21 results on '"Seno, H."'
Search Results
2. Reduction of butyrate-producing bacteria in the gut microbiome of Japanese patients with pancreatic cancer.
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Sono M, Iimori K, Nagao M, Ogawa S, Maruno T, Nakanishi Y, Anazawa T, Nagai K, Masui T, Mori H, Hosomi K, Kunisawa J, Yokota H, Tanaka Y, Ohno H, Hatano E, Fukuda A, and Seno H
- Abstract
Background: The incidence of pancreatic cancer is on the rise, and its prognosis remains poor. Recent reports have established a link between the gut and oral microbiome and pancreatic cancer. However, the intricacies of this association within the Japanese population remain unclear. In this study, we investigated the gut and oral microbiomes of Japanese patients with pancreatic cancer, comparing them with those of healthy individuals., Methods: We recruited 30 patients with untreated pancreatic cancer and 18 healthy controls at Kyoto University Hospital (2018-2022). We performed a comprehensive 16S rRNA gene sequencing to analyze their gut and oral microbiomes., Results: Analysis revealed that the diversity of the gut and oral microbiomes of patients with pancreatic cancer was reduced compared to that of the healthy controls. Specifically, we observed an increase in the genus Streptococcus in both the gut and oral microbiomes and a significant decrease in several butyrate-producing bacteria in fecal samples. Moreover, bacteria such as Streptococcus mitis and Holdemanella biformis were present in pancreatic cancer tissues, suggesting that they might influence the carcinogenesis and progression of pancreatic cancer., Conclusions: The gut and oral microbiome differed between patients with pancreatic cancer and healthy controls, with a notable decrease in butyrate-producing bacteria in the gut microbiome of the patients. This suggests that there may be a distinct microbial signature associated with pancreatic cancer in the Japanese population. Further studies are required to elucidate the microbiome's causal role in this cancer and help develop prognostic markers or targeted therapies., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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3. Wnt-deficient and hypoxic environment orchestrates squamous reprogramming of human pancreatic ductal adenocarcinoma.
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Tamagawa H, Fujii M, Togasaki K, Seino T, Kawasaki S, Takano A, Toshimitsu K, Takahashi S, Ohta Y, Matano M, Kawasaki K, Machida Y, Sekine S, Machinaga A, Sasai K, Kodama Y, Kakiuchi N, Ogawa S, Hirano T, Seno H, Kitago M, Kitagawa Y, Iwasaki E, Kanai T, and Sato T
- Abstract
Human pancreatic cancer is characterized by the molecular diversity encompassing native duct-like and squamous cell-like identities, but mechanisms underlying squamous transdifferentiation have remained elusive. To comprehensively capture the molecular diversity of human pancreatic cancer, we here profiled 65 patient-derived pancreatic cancer organoid lines, including six adenosquamous carcinoma lines. H3K27me3-mediated erasure of the ductal lineage specifiers and hijacking of the TP63-driven squamous-cell programme drove squamous-cell commitment, providing survival benefit in a Wnt-deficient environment and hypoxic conditions. Gene engineering of normal pancreatic duct organoids revealed that GATA6 loss and a Wnt-deficient environment, in concert with genetic or hypoxia-mediated inactivation of KDM6A, facilitate squamous reprogramming, which in turn enhances environmental fitness. EZH2 inhibition counterbalanced the epigenetic bias and curbed the growth of adenosquamous cancer organoids. Our results demonstrate how an adversarial microenvironment dictates the molecular and histological evolution of human pancreatic cancer and provide insights into the principles and significance of lineage conversion in human cancer., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2024
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4. Early detection of pancreatic cancer by comprehensive serum miRNA sequencing with automated machine learning.
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Kawai M, Fukuda A, Otomo R, Obata S, Minaga K, Asada M, Umemura A, Uenoyama Y, Hieda N, Morita T, Minami R, Marui S, Yamauchi Y, Nakai Y, Takada Y, Ikuta K, Yoshioka T, Mizukoshi K, Iwane K, Yamakawa G, Namikawa M, Sono M, Nagao M, Maruno T, Nakanishi Y, Hirai M, Kanda N, Shio S, Itani T, Fujii S, Kimura T, Matsumura K, Ohana M, Yazumi S, Kawanami C, Yamashita Y, Marusawa H, Watanabe T, Ito Y, Kudo M, and Seno H
- Abstract
Background: Pancreatic cancer is often diagnosed at advanced stages, and early-stage diagnosis of pancreatic cancer is difficult because of nonspecific symptoms and lack of available biomarkers., Methods: We performed comprehensive serum miRNA sequencing of 212 pancreatic cancer patient samples from 14 hospitals and 213 non-cancerous healthy control samples. We randomly classified the pancreatic cancer and control samples into two cohorts: a training cohort (N = 185) and a validation cohort (N = 240). We created ensemble models that combined automated machine learning with 100 highly expressed miRNAs and their combination with CA19-9 and validated the performance of the models in the independent validation cohort., Results: The diagnostic model with the combination of the 100 highly expressed miRNAs and CA19-9 could discriminate pancreatic cancer from non-cancer healthy control with high accuracy (area under the curve (AUC), 0.99; sensitivity, 90%; specificity, 98%). We validated high diagnostic accuracy in an independent asymptomatic early-stage (stage 0-I) pancreatic cancer cohort (AUC:0.97; sensitivity, 67%; specificity, 98%)., Conclusions: We demonstrate that the 100 highly expressed miRNAs and their combination with CA19-9 could be biomarkers for the specific and early detection of pancreatic cancer., (© 2024. The Author(s).)
