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Lymphocyte-to-monocyte ratio is a short-term predictive marker of ulcerative colitis after induction of advanced therapy

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Gastroenterology Report 2022年第1期10卷 370-376页

作者： Natsuki Ishida Yusuke Asai Takahiro Miyazu Satoshi Tamura Shinya Tani Mihoko Yamade Moriya Iwaizumi yasushi hamaya Satoshi Osawa Takahisa Furuta Ken Sugimoto First Department of Medicine Hamamatsu University School of MedicineHamamatsuShizuokaJapan Department of Endoscopic and Photodynamic Medicine Hamamatsu University School of MedicineHamamatsuShizuokaJapan Department of Laboratory Medicine Hamamatsu University School of MedicineHamamatsuShizuokaJapan Center for Clinical Research Hamamatsu University School of MedicineHamamatsuShizuokaJapan

Advanced therapies for patients with mild-to-severe ulcerative colitis(UC)may result in treatment failure.We examined whether the lymphocyte-to-monocyte ratio(L/M ratio)could predict the failure of advanced therapies.This retrospective,observational,cohort study included 73 patients who were treated with advanced therapies at the Hamamatsu University School of Medicine(Shizuoka,Japan)between February 2011 and November 2020.The patients were divided into the nonfailure and failure groups,and their leukocyte counts and ratios before induction were examined.Univariate and multivariate analyses were performed to identify the prognostic factors.Advanced therapies failed within 3 months in 15(20.5%)patients.Only the L/M ratio was significantly lower in the failure group than in the non-failure group(P=0.004).Receiveroperating characteristic(ROC)curve analysis revealed that an L/M ratio of ≤3.417 was predictive of treatment failure;the area under the curve(AUC)was 0.747(95%CI,0.620–0.874).Kaplan–Meier analysis revealed that the failure-free rate was significantly lower in the group with an L/M ratio of≤3.417 than in the group with an L/M ratio of>3.417(log-rank test P=0.002).Cox proportional hazard regression analysis identified an L/M ratio of≤3.417 as an independent risk factor for failure within 3 months after the induction of advanced therapies.Furthermore,ROC analysis of patients who did not receive immunomodulators also revealed that the cut-off L/M ratio was 3.417 and the AUC was 0.796(95%CI,0.666–0.925).In patients receiving advanced therapies for active UC,the L/M ratio can predict treatment failure within 3 months.L/M ratios could facilitate the transition from advanced therapies to subsequent treatments.

关键词： advanced therapy failure lymphocyte-to-monocyte ratio ulcerative colitis

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Intrahepatic cholangiocarcinoma in patients with primary sclerosing cholangitis and ulcerative colitis: Two case reports

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World Journal of Gastrointestinal Surgery 2023年第6期15卷 1224-1231页

作者： Takahiro Miyazu Natsuki Ishida Yusuke Asai Satoshi Tamura Shinya Tani Mihoko Yamade Moriya Iwaizumi yasushi hamaya Satoshi Osawa Satoshi Baba Ken Sugimoto First Department of Medicine Hamamatsu University School of MedicineHamamatsu 431-3192Japan Department of Endoscopic and Photodynamic Medicine Hamamatsu University School of MedicineHamamatsu 431-3192Japan Department of Laboratory Medicine Hamamatsu University School of MedicineHamamatsu 431-3192Japan Department of Diagnostic Pathology Hamamatsu University School of MedicineHamamatsu 431-3192Japan

BACKGROUND Primary sclerosing cholangitis(PSC)is an extraintestinal manifestation of ulcerative colitis(UC).PSC is a well-known risk factor for intrahepatic cholangiocarcinoma(ICC),and ICC is known to have a poor prognosis.CASE SUMMARY We present two cases of ICC in patients with PSC associated with UC.In the first case,a tumor was found by magnetic resonance imaging(MRI)in the liver of a patient with PSC and UC who presented to our hospital with right-sided rib pain.The second patient was asymptomatic,but we unexpectedly detected two liver tumors in an MRI performed to evaluate bile duct stenosis associated with PSC.ICC was strongly suspected by computed tomography and MRI in both cases,and surgery was performed,but unfortunately,the first patient died of ICC recurrence 16 mo postoperatively,and the second patient died of liver failure 14 mo postoperatively.CONCLUSION Careful follow-up of patients with UC and PSC with imaging and blood tests is necessary for early detection of ICC.

