1.WWP2 ubiquitin ligase promotes colorectal cancer progression by targeting p53 for degradation:an experimental study
Seung-Jun LEE ; Han-Gil KIM ; Young-Tae JU ; Young-Sool HAH ; Jeongyun HWANG ; Jihun CHOI ; Jin-Kyu CHO ; Chi-Young JEONG ; Young-Joon LEE ; Ji-Ho PARK ; Ju-Yeon KIM ; Jae-Myung KIM ; Seung-Jin KWAG
Annals of Surgical Treatment and Research 2026;110(5):331-346
Purpose:
Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, necessitating the identification of novel therapeutic targets. The E3 ubiquitin ligase WW domain-containing E3 ubiquitin protein ligase 2 (WWP2) has been implicated in various cancers, yet its specific role and underlying molecular mechanisms in CRC are poorly understood. This study aimed to investigate the functional role of WWP2 in CRC progression and to elucidate its regulatory mechanisms.
Methods:
WWP2 expression was evaluated in CRC patient tissues and cell lines using immunohistochemistry, quantitative real-time polymerase chain reaction, and western blotting. The biological functions of WWP2 were assessed using in vitro assays for cell proliferation, migration, and invasion following adenovirus-mediated overexpression. The molecular mechanism was investigated by analyzing the protein expression levels of p53 and its downstream target, p21, via western blot. An in vivo xenograft mouse model was used to confirm the oncogenic role of WWP2.
Results:
WWP2 expression was significantly upregulated in CRC tissues. Overexpression of WWP2 promoted CRC cell proliferation, migration, and invasion. Mechanistically, increased WWP2 expression led to a marked reduction in the protein levels of the tumor suppressor p53. Consequently, the expression of the p53 downstream target, the cell cycle inhibitor p21, was also suppressed. In the xenograft model, WWP2 overexpression significantly enhanced tumor growth.
Conclusion
Our findings demonstrate that WWP2 functions as an oncogene in CRC. It promotes cancer progression by destabilizing the tumor suppressor p53 and downregulating p21. This study highlights the WWP2-p53-p21 axis as a potential novel therapeutic target for CRC.
2.Guidelines for the Management of Adult Subglottic and Tracheal Stenosis From the Korean Bronchoesophagological Society
Jung-Hae CHO ; Gene HUH ; Jae-Keun CHO ; Jae Won CHANG ; Jun-Ook PARK ; Young Chan LEE ; Jae Hyun JEON ; Jeon Yeob JANG ; Byeong-Ho JEONG ; Yeon Soo KIM ; Inn-Chul NAM ; Gil Joon LEE ; Woo Sik YU ; Heejin KIM ; Minhyung LEE ; Ji Won KIM ; Seung Hoon WOO ; Il-Seok PARK ; Jin Pyeong KIM ;
Clinical and Experimental Otorhinolaryngology 2026;19(1):1-20
Subglottic stenosis (SGS) and tracheal stenosis (TS) are rare conditions that can cause significant breathing difficulties and, if not properly managed, may lead to life-threatening complications. Despite their clinical importance, debate continues regarding the optimal management of adult SGS and TS, and no comprehensive guidelines have been established to date. The Korean Bronchoesophagological Society appointed a task force to develop clinical practice guidelines with the goal of providing evidence-based recommendations for managing SGS and TS in adults. The task force conducted a systematic review of the relevant literature by searching PubMed, Embase, and the Cochrane Library using predefined search terms aligned with key clinical questions. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, which also informed the formulation and reporting of the recommendations. The strength of each recommendation reflects the guideline panel’s confidence that the benefits of an intervention outweigh its risks for eligible patients. After drafting the guidelines, feedback was obtained through Delphi questionnaires completed by members of the Korean Bronchoesophagological Society. Ultimately, the committee developed 17 evidence-based recommendations across four categories: initial evaluation, medical management, surgical treatment, and postoperative management and rehabilitation. These guidelines aim to support clinicians in delivering optimal care to adult patients with SGS and TS.