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- 2024
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5. Lynch syndrome screening in patients with young-onset extra-colorectal Lynch syndrome-associated cancers.
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Yamada A, Doi Y, Minamiguchi S, Kondo T, Sunami T, Horimatsu T, Hamanishi J, Mandai M, Hatano E, Kobayashi T, Hisamori S, Obama K, Seno H, Haga H, Torishima M, Murakami H, Nakajima T, Yamada T, Kosugi S, Sugano K, and Muto M
- Abstract
Background: Lynch syndrome (LS) is a hereditary cancer syndrome caused by pathogenic germline variants in mismatch repair (MMR) genes, which predisposes to various types of cancers showing deficient MMR (dMMR). Identification of LS probands is crucial to reduce cancer-related deaths in affected families. Although universal screening is recommended for colorectal and endometrial cancers, and age-restricted screening is proposed as an alternative, LS screening covering a broader spectrum of cancer types is needed. In the current study, we elucidated the rate of dMMR tumors and evaluated the outcome of LS screening in young-onset extra-colorectal LS-associated cancers., Methods: Immunohistochemistry for MMR proteins were retrospectively performed in a total of 309 tissue samples of endometrial, non-mucinous ovarian, gastric, urothelial, pancreatic, biliary tract, and adrenal cancers in patients < 50 years of age. Clinicopathological information and the results of genetic testing were obtained from medical charts., Results: There were 24 dMMR tumors (7.8%) including 18 endometrial, three ovarian, two urothelial, and one gastric cancer. Co-occurrence of colorectal cancer and family history of LS-associated cancers was significantly enriched in patients with dMMR tumors. Among the 16 patients with dMMR tumors who were informed of the immunohistochemistry results, five with endometrial and one with urothelial cancer were diagnosed as LS with positive pathogenic variants in MMR genes., Conclusions: We report the outcome of immunohistochemistry for MMR proteins performed in multiple types of young-onset extra-colorectal LS-associated cancers. Our study demonstrates the feasibility of a comprehensive LS screening program incorporating young-onset patients with various types of extra-colorectal LS-associated cancers., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)
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- 2024
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6. Near-infrared photoimmunotherapy as a complementary modality to in situ vaccine in a preclinical pancreatic cancer model.
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Yaku H, Takahashi K, Okada H, Kobiyama K, Shiokawa M, Uza N, Kodama Y, Ishii KJ, and Seno H
- Abstract
Pancreatic cancer is one of the most refractory malignancies. In situ vaccines (ISV), in which intratumorally injected immunostimulatory adjuvants activate innate immunity at the tumor site, utilize tumor-derived patient-specific antigens, thereby allowing for the development of vaccines in patients themselves. Near-infrared photoimmunotherapy (NIR-PIT) is a novel therapy that selectively kills cancer cells exclusively in the NIR-irradiated region. Extending our previous research showing that ISV using the unique nanoparticulate Toll-like receptor 9 (TLR9) ligand K3-SPG induced effective antitumor immunity, here we incorporated NIR-PIT into K3-SPG-ISV so that local tumor destruction by NIR-PIT augments the antitumor effect of ISV. In the mouse model of pancreatic cancer, the combination of K3-SPG-ISV and CD44-targeting NIR-PIT showed synergistic systemic antitumor effects and enhanced anti-programmed cell death-1 (PD-1) blockade. Mechanistically, strong intratumoral upregulation of interferon-related genes and dependency on CD8
+ T cells were observed, suggesting the possible role of interferon and cytotoxic T cell responses in the induction of antitumor immunity. Importantly, this combination induced immunological memory in therapeutic and neoadjuvant settings. This study represents the first attempt to integrate NIR-PIT with ISV, offering a promising new direction for cancer immunotherapy, particularly for pancreatic cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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7. A case of spontaneous acute obstructive suppurative pancreatic ductitis associated with intraductal papillary mucinous neoplasms.
