1.Predictive Value of Insertion/Deletion Rate in Patients With Gastric Cancer Treated With Nivolumab Plus Chemotherapy
Hyung-Don KIM ; Hyungeun LEE ; Sun Young LEE ; Yuna LEE ; Jaewon HYUNG ; Meesun MOON ; Jinho SHIN ; Young Soo PARK ; Min-Hee RYU
Journal of Gastric Cancer 2026;26(2):219-231
Purpose:
Immune checkpoint inhibitor plus chemotherapy is the standard first-line treatment for advanced gastric cancer; however, predictive biomarkers for optimal patient selection remain unsatisfactory. This study was aimed at evaluating the predictive value of tumor mutational burden (TMB) and insertion/deletion (Indel) rate in patients with gastric cancer treated with nivolumab plus chemotherapy.
Materials and Methods:
This retrospective study included 132 patients with gastric cancer treated with first-line nivolumab plus chemotherapy and 185 patients treated with chemotherapy alone, all of whom had next-generation sequencing data available. The TMB and Indel cut-offs were set at 15.63 mutations per megabase and 18.19%, respectively, as determined based on their ability to best distinguish progression-free survival (PFS) among the patients who received nivolumab plus chemotherapy.
Results:
PFS was favorable for nivolumab and chemotherapy than for chemotherapy alone in both the high and low TMB groups; nevertheless, survival benefits were observed only in the high Indel group. Among the subgroups defined based on both TMB and Indel rates, the high TMB and high Indel rate subgroup showed the greatest benefit from nivolumab plus chemotherapy compared with that from chemotherapy alone. The benefit of this subgroup remained significant in patients with proficient mismatch repair (MMR) tumors, whose survival outcomes were comparable to those of patients with deficient MMR tumors.Among patients treated with nivolumab plus chemotherapy, high TMB and Indel rate were independently associated with favorable survival outcomes.
Conclusions
Thus, Indel rate, particularly in combination with TMB, may be a promising predictive biomarker for gastric cancer. However, further validation of their predictive value is warranted.
2.Molecular and Phenotypic Characterization of Fluid-Derived Patient-Derived Cell and Organoid Models in Advanced Gastric Cancer
Ye Jin MOON ; Woo Sun KWON ; Chan Hee PARK ; Jinsoo JANG ; Juin PARK ; Byeong Gyu YOON ; Han Byeol MUN ; Namju KIM ; Choong-kun LEE ; Hei Cheul JEUNG ; Su-Jin SHIN ; Tae Soo KIM ; Sun Young RHA
Journal of Gastric Cancer 2026;26(2):260-278
Purpose:
Patient-derived cells (PDCs) and patient-derived organoids (PDOs) are complementary preclinical models widely used in translational cancer research. However, their molecular and functional differences have not been systematically characterized. This study established and analyzed paired PDC and PDO models derived from the same gastric cancer ascites to delineate platform-dependent molecular and functional profiles.
Materials and Methods:
Malignant ascites or pleural fluid obtained from 6 patients with advanced gastric cancer were used to establish paired PDC and PDO models. All pairs underwent comprehensive multi-omics profiling, integrating genomic, transcriptomic, and proteomic data. Phenotypic characterization included morphological, histological, proliferative, and cell cycle analyses. Drug sensitivity assays were performed using 4 chemotherapeutic agents commonly used to treat gastric cancer.
Results:
The 6 paired PDC and PDO models exhibited distinct morphological characteristics.Whole-genome analyses demonstrated high concordance among primary tumors, PDCs, and PDOs, confirming tumor representation across platforms. Multi-omics profiling identified platform-dependent molecular signatures; PDOs were enriched for extracellular matrix remodeling and stemness, whereas PDCs displayed proliferation- and immune-related signatures. Clinically relevant biomarkers, including HER2 and MET alterations, were concordant with primary tumors. Notably, drug responses differed between platforms and patients, indicating platform-dependent and patient-specific chemosensitivity.
Conclusions
Paired PDC and PDO models derived from the same patients preserved core patient-specific tumor characteristics while exhibiting distinct molecular and functional profiles. These findings underscore the culture platform as a critical determinant of experimental outcomes and therapeutic responses. Therefore, careful selection of an appropriate preclinical model is essential to accurately address biological questions and optimize precision oncology strategies.