3.Performance Evaluation of the 2020 European Society of Cardiology 0-hour/1-hour Algorithm Using High-sensitivity Cardiac Troponin I for Non-ST-segment Elevation Acute Coronary Syndrome and Mortality Assessment Based on 1-year Real-world Data
Changhee HA ; Yeon Jae LEE ; Jong Do SEO ; Hanah KIM ; Hee-Won MOON ; Mina HUR ; Young Hwan LEE ; Sang O PARK ; Kyeong Ryong LEE ; Hyun-Joong KIM ; Yeo-Min YUN
Annals of Laboratory Medicine 2026;46(1):52-61
Background:
The 2020 European Society of Cardiology (ESC) 0-hr/1-hr algorithm using high-sensitivity cardiac troponin I (hs-cTnI) for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) aims at early diagnosis and shorter emergency department (ED) stays. While this algorithm has been well-established in controlled studies, real-world implementation remains challenging. We evaluated the algorithm’s clinical performance and risk stratification capability in patients with chest pain or discomfort.
Methods:
We measured hs-cTnI in 4,678 patients suspected of NSTE-ACS between August 2022 and July 2023, using an Atellica IM Analyzer (Siemens Healthineers, Erlangen, Germany). We categorized patients into rule-in, observe, or rule-out groups according to the algorithm and assessed its diagnostic performance for NSTE-ACS. The final diagnosis of NSTE-ACS was adjudicated by two independent physicians. Additionally, we evaluated 30-day all-cause mortality, hazard risk, and ED length of stay across the three groups.
Results:
The algorithm categorized 3,408 (72.9%), 573 (12.2%), and 697 (14.9%) patients into the rule-out, observe, and rule-in groups, respectively. Among 90 patients diagnosed as having NSTE-ACS, none were falsely categorized into the rule-out group. Survival analysis revealed significant differences (P < 0.001), with Cox hazard ratios of 2.38 (95% confidence interval: 1.20–4.71) and 6.39 (3.45–11.86) in the observe and rule-in groups, respectively. ED stays shortened in the order of rule-out, observe, and rule-in groups (P < 0.001).
Conclusions
The 2020 ESC 0-hr/1-hr algorithm demonstrates excellent diagnostic accuracy without false rule-outs and effective risk stratification, and contributes to efficient ED throughput, supporting its clinical utility in real-world emergency settings.
4.Loss of Inspiratory Augmentation as a Predictive Factor for the Development of Gastroesophageal Reflux Disease After Peroral Endoscopic Myotomy in Patients With Achalasia
Min-Jae KIM ; Se Yeon JEON ; Jun Chul PARK ; Young Hoon YOUN ; Hyojin PARK
Journal of Neurogastroenterology and Motility 2026;32(1):129-135
Background/Aims:
Gastroesophageal reflux disease (GERD) after peroral endoscopic myotomy (POEM) is a significant challenge. Disruption of the lower esophageal sphincter during POEM and dysfunction of the crural diaphragm, which contributes to esophagogastric junction pressure, may lead to GERD after POEM. We aim to identify predictors of GERD after POEM and focus on physiological parameters of esophagogastric junction pressure in patients with achalasia before POEM.
Methods:
We retrospectively analyzed a prospectively collected database of patients who underwent POEM between July 2016 and August 2023. Ninety-two patients with achalasia who underwent high-resolution manometry and endoscopy before and after POEM were included.
Results:
Forty-nine (53.3%) patients were diagnosed with GERD. Patient demographics, achalasia subtypes, prior treatments, myotomy length, and myotomy orientation were not associated with GERD after POEM. Loss of inspiratory augmentation before POEM was associated with GERD after POEM (P < 0.05). GERD occurred more frequently in patients with a shorter intra-abdominal lower esophageal sphincter length before POEM. Type III esophagogastric junction morphology in the GERD group (37.1%) was more common than that in the non-GERD group (15.8%). Loss of inspiratory augmentation occurred more frequently in patients with type III esophagogastric junction pressure morphology.