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Nakayama S, Fukuda A, Nishikawa S, Hirata A, Teramura M, Takai A, and Seno H
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- Humans, Aged, Female, Pancreatitis complications, Carcinoma, Pancreatic Ductal complications, Carcinoma, Pancreatic Ductal diagnosis, Suppuration, Pancreatic Ducts pathology, Pancreatic Ducts diagnostic imaging, Cholangiopancreatography, Endoscopic Retrograde, Tomography, X-Ray Computed, Acute Disease, Pancreatic Intraductal Neoplasms complications, Anti-Bacterial Agents therapeutic use, Drainage, Pancreatic Neoplasms complications, Adenocarcinoma, Mucinous complications, Adenocarcinoma, Mucinous diagnosis
- Abstract
A 77-year-old woman was referred to our hospital due to left upper abdominal pain, appetite loss and body weight loss for 1 month. Her past medical history was diabetes and intraductal papillary mucinous neoplasms (IPMNs). She had no fever and physical examination revealed mild tenderness in the left upper abdomen. Blood tests showed elevated inflammatory response with normal serum pancreatic enzymes. Contrast-enhanced CT showed marked swelling of the pancreatic tail, increased peripancreatic fatty tissue density, multiple IPMNs and obscuration of the enlarged main pancreatic duct at the tail. EUS showed there was no obvious mass in the pancreas and protein plug was suspected in the main pancreatic duct. EUS-FNA was performed and pathology showed no malignancy. ERCP showed discharge of purulent pancreatic fluid from the major duodenal papilla and stenosis of the main pancreatic duct at the tail. The culture of the purulent pancreatic fluid revealed Streptococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa, leading to diagnosis of acute obstructive suppurative pancreatic ductitis (AOSPD). Endoscopic nasopancreatic drainage and antimicrobial treatment were started. The inflammatory response improved rapidly and the patient was discharged 30 days after admission. To our knowledge, this is the second reported case of spontaneous AOSPD associated with IPMNs., (© 2024. Japanese Society of Gastroenterology.)
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- 2024
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8. Development of an LC-MS/MS method for the determination of five psychoactive drugs in postmortem urine by optimization of enzymatic hydrolysis of glucuronide conjugates.
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Matsuo T, Ogawa T, Iwai M, Kubo K, Kondo F, and Seno H
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- Humans, Hydrolysis, Chromatography, Liquid methods, Amitriptyline urine, Oxazepam urine, Dronabinol urine, Dronabinol analogs & derivatives, Temazepam urine, Lorazepam urine, Male, Liquid Chromatography-Mass Spectrometry, Tandem Mass Spectrometry methods, Psychotropic Drugs urine, Psychotropic Drugs metabolism, Glucuronides urine, Glucuronides metabolism, Glucuronidase metabolism, Glucuronidase chemistry, Forensic Toxicology methods
- Abstract
Purpose: Toxicological analyses of biological samples play important roles in forensic and clinical investigations. Ingested drugs are excreted in urine as conjugates with endogenous substances such as glucuronic acid; hydrolyzing these conjugates improves the determination of target drugs by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this study, we sought to improve the enzymatic hydrolysis of glucuronide conjugates of five psychoactive drugs (11-nor-9-carboxy-Δ
9 -tetrahydrocannabinol, oxazepam, lorazepam, temazepam, and amitriptyline)., Methods: The efficiency of enzymatic hydrolysis of glucuronide conjugates in urine was optimized by varying temperature, enzyme volume, and reaction time. The hydrolysis was performed directly on extraction columns. This analysis method using LC-MS/MS was applied to forensic autopsy samples after thorough validation., Results: We found that the recombinant β-glucuronidase B-One® quantitatively hydrolyzed these conjugates within 3 min at room temperature directly on extraction columns. This on-column method saved time and eliminated the loss of valuable samples during transfer to the extraction column. LC-MS/MS-based calibration curves processed with this method showed good linearity, with r2 values exceeding 0.998. The intra- and inter-day accuracies and precisions of the method were 93.0-109.7% and 0.8-8.8%, respectively. The recovery efficiencies were in the range of 56.1-104.5%. Matrix effects were between 78.9 and 126.9%., Conclusions: We have established an LC-MS/MS method for five psychoactive drugs in urine after enzymatic hydrolysis of glucuronide conjugates directly on extraction columns. The method was successfully applied to forensic autopsy samples. The established method will have broad applications, including forensic and clinical toxicological investigations., (© 2024. The Author(s).)- Published
- 2024
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9. Two Cases of Gastric Adenocarcinoma with Enteroblastic Differentiation which Demonstrated Rapid Progressive Courses.
