Treat to target in Crohn’s disease:A practical guide for clinicians

A treat-to-target(T2T)approach applies the principles of early intervention and tight disease control to optimise long-term outcomes in Crohn's disease.The Selecting Therapeutic Targets in Inflammatory Bowel Disease(STRIDE)-II guidelines specify short,intermediate,and long-term treatment goals,documenting specific treatment targets to be achieved at each of these timepoints.Scheduled appraisal of Crohn’s disease activity against pre-defined treatment targets at these timepoints remains central to determining whether current therapy should be continued or modified.Consensus treatment targets in Crohn’s disease comprise combination clinical and patient-reported outcome remission,in conjunction with biomarker normalisation and endoscopic healing.Although the STRIDE-II guidelines endorse the pursuit of endoscopic healing,clinicians must consider that this may not always be appropriate,acceptable,or achievable in all patients.This underscores the need to engage patients at the outset in an effort to personalise care and individualise treatment targets.The use of non-invasive biomarkers such as faecal calprotectin in conjunction with cross-sectional imaging techniques,particularly intestinal ultrasound,holds great promise;as do emerging treatment targets such as transmural healing.Two randomised clinical trials,namely,CALM and STARDUST,have evaluated the efficacy of a T2T approach in achieving endoscopic endpoints in patients with Crohn’s disease.Findings from these studies reflect that patient subgroups and Crohn’s disease characteristics likely to benefit most from a T2T approach,remain to be clarified.Moreover,outside of clinical trials,data pertaining to the real-world effectiveness of a T2T approach remains scare,highlighting the need for pragmatic real-world studies.Despite the obvious promise of a T2T approach,a lack of guidance to support its integration into real-world clinical practice has the potential to limit its uptake.This highlights the need to describe strategies,processes,and models of care capable of supporting the integration and execution of a T2T approach in real-world clinical practice.Hence,this review seeks to examine the current and emerging literature to provide clinicians with practical guidance on how to incorporate the principles of T2T into routine clinical practice for the management of Crohn’s disease.

Surgical and non-surgical risk factors affecting the insufficiency of ileocolic anastomosis after first-time surgery in Crohn’s disease patients

BACKGROUND Crohn's disease(CD)often necessitates surgical intervention,particularly when it manifests in the terminal ileum and ileocecal valve.Despite undergoing radical surgery,a subset of patients experiences recurrent inflammation at the anasto-motic site,necessitating further medical attention.AIM To investigate the risk factors associated with anastomotic insufficiency following ileocecal resection in CD patients.METHODS This study enrolled 77 patients who underwent open ileocolic resection with pri-mary stapled anastomosis.Patients were stratified into two groups:Group I co-mprised individuals without anastomotic insufficiency,while Group II included patients exhibiting advanced anastomotic destruction observed endoscopically or those requiring additional surgery during the follow-up period.Surgical and non-surgical factors potentially influencing anastomotic failure were evaluated in both cohorts.RESULTS Anastomotic insufficiency was detected in 12 patients(15.6%),with a mean time interval of 30 months between the initial surgery and recurrence.The predomi-nant reasons for re-intervention included stenosis and excessive perianastomotic lesions.Factors associated with a heightened risk of anastomotic failure encompassed prolonged postoperative obstruction,anastomotic bleeding,and clinically confirmed micro-leakage.Additionally,patients in Group II exhibited preoperative malnutrition and early recurrence of symptoms related to CD.CONCLUSION Successful surgical outcomes hinge on the attainment of a fully functional anastomosis,optimal metabolic status,and clinical remission of the underlying disease.Vigilant endoscopic surveillance following primary resection facilitates the timely identification of anastomotic failure,thereby enabling noninvasive interventions.

Short- and long-term efficacy of endoscopic balloon dilation in Crohn's disease strictures

AIM:To evaluate short- and long-term efficacy of endoscopic balloon dilation in a cohort of consecutive patients with symptomatic Crohn's disease (CD)-related strictures. METHODS:Twenty-six CD patients (11 men; median age 36.8 year, range 11-65 years) with 27 symptomatic strictures underwent endoscopic balloon dilation (EBD).Both naive and post-operative strictures, of any length and diameter, with or without associated fistula were included. After a clinical and radiological assessment, EBD was performed with a Microvasive Rigiflex through the scope balloon system. The procedure was considered successful if no symptom reoccurred in the following 6 mo. The long-term clinical outcome was to avoid surgery. RESULTS:The mean follow-up time was 40.7 ± 5.7 mo (range 10-94 mo). In this period, forty-six EBD were performed with a technical success of 100%. No procedure-related complication was reported. Surgery was avoided in 92.6% of the patients during the entire follow-up. Two patients, both presenting ileocecal strictures associated with fistula, failed to respond to the treatment and underwent surgical strictures resection. Of the 24 patients who did not undergo surgery, 11 patients received 1 EBD, and 13 required further dilations over time for the treatment of relapsing strictures (7 patients underwent 2 dilations, 5 patients 3 dilations, and 1 patient 4 dilations). Overall, the EBD success rate after the first dilation was 81.5%. No difference was observed between the EBD success rate for naive (n = 12) and post-operative (n = 15) CD related strictures (P > 0.05). CONCLUSION:EBD appears to be a safe and effective procedure in the therapeutic management of CD-related strictures of any origin and dimension in order to prevent surgery.

