Small bowel adenocarcinoma and Crohn's disease: Any further ahead than 50 years ago?

This review of the literature on small bowel carcinoma associated with Crohn’s disease specifically addresses the incidence, risk factors, and protective factors which have been identified. It also reviews the clinical presentation, the current modalities of diagnosis, the pathology, treatment, and surveillance. Finally, the prognosis and future direction are addressed. Our experience with small bowel adenocarcinoma in Crohn’s disease is reported. Readers will be provided with a better understanding of this rare and often poorly recognized complication of Crohn’s disease.     

Effectiveness and Power of Abdominal Ultrasonography in the Assessment of Crohn’s Disease Activity: Comparison with Clinical,Endoscopic, and CT Enterography Findings

Background: Non-invasive methods play an important role in clinical assessment of Crohn’s disease. Recent studies have highlighted the effectiveness and reliability of intestinal ultrasonography. We aimed to examine the relationship between intestinal ultrasonography and the clinical, endoscopic, and computed tomography enterography findings, and to assess the activity of Crohn’s disease.Methods: This was a 1-year prospective study involving patients diagnosed with Crohn’s Disease. Clinical and endoscopic activity indices, and intestinal ultrasonography and computed tomography enterography findings were evaluated. Intestinal wall thickness, mesenteric inflammation, lymphadenopathy, and complications were evaluated by intestinal ultrasonograpy and computed tomography enterography, while the superior mesenteric artery flow velocity, resistive index, and Limberg score were assessed by Doppler intestinal ultrasonography.Results: Seventy-nine patients with Crohn’s disease were included. A significant correlation was found between intestinal wall thickness, mesenteric inflammation, and complications in intestinal ultrasonography and computed tomography enterography (P = .0001). According to the receiver operating curve analysis, the intestinal wall thickness, and mesenteric inflammation were correlated with the Crohn’s Disease Activity Index, Harvey–Bradshaw Index, and SES-CD scores (P ˂ .05), and they were very effective in distinguishing active from inactive disease. According to the Crohn’s Disease Activity Index and SES-CD scores, Doppler flow velocity of the superior mesenteric artery was significantly higher in the active group than in the inactive group (P ˂ .05). The Limberg score was very consistent with the Crohn’s Disease Activity Index, Harvey–Bradshaw Index , and the results of the Simple Endoscopic Score for Crohn’s Disease (P < .0001).Conclusion: Our study showed that intestinal ultrasonography is an effective and reliable method for assessment of Crohn’s disease activity compared to clinical, endoscopic, and CTE findings.     

Rapid fecal calprotectin testing to assess for endoscopic disease activity in inflammatory bowel disease: A diagnostic cohort study

Results:One hundred and twenty-six patients, of whom 52% were females, were included in the final analysis with a mean age of 44.4 ± 16.7 years. Comparing FC to endoscopic findings, the following results were calculated: A cutoff point of 100 μg/g showed Sn = 83%, Sp = 67%, PPV = 65%, and NPV = 85%; and 200 μg/g showed Sn = 66%, Sp = 82%, PPV = 73%, and NPV = 77%. Based on ROC curve, the best FC cutoff point to predict endoscopic disease activity was 140 μg/g. Using this reference, FC levels strongly correlated with colorectal, ileocolonic, and ileal disease and predicted endoscopic activity.Conclusions:FC is an accurate test when used as an initial screening tool for patients suspected of having active IBD. Given its noninvasive nature, it may prove to reduce the need for colonoscopy and be an added tool in the management of IBD.     

