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.Comparison of Surveillance with Low-Dose and Contrast-Enhanced Chest Computed Tomography in Patients Disease-Free for 2 Years after Curative Resection for Lung Cancer
Bubse NA ; Ji Hyeon PARK ; Kwon Joong NA ; Samina PARK ; Chang Hyun KANG ; Young Tae KIM ; In Kyu PARK
Cancer Research and Treatment 2026;58(2):454-464
Purpose:
Low-dose chest computed tomography (LDCT) is recommended for surveillance 2–3 years after curative resection of non-small cell lung cancer (NSCLC); however, supporting clinical evidence is limited. This study compared LDCT with contrast-enhanced chest computed tomography (CECT) in terms of recurrence detection and overall survival (OS) in patients 2 years after curative resection of NSCLC.
Materials and Methods:
Among patients who underwent curative resection for NSCLC between January 2011 and December 2017 and survived for 2 years without recurrence, 2,083 patients were included. Comparisons between the LDCT and CECT groups were performed in both the entire cohort and propensity score-matched cohort. The primary outcome was the difference in overall survival. Secondary outcomes included time-to-recurrence, recurrence-free survival, and post-recurrence survival in each group.
Results:
In the propensity score-matched population, the 5-year OS (96.0% for LDCT, 98.0% for CECT, p=0.097) and recurrence-free survival (RFS) (95.4% for LDCT, 96.0% for CECT, p=0.761) did not differ. The OS and RFS did not differ in subgroup analyses stratified by pathologic stage and histologic type. In the competing risk analysis, the overall 5-year cumulative incidence of recurrence did not differ between the two groups (4.56% for LDCT, 3.93% for CECT, p=0.765). When stratified by pathologic stage and histologic type, there was no significant difference in the cumulative incidence of recurrence. The distribution of recurrence sites did not differ between groups.
Conclusion
Similar OS and RFS were observed in LDCT and CECT surveillance in patients who achieved a 2-year disease-free status after curative resection for NSCLC.
3.Endoscopic Management of Post-Sleeve Gastrectomy Leaks Using Long, Fully Covered Stents
Chan SUNWOO ; Jong Kyu PARK ; Tae Yeong LEE ; Sang Jin LEE
The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2026;26(1):89-94
Gastric leaks after laparoscopic sleeve gastrectomy are serious complications with mortality rates of up to 10%. Conventional self-expanding metal stents exhibit high migration rates (up to 58%), limiting their efficacy. Large, fully covered megastents that reduce migration rates are poorly tolerated and associated with traumatic ulcers and discomfort. We present two cases of successful endoscopic management of persistent gastric leaks following laparoscopic sleeve gastrectomy using long, fully covered Gastro-Seal stents (240 mm) after failed surgical re-exploration. These patients achieved complete fistula closure without stent migration or traumatic ulceration within 26 days and 45 days, respectively. The extended length and round-ended design of the Gastro-Seal stent effectively addressed the key limitations of both conventional and mega-stents. Long, fully covered gastroseal stents may thus be an effective treatment option for managing persistent post-bariatric leaks.
4.Association of Age, Sex and Education With Access to the Intravenous Thrombolysis for Acute Ischemic Stroke
Yoona KO ; Beom Joon KIM ; Youngran KIM ; Jong-Moo PARK ; Kyusik KANG ; Jae Guk KIM ; Jae-Kwan CHA ; Tai Hwan PARK ; Kyungbok LEE ; Jun LEE ; Keun-Sik HONG ; Byung-Chul LEE ; Kyung-Ho YU ; Dong-Eog KIM ; Joon-Tae KIM ; Jay Chol CHOI ; Jee Hyun KWON ; Wook-Joo KIM ; Kyu Sun YUM ; Sung-Il SOHN ; Hyungjong PARK ; Sang-Hwa LEE ; Kwang-Yeol PARK ; Chi Kyung KIM ; Sung Hyuk HEO ; Moon-Ku HAN ; Anjail Z. SHARRIEF ; Sunil A. SHETH ; Hee-Joon BAE ;
Journal of Korean Medical Science 2025;40(13):e49-
Background:
Barriers to treatment with intravenous thrombolysis (IVT) for patients with acute ischemic stroke (AIS) in South Korea remain incompletely characterized. We analyze a nationwide prospective cohort to determine patient-level features associated with delayed presentation and non-treatment of potential IVT-eligible patients.
