Pediatric stricturing Crohn's disease

Crohn’s disease(CD)is a chronic inflammatory disease of the digestive tract.The incidence of pediatric CD is increasing and is currently 2.5-11.4 per 100000 world-wide.Notably,approximately 25%of children with CD develop stricturing CD(SCD)that requires intervention.Symptomatic stricturing diseases refractory to pharmacological management frequently require non-pharmacological interventions.Non-pharmacological therapeutic strategies include endoscopic balloon dilatation,stricturoplasty,and surgical resection of the strictured seg-ment.However,strictures tend to recur postoperatively regardless of treatment modality.The lifetime risk of surgery in patients with childhood SCD remains at 50%-90%.Thus,new and emerging strategies,advanced diagnostic tools,and minimally invasive approaches are under investigation to improve the outcomes and overall quality of life of pediatric patients with SCD.

Impact of different anastomosis methods on post-recurrence after intestinal resection for Crohn's disease:A meta-analysis

BACKGROUND Crohn's disease(CD)is a chronic inflammatory disease of the gastrointestinal tract,often requiring intestinal resection as a common treatment.However,recurrence after surgery is common.The anastomotic configuration after bowel resection appears to be associated with the recurrence of CD.Previous studies have suggested that the Kono-S anastomosis may help to reduce the recurrence rate.However,the results remain controversial.Therefore,evidence-based evidence is needed to prove the advantages of Kono-S anastomosis.AIM To measure the influence of anastomosis techniques on the long-term relapse rate of CD by conducting a meta-analysis.METHODS PubMed,Scopus,and Cochrane Library were searched until October 8,2023.Patients who underwent intestinal resection due to CD were included.The intervention measures included Kono-S anastomosis,whereas the control group received traditional anastomosis such as end-to-end,end-to-side,and side-to-side anastomosis.Only randomized clinical trials and observational studies were included.The primary outcome measures were hospital stay post-surgery,overall postoperative complication incidence,the proportion of Clavien-Dindo grade IIIa or higher,overall postoperative recurrence rate,and Rutgeerts score.RESULTS From 2011 to 2023,six articles met the inclusion and exclusion criteria.The results indicated that Kono-S anastomosis can reduce the hospital stay post-surgery of patients with CD[MD=-0.26,95%CI:-0.42 to-0.10,P=0.002]than other traditional anastomosis methods.Compared to other traditional anastomosis methods,Kono-S anastomosis can significantly reduce the total recurrence rate[MD=0.40,95%CI:0.17 to 0.98,P=0.05]and postoperative Rutgeerts score[MD=-0.81,95%CI:-0.96 to-0.66,P<0.001]in patients with CD.However,there is no significant disparity in the overall occurrence of postoperative complications and the proportion of Clavien-Dindo≥IIIa.CONCLUSION Kono-S anastomosis has the potential to expedite the recuperation of CD and diminish relapse hazards;however,additional larger trials are necessary to authenticate its effectiveness.

Saccharomyces cerevisiae prevents postoperative recurrence of Crohn's disease modeled by ileocecal resection in HLA-B27 transgenic rats