Assessment of Imaging Features of Crohn’s Disease with MR Enterography

Background: To evaluate the frequency of pathological findings determined on magnetic resonance (MR) enterography (MRE) in patients with Crohn’s Disease.Methods: A retrospective analysis of the MRE images was made in 34 female and 41 male patients (mean age 41 years) with Crohn’s disease. The prevalence of bowel wall (mural thickening, mural edema, mural fat deposits, mucosal enhancement, ulceration, cobblestone appearance, pseudopolyps) and mesenteric fatty tissue alterations (fatty tissue proliferation, mesenteric hypervascularity, enlarged lymph nodes, peri-enteric inflammation, reactive fluid), complications due to penetrating (fistula, sinus tract, abscess) and stenosing processes (fibrotic and inflammatory stenosis, obstruction, dilatation), and involvement of the colon were determined.Results: The most frequently observed changes in the bowel wall and mesenteric fatty tissue were mural thickening (98.7%) and enlargement of mesenteric lymph nodes (76%), respectively. Stenosis was the most common complication (76%). The most frequently seen pathology of the colon was ileocecal valve thickening and enhancement (74.7%).Conclusion: MR enterography is a useful imaging modality for the evaluation of changes in both the mesenteric fatty tissue and the bowel wall. As there is no use of ionizing radiation, MR enterography should be the preferred imaging modality during follow-up of patients with Crohn’s disease.     

Enteroscopy in small bowel Crohn’s disease: A review

Crohn’s disease (CD) is a chronic inflammatory condition of the gastrointestinal tract resulting in inflammation, stricturing and fistulae secondary to transmural inflammation. Diagnosis relies on clinical history, abnormal laboratory parameters, characteristic radiologic and endoscopic changes within the gastrointestinal tract and most importantly a supportive histology. The article is intended mainly for the general gastroenterologist and for other interested physicians. Management of small bowel CD has been suboptimal and limited due to the inaccessibility of the small bowel. Enteroscopy has had a significant renaissance recently, thereby extending the reach of the endoscopist, aiding diagnosis and enabling therapeutic interventions in the small bowel. Radiologic imaging is used as the first line modality to visualise the small bowel. If the clinical suspicion is high, wireless capsule endoscopy (WCE) is used to rule out superficial and early disease, despite the above investigations being normal. This is followed by push enteroscopy or device assisted enteroscopy (DAE) as is appropriate. This approach has been found to be the most cost effective and least invasive. DAE includes balloon-assisted enteroscopy, [double balloon enteroscopy (DBE), single balloon enteroscopy (SBE) and more recently spiral enteroscopy (SE)]. This review is not going to cover the various other indications of enteroscopy, radiological small bowel investigations nor WCE and limited only to enteroscopy in small bowel Crohn’s. These excluded topics already have comprehensive reviews. Evidence available from randomized controlled trials comparing the various modalities is limited and at best regarded as Grade C or D (based on expert opinion). The evidence suggests that all three DAE modalities have comparable insertion depths, diagnostic and therapeutic efficacies and complication rates, though most favour DBE due to higher rates of total enteroscopy. SE is quicker than DBE, but lower complete enteroscopy rates. SBE has quicker procedural times and is evolving but the least available DAE today. Larger prospective randomised controlled trial’s in the future could help us understand some unanswered areas including the role of BAE in small bowel screening and comparative studies between the main types of enteroscopy in small bowel CD.     

Association between orofacial granulomatosis and Crohn’s disease in children: Systematic review