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Matsuyama S, Fukuda A, Matsumoto A, Ueo T, Ohana M, and Seno H
- Abstract
We herein report two extremely rare cases of gastric adenocarcinoma with enteroblastic differentiation (GAED) that underscore the aggressive nature of GAED. Case 1: ESD was scheduled for early-stage gastric cancer, however, the tumor increased in size drastically and the morphology changed to type "0-I + IIc" in one month. Surgery was performed and the patient was diagnosed with GAED. Case 2: ESD was performed for early-stage gastric cancer, and the pathological findings revealed GAED. The horizontal margin was positive for clear cells in the muscularis mucosa. Additional surgery was performed; however, recurrence occurred one year later. Therefore, the treatment strategies should be carefully considered for GAED.
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- 2024
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10. Explainable localization of premature ventricular contraction using deep learning-based semantic segmentation of 12-lead electrocardiogram.
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Kujime K, Seno H, Nakajima K, Yamazaki M, Sakuma I, Yamagata K, Kusano K, and Tomii N
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Background: Predicting the origin of premature ventricular contraction (PVC) from the preoperative electrocardiogram (ECG) is important for catheter ablation therapies. We propose an explainable method that localizes PVC origin based on the semantic segmentation result of a 12-lead ECG using a deep neural network, considering suitable diagnosis support for clinical application., Methods: The deep learning-based semantic segmentation model was trained using 265 12-lead ECG recordings from 84 patients with frequent PVCs. The model classified each ECG sampling time into four categories: background (BG), sinus rhythm (SR), PVC originating from the left ventricular outflow tract (PVC-L), and PVC originating from the right ventricular outflow tract (PVC-R). Based on the ECG segmentation results, a rule-based algorithm classified ECG recordings into three categories: PVC-L, PVC-R, as well as Neutral, which is a group for the recordings requiring the physician's careful assessment before separating them into PVC-L and PVC-R. The proposed method was evaluated with a public dataset which was used in previous research., Results: The evaluation of the proposed method achieved neutral rate, accuracy, sensitivity, specificity, F1-score, and area under the curve of 0.098, 0.932, 0.963, 0.882, 0.945, and 0.852 on a private dataset, and 0.284, 0.916, 0.912, 0.930, 0.943, and 0.848 on a public dataset, respectively. These quantitative results indicated that the proposed method outperformed almost all previous studies, although a significant number of recordings resulted in requiring the physician's assessment., Conclusions: The feasibility of explainable localization of premature ventricular contraction was demonstrated using deep learning-based semantic segmentation of 12-lead ECG.Clinical trial registration: M26-148-8., Competing Interests: None., (© 2024 The Author(s). Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)
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- 2024
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11. A rare case of acute obstructive suppurative pancreatic ductitis (AOSPD) which developed pyogenic spondylitis.
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Hirata A, Matsumori T, Yasuda M, Nishikawa Y, Shiokawa M, Uza N, and Seno H
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Acute obstructive suppurative pancreatic ductitis (AOSPD) is an acute suppuration of the pancreatic duct. Endoscopic retrograde cholangiopancreatography (ERCP) drainage and intravenous antibiotics treatment is the mainstay of therapy. Herein we describe an extremely rare case of AOSPD leading to pyogenic spondylitis. A 61-year-old male with a past medical history of chronic pancreatitis and diabetes mellitus presented to our hospital with abdominal and dorsal pain, fever, and shock status. Laboratory data showed severe inflammation, disseminated intravascular coagulation, and normal pancreatic enzymes. Computed tomography showed dilated main pancreatic duct and surrounding pancreatic abscesses. Spinal abnormalities were not detected at this point. He was initially diagnosed as infected pancreatic pseudocyst, but did not respond well to conservative intravenous antibiotic treatment. ERCP performed one week later revealed purulent pancreatic juice and the diagnosis was changed to AOSPD. Upon ERCP, we experienced technical difficulty in passing obstructing calculi. However, successful pancreatic drainage was achieved using new dilation and penetration devices. The patient responded quickly to drainage, but later developed pyogenic spondylitis. Our case highlights the difficulty of diagnosing AOSPD, the usefulness of new devices in urgent endoscopic drainage, and underscores the possibility of progression of pyogenic spondylitis even after adequate treatment., (© 2024. Japanese Society of Gastroenterology.)
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- 2024
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12. Single Nucleotide Polymorphisms of the MEFV Gene E148Q Are Highly Associated With Disease Phenotype in Crohn's Disease.