Clinical utility of a new endoscopic scoring system for Crohn's disease

AIM:To evaluate the clinical value of the newly modified Simple Endoscopic Score for Crohn's disease(m SES-CD).METHODS:Seventy-six Crohn's disease(CD) patients who underwent transanal double balloon endoscopy(DBE) in our hospital between 2003 and 2012 were retrospectively reviewed. DBE is defined as small intestinal endoscopy using two attached balloons. We included patients with stenosis which hampered passage of the scope and those who underwent DBE with observation for at least 80 cm from the ileocecal valve. Our new m SES-CD assesses the endoscopic activity of two consecutive small intestinal segments located 0-40 cm and 40-80 cm from the ileocecal valve by DBE,in addition to the activity of four colorectal segments. To compare the usefulness of m SES-CD with SES-CD,we similarly divided the patients into two groups according to total m SES-CD score(low disease activity group,< 4; high disease activity group,≥ 4). The clinical value of m SES-CD in predicting clinical outcome in patients with CD was evaluated using the occurrence of surgery after DBE as an endpoint.RESULTS:Median age of the 76 CD patients was 36 years(range,16-71). Thirty-nine patients had stenosis which hampered passage of the DBE to 80 cm on the proximal side from the ileocecal valve. Median evaluable length of small intestine by DBE was 80 cm(range,3-200). A total of 74 patients had one or more small intestinal lesions detected by DBE,of which 62(83.8%) were within 80 cm of the ileocecal valve on the proximal side. Only two patients(2.7%) with proximal-side lesions more than 80 cm from the ileocecal valve did not have lesions within 80 cm. Patients with high m SES-CD scores showed significantly shorter surgeryfree survival than those with low scores(P < 0.05). In contrast,surgery-free survival did not significantly differ between the low and high SES-CD groups(P > 0.05). Multivariate analysis by a Cox proportional hazards model identified m SES-CD as an independent factor for surgery-free survival.CONCLUSION:m SES-CD is useful in evaluating the risk of surgery-free survival in patients with CD.

Short and long-term outcomes of endoscopic balloon dilatation for Crohn's disease strictures

AIM:To investigate the short and long-term outcomes of endoscopic balloon dilatation(EBD) for Crohn's disease(CD) strictures.METHODS:Between January 1995 and December 2011,47 EBD procedures were performed in 30 patients(8 females and 22 males) with CD.All patients had strictures through which an endoscope could not pass,and symptoms of these strictures included abdominal pain,abdominal fullness,nausea,and/or vomiting.The 47 strictures included 17 anastomotic and 30 de novo strictures.Endoscopy and dilatation were performed under conscious sedation with intravenous diazepam or flunitrazepam.The dilatations were all performed using through-the-scope balloons with diameters from 8 mm to 20 mm on inflation and lengths of 30-80 mm.Each dilatation session consisted of two to four,3-min multistep inflations of the balloon,repeated at intervals of 1 wk until adequate dilatation(up to 15-20 mm in diameter) was achieved.The follow-up data were collected from medical records and analyzed retrospectively.Primary success was defined as passage of the scope through the stricture after EBD.Longterm outcomes were analyzed focusing on interventionfree survival and surgery-free survival demonstrated by the Kaplan-Meier method.(Intervention-free meant cases in which neither endoscopic balloon re-dilatation nor surgery was needed after the first dilatation during the observation period).The log rank test was used to evaluate the difference in long-term outcomes between anastomotic and de novo stricture cases.RESULTS:Primary success was achieved in 44 of the 47 strictures(93.6%).Balloon dilatations failed in 3 cases(6.4%).In 1 case,EBD was a technical failure because the guide-wire could not be passed through the stricture which showed severe adhesion and was a flexural lesion of the intestine.In 2 cases,unexpected perforations occurred immediately after balloon dilatation.Of the 47 treatments,complications occurred in 5(10.6%).All 5 patients had de novo strictures.One suffered bleeding,two high fever and there were colorectal perforations.One of the patients with a colorectal perforation was treated surgically,the other was managed conservatively.These 2 cases correspond to the two aforementioned EBD failures.Long-term outcomes were evaluated for the 44 successfully-treated strictures after a median follow-up of 26 mo(range,2-172 mo).During the observation period,re-strictures after EBDs occurred in 26 cases(60.5%).Fourteen of these 26 re-stricture cases underwent EBD again,but in two EBD failed and surgery was ultimately performed in both cases.Twelve of the 26 re-stricture cases were initially treated surgically when the re-strictures occurred.Finally,30 of the 47 strictures(63.8%) were successfully managed with EBD,allowing surgery to be avoided.Intervention-free survival evaluated by the Kaplan-Meier method was 75% at 12 mo,58% at 24 mo,and 43% at 36 mo.There was no significant difference between the anastomotic strictures(n = 16) and de novo strictures(n = 28) in the intervention-free survival as evaluated by the log-rank test.Surgery-free survival evaluated by the Kaplan-Meier method was 90% at 12 mo,75% at 24 mo,and 53% at 36 mo.The 16 anastomotic strictures were associated with significantly better surgery-free survivals than the 28 de novo strictures(log-rank test:P < 0.05).CONCLUSION:Anastomotic strictures were associated with better long-term outcomes than de novo strictures,indicating that stricture type might be useful for predicting the long-term outcomes of EBD.