BACKGROUND Postoperative recurrence(POR)after ileocecal resection(ICR)affects most Crohn's disease patients within 3-5 years after surgery.Adherent-invasive Escherichia coli(AIEC)typified by the LF82 strain are pathobionts that are frequently detected in POR of Crohn's disease and have a potential role in the early stages of the disease pathogenesis.Saccharomyces cerevisiae CNCM I-3856 is a probiotic yeast reported to inhibit AIEC adhesion to intestinal epithelial cells and to favor their elimination from the gut.AIM To evaluate the efficacy of CNCM I-3856 in preventing POR induced by LF82 in an HLA-B27 transgenic(TgB27)rat model.METHODS Sixty-four rats[strain F344,38 TgB27,26 control non-Tg(nTg)]underwent an ICR at the 12th wk(W12)of life and were sacrificed at the 18th wk(W18)of life.TgB27 rats were challenged daily with oral administration of LF82(109 colony forming units(CFUs)/day(d),n=8),PBS(n=5),CNCM I-3856(109 CFUs/d,n=7)or a combination of LF82 and CNCM I-3856(n=18).nTg rats receiving LF82(n=5),PBS(n=5),CNCM I-3856(n=7)or CNCM I-3856 and LF82(n=9)under the same conditions were used as controls.POR was analyzed using macroscopic(from 0 to 4)and histologic(from 0 to 6)scores.Luminal LF82 quantifications were performed weekly for each animal.Adherent LF82 and inflammatory/regulatory cytokines were quantified in biopsies at W12 and W18.Data are expressed as the median with the interquartile range.RESULTS nTg animals did not develop POR.A total of 7/8(87%)of the TgB27 rats receiving LF82 alone had POR(macroscopic score≥2),which was significantly prevented by CNCM I-3856 administration[6/18(33%)TgB27 rats,P=0.01].Macroscopic lesions were located 2 cm above the anastomosis in the TgB27 rats receiving LF82 alone and consisted of ulcerations with a score of 3.5(2-4).Seven out of 18 TgB27 rats(39%)receiving CNCM I-3856 and LF82 had no macroscopic lesions.Compared to untreated TgB27 animals receiving LF82 alone,coadministration of CNCM I-3856 and LF82 significantly reduced the macroscopic[3.5(2-4)vs 1(0-3),P=0.002]and histological lesions by more than 50%[4.5(3.3-5.8)vs 2(1.3-3),P=0.003].The levels of adherent LF82 were correlated with anastomotic macroscopic scores in TgB27 rats(r=0.49,P=0.006),with a higher risk of POR in animals having high levels of luminal LF82(71.4%vs 25%,P=0.02).Administration of CNCM I-3856 significantly reduced the levels of luminal and adherent LF82,increased the production of interleukin(IL)-10 and decreased the production of IL-23 and IL-17 in TgB27 rats.CONCLUSION In a reliable model of POR induced by LF82 in TgB27 rats,CNCM I-3856 prevents macroscopic POR by decreasing LF82 infection and gut inflammation.

Crohn's disease and clinical management today:How it does?

Crohn’s Disease(CD)is an Inflammatory Bowel Disease and is characterized by an immune-mediated nature.Its etiology results from the interaction between genetic,enviromental and microbial factors.Regarding pathophysiology,it involves high levels of interleukin(IL)-12,IL-17,and Th1 profile,along with loss of tolerance mechanisms,an increase in pro-inflammatory interleukins,beyond the possibility to affect any part of the gastrointestinal tract.Its symptoms include abdominal pain,chronic diarrhea,weight loss,anorexia,and fatigue,as well as blood in the stool or rectum.Additionally,conditions comprising musculoskeletal,cutaneous,ocular,hepatic,and hematological alterations may be associated with this scenario and extra-intestinal presentation,such as erythema nodosum,anterior uveitis,osteoporosis,and arthritis can also occur.Today,clinical history,exams as fecal calprotectin,ileocolonocopy,and capsule endoscopy can be performed in the diagnosis investigation,along with treatments to induce and maintain remission.In this sense,anti-inflammatory drugs,such as corticosteroids,immunomodulators,and biological agents,as well as surgery and non-pharmacological interventions plays a role in its therapy.The aim of this review is to bring more current evidence to clinical management of CD,as well as to briefly discuss aspects of its pathophysiology,surveillance,and associated disorders.

Postoperative diarrhea in Crohn's disease:Pathogenesis,diagnosis,and therapy

Diarrhea is a frequent symptom in postoperative patients with Crohn’s diseases(CD),and several different mechanisms likely account for postoperative diarrhea in CD.A targeted strategy based on a comprehensive understanding of postoperative diarrhea is helpful for better postoperative recovery.

Changes in the gut mycobiome in pediatric patients in relation to the clinical activity of Crohn's disease

BACKGROUND Numerous studies have shown that in Crohn’s disease(CD),the gut microbiota is of great importance in the induction and maintenance of inflammation in the gastrointestinal tract.Until recently,studies have focused almost exclusively on bacteria in the gut.Lately,more attention has been paid to the role of intestinal fungi.AIM To study the gut mycobiome analysis of pediatric patients with CD(in different stages of disease activity)compared to healthy children.METHODS Fecal samples were collected from patients:With active,newly diagnosed CD(n=50);active but previously diagnosed and treated CD(n=16);non-active CD and who were in clinical remission(n=39)and from healthy volunteers(n=40).Fungal DNA was isolated from the samples.Next,next generation sequencing(MiSeq,Illumina)was performed.The composition of mycobiota was correlated with clinical and blood parameters.RESULTS Candida spp.were overrepresented in CD patients,while in the control group,the most abundant genus was Saccharomyces.In CD patients,the percentage of Malassezia was almost twice that of the control(P<0.05).In active CD patients,we documented a higher abundance of Debaryomyces hansenii(D.hansenii)compared to the non-active CD and control(P<0.05)groups.Moreover,statistically significant changes in the abundance of Mycosphaerella,Rhodotorula,and Microidium were observed.The analyses at the species level and linear discriminant analysis showed that in each group it was possible to distinguish a specific species characteristic of a given patient population.Moreover,we have documented statistically significant correlations between:D.hansenii and patient age(negative);C.zeylanoides and patient age(positive);C.dubliniensis and calprotectin(positive);C.sake and calprotectin(positive);and C.tropicalis and pediatric CD activity index(PCDAI)(positive).CONCLUSION Mycobiome changes in CD patients,and the positive correlation of some species with calprotectin or PCDAI,give strong evidence that fungi may be of key importance in the development of CD.