AIM: To review pediatric cases of orofacial granulomatosis (OFG), report disease characteristics, and explore the association between OFG and Crohn’s disease.METHODS: We conducted a systematic review according to the PRISMA guidelines. We searched Medline, LILACS, Virtual Health Library, and Web of Knowledge in September 2013 for cases of OFG in the pediatric age range (< 18 years), with no language limitations. All relevant articles were accessed in full text. The manual search included references of retrieved articles. We extracted data on patients’ characteristics, disease characteristics, association with other diseases, and treatment. We analyzed the data and reported the results in tables and text.RESULTS: We retrieved 173 reports of OFG in children. Mean age at onset was 11.1 ± 3.8 years (range: 2.0-18 years). Prevalence in males was significant higher than in females (P < 0.001), with a male:female ratio of 2:1. Gastrointestinal signs or symptoms were present in 26.0% of children at the time of OFG diagnosis. Overall, 70/173 (40.4%) children received a concomitant diagnosis of Crohn’s disease. In about half (51.4%) of the cases the onset of OFG anticipated the diagnosis of Crohn’s disease, with a mean time between the two diagnoses of 13.1 ± 11.6 mo (range: 3-36 mo). Overall, 21/173 (12.1%) of the children with OFG had perianal disease, while 11/173 (6.4%) had a family history of Crohn’s disease. Both perianal disease and a family history of Crohn’s disease were significantly associated with a higher risk of Crohn’s disease diagnosis in children with OFG [relative risk (RR) = 3.10, 95% confidence interval (CI): 2.46-3.90; RR = 2.74, 95%CI: 2.24-3.36, P < 0.0001 for both). Treatment of OFG included steroids (70.8% of children) and other immunosuppressive drugs (42.7%), such as azathioprine, thalidomide and infliximab.CONCLUSION: High prevalence of Crohn’s disease in children with OFG suggests that OFG may be a subtype of Crohn’s disease.     

Pregnancy and inflammatory bowel disease: Do we provide enough patient education? A British study of 1324 women

AIM To examine patient knowledge and factors influencing knowledge about pregnancy in British women with inflammatory bowel disease(IBD).METHODS This is a post hoc analysis of a study of female members of Crohn's and Colitis United Kingdom, aged 18-45 years who were sent an online questionnaire recording patient demographics, education, employment, marital status, and disease characteristics. Disease related pregnancy knowledge was recorded using Crohn's and colitis pregnancy knowledge score(CCPKnow).RESULTS Of 1324 responders, 776(59%) suffered from Crohn's disease, 496(38%) from ulcerative colitis and 52(4%) from IBD-uncategorised. CCPKnow scores were poor(0-7) in 50.8%, adequate(8-10) in 23.6%, good(11-13) in 17.7% and very good(≥ 14) in 7.8%. Multiple linear regression analysis revealed that higher CCPKnow scores were independently associated with higher educational achievement(P 0.001), younger age at diagnosis(P = 0.003) and having consulted a health care professional about pregnancy and IBD(P = 0.001). CONCLUSION Knowledge was poor in 50%. Speaking with healthcare professionals was a modifiable factor associated with better knowledge. This illustrates the importance of disease related pregnancy education     

Diagnostic precision of fecal calprotectin for inflammatory bowel disease and colorectal malignancy

OBJECTIVES: Fecal calprotectin (FC) is a relatively new marker of intraluminal intestinal inflammation. Using meta-analytical techniques, the study aimed to evaluate the diagnostic precision of FC for inflammatory bowel disease (IBD) and colorectal cancer (CRC) in adults and children. METHODS: Quantitative meta-analysis was performed on prospective studies, comparing FC levels against the histological diagnosis. Sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated for each study. Summary receiver-operating characteristic (sROC) curves and subgroup analysis were undertaken. Study quality and heterogeneity were evaluated. RESULTS: Thirty studies of 5,983 patients were included. FC levels in patients with IBD were higher by 219.2 micrograms per gram (microg/g) compared with normal patients (P < 0.001). sROC curve analysis showed a sensitivity of 0.95 (95% CI 0.93-0.97), specificity of 0.91 (95% CI 0.86-0.91), and an area under the curve (AUC) of 0.95 for the diagnosis of IBD. Patients with colorectal neoplasia had nonsignificantly higher FC levels by 132.2 microg/g compared with noncancer controls (P= 0.18). Sensitivity and specificity of FC for the diagnosis of CRC were 0.36 and 0.71, respectively, with an AUC of 0.66. The diagnostic precision of FC for IBD was higher in children than adults with better accuracy at a cutoff level of 100 microg/g versus 50 microg/g. Sensitivity analysis and metaregression analysis did not significantly alter the results. CONCLUSIONS: FC cannot be recommended as a screening test for CRC in the general population. FC appeared to offer a good diagnostic precision in distinguishing IBD from non-IBD diagnoses, with higher precision at a cutoff of 100 microg/g.     

