Ehime University Hospital

Chemotherapy-induced nausea and vomiting (CINV) remain major challenges during concurrent chemoradiotherapy (CCRT) for cervical cancer. Mannitol and furosemide are agents widely used to prevent cisplatin-induced nephrotoxicity; however, the differences in their effect on CINV have not been characterized. This study aimed to evaluate the impact of concomitant diuretic administration (mannitol versus furosemide) on the incidence and timing of vomiting in patients with cervical cancer undergoing CCRT. This multicenter, retrospective study evaluated the impact of concomitant diuretic administration on CINV in 485 patients receiving weekly, cisplatin-based CCRT between 2016 and 2024, including 206 who received mannitol and 279 who received furosemide. Vomiting occurred more frequently in the mannitol group than in the furosemide group (18.4% vs. 10.4%). Time-to-event analysis found that vomiting occurred earlier with mannitol during the entire CCRT course. These findings may reflect mannitol's osmotic properties and the increased, intestinal permeability associated with CCRT-related mucosal injury. To the best of our knowledge, this study is the largest investigation to date comparing diuretic agents in this setting. The results suggested that furosemide may be a more appropriate option for patients with a high risk of CINV.

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.

Myelofibrosis (MF) is a myeloproliferative neoplasm frequently complicated by splenomegaly, with vascular abnormalities, such as splenic artery aneurysm (SAA), rarely reported. We herein report a 74-year-old woman with secondary MF harboring a JAK2 V617F mutation who developed SAA requiring intervention because of its potential risk of rupture. Ruxolitinib therapy markedly reduced splenomegaly and improved constitutional symptoms, thereby optimizing hemodynamic conditions and overall status for safe spleen-preserving coil embolization. This case highlights the potential relationship between MF and aneurysm formation while demonstrating that concomitant JAK inhibitor therapy may facilitate safe endovascular treatment in select patients.

Abstract Background A fully automated echocardiographic analysis system utilizing artificial intelligence was provided. It enables to generate diagnostic reports based on guidelines through zero-click measurements. While the system is expected to shorten examination time, the accuracy of both measurements and diagnoses remains to be verified. In particular, left ventricular wall thickness and the four classifications of left ventricular hypertrophy (normal, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy) are prone to variation in real-world clinical practice. In this study, we aimed to investigate the diagnostic accuracy of the four classifications of left ventricular hypertrophy by automated measurement using this system. Methods A total of 100 patients with hypertension, observed during echocardiographic examination, were included to the study. The average measurements by a total of eight experts from four centers were used as the gold standard, and the same left ventricular long-axis cross-sectional moving images were compared for agreement between the fully automated measurements and the four classifications of left ventricular hypertrophy. For expert measurements of left ventricular wall thickness, after learning in a preliminary meeting using guidelines published by the Association for Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACVI), experts at each institution paired up and performed measurements engaging in discussion. For statistical analysis, we used the Student's t-test to compare continuous variables and the weighted kappa coefficients to assess diagnostic agreement. Results The fully automated echocardiographic analysis system was able to measure 89 of 100 cases. Automatic measurements of ventricular septal wall thickness and left ventricular posterior wall thickness were significantly higher than the average of four-center (10.7±2.2mm vs. 9.1±1.8mm, p< 0.05, and 10.1±2.3 mm vs. 8.9±1.7mm, p< 0.05, respectively). The weighted kappa coefficient for the four categories of left ventricular hypertrophy was 0.84. Analysis of the agreement rate by classification revealed that concentric hypertrophy showed the highest agreement rate (89.3%), followed by concentric remodeling (88.9%). In contrast, eccentric hypertrophy (40.5%) and normal (26.7%) showed lower concordance rates (Figure). Conclusions Although the fully automated echocardiographic analysis system tended to overestimate wall thickness, the agreement rate for left ventricular hypertrophy classification was high.