Methods:
We identified consecutive patients with AIS from 01/2011 to 08/2023 from a multicenter and prospective acute stroke registry in Korea. Patients were defined as IVT candidates if they presented within 4.5 hours from the last known well, had no lab evidence of coagulopathy, and had National Institute of Health Stroke Scale (NIHSS) ≥ 4. Multivariable generalized linear mixed regression models were used to investigate the associations between their characteristics and the IVT candidates or the use of IVT among the candidates.
Results:
Among 84,103 AIS patients, 41.0% were female, with a mean age of 69 ± 13 years and presentation NIHSS of 4 [interquartile range, 1–8]. Out of these patients, 13,757 (16.4%) were eligible for IVT, of whom 8,179 (59.5%) received IVT. Female sex (adjusted risk ratio [RR], 0.90; 95% confidence interval [CI], 0.86–0.94) and lower years of education (adjusted RR, 0.90; 95% CI, 0.84–0.97 for 0–3 years, compared to ≥ 13 years) were associated with a decreased likelihood of presenting as eligible for IVT after AIS; meanwhile, young age (adjusted RR, 1.12; 95% CI, 1.01–1.24 for ≤ 44 years, compared to 75–84 years) was associated with an increased likelihood of being an IVT candidate. Among those who were eligible for IVT, only age was significantly associated with the use of IVT (adjusted RR, 1.09; 95% CI, 1.03–1.16 for age 65–74 and adjusted RR, 0.83; 95% CI, 0.76–0.90 for ≥ 85 years, respectively).
Conclusion
Most patients with AIS present outside IVT eligibility in South Korea, and only 60% of eligible patients were ultimately treated. We identified increased age, female sex and lower education as key features on which to focus interventions for improving IVT utilization.
5.Importance of Preoperative Pupillary Reflex in Traumatic Optic Neuropathy
Journal of Korean Neurosurgical Society 2025;68(1):19-24
Objective:
: Traumatic optic neuropathy (TON) refers to a pathological condition caused by direct or indirect injury to the optic nerves. In the case of patients with traumatic brain injury, adequate vision evaluation is difficult in many cases due to altered mentality. In order to address this problem, we investigated preoperative pupillary light reflex in TON patients as a predictive factor of surgical outcomes after optic nerve decompression.
Methods:
: From April 2020 to September 2022, we enrolled patients who were diagnosed with TON and underwent endoscopic optic nerve decompression at our institution. Vision and pupil reflex tests were performed by an ophthalmologist before and after surgery.
Results:
: Seven patients were enrolled. Their ages ranged from 9 to 78 years and all were male. Among the seven patients, the patient whose pupillary light reflex was sluggish with 6 mm-sized pupil and absent with 7 mm-sized pupil before surgery showed no improvement in vision. Patients with some response to direct reflex or contralateral indirect reflex testing preoperative showed vision improvement after operation.
Conclusion
: Direct and indirect pupillary reflexes can be important factors determining treatment outcome for TON. In unconscious patients with a fracture involving the optic canal, timely surgical intervention based on pupillary reflex can prevent permanent loss of vision.
6.Association of Age, Sex and Education With Access to the Intravenous Thrombolysis for Acute Ischemic Stroke
Yoona KO ; Beom Joon KIM ; Youngran KIM ; Jong-Moo PARK ; Kyusik KANG ; Jae Guk KIM ; Jae-Kwan CHA ; Tai Hwan PARK ; Kyungbok LEE ; Jun LEE ; Keun-Sik HONG ; Byung-Chul LEE ; Kyung-Ho YU ; Dong-Eog KIM ; Joon-Tae KIM ; Jay Chol CHOI ; Jee Hyun KWON ; Wook-Joo KIM ; Kyu Sun YUM ; Sung-Il SOHN ; Hyungjong PARK ; Sang-Hwa LEE ; Kwang-Yeol PARK ; Chi Kyung KIM ; Sung Hyuk HEO ; Moon-Ku HAN ; Anjail Z. SHARRIEF ; Sunil A. SHETH ; Hee-Joon BAE ;
Journal of Korean Medical Science 2025;40(13):e49-
Background:
Barriers to treatment with intravenous thrombolysis (IVT) for patients with acute ischemic stroke (AIS) in South Korea remain incompletely characterized. We analyze a nationwide prospective cohort to determine patient-level features associated with delayed presentation and non-treatment of potential IVT-eligible patients.
Methods:
We identified consecutive patients with AIS from 01/2011 to 08/2023 from a multicenter and prospective acute stroke registry in Korea. Patients were defined as IVT candidates if they presented within 4.5 hours from the last known well, had no lab evidence of coagulopathy, and had National Institute of Health Stroke Scale (NIHSS) ≥ 4. Multivariable generalized linear mixed regression models were used to investigate the associations between their characteristics and the IVT candidates or the use of IVT among the candidates.
