Relationships Of Capsule Endoscopy Activity Index With Clinical Disease Activity Indices, C-reactive Protein And Small Bowel Transit Time In Patients With Small Bowel Crohn’s Disease

BackgroundCapsule endoscopy(CE)is a milestone in the history of endoscopic technology,which is a major breakthrough in the routine that the conventional endoscopy is incapable of exploring the small intestine.Since CE emerged and was approved the use for evaluating small intestinal lesions in adults by the Food and Drug Administration(FDA)in 2001,small bowel CE has brought lots of benefits so as to strengthen the management of small bowel disease.And in 2004,CE was approved for patients aged between 10 and 18 years old.Both the patency capsule and CE were approved for patients older than 2 years in 2009.There is a paucity of data on the safety and tolerance of CE in pediatric patients in China,and the related sample was small.The specific indications and contraindications of CE in pediatric patients were demonstrated in a Spanish guideline.To begin with,the main indication for CE in pediatric patients is the assessment of Crohn’s disease(CD).Other indications include obscure gastrointestinal bleeding,malabsorption and protein-losing enteropathies,abdominal pain,small bowel polyps and tumors.As the chiefly indication for pediatric CE,CE is of great significance in the diagnosis and treatment in children with CD.In terms of contraindications for CE in pediatric patients,the main contraindication is suspected intestinal obstruction.And currently the major drawbacks of CE encountered with pediatric patients were dysphagia and CE retention.In pediatric patients who are incapable of swallowing the capsule,the method to introduce the capsule is by using gastrduodenoscopy.As for capsule retention,the utility of small bowel enteroscopy and surgery could be performed to remove the capsule.There is a sustainable rise in the incidence of inflammatory bowel disease in Asians over the past few decades.And approximately 25-33%of patients with CD present during childhood or adolescene.Suffering from CD in pediatric patients may exert great effects on their growth and development,life and study.CD in children can present with the typically initial symptoms of abdominal pain and diarrhea.However,several patients manifest with growth failure and weight loss,which poses a great challenge for gastroenterologists to make a diagnosis in this condition.It is noteworthy that the disease location in pediatric CD is inclined to be unstable,which is different from adult CD.The disease location could be changed during the disease course,specifically,it may along with the increasing of the anatomic extent.And as such,it is essential for pediatric CD patients to be diagnosed and treated in time.As a noninvasive and safe tool,CE is preferred in children,which has great advantages in the diagnosis of pediatric CD and assessing the disease extent.The main focus on the established CD is to assess the disease activity,and it is important to evaluate patient condition and the next therapeutic schedule.Quantitative measurements are adopted for better analyzing on the grade of inflammation,which yields variable indices.Of all the indices of inflammatory severity,Abbreviated Pediatric Crohn’s Disease Activity Index(aPCDAI)is usually used in pediatric patients.Harvey-Bradshaw Simple Index(HBI)is applied in adults.And CRP serum level is widely used.sa an inflammatory measurement both in the researches and clinical evaluation.The evaluation of endoscopic mucosa is mainly on the inflammation of small intestinal mucosa,capsule Endoscopy Lewis score(LS)is extensively utilized in clinical researches.The evaluation of inflammation severity in CD incorporate the clinical,laboratory and endoscopic assessment,while the inflammation detected by endoscopy is the direct parameter indicating the disease activity,and it is contentious that whether clinical disease activity and experimental biomarker are related to the real disease activity observed by CE.In the adult patients with CD,the majority of the studies demonstrated the poor relationship between them.That is to say,the assessment of clinical disease activity and experimental indicators could not present the true inflammatory activity of mucosa.Data on pediatric patients are relatively less.So it is necessary to explore the relationship of capsule endoscopic disease activity with clinical disease activity and inflammatory factors in pediatric and adult patients with small bowel CD.The aim of present study is to retrospectively analyze the utility of CE in pediatric patients,especially the pediatric patients with CD,and to explore the relationship of capsule endoscopic disease activity with clinical disease activity and inflammatory factors in pediatric and adult patients with small bowel CD.Materials and MethodsInclusion criteria and observational indexIn our study,we enrolled pediatric patients who underwent CE in the department of gastroenterology,Nanfang hospital between 2012 to September 2017.Firstly,we retrospectively analyzed the utility of pediatric CE enrolled.Secondly,we enrolled the pediatric patients with established CD and analyzed the clinical and capsule endoscopic data.At last,we explore the relationships of CE Lewis score with clinical disease activity index,CRP and SBTT in pediatric and adult patients with small bowel CD.CE procedure and types of scoreThe CE was performed with three different CE systems:MiroCam(IntroMedic Co.Ltd.,Seoul,South Korea),OMOM(Jinshan Science and Technology Co.Ltd.,Chongqing,China)and NaviCam(Ankon Technologies Co.Ltd,Wuhan,Shanghai,China).A low-residue,liquid diet at least 1 day before CE procedure was required.Subjects underwent CE after a 12 hours overnight fast.The adult patients were asked to ingest 2L of polyethylene glycol(PEG)solution within 2 hours,starting 4 hours before swallowing the capsule.While children and