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.

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.

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.

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.

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.

Objective: To prospectively evaluate the effect of accelerated deep learning-based reconstruction (Accel-DL) on improving brain magnetic resonance imaging (MRI) quality and reducing scan time compared to that in conventional MRI. Materials and Methods: This study included 150 participants (51 male; mean age 57.3 ± 16.2 years). Each group of 50 participants was scanned using one of three 3T scanners from three different vendors. Conventional and Accel-DL MRI images were obtained from each participant and compared using 2D T1- and T2-weighted and 3D gradient-echo sequences. Accel-DL acquisition was achieved using optimized scan parameters to reduce the scan time, with the acquired images reconstructed using U-Net-based software to transform low-quality, undersampled k-space data into high-quality images. The scan times of Accel-DL and conventional MRI methods were compared. Four neuroradiologists assessed the overall image quality, structural delineation, and artifacts using Likert scale (5- and 3-point scales). Inter-reader agreement was assessed using Fleiss’ kappa coefficient. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated, and volumetric quantification of regional structures and white matter hyperintensities (WMHs) was performed. Results: Accel-DL showed a mean scan time reduction of 39.4% (range, 24.2%–51.3%). Accel-DL improved overall image quality (3.78 ± 0.71 vs. 3.36 ± 0.61, P < 0.001), structure delineation (2.47 ± 0.61 vs. 2.35 ± 0.62, P < 0.001), and artifacts (3.73 ± 0.72 vs. 3.71 ± 0.69, P = 0.016). Inter-reader agreement was fair to substantial (κ = 0.34–0.50). SNR and CNR increased in Accel-DL (82.0 ± 23.1 vs. 31.4 ± 10.8, P = 0.02; 12.4 ± 4.1 vs. 4.4 ± 11.2, P = 0.02). Bland-Altman plots revealed no significant differences in the volumetric measurements of 98.2% of the relevant regions, except in the deep gray matter, including the thalamus. Five of the six lesion categories showed no significant differences in WMH segmentation, except for leukocortical lesions (r = 0.64 ± 0.29). Conclusion Accel-DL substantially reduced the scan time and improved the quality of brain MRI in both spin-echo and gradientecho sequences without compromising volumetry, including lesion quantification.

Background/Aims: As the number of lower gastrointestinal endoscopies and high-risk examinees increases, the incidence of adverse events associated with these endoscopies has also increased. Medical disputes and lawsuits related to adverse events are rapidly increasing. Methods: Medical disputes related to lower gastrointestinal endoscopy that had been filed in Korean Medical Dispute Mediation and Arbitration Agency (K-medi) from April 2012 to August 2020 were evaluated with the corresponding medical records and written appraisal. Facilities, patients, procedures, adverse events, and outcome-related variables related to medical disputes were analyzed. Results: As the number of lower gastrointestinal endoscopies in Korea increases each year, the number of medical disputes related to lower gastrointestinal endoscopy appraised by K-medi has also increased yearly during the same period. Among the 121 cases analyzed, 86 (71.1%) were conciliated and 35 (28.9%) were cosigned by prosecution. Perforations accounted for the largest proportion of cases (93 cases, 76.9%). Most patients (n = 119, 98.3%) underwent non-emergent procedures, and only 10 (8.3%) underwent them for therapeutic purposes. Approximately one-fifth of the patients (n = 25, 20.7%) died. Conclusions The number of medical disputes related to lower gastrointestinal endoscopy are increasing. To prevent this, it is important to review the data on existing cases and establish specific response guidelines.

Renal cell carcinoma (RCC) presents significant clinical challenges, highlighting the importance of understanding its molecular mechanisms. While store-operated Ca2+ entry (SOCE) is known to play an essential role in tumorigenesis and metastasis, its specific implications across various RCC subtypes remain underexplored.This study analyzed SOCE-related mRNA profiles from the KIRC and KIRP projects in The Cancer Genome Atlas (TCGA) database, focusing on differential gene expression and overall survival outcomes. Functional studies in clear cell RCC (Caki-1) and papillary RCC cell lines (pRCC, Caki-2) revealed increased expression of Orai1 and Orai3, along with STIM1, exhibited in both subtypes, with decreased STIM2 and increased Orai2 expression in pRCC. Notably, Orai3 expression had a gender-specific impact on survival, particularly in females with pRCC, where it inversely correlated with STIM2 expression. Functional assays showed Orai3 dominance in Caki-2 and Orai1 in Caki-1. Interestingly, 2-APB inhibited SOCE in Caki-1 but enhanced it in Caki-2, suggesting Orai3 as the primary SOCE channel in pRCC. Knockdown of Orai1 and Orai3 reduced cell migration and proliferation via regulating focal adhesion kinase (FAK) and Cyclin D1 in both cell lines. These findings highlight the critical roles of Orai1 and Orai3 in RCC metastasis, with Orai3 linked to poorer prognosis in females with pRCC. This study offers valuable insights into RCC diagnostics and potential therapeutic strategies targeting ORAI channels and STIM proteins.

Background: Small cell lung cancer (SCLC) is called ‘smoker’s disease’ because it is strongly associated with smoking and most cases occur in smokers. However, it can also occur in never smokers. We investigated the clinical features of never smokers with SCLC and compared their treatment outcomes with those of smokers with SCLC. Methods: We retrospectively reviewed the clinical data of patients who had proven SCLC and had received chemotherapy at a single cancer center between July 2002 and April 2021. Results: Of 1,643 patients, 1,416 (86.2%) were enrolled in this study. A total of 162 (11.4%) and 1,254 (88.6%) patients were never smokers and smokers, respectively. There were more female never smokers than smokers (n=130; 80.2% vs. 79, 6.3%, p=0.000), and the incidence of ischemic heart disease was lower among never smokers than among smokers (4/1,416, [2.5%] vs. 83/1,416 [6.6%], p=0.036). Never smokers showed less symptoms at diagnosis than smokers (80.9% vs. 87.2%, p=0.037); however, they showed more toxicity after first-line treatment (61.7% vs. 47.8%, p=0.001). The objective response rate (ORR) was significantly higher in never smokers (74.1% vs. 59.6%, p=0.000). In the multivariate analysis, never smoking and second-line treatment were associated with a better ORR. However, progression-free survival and overall survival were not significantly different between never smokers and smokers. Conclusion In conclusion, never smokers accounted for 11.4% of patients with SCLC. They had distinguishing clinical characteristics and showed better chemotherapeutic responses than smokers.