Results:
Among 84,103 AIS patients, 41.0% were female, with a mean age of 69 ± 13 years and presentation NIHSS of 4 [interquartile range, 1–8]. Out of these patients, 13,757 (16.4%) were eligible for IVT, of whom 8,179 (59.5%) received IVT. Female sex (adjusted risk ratio [RR], 0.90; 95% confidence interval [CI], 0.86–0.94) and lower years of education (adjusted RR, 0.90; 95% CI, 0.84–0.97 for 0–3 years, compared to ≥ 13 years) were associated with a decreased likelihood of presenting as eligible for IVT after AIS; meanwhile, young age (adjusted RR, 1.12; 95% CI, 1.01–1.24 for ≤ 44 years, compared to 75–84 years) was associated with an increased likelihood of being an IVT candidate. Among those who were eligible for IVT, only age was significantly associated with the use of IVT (adjusted RR, 1.09; 95% CI, 1.03–1.16 for age 65–74 and adjusted RR, 0.83; 95% CI, 0.76–0.90 for ≥ 85 years, respectively).
Conclusion
Most patients with AIS present outside IVT eligibility in South Korea, and only 60% of eligible patients were ultimately treated. We identified increased age, female sex and lower education as key features on which to focus interventions for improving IVT utilization.
7.Importance of Preoperative Pupillary Reflex in Traumatic Optic Neuropathy
Journal of Korean Neurosurgical Society 2025;68(1):19-24
Objective:
: Traumatic optic neuropathy (TON) refers to a pathological condition caused by direct or indirect injury to the optic nerves. In the case of patients with traumatic brain injury, adequate vision evaluation is difficult in many cases due to altered mentality. In order to address this problem, we investigated preoperative pupillary light reflex in TON patients as a predictive factor of surgical outcomes after optic nerve decompression.
Methods:
: From April 2020 to September 2022, we enrolled patients who were diagnosed with TON and underwent endoscopic optic nerve decompression at our institution. Vision and pupil reflex tests were performed by an ophthalmologist before and after surgery.
Results:
: Seven patients were enrolled. Their ages ranged from 9 to 78 years and all were male. Among the seven patients, the patient whose pupillary light reflex was sluggish with 6 mm-sized pupil and absent with 7 mm-sized pupil before surgery showed no improvement in vision. Patients with some response to direct reflex or contralateral indirect reflex testing preoperative showed vision improvement after operation.
Conclusion
: Direct and indirect pupillary reflexes can be important factors determining treatment outcome for TON. In unconscious patients with a fracture involving the optic canal, timely surgical intervention based on pupillary reflex can prevent permanent loss of vision.
8.Does Hip Abduction during Intramedullary Nail Fixation Help Correct Residual Varus Alignment in Subtrochanteric Fractures? A Retrospective Cohort Study
Incheol KOOK ; Young Woon GIL ; Kyu Tae HWANG
Clinics in Orthopedic Surgery 2025;17(2):194-203
Background:
Varus malalignment is a risk factor for nonunion and mechanical complications in subtrochanteric femoral fractures (SFFs). Although various reduction techniques have been reported to avoid varus malalignment in SFFs, achieving anatomic reduction remains challenging, often resulting in residual varus alignment (RVA) after reduction. This study aimed to investigate the radiographic and clinical outcomes of a novel method resolving RVA by abducting the ipsilateral hip after cephalomedullary fixation with an intramedullary nail and subsequently inserting distal interlocking screws.
Methods:
This retrospective study, conducted between March 2016 and March 2022, included patients who underwent hip abduction during intramedullary nailing due to RVA. Demographics and fracture patterns (Arbeitsgemeinschaft für Osteosynthesefragen/Orthopedic Trauma Association [AO/OTA]) and types (typical or atypical) were analyzed. Radiographic outcomes included Baumgaertner reduction quality criteria (BRQC), tip-apex distance (TAD), neck-shaft angle (NSA), lateral cortex residual gap, union, and time to union. Clinical outcomes included ambulatory level using the Palmer-Parker Mobility Score (PPM), complications, and reoperation.