IgA nephropathy associated with Crohn's disease

The relationship between IgA nephropathy(IgAN)and Crohn’s disease was reported.IgAN is the most common primary glomerulonephritis and one of the leading causes of chronic kidney disease and end-stage renal failure,and up to 50%of cases progressed to end-stage renal disease within 25 years after IgAN diagnosis.However,specific and effective therapeutic strategies are still lacking.In this review,we discuss the possibility of the mechanism involved in IgAN associated with Crohn’s disease based on the findings of basic and clinical studies.Although the etiology of IgAN associated with Crohn’s disease is not permanent and various factors are thought to be involved,the stabilization of the disease condition of Crohn’s disease is believed to help treat IgAN.

Surgical management of duodenal Crohn's disease

BACKGROUND The case of Crohn's disease involving the duodenum is rare,and its surgical management requires a thorough understanding.AIM To investigate the surgical management of duodenal Crohn’s disease.METHODS We systematically reviewed patients diagnosed with duodenal Crohn's disease who underwent surgery in the Department of Geriatrics Surgery of the Second Xiangya Hospital of Central South University from January 1,2004,to August 31,2022.The general information,surgical procedures,prognosis,and other information of these patients were collected and summarized.RESULTS A total of 16 patients were diagnosed with duodenal Crohn’s disease,where 6 cases had primary duodenal Crohn’s disease,and 10 had secondary duodenal Crohn’s disease.Among patients with primary disease,5 underwent duodenal bypass and gastrojejunostomy,and 1 received pancreaticoduodenectomy.Among those with a secondary disease,6 underwent closure of duodenal defect and colectomy,3 received duodenal lesion exclusion and right hemicolectomy,and 1 underwent duodenal lesion exclusion and double-lumen ileostomy.CONCLUSION Crohn's disease involving the duodenum is a rare condition.Different surgical management should be applied for patients with Crohn's disease presenting with different clinical manifestations.

Intestinal complications in patients with Crohn's disease in the Brazilian public healthcare system between 2011 and 2020

BACKGROUND This is a secondary database study using the Brazilian public healthcare system database.AIM To describe intestinal complications(ICs)of patients in the Brazilian public healthcare system with Crohn’s disease(CD)who initiated and either only received conventional therapy(CVT)or also initiated anti-tumor necrosis factor(anti-TNF)therapy between 2011 and 2020.METHODS This study included patients with CD[international classification of diseases–10th revision(ICD-10):K50.0,K50.1,or K50.8](age:≥18 years)with at least one claim of CVT(sulfasalazine,azathioprine,mesalazine,or methotrexate).IC was defined as a CD-related hospitalization,pre-defined procedure codes(from rectum or intestinal surgery groups),and/or associated disease(pre-defined ICD-10 codes),and overall(one or more type of ICs).RESULTS In the 16809 patients with CD that met the inclusion criteria,the mean follow-up duration was 4.44(2.37)years.In total,14697 claims of ICs were found from 4633 patients.Over the 1-and 5-year of follow-up,8.3%and 8.2%of the patients with CD,respectively,presented at least one IC,of which fistula(31%)and fistulotomy(48%)were the most commonly reported.The overall incidence rate(95%CI)of ICs was 6.8(6.5–7.04)per 100 patient years for patients using only-CVT,and 9.2(8.8–9.6)for patients with evidence of anti-TNF therapy.CONCLUSION The outcomes highlighted an important and constant rate of ICs over time in all the CD populations assessed,especially in patients exposed to anti-TNF therapy.This outcome revealed insights into the real-world treatment and complications relevant to patients with CD and highlights that this disease remains a concern that may require additional treatment strategies in the Brazilian public healthcare system.

