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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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Characteristics of non-erosive gastroesophageal reflux disease refractory to proton pump inhibitor therapy

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World Journal of Gastroenterology 2011年第14期17卷 1858-1865页

作者： Mitsushige Sugimoto Masafumi Nishino Chise Kodaira mihoko yamade Takahiro Uotani Mutsuhiro Ikuma Kazuo Umemura Takahisa Furuta Center for Clinical Research Hamamatsu University School of MedicineShizuoka Hamamatsu 431-3192Japan First Department of Medicine Hamamatsu University School of MedicineShizuoka Hamamatsu 431-3192Japan Department of Pharmacology Hamamatsu University School of MedicineShizuoka Hamamatsu 431-3192Japan

AIM:To investigate whether potent acid inhibition is effective in non-erosive reflux disease (NERD) refractory to standard rabeprazole (RPZ) treatment. METHODS:We treated 10 Japanese patients with NERD resistant to standard dosages of RPZ:10 mg or 20 mg od,20 mg bid,or 10 mg qid for 14 d. All patients completed a frequency scale for symptoms of gastroesophageal reflux disease questionnaire frequency scale for the symptoms of GERD (FSSG); and underwent 24 h pH monitoring on day 14. RESULTS:With increased dosages and frequency of administration of RPZ,median intragastric pH significantly increased,and FSSG scores significantly decreased. With RPZ 10 mg qid,potent acid inhibition was attained throughout 24 h. However,five subjects were refractory to RPZ 10 mg qid,although the median intragastric pH in these subjects (6.6,range:6.2-7.1) was similar to that in the remaining five responsive subjects (6.5,range:5.3-7.3). With baseline RPZ 10 mg od,FSSG scores in responsive patients improved by > 30%,whereas there was no significant decrease in the resistant group. CONCLUSION:NERD patients whose FSSG score fails to decrease by > 30% after treatment with RPZ 10 mg od for 14 d are refractory to higher dosage.

关键词：质子泵抑制剂反流治疗食管糜烂胃频率范围 pH监测

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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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Pharmacogenomics-based tailored strategy for Helicobacter pylori infection

Pharmacogenomics-based tailored strategy for Helicobacter py...

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第三届中日双边药理学和临床药理学学术会议

作者： FURUTA Takahisa SUGIMOTO Mitsushige SHIRAI Naohito KODAIRA Chise NISHINO Masafumi yamade mihoko IKUMA Mutsuhiro WATANABE Hiroshi UMEMURA Kazuo OHASHI Kyoichi ISHIZAKI Takashi HISHIDA Akira Center for Clinical Research First Department of Medicine Department of Laboratory Medicine First Department of Medicine First Department of Medicine First Department of Medicine First Department of Medicine Department of Clinical Pharmacology and Therapeutics Department of Pharmacology Hamamatsu University School of MedicineHamamatsuJapan Department of Clinical Pharmacology and Therapeutics Clinical Pharmacology CenterFaculty of MedicineOita UniversityOitaJapan Department of Clinical Pharmacology and Therapeutics First Department of Medicine

＜正＞AIM Helicobacter pylori eradication rates by triple therapy with a proton pump inhibitor,amoxicillin and clarithromycin at standard doses depend on bacterial susceptibility to clarithromycin and patient CYP2C19 gen- otypes.We examined the usefulness of a personalized therapy for H.pylori infection based on these factors as determined by genetic testing.METHODS First,opti- mal lansoprazole dosing schedules that would achieve suffi- cient acid inhibition to allow H.pylori eradication therapy in each of different CYP2C19 genotype groups were deter- mined by a 24-h intragastric pH monitoring.Next,300 H. pylori-positive patients were randomly assigned to the standard regimen group （lansoprazole 30 mg bid,clar- ithromycin 400 mg bid,and amoxicillin 750 mg bid for one week）or the tailored regimen group based on CYP2C19 status and bacterial susceptibility to clarithromy- cin assessed by genetic testing.Patients with failure of e- radication underwent the second-line regimen.RESULTS In the first-line therapy,the intention-to-treat eradication rate in the tailored regimen group was 96.0%,significant- ly higher than that in the standard regimen group （70.0%）.CONCLUSION The phannacogenomics- based tailored treatment for H.pylori infection allowed a higher eradication rate by the initial treatment.

关键词： CYP2C19 Helicobacter pylori lansoprazole clarithromycin pharmacogenomics

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