关键词： Ulcerative colitis Primary sclerosing cholangitis Intrahepatic cholangiocarcinoma Hepatic lobectomy Inflammatory bowel disease Case report

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Comparison of fecal calprotectin levels and endoscopic scores for predicting relapse in patients with ulcerative colitis in remission

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World Journal of Gastroenterology 2023年第47期29卷 6111-6121页

作者： Natsuki Ishida Tatsuhiro Ito Kenichi Takahashi Yusuke Asai Takahiro Miyazu Tomohiro Higuchi Satoshi Tamura Shinya Tani Mihoko Yamade Moriya Iwaizumi yasushi hamaya Satoshi Osawa Ken Sugimoto Department of Endoscopic and Photodynamic Medicine Hamamatsu University of School of MedicineHamamatsu 431-3192Japan First Department of Medicine Hamamatsu University of School of MedicineHamamatsu 431-3192Japan Department of Laboratory Medicine Hamamatsu University of School of MedicineHamamatsu 431-3192Japan

BACKGROUND Although the usefulness of endoscopic scores,such as the Mayo Endoscopic Subscore(MES),Ulcerative Colitis Endoscopic Index of Severity(UCEIS),and Ulcerative Colitis Colonoscopic Index of Severity(UCCIS),and biomarkers such as fecal calprotectin(FC)for predicting relapse in ulcerative colitis(UC)has been reported,few studies have included endoscopic scores for evaluating the entire colon.AIM To compare the usefulness of FC value and MES,UCEIS,and UCCIS for predicting relapse in patients with UC in clinical remission.METHODS In total,75 patients with UC in clinical and endoscopic remission who visited our institution between February 2019 and March 2022 were enrolled.The diagnosis of UC was confirmed based on the clinical presentation,endoscopic findings,and histology,according to the current established criteria for UC.Fecal samples were collected the day before or after the colonoscopy for measurement of FC.Endoscopic evaluations were performed using MES,UCEIS,and UCCIS.The primary outcome measure of this study was the assessment of the association between relapse within 12 mo and MES,UCEIS,UCCIS,and FC.The secondary outcome was the comparison between endoscopic scores and biomarkers in en-rolled patients with UC with mucosal healing.RESULTSFC and UCCIS showed a significant correlation with UCEIS (r = 0.537, P < 0.001 and r = 0.957, P < 0.001, respectively).Receiver-operating characteristic analysis for predicting MES 0 showed that the area under the curve ofUCCIS was significantly higher than that of FC (P < 0.01). During the 1-year observation period, 18 (24%) patientsexperienced a relapse, and both the FC and UCCIS of the relapse group were significantly higher than that of theremission group. The cut-off values for predicting relapse were set at FC = 323 mg/kg and UCCIS = 10.2. The areaunder the curve of the receiver-operating characteristic analysis for predicting relapse did not show a significantdifference between FC and UCCIS. The accuracy of the endoscopic scores and biomarkers in predicting r

关键词： Ulcerative colitis Mayo Endoscopic Subscore Ulcerative Colitis Endoscopic Index of Severity Ulcerative Colitis Colonoscopic Index of Severity Fecal calprotectin Relapse

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Early serum albumin changes in patients with ulcerative colitis treated with tacrolimus will predict clinical outcome

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World Journal of Gastroenterology 2021年第22期27卷 3109-3120页

作者： Natsuki Ishida Takahiro Miyazu Satoshi Tamura Shinya Tani Mihoko Yamade Moriya Iwaizumi yasushi hamaya Satoshi Osawa Takahisa Furuta Ken Sugimoto First Department of Medicine Hamamatsu University of School of MedicineHamamatsu 431-3192Japan Department of Laboratory Medicine Hamamatsu University of School of MedicineHamamatsu 431-3192Japan Department of Endoscopic and Photodynamic Medicine Hamamatsu University of School of MedicineHamamatsu 431-3192Japan Center for Clinical Research Hamamatsu University of School of MedicineHamamatsu 43131Japan