Conclusion
Loss of inspiratory augmentation may predict GERD after POEM.
5.Changes in Esophageal Transit Scintigraphy After Peroral Endoscopic Myotomy in Patients With Achalasia
Young Hoon YOUN ; Kyung Soo KIM ; Yeon Jin JE ; Jae-Hoon LEE ; Young Hoon RYU ; Hyojin PARK
Journal of Neurogastroenterology and Motility 2026;32(1):30-34
Background/Aims:
Esophageal transit scintigraphy is a non-invasive nuclear medicine imaging modality for people with esophageal transit problems. In particular, changes in esophageal motor function can be evaluated non-invasively before and after the treatment in patients undergoing peroral endoscopic myotomy (POEM) for achalasia. This study compared the changes in several parameters of esophageal transit and manometry in patients with achalasia who underwent POEM.
Methods:
This study retrospectively analyzed prospectively collected data from POEM participants. We included 38 patients with achalasia who underwent high-resolution manometry and esophageal transit scintigraphy before POEM and after POEM from 2016 to 2023.
Results:
All patients had clinical treatment successfully (Eckardt score < 3). Lower esophageal sphincter (LES) pressures were significantly reduced after POEM, including basal resting LES pressure and integrated relaxation pressure (P < 0.001).Esophageal emptying, as assessed by the residual fraction of retained radioactivity at 10 seconds after isotope ingestion, improved from 54.3% to 27.3% (P < 0.001). Analysis of the change in time-to-peak on the time-radioactivity curve showed that it shortened significantly in the upper and middle portions of the esophagus (P < 0.05) but not in the lower portion.The Eckardt symptom score significantly correlated with pre-POEM integrated relaxation pressure (P < 0.05). Post-POEM, the symptom score significantly correlated with time-to-peak of the upper portion of the esophagus (P < 0.05).
Conclusions
Patients with achalasia who received POEM showed improved not only manometric LES parameters but also esophageal transit. Analysis of the radiation curve’s time-to-peak showed that improved retention in the upper portion is an indicator of symptoms improvement in patients who underwent POEM.
6.Multicenter evaluation of the PASS score as a negative predictive tool and the impact of inter-observer variability in pheochromocytoma and paraganglioma risk stratification
Sungyeon JUNG ; Hye-Ri SHIN ; Su-Jin SHIN ; Hee Young NA ; Soon-Won HONG ; So Yeon PARK ; Chan Kwon JUNG ; Kyeong Cheon JUNG ; Young Lyun OH ; Jae-Kyung WON
Journal of Pathology and Translational Medicine 2026;60(2):202-213
The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) is widely used for risk stratification in pheochromocytoma and paraganglioma (PPGL), but its clinical utility is limited by inter-observer variability of its parameters and inconsistent predictive performance. Methods: We conducted a multicenter retrospective study of 1,518 patients with PPGL from five tertiary referral centers in Korea. Prognostic utility of PASS system was assessed using logistic regression, Kaplan-Meier analysis, and receiver operating characteristic (ROC) curve analysis. Inter-observer variability was inferred by comparing area under the ROC curve (AUCs) across institutions. Simplified PASS systems were developed based on multivariable analysis of key histopathological parameters. Results: The PASS system was a significant predictor of adverse events and recurrence-free survival. Although the PASS system demonstrated only modest discriminative ability (AUC, 0.673), it showed a high negative predictive value (NPV, 0.885), supporting its usefulness as a screening tool for benign behavior. However, there was significant inter-institutional variability in PASS performance (AUC; range, 0.513 to 0.727; p < .05). The 3-factor Simple PASS, which incorporates necrosis, spindling, and mitotic figures, exhibited less inter-observer variation. The 4-factor Simple PASS, which adds vascular invasion to the 3-factor model, also showed reduced inter-observer variability and improved AUC and NPV compared to the original PASS system. Conclusions: In this multicenter cohort, the PASS system demonstrated high NPV and screening potential, but significant inter-observer variability remains a challenge. Simplification of the PASS system and enhanced pathologist training may improve reproducibility and clinical utility in PPGL risk stratification.