Crohn's disease and growth deficiency in children and adolescents

Nutritional concerns, linear growth deficiency, and delayed puberty are currently detected in up to 85% of patients with Crohn’s disease (CD) diagnosed at childhood. To provide advice on how to assess and manage nutritional concerns in these patients, a Medline search was conducted using “pediatric inflammatory bowel disease”, “pediatric Crohn’s disease”, “linear growth”, “pubertal growth”, “bone health”, and “vitamin D” as key words. Clinical trials, systematic reviews, and meta-analyses published between 2008 and 2013 were selected to produce this narrative review. Studies referring to earlier periods were also considered if the data was relevant to our review. Although current treatment strategies for CD that include anti-tumor necrosis factor-α therapy have been shown to improve patients’ growth rate, linear growth deficiencies are still common. In pediatric CD patients, prolonged diagnostic delay, high initial activity index, and stricturing/penetrating type of behavior may cause growth deficiencies (in weight and height) and delayed puberty, with several studies reporting that these patients may not reach an optimal bone mass. Glucocorticoids and inflammation inhibit bone formation, though their impact on skeletal modeling remains unclear. Long-term control of active inflammation and an adequate intake of nutrients are both fundamental in promoting normal puberty. Recent evidence suggests that recombinant growth factor therapy is effective in improving short-term linear growth in selected patients, but is of limited benefit for ameliorating mucosal disease and reducing clinical disease activity. The authors conclude that an intense initial treatment (taking a “top-down” approach, with the early introduction of immunomodulatory treatment) may be justified to induce and maintain remission so that the growth of children with CD can catch up, ideally before puberty. Exclusive enteral nutrition has a key role in inducing remission and improving patients’ nutritional status.     

Association between Fecal Calprotectin and Mucosal Healing in Pediatric Patients with Crohn’s Disease Who Have Achieved Sustained Clinical Remission with Anti-Tumor Necrosis Factor Agents

Background/AimsAlthough mucosal healing (MH) is acknowledged as the treatment target in the treat-to-target era, there are limitations on repeated endoscopic examinations, especially in pediatric patients. We aimed to investigate whether fecal calprotectin (FC) could serve as a surrogate marker for the assessment of MH in pediatric patients with Crohn’s disease (CD) who have achieved sustained clinical remission (CR) while treated with anti-tumor necrosis factor (TNF) agents.MethodsThis multicenter retrospective cross-sectional study included pediatric CD patients who had sustained a CR for at least 6 months with anti-TNF agents and who simultaneously underwent ileocolonoscopy and FC tests during follow-up. MH was defined as the absence of any ulcer on ileocolonoscopy.ResultsA total of 131 patients were included in this study. MH was observed in 87 patients (66.7%). The FC level was significantly lower in patients with MH than in those without MH (median 49.0 mg/kg vs 599.0 mg/kg; p<0.001). According to the multivariate logistic regression analysis, FC was the only factor associated with MH (odds ratio, 0.62; 95% confidence interval [CI], 0.52 to 0.73; p<0.001). According to the receiver operating characteristic curve analysis, the optimal cutoff value for FC for the association with MH was <140 mg/kg (area under the curve 0.890, 95% CI 0.829 to 0.951, sensitivity 78.2%, specificity 88.6%, p<0.001).ConclusionsFC was associated with MH in pediatric patients with CD who had achieved a sustained CR for at least 6 months with anti-TNF agents. In these patients, FC can be used to stratify patients and guide decisions regarding ileocolonoscopy in the treat-to-target era.     