Endoscopic response to tumor necrosis factor inhibitors predicts long term benefits in Crohn's disease

BACKGROUND Identifying predictors of therapeutic response is the cornerstone of personalized medicine.AIM To identify predictors of long-term mucosal healing(MH) in patients with Crohn's disease(CD) treated with tumor necrosis factor α(TNF-α) inhibitors.METHODS Prospective single center study. Consecutive patients with clinically active CD requiring treatment with a TNF-α inhibitor were included. A baseline segmental CD Endoscopic Index of Severity(CDEIS) ≥ 10 in at least one segment or the presence of ulcerations were required for inclusion. Clinical, biological and endoscopic data were obtained at baseline, weeks 14 and 46. Endoscopic response(ER) was defined as a decrease ≥ 50% from baseline CDEIS and MH as partial CDEIS ≤ 5 in all segments.RESULTS Of 62 patients were included. At baseline, median CD Activity Index and CDEIS were 201 and 6.7, respectively with a significant reduction after one year of treatment(53 and 3.0 respectively, P < 0.001). At week 14, 56% of patients achieved ER and 34% MH. At week 46, the corresponding percentages were 52%and 44%. Baseline disease characteristics or biomarkers did not predict MH. A decrease from baseline CDEIS at week 14 of at least 80% was the best predictor of MH at week 46(59% sensitivity and 91% specificity; area under the curve =0.778).CONCLUSION Clinical and biomarker data are not useful predictors of response to TNF-αinhibitors in CD, whereas ER to induction therapy, defined as 80% reduction in global CDEIS, is a robust predictor of long-term MH. Achievement of this endoscopic endpoint may be considered as a therapeutic target for anti-TNF-αtherapy.

Magnetic resonance imaging and Crohn's disease endoscopic index of severity: Correlations and concordance

AIM To examine the correlation between magnetic resonance imaging(MRI) and endoscopic index of severity(CDEIS) in patients with Crohn's disease(CD).METHODS This was a retrospective study of 104 patients with CD that were treated at the Ruijin Hospital between March 2015 and May 2016. Among them, 61 patients with active CD were evaluated before/after treatment. MRI and endoscopy were performed within 7 d. CDEIS was evaluated. MRI parameters included Ma RIA scores, total relative contrast enhancement(tRCE), arterialRCE(aRCE), portalRCE(pRCE), delay phaseRCE(dRCE), and apparent diffusion coefficient. The correlation and concordance between multiple MRI findings and CDEIS changes before and after CD treatment were examined.RESULTS Among the 104 patients, 61 patients were classified as active CD and 43 patients as inactive CD. Gender, age, disease duration, and disease location were not significantly different between the two groups(all P > 0.05). CRP levels were higher in the active group than in the inactive group(25.12 ± 4.12 vs 5.14 ± 0.98 mg/L, P < 0.001). Before treatment, the correlations between CDEIS and MaRIAs in all patients were r = 0.772 for tRCE, r = 0.754 for aRCE, r = 0.738 for pRCE, and r = 0.712 for dRCE(all MaRIAs, P < 0.001), followed by MRI single indexes. Among the active CD patients, 44 cases were remitted to inactive CD after treatment. The correlations between CDEIS and MaRIAs were r = 0.712 for aRCE, r = 0.705 for tRCE, r = 0.685 for pRCE, and r = 0.634 for dRCE(all MaRIAs, P < 0.001).CONCLUSION Arterial Ma RIA should be an indicator for CD follow-up and dynamic assessment. CD treatment assessment was not completely concordant between CDEIS and MRI.