adolescents were asked to ingest 1-2L of PEG solution following the same steps(adjust according to the practical circumstances).All patients or guardians provided informed written consent.Disease activity index under CE was applied with LS.The clinical disease activity index was determined using the aPCDAI in pediatric patients and HBI in adults.A serum CRP level below 5mg/L was considered normal.Data analysisResults of quantitative data are expressed as mean±SD and range.Spearman’s rank correlation coefficient(r)was used to assess the correlation between LS and HBI and that between LS and CRP,aPCDAI,SBTT.The strength of correlation was defined as follows:r value ≤0.1 were considered to denote no correlation:0.1 to 0.3 weak to moderate;0.3 to 0.49 moderate;0.5 to 0.79 strong;and>0.8 very strong correlation.Comparisons of HBI,aPCDAI,CRP,SBTT among inactive,mild and moderate-severe CD subgroups(according to LS)were carried out with nonparametric statistical analysis using Mann-Whitney and Kruskal-Wallis tests.Results at baseline and follow-up were compared using 2-tailed Wilcoxon analysis.A 2-tailed probability(P)value of less than 0.05 was regarded as be statistically significant for all tests.All the statistical analyses were carried out with a Statistical Package for the Social Sciences software version 22.0(IBM,Armonk,NY)and Microsoft Word 2010.Results1.186 pediatric patients were enrolled(with 131 MiroCam CEs,29 OMOM CEs,26 NaviCam CEs).Of all the patients,dysphagia was found in 1 child(male,11 years old),and he was able to swallow the capsule after repeated attempts.Gastric retention was found in 2 cases,endoscopic placement and medication(Metoclopramide Dihydrochloride)were performed with each patient.CE was well-tolerated in the rest patients.However,19 CEs were incomplete small bowel examinations,the completion rate was 89.8%,and CE retention was not found in our cohort.167 cases were complete small bowel examinations,132 of them were detected positive lesions in small intestine,the detection rate was 79.0%.While after further examinations,treatments and follow-up,we demonstrated the cases with confirmed diagnosis were 68,the diagnostic yield was 51.5%.2.The utility of CE in pediatric patients with CD:43 of 186 patients were diagnosed with CD,while CE detected 39 cases,so the detection rate was 90.7%.Of all the established CD patients,there were 30 boys and 13 girls,and the mean age of them was 15.9 years old(range:11-17 years old).According to the Montreal classification,the disease behavior indicated that B1(non-stricturing,nonpenetrating),B2(stricturing)and B3(penetrating)were 41,1,and 1 in pediatric patients.The disease location indicated that L1(ileal),L2(colonic)and L3(ileocolonic)were 9,5,and 29 cases.While the LS indicated that inactive(<135),mild(135-790),and moderate-severe(≥790)were 10,17,and 16 patients,respectively.Numbers of pediatric patients who participated in the follow-up study were 13,the average follow-up time is 12.8 months(range:3-33 months).During the follow-up study,10 patients achieved mucosal healing/capsule endoscopic remission(LS<135),the average follow-up time is 10.5 months(range:3-22months).3 children were still endoscopic active CD(LS≥135),and their average follow-up time is 20.7 months(range:4-33months).3.In pediatric patients,moderate correlations were found between LS and aPCDAI,CRP(r1=0.413;r2=0.370;P1=0.023;P2=0.044).There was no correlation between LS and SBTT(r=-0.029;P=0.880).The correlation between CRP and aPCDAI was strong(r=0.633,P<0.001).The degree of small intestinal inflammation was stratified to different subgroups by the LS.aPCDAI and CRP could differentiate inactive subgroup from mild or moderate-severe subgroup,whereas they could not discriminate the mild subgroup from the moderate-severe subgroup.Differences of SBTT among the 3 subgroups were not found.In the pediatric patients who participated the follow-up study,difference of aPCDAI between baseline and follow-up was found(P=0.007).And the average LS and CRP at follow-up were lower than that at baseline(359.7 vs 727,4.8 vs 21.7),whereas difference of CRP was not found to be statistically significant.There was no difference of SBTT between follow-up and baseline.In adult patients,weak but significant correlations were found between LS and HBI,SBTT(r1=0.213;r2=0.237;Pl=0.019;P2=0.009).Moderate correlation was found between LS and CRP(r=0.326;P<0.001).And the correlation between CRP and HBI was strong(r=0.522;P<0.001).In the 3 LS subgroups,differences in HBI and SBTT were not found among these groups,while CRP levels were significantly different between the inactive and mild subgroup and that between the mild and moderate-severe subgroup.In adult patients who participated in follow-up study,the average HBI at baseline were higher than that at the follow-up(P=0.002).Differences in LS and SBTT between baseline and follow-up were not found.Also,CRP was lower at follow-up than that at baseline with statistically significant difference(7.6 vs 22.6)ConclusionsFirstly,it is demonstrated that CE is safe and well-tolerated in pediatric patients,and the diagnostic yield of CE is impressive in some diseases.Secondly,the role of CE is of great significance in pediatric CD patients,it brought great advantages in the diagnosis,treatment and prognosis of CD.Moreover,there are different strength correlations between capsule endoscopic inflammatory severity and clinical disease activity,CRP,while change of the clinical disease activity and CRP were inconsistent with the change of the direct mucosal inflammation under the detection of CE in a considerable amount of patients.Therefore,to reduce progressive bowel damage and monitor long-term prognosis of CD,attention should be paid to the capsule endoscopic evaluation both in pediatric and adult patients.Furthermore,the small bowel transit time may not be affected by the grade of small intestinal inflammation.