Immune checkpoint inhibitor therapy-induced autoimmune polyendocrine syndrome typeⅡand Crohn's disease:A case report

BACKGROUND The development of immune checkpoint inhibitors(ICIs)has heralded a new era in cancer treatment,enabling the possibility of long-term survival in patients with metastatic disease.Unfortunately,ICIs are increasingly implicated in the development of autoimmune diseases.CASE SUMMARY We present a man with squamous cell carcinoma of the oropharynx on a combination of teriprizumab,docetaxel,and cisplatin therapy who developed autoimmune polyendocrine syndrome typeⅡ(APS-2)including thyroiditis and type 1 diabetes mellitus and Crohn’s disease(CD).He developed thirst,abdominal pain,and fatigue after two-week treatment with the protein 1 ligand inhibitor teriprizumab.Biochemistry confirmed APS-2 and thyrotoxicosis.He was commenced on an insulin infusion.However,his abdominal pain persisted.Follow-up surgery confirmed CD and his abdominal pain was relieved by mesalazine.He was continued on insulin and mesalazine therapy.CONCLUSION Immunotherapy can affect all kinds of organs.When clinical symptoms cannot be explained by a single disease,clinicians should consider the possibility of multisystem damage.

Real-world cost-effectiveness associated with infliximab maintenance therapy for moderate to severe Crohn's disease in China

BACKGROUND Infliximab was the first approved biologic treatment for moderate to severe Crohn's disease(MS-CD) in China. However, the cost-effectiveness of infliximab maintenance therapy(IMT) for MS-CD relative to conventional maintenance therapy remained unclarified.AIM To assess the cost-effectiveness of IMT for MS-CD in Chinese patients from the perspective of Chinese public insurance payer.METHODS A cohort of MS-CD patients managed in a Chinese tertiary care hospital was created to compare IMT with conventional maintenance therapy(CMT) for clinical outcomes and direct medical costs over a 1-year observation time using conventional regression analyses. A decision-analytic model with the generated evidence was constructed to assess the cost-effectiveness of IMT relative to CMT using reimbursed medical costs.RESULTS Based on the included 389 patients, IMT was associated with significantly higher disease remission chance [odds ratio: 4.060, P = 0.003], lower risk of developing new complications(odds ratio: 0.527, P = 0.010), higher utility value for quality of life(coefficient 0.822, P = 0.008), and lower total hospital costs related to disease management(coefficient-0.378, P = 0.008) than CMT. Base-case cost-effectiveness analysis estimated that IMT could cost Chinese health insurance payers $55260 to gain one quality-adjusted life year(QALY). The cost-effectiveness of IMT was mainly driven by the estimate of quality of life, treatment efficacy of maintenance therapy, mortality risk associated with active disease, and unit price of infliximab. The probability that IMT was cost-effective at a willingness-to-pay threshold of three times gross domestic product [2018 Chinese gross domestic product per capita(GDPPC)] was 86.4%.CONCLUSION IMT significantly improved real-world health outcomes and cost the Chinese public health insurance payers less than one GDPPC to gain one QALY in Chinese MS-CD patients.

Infectious etiopathogenesis of Crohn's disease

Important advances during the last decade have been made in understanding the complex etiopathogenesis of Crohn’s disease(CD).While many gaps in our knowledge still exist,it has been suggested that the etiology of CD is multifactorial including genetic,environmental and infectious factors.The most widely accepted theory states that CD is caused by an aggressive immune response to infectious agents in genetically predisposed individuals.The rise of genome-wide association studies allowed the identification of loci and genetic variants in several components of host innate and adaptive immune responses to microorganisms in the gut,highlighting an implication of intestinal microbiota in CD etiology.Moreover,numerous independent studies reported a dysbiosis,i.e.,a modification of intestinal microbiota composition,with an imbalance between the abundance of beneficial and harmful bacteria.Although microorganisms including viruses,yeasts,fungi and bacteria have been postulated as potential CD pathogens,based on epidemiological,clinicopathological,genetic and experimental evidence,their precise role in this disease is not clearly defined.This review summarizes the current knowledge of the infectious agents associated with an increased risk of developing CD.Therapeutic approaches to modulate the intestinal dysbiosis and to target the putative CD-associated pathogens,as well as their potential mechanisms of action are also discussed.