Infliximab trough level combined with inflammatory biomarkers predict long-term endoscopic outcomes in Crohn’s disease under infliximab therapy

BACKGROUND Infliximab trough level(ITL)severely affects therapeutic outcomes of Crohn’s disease(CD)patients under infliximab(IFX).Recently,frontier research has focused on identifying ITL based on different therapeutic targets.Although previous studies have elaborated clinical value of ITL monitoring on short-term outcomes in CD patients during therapy,studies contraposing the predictive value of ITL on long-term endoscopic outcomes in CD patients are still scarce domestically and overseas.AIM To explore the predictive value of ITL in combination with inflammatory biomarkers on long-term endoscopic outcomes in CD with clinical remission during IFX maintenance therapy.METHODS CD patients with endoscopic remission under long-term IFX maintenance therapy in the First Affiliated Hospital of Zhejiang Chinese Medicine University from January 2012 to December 2020 were collected.ITL and inflammatory biomarkers were continuously monitored during the therapy.The Step I study was conducted from weeks 14 to 54 of IFX treatment.The Step II study was conducted from weeks 54 to 108 of IFX treatment.Endoscopic outcomes were defined as endoscopic activity(Crohn’s disease endoscopic index of severity score>2 points or Rutgeerts score>i1)and endoscopic remission(Crohn’s disease endoscopic index of severity score≤2 points or Rutgeerts≤i1).Endoscopic relapse free survival was defined as endoscopic remission at the beginning of the study stage and maintaining endoscopic remission during the study stage.RESULTS At week 14,low ITL[odds ratio(OR)=0.666,95%confidence interval(CI):0.514-0.862,P<0.01]and high fecal calprotectin(FCP)level(OR=1.002,95%CI:1.001-1.004,P<0.01)increased the risk of endoscopic activity at week 54.At week 54,low ITL(OR=0.466,95%CI:0.247-0.877,P<0.01)and high C-reactive protein(CRP)level(OR=1.590,95%CI:1.007-2.510,P<0.01)increased the risk of endoscopic activity at week 108.At week 14,ITL≤5.60μg/mL[area under the curve(AUC)=0.83,95%CI:0.73-0.90,P<0.001]and FCP>238μg/g(AUC=0.82,95%CI:0.72-0.89,P<0.001)moderately predicted endoscopic activity at week 54.ITL≤5.60μg/mL in combination with FCP>238μg/g indicated 82.0%possibility of endoscopic activity.At week 54,ITL≤2.10μg/mL(AUC=0.85,95%CI:0.72-0.93,P<0.001)and CRP>3.00 mg/L(AUC=0.73,95%CI:0.60-0.84,P=0.012)moderately predicted moderate endoscopic activity at week 108.ITL≤2.10μg/mL in combination with CRP>3.00 mg/L indicated 100.0%possibility of endoscopic activity.From weeks 14 to 54 of IFX treatment,patients with ITL>5.60μg/mL had higher rate of endoscopic relapse free survival than those with ITL≤5.60μg/mL(95.83%vs 46.67%).From weeks 54 to 108 of IFX treatment,patients with ITL>2.10μg/mL had higher rate of endoscopic survival free relapsed rate than those with ITL≤2.10μg/mL(92.68%vs 30.77%).CONCLUSION Combination of ITL,CRP,and FCP contribute to long-term endoscopic prognosis monitoring.During IFX maintenance treatment,low ITL,high CRP level,and high FCP level were independent risk factors of CD patients with clinical remission in adverse endoscopy outcomes within 1-year follow-up.

Endoscopic balloon dilation for management of stricturing Crohn’s disease in children

BACKGROUND Crohn’s disease(CD)has a multitude of complications including intestinal strictures from fibrostenotic disease.Fibrostenotic disease has been reported in 10%-17%of children at presentation and leads to surgery in 20%-50%of cases within ten years of diagnosis.When symptoms develop from these strictures,the treatment in children has primarily been surgical resection.Endoscopic balloon dilation(EBD)has been shown to be a safe and efficacious alternative to surgery in adults,but evidence is poor in the literature regarding its safety and efficacy in children.AIM To evaluate the outcomes of children with fibrostenosing CD who underwent EBD vs surgery as a treatment.METHODS In a single-center retrospective study,we looked at pediatric patients(ages 0-18)who carry the diagnosis of CD,who were diagnosed after opening a dedicated Inflammatory Bowel Disease clinic on July 1,2012 through May 1,2019.We used diagnostic codes through our electronic medical record to identify patients with CD with a stricturing phenotype.The type of intervention for patients’strictures was then identified through procedural and surgical billing codes.We evaluated their demographics,clinical variables,whether they underwent EBD vs surgery or both,and their clinical outcomes.RESULTS Of the 139 patients with CD,25(18%)developed strictures.The initial intervention for a stricture was surgical resection in 12 patients(48%)and EBD in 13 patients(52%).However,4(33%)patients whom initially had surgical resection required follow up EBD,and thus 17 total patients(68%)underwent EBD at some point in their treatment process.For those 8 patients who underwent successful surgical resection alone,4 of these patients(50%)had a fistula present near the stricture site and 4(50%)had strictures greater than 5 cm in length.All patients who underwent EBD had no procedural complications,such as a perforation.Twenty-two(88%)of the treated strictures were successfully managed by EBD and did not require any further surgical intervention during our follow up period.CONCLUSION EBD is safe and efficacious as an alternative to surgery for palliative management of strictures in selected pediatric patients with CD.

