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Biomedical subjects

Yuji Toiyama

Publications and source records attributed to Yuji Toiyama.

4 recordsLinked to original sources

Liquid biopsy for early detection of pancreatic ductal adenocarcinoma.

There is no clinically relevant blood-based assay for the detection of early-stage pancreatic ductal adenocarcinoma (PDAC), a solid malignancy characterized by poor outcomes. Here we developed, validated and tested a blood-based microRNA (miRNA) assay (which included hsa-miR-142-3p, hsa-miR-30c-5p, hsa-miR-335-5p, hsa-miR-340-5p, hsa-miR-200b-3p, hsa-miR-1260b, hsa-miR-145-3p, hsa-miR-145-5p, hsa-miR-429 and hsa-miR-200a-3p) and a composite score, PANXEON (PANcreatic cancer eXosome Early detectiON), that integrates the miRNA signature with carbohydrate antigen 19-9 for the detection of early-stage PDAC. We conducted an international, multicenter, observational, prospective biomarker study that involved 1,785 individuals with and without PDAC from four countries. The miRNA signature achieved an area under the receiver operating characteristic curve of 88.6% in the testing cohort, with a sensitivity of 83.8% for early-stage PDAC, while showing minimal cross-reactivity with other gastrointestinal cancers. In a cohort of 19 individuals, the miRNA signature levels decreased during neoadjuvant chemotherapy and after surgery and increased before disease recurrence. When combined with carbohydrate antigen 19-9 levels, this blood assay demonstrated a sensitivity of 86.8% for stage I-II PDAC, false-positive rates of 3.2% in low-risk controls and 15.6% in high-risk controls in the testing cohort. PANXEON demonstrates potential for detecting high-grade dysplasia in individuals with high-risk pancreatic cysts (64.3%). Collectively, we present a composite biomarker that may complement existing strategies for the detection of early-stage PDAC and warrants further large-scale prospective studies. ClinicalTrials.gov registration: NCT06388967 .

Journal Article

Prognostic Significance of Peri-Treatment Inflammatory Burden Index in Patients with Rectal Cancer Undergoing Preoperative Chemoradiotherapy.

Background/Objectives: Systemic inflammatory responses influence treatment response and oncological outcomes in patients with cancer. Growing evidence indicates that the inflammatory burden index (IBI) serves as a reliable prognostic indicator across various malignancies. However, the clinical significance of the peri-treatment inflammatory status in patients with rectal cancer (RC) undergoing preoperative chemoradiotherapy (CRT) remains unclear. Methods: We assessed the pre- and post-treatment IBI in 97 patients with RC who received preoperative CRT followed by total mesorectal excision at our institution. Results: Although no significant changes were observed in the pre- or post-CRT IBI and no associations were found with most clinicopathological factors, survival analysis revealed that a high pre-CRT IBI was significantly associated with shorter overall survival (OS) and disease-free survival (DFS). Multivariable analysis revealed that a high pre-CRT IBI and pathological lymph node metastasis remained independent prognostic factors for both outcomes. Subgroup analysis demonstrated that the prognostic value of the peri-treatment IBI differed according to the ypN status, with the pre-CRT IBI showing particularly strong prognostic performance in patients without pathological lymph node metastasis (ypN-). Conclusions: Pre-treatment assessment of the IBI may improve risk stratification in patients with RC undergoing preoperative CRT followed by curative resection.

chemoradiotherapy

Lymphocyte-C-Reactive Protein Ratio as Promising New Marker for Predicting Surgical Site Infection in Children With Ulcerative Colitis.

BACKGROUND: Surgical site infection (SSI) is a major complication after ileal pouch-anal anastomosis (IPAA) in pediatric ulcerative colitis (UC), significantly impairing quality of life. The lymphocyte-to-C-reactive protein ratio (LCR), a composite marker of systemic inflammation and immune/nutritional status, has emerged as a potential predictor of postoperative outcomes. This study assessed the utility of preoperative LCR in predicting SSI in pediatric UC. METHODS: We retrospectively reviewed pediatric UC patients who underwent IPAA at Mie University Hospital between 2000 and 2024. Preoperative LCR values were analyzed, and the optimal cutoff for SSI prediction was determined using receiver operating characteristic (ROC) analysis. Multivariate logistic regression was performed to identify independent risk factors. SSI was defined according to CDC criteria within 30&#x2009;days postoperatively. RESULTS: Among 57 patients, 11 (19.3%) developed SSI. The incidence was higher in three-stage procedures than in two-stage procedures (22.7% vs. 17.1%). In both groups, preoperative LCR was significantly lower in SSI-positive patients. ROC analysis demonstrated good discrimination (AUC: 0.80), with an optimal cutoff of LCR <&#x2009;5000 (sensitivity: 90.9%, specificity: 71.7%). Multivariate analysis confirmed LCR <&#x2009;5000 as an independent predictor of SSI (odds ratio [OR]: 6.34, 95% CI: 1.23-48.2, p&#x2009;=&#x2009;0.027). CONCLUSION: Preoperative LCR is a simple, objective biomarker that reliably predicts SSI risk in pediatric UC patients undergoing IPAA. Incorporating LCR into preoperative risk stratification may enable personalized interventions, including nutritional optimization and tailored prophylaxis, to improve surgical outcomes.

inflammatory bowel disease

Dynamic Pathology of Enteric Neural Network Using Curcumin-assisted Multiphoton Laser Imaging in Hirschsprung Disease.

BACKGROUND: In living tissue, it has been difficult to make microscopic-level observations without damaging the tissue. We have invented a novel intravital fluorescent observation method (IFOM) for real-time tissue observation, combining multiphoton laser scanning microscopy with curcumin vital staining (CVS-IFOM). The aim of this study was to use CVS-IFOM to analyze the enteric nervous system (ENS) in mice and human patients with hypoganglionosis and Hirschsprung disease (HSCR). METHODS: In an initial viability study, we compared live ENS images from nonfluorescent C57BL6 mice stained with curcumin (n = 5) and green fluorescent protein mice (n = 5) using multiphoton laser scanning microscopy. We then explored CVS-IFOM for the live examination of resected colon tissues from 1 patient with hypoganglionosis and 3 patients with HSCR. RESULTS: In the viability study, detailed ENS histologic features were only observed in the curcumin-stained mice. In the patient with hypoganglionosis, CVS-IFOM provided ENS details that were not visualized under hematoxylin and eosin staining or calretinin immunohistochemistry, allowing the analysis of ENS size, neural bundle number, and neural cell number per plexus. In patients with HSCR, CVS-IFOM showed a gradual hypoplastic change in the ENS from the oral edge to the anal edge, detecting disproportionate changes in the ENS within the same intestinal level, supporting a circumferentially uneven distribution of the intestinal ENS. CONCLUSIONS: CVS-IFOM may be supportive for intraoperative pathologic diagnosis during surgeries for HSCR.

Hirschsprung Disease