BACKGROUND Oral tacrolimus is a therapeutic agent for moderate to severe steroid-dependent or resistant ulcerative colitis(UC),but remission induction is difficult,and it is necessary to treat the patient while considering the next treatment.AIM To examine serum albumin(Alb)level as a prognostic factor for the therapeutic effect of tacrolimus in clinical practice.METHODS Forty-seven patients with UC treated with tacrolimus at our institution were divided into remission and failure groups(colectomy or switch to biologics),and the biological data at the start of observation and at weeks 1 and 2 were retrospectively examined.Kaplan-Meier and multivariate analyses were performed using Alb as a prognostic factor in UC treatment.RESULTS During the three months observed,17(36.2%)patients failed treatment with tacrolimus.A comparison between the failure and remission groups showed a significant difference only in Alb in week 2,and in the week 2/week 0 Alb ratio,which showed the rate of change in Alb.The cut-off value of the week 2/week 0 Alb ratio that predicted failure was 1,and its area under the curve was 0.751(95%CI:0.604-0.898).In the Kaplan-Meier analysis,a week 2/week 0 Alb ratio≤1 had a significantly higher failure rate than that of>1;Cox proportional hazard regression analysis also showed that a week 2/week 0 Alb ratio≤1 was an independent prognostic factor for failure within 3 mo after the start of tacrolimus treatment.CONCLUSION A week 2/week 0 Alb ratio≤1 predicts failure within 3 mo of tacrolimus administration for UC.High failure risk exists with week 2 Alb values≤1 on admission.

关键词： Ulcerative colitis Tacrolimus Albumin

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Evaluating mucosal healing using colon capsule endoscopy predicts outcome in patients with ulcerative colitis in clinical remission

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World Journal of Clinical Cases 2018年第15期6卷 952-960页

作者： Ryosuke Takano Satoshi Osawa Takahiro Uotani Shinya Tani Natsuki Ishida Satoshi Tamura Mihoko Yamade Moriya Iwaizumi yasushi hamaya Takahisa Furuta Hiroaki Miyajima Ken Sugimoto First Department of Medicine Hamamatsu University School of Medicine Department of Endoscopic and Photodynamic Medicine Hamamatsu University School of Medicine Department of Laboratory Medicine Hamamatsu University School of Medicine Center for Clinical Research Hamamatsu University School of Medicine

AIM To examine whether second generation of colon capsule endoscopy(CCE-2) is acceptable for assessing the severity of mucosal inflammation and evaluating mucosal healing using CCE-2 is able to predict outcome in ulcerative colitis(UC) patients, especially in clinical remission.METHODS A total of 30 consecutive UC patients in clinical remission were enrolled to undergo CCE-2. Clinical remission was defined as clinical activity index(CAI) ≤ 4 according to Rachmilewitz index. The rate of total colon observation and colon cleansing level were evaluated. Severity of mucosal inflammation in UC was assessed according to the Mayo endoscopic subscore(MES) and Ulcerative Colitis Endoscopic Index of Severity(UCEIS). Relapsefree survival was assessed. Acceptability of CCE-2 was assessed using a questionnaire survey.RESULTS The rate of total colon observation within its battery life was 93.3%. The proportion of "excellent" plus "good" cleansing level was 73.3%. The rate of mucosal healing(MES 0, 1) assessed by CCE-2 was 77.0%. The relapse-free survival rate was significantly higher in MES 0, 1 than in MES 2, 3(P = 0.0435), and in UCEIS 0-3 than in UCEIS 4-8(P = 0.0211), whereas there was no significant difference between CAI 0 and CAI 1-4 groups. A questionnaire survey revealed an overall acceptability of CCE.CONCLUSION CCE-2 is acceptable for assessing the severity of mucosal inflammation in UC patients, especially in clinical remission. Evaluating mucosal healing using CCE-2 was able to predict outcome.