Endoscopic balloon dilation of crohn's disease stricturessafety,efficacy and clinical impact

AIM To evaluate the incidence of anastomotic strictures after intestinal resection in Crohn's disease(CD), demonstrate long-term efficacy and safety of endoscopic balloon dilation(EBD) in CD strictures and its impact on the diagnosis of subclinical postoperative endoscopic recurrence. METHODS Retrospective single tertiary center study based on prospectively collected data between 2010 and 2015including anastomotic and non-anastomotic strictures. RESULTS29% of 162 CD patients included developed an anastomotic stricture. 43 patients with anastomotic strictures and 37 with non-anastomotic strictures underwent EBD; technical success was 97.7% and 100%, respectively, however, 63% and 41% needed repeat dilation during the 4.4-year follow-up. Longer periods between surgery and index colonoscopy and higher lactoferrin levels were associated with the presence of stricture after surgery. Calprotectin levels > 83.35 μg/g and current or past history of smoking were associated with a shorter time until need for dilation(HR = 3.877, 95%CI: 1.480-10.152 and HR = 3.041, 95%CI: 1.213-7.627). Anastomotic strictures had a greater need for repeat dilation(63% vs 41%, P = 0.047). No differences were found between asymptomatic and symptomatic cohorts. Disease recurrence diagnosis was only possible after EBD in a third of patients. CONCLUSION EBD is an effective and safe alternative to surgery, with a good short and long-term outcome, postponing or even avoiding further surgery. EBD may allow to diagnose disease recurrence in patients with no clinical signs/biomarkers of disease activity.

Application of Percutaneous Endoscopic Gastrojejunostomy in Duodenal Crohn’s Disease-Associated Strictures

Background Duodenal Crohn’s disease(CD)-associated strictures are related to a high risk of malnutrition,and effective methods of enteral nutrition(EN)are needed to support these patients.The purpose of this study was to evaluate the efficacy and safety of percutaneous endoscopic gastrojejunostomy(PEG-J)for the treatment of duodenal CD-associated strictures.Methods Patients with strictures associated with duodenal CD were recruited.The clinical data,stricture characteristics,nutritional status,duration of PEG-J tube placement,complications,and follow up periods were recorded.Results A total of 24 patients with duodenal CD-associated strictures underwent PEG-J tube placement.The PEG-J tubes were successfully placed in 100%of the patients within an average of 19.04±2.94 minutes.There were no procedure-related complications.There were no major complications after PEG-J tube placement,and only two minor complications(8.33%)occurred.PEG-J was well tolerated in all patients.The mean Karnofsky score was 67.50±7.94 points and 83.33±7.02 points(P=0.000),the mean body mass index was 17.02±1.85 kg/m^(2)and 18.10±1.78 kg/m^(2)(P=0.045),and the mean Alb level was 35.28±5.35 g/dl and 38.68±5.10 g/dl(P=0.029)before PEG-J and 3 months after PEG-J,respectively.The median CD Activity Index(CDAI score)was 144(range 87-280)and the median C-reactive protein(CRP)was 1.90 mg/L(0.5-67.9 mg/L)after PEG-J,which were significantly lower than the respective 196 mg/L(range 114-331 mg/L)(P=0.044)and 3.75 mg/L(range 0.5-67 mg/L)(P=0.033)before PEG-J.Conclusion PEG-J was a safe,well-tolerated and effective method for the treatment of duodenal CD-associated strictures.PEG-J improved the patient’s nutritional status and reduced disease CD activity.These findings suggest that PEG-J is an option for EN in patients with duodenal CD-associated strictures.

