Background: As nationwide government-led whole-genome sequencing (WGS) projects progress, optimizing the clinical integration of large-scale WGS results is crucial. We explored how the initial analysis from Korea’s First WGS Pilot Study for Rare Diseases was applied in clinical practice, and then we reanalyzed the data comprehensively at Samsung Medical Center (SMC) Seoul, Korea. Methods: A prospective cohort study designed to collect WGS data under a Korean national initiative was conducted from August 2020 to December 2021. We focused on patients with rare diseases recruited from 16 university hospitals. The participants included 5,000 individuals (2,200 probands and 2,800 family members). The initial WGS data and diagnostic reference reports (from 682 probands and 484 family members), generated based on the First Korean WGS Pilot Study for Rare Diseases, were subsequently reanalyzed by SMC. Results: The initial analysis of the First Korean WGS Pilot Study data revealed a diagnostic rate of 17%. Upon receiving these results, the SMC conducted two rounds of reanalysis, increasing the diagnostic rate from 15% in the first analysis, to 18% in the second, and finally to 24% in the third (P = 1.6 × 10 −5 ). Key factors in improving the genetic diagnosis included increased detection of novel (likely) pathogenic variants (P = 1.0 × 10 −4 ), improved diagnostic rates with larger family recruitment (P = 0.004), and refined clinical information for more precise genotype–phenotype correlation analysis (40%). Conclusions Although national WGS projects lay a foundation for rare disease diagnosis, hospital-level reanalysis and multidisciplinary collaborations are crucial for optimizing diagnostic outcomes.

Background: Fusion genes are major drivers of acute leukemia. Conventional diagnostics are limited in detecting the diverse fusions included in recently updated acute leukemia classifications. We evaluated the fusion detection performance of RNA sequencing (RNAseq) compared with that of conventional diagnostics in patients with acute leukemia. Methods: We retrospectively obtained the data of 101 patients with acute leukemia who underwent conventional diagnostics (i.e., karyotyping, FISH, or multiplex reverse transcription PCR) at diagnosis at Samsung Medical Center, Seoul, Korea, between September 2022 and September 2023. Whole RNA-seq was performed using the Illumina Stranded mRNA Prep kit (Illumina, San Diego, CA, USA). The concordance, sensitivity, and specificity of RNA-seq for fusion gene detection were compared with those of conventional diagnostics. Results: RNA-seq helped identify 52 fusion genes in 51 (50.5%) of 101 patients, with detection rates of 40.7%, 70.3%, 37.5%, and 50% in acute myeloid leukemia, B-cell acute lymphoblastic leukemia, T-cell acute lymphoblastic leukemia, and mixed-phenotype acute leukemia, respectively. RNA-seq showed 83.3% sensitivity and 80.8% concordance with conventional diagnostics; it missed eight fusions, likely because of low transcript abundance or enhancer hijacking. RNA-seq also helped clarify three previously unspecified rearrangements and detected 12 fusions (21.4%) in 56 cases that tested negative with conventional diagnostics, including four novel (KMT2A::THAP12 , RUNX1::PRPF19 , MLLT10::UBE2L6, and FUS::ZNF362) and three rare (HNRNPH1::ERG, RUNX1::USP42, and ETV6::NCOA2) fusions. Conclusions This was the first study to evaluate the performance of whole RNA-seq in fusion detection in patients with acute leukemia in Korea. Incorporating RNA-seq into diagnostic workflows may facilitate earlier and more precise therapeutic decisions and improve prognostic assessment in patients with acute leukemia.

Objective: Thoracic pedicle screw fixation is technically demanding because of the natural variability in pedicle anatomy, a challenge that is further exacerbated in patients with spinal tumors who often have compromised pedicles. The L-point entry, juxtapedicular, and endplate-parallel trajectory (L-JET) technique was developed to provide a uniform entry point, a predictable screw trajectory, and the capacity to accommodate larger-diameter screws at levels T3–10. This study aimed to evaluate the safety and feasibility of the L-JET technique in comparison with the conventional transpedicular method. Methods: A comparative analysis of consecutively collected data was performed to evaluate outcomes associated with the L-JET technique in patients undergoing surgery for thoracic extradural spinal tumors. The L-point was defined as the intersection of a vertical line along the lateral margin of the facet joint and a horizontal line along the upper edge of the transverse process. The screw trajectory was planned with 30° of medial convergence in the axial plane, creating a juxtapedicular path, and a straightforward trajectory in the sagittal plane. Primary outcome measures included screw diameter, screw length, cortical breach rate, and the need for revision surgery, as assessed using computed tomography scans and medical records. Results: A total of 108 screws were placed in 22 patients using the L-JET technique, while 98 screws were placed in 18 patients using the conventional technique. The L-JET group used significantly larger-diameter screws (6.06±0.65 mm) than the conventional group (5.74±0.80 mm, p=0.02), with no significant difference observed in screw length between groups. Medial cortical breach occurred in one screw in each group, and no supra- or infrapedicular breaches were identified. No screw-related neurovascular complications or revision surgeries occurred in either group. Conclusion The L-JET technique enables consistent screw placement with larger-diameter screws, even in compromised pedicles associated with thoracic spinal tumors, without increasing the risk of complications or the need for revision surgery.