7.HER2-low and ultralow breast cancer: interobserver challenges and lessons from a consensus study
Jiwon KOH ; Yoon Jin CHA ; Eun Yoon CHO ; Ahwon LEE ; Ja Seung KOO ; So Yeon PARK ; Min Hwan KIM ; Jae Ho JEONG ; Gyungyub GONG
Journal of Pathology and Translational Medicine 2026;60(3):331-337
The recent approval of trastuzumab deruxtecan for human epidermal growth factor receptor 2 (HER2)–low and HER2-ultralow breast cancer mandates an adequate assessment of these categories. Methods: Seven breast pathologists from the Breast Pathology Study Group of the Korean Society of Pathologists held an on-site expert consensus meeting. Fifteen sets of virtual whole slide images (WSI) of hematoxylin and eosin stain and HER2 immunohistochemistry were provided. The pathologists were given 60 minutes to submit their diagnosis of HER2 expression into null, ultralow, 1+, 2+, or 3+. Afterwards, in-depth discussion and consensus diagnoses were made by real-time visualization of the WSI. Results: After the consensus meeting, unanimous 100% agreements were seen only in five (33.3%) of the examined cases, which consisted of three 1+ cases and two 2+ cases. Two cases (13.3%) had mild disagreement, with only one pathologist’s disagreement. Of note, eight cases (53.3%) showed significant disagreement, defined by more than two pathologists’ disagreement. All HER2-null cases were reclassified as ultralow after consensus review, suggesting potential widespread underclassification of ultralow cases in clinical practice. Conclusions: Experts had significant discrepancies in interpreting HER2-low/ultralow status. It is important to assess if the distinction between HER2-low and ultralow is strictly required and if HER2-null breast cancer exists in reality.
8.Myopia Management Consensus Statement in South Korean Children 2025 by the Korean Myopia Society for the Korean Association for Pediatric Ophthalmology and Strabismus
Yeon-Hee LEE ; Jae Yun SUNG ; Sun Young SHIN ; Young-Woo SUH ; Ungsoo Samuel KIM ; Hyunkyung KIM ; Kyung-Ah PARK ; Su Jin KIM ; MiRae KIM ; Hyun Jin SHIN ; Kyeong Wook LEE ; Haeng-Jin LEE ; So Young HAN ; Jinu HAN ; Eun Hee HONG ; Seung-Hee Hannah BAEK ; Hae Jung PAIK ;
Korean Journal of Ophthalmology 2026;40(2):185-205
Myopia, particularly high myopia, is a significant risk factor for several ocular pathologies including cataract, glaucoma, and retinal detachment. Excessive axial elongation associated with high myopia can induce biomechanical stretching, increasing the risk of serious complications like posterior staphyloma and myopic maculopathy. Global meta-analyses estimate that approximately 10 million people were visually impaired due to myopic maculopathy in 2015, with 3 million being blind. Recent nationwide surveys in South Korea revealed a prevalence of 65.4% for myopia and 6.9% for high myopia in children and adolescents, highlighting the urgent need for effective management. Delaying the onset and slowing the progression of myopia during childhood and adolescence is crucial for reducing the potential lifetime risk of these complications. This consensus statement, prepared by the Korean Myopia Society for the Korean Association for Pediatric Ophthalmology and Strabismus (KAPOS), reviews the current evidence for myopia control interventions and provides management strategies applicable to the South Korean clinical setting. Key interventions covered include lifestyle modifications (outdoor time, near work adjustment), optical methods (myopia-control spectacle lenses, dual-focus soft contact lenses, orthokeratology), and pharmacologic treatment (low-concentration atropine), as well as combination therapies. The statement also addresses patient selection, treatment outcome evaluation using spherical equivalent and axial length changes, and the crucial aspects related to treatment cessation and the rebound effect.