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Yamada S, Honzawa Y, Yamamoto S, Matsuura M, Kitamoto H, Okabe M, Kakiuchi N, Toyonaga T, Kobayashi T, Hibi T, Seno H, and Nakase H
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- Humans, Male, Female, Adult, Middle Aged, Interleukin-1beta genetics, Colitis, Ulcerative genetics, Genetic Predisposition to Disease, Inflammasomes genetics, Young Adult, HSP47 Heat-Shock Proteins genetics, Cytoskeletal Proteins genetics, Collagen Type I genetics, Pyrin genetics, Polymorphism, Single Nucleotide, Crohn Disease genetics, Phenotype, Leukocytes, Mononuclear metabolism, Interleukin-18 genetics
- Abstract
Background: Single nucleotide polymorphisms (SNPs) of the MEFV gene may modify inflammatory bowel disease (IBD) activity. The prevalence of MEFV gene SNPs in IBD patients and their involvement in IBD pathophysiology remains unclear., Methods: We analyzed 12 MEFV gene SNPs in peripheral leukocytes of Japanese IBD patients (Crohn's disease [CD]: 69 patients, ulcerative colitis: 32 patients) by polymerase chain reaction using next-generation DNA sequencing and evaluated their prevalence and association with the disease characteristics. Inflammasome activity and mature interleukin (IL)-1β and IL-18 production were evaluated in peripheral blood mononuclear cells obtained from CD patients stimulated with lipopolysaccharides and adenosine triphosphate, and compared between those with and without the E148Q SNP. COL1A1 and HSP47 gene expression was analyzed in CCD-18Co cells costimulated with IL-1β and other inflammatory cytokines., Results: The prevalence of MEFV gene SNPs in IBD patients was similar to that in the human gene database. E148Q was the most common SNP. Compared with CD patients without E148Q, those with E148Q had a significantly greater frequency of the stricture phenotype, and their peripheral blood mononuclear cells exhibited significantly higher IL-1β and IL-18 levels and higher caspase-1 activity. IL-1β and IL-17A synergistically increased COL1A1 and HSP47 gene expression., Conclusions: MEFV gene SNPs, including E148Q, modify the behavior of CD. IL-1β and IL-18 are produced through enhanced caspase-1 activity in monocytes of CD patients with E148Q. IL-1β promotes gene expression of fibrosis-related genes by cooperating with IL-17A in myofibroblasts. Therefore, E148Q might be a disease-modifying gene associated with the fibrostenosis phenotype in CD patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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13. Maintenance steroid therapy is associated with decreased risk of malignancy and better prognosis of patients with autoimmune pancreatitis: A multicenter cohort study in Japan.
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Takikawa T, Kikuta K, Sano T, Ikeura T, Fujimori N, Umemura T, Naitoh I, Nakase H, Isayama H, Kanno A, Kamata K, Kodama Y, Inoue D, Ido A, Ueki T, Seno H, Yasuda H, Iwasaki E, Nishino T, Kubota K, Arizumi T, Tanaka A, Uchida K, Matsumoto R, Hamada S, Nakamura S, Okazaki K, Takeyama Y, and Masamune A
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- Humans, Aged, Japan, Retrospective Studies, Neoplasm Recurrence, Local, Prognosis, Steroids, Autoimmune Pancreatitis complications, Autoimmune Diseases diagnosis, Diabetes Mellitus, Pancreatic Neoplasms complications, Osteoporosis complications
- Abstract
Background/objectives: The association between autoimmune pancreatitis (AIP) and pancreatic cancer (PC) remains controversial. This study aimed to clarify the long-term prognosis and risk of malignancies in AIP patients in Japan., Methods: We conducted a multicenter retrospective cohort study on 1364 patients with type 1 AIP from 20 institutions in Japan. We calculated the standardized incidence ratio (SIR) for malignancies compared to that in the general population. We analyzed factors associated with overall survival, pancreatic exocrine insufficiency, diabetes mellitus, and osteoporosis., Results: The SIR for all malignancies was increased (1.21 [95 % confidence interval: 1.05-1.41]) in patients with AIP. Among all malignancies, the SIR was highest for PC (3.22 [1.99-5.13]) and increased within 2 years and after 5 years of AIP diagnosis. Steroid use for ≥6 months and ≥50 months increased the risk of subsequent development of diabetes mellitus and osteoporosis, respectively. Age ≥65 years at AIP diagnosis (hazard ratio [HR] = 3.73) and the development of malignancies (HR = 2.63), including PC (HR = 7.81), were associated with a poor prognosis, whereas maintenance steroid therapy was associated with a better prognosis (HR = 0.35) in the multivariate analysis. Maintenance steroid therapy was associated with a better prognosis even after propensity score matching for age and sex., Conclusions: Patients with AIP are at increased risk of developing malignancy, especially PC. PC is a critical prognostic factor for patients with AIP. Although maintenance steroid therapy negatively impacts diabetes mellitus and osteoporosis, it is associated with decreased cancer risk and improved overall survival., Competing Interests: Declaration of competing interest None., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)
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- 2024
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14. Anti-integrin αvβ6 autoantibodies are a potential biomarker for ulcerative colitis-like immune checkpoint inhibitor-induced colitis.