Endoscopic surgery has emerged as a viable treatment option for cervical stenotic myelopathy, offering several advantages over conventional approaches. In multilevel cervical myelopathy, traditional microscopic laminoplasty via the posterior approach requires muscle dissection along the spinous process, which serves as the insertion point for stabilizing muscles, thereby disrupting the posterior tension band. Recently, endoscopic laminoplasty techniques have been explored; however, these often involve detaching the spinous tip from the lamina, compromising the cervical fulcrum. In this report, we introduce a novel surgical technique using a unilateral biportal endoscopy (UBE) system that preserves key cervical structures typically damaged by prior open or endoscopic laminoplasty methods. An 82-year-old man presented with bilateral lower-extremity weakness. Imaging revealed stenosis at C3–4–5 with associated cord signal changes. Maintain anatomy laminoplasty was performed using the UBE system, preserving both the posterior tension band and the spinous process fulcrum. Postoperatively, the modified Japanese Orthopaedic Association and Numeric Rating Scale scores improved. The patient was discharged on postoperative day 4. This new unilateral biportal endoscopic cervical laminoplasty is a safe, effective, and minimally invasive technique that achieves complete decompression in multilevel cervical stenotic myelopathy while maintaining critical anatomical structures.

Objective: To investigate the associations between T2-weighted imaging (T2WI) features and clinicopathologic characteristics in invasive breast cancer, as well as their relationship with treatment response to neoadjuvant chemotherapy (NAC). Materials and Methods: This retrospective study included 179 women with invasive breast cancer who underwent preoperative 3T breast MRI between November 2020 and February 2021. Intratumoral T2 signal intensity (SI) and peritumoral edema were graded on T2WI, and T2 relaxation times were calculated both including and excluding necrotic or cystic areas. T2 relaxation times were compared across T2 SI grades using the Kruskal–Wallis test. Associations between T2 features and clinicopathologic factors were assessed using chi-square tests and logistic regression analyses. In patients who received NAC (n = 68), associations between T2 features and NAC outcomes were also evaluated. Results: Higher intratumoral T2 SI and peritumoral edema grades were significantly associated with longer T2 relaxation times (P < 0.001). Intratumoral T2 SI grades were associated with higher clinical T category, axillary lymph node metastasis, and tumor multiplicity (all P < 0.05). Longer intratumoral T2 relaxation times were associated with higher clinical T category, hormone receptor (HR) negativity, and the triple-negative subtype (all P < 0.05), even after excluding necrotic or cystic areas.Higher peritumoral edema grades were associated with advanced clinical T category, HR negativity, and the triple-negative subtype (all P < 0.05). T2 relaxation times of peritumoral edema showed no significant associations, except with higher clinical T category (P = 0.005) and estrogen receptor status (P = 0.030). In the NAC subgroup, higher intratumoral T2 SI grades and longer T2 relaxation times were significantly associated with disease progression during NAC (P < 0.05), but not with non-pathologic complete response. Peritumoral edema showed no significant association with NAC outcomes (P > 0.05). Conclusion T2-weighted MRI features were associated with clinicopathologic factors, including clinical T category, HR status, triple-negative subtype, and disease progression during NAC.

Purpose: Metabolic bariatric surgery (MBS) efficacy and safety is established for older patients, but East Asian data are limited. This study aimed to evaluate the safety and efficacy of MBS by comparing older (≥55 years) and younger (<55 years) East Asian patients with obesity. Methods: This multicenter, retrospective review included 410 patients undergoing MBS from January to December 2019.Patients were stratified into the older group (OG, age ≥55 years; n = 39) and the younger group (YG, age <55 years; n = 371). We compared surgical safety, weight parameters, and comorbidity resolution rates. Results: The OG had lower mean body weight (97.9 ± 16.4 kg vs. 113.2 ± 23.1 kg, P < 0.001) but more comorbidities and lower average ABCD score for type 2 diabetes mellitus (T2DM) remission. Postoperative complication rate (12.8% vs. 7.5%, P = 0.400) and postoperative hospital stay (4.1 ± 1.8 days vs. 4.0 ± 8.9 days, P = 0.773) showed no significant differences.At 12 months, the percentage of total weight loss was significantly lower in the OG (23.7 ± 6.9% vs. 27.8 ± 8.4%, P = 0.014).Remission rates for T2DM (47.6% vs. 80.5%, P < 0.001), hypertension (34.6% vs. 57.5%, P = 0.073), and dyslipidemia (12.5% vs. 44.4%, P = 0.012) were also lower in the OG, yet still demonstrated clinically meaningful metabolic improvement. Conclusion MBS is a safe and effective treatment for older East Asians with obesity, offering substantial comorbidity resolution despite achieving a lower weight loss compared to the younger patients.

