Takayuki Matsumoto’s research while affiliated with Iwate Medical University and other places

Background Lugol chromoendoscopy has been shown to increase the sensitivity of detection of esophageal squamous cell carcinoma (ESCC). We aimed to develop a deep learning–based virtual lugol chromoendoscopy (V‐LCE) method. Methods We developed still V‐LCE images for superficial ESCC using a cycle‐consistent generative adversarial network (CycleGAN). Six endoscopists graded the detection and margins of ESCCs using white‐light endoscopy (WLE), real lugol chromoendoscopy (R‐LCE), and V‐LCE on a five‐point scale ranging from 1 (poor) to 5 (excellent). We also calculated and compared the color differences between cancerous and non‐cancerous areas using WLE, R‐LCE, and V‐LCE. Results Scores for the detection and margins were significantly higher with R‐LCE than V‐LCE (detection, 4.7 vs. 3.8, respectively; p < 0.001; margins, 4.3 vs. 3.0, respectively; p < 0.001). There were nonsignificant trends towards higher scores with V‐LCE than WLE (detection, 3.8 vs. 3.3, respectively; p = 0.089; margins, 3.0 vs. 2.7, respectively; p = 0.130). Color differences were significantly greater with V‐LCE than WLE ( p < 0.001) and with R‐LCE than V‐LCE ( p < 0.001) (39.6 with R‐LCE, 29.6 with V‐LCE, and 18.3 with WLE). Conclusions Our V‐LCE has a middle performance between R‐LCE and WLE in terms of lesion detection, margin, and color difference. It suggests that V‐LCE potentially improves the endoscopic diagnosis of superficial ESCC.

Background Three Janus kinase (JAK) inhibitors are approved for ulcerative colitis (UC) in Japan. Aim To compare the real‐world efficacy and safety of these three JAK inhibitors in UC. Methods This was a multicentre, retrospective study of patients with UC started on JAK inhibitors. The primary outcome was clinical remission at 10, 26 and 58 weeks, and at the most recent follow‐up. To compare the efficacy and safety among the JAK inhibitors, we created three matched cohorts (upadacitinib vs. filgotinib, tofacitinib vs. filgotinib and upadacitinib vs. tofacitinib) using propensity score matching. Results We identified 228 upadacitinib‐treated patients (median follow‐up 49 weeks; IQR 25–72), 215 filgotinib‐treated patients (follow‐up 56 weeks; IQR 17–82) and 159 tofacitinib‐treated patients (follow‐up 112 weeks; IQR 10–258). Clinical remission rates for upadacitinib, filgotinib and tofacitinib at the most recent follow‐up were 72.8%, 50.6% and 45.8%, respectively. Over 70% of the patients previously treated with other biologics or JAK inhibitors achieved clinical remission with upadacitinib. On multivariate analysis, the number of previous advanced therapies was inversely associated with the efficacy of filgotinib and tofacitinib. Comparative analysis showed that upadacitinib‐treated patients had higher efficacy and lower risk of discontinuation than patients treated with other JAK inhibitors. However, upadacitinib had a significant risk of acne. Conclusions Considering the particularly high efficacy of upadacitinib, even in patients with refractory UC, filgotinib or tofacitinib may be considered as an upfront JAK inhibitor before using upadacitinib.

Background The involvement of Mediterranean fever (MEFV) gene mutations in patients with inflammatory bowel disease unclassified (IBDU) remains unclear. This study aimed to determine the clinical characteristics and responsiveness to colchicine in Japanese patients with IBDU carrying MEFV mutations. Methods In this retrospective cohort study, we examined MEFV mutations using gene analysis, clinical information, and colchicine responsiveness. Furthermore, we examined cytokine production in exon 2-mutated THP-1 cells (a monocytic cell line) and microbiome analysis. Findings Of the 396 patients diagnosed with IBDU, 60.1% had MEFV mutations. Exon 2 mutations were the most common (83.7%). Among patients with available clinical information, 43.3% of patients with IBDU had typical Familial Mediterranean fever (FMF). The efficacy of colchicine in patients with IBDU carrying MEFV mutations was 84.6%. Significant differences were noted in the production of inflammatory; cytokines between THP-1 cells with and without MEFV mutations. Microbial compositions differed between patients with IBDU carrying MEFV mutations and patients with IBD and healthy controls. Interpretation Patients with IBDU carrying MEFV mutations responded well to colchicine treatment. A notable subset of patients met the criteria for typical FMF. Alterations in intestinal microbiota may contribute to disease pathogenesis. Funding This work was supported by the 10.13039/100009619Japan Agency for Medical Research and Development (21ek0410057h0003), a grant from the 10.13039/100008732Uehara Memorial Foundation, and the Health and Labour Sciences Research Grants for research on intractable diseases from the 10.13039/501100003478Ministry of Health, Labour and Welfare (MHLW) of Japan (Investigation and Research for Intractable Inflammatory Bowel Disease; Grant Number 20316729).

