KOSÉ (Japan)

Background This study aimed to identify tumor lesion-related factors associated with possible missed gastric cancer (PMGC) during screening endoscopy, with particular focus on cases following Helicobacter pylori (HP) eradication. Methods We analyzed consecutive gastric cancer (GC) cases detected at 11 health check-up institutions in Akita prefecture, Japan. The study focused on 171 GC cases with at least one negative endoscopy within the preceding 2 years. Based on histological assessment, GCs with pT1b or deeper invasion were classified as PMGCs. Their clinical characteristics were compared with those of the remaining pT1a GCs. A backward stepwise logistic regression analysis was performed to identify tumor lesion-related factors associated with PMGC. Results Among 171 GC cases, 39 (22.8%) were classified as PMGC, while the remaining 132 served as controls. Overall, 108 cases (63.2%) occurred in individuals with prior HP eradication, and eradication status was not statistically associated with PMGC. Multivariable regression analysis limited to post-eradication cases revealed that upper third location and undifferentiated histology were significantly associated with PMGC, with odds ratios (95% confidence intervals) of 5.65 (1.88–16.90) and 8.35 (2.22–31.40), respectively. Conclusions Undifferentiated histology and upper third location were associated with missed diagnoses of GC during screening endoscopy in individuals with prior HP eradication. These findings are clinically relevant for improving the quality of endoscopic examinations in health check-up settings, especially given the increasing prevalence of post-eradication GC.

Background:EGFR L858R mutation is associated with poorer efficacy of EGFR-tyrosine kinase inhibitors (TKIs) than EGFR Ex19del in patients with non-small cell lung cancer (NSCLC). However, ramucirumab (RAM) + erlotinib (ERL) therapy exhibited comparable efficacy between patients with L858R mutation and Ex19del mutation (median progression-free survival (PFS): 19.6 vs 19.4 months) in the RELAY study, with favorable PFS for both gene mutations at 19.4 months in the Japanese subset. Meanwhile, the FLAURA study revealed shorter PFS with osimertinib (OSI) for L858R mutation than Ex19del mutation, with poorer PFS in the Japanese subset than in the overall population. The treatment discontinuation rates of RAM + ERL and OSI in Japanese patients were 18% and 29%, respectively. Consequently, RAM + ERL may exhibit superior efficacy and safety in Japanese patients with the L858R mutation.Objectives:To evaluate the therapeutic efficacy and safety of RAM + ERL as a first-line treatment for advanced or recurrent NSCLC harboring the L858R mutation in Japanese patients.Design:A multicenter, noninterventional, retrospective cohort study.Methods and analysis:This study will involve patients with advanced or recurrent NSCLC (ECOG PS score 0–2) with L858R mutation who received RAM + ERL between November 1, 2020 and August 31, 2023, with the planned sample size of 200 patients. The primary endpoint is time to treatment failure, and the secondary endpoints are overall survival, PFS, PFS2, time to discontinuation of any EGFR-TKI, time to failure of strategy, objective response rate, disease control rate, and safety. Exploratory endpoints are effects of ERL and RAM on PD-L1 expression and neutrophil-to-lymphocyte ratio.Discussion:To the best of our knowledge, this is the first retrospective study focusing on L858R mutations associated with the RELAY regimen, providing the corresponding real-world data.Trial registration:UMIN Clinical Trials Registry identifier: UMIN000052047.

BackgroundPeak creatine kinase-MB (CK-MB) level is an established predictor of clinical outcomes following acute myocardial infarction (AMI). However, the significance of the duration between balloon inflation and peak CK-MB level (BP time) after primary percutaneous coronary intervention (PCI) remains underexplored in terms of prognostic impact.ObjectivesThis study aimed to elucidate the relationship between BP time and prognostic outcomes in patients with AMI.MethodsIn this multicenter observational study, 935 AMI patients who underwent primary PCI and achieved TIMI flow grade 3 on final angiography were included. CK-MB levels were measured systematically at admission and at 3-hour intervals post-PCI. Based on a BP time threshold of 553 minutes, patients were categorized into 2 groups: the long BP-time group (n = 183) and the short BP-time group (n = 752).ResultsThe mean age of the patients was 67 years, with a median BP time of 334 minutes (Q1-Q3: 248-491 minutes). The long BP-time group exhibited a higher prevalence of male patients and a history of prior PCI. Cardiovascular mortality was significantly greater in the long BP-time group (log-rank test: P = 0.002). Multivariable Cox regression analysis indicated that a prolonged BP time was independently associated with increased cardiovascular mortality (HR: 2.63; 95% CI: 1.19-5.78).ConclusionsOur findings reveal a significant association between BP time and 1-year cardiovascular mortality in patients with AMI. As a readily assessable parameter, BP time can be a valuable tool for early mortality risk stratification in patients post-primary PCI. (Prognostic Implications of Time between Balloon to Peak Creatinine Kinase-MB in patients with Acute Myocardial Infarction Undergoing Primary PCI: Multicenter Cohort Study; UMIN000049942)

Plasmablastic lymphoma (PBL) is a malignant lymphoma with poor prognosis that occurs in immunocompromised and elderly patients. We describe the case of a 75-year-old woman with PBL as a methotrexate-associated lymphoproliferative disorder (MTX-LPD). She presented with multiple oral ulcers and mass-like shadows in the lung fields. Biopsy of the oral ulcer revealed medium to large irregular round monotypic B cells positive for cluster of differentiation (CD)138, CD79a, immunoglobulin λ, and Epstein-Barr virus-encoded small ribonucleic acid in situ hybridization, and PBL was diagnosed. The patient showed negative results for human immunodeficiency virus and had a history of taking MTX for rheumatoid arthritis, suggesting MTX-LPD. Following discontinuation of MTX, the oral ulcers resolved 1 month later without recurrence, and lung lesions decreased in size over time. Because MTX-LPD can take the form of PBL and may resolve with MTX withdrawal alone, therapeutic interventions should be carefully considered. While PBL is typically highly aggressive and requires prompt treatment, MTX-LPD cases can sometimes resolve without further treatment, depending on the clinical course. However, in cases where the disease shows progression or when spontaneous regression does not occur, additional therapeutic interventions may be necessary to manage the disease effectively.

