Purpose: The original eCura system was designed to stratify the risk of lymph node metastasis (LNM) after endoscopic resection (ER) in patients with early gastric cancer (EGC).We assessed the effectiveness of a modified eCura system for reflecting the characteristics of undifferentiated-type (UD)-EGC. Materials and Methods: Six hundred thirty-four patients who underwent non-curative ER for UD-EGC and received either additional surgery (radical surgery group; n=270) or no further treatment (no additional treatment group; n=364) from 18 institutions between 2005 and 2015 were retrospectively included in this study. The eCuraU system assigned 1 point each for tumors >20 mm in size, ulceration, positive vertical margin, and submucosal invasion <500 µm; 2 points for submucosal invasion ≥500 µm; and 3 points for lymphovascular invasion. Results: LNM rates in the radical surgery group were 1.1%, 5.4%, and 13.3% for the low-(0–1 point), intermediate- (2–3 points), and high-risk (4–8 points), respectively (P-fortrend<0.001). The eCuraU system showed a significantly higher probability of identifying patients with LNM as high-risk than the eCura system (66.7% vs. 22.2%; McNemar P<0.001).In the no additional treatment group, overall survival (93.4%, 87.2%, and 67.6% at 5 years) and cancer-specific survival (99.6%, 98.9%, and 92.9% at 5 years) differed significantly among the low-, intermediate-, and high-risk categories, respectively (both P<0.001). In the high-risk category, surgery outperformed no treatment in terms of overall mortality (hazard ratio, 3.26; P=0.015). Conclusions The eCuraU system stratified the risk of LNM in patients with UD-EGC after ER. It is strongly recommended that high-risk patients undergo additional surgery.

Purpose: This study aimed to analyze the treatment outcomes of combined definitive radiation therapy (RT) and androgen deprivation therapy (ADT) for clinically node-positive prostate cancer. Materials and Methods: Medical records of 60 patients with clinically suspected metastatic lymph nodes on radiological examination were retrospectively analyzed. Eight patients (13.3%) were suspected to have metastatic common iliac or para-aortic lymph nodes. All patients underwent definitive RT with a dose fractionation of 70 Gy in 28 fractions. ADT was initiated 2–3 months before RT and continued for at least 2 years. Biochemical failure rate (BFR), clinical failure rate (CFR), overall survival (OS), and prostate cancer-specific survival (PCSS) were calculated, and genitourinary and gastrointestinal adverse events were recorded. Results: The median follow-up period was 5.47 years. The 5-year BFR, CFR, OS, and PCSS rates were 19.1%, 11.3%, 89.0%, and 98.2%, respectively. The median duration of ADT was 2.30 years. BFR and CFR increased after 3 years, and 11 out of 14 biochemical failures occurred after the cessation of ADT. Grade 2 and beyond late genitourinary and gastrointestinal toxicity rates were 5.0% and 13.3%, respectively. However, only two grade 3 adverse events were reported, and no grade 4–5 adverse events were reported. Patients with non-regional lymph node metastases did not have worse BFR, CFR, or adverse event rates. Conclusion This study reported the efficacy and tolerable toxicity of hypofractionated definitive RT combined with ADT for clinically node-positive prostate cancer. Additionally, selected patients with adjacent non-regional lymph node metastases might be able to undergo definitive RT combined with ADT.

Purpose: In patients with epidermal growth factor receptor (EGFR)-mutant non–small cell lung cancer (NSCLC), EGFR tyrosine kinase inhibitors (TKIs) improve response rate and survival. However, most patients eventually develop resistance. This study aimed to identify the role of CD73 in EGFR-mutant NSCLC and explore whether CD73 inhibition may serve as a therapeutic strategy in NSCLC patients with acquired resistance to EGFR-TKIs. Materials and Methods: We evaluated the prognostic role of CD73 expression in EGFR-mutant NSCLC using tumor samples from a single institution. We silenced CD73 in EGFR-TKI–resistant cell lines using short hairpin RNA (shRNA) targeting CD73 and also transfected a vector alone as a negative control. Using these cell lines, cell proliferation and viability assays, immunoblot assays, cell cycle analysis, colony-forming assays, flow cytometry, and apoptosis analysis were performed. Results: High expression of CD73 was associated with shorter survival in patients with metastatic EGFR-mutant NSCLC treated with first-generation EGFR-TKI. CD73 inhibition synergistically inhibited cell viability with first-generation EGFR-TKI treatment compared with the negative control. When CD73 inhibition and EGFR-TKI treatment were combined, G0/G1 cell cycle arrest was induced through the regulation of p21 and cyclin D1. In addition, the apoptosis rate was increased in CD73 shRNA-transfected cells treated with EGFR-TKI. Conclusion High expression of CD73 adversely affects the survival of patients with EGFR-mutant NSCLC. The study demonstrated that inhibiting CD73 in EGFR-TKI–resistant cell lines resulted in increased apoptosis and cell cycle arrest, which overcame the acquired resistance to first-generation EGFR-TKIs. Further research is needed to determine whether blocking CD73 plays a therapeutic role in EGFR-TKI–resistant patients with EGFR-mutant NSCLC.