3.Ultrasound Imaging Features Associated With Neoplastic Gallbladder Polyps: A Systematic Review and Meta-Analysis
Sunyoung LEE ; Won CHANG ; Yeun-Yoon KIM ; Jin Young PARK ; Sun Kyung JEON ; Jeong Eun LEE ; Jeongin YOO ; Seungchul HAN ; So Hyun PARK ; Jae Hyun KIM ; Hyo Jung PARK ; Hyun-Soo ZHANG ; Jeong Hee YOON
Korean Journal of Radiology 2026;27(4):332-343
Objective:
Although most gallbladder polyps are benign, some neoplastic polyps may be malignant or may serve as precursors to malignancy. Distinguishing neoplastic and non-neoplastic polyps using imaging examinations remains a major challenge.This meta-analysis aimed to identify the ultrasound (US) features that are significantly associated with neoplastic polyps.
Materials and Methods:
The MEDLINE, EMBASE, Cochrane, and KoreaMed databases were searched for articles published up to August 31, 2025. Bivariate random-effects models were used to calculate the meta-analytic pooled diagnostic odds ratios (DORs), sensitivities, and specificities, along with their 95% confidence intervals (CIs), for each US imaging feature in the diagnosis of neoplastic polyps.
Results:
Thirty studies evaluating 8,953 patients, including 1,216 (13.6%) patients with neoplastic polyps, were included.Among the nine evaluated US imaging features, namely, size ≥10 mm, sessile morphology, single polyp, coexisting gallstones, hypoechogenicity, heterogeneous echogenicity, gallbladder wall thickening (GBWT), absence of hyperechoic spot, and vascularity, eight were significantly associated with neoplastic polyps: size ≥10 mm (DOR: 6.23 [95% CI: 1.86– 20.90]), sessile morphology (DOR: 3.54 [1.93–5.97]), single polyp (DOR: 2.21 [1.76–2.74]), coexisting gallstones (DOR:1.86 [1.29–2.60]), hypoechogenicity (DOR: 3.55 [1.47–7.30]), GBWT (DOR: 9.38 [1.47–32.20]), absence of hyperechoic spots (DOR: 4.23 [2.46–6.83]), and vascularity (DOR: 9.72 [5.81–15.30]). Of these, size ≥10 mm demonstrated the highest pooled sensitivity (0.79 [95% CI: 0.68–0.87]), whereas hypoechogenicity showed the highest pooled specificity (0.93 [95% CI: 0.82–0.98]).
Conclusion
Eight US imaging features (size ≥10 mm, sessile morphology, single polyp, coexisting gallstones, hypoechogenicity, GBWT, absence of hyperechoic spots, and vascularity) were significantly associated with the presence of neoplastic polyps.These features may facilitate the management of gallbladder polyps.
4.Lumbar spinal stenosis: current concept of management
Ji-Won KWON ; Kyung-Soo SUK ; Seong-Hwan MOON ; Si-Young PARK ; Namhoo KIM ; Sub-Ri PARK ; Jae-Won SHIN ; Hak-Sun KIM ; Byung Ho LEE
Asian Spine Journal 2026;20(1):143-157
Lumbar spinal stenosis (LSS) is a common degenerative spinal condition where spinal canal narrowing causes symptoms such as neurogenic claudication, radiculopathy, and lower back pain. While non-operative and surgical approaches yield similar long-term outcomes, surgical intervention—particularly decompression—can provide earlier symptom relief, functional recovery, and fall prevention in selected patients with refractory symptoms. Recent advancements in surgical technologies and image guidance have brought about a paradigm shift in LSS management. Biportal endoscopic spine surgery (BESS) has gained global traction as a minimally invasive alternative to traditional decompression methods, offering superior visualization, less soft tissue damage, shorter hospital stays, and faster recovery. High-quality studies, including randomized controlled trials, have shown promising outcomes for this technique. Furthermore, the integration of navigation systems, robot-assisted instrumentation, and artificial intelligence (AI)-driven diagnostics and surgical planning tools is transforming spinal surgery by enhancing precision in preoperative evaluation and intraoperative execution. These innovations enable accurate targeting, reduce complications, and improve reproducibility across diverse surgical settings. This review provides an updated overview of LSS, covering its pathophysiology, clinical assessment, diagnosis, and treatment. Special emphasis is placed on the growing role of BESS and the transformative impact of digital technologies such as navigation, robotics, and AI in the evolving landscape of spinal stenosis care.