Results:
This study included 45 patients (mean age, 65.8 years; mean follow-up period, 18.4 months). The most common fracture pattern was 32A2 in 15 patients and 29 were typical and 16 were atypical fractures. The BRQC was good in 36 patients, and TAD was < 25 mm in 43 patients. Pre-abduction NSA (126.0° ± 3.8°) was significantly smaller than post-abduction NSA (129.9° ± 3.4°, p < 0.001). Post-abduction NSA was comparable to contralateral NSA of 128.9° ± 2.8° (p = 0.155). Residual gap was significantly reduced from 6.1 ± 2.9 mm pre-abduction to 1.7 ± 1.0 mm post-abduction (p < 0.001). Union was achieved in 44 patients (97.8%;mean duration, 5.9 months). PPM decreased from 7.8 ± 2.0 pre-injury to 7.0 ± 2.1 1-year postoperatively. One nonunion case required reoperation. Radiographic outcomes did not significantly differ by fracture pattern (p = 0.470 for NSA and p = 0.334 for residual gap).
Conclusions
Hip abduction during intramedullary nailing corrects alignment and reduces the gap in SFFs with residual varus alignment. This method can be applied to various fracture patterns in a straightforward manner and considered valuable for managing SFFs.
9.Factors Associated with Postoperative Recurrence in Stage I to IIIA Non–Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation: Analysis of Korean National Population Data
Kyu Yean KIM ; Ho Cheol KIM ; Tae Jung KIM ; Hong Kwan KIM ; Mi Hyung MOON ; Kyongmin Sarah BECK ; Yang Gun SUH ; Chang Hoon SONG ; Jin Seok AHN ; Jeong Eun LEE ; Jae Hyun JEON ; Chi Young JUNG ; Jeong Su CHO ; Yoo Duk CHOI ; Seung Sik HWANG ; Chang Min CHOI ; Seung Hun JANG ; Jeong Uk LIM ;
Cancer Research and Treatment 2025;57(1):83-94
Purpose:
Recent development in perioperative treatment of resectable non–small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection.
Materials and Methods:
Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee.
Results:
A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors.
Conclusion
Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.
10.Does Hip Abduction during Intramedullary Nail Fixation Help Correct Residual Varus Alignment in Subtrochanteric Fractures? A Retrospective Cohort Study
Incheol KOOK ; Young Woon GIL ; Kyu Tae HWANG
Clinics in Orthopedic Surgery 2025;17(2):194-203
Background:
Varus malalignment is a risk factor for nonunion and mechanical complications in subtrochanteric femoral fractures (SFFs). Although various reduction techniques have been reported to avoid varus malalignment in SFFs, achieving anatomic reduction remains challenging, often resulting in residual varus alignment (RVA) after reduction. This study aimed to investigate the radiographic and clinical outcomes of a novel method resolving RVA by abducting the ipsilateral hip after cephalomedullary fixation with an intramedullary nail and subsequently inserting distal interlocking screws.
Methods:
This retrospective study, conducted between March 2016 and March 2022, included patients who underwent hip abduction during intramedullary nailing due to RVA. Demographics and fracture patterns (Arbeitsgemeinschaft für Osteosynthesefragen/Orthopedic Trauma Association [AO/OTA]) and types (typical or atypical) were analyzed. Radiographic outcomes included Baumgaertner reduction quality criteria (BRQC), tip-apex distance (TAD), neck-shaft angle (NSA), lateral cortex residual gap, union, and time to union. Clinical outcomes included ambulatory level using the Palmer-Parker Mobility Score (PPM), complications, and reoperation.
Results:
This study included 45 patients (mean age, 65.8 years; mean follow-up period, 18.4 months). The most common fracture pattern was 32A2 in 15 patients and 29 were typical and 16 were atypical fractures. The BRQC was good in 36 patients, and TAD was < 25 mm in 43 patients. Pre-abduction NSA (126.0° ± 3.8°) was significantly smaller than post-abduction NSA (129.9° ± 3.4°, p < 0.001). Post-abduction NSA was comparable to contralateral NSA of 128.9° ± 2.8° (p = 0.155). Residual gap was significantly reduced from 6.1 ± 2.9 mm pre-abduction to 1.7 ± 1.0 mm post-abduction (p < 0.001). Union was achieved in 44 patients (97.8%;mean duration, 5.9 months). PPM decreased from 7.8 ± 2.0 pre-injury to 7.0 ± 2.1 1-year postoperatively. One nonunion case required reoperation. Radiographic outcomes did not significantly differ by fracture pattern (p = 0.470 for NSA and p = 0.334 for residual gap).
Conclusions
Hip abduction during intramedullary nailing corrects alignment and reduces the gap in SFFs with residual varus alignment. This method can be applied to various fracture patterns in a straightforward manner and considered valuable for managing SFFs.

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