Purpose: Radiotherapy is used to reduce the risk of breast cancer recurrence after surgery, but it is a potential cause of secondary cancer. We validated the risk of secondary cancer in primary breast cancer who received radiotherapy compared with those who did not from a matched cohort using a large-scale observational study of the Observational Health Data Sciences and Informatics (OHDSI) data network. Materials and Methods: A retrospective comparative cohort study using propensity score-matched cohorts was performed using two Observational Medical Outcome Partnership common data model databases, from tertiary general hospitals in South Korea. Among female patients who underwent surgery after the diagnosis of breast cancer, the risk of secondary primary malignant occurrence after 1:1 matching was analyzed. Results: Among 27,078 patients with breast cancer, there was no significant difference in the risk of secondary cancer following radiotherapy in 4,426 patients after 1:1 propensity-score matching. Further, there were no significant differences in the sensitivity analysis according to age, latency period, and number of radiation treatments. Conclusion There was no difference in the risk of secondary cancer in the patients diagnosed with breast cancer depending on whether or not radiotherapy was performed after surgery. In the future, it is necessary to analyze including data generated during cancer treatment.

Purpose: The aim of this study is to compare the detection ability of quality of life (QoL) changes and responsiveness of the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS)-40 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Materials and Methods: A multicenter prospective observational study was conducted to evaluate QoL changes after various gastrectomies between January 2021 and April 2022. Participants were instructed to complete the KOQUSS-40 and EORTC QLQ-C30/STO22 preoperatively and at 1, 3, 6, and 12 months postoperatively. QoL changes over time and QoL responsiveness were assessed for each questionnaire. Results: Data from 491 patients who underwent curative gastrectomy for gastric cancer at 22 institutions were analyzed. The summary scores of the KOQUSS-40 and EORTC QLQ-STO22 showed significant differences between the total and proximal gastrectomy groups (p=0.044 and p=0.038, respectively), but no difference was observed for the EORTC QLQ-C30. Dysphagia on the KOQUSS-40 was significantly different between the total and proximal gastrectomy groups (p=0.031); however, dysphagia on the EORTC QLQ-STO22 did not differ. The responsiveness of the KOQUSS-40 was similar to that of the EORTC QLQ in patients who experienced ≥ 10% body weight loss, but approximately 10% less in patients receiving adjuvant chemotherapy than the EORTC QLQ. Conclusion KOQUSS-40 has several advantages over EORTC QLQ-C30/STO22 when comparing QoL between the total and proximal gastrectomy groups. The findings provide information for researchers investigating the QoL of patients who have undergone curative gastrectomy for gastric cancer.

Purpose: Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer, with approximately 30% of patients eventually developing brain metastases (BM), which result in poor outcomes. An understanding of the tumor microenvironment (TME) at both primary and metastatic sites offers insights into the mechanisms underlying BM and potential therapeutic targets. Materials and Methods: Spatial RNA sequencing (spRNA-seq) was performed on primary TNBC and paired BM tissues from three patients, one of whom had previously received immune checkpoint inhibitors before BM diagnosis. Specimen regions were categorized into tumor, proximal, and distal TME based on their spatial locations. Gene expression differences across these zones were analyzed, and immune cell infiltration was estimated using TIMER. A gene module analysis was conducted to identify key gene clusters associated with BM. Results: Distinct gene expression profiles were noted in the proximal and distal TMEs. In BM, the proximal TME exhibited neuronal gene expression, suggesting neuron-tumor interactions compared to tumor, and upregulation of epithelial genes compared to the distal TME. Immune cell analysis revealed dynamic changes in CD8+ T cells and macrophages across the tumor and TME zones. Gene module analysis identified five key modules, including one related to glycolysis, which correlated with patient survival. Drug repurposing analysis identified potential therapeutic targets, including VEGFA, RAC1, EGLN3, and CAMK1D. Conclusion This study provides novel insights into the transcriptional landscapes in TNBC BM using spRNA-seq, emphasizing the role of neuron-tumor interactions and immune dynamics. These findings suggest new therapeutic strategies and underscore the importance of further research.