Tokyo Metropolitan Komagome Hospital

Bacterial extracellular vesicles (EVs) are emerging mediators of host-microbe communication; however, their role in human disease remains unclear. Here, we identify two bacterial small tRNAs (tsRNAs) enriched in gut commensal Klebsiella pneumoniae-derived EVs (KpEVs) that are markedly elevated in the serum of patients with hepatocellular carcinoma (HCC). These tsRNAs suppress the production of nitric oxide (NO) by macrophages, a critical antitumor molecule. Notably, KpEVs reach the liver more efficiently than bacterial cells, thus facilitating bacterial translocation from the gut by inducing distinctive immunosuppressive macrophages. Mechanistically, KpEVs drive an M2-like macrophage phenotype, enhance phagocytosis, and inhibit both NO production and caspase-1-dependent pyroptosis during infection. The results show that KpEVs shape a liver microenvironment promoting gut-liver bacterial translocation, which may also influence HCC progression. Our study uncovers a previously unrecognized strategy by which K. pneumoniae exploits EVs to modulate host immunity of distant organs, highlighting tsRNAs as potential biomarkers and therapeutic targets.

Metastatic colorectal cancer (mCRC) differs clinically based on RAS and BRAF mutations or DNA methylation. However, in mCRC, the prognostic value and biological characteristics of genome-wide DNA methylation status (GWMS) in each RAS/BRAF genotype is unknown. To clarify this, primary tumor samples from patients with informed consent in the phase III TRICOLORE study were collected, and RAS and BRAF mutations, immunohistochemical staining of mismatch repair-related proteins, comprehensive gene expression, and genome-wide DNA methylation were analyzed. The tumor samples were classified into high-methylated colorectal cancer (HMCC) and low-methylated colorectal cancer (LMCC). Gene set enrichment analysis (GSEA) was conducted using microarray data. A total of 226 patients were included and classified into the RAS/BRAF wild-type (wt) (n = 125), RAS mutant (mt) (n = 87), and BRAF mt (n = 14), of whom 22 (17.6%), 30 (34.5%), and 14 (100%) had HMCC. HMCC exhibited significantly worse overall survival (OS) than that of LMCC in the RAS/BRAF wt group but not in the RAS mt group. In GSEA, RAS/BRAF wt HMCC was associated with microsatellite instability and BRAF V600E mutation. The poor prognosis of RAS/BRAF wt HMCC may be attributed to gene expression patterns associated with microsatellite instability and BRAF V600E mutation.

ABSTRACTConventional endobronchial ultrasound‐guided transbronchial mediastinal cryobiopsy (EBUS‐TBMC) requires simultaneous withdrawal of the EBUS scope and cryoprobe to retrieve the specimen. This process complicates immediate haemostasis and frequently requires cumbersome intubation to ensure procedural safety. As airway haemorrhage can be fatal, a prompt response must always be ensured despite its rare occurrence. We have developed a novel dual‐scope method for EBUS‐TBMC. This technique involves the simultaneous transoral insertion of a thin bronchoscope for haemostasis alongside the EBUS scope for cryobiopsy without intubation. Immediate haemostasis under real‐time visualisation was performed using a thin bronchoscope remaining in the airway after withdrawal of the EBUS scope. This approach eliminates the ‘blind time’ experienced in conventional methods, significantly enhancing overall procedural safety. Herein, we report a case of methotrexate‐associated lymphoproliferative disorder (malignant lymphoma) that was successfully diagnosed using the dual‐scope method.

This study aimed to identify patient groups in which myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) regimens induced superior progression-free survival (PFS) in patients with acute myeloid leukemia (AML) in complete remission (CR) using a machine-learning approach. Our study included 3273 patients aged 40–69 with AML in CR. The patients were divided into training (N = 2020) and validation cohorts (N = 1253). We employed a machine learning-based group identification model in the training cohort. Subsequently, in the validation cohort, we estimated the impact of the optimal conditioning group compared with the non-optimal conditioning group on PFS using an inverse probability weight analysis. The developed model was consistent with the eight factors and combinations, and the high score suggested that RIC was more appropriate than MAC. In the validation cohort, 127 patients with high scores and who received RIC and 769 patients with low scores and who received MAC were categorized into the optimal conditioning group (896, 71.5%). The weighted hazard ratio for PFS was 0.73 (95% confidence interval: 0.57–0.94) in the optimal conditioning group compared with the non-optimal conditioning group (P = 0.016). In conclusion, we developed an easy-to-use model that helps the physician choose a patient-specific conditioning regimen for patients with AML in CR.

