P=0.027). Conclusion C5-CN, indicative of low muscle mass, is a potential circulating biomarker for sarcopenia in men. Further studies are required to confirm these results and explore sarcopenia-related metabolomic changes.

Background/Aims: Small bowel capsule endoscopy (SBCE) has become the standard for initial evaluation in the diagnosis of small bowel lesions. Although optimal visualization of the mucosa is important, patients experience difficulty in consuming a large volume of bowel preparation agents. This study aimed to compare the efficacy and safety of 1-L polyethylene glycol (PEG) with ascorbic acid (AA) and 2-L PEG with AA. Methods: In this prospective, multicenter, non-inferiority study, patients who received SBCE were randomly assigned to consume 1-L PEG with AA or 2-L PEG with AA for small bowel preparation. The primary outcome was adequate small bowel visibility quality (SBVQ). The secondary outcomes included diagnostic yield, cecal complete rate, and adverse events. Results: One hundred and forty patients were enrolled in this study, 70 patients per group. In the per-protocol analysis, there were no significant differences in the adequate SBVQ rate (94.0% vs 94.3%; risk difference, –0.3; 95% confidence interval, –8.1 to 7.6; p=1.000), diagnostic yield rate (49.3% vs 48.6%, p=0.936), or cecal complete rate (88.1% vs 92.9%, p=0.338) between the 1-L PEG with AA group and 2-L PEG with AA group. The incidence of adverse events did not differ significantly between the groups (12.9% vs 11.9%, p=0.871). Conclusions One liter-PEG with AA is not inferior to 2-L PEG with AA in terms of adequate SBVQ for SBCE. One liter-PEG with AA can be recommended as the standard method for bowel cleansing for SBCE.

Purpose: Breast cancer gene (BRCA) mutation is a well-known risk factor for breast cancer, and clinical interest in prophylactic mastectomy has increased in recent years.We investigated patients who were BRCA mutation carriers and underwent contralateral risk-reducing mastectomy (RRM), focusing on the incidence of occult malignancy after contralateral RRM. Methods: Prospectively collected data of patients with breast cancer treated at a single institution were retrospectively reviewed. Patients who underwent RRM with BRCA mutation who underwent RRM between January 2010 and November 2023 were included in this study.Among patients who underwent contralateral RRM, those with a primary cancer diagnosis were included, and those with occult malignancy on the contralateral RRM side were reviewed additionally. The demographics and pathologies of both primary breast cancer and occult malignancies were evaluated. Results: In our institution, 925 patients were identified as BRCA mutation carriers, and 320 patients underwent contralateral RRM along with primary breast cancer surgery. BRCA2 mutation occurred more frequently (54.8%) in the overall BRCA mutation cohort. Furthermore, we reviewed 320 patients diagnosed with breast cancer and detected as BRCA mutation carriers who underwent contralateral RRM; high proportion of them were BRCA1 mutation carriers.Interestingly, we found a low incidence of only seven patients (2.2%) with occult malignancy on contralateral RRM side, which is different from that reported in other nations. Conclusion The incidence of occult malignancy in the contralateral breast of breast cancer patients with breast cancer with BRCA mutation is significantly low, and may be influenced by several factors. Increased utilization of screening and advancements in diagnostic technologies in South Korea have reduced the chance of occult malignancy in RRM, and a variety of pathologic examination methods may affect the rate of incidence.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Purpose: Since 1995, the Korean Gastric Cancer Association (KGCA) has been periodically conducting nationwide surveys on patients with surgically treated gastric cancer. This study details the results of the survey conducted in 2023. Materials and Methods: The survey was conducted from March to December 2024 using a standardized case report form. Data were collected on 86 items, including patient demographics, tumor characteristics, surgical procedures, and surgical outcomes. The results of the 2023 survey were compared with those of previous surveys. Results: Data from 12,751 cases were collected from 66 institutions. The mean patient age was 64.6 years, and the proportion of patients aged ≥71 years increased from 9.1% in 1995 to 31.7% in 2023. The proportion of upper-third tumors slightly decreased to 16.8% compared to 20.9% in 2019. Early gastric cancer accounted for 63.1% of cases in 2023.Regarding operative procedures, a totally laparoscopic approach was most frequently applied (63.2%) in 2023, while robotic gastrectomy steadily increased to 9.5% from 2.1% in 2014.The most common anastomotic method was the Billroth II procedure (48.8%) after distal gastrectomy and double-tract reconstruction (51.9%) after proximal gastrectomy in 2023.However, the proportion of esophago-gastrostomy with anti-reflux procedures increased to 30.9%. The rates of post-operative mortality and overall complications were 1.0% and 15.3%, respectively. Conclusions The results of the 2023 nationwide survey demonstrate the current status of gastric cancer treatment in Korea. This information will provide a basis for future gastric cancer research.

Gastric cancer is one of the most common cancers in both Korea and worldwide. Since 2004, the Korean Practice Guidelines for Gastric Cancer have been regularly updated, with the 4th edition published in 2022. The 4th edition was the result of a collaborative work by an interdisciplinary team, including experts in gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology, and guideline development methodology. The current guideline is the 5th version, an updated version of the 4th edition. In this guideline, 6 key questions (KQs) were updated or proposed after a collaborative review by the working group, and 7 statements were developed, or revised, or discussed based on a systematic review using the MEDLINE, Embase, Cochrane Library, and KoreaMed database. Over the past 2 years, there have been significant changes in systemic treatment, leading to major updates and revisions focused on this area.Additionally, minor modifications have been made in other sections, incorporating recent research findings. The level of evidence and grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation system. Key factors for recommendation included the level of evidence, benefit, harm, and clinical applicability. The working group reviewed and discussed the recommendations to reach a consensus. The structure of this guideline remains similar to the 2022 version.Earlier sections cover general considerations, such as screening, diagnosis, and staging of endoscopy, pathology, radiology, and nuclear medicine. In the latter sections, statements are provided for each KQ based on clinical evidence, with flowcharts supporting these statements through meta-analysis and references. This multidisciplinary, evidence-based gastric cancer guideline aims to support clinicians in providing optimal care for gastric cancer patients.

Objective: We evaluated the occupational exposure levels of healthcare workers while conducting rotational pressurized intraperitoneal aerosol chemotherapy (RIPAC) using cisplatin in a large animal model. Methods: We performed RIPAC using cisplatin in 6 female pigs and collected surface and air samples during the procedure. Surface samples were obtained from RIPAC devices and personal protective equipment (PPE) by wiping, and air samples were collected around the operating table.All samples were analyzed by inductively coupled plasma–mass spectrometry to detect platinum. Results: Among all surface samples (n=44), platinum was detected in 41 samples (93.2%) but not in all air samples (n=16). Among samples collected from RIPAC devices (n=23), minimum and maximum cisplatin levels of 0.08 and 235.09 ng/cm2 were detected, mainly because of direct aerosol exposure in the abdominal cavity. Among samples collected from healthcare workers’ PPE (n=21), 18 samples (85.7%) showed contamination levels below the detection limit, with a maximum of 0.23 ng/cm2 . There was no significant contamination among samples collected from masks, shoes, or gloves. Conclusion During the RIPAC procedures, there is a potential risk of dermal exposure, as platinum, a surrogate material for cisplatin, was detected at low concentration levels in some surface samples. However, the respiratory exposure risk was not identified, as platinum was not detected in the airborne samples in this study.