5.Pluviatolide Attenuates Type I Hypersensitivity through Regulation of Mast Cell Activation
Seon Young KIM ; Jeong Won PARK ; Juhyun SHIN ; Ji-Ae LEE ; Sun-Hee LEEM ; Min Geun JO ; Min Yeong CHOI ; Wahn Soo CHOI ; Keun Young MIN ; Geunwoong NOH ; Sung-Jin BAE ; Yung Hyun CHOI ; Hyuk Soon KIM
Biomolecules & Therapeutics 2026;34(2):413-422
This study examined the inhibitory effects of pluviatolide, a lignan derived from Podophyllum hexandrum, on mast cell activation and IgE-mediated type I hypersensitivity, focusing on FcεRI-dependent and calcium-mediated pathways. Using bone marrowderived mast cells (BMMCs) and rat basophilic leukemia (RBL)-2H3 cells, we found that pluviatolide significantly decreased β-hexosaminidase release and suppressed the expression and secretion of TNF-α and IL-6 in a concentration-dependent manner, without causing cytotoxicity. While we initially hypothesized that it would selectively modulate antigen-specific FcεRI signaling, pluviatolide also inhibited degranulation induced by calcium ionophore and thapsigargin, indicating its effects extend to receptorindependent, Ca2+-dependent activation mechanisms. Immunoblot analyses revealed decreased phosphorylation of proximal kinases (Lyn, Syk), adaptor proteins (LAT, PLCγ1), MAPKs (ERK1/2, JNK, p38), and NF-κB p65. In a passive cutaneous anaphylaxis (PCA) mouse model, oral administration of pluviatolide significantly reduced Evans blue extravasation and mast cell degranulation in ear tissues. These findings demonstrate that pluviatolide suppresses both early and late-phase mast cell responses through multi-nodal inhibition of activation pathways, highlighting its potential as a therapeutic candidate for both IgE-mediated and non-IgE-mediated allergic disorders.
6.Combination Therapy with Betulinic Acid and TRAIL Increases ROS-Dependent Cytotoxicity and Inhibits PI3K/Akt Signaling in Human Bladder Cancer Cells
Cheol PARK ; Hee-Jae CHA ; Su Hyun HONG ; Heui-Soo KIM ; Sun-Hee LEEM ; Jung-Hyun SHIM ; Gi-Young KIM ; Kyoung Ah KANG ; Jin Won HYUN ; Yung Hyun CHOI
Biomolecules & Therapeutics 2026;34(3):641-651
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine that selectively targets cancer cells and induces apoptosis. However, many cancers, including bladder cancer, develop resistance to TRAIL, limiting the efficacy of TRAIL-based therapies. This study investigated whether betulinic acid (BA), a pentacyclic triterpenoid with anticancer and chemosensitizing properties, increases TRAIL-mediated apoptosis in TRAIL-resistant human bladder cancer cells. Combination treatment with BA and TRAIL significantly increased cytotoxicity and apoptosis compared to either treatment alone. This combination treatment also increased reactive oxygen species (ROS) production, increased Bax expression and Bid cleavage (tBid formation), and downregulated Bcl-2 levels. These effects were accompanied by caspase activation via extrinsic and intrinsic pathways, leading to cytochrome c release via mitochondrial membrane destabilization, thereby contributing to increased apoptosis. Furthermore, the combination treatment inhibited phosphoinositide 3-kinase (PI3K) and Akt phosphorylation; this effect was amplified by a PI3K inhibitor but abrogated by ROS inhibition. Collectively, our results suggest that BA sensitizes bladder cancer cells to TRAILinduced apoptosis via ROS-dependent activation of the apoptotic pathway and inhibition of PI3K/Akt signaling. Therefore, the BA and TRAIL combination exhibits potential to overcome TRAIL resistance in human bladder cancer.