关键词： Colon capsule endoscopy Ulcerative colitis Mucosal healing Mayo endoscopic subscore Ulcerative Colitis Endoscopic Index of Severity

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Tuberous sclerosis patient with neuroendocrine carcinoma of the esophagogastric junction:A case report

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World Journal of Gastroenterology 2020年第45期26卷 7263-7271页

作者： Natsuki Ishida Takahiro Miyazu Satoshi Tamura Satoshi Suzuki Shinya Tani Mihoko Yamade Moriya Iwaizumi Satoshi Osawa yasushi hamaya Kazuya Shinmura Haruhiko Sugimura Katsutoshi Miura Takahisa Furuta Ken Sugimoto First Department of Medicine Hamamatsu University School of MedicineHamamatsu 431-3192Japan Department of Endoscopic and Photodynamic Medicine Hamamatsu University School of MedicineHamamatsu 431-3192Japan Department of Laboratory Medicine Hamamatsu University School of MedicineHamamatsu 431-3192Japan Haruhiko Sugimura Department of Tumor PathologyHamamatsu University School of MedicineHamamatsu 431-3192Japan Department of Health Science Hamamatsu University School of MedicineHamamatsu 431-3192Japan Center for Clinical Research Hamamatsu University School of MedicineHamamatsu 431-3192Japan

BACKGROUND Tuberous sclerosis complex(TSC)is a rare inherited disease with non-cancerous tumor growths in the skin,brain,kidneys,heart,and lungs.The co-occurrence of neuroendocrine neoplasm(NEN)with TSC is even rarer.There have been few reports on the relationship between TSC and neuroendocrine tumors(NETs),and fewer on the relationship between TSC and neuroendocrine carcinoma(NEC),a subtype of NEN.This is the first reported case of NEC occurring at the esophagogastric junction in a patient with TSC.CASE SUMMARY A 46-year-old woman visiting our hospital for the treatment of TSC was admitted to the emergency department with tarry stools and dizziness.Computed tomography scans revealed thickness of the gastric cardia,multiple metastatic lesions of the liver,and enlarged lymph nodes near the lesser curvature of the stomach.Esophagogastroduodenoscopy revealed a type 3 tumor located from the esophagogastric junction to the fundus,and the pathological diagnosis by biopsy was NEC.The patient was treated with seven courses of cisplatin+irinotecan,followed by eight courses of ramucirumab+nab-paclitaxel,one course of nivolumab,and two courses of S-1+oxaliplatin.Twenty-three months after the first treatment,the patient died because of disease progression and deterioration of the general condition.CONCLUSION This case of NEC occurring in a patient with TSC indicates a difference in the occurrence of NETs and NECs.

关键词： Tuberous sclerosis complex Neuroendocrine carcinoma Neuroendocrine tumor mTOR inhibitor Esophagogastric junction Chemotherapy Case report

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Inverted Meckel's diverticulum preoperatively diagnosed using double-balloon enteroscopy

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World Journal of Gastroenterology 2016年第17期22卷 4416-4420页

作者： Kosuke Takagaki Satoshi Osawa Tatsuhiro Ito Moriya Iwaizumi yasushi hamaya Hiroe Tsukui Takahisa Furuta Hidetoshi Wada Satoshi Baba Ken Sugimoto First Department of Medicine Hamamatsu University School of Medicine Department of Endoscopic and Photodynamic Medicine Hamamatsu University School of Medicine Department of Diagnostic Pathology Hamamatsu University School of Medicine Center for Clinical Research Hamamatsu University School of Medicine First Department of Surgery Hamamatsu University School of Medicine

An inverted Meckel's diverticulum is a rare gastrointestinal congenital anomaly that is difficult to diagnose prior to surgery and presents with anemia, abdominal pain, or intussusception. Here, we report the case of 57-year-old men with an inverted Meckel's diverticulum, who was preoperatively diagnosed using doubleballoon enteroscopy. He had repeatedly experienced epigastric pain for 2 mo. Ultrasonography and computed tomography showed intestinal wall thickening in the pelvis. Double-balloon enteroscopy via the anal route was performed for further examination, which demonstrated an approximately 8-cm, sausage-shaped, submucosal tumor located approximately 80 cm proximal to the ileocecal valve. A small depressed erosion was observed at the tip of this lesion. Forceps biopsy revealed heterotopic gastric mucosa. Thus, the patient was diagnosed with an inverted Meckel's diverticulum, and single-incision laparoscopic surgery was performed. This case suggests that an inverted Meckel's diverticulum should be considered as a differential diagnosis for a submucosal tumor in the ileum. Balloon-assisted enteroscopy with forceps biopsy facilitate a precise diagnosis of this condition.