The Efficacy and Role of Probiotics for Maintenance of Remission in Crohn’s Disease: A Meta-Analysis and Survey

Crohn’s disease (CD) is a chronic inflammatory disease whose pathogenesis involves disturbances of the gastrointestinal microbiota. As the prevalence of CD increases, the need for a more effective and safe treatment is integral. Probiotics have been reported to be beneficial for numerous gastrointestinal diseases, providing health benefits and considering the microbial characteristics of CD’s pathogenesis. However, our knowledge of the efficacy of probiotic therapy in preventing relapse in CD is limited. How gastroenterologists have incorporated probiotics into their practice or probiotics observed implications for patients with CD has not been assessed. A quantitative survey was distributed to determine how gastroenterologists perceive and use probiotic-based therapies in CD practice. The second objective was to conduct a meta-analysis of the efficacy of probiotics for maintaining remission and preventing clinical and endoscopic relapse in CD. Performing a meta-analysis and survey will examine the role of probiotics in CD treatment. Surveyed gastroenterologists cited that probiotics have an adjunctive role and have been observed to alleviate common CD symptoms. Probiotics seem effective in reducing the relapse rate, specifically those of the multi-strain variety are more likely to be effective in maintaining CD remission. Further research with larger trials is required to replicate and solidify this efficacy. The meta-analysis only assessed the efficacy of probiotics as a maintenance treatment as measured by the risk of relapse;thus, no evidence supports probiotics’ ability to induce remission. The results of the meta-analysis and survey indicate that probiotics cannot treat CD without accompanying conventional drug therapies;nevertheless, independent of treatment capacities, probiotics still yield health benefits for CD patients.

Endoscopic management of inflammatory bowel disease strictures

Stricture formation is a common complication of Crohn’s disease, occurring in approximately one third of all patients with this condition. While the traditional management of such strictures has been largely surgical, there have been case series going back three decades high-lighting the potential role of endoscopic balloon dilation in this clinical setting. This review article summarizes the stricture pathogenesis, focusing on known clinical and genetic risk factors. It then highlights the endo-scopic balloon dilation research to date, with particular emphasis on three large recent case series. It concludes by describing the literature consensus regarding specific methodology and presenting avenues for future investigations.

Endoscopic management of Crohn's strictures

Symptomatic intestinal strictures develop in more than one third of patients with Crohn's disease(CD) within 10 years of disease onset. Strictures can be inflammatory, fibrotic or mixed and result in a significant decline in quality of life, frequently requiring surgery for palliation of symptoms. Patients under the age of 40 with perianal disease are more likely to suffer from disabling ileocolonic disease thus may have a greater risk for fibrostenotic strictures. Treatment options for fibrostenotic strictures are limited to endoscopic and surgical therapy. Endoscopic balloon dilatation(EBD) appears to be a safe, less invasive and effective alternative modality to replace or defer surgery. Serious complications are rare and occur in less than 3% of procedures. For non-complex strictures without adjacent fistulizaation or perforation that are less than 5 cm in length, EBD should be considered as first-line therapy. The aim of this review is to present the current literature on the endoscopic management of small bowel and colonic strictures in CD, which includes balloon dilatation, adjuvant techniques of intralesional injection of steroids and anti-tumor necrosis factor, and metal stent insertion. Short and long-term outcomes, complications and safety of EBD will be discussed.

Prevention of recurrence after surgery for Crohn's disease: Efficacy of infliximab

After surgery for Crohn's disease (CD), early endoscopic lesions are frequently observed despite no symptomatic recurrence. The severity of lesions found at postoperative endoscopy is reported to be a strong predictive factor for future clinical recurrence. If endoscopic lesions in the early postoperative period can be reduced with medications, symptomatic recurrence will likely be delayed and decreased. Before the introduction of biologic therapies, various medications were used for the maintenance of clinical remission after surgery; however, few demonstrated consistent efficacy. Infliximab is a recombinant anti-tumor necrosis factor-α antibody. Although infliximab is one of the most effective medications in the management of CD, its efficacy for early endoscopic lesions after surgery has not yet been assessed. The author and colleagues recently conducted a prospective study in order to investigate the impact of infliximab on early endoscopic lesions after resection for CD. We found that infliximab therapy showed clear suppressive effects on clinical and endoscopic disease activity in patients with early endoscopic lesions after resection.