7.Cervical Spinal Melanocytoma: A Case Report and Literature Review
Chan Joo PARK ; Soo Hyun LEE ; Do Heum YOON ; Seong Bae AN ; Inbo HAN ; Seung Hun SHEEN ; Sun-Yoon CHUNG ; Jinhyung HEO ; Hye Jeong CHOI ; Seil SOHN
The Nerve 2026;12(1):56-60
Spinal melanocytoma (SMC) is a rare, slow-growing tumor arising from melanocytes in the spinal cord. We report a patient with a cervical intra- and extradural spinal tumor causing progressive weakness and numbness. On magnetic resonance imaging (MRI), the lesion showed intense homogeneous enhancement, similar to that seen in common neurogenic spinal tumors. After complete resection, pathological examination confirmed melanocytoma. A review of previously reported cases identified 26 reports of this tumor in the cervical spine, most of which were treated with complete surgical resection. Gross total resection is the preferred treatment, although radiation therapy may be considered when residual tumor remains. We report a 25-year-old male patient who presented with progressive weakness and numbness in both the upper and lower extremities for 3 months. MRI showed homogeneous enhancement. The mass compressed the spinal cord at C6–7 and extended through the neural foramen. Based on the MRI findings, spinal schwannoma was suspected preoperatively. Surgical resection was performed with laminectomy, durotomy, and right facetectomy. A dark-colored mass with well-demarcated margins was exposed and removed. Postoperative MRI confirmed complete removal of the mass. The patient recovered well, and his preoperative myelopathic symptoms gradually improved. SMC is a rare benign tumor that may be mistaken for schwannoma. The treatment of choice is gross total resection.
8.Molecular determinants of outcome to gemcitabine, cisplatin, and nab-paclitaxel in patients with advanced biliary tract cancer
Daeseong KIM ; Nam Suk SIM ; Seonjeong WOO ; Min Hwan KIM ; Choong-kun LEE ; Seung Soo HONG ; Sung Hyun KIM ; Ho Kyoung HWANG ; Chang Moo KANG ; Woo Jung LEE ; Jung Hyun JO ; Taek CHUNG ; Sohyun HWANG ; Beodeul KANG ; Jung Sun KIM ; Chang-Il KWON ; Sangwoo KIM ; Hong Jae CHON ; Chang Gon KIM ; Young Nyun PARK ; Hye Jin CHOI
Clinical and Molecular Hepatology 2026;32(2):721-736
Background/Aims:
Biliary tract cancer (BTC) is a rare malignancy with poor prognosis. We investigated genomic determinants of clinical benefit from gemcitabine, cisplatin, and nab-paclitaxel (GAP) versus gemcitabine and cisplatin (GC) in advanced BTC.
Methods:
Clinical and genomic data using TruSight Oncology 500 were analyzed from patients treated with GAP (N=198) or GC (N=89) as first-line therapy.
Results:
With a median follow-up of 33.0 months, GAP modestly improved progression-free survival (PFS) (hazard ratio [HR] 0.764; 95% confidence interval [CI] 0.591–0.989) without significant overall survival (OS) difference compared to GC. Genomic profiling revealed frequent alterations in TP53 (35.2%), KRAS (16.4%), SMAD4 (10.5%), and TNFRSF14 (10.5%), involving RTK/RAS (44.3%), TP53 (41.8%), and PI3K (20.2%) pathways. Single-gene mutations did not predict treatment benefit. However, pathway-level analysis identified PI3K pathway activation as significantly associated with inferior PFS (HR 2.148; 95% CI 1.478–3.124) and OS (HR 2.096; 95% CI 1.413–3.109) in patients receiving GAP, an effect not observed with GC. Importantly, GAP conferred clinical benefit only in patients without PI3K pathway activation, while no survival advantage was seen in those with such alterations (Pinteraction=0.023 for PFS, Pinteraction=0.003 for OS). Similar results were obtained in the independent validation cohort treated with GAP (N=103) or GC (N=64) for BTC.