9.Usability Test of Vocal Hygiene Program Application for Patients With Voice Disorders
Seo Yeon CHO ; Jae Deuk JO ; Chae Rim PARK ; Gil Joon LEE ; Sung Min JIN ; Sang Hyuk LEE
Journal of the Korean Society of Laryngology Phoniatrics and Logopedics 2026;37(1):43-47
Background and Objectives:
Patients with voice disorders often face difficulties in managing their vocal health in daily life, highlighting the need for voice management and hygiene education without temporal or spatial limitations. This study aimed to evaluate the usability of a smartphone-based voice hygiene application developed for patients with voice disorders.Materials and Method Thirty patients diagnosed with voice disorders who underwent voice therapy participated in the study. After using the voice hygiene application for 4 weeks, participants completed a usability questionnaire composed of ten items across five key categories: aesthetics, functionality, engagement, usability, and reliability (two items per category).
Results:
The overall usability score of the voice hygiene application was 3.94 out of 5. The highest ratings were observed in aesthetic design and convenience. Engagement was positively influenced by the app’s reminder feature, and satisfaction regarding information reliability and system functionality was also generally high.
Conclusion
The voice hygiene application was found to be a useful tool for supporting self-management and maintaining vocal hygiene among patients with voice disorders through unrestricted accessibility. This study suggests that such applications can promote consistent voice hygiene practices and contribute to the improvement of vocal health.
10.Clinical Guideline for the Use of Biodegradable Rectal Spacers During Radiotherapy for Prostate Cancer
Hyun Ho HAN ; Jong Kyou KWON ; Do Kyung KIM ; Jin Hyung JEON ; Chan Woo WEE ; Jae Ho CHO ; Ji Hee JUNG ; A Young YOO ; Jae Young JOUNG ; Gee Hyun SONG ; Seung Ju LEE ; Won PARK ; Chan Kyo KIM ; Young Seok KIM ; Yeon Joo KIM ; Ah Ram CHANG ; Jae Sik KIM ; Sung Hwan BAE ; Byoung Kyu HAN ; Kang Su CHO
Journal of Urologic Oncology 2026;24(1):3-12
Purpose:
Radiotherapy (RT) remains a cornerstone of curative treatment for localized and locally advanced prostate cancer. However, dose escalation to improve tumor control is often constrained by the proximity of the rectum, which increases the risk of gastrointestinal (GI) and genitourinary toxicities. Biodegradable rectal spacers inserted between the prostate and rectum have emerged as an effective approach to reduce rectal radiation exposure. This guideline provides evidence-based recommendations on indications, contraindications, procedural standards, and clinical management for biodegradable rectal spacer insertion during prostate cancer RT.
Materials and Methods:
This guideline was developed by a multidisciplinary expert panel through a systematic review of the literature, analysis of international guidelines (National Comprehensive Cancer Network, European Association of Urology, American Society for Radiation Oncology), and expert consensus among radiation oncologists, radiologists, and urologists with clinical experience in spacer insertion. The strength of each recommendation and the level of evidence were classified according to the modified GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system.
Results:
Spacer insertion is conditionally recommended (Grade C, Level I) for patients receiving definitive external-beam RT without rectal invasion. It reduces the high-dose rectal irradiation volume (V70–75) by >50%, decreases acute GI toxicity, and helps maintain bowel-related quality of life. However, the benefit for late severe toxicity (grade 2 or higher) remains debated in recent meta-analyses. Contraindications include rectal invasion, anatomical inaccessibility, infection, and material hypersensitivity. Procedures should be performed under local anesthesia in a sterile environment by trained physicians. Short-course antibiotics and simulator-based training, including completion of multiple supervised cases, are advised.
Conclusion
Biodegradable rectal spacer insertion is clinically validated and effective in reducing acute rectal toxicity. Although pivotal trials demonstrated a favorable procedural safety profile, real-world postmarket data include reports of rare but severe procedural complications. This guideline provides standardized recommendations tailored to Korean clinical practice while remaining consistent with international standards, emphasizing the importance of operator training and careful patient selection.

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