High prevalence of vitamin A deficiency in Crohn's disease patients according to serum retinol levels and the relative dose-response test

AIM:To assess the vitamin A status of patients with Crohn's disease(CD) by evaluating serum retinol levels and the relative dose response(RDR) test(liver retinol stores).METHODS:Vitamin A nutritional status was measured by serum retinol obtained by high performance liquid chromatography and the RDR test for evaluation of the hepatic stores.Body composition was performed by densitometry by dual-energy X-ray absorptiometry.Vitamin A dietary intake was assessed from a semiquantitative food frequency questionnaire.RESULTS:This study included 38 CD patients and 33 controls.Low serum retinol concentrations were detected in 29% of CD patients vs 15% in controls(P < 0.005).The RDR test was positive in 37% of CD patients vs 12% in controls,which indicated inadequate hepatic vitamin A stores(P < 0.005).Individuals with hypovitaminosis A had lower BMI and body fat compared with those without this deficiency.There was no association between vitamin A deficiency and its dietary intake,ileal location,presence of disease activity and prior bowel resections.CONCLUSION:Patients with CD have higher prevalence of vitamin A deficiency,as assessed by two independent methods.

Incidental adenocarcinoma in patients undergoing surgery for stricturing Crohn's disease

AIM To evaluate frequency and clinical course of incidental adenocarcinoma in patients with stricturing Crohn's disease(CD).METHODS In this study, consecutive patients, who were operated on for stricturing CD between 1997-2012, were included at an academic tertiary referral center. Demographic data and clinical course were obtained by an institutional database and individual chart review. Besides baseline characteristics, intraoperative findings and CD related history were also recorded. Colorectal cancer was classified and staged according to the Union for International Cancer Control(UICC).RESULTS During the study period 484 patients underwent resections due to stricturing CD. Incidental adenocarcinoma was histologically confirmed in 6(1.2%) patients(4 males, 2 females). Patients diagnosed with colorectal cancer had a median age of 43(27-66)years and a median history of CD of 16(7-36) years. Malignant lesions were found in the rectum(n = 4, 66.7%), descending colon(n = 1, 16.7%) and ileocolon(n = 1, 16.7%). According to the UICC classification two patients were stages as?Ⅰ(33.3%), whereas the other patients were classified as stage ⅡA(16.7%), stage ⅢB(16.7%), stage ⅢC(16.7%) and stage Ⅳ(16.7%), respectively. After a median follow-up of 2(0.03-8) years only 1 patient is still alive.CONCLUSION The frequency of incidental colorectal cancer in patients, who undergo surgery for stenotic CD, is low but associated with poor prognosis. However, surgeons need to be aware about the possibility of malignancy in stricturing CD, especially if localized in the rectum.

NOD2-and disease-specific gene expression profiles of peripheral blood mononuclear cells from Crohn's disease patients

AIM To investigate disease-specific gene expression profiles of peripheral blood mononuclear cells(PBMCs) from Crohn's disease(CD) patients in clinical remission.METHODS Patients with CD in clinical remission or with very low disease activity according to the Crohn's disease activity index were genotyped regarding nucleotidebinding oligomerization domain 2(NOD2),and PBMCs from wild-type(WT)-NOD2 patients,patients with homozygous or heterozygous NOD2 mutations and healthy donors were isolated for further analysis.The cells were cultured with vitamin D,peptidoglycan(PGN) and lipopolysaccharide(LPS) for defined periods of time before RNA was isolated and subjected to microarray analysis using Clariom S assays and quantitative realtime PCR.NOD2-and disease-specific gene expression profiles were evaluated with repeated measure ANOVA by a general linear model.RESULTS Employing microarray assays,a total of 267 genes were identified that were significantly up-or downregulated in PBMCs of WT-NOD2 patients,compared to healthy donors after challenge with vitamin D and/or a combination of LPS and PGN(P < 0.05;threshold:≥ 2-fold change).For further analysis by real-time PCR,genes with known impact on inflammation and immunity were selected that fulfilled predefined expression criteria.In a larger cohort of patients and controls,a disease-associated expression pattern,with higher transcript levels in vitamin D-treated PBMCs from patients,was observed for three of these genes,CLEC5 A(P < 0.030),lysozyme(LYZ;P < 0.047) and TREM1(P < 0.023).Six genes were found to be expressed in a NOD2-dependent manner(CD101,P < 0.002;CLEC5 A,P < 0.020;CXCL5,P < 0.009;IL-24,P < 0.044;ITGB2,P < 0.041;LYZ,P < 0.042).Interestingly,the highest transcript levels were observed in patients with heterozygous NOD2 mutations.CONCLUSION Our data identify CLEC5 A and LYZ as CD-and NOD2-associated genes of PBMCs and encourage further studies on their pathomechanistic roles.