To develop and validate a prognostic risk model for high-risk metastatic hormone-sensitive prostate cancer (mHSPC) patients treated with upfront abiraterone acetate (ABI). This retrospective multicenter study involved 233 high-risk mHSPC patients who received upfront ABI, developed by three academic centers. The model was externally validated with an independent cohort of 282 patients. To identify independent prognostic factors for second progression-free survival (PFS2) and develop the best-fitted model, Cox proportional hazards regression, followed by the Akaike information criterion, was used. Patients were categorized into three groups based on their risk scores. PFS2 and overall survival (OS) were evaluated according to the risk groups in the discovery and validation cohorts. The median age was 72 (range 51-89) years, with a median follow-up duration of 27 months. Independent factors linked to PFS2 included an Eastern Cooperative Oncology Group performance status ≥2, a primary Gleason score of 5, an extent of disease score of ≥3 or liver metastasis, and lactate dehydrogenase >220 U/L. Median PFS2 for favorable-, intermediate-, and poor-risk groups were not reached, 43 months, and 16 months, respectively. The median OS was 29 months in the poor-risk group, whereas it was not reached in the favorable- and intermediate-risk groups. The 2-year OS rates in the favorable-, intermediate- and poor-risk groups were 94.5%, 80.1%, and 60.3%, respectively. The validation cohort confirmed the risk model's relationship with PFS2 and OS. The median PFS2 and OS in the high-risk group were 21 months and 32 months, respectively. Our prognostic model, including five clinical factors, is useful for patient care and treatment selection in high-risk mHSPC patients treated with ADT plus ABI. The developed model could provide more accurate information, guide treatment decisions, or classify patients in future clinical trials.

Peripheral pulmonary stenosis (PPS) is a condition characterized by the narrowing of the pulmonary arteries, which impairs blood flow to the lung. The mechanisms underlying PPS pathogenesis remain unclear. Thus, the aim of this study was to investigate the genetic background of patients with severe PPS to elucidate the pathogenesis of this condition. We performed genetic testing and functional analyses on a pediatric patient with PPS and Williams syndrome (WS), followed by genetic testing on 12 patients with WS and mild-to-severe PPS, 50 patients with WS but not PPS, and 21 patients with severe PPS but not WS. Whole-exome sequencing identified a rare PTGIS nonsense variant (p.E314X) in a patient with WS and severe PPS. Prostaglandin I2 synthase (PTGIS) expression was significantly downregulated and cell proliferation and migration rates were significantly increased in cells transfected with the PTGIS p.E314X variant-encoding construct when compared with that in cells transfected with the wild-type PTGIS-encoding construct. p.E314X reduced the tube formation ability in human pulmonary artery endothelial cells and caspase 3/7 activity in both human pulmonary artery endothelial cells and human pulmonary artery smooth muscle cells. Compared with healthy controls, patients with PPS exhibited downregulated pulmonary artery endothelial prostaglandin I2 synthase levels and urinary prostaglandin I metabolite levels. We identified another PTGIS rare splice-site variant (c.1358+2T>C) in another pediatric patient with WS and severe PPS. In total, 2 rare nonsense/splice-site PTGIS variants were identified in 2 pediatric patients with WS and severe PPS. PTGIS variants may be involved in PPS pathogenesis, and PTGIS represents an effective therapeutic target.

Abstract ObjectiveThis study aimed to describe the usefulness of our teleconsultation system for managing multiple sclerosis (MS) in regions without specialists.MethodsA cross‐sectional questionnaire survey involving 11 MS patients and their primary neurologists was carried out between May and December 2023. Real‐time video conferences were conducted between an MS specialist at a hub hospital and patients with their primary neurologists at one of the four regional core hospitals in Hokkaido, Japan. Patients and their primary neurologists completed questionnaires to evaluate the usefulness of the teleconsultation system.ResultsThe patients and their primary neurologists were generally satisfied with the teleconsultations and expressed willingness to continue using the system. In particular, alleviating the burden of visiting distant MS‐specialized clinics was highly appreciated by patients. In addition, patients gave high scores for questions regarding increased satisfaction with the primary neurologists' care and the treatments they offered. The primary neurologists thought the system enhanced their knowledge of MS management. However, they did not think that the system could ease their burden for managing MS patients because of challenges in time allocation and scheduling for teleconsultation sessions.ConclusionsThe present study suggested that our expert teleconsultation system for MS reduces the burden on patients of visiting distant MS‐specialized clinics, and enhances knowledge of MS management for the primary neurologists. It also promotes trust between patients and their primary neurologists, and taken together, these aspects could collectively lead to independent and sustainable MS management in regions without MS specialists.