关键词： Inverted Meckel’s diverticulum Doubleballoon enteroscopy Small bowel tumor Epigastric pain Heterotop

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EPH-EPHRIN in human gastrointestinal cancers

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World Journal of Gastrointestinal Oncology 2010年第12期2卷 421-428页

作者： Haruhiko Sugimura Hiroki Mori Masaru Tsuboi Kiyoko Nagura Hisaki Igarashi Ritsuko Nakamura Hiroko Natsume Tomoaki Kahyo Kazuya Shinmura Hiroyuki Konno yasushi hamaya Shigeru Kanaoka Hideki Kataoka Department of Pathology I Hamamatsu University School of MedicineHamamatsu 431-3192Japan Department of Surgery II Hamamatsu Uni- versity School of MedicineHamamatsu431-3192Japan Department of Molecular Diagnostics Hamamatsu University School of MedicineHamamatsu 431-3192Japan Department of Medicine I Hamamatsu University School of MedicineHamamatsu431-3192Japan

Ever since its discovery two decades ago,the erythro- poietin-producing hepatoma (EPH)-EPHRIN system has been shown to play multifaceted roles in human gastroenterological cancer as well as neurodevelopment.Overexpression,amplif ication and point mutations have been found in many human cancers and many investigators have shown correlations between these up-regulationsand tumor angiogenesis.Thus,the genes in this family are considered to be potential targets of cancer therapy.On the other hand,the down-regulation of some members as a result of epigenetic changes has also been reported in some cancers.Furthermore,the correlation between altered expressions and clinical prognosis seems to be inconclusive.A huge amount of protein-protein interaction studies on the EPH-EPHRIN system have provided a basic scheme for signal transductions,especially bi-directional signaling involving EPH-ERPHRIN molecules at the cell membrane.This information also provides a manipulative strategy for harnessing the actions of these molecules.In this review,we summarize the known alterations of EPH-EPHRIN genes in human tumors of the esophagus,stomach,colorectum,liver and pancreas and present the perspective that the EPH-EPHRIN system could be a potential target of cancer therapy.

关键词： Erythropoietin-producing hepatoma EPH-EPHRIN Gastric cancer Colorectal cancer Methylation Secreted form

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On the Asymptotic Stability of Discrete Crocodilians Model

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Advances in Pure Mathematics 2023年第5期13卷 211-225页

作者： Kaori Saito Yoshihiro hamaya Meise University Tokyo Japan Okayama University of Science Okayama Japan

The sex ratio of crocodiles is strongly biased towards females, often as high as 10 females to 1 male. In crocodilians, the temperature of egg incubation is the environmental factor determining sex. If the temperature is low, around 30˚C, the hatchlings are all females. Higher temperature, around 34˚C, hatch all males. This study was made to consider the asymptotic stability of a positive equilibrium point in a nonlinear discrete model of the basic nesting population model, which is described in three-region depending on the temperature of egg incubation. This model is based on key life-historical data and Murray’s research. To study above, we have applied the classical linearization method and P. Cull’s method and moreover, we employ non-standard discretization methods for later our Equations (6)-(8) and (15).

关键词： Asymptotic Stability Crocodilians Population Model Positive Equilibrium Point

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Global Asymptotically Stable of a Generalized Discrete Ricker Competition System

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Journal of Mathematics and System Science 2013年第6期3卷 282-288页

作者： Yoshihiro hamaya Department of Information Science Okayama University of Science Okayama 7000005 Japan

The purpose of this article is to investigate the sufficient conditions for the global asymptotic stability of one equilibrium point of a generalized Ricker competition system, which appears as a model for dynamics with one extinct species, by applying the technique of average functions and the new principle of competitive exclusion.

关键词：全局渐近稳定广义离散赛制充分条件竞争排斥平衡点物种灭绝

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