Purpose: Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare and poorly understood oncogenic mutation in non–small cell lung cancer (NSCLC). We aimed to investigate the acquired resistance mechanism of EGFR-KDD against EGFR-TKIs. Materials and Methods: We identified EGFR-KDD in tumor tissue obtained from a patient with stage IV lung adenocarcinoma and established the patient-derived cell line SNU-4784. We also established several EGFR-KDD Ba/F3 cell lines: EGFR-KDD wild type (EGFR-KDDWT), EGFR-KDD domain 1 T790M (EGFR-KDDD1T), EGFR-KDD domain 2 T790M (EGFR-KDDD2T), and EGFR-KDD both domain T790M (EGFR-KDDBDT). We treated the cells with EGFR tyrosine kinase inhibitors (TKIs) and performed cell viability assays, immunoblot assays, and ENU (N-ethyl-N-nitrosourea) mutagenesis screening. Results: In cell viability assays, SNU-4784 cells and EGFR-KDDWT Ba/F3 cells were sensitive to 2nd generation and 3rd generation EGFR TKIs. In contrast, the T790M-positive EGFR-KDD Ba/F3 cell lines (EGFR-KDDT790M) were only sensitive to 3rd generation EGFR TKIs. In ENU mutagenesis screening, we identified the C797S mutation in kinase domain 2 of EGFR-KDDBDT Ba/F3 cells. Based on this finding, we established an EGFR-KDD domain 1 T790M/domain 2 cis-T790M+C797S (EGFR-KDDT/T+C) Ba/F3 model, which was resistant to EGFR TKIs and anti-EGFR monoclonal antibody combined with EGFR TKIs. Conclusion Our study reveals that the T790M mutation in EGFR-KDD confers resistance to 1st and 2nd generation EGFR TKIs, but is sensitive to 3rd generation EGFR TKIs. In addition, we identified that the C797S mutation in kinase domain 2 of EGFR-KDDT790M mediates a resistance mechanism against 3rd generation EGFR TKIs.

Objective: Comprehensive understanding of polyenvironmental risk factors for the development of psychosis is important. Based on a review of related evidence, we developed the Korea Polyenvironmental Risk Score (K-PERS) for psychosis. We investigated whether the K-PERS can differentiate patients with schizophrenia spectrum disorders (SSDs) from healthy controls (HCs). Methods: We reviewed existing tools for measuring polyenvironmental risk factors for psychosis, including the Maudsley Environmental Risk Score (ERS), polyenviromic risk score (PERS), and Psychosis Polyrisk Score (PPS). Using odds ratios and relative risks for Western studies and the “population proportion” (PP) of risk factors for Korean data, we developed the K-PERS, and compared the scores thereon between patients with SSDs and HCs. In addition, correlation was performed between the K-PERS and Positive and Negative Syndrome Scale (PANSS). Results: We first constructed the “K-PERS-I,” comprising five factors based on the PPS, and then the “K-PERS-II” comprising six factors based on the ERS. The instruments accurately predicted participants’ status (case vs. control). In addition, the K-PERS-I and -II scores exhibited significant negative correlations with the negative symptom factor score of the PANSS. Conclusion The K-PERS is the first comprehensive tool developed based on PP data obtained from Korean studies that measures polyenvironmental risk factors for psychosis. Using pilot data, the K-PERS predicted patient status (SSD vs. HC). Further research is warranted to examine the relationship of K-PERS scores with clinical outcomes of psychosis and schizophrenia.

Objectives: Rasmussen’s aneurysm may cause life-threatening hemoptysis. We investigated the clinical characteristics and outcomes of patients with hemoptysis and Rasmussen’s aneurysm. Methods: We retrospectively investigated patients who clinically presented with hemoptysis and were diagnosed with a Rasmussen’s aneurysm on spiral chest computed tomography (CT). Results: Our study included 16 patients (men:women, 12:4; mean age, 65.25 ± 13.0 years). Massive hemoptysis was observed in nine patients (56%) and blood-tinged sputum in four patients (25%). Ten patients (62.5%) had a history of pulmonary tuberculosis, and three patients (18.7%) had underlying lung cancer. Chest CT revealed coexisting fungal balls in seven patients (43.7%). Bronchial artery embolization (BAE) was performed in 12 patients (75%). One patient died of uncontrolled massive hemoptysis. Conclusions Patients with Rasmussen’s aneurysm showed hemoptysis during the course of the disease; however, bleeding can be controlled with conservative therapy and radiological interventions, such as BAE.