Intestinal dysbiosis in pediatric Crohn's disease patients with IL10RA mutations

BACKGROUND Several studies have employed animal models to explore the association between microbiota and interleukin(IL) 10 signaling;however,limited information is available about the human microbiome.AIM To characterize the microbiome in patients with IL10 RA mutations and to explore the association between gut dysbiosis and disease severity.METHODS Fecal samples were collected from patients who were diagnosed with loss-offunction mutations in the IL10 RA gene between January 2017 and July 2018 at the Children’s Hospital of Fudan University.Age-matched volunteer children were recruited as healthy controls.Patients with Crohn’s disease(CD) were used as disease controls to standardize the antibiotic exposure.Microbial DNA was extracted from the fecal samples.All analyses were based on the 16 S rRNA gene sequencing data.RESULTS Seventeen patients with IL10 RA mutations(IL10 RA group),17 patients with pediatric CD, and 26 healthy children were included.Both patients with IL10 RA mutations and those with CD exhibited a reduced diversity of gut microbiome with increased variability.The relative abundance of Firmicutes was substantially increased in the IL10 RA group(P=0.02).On further comparison of the relative abundance of taxa between patients with IL10 RA mutations and healthy children,13 taxa showed significant differences.The IL10 RA-specific dysbiosis indices exhibited a significant positive correlation with weighted pediatric CD activity index and simple endoscopic score for CD.CONCLUSION In patients with IL10 RA mutations and early onset inflammatory bowel disease,gut dysbiosis shows a moderate association with disease severity.

Capsule enteroscopy is useful for the therapeutic management of Crohn's disease

AIM: To analyze therapeutic changes in Crohn's disease(CD) patients following video capsule endoscopy(VCE) and to assess the usefulness of Lewis score and the Patency Capsule.METHODS: Patency Capsule was performed in every patient that had indication for VCE, and those with negative patency did not undergo VCE. Patients with established CD that underwent VCE between January 2011 and February 2014 were selected for this study; those with suspected CD were excluded, independent of VCE results, since our purpose was to address differences in therapeutic regimen in CD patients before and after VCE. Patients with inconclusive VCE were also excluded. Patients had to be free of non-steroidal anti-inflammatories for at least 1 mo. Those patients who met these criteria were allocated into one of three groups: Staging group(asymptomatic CD patients that underwent VCE for staging of CD), Flare group(patients with active CD), or Post-op group(CD patients evaluated for post-operative recurrence). Lewis score was calculated for every VCE procedure. Statisticalanalysis was performed to address the impact of VCE findings on the therapeutic management of CD patients and to evaluate the utility of the Lewis score.RESULTS: From a total of 542 VCEs, 135 were performed in patients with CD. Patency capsule excluded nearly 25% of the patients who were supposed to undergo VCE. No videocapsule retention during VCE was reported. From these 135 patients, 29 were excluded because CD diagnosis was not established at the time of VCE. Therefore, a total of 106 patients were included in the final analysis. From these, the majority were in the Staging group(n = 73, 69%), and the remaining were in the Flare(n = 23, 22%) or Post-op(n = 10, 9%) group. Median time between diagnosis and VCE was 5.5 years. Overall, VCE determined changes in the treatment of 40% of patients: only 21% remained free of immunosuppressors after VCE compared to 44% before VCE(P < 0.001). The differences in therapy before and after VCE achieved statistical significance in the Staging and Flare groups. In addition, patients were significantly different when stratified regarding time since diagnosis to the date of VCE. A higher Lewis score was associated with therapeutic modifications(P < 0.0001); where a score higher than 1354 was related to 90% probability of changing therapy [area under the receiver operative characteristic(AUROC) 0.80(95%CI: 0.69-0.88)]. CONCLUSION: VCE significantly changed the therapeutic management of CD patients, even in those with long-term disease. Systematic use of Patency capsule allowed for no videocapsule retention.