Serum immune-activation potency and response to anti-TNF-α therapy in Crohn's disease

AIM:To study whether immune-activation stage in serum of adult Crohn's disease (CD) patients correlates with disease activity and with treatment response to antitumor necrosis factor-α (TNF-α) therapy.METHODS:Serum samples were obtained from 15 adult CD patients introduced to anti-TNF-α therapy.The individual stage of immune activation was studied applying our new in vitro assay,in which target cells (donor derived peripheral blood mononuclear cells) were cultured with patient serum and the T-cell activation induced by the patient serum was studied using a panel of markers for effector [interferon γ (IFNγ),interleukin (IL)-5] and regulatory T-cells [forkhead transcription factor 3 (FOXP3) and glucocorticoid-induced tumour necrosis factor receptor (GITR)].The endoscopic disease activity was assessed with the Crohn's disease endoscopic index of severity (CDEIS) before and 3 mo after therapy with an anti-TNF-α agent.RESULTS:Low induction of FOXP3 and GITR in target cells cultured in the presence of patient serum was associated with high disease activity i.e.CDEIS assessed before therapy (r=-0.621,P=0.013 and r=-0.625,P=0.013,respectively).FOXP3 expression correlated inversely with pre-treatment erythrocyte sedimentation rate (r=-0.548,P=0.034).Low serum induced FOXP3 (r=-0.600,P=0.018) and GITR (r=-0.589,P=0.021) expression and low IFNγ secretion from target cells (r =-0.538,P=0.039) associated with treatment response detected as a decrease in CDEIS.CONCLUSION:The immune-activation potency in the patient serum prior to anti-TNF-α therapy reflected intestinal inflammation and the therapeutic response.

Risk factors for recurrence after bowel resection for Crohn’s disease

BACKGROUND Complications of Crohn’s disease such as intestinal obstruction,fistula or perforation often need surgical treatment.Nearly 70%-80%patients with Crohn’s disease would receive surgical treatment during the lifetime.However,surgical treatment is incurable for Crohn’s disease.The challenge of recurrence postoperatively troubles both doctors and patients.Over 50%patients would suffer recurrence postoperatively.Some certain risk factors are associated with recurrence of Crohn’s disease.AIM To evaluate the risk factors for endoscopic recurrence and clinical recurrence after bowel resection in Crohn’s disease.METHODS Patients diagnosed Crohn’s disease and received intestinal resection between April 2007 and December 2013 were included in this study.Data on the general demographic information,preoperative clinical characteristics,surgical information,postoperative clinical characteristics were collected.Continuous data are expressed as median(inter quartile range),and categorical data as frequencies and percentages.Kaplan-Meier method was applied to estimate the impact of the clinical variables above on the cumulative rate of postoperative endoscopic recurrence and clinical recurrence,then log-rank test was applied to test the homogeneity of those clinical variables.Multivariate Cox proportional hazard regression analysis was performed to identify the risk factors of postoperative endoscopic recurrence and clinical recurrence.RESULTS A total of 64 patients were included in this study.The median follow-up time for the patients was 17(9.25-25.75)mo.In this period,41 patients(64.1%)had endoscopic recurrence or clinical recurrence.Endoscopic recurrence occurred in 34(59.6%)patients while clinical recurrence occurred in 28(43.8%)patients,with the interval between the operation and recurrence of 13.0(8.0-24.5)months and 17.0(8.0-27.8)mo,respectively.In univariate analysis,diagnosis at younger age(P<0.001),disease behavior of penetrating(P=0.044)and preoperative use of anti-tumor necrosis factor(TNF)(P=0.020)were significantly correlated with endoscopic recurrence,while complication with perianal lesions(P=0.032)and preoperative use of immunomodulatory(P=0.031)were significantly correlated with clinical recurrence.As to multivariate analysis,diagnostic age(P=0.004),disease behavior(P=0.041)and preoperative use of anti-TNF(P=0.010)were independent prognostic factors for endoscopic recurrence,while complication with perianal lesions(P=0.023)was an independent prognostic factor for clinical recurrence.CONCLUSION Diagnostic age,disease behavior,preoperative use of anti-TNF and complication with perianal lesions were independent risk factors for postoperative recurrence in Crohn’s disease.

Diagnostic classification of endosonography for differentiating colorectal ulcerative diseases: A new statistical method

AIM To establish a classification method for differential diagnosis of colorectal ulcerative diseases, especially Crohn's disease(CD), primary intestinal lymphoma(PIL) and intestinal tuberculosis(ITB).METHODS We searched the in-patient medical record database for confirmed cases of CD, PIL and ITB from 2008 to 2015 at our center, collected data on endoscopic ultrasound(EUS) from randomly-chosen patients who formed the training set, conducted univariate logistic regression analysis to summarize EUS features of CD, PIL and ITB, and created a diagnostic classification method. All cases found to have colorectal ulcers using EUS were obtained from the endoscopy database and formed the test set. We then removed the cases which were easily diagnosed, and the remaining cases formed the perplexing test set. We re-diagnosed the cases in the three sets using the classification method, determined EUS diagnostic accuracies, and adjusted the classification accordingly. Finally, the re-diagnosing and accuracy-calculating steps were repeated.RESULTS In total, 272 CD, 60 PIL and 39 ITB cases were diagnosed from 2008 to 2015 based on the in-patient database, and 200 CD, 30 PIL and 20 ITB cases were randomly chosen to form the training set. The EUS features were summarized as follows: CD: Thickened submucosa with a slightly high echo level and visible layer; PIL: Absent layer and diffuse hypoechoic mass; and ITB: Thickened mucosa with a high or slightly high echo level and visible layer. The test set consisted of 77 CD, 30 PIL, 23 ITB and 140 cases of other diseases obtained from the endoscopy database. Seventy-four cases were excluded to form the perplexing test set. After adjustment of the classification, EUS diagnostic accuracies for CD, PIL and ITB were 83.6%(209/250), 97.2%(243/250) and 85.6%(214/250) in the training set, were 89.3%(241/270), 97.8%(264/270) and 84.1%(227/270) in the test set, and were 86.7%(170/196), 98.0%(192/196) and 85.2%(167/196) in the perplexing set, respectively.CONCLUSION The EUS features of CD, PIL and ITB are different. The diagnostic classification method is reliable in the differential diagnosis of colorectal ulcerative diseases.