Optimal b value of diffusion-weighted imaging on a 3.0T magnetic resonance scanner in Crohn’s disease

AIM: To determine the optimal b value of diffusion-weighted imaging for detecting active inflammation in Crohn’s disease.METHODS: Thirty-one patients clinically diagnosed with active Crohn’s disease were referred for magnetic resonance examination. All patients were scanned on a 3.0T magnetic resonance scanner using the same protocol involving four different b values (800, 1500, 2000 and 2500 s/mm²). The diagnostic effect of diffusion-weighted imaging was evaluated and compared with endoscopic findings. The diffusion-weighted image quality of four b value groups was evaluated and apparent diffusion coefficient was measured for both normal and inflammatory intestinal segments.RESULTS: The contrast-to-noise ratio and signal-to-noise ratio were not satisfied when b value 2000 or 2500 s/mm² was adopted (36.52 ± 14.95 vs 34.78 ± 24.83, P > 0.05; 53.58 ± 23.45 vs 47.58 ± 29.67, P > 0.05). The qualitative image quality was not enough to meet diagnostic requirement. No matter which b value was chosen, the apparent diffusion coefficient of inflammatory intestinal segments was significantly lower than that of normal intestinal segments (1.38 ± 0.28 vs 2.00 ± 0.38, P < 0.01; 1.09 ± 0.20 vs 1.50 ± 0.28, P < 0.01; 0.95 ± 0.19 vs 1.34 ± 0.28, P < 0.01; 0.88 ± 0.14 vs 1.20 ± 0.21, P < 0.01). The lesion detection rate (90.32%), diagnostic sensitivity (81.18%) and specificity (95.10%) would be appropriate when b value 1500 s/mm² was adopted.CONCLUSION: High b value is suitable for intestinal DW examination on a high field MR scanner.     

Self-reported Treatment Goals in Chinese Patients with Inflammatory Bowel Disease During the Coronavirus Disease 2019 Pandemic

Background:Inflammatory bowel disease is a chronic recurrent disease, and the treatment goals of inflammatory bowel disease are mainly based on doctors’ perspective, but there are some differences between the doctor’s perspective and the patient’s perspective. The aim of this study is to understand the treatment goals and the related factors from the patients’ perspective during the coronavirus disease 2019 pandemic.Methods:A total of 212 participants were recruited to fill out the questionnaires including clinical characteristics and treatment goals. Eleven treatment goals were measured by a Short-Form 34 questionnaire. Univariate and multivariate regression analyses were used to explore the related factors about these treatment goals.Results:A total of 212 inflammatory bowel disease patients were enrolled in this study. The most concerned treatment goal was the improvement of quality of life (mean score was 8.54), while mean score of ulcerative colitis patients and Crohn’s disease patients was 9.10 and 8.45, respectively. We had also found some related factors such as the type of disease, the course of disease, the frequency of hematochezia, and defecation.Conclusion:Our survey showed that inflammatory bowel disease patients pay more attention to the improvement of quality of life and few drugs during the coronavirus disease 2019 pandemic. There are some related factors such as the type of disease, the course of disease, the frequency of hematochezia, and defecation. Our results help clinicians understand the patients’ treatment goals, which can contribute to better management of inflammatory bowel disease patients.     

Clinicians’ guide to the use of fecal calprotectin to identify and monitor disease activity in inflammatory bowel disease

BACKGROUND:

Objective monitoring of the severity of inflammation in patients with inflammatory bowel disease (IBD) is an essential part of disease management. However, repeat endoscopy to define extent and severity of inflammation is not practical. Fecal calprotectin (FC) is a biomarker that can be used as a surrogate test to distinguish inflammatory from noninflammatory gastrointestinal disease.

METHODS:

A targeted search of the literature regarding FC, focusing primarily on the past three years, was conducted to develop practical clinical guidance on the current utility of FC in the routine management of IBD patients.