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Yokode M, Shiokawa M, Kawakami H, Kuwada T, Nishikawa Y, Muramoto Y, Kitamoto H, Okabe M, Yamazaki H, Okamoto N, Morita T, Ohno K, Nakanishi R, Takimoto I, Yasuda M, Chikugo K, Matsumoto S, Yoshida H, Ota S, Nakamura T, Okada H, Hirano T, Kakiuchi N, Matsumori T, Yamamoto S, Uza N, Ooi M, Kodama Y, Chiba T, Hayashi H, and Seno H
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- Humans, Male, Female, Middle Aged, Aged, Adult, Antigens, Neoplasm immunology, Colitis chemically induced, Colitis immunology, Autoantibodies blood, Autoantibodies immunology, Colitis, Ulcerative immunology, Colitis, Ulcerative drug therapy, Colitis, Ulcerative blood, Integrins immunology, Integrins antagonists & inhibitors, Immune Checkpoint Inhibitors adverse effects, Immune Checkpoint Inhibitors therapeutic use, Biomarkers blood
- Abstract
Background: No specific biomarker for immune checkpoint inhibitor (ICI)-induced colitis has been established. Previously, we identified anti-integrin αvβ6 autoantibodies in >90% of patients with ulcerative colitis (UC). Given that a subset of ICI-induced colitis is similar to UC, we aimed to clarify the relationship between such autoantibodies and ICI-induced colitis., Methods: Serum anti-integrin αvβ6 autoantibody levels were compared between 26 patients with ICI-induced colitis and 157 controls. Endoscopic images of ICI-induced colitis were centrally reviewed. Characteristics of anti-integrin αvβ6 autoantibodies in the ICI-induced colitis patients were compared with those of UC patients., Results: Anti-integrin αvβ6 autoantibodies were found in 8/26 (30.8%) patients with ICI-induced colitis and 3/157 (1.9%) controls (P < 0.001). Patients with anti-integrin αvβ6 autoantibodies had significantly more typical UC endoscopic features than those without the autoantibodies (P < 0.001). Anti-integrin αvβ6 autoantibodies in ICI-induced colitis patients were associated with grade ≥3 colitis (P = 0.001) and steroid resistance (P = 0.005). Anti-integrin αvβ6 autoantibody titers correlated with ICI-induced colitis disease activity. Anti-integrin αvβ6 autoantibodies of ICI-induced colitis exhibited similar characteristics to those of UC., Conclusions: Anti-integrin αvβ6 autoantibodies may serve as potential biomarkers for the diagnosis, classification, risk management, and monitoring the disease activity, of ICI-induced colitis., (© 2024. The Author(s).)
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- 2024
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15. Integrated analyses of the genetic and clinicopathological features of cholangiolocarcinoma: cholangiolocarcinoma may be characterized by mismatch-repair deficiency.
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Makino K, Ishii T, Takeda H, Saito Y, Fujiwara Y, Fujimoto M, Ito T, Wakama S, Kumagai K, Munekage F, Horie H, Tomofuji K, Oshima Y, Uebayashi EY, Kawai T, Ogiso S, Fukumitsu K, Takai A, Seno H, and Hatano E
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- Humans, Bile Ducts, Intrahepatic pathology, Liver Neoplasms pathology, Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular pathology, Cholangiocarcinoma pathology, Bile Duct Neoplasms pathology, Brain Neoplasms, Neoplastic Syndromes, Hereditary, Colorectal Neoplasms
- Abstract
Cholangiolocarcinoma (CLC) is a primary liver carcinoma that resembles the canals of Hering and that has been reported to be associated with stem cell features. Due to its rarity, the nature of CLC remains unclear, and its pathological classification remains controversial. To clarify the positioning of CLC in primary liver cancers and identify characteristics that could distinguish CLC from other liver cancers, we performed integrated analyses using whole-exome sequencing (WES), immunohistochemistry, and a retrospective review of clinical information on eight CLC cases and two cases of recurrent CLC. WES demonstrated that CLC includes IDH1 and BAP1 mutations, which are characteristic of intrahepatic cholangiocarcinoma (iCCA). A mutational signature analysis showed a pattern similar to that of iCCA, which was different from that of hepatocellular carcinoma (HCC). CLC cells, including CK7, CK19, and EpCAM, were positive for cholangiocytic differentiation markers. However, the hepatocytic differentiation marker AFP and stem cell marker SALL4 were completely negative. The immunostaining patterns of CLC with CD56 and epithelial membrane antigen were similar to those of the noncancerous bile ductules. In contrast, mutational signature cluster analyses revealed that CLC formed a cluster associated with mismatch-repair deficiency (dMMR), which was separate from iCCA. Therefore, to evaluate MMR status, we performed immunostaining of four MMR proteins (PMS2, MSH6, MLH1, and MSH2) and detected dMMR in almost all CLCs. In conclusion, CLC had highly similar characteristics to iCCA but not to HCC. CLC can be categorized as a subtype of iCCA. In contrast, CLC has characteristics of dMMR tumors that are not found in iCCA, suggesting that it should be treated distinctly from iCCA. © 2024 The Pathological Society of Great Britain and Ireland., (© 2024 The Pathological Society of Great Britain and Ireland.)