Objective: To compare the convenience and effectiveness of the existing lumbosacral orthoses (LSO) (classic LSO and Cybertech) and a newly developed LSO (V-LSO) by analyzing postoperative data. Methods: This prospective cohort study was performed from May 2019 to November 2019 and enrolled and analyzed 88 patients with degenerative lumbar spine disease scheduled for elective lumbar surgery. Three types of LSO that were provided according to the time of patient registration were applied for 6 weeks. Patients were randomized into the classic LSO group (n=31), Cybertech group (n=26), and V-LSO group (n=31). All patients were assessed using the Oswestry Disability Index (ODI) preoperatively and underwent plain lumbar radiography (anteroposterior and lateral views) 10 days postoperatively. Lumbar lordosis (LS angle) and frontal imbalance were measured with and without LSO. At the sixth postoperative week, a follow-up assessment with the ODI and orthosis questionnaire was conducted. Results: No significant differences were found among the three groups in terms of the LS angle, frontal imbalance, ODI, and orthosis questionnaire results. When the change in the LS angle and frontal imbalance toward the reference value was defined as a positive change with and without LSO, the rate of positive change was significantly different in the V-LSO group (LS angle: 41.94% vs. 61.54% vs. 83.87%; p=0.003). Conclusion The newly developed LSO showed no difference regarding its effectiveness and compliance when compared with the existing LSO, but it was more effective in correcting lumbar lordosis.

Background/Aims: Programmed death-ligand 1 (PD-L1) expression, a validated predictive biomarker for anti-PD-1/PD-L1 inhibitors, is reported to change over time. This poses challenges during clinical application in non-small cell lung cancer. Methods: This study included patients with non-small cell lung cancer who underwent surgery or biopsy and evaluation of PD-L1 expression in tumor cells via immunohistochemistry more than twice. We set the threshold of PD-L1 positivity to 10% and categorized patients into four groups according to changes in PD-L1 expression. Clinicopathologic information was collected from medical records. Statistical analyses, including Fisher’s exact test and log-rank test, were performed. Results: Of 109 patients, 38 (34.9%) and 45 (41.3%) had PD-L1 positivity in archival and recent samples, respectively. PD-L1 status was maintained in 78 (71.6%) patients, but changed in 31 (28.4%), with 19 (17.4%) from negative to positive. There were no significant differences in characteristics between patients who maintained PD-L1 negativity and whose PD-L1 status changed from negative to positive. Patients harboring PD-L1 positivity in either archival or recent samples achieved better responses (p = 0.129) and showed longer overall survival than those who maintained PD-L1 negativity when they received immune checkpoint inhibitors after platinum failure (median overall survival 14.4 months vs. 4.93 months; hazard ratio, 0.43; 95% confidence interval, 0.20 to 0.93). Conclusions PD-L1 status changed in about one-fourth of patients. PD-L1 positivity in either archival or recent samples was predictive of better responses to immune checkpoint inhibitors. Therefore, archival samples could be used for assessment of PD-L1 status. The need for new biopsies should be decided individually.

Background/Aims: Programmed death-ligand 1 (PD-L1) expression, a validated predictive biomarker for anti-PD-1/PD-L1 inhibitors, is reported to change over time. This poses challenges during clinical application in non-small cell lung cancer. Methods: This study included patients with non-small cell lung cancer who underwent surgery or biopsy and evaluation of PD-L1 expression in tumor cells via immunohistochemistry more than twice. We set the threshold of PD-L1 positivity to 10% and categorized patients into four groups according to changes in PD-L1 expression. Clinicopathologic information was collected from medical records. Statistical analyses, including Fisher’s exact test and log-rank test, were performed. Results: Of 109 patients, 38 (34.9%) and 45 (41.3%) had PD-L1 positivity in archival and recent samples, respectively. PD-L1 status was maintained in 78 (71.6%) patients, but changed in 31 (28.4%), with 19 (17.4%) from negative to positive. There were no significant differences in characteristics between patients who maintained PD-L1 negativity and whose PD-L1 status changed from negative to positive. Patients harboring PD-L1 positivity in either archival or recent samples achieved better responses (p = 0.129) and showed longer overall survival than those who maintained PD-L1 negativity when they received immune checkpoint inhibitors after platinum failure (median overall survival 14.4 months vs. 4.93 months; hazard ratio, 0.43; 95% confidence interval, 0.20 to 0.93). Conclusions PD-L1 status changed in about one-fourth of patients. PD-L1 positivity in either archival or recent samples was predictive of better responses to immune checkpoint inhibitors. Therefore, archival samples could be used for assessment of PD-L1 status. The need for new biopsies should be decided individually.