RESULTS:

It is recommended that samples for FC testing be obtained from the first bowel excretion of the day. FC testing should be used as standard of care to accurately confirm inflammation and ‘real-time’ disease activity when a clinician suspects an IBD flare. Although FC is a reliable marker of inflammation, its role in routine monitoring in improving long-term outcomes has not yet been fully assessed. Based on available evidence, the authors suggest the following cut-off values and management strategies: when FC levels are <50 μg/g to 100 μg/g, quiescent disease is likely and therapy should be continued; when FC levels are >100 μg/g to 250 μg/g, inflammation is possible and further testing (eg, colonoscopy) is required to confirm inflammation; and when FC levels are >250 μg/g, active inflammation is likely and strategies to control inflammation should be initiated (eg, optimizing current therapies or switching to an alternative therapy).

DISCUSSION:

FC is a useful biomarker to accurately assess the degree of inflammation and should be incorporated into the management of patients with IBD.     

Original research: Clinical utility of small bowel ultrasound assessment of Crohn’s disease in adults: a systematic scoping review

BackgroundUltrasound (US) is an alternative to magnetic resonance enterography, and has the potential to significantly reduce waiting times, expedite clinical decision-making and improve patient experience. Point of care US is an advantage of the US imaging modality, where same day scanning, interpretation and treatment decisions can be made.AimTo systematically scope the literature on point of care US use in small bowel Crohn’s disease, generating a comprehensive list of factors relating to the current understanding of clinical utility of this imaging modality.MethodsSearches included MEDLINE, EMBASE, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, clinicaltrial.gov,‘TRIP’ and Epistemonikos. Reference lists of included studies were hand searched. Search terms were searched for as both keywords and subject headings (MeSH) as appropriate. Searches were performed with the ‘suggested search terms’ and ‘explode’ selection, and restricted to ‘human’, ‘adult’ and ‘English language’ publications. No date limits were applied to be as inclusive as possible. Two investigators conducted abstract and full-text review. No formal quality appraisal process was undertaken; however, quality of sources was considered when reporting findings. A narrative synthesis was conducted.ResultsThe review included 42 sources from the UK, Europe, Japan, Canada and the USA. Small bowel ultrasound (SBUS) has been shown to be as accurate in detecting the presence of small bowel Crohn’s disease, is quicker, safer and more acceptable to patients, compared with magnetic resonance enterography. SBUS is used widely in central Europe and Canada but has not been embraced in the UK. Further research considering economic evaluation, clinical decision-making and exploration of perceived barriers to future implementation of SBUSs is required.     

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

BACKGROUNDInfliximab 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. AIMTo 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.METHODSCD 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.RESULTSAt 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 ≤ 5.60 μg/mL [area under the curve (AUC) = 0.83, 95%CI: 0.73-0.90, P < 0.001] and FCP > 238 μg/g (AUC = 0.82, 95%CI: 0.72-0.89, P < 0.001) moderately predicted endoscopic activity at week 54. ITL ≤ 5.60 μg/mL in combination with FCP > 238 μg/g indicated 82.0% possibility of endoscopic activity. At week 54, ITL ≤ 2.10 μg/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 ≤ 2.10 μg/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 > 5.60 μg/mL had higher rate of endoscopic relapse free survival than those with ITL ≤ 5.60 μg/mL (95.83% vs 46.67%). From weeks 54 to 108 of IFX treatment, patients with ITL > 2.10 μg/mL had higher rate of endoscopic survival free relapsed rate than those with ITL ≤ 2.10 μg/mL (92.68% vs 30.77%).CONCLUSIONCombination 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.     