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- 2024
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16. Rapid Progression of a Sessile Serrated Lesion.
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Hiramatsu Y, Utsumi T, Ikeda M, and Seno H
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- 2024
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17. Stage at diagnosis of colorectal cancer through diagnostic route: Who should be screened?
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Agatsuma N, Utsumi T, Nishikawa Y, Horimatsu T, Seta T, Yamashita Y, Tanaka Y, Inoue T, Nakanishi Y, Shimizu T, Ohno M, Fukushima A, Nakayama T, and Seno H
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- Humans, Early Detection of Cancer, Logistic Models, Retrospective Studies, Male, Female, Colonoscopy, Colorectal Neoplasms diagnosis, Colorectal Neoplasms epidemiology, Colorectal Neoplasms pathology
- Abstract
Background: Colorectal cancer (CRC) is a global health concern, with advanced-stage diagnoses contributing to poor prognoses. The efficacy of CRC screening has been well-established; nevertheless, a significant proportion of patients remain unscreened, with > 70% of cases diagnosed outside screening. Although identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources, the association between the diagnostic routes and identification of these subgroups has been less appreciated. In the Japanese cancer registry, the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related symptoms., Aim: To clarify the stage at CRC diagnosis based on diagnostic routes., Methods: We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two hospitals. The diagnostic routes were primarily classified into three groups: Cancer screening, follow-up, and symptomatic. The early-stage was defined as Stages 0 or I. Multivariate and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups, referencing the follow-up group. The adjusted covariates were age, sex, and tumor location., Results: Of the 2083 patients, 715 (34.4%), 1064 (51.1%), and 304 (14.6%) belonged to the follow-up, symptomatic, and cancer screening groups, respectively. Among the 2083 patients, CRCs diagnosed at an early stage were 57.3% (410 of 715), 23.9% (254 of 1064), and 59.5% (181 of 304) in the follow-up, symptomatic, and cancer screening groups, respectively. The symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group [ P < 0.001, adjusted odds ratio (aOR), 0.23; 95% confidence interval (95%CI): 0.19-0.29]. The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening groups ( P = 0.493, aOR for early-stage diagnosis in the cancer screening group vs follow-up group = 1.11; 95%CI = 0.82-1.49)., Conclusion: CRCs detected during hospital visits for comorbidities were diagnosed earlier, similar to cancer screening. CRC screening should be recommended, particularly for patients without periodical hospital visits for comorbidities., Competing Interests: Conflict-of-interest statement: Yoshitaka Nishikawa reports a donation from Datack outside the submitted work. Takeo Nakayama reports the following potential conflicts of interest outside the submitted work: Grants from I&H Co., Ltd, Cocokarafine Group Co., Ltd, Konica Minolta, Inc., and NTT DATA.; consulting fees from Ohtsuka Pharmaceutical Co., Takeda Pharmaceutical Co., Johnson & Johnson K.K., and Nippon Zoki Pharmaceutical Co., Ltd.; honoraria from Pfizer Japan Inc., MSD K.K., Chugai Pharmaceutical Co., Takeda Pharmaceutical Co., Janssen Pharmaceutical K.K., Boehringer Ingelheim International GmbH, Eli Lilly Japan K.K., Maruho Co., Ltd, Mitsubishi Tanabe Pharma Co., Novartis Pharma K.K., Allergan Japan K.K., Novo Nordisk Pharma Ltd, Toa Eiyo Ltd, Dentsu Co., Ono Pharmaceutical Co., Ltd, GSK, Alexion Pharmaceuticals, Inc., Canon Medical Systems Co., Kowa Company Ltd, Araya, and AbbVie Inc.; stock option from BonBon Inc.; and donation from CancerScan and YUYAMA Co., Ltd. All the other authors declare no competing interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)
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- 2024
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18. What Influence Could the Acceptance of Visitors Cause on the Epidemic Dynamics of a Reinfectious Disease?: A Mathematical Model.