Introduction: The prognosis of patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer has improved with the introduction of oral EGFR-tyrosine kinase inhibitor (TKI). Lower adherence to oral anticancer medications is reportedly associated with a poor prognosis. It is important to understand the causes of lower adherence to oral anticancer medications. We aimed to assess the potential risk factors associated with low adherence to EGFR-TKIs in a real-world clinical setting using administrative claims data in Japan. Methods: We identified 10,809 outpatients routinely prescribed EGFR-TKIs between December 2015 and January 2023. Adherence to EGFR-TKIs was assessed based on the medication possession ratio (MPR) during the 12-month follow-up period from the date of first outpatient EGFR-TKI prescription. Multivariable linear regression analysis was performed to identify the potential risk factors associated with lower adherence. Results: The mean (standard deviation) MPR was 94.1% (14.0). Lower adherence was associated with increasing age (per 10-year increase), female sex, dysphagia, and a higher number of concomitant oral medications (per doubling of the count). Conclusion: Adherence to EGFR-TKIs was generally high, but the findings support tailored adherence strategies, especially for older patients and for those with a higher number of concomitant oral medications, including medication review to reduce pill burden and proactive support for swallowing difficulties.

AimChildren and adolescents get fewer than the recommended hours of sleep. The Child and Adolescent Sleep Checklist for parents (CASC-P) was designed to identify sleep habits and screen for sleep problems in junior high school students in Japan. This study aimed to validate the Japanese version of the CASC-P for junior high school students and determine its internal consistency.MethodsWe used confirmatory factor analysis (CFA) and Cronbach's α to validate the scale and examine reliability. The analysis involved 218 parents of students aged 12–15 years.ResultsCronbach's α for the overall scale was 0.771. The prevalence of sleep problems was 15.6%. Factorial construct validity was assessed using the four-factor model used in the original CASC-P. Almost all items loaded meaningfully on their designated factors, and standardized factor-loading values ranged from 0.278 to 0.878 (except for items 1, 2, 9, 16, and 21).Conclusion: The CASC-P is a suitable questionnaire for assessing parents’ perspectives on adolescent sleep behavior.

Abstract Introduction and Objective: Intraductal carcinoma of the prostate (IDC-P) is a form of prostate cancer where abnormal cells grow inside the ducts and glands, while the outer basal cell layer stays intact. IDC-P is often linked to certain genetic changes, including TMPRSS2-ERG fusions, as well as mutations or deletions in key genes like TP53, RB1, and PTEN. Given these findings, NCCN guidelines advise early genetic testing for IDC-P patients. Correctly diagnosing IDC-P and applying this knowledge to tailor treatments is essential for improving patient outcomes. Methods: We performed spatial gene expression analysis (using CytAssist Visium) on prostate cancer tissue samples with IDC-P. The goal was to identify gene abnormalities that could help in diagnosing IDC-P or serve as targets for future treatments. We analyzed how gene expression was distributed in IDC-P regions compared to other parts of prostate cancer tissue. Results: Our analysis showed that IDC-P regions had a unique gene expression profile, distinct from other prostate cancer areas. Specific genes such as MUC6, MYO16, NPY, and KLK12 were highly expressed in IDC-P, and these genes are associated with more aggressive cancer behavior. Additionally, genes related to hypoxia like HIF1A, BNIP3L, PDK1, and POGLUT1 were highly upregulated in IDC-P areas. At the same time, markers for immune cells (CCR5, FCGR3A) and fibroblasts (CCL5, TRAC) were downregulated. This suggests that IDC-P may be more aggressive due to hypoxia and fewer immune and fibroblast cells in the tumor environment. Conclusions: This study used spatial gene expression analysis to characterize IDC-P (Watanabe et al., IJMS 2024), providing valuable insights. However, this method also has some challenges, such as capturing signals from different cell types in the same spots, which makes it harder to distinguish between them. In future studies, combining spatial gene analysis with single-cell RNA sequencing or using more advanced techniques like Xenium could address these challenges. We are currently working on those studies and will be able to present the latest data on the day of the presentation. These approaches may help identify new diagnostic markers and lead to more personalized treatment options for patients with IDC-P. Citation Format: Ryuta Watanabe, Haruna Arai, Mie Kurata, Noriyoshi Miura, Riko Kitazawa, Tadahiko Kikugawa, Takashi Saika. Identifying gene expression patterns in intraductal carcinoma of the prostate using spatial gene expression analysis: Potential for new biomarkers and treatments [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 776.