PillCam COLON 2~ in Crohn's disease:A new concept of pan-enteric mucosal healing assessment

AIM: To evaluate mucosal healing in patients with small bowel plus colonic Crohn's disease(CD) with a single non-invasive examination, by using PillCam COLON 2.(PCC2).METHODS: Patients with non-stricturing nonpenetrating small bowel plus colonic CD in sustained corticosteroid-free remission were included. At diagnosis,patients had undergone ileocolonoscopy to identify active CD lesions, such as ulcers and erosions, and small bowel capsule endoscopy to assess the Lewis Score(LS). After ≥ 1 year of follow-up, patients underwent entire gastrointestinal tract evaluation with PCC2. The primary endpoint was assessment of CD mucosal healing, defined as no active colonic CD lesions and LS 135.RESULTS: Twelve patients were included(7 male;mean age: 32 years), and mean follow-up was 38 mo.The majority of patients(83.3%) received immunosuppressive therapy. Three patients(25%) achieved mucosal healing in both the small bowel and the colon,while disease activity was limited to either the small bowel or the colon in 5 patients(42%). It was possible to observe the entire gastrointestinal tract in 10 of the12 patients(83%) who underwent PCC2.CONCLUSION: Only three patients in sustainedcorticosteroid-free clinical remission achieved mucosal healing in both the small bowel and the colon, highlighting the limitations of clinical assessment when stratifying disease activity, and the need for pan-enteric endoscopy to guide therapeutic modification.     

Endoscopic Features and Clinical Characteristics of Ulcerations With Isolated Involvement of the Small Bowel

BackgroundDouble-balloon enteroscopy (DBE) enables the detection of ulcerations in the small bowel. However, determining an etiological diagnosis remains challenging. This study was conducted to investigate the clinical and endoscopic features of ulcerations with isolated involvement of the small bowel (UIISB) to improve diagnostic ability.MethodsPatients (n = 565) who underwent DBE and presented with ulcerations in the small bowel at Nanfang Hospital from January 2005 to January 2018 were eligible. Medical records were retrospectively examined. Predictors to determine ulceration etiology were identified by logistic regression analysis.ResultsAfter excluding patients with extra-ulcerations in other sites (n = 306) and those without follow-up records (n = 50), 209 patients with UIISB were enrolled. Among them, 59.3% of the ulcers were in the ileum, 26.8% in the jejunum, and 13.4% in the jejunoileum. Initial symptoms included abdominal pain (54.1%) and obscure gastrointestinal bleeding (30.0%). The multiplicity of ulceration was categorized as a single (22.0%) or multiple (78.0%). Cases were diagnosed with Crohn’s disease (50.7%), chronic nonspecific inflammation (21.5%), diverticulum (9.1%), lymphoma (6.2%), gastrointestinal stromal tumor (4.3%), intestinal tuberculosis (1.9%), adenocarcinoma (1.4%), infective enteritis (1.4%), hemangioma (1.0%), cryptogenic multifocal ulcerous stenosing enteritis (1.0%), anastomotic ulcer (0.5%), intestinal duplication (0.5%), or neuroendocrine tumor (0.5%). Etiology identification indicated the if patients were aged 40 years or more, or had overt bleeding, single ulceration, and ulcer at jejunum, it as more prone to be neoplastic (P < .05).ConclusionWhen we manage patients with UIISB, Crohn’s disease should be first under consideration. Age≥40, overt bleeding, single ulceration, and ulcer at jejunum were reasonable indications for etiology of neoplasm or non-neoplasm.     