Conclusions
Genomic profiling using next-generation sequencing identified PI3K pathway activation as key molecular determinant that differentiates patient outcomes between GAP and GC treatments in advanced BTC.
9.Safety and Effectiveness of Eribulin in Patients with Advanced or Metastatic Breast Cancer Previously Treated with Anthracyclines and Taxanes in Real-World Clinical Practice: A 6-Year Post-marketing Surveillance Study in South Korea
Yee Soo CHAE ; Kyung A KWON ; Moon Hee LEE ; Mi Sun AHN ; Kyung-Hun LEE ; Su-Jin KOH ; Joohyuk SOHN ; Keon Uk PARK ; Min Young KIM ; Youngji PYO ; Bo Young KIM ; Kyung Hae JUNG
Cancer Research and Treatment 2026;58(2):513-524
Purpose:
This 6-year post-marketing surveillance (PMS) study was conducted in South Korea to evaluate the real-world safety and effectiveness of eribulin in patients with advanced or metastatic breast cancer previously treated with anthracyclines and taxanes.
Materials and Methods:
During the study period (17 August 2012 to 16 August 2018), case-report files (CRFs) of patients receiving eribulin were collected. The main study endpoint was to assess the safety of eribulin. Evaluation of the effectiveness of eribulin was an exploratory endpoint. Patients were followed for 1 year after eribulin initiation.
Results:
CRFs were collected from 64 investigators at 64 sites for 1,079 patients. The safety analysis set (SAS) included 1,001 eribulin recipients; effectiveness was assessed in 244 patients. In the SAS, patients were predominantly female (99.6%), with a median age of 53.0 years, and diagnosed with metastatic breast cancer (92.0%). Eribulin was administered as a median 4th line chemotherapy. A total of 2,124 treatment-emergent adverse events (TEAEs) were reported in 661 patients (66.0%). Neutropenia was the most common TEAE (32.5% of patients), occurring at a median of 9-11 days from initial eribulin administration. Overall response and disease control rates were 31.7% and 95.6%, respectively, and the median duration of eribulin use (time to treatment failure) was 3.0 months.
Conclusion
This large real-world PMS analysis in patients with advanced or metastatic breast cancer demonstrated the effectiveness of eribulin and found no new safety concerns relative to safety information from prior clinical and real-world studies, and approvals in South Korea and other countries.
10.Association of Sleep Patterns with the Development of Idiopathic Scoliosis:A Nationwide Pediatric Cohort Study
Weonmin CHO ; Soo-Bin LEE ; Sahyun SUNG ; Ji-Won KWON ; Seong-Hwan MOON ; Kyung-Soo SUK ; Hak-Sun KIM ; Si-Young PARK ; Byung Ho LEE
Clinics in Orthopedic Surgery 2026;18(1):78-86
Background:
The etiology of adolescent idiopathic scoliosis is multifactorial, and the influence of lifestyle factors such as sleep is not clearly understood. Differences in scoliosis incidence between urban and rural areas have been reported, but the contributing factors remain unclear. Therefore, this study investigated the association between sleep patterns and the incidence of idiopathic scoliosis and explored whether these patterns contribute to the observed urban-rural disparity.
Methods:
This retrospective study utilized data from the Korea Children and Youth Panel Survey (2010–2016) and the Health Insurance Review and Assessment Service for 4,693 students (age, 7–18 years). Various lifestyle factors including sleep patterns, learning time, and activity times, were compared between urban and rural areas, and a correlation analysis was performed between these factors and the age-specific incidence of idiopathic scoliosis.
Results:
Urban students, who exhibited higher idiopathic scoliosis incidence rates, tended to have later bedtimes and shorter total sleep durations than rural students. Longer learning hours were also observed in urban areas. Significant correlations were found between idiopathic scoliosis incidence and bedtime (p = 0.031), total sleep time (p = 0.026), and changes in total sleep time (p = 0.011).
Conclusions
Our findings indicate that later bedtimes and shorter sleep durations may contribute to idiopathic scoliosis development in children and adolescents. The higher idiopathic scoliosis incidence in urban students than in rural students could be partially explained by these sleep pattern differences, highlighting the need for further research into the role of sleep in scoliosis onset and prevention.

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