Background and study aims Diagnostic performance of a computer-aided diagnosis (CAD) system for deep submucosally invasive (T1b) colorectal cancer was excellent, but the “regions of interest” (ROI) within images are not obvious. Class activation mapping (CAM) enables identification of the ROI that CAD utilizes for diagnosis. The purpose of this study was a quantitative investigation of the difference between CAD and endoscopists. Patients and methods Endoscopic images collected for validation of a previous study were used, including histologically proven T1b colorectal cancers (n = 82; morphology: flat 36, polypoid 46; median maximum diameter 20 mm, interquartile range 15–25 mm; histological subtype: papillary 5, well 51, moderate 24, poor 2; location: proximal colon 26, distal colon 27, rectum 29). Application of CAM was limited to one white light endoscopic image (per lesion) to demonstrate findings of T1b cancers. The CAM images were generated from the weights of the previously fine-tuned ResNet50. Two expert endoscopists depicted the ROI in identical images. Concordance of the ROI was rated by intersection over union (IoU) analysis. Results Pixel counts of ROIs were significantly lower using 165K[x103] [108K-227K] than by endoscopists (300K [208K-440K]; P < 0.0001) and median [interquartile] of the IoU was 0.198 [0.024-0.349]. IoU was significantly higher in correctly identified lesions (n = 54, 0.213 [0.116-0.364]) than incorrect ones (n=28, 0.070 [0.000-0.2750, P = 0.033). Concusions IoU was larger in correctly diagnosed T1b colorectal cancers. Optimal annotation of the ROI may be the key to improving diagnostic sensitivity of CAD for T1b colorectal cancers.

Background Subharmonic-aided pressure estimation (SHAPE) is a technique for determining changes in ambient pressure. We aimed to analyze a novel SHAPE integrated into ultrasound diagnostic equipment to predict patients with liver cirrhosis at high risk of esophagogastric varices (EV). Methods This prospective study included 111 patients with liver cirrhosis diagnosed between 2020 and 2023. We obtained liver stiffness measurements (LSM) and spleen stiffness measurements (SSM) using shear wave elastography and hepatic vein-portal vein (HV-PV) gradient using the SHAPE method. The EV risk was determined either as null, low, or high by esophagoscopy and Child–Pugh stage. Results HV-PV gradient increased concordantly with the increase in EV risk (− 7.0 dB in null-risk, − 4.4 dB in low-risk, and − 2.0 dB in high-risk) with statistically significant difference among any two groups. The most appropriate cut-off value of the HV-PV gradient was − 3.5 dB, and sensitivity, specificity, and positive and negative predictive values were 80.0%, 89.0%, 80.0%, and 88.0%, respectively. The areas under the curve values for predicting the high-risk EV were 0.920, 0.843, and 0.824 for the HV-PV gradient, LSM, and SSM, respectively. Conclusions The novel SHAPE system demonstrated high accuracy in identifying patients with liver cirrhosis at a high risk of EV.

Background Steatotic liver disease, characterized by a combination of metabolic dysfunction, alcohol use, or specific etiologies, is a leading cause of chronic liver disease. However, the role of metabolic dysfunction in chronic liver disease with harmful alcohol use remains unclear. This study aimed to investigate factors associated with hepatic steatosis and fibrosis in patients with harmful alcohol use. Methods Over a 2‐year period, we registered patients with harmful alcohol use, defined by an Alcohol Use Disorders Identification Test score of 8 or higher. We retrospectively analyzed background information, blood test results, ultrasound‐guided attenuation parameter (attenuation coefficient), and liver stiffness measurement. Hepatic steatosis was defined as attenuation coefficient ≥0.65 dB/cm/MHz, and fibrosis as liver stiffness measurement ≥7.5 kPa. Results The study included 131 patients (82% men, median age 59 years). Linear regression analysis revealed significant associations with attenuation coefficient for body mass index ≥23 (0.08, p < 0.0001) and age (−0.002, p = 0.002). Liver stiffness measurement was associated with body mass index ≥23 (2.52, p = 0.001), aspartate aminotransferase (0.02, p = 0.0189), gamma‐glutamyl transpeptidase (0.008, p < 0.0001), platelet count (−0.02, p = 0.001), and prothrombin international normalized ratio (26.40, p < 0.0001). Among the four groups classified by the presence or absence of steatosis and fibrosis, patients with fibrosis, but without steatosis, demonstrated the lowest liver reserve. In contrast, patients with both steatosis and fibrosis showed higher aspartate aminotransferase and gamma‐glutamyl transpeptidase levels. Conclusions Body mass index is associated with both hepatic steatosis and fibrosis in patients with harmful alcohol use.

Durvalumab plus tremelimumab (Durva/Treme) has recently been approved as a first-line or later-line treatment for patients with unresectable hepatocellular carcinoma (u-HCC) in Japan. We assessed the real-world outcomes of Durva/Treme for u-HCC, with a focus on treatment efficacy and safety. We retrospectively evaluated 22 patients with u-HCC treated with Durva/Treme at Iwate Medical University during the period from 2023 to 2024, with a comparison of the clinical outcomes between patients who received Durva/Treme as first-line and later-line treatments. We further evaluated changes in the modified albumin-bilirubin (mALBI) grade during treatment. There were 10 patients in the first-line group and 12 patients in the later-line treatment group. During the follow-up with a median duration of 7.6 months, the median progression-free survival (first-line versus later-line: 4.7 months versus 2.9 months, p = 0.85), the objective response rate (0.0% versus 16.7%, p = 0.48), the disease control rate (60.0% versus 58.4%, p = 1.00), and the incidence of any adverse event (50.0% versus 75.0%, p = 0.38) were not statistically different between the two groups. The changes in the mALBI scores were not statistically significant (p = 0.75). Durva/Treme may be effective and safe for patients with u-HCC, even in patients who receive Durva/Treme as a later-line treatment.