FOCUS: Future of fecal calprotectin utility study in inflammatory bowel disease

AIMTo evaluate the perspective of gastroenterologists regarding the impact of fecal calprotectin (FC) on the management of patients with inflammatory bowel disease (IBD).METHODSPatients with known IBD or symptoms suggestive of IBD for whom the physician identified that FC would be clinically useful were recruited. Physicians completed an online “pre survey” outlining their rationale for the test. After receipt of the test results, the physicians completed an online “post survey” to portray their perceived impact of the test result on patient management. Clinical outcomes for a subset of patients with follow-up data available beyond the completion of the “post survey” were collected and analyzed.RESULTSOf 373 test kits distributed, 290 were returned, resulting in 279 fully completed surveys. One hundred and ninety patients were known to have IBD; 147 (77%) with Crohn’s Disease, 43 (21%) Ulcerative Colitis and 5 (2%) IBD unclassified. Indications for FC testing included: 90 (32.2%) to differentiate a new diagnosis of IBD from Irritable Bowel Syndrome (IBS), 85 (30.5%) to distinguish symptoms of IBS from IBD in those known to have IBD and 104 (37.2%) as an objective measure of inflammation. FC levels resulted in a change in management 51.3% (143/279) of the time which included a significant reduction in the number of colonoscopies (118) performed (P < 0.001). Overall, 97.5% (272/279) of the time, the physicians found the test sufficiently useful that they would order it again in similar situations. Follow-up data was available for 172 patients with further support for the clinical utility of FC provided.CONCLUSIONThe FC test effected a change in management 51.3% of the time and receipt of the result was associated with a reduction in the number of colonoscopies performed.     

Induction and rescue of Nod2-dependent Th1-driven granulomatous inflammation of the ileum

Mutations in the NOD2 gene are strong genetic risk factors for ileal Crohn’s disease. However, the mechanism by which these mutations predispose to intestinal inflammation remains a subject of controversy. We report that Nod2-deficient mice inoculated with Helicobacter hepaticus, an opportunistic pathogenic bacterium, developed granulomatous inflammation of the ileum, characterized by an increased expression of Th1-related genes and inflammatory cytokines. The Peyer’s patches and mesenteric lymph nodes were markedly enlarged with expansion of IFN-γ–producing CD4 and CD8 T cells. Rip2-deficient mice exhibited a similar phenotype, suggesting that Nod2 function likely depends on the Rip2 kinase in this model. Transferring wild-type bone marrow cells into irradiated Nod2-deficient mice did not rescue the phenotype. However, restoring crypt antimicrobial function of Nod2-deficient mice by transgenic expression of α-defensin in Paneth cells rescued the Th1 inflammatory phenotype. Therefore, through the regulation of intestinal microbes, Nod2 function in nonhematopoietic cells of the small intestinal crypts is critical for protecting mice from a Th1-driven granulomatous inflammation in the ileum. The model may provide insight into Nod2 function relevant to inflammation of ileal Crohn’s disease.     

Parenteral Methotrexate Is Efficient in the Treatment of Azathioprine Refractory Crohn’s Disease

BackgroundThere is limited data in the literature analyzing the efficacy of methotrexate in Crohn’s disease used after thiopurine analogs. We aimed in our study to show the efficacy of methotrexate in Crohn’s disease patients who failed to respond to thiopurine treatment.MethodsThe study included 29 azathioprine refractory patients with Crohn’s disease. Intramuscular methotrexate (25 mg/week) in the induction of remission and intramuscular methotrexate (15 mg/week) in 29 CD patients with a median follow-up time of 13 months was performed. In 15 (51.7%) patients, methotrexate was used in combination with anti-Tumour necrosis factor (TNF) (combination group), while it was used in 14 (48.3%) patients in monotherapy (monotherapy group).ResultsThe mean Harvey–Bradshaw index score significantly decreased in the follow-up period (Wk0 = 7.6, last visit = 4.5, P < .001). Remission and response rates at week 12 were 75.9% and 79.3%, respectively. Maintenance of remission (77.8% vs 37.5%, respectively, P = .1) and response rates (77.8% vs 50%, respectively, P = .3) due to last visit examination were numerically higher in combination group but they were not statistically significant. The cumulative probability of remission maintenance in patients with methotrexate therapy was 72.7%, 33.1%, and 22.0% at 1, 2 ,and 4 years after starting methotrexate, respectively.ConclusionOur results show that parenteral use of methotrexate is efficacious in inducing and maintaining remission as a step-up agent in azathioprine refractory Crohn’s disease patients.