Hematopoietic stem cell transplantation for Crohn's disease: Gaps, doubts and perspectives

Crohn's disease(CD) is an inflammatory bowel disease that can affect any site of the digestive system. It occurs due to an immunological imbalance and is responsible for intestinal mucosal lesions and complications such as fistulas and stenoses. Treatment aims to stabilize the disease, reducing the symptoms and healing intestinal lesions. Surgical procedures are common in patients. Cell therapy was initially used to treat this disease in patients who also suffered from lymphoma and leukemia and were considered to be good candidates for autologous and allogeneic transplantation. After transplantation, an improvement was also observed in their CD. In 2003, the procedure began to be used to treat the disease itself, and several case series and randomized studies have been published since then; this approach currently comprises a new option in the treatment of CD. However, considerable doubt along with significant gaps in our knowledge continue to exist in relation to cell therapy for CD. Cell therapy is currently restricted to the autologous modality of hematopoietic stem cell transplantation and, experimentally, to mesenchymal stromal cells to directly treat lesions of the anal mucosa. This article presents the supporting claims for transplantation as well as aspects related to the mobilization regime, conditioning and perspectives of cell therapy.

Fecal marker levels as predictors of need for endoscopic balloon dilation in Crohn's disease patients with anastomotic strictures

AIM To evaluate the accuracy and best cut-off value of fecal calprotectin(FC) and fecal lactoferrin(FL) to predict disease recurrence in asymptomatic patients presenting with anastomotic strictures. METHODS This was a longitudinal single tertiary center study based on prospectively collected data(recorded in a clinical database created for this purpose) performed between March 2010 and November 2014. Crohn's disease(CD) patients with anastomotic stricture who submitted to postoperative endoscopic evaluation were included. Stools were collected on the day before bowel cleaning for FC and FL. Endoscopic balloon dilation(EBD) was performed if the patient presented an anastomotic stricture not traversed by the colonoscope, regardless of patients' symptoms. Successful dilation was defined as passage of the colonoscope through the dilated stricture into the neotermimal ileum.Postoperative recurrence was defined as a modified Rutgeerts score of ≥ i2 b. RESULTS In a total of 178 patients who underwent colonoscopy, 58 presented an anastomotic stricture, 86% were asymptomatic, and 48(54% male; median age of 46.5 years) were successfully dilated. Immediate success rate was 92% and no complications were recorded. FC and FL levels correlated significantly with endoscopic recurrence(P < 0.001) with an optimal cut-off value of 90.85 μg/g(sensitivity of 95.5%, specificity of 69.2%, positive predictive value(PPV) of 72.4%, negative predictive value(NPV) of 94.7% and accuracy of 81%] for FC and of 5.6 μg/g(sensitivity of 77.3%, specificity of 69.2%, PPV of 68%, NPV of 78.4% and accuracy of 72.9%) for FL.CONCLUSION Fecal markers are good predictors of CD endoscopic recurrence in patients with asymptomatic anastomotic stricture. FC and FL may guide the need for EBD in this context.

Postprandial response of bone turnover markers in patients with Crohn's disease

AIM:To investigate the postprandial response of bone turnover markers in patients with Crohn’s disease(CD).METHODS:Fifty nine patients with CD aged 38±14years,and 45 healthy individuals matched for age and body mass index were included in the study.All participants underwent an oral glucose tolerance test(OGTT)after an overnight fast and serum levels of the bone resorption marker C-terminal crosslinking telopeptide of type?Ⅰ?collagen(CTX-Ⅰ)and the bone formation marker procollagen type?Ⅰ?N propeptide were measured.Activity of the disease was assessed by calculation of the Crohn’s disease activity index(CDAI).RESULTS:Serum CTX-I was significantly higher in patients compared to controls(CTX-I:453±21 pg/mL vs 365±25 pg/mL,P=0.008),and values were significantly correlated with the activity of the disease(r=0.435,P=0.001).Results from OGTT-induced suppression of CTX-I showed two different trends.Patients with more active disease(assessed as CDAI>150)had a more excessive suppression of CTX-I compared to controls(55%vs 43%P<0.001),while patients on remission(assessed as CDAI<150)demonstrated an attenuated CTX-I suppression(30%vs 43%P<0.001).In line with this,CTX-I suppression after oral glucose load was significantly correlated with the activity of the disease(r=0.913,P<0.001).CONCLUSION:The physiological skeletal response of postprandial suppression of bone resorption is maintained in patients with CD and is strongly dependent to the activity of the disease.