Abstract Background: Tumor-infiltrating lymphocytes (TILs) reflect host immune response and are associated with prognosis and treatment response in HER2-positive and triple-negative breast cancer (TNBC). While the International Immuno-Oncology Biomarker Working Group recommends evaluating stromal TILs in tumor areas, intratumoral heterogeneity and small sample size in core needle biopsy (CNB) specimens limit consistent assessment. It remains unclear whether central tumor (CT) or invasive margin (IM) regions should be prioritized and what cut-off values are clinically relevant. Ultrasonographic (US) features may also reflect the immune microenvironment. We previously proposed a TILs-US score based on three US features that predicts lymphocyte-predominant breast cancer (LPBC). This study evaluated the clinical utility of TILs assessment from CT and IM regions, appropriate cut-off values for predicting response in HER2-positive and TNBC using CNB, and explored optimal biopsy targeting through pathologic and US comparisons. Methods: In this multicenter retrospective study, we analyzed 239 patients (124 HER2-positive, 115 TNBC) with cT1-3/cN0-2 breast cancer who underwent surgery after neoadjuvant chemotherapy (NAC). TILs were evaluated using CNB specimens obtained before NAC and assessed separately in the central tumor (CT) and invasive margin (IM) regions. The IM was defined as a 1-mm-wide area centered on the interface between the tumor and surrounding stroma, while the CT was defined as the remaining intratumoral area within the IM boundary. TILs were analyzed using binary cut-offs of 30% and 50%, as well as a three-tier classification: low (0-10%), intermediate (11-49%), and high (≥50%). Pre-treatment ultrasound (US) findings included tumor shape (scored 0-2), internal echo (0-2), and posterior echo (0-3), which were used to calculate a composite TILs-US score ranging from 0 to 7. Associations between TIL levels, US features, and pathological complete response (pCR) were analyzed. Results: Overall, 104 patients achieved pCR (HER2-positive: 39; TNBC: 65). Using a 30% cut-off, TILs were evenly distributed both CT and IM, while ≥50% cases were relatively rare especially CT (CT: 10%; IM: 20%). CT TILs ≥30% was significantly associated with pCR (p=0.001), whereas the ≥50% cut-off was not (p=0.128). In contrast, both 30% and 50% cut-offs in the IM region were predictive of pCR (p<0.001 and p=0.009, respectively). Subtype analysis revealed that in TNBC, TILs ≥30% in both CT and IM regions were significantly correlated with pCR. In HER2-positive cases, however, only IM TILs ≥30% was predictive of pCR. Similar trends were observed with the three-tier classification. Among US features, a small lobulated shape was associated with high TILs levels in both CT and IM regions, while an enhanced posterior echo was correlated with high TILs in the IM region. Conclusion: Our findings suggest that TILs assessment should include the IM in addition to the CT, especially in CNB specimens as provide valuable information. Given the limited tissue area available in CNB specimen, using a 30% cut-off for TILs may offer a clinically meaningful threshold to predict treatment response. In cases where US findings suggest central fibrosis, targeting only the tumor center may result in sampling fibrotic areas with sparse immune and tumor cells, potentially hindering proper evaluation. Therefore, selecting the biopsy target based on US imaging is essential. Especially in HER2-positive breast cancer, as well as TNBC, it is important for operators to consider the optimal needle insertion angle and sampling site to ensure appropriate sampling of viable tumor tissue and immune microenvironment for accurate pathological and immunological evaluation. Citation Format: Y. Kimura, R. Yamaguchi, K. Fukui, A. Kanou, M. Noma, S. Akashi-Tanaka, K. Arihiro, N. Iwamoto, Y. Ohta, T. Okuno, S. Kashiwagi, Y. Kamei, Y. Tanada, S. Nakano, A. Nagata, A. Murakami, Y. Mochitomi, A. Yamakawa, M. Yamaguchi, H. Shima, A. Emi. Ultrasound-guided biopsy-based tils assessment at tumor margins as a predictive biomarker of neoadjuvant treatment response in early her2-positive and triple-negative breast cancer: a multicenter study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-13-18.

Long-term follow-up (LTFU) outpatient clinics play a primary role in screening, preventing, and addressing late effects after hematopoietic cell transplantation (HCT). Following the 2018 nationwide survey, which led to the development of standardized nationwide tools to deliver information to HCT survivors, we re-evaluated changes in the current status of LTFU clinics. We targeted 267 HCT centers certified by the Japanese society for transplantation and cellular therapy. Several questionnaire categories were retained from the 2018 survey to compare results (e.g., LTFU clinic establishment and institutional practices for late-effect screening). The response rate was high in both adult (90%) and pediatric HCT centers (88%), and the establishment rate of post-HCT LTFU clinics increased to 82% (adult, 90%; pediatric, 64%). Pediatric centers were more likely to continue follow-up of patients who received HCT beyond 5 years post-HCT. Regarding transitional medical care for long-term survivors at non-HCT institutions, only a few HCT centers conducted routine transitions to specific referral facilities. We observed significant changes in recommendations for secondary cancer screenings compared to 2018, with a substantial decrease in the proportions of "not routinely included as a screening issue." In the future, it is essential to create a sustainable follow-up system, establish networks with non-HCT facilities, and educate patients to encourage behavioral changes for lifelong health screenings.

Remnant gastric cancer (RGC) is technically difficult for surgery due to adhesion of remnant stomach to surrounding organs. To optimize RGC treatment, it is necessary to clarify the clinical features and prognostic factors of RGC. Therefore, we aimed to clarify the clinical features and prognostic factors of RGC. The patients were selected from the consecutive database of the Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Department of Gastric Surgery, according to the following criteria: (i) histologically-proven gastric adenocarcinoma, (ii) patients who underwent curative gastrectomy for gastric cancer as a primary treatment and archived R0 resection between 2005 and 2025. RGC is defined as GC develops at the remnant stomach after gastrectomy for benign or malignant disease. A total of 2,013 patients were eligible for the present study. In the present study, 45 patients were categorized as the RGC group, and 1,968 patients were in the non-RGC group. When comparing the patient background between RGC group and non-RGC group, significant differences were observed in median age (72 years vs. 69 years, p=0.042), preoperative body mass index (BMI) (21.3 vs. 22.5, p=0.004), and clinical lymph node metastasis (11.1% vs. 29.4%, p=0.007). Three- and five-year OS were 83.4% and 78.5% in RGC group, 85.3% and 81.0% in non-RGC group, respectively. No significant differences were found (p=0.529). In the prognostic analysis of RGC, lymphatic invasion was an independent prognostic factors for OS [hazard ratio (HR)=10.245, 95% confidence interval (CI)=1.150-91.281, p=0.037]. Although there are surgical, perioperative diagnosis, and tumor evaluation difficulties in RGC treatment, the survival of RGC patients was almost similar to non-RGC patients. RGC patients with lymphatic invasion were poorer than those without lymphatic invasion.