- Author
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Xie Y, Ahmad I, Ikpe TIS, Sofia EF, and Seno H
- Subjects
- Disease Outbreaks, Commerce, Policy, Models, Theoretical, Epidemics
- Abstract
The globalization in business and tourism becomes crucial more and more for the economical sustainability of local communities. In the presence of an epidemic outbreak, there must be such a decision on the policy by the host community as whether to accept visitors or not, the number of acceptable visitors, or the condition for acceptable visitors. Making use of an SIRI type of mathematical model, we consider the influence of visitors on the spread of a reinfectious disease in a community, especially assuming that a certain proportion of accepted visitors are immune. The reinfectivity of disease here means that the immunity gained by either vaccination or recovery is imperfect. With the mathematical results obtained by our analysis on the model for such an epidemic dynamics of resident and visitor populations, we find that the acceptance of visitors could have a significant influence on the disease's endemicity in the community, either suppressive or supportive., (© 2024. The Author(s).)
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- 2024
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19. Pancreatic stent removal with a novel drill dilator.
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Yanaidani T, Matsumori T, Muramoto Y, Nishikawa Y, Maruno T, Shiokawa M, Uza N, and Seno H
- Abstract
Video 1Pancreatic stent removal with a novel drill dilator., Competing Interests: The authors disclosed no financial relationships relevant to this publication., (© 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc.)
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- 2024
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20. Sporadic gastric juvenile polyposis with a novel SMAD4 nonsense mutation in a mosaic pattern.
- Author
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Matsuyama S, Fukuda A, Matsumoto A, Eguchi H, Ueo T, Ohana M, and Seno H
- Subjects
- Female, Humans, Middle Aged, Codon, Nonsense, Smad4 Protein genetics, Smad4 Protein metabolism, Stomach Neoplasms genetics, Stomach Neoplasms surgery, Stomach Neoplasms diagnosis, Polyps, Intestinal Polyposis, Neoplastic Syndromes, Hereditary, Adenomatous Polyps
- Abstract
A 50-year-old female was diagnosed with gastric hyperplastic polyps 7 years before and was followed up at another hospital. She was referred to our hospital because of the growth of gastric polyps and progression of anemia. She had no family history of polyposis. The polyps were observed only in the stomach, increased in size and number, and the erythematous edema got worse. Endoscopic mucosal resection (EMR) of the gastric polyp was performed. Pathologically, the gastric polyp was hamartomatous polyp, and the intervening mucosa between polyps showed no atypical structure without inflammation. Given that gastric juvenile polyposis (GJP) was clinically suspected, a genetic test using peripheral blood was performed. Target resequencing and Sanger sequencing analysis revealed a nonsense mutation in the SMAD4 gene at codon 169. The mutation was detected at a low frequency of 11%, and considered a mosaic mutation. Therefore, she was diagnosed with a sporadic GJP, and total gastrectomy was performed. Immunostaining of SMAD4 for the resected specimen showed a mixture of stained and unstained area in the epithelium of the polyp, indicating partial loss of SMAD4 expression. To our knowledge, this is the first reported case of GJP with a nonsense SMAD4 mutation at codon 169 in a mosaic pattern., (© 2023. Japanese Society of Gastroenterology.)
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- 2024
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21. Comprehensive analyses of the clinicopathological features and genomic mutations of combined hepatocellular-cholangiocarcinoma.
- Author
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Ito T, Ishii T, Takeda H, Sumiyoshi S, Tomofuji K, Wakama S, Makino K, Horie H, Kumagai K, Takai A, Uebayashi EY, Ogiso S, Fukumitsu K, Haga H, Seno H, and Hatano E
- Abstract
Aim: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer that has two different tumor phenotypes in a single tumor nodule. The relationship between genetic mutations and clinicopathological features of cHCC-CCA remains to be elucidated., Methods: Whole-exome sequencing analyses were carried out in 13 primary and 2 recurrent cHCC-CCAs. The whole-exome analyses and clinicopathological information were integrated., Results: TP53 was the most frequently mutated gene in this cohort, followed by BAP1, IDH1/2, and NFE2L2 mutations in multiple cases. All tumors with diameters <3 cm had TP53 mutations. In contrast, six of seven tumors with diameters ≥3 cm did not have TP53 mutations, but all seven tumors had mutations in genes associated with various pathways, including Wnt, RAS/PI3K, and epigenetic modulators. In the signature analysis, the pattern of mutations shown in the TP53 mutation group tended to be more similar to HCC than the TP53 nonmutation group. Mutations in recurrent cHCC-CCA tumors were frequently identical to those in the primary tumor, suggesting that those tumors originated from identical clones of the primary cHCC-CCA tumors. Recurrent and co-occurrent HCC tumors in the same patients with cHCC-CCA had either common or different mutation patterns from the primary cHCC-CCA tumors in each case., Conclusions: The study suggested that there were two subtypes of cHCC-CCA, one involving TP53 mutations in the early stage of the carcinogenic process and the other not involving such mutations. The comparison of the variants between primary and recurrent tumors suggested that cHCC-CCA was derived from an identical clone., (© 2023 Japan Society of Hepatology.)
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- 2024
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