Urotensin II levels in patients with inflammatory bowel disease

BACKGROUND Patients with inflammatory bowel disease(IBD)are associated with increased cardiovascular risk and have increased overall cardiovascular burden.On the other hand,urotensin II(UII)is one of the most potent vascular constrictors with immunomodulatory effect that is connected with a number of different cardiometabolic disorders as well.Furthermore,patients with ulcerative colitis have shown increased expression of urotensin II receptor in comparison to healthy controls.Since the features of IBD includes chronic inflammation and endothelial dysfunction as well,it is plausible to assume that there is connection between increased cardiac risk in IBD and UII.AIM To determine serum UII levels in patients with IBD and to compare them to control subjects,as well as investigate possible associations with relevant clinical and biochemical parameters.METHODS This cross sectional study consecutively enrolled 50 adult IBD patients(26 with Crohn’s disease and 24 with ulcerative colitis)and 50 age and gender matched controls.Clinical assessment was performed by the same experienced gastroenterologist according to the latest guidelines.Ulcerative Colitis Endoscopic Index of Severity and Simple Endoscopic Score for Crohn’s Disease were used for endoscopic evaluation.Serum levels of UII were determined using the enzyme immunoassay kit for human UII,according to the manufacturer’s instructions.RESULTS IBD patients have significantly higher concentrations of UII when compared to control subjects(7.57±1.41 vs 1.98±0.69 ng/mL,P<0.001),while there were no significant differences between Crohn’s disease and ulcerative colitis patients(7.49±1.42 vs 7.65±1.41 ng/mL,P=0.689).There was a significant positive correlation between serum UII levels and high sensitivity C reactive peptide levels(r=0.491,P<0.001)and a significant negative correlation between serum UII levels and total proteins(r=-0.306,P=0.032).Additionally,there was a significant positive correlation between serum UII levels with both systolic(r=0.387,P=0.005)and diastolic(r=0.352,P=0.012)blood pressure.Moreover,serum UII levels had a significant positive correlation with Ulcerative Colitis Endoscopic Index of Severity(r=0.425,P=0.048)and Simple Endoscopic Score for Crohn’s Disease(r=0.466,P=0.028)scores.Multiple linear regression analysis showed that serum UII levels retained significant association with high sensitivity C reactive peptide(β±standard error,0.262±0.076,P<0.001)and systolic blood pressure(0.040±0.017,P=0.030).CONCLUSION It is possible that UII is involved in the complex pathophysiology of cardiovascular complications in IBD patients,and its purpose should be investigated in further studies.

Enteroscopy in children and adults with inflammatory bowel disease

Inflammatory bowel disease(IBD)includes Crohn’s disease(CD),ulcerative colitis and unclassified entities.CD commonly involves the terminal ileum and colon but at the time of diagnosis it can be confined to the small bowel(SB)in about 30%of the patients,especially in the young ones.Management of isolated SB-CD can be challenging and objective evaluation of the SB mucosa is essential in differentiating CD from other enteropathies to achieve therapeutic decisions and to plan the follow-up.The introduction of cross-sectional imaging techniques and capsule endoscopy(CE)have significantly expanded the ability to diagnose SB diseases providing a non-invasive test for the visualization of the entire SB mucosa.The main CE limitations are the low specificity,the lack of therapeutic capabilities and the impossibility to take biopsies.Device assisted enteroscopy(DAE)enables histological confirmation when traditional endoscopy,capsule endoscopy and cross-sectional imaging are inconclusive and also allows therapeutic interventions such as balloon stricture dilation,intralesional steroid injection,capsule retrieval and more recently stent insertion.In the current review we will discuss technical aspect,indications and safety profile of DAE in children and adults with IBD.