Active Small Bowel Research Articles

Diagnostic accuracies of MR enterography and CT enterography in symptomatic Crohn's disease

Objective. In patients, with symptomatic Crohn's disease (CD), valid information about the presence or absence of small bowel disease activity and stenosis is clinically important. Such information supports decisions about medical or surgical therapy and can be obtained with MR enterography (MRE) or CT enterography (CTE). Materials and methods. A total of 50 patients with symptomatic pre-existing CD and a demand for small bowel imaging to support changes in treatment strategy were included in this prospective and blinded study. MRE and CTE were performed on the same day in alternating order and subsequently compared with the gold standard: pre-defined lesions at ileoscopy (n = 30) or surgery with (n = 12) or without (n = 3) intra-operative enteroscopy. Results. A total of 35 patients had active small bowel CD (jejunum 0, ileum 1, (neo)-terminal ileum 34) and 20 had small bowel stenosis. The sensitivity and specificity of MRE for detection of small bowel CD was 74% and 80% compared to 83% and 70% with CTE (p ≥ 0.5). MRE and CTE detected small bowel stenosis with 55% and 70% sensitivities, respectively (p = 0.3) and 92% specificities. Conclusions. MRE and CTE have comparable diagnostic accuracies for detection of small bowel CD and stenosis. In symptomatic patients with CD and high disease prevalence, positive predictive values are favorable but negative predictive values are low. Consequently, MRE and CTE can be relied upon, if a positive result is obtained whereas a negative enterography should be interpreted with caution.

Circulating citrulline levels: a biomarker for intestinal functionality assessment

Circulating citrulline is emerging as an innovating biomarker candidate for assessment of intestinal function. Amino acid synthesized by enterocytes of intestinal mucosal, citrulline is not included in proteins or nutrition products and is a precursor for production of arginine by the kidney. Plasma citrulline is, in clinical situation, an established biomarker of enterocyte functional metabolic mass (trophicity) in children and in adult patients due to its high relation to active functional small bowel remnant length in intestinal diseases (short bowel, extensive enteropathies, intestinal toxicity of chemotherapy and radiotherapy. Plasma citrulline concentration (30-50 μmol/L), independent of nutritional status, if less than 10 μmol/L can give an objective threshold for nutrition parenteral use in case of intestinal failure due to enterocyte abnormalities or lack. Its regular dosage allows the monitoring of intestinal function except in case of significant renal failure.

A Predominant Pelvic Gastrointestinal Stromal Tumor (GIST) Mass Observed on Tc-99m Red Blood Cell Gastrointestinal Bleeding Scintigraphy

A 51-year-old woman presented with recurrent bleeding per rectum. Her earlier endoscopies were negative. Tc-99m RBC GI bleeding scintigraphy was performed. It demonstrated an apparent hypervascular pelvic mass, and active small bowel bleeding. Based on scintigraphic finding of a predominant pelvic mass indicating tumor, CT of the abdomen and pelvis was performed for further gastrointestinal bleeding localization work up instead of an invasive angiography or endoscopy, which detected a small bowel tumor in the pelvis. A small bowel gastrointestinal stromal tumor was resected subsequently.

Role of Magnetic Resonance Enterography in Differentiating between Fibrotic and Active Inflammatory Small Bowel Stenosis in Patients with Crohn's Disease

Objective:To assess the diagnostic accuracy of magnetic resonance imaging (MRI) in prospectively differentiating between fibrotic and active inflammatory small bowel stenosis in patients with Crohn's disease (CD).Materials and Methods:A total of 111 patients with histologically proven CD presenting with clinical and plain radiographic signs of small bowel obstruction underwent coronal and axial MRI scans after oral administration of polyethylene glycol solution. A stenosis was judged present if a small bowel segment had >80% lumen reduction as compared to an adjacent normal loop and mural thickening of >3 mm. At the level of the stenosis, both T2 signal intensity and post-gadolinium T1 enhancement were quantified using a 5-point scale (0: very low; 1: low; 2: moderate; 3: high; and 4: very high). A stenosis was considered fibrotic if the sum of the two values (activity score: AS) did not exceed 1.Results:A small bowel stenosis was identified in 48 out of 111 patients. Fibrosis was confirmed at histology in all of the 23 patients with AS of 0 or 1, who underwent surgery within 3 days of the MRI examination. In the remaining 25 patients (AS: 2–8), an active inflammatory stenosis was suspected and remission of the obstructive symptoms was obtained by means of medical treatment. One of these patients (AS: 2), however, underwent surgery after 14 days, due to recurrence. MRI had 95.8% sensitivity, 100% specificity, and 97.9% accuracy in the diagnosis of fibrotic stenosis.Conclusion:MRI is reliable in differentiating fibrotic from inflammatory small bowel stenosis in CD.

Dipeptidyl Peptidase IV Expression in a Cellular and Human Model of Intestinal Inflammation

Introduction Dipeptidyl peptidase IV (DP IV) is a serine protease. It modulates the physiological activity of satiety inducing hormones such as glucagon like peptide 1 (GLP-1) and polypeptide YY (PYY). It also inactivates GLP-2, an enteroendocrine hormone with cytoprotective and reparative properties. By cleaving chemokines essential for the Th-2 inflammatory pathway, DP IV enhances the Th-1 pathway. Reduced serum DP IV activity has been observed in patients with inflammatory bowel disease (IBD) including Crohn9s disease (CD). Plasma levels and tissue expression have never been described together. The latter is of particular clinical significance since this is the local site of action of trophic GLP-2 and GLP-1 mediated vagal afferent stimulation. Methods Experiments were also carried out on a Caco-2 cell line model of intestinal inflammation with TNFα incubation in a graded concentration/time course. DP IV expression was studied at the mRNA level through quantitative PCR (qPCR) and protein level by tissue western blotting and plasma ELISA. DP IV expression was also studied in active small (n=18) and large bowel CD (n=5). A subgroup of patients were restudied when inactive (n=6) and all results were compared to healthy controls (n=17). Results In Caco-2 cells an ∼ 18-fold increase (p Conclusion Results in the reductionist cellular model of intestinal inflammation support an increase in DP IV in an inflammatory milieu. However, in the complex, chronic human disease DP IV expression is decreased, as observed in other inflammatory states such human inflammatory arthritis and systemic lupus erythematosus. It is possible that a decrease in DP IV would preserve more biologically active GLP-2, enhancing trophic activity and promoting repair. DP IV may present a potential therapeutic target in IBD.

Enteroendocrine Cells and Appetite Dysregulation in Crohn's Disease

Introduction Loss of appetite and malnutrition in active Crohn9s disease (CD) are important problems. The biological mechanisms underpinning appetite loss are unclear. Enteroendocrine cells (EEC) form a pivotal part of the brain-gut axis that controls appetite and satiety. They secrete gut hormones such as glucagon like peptide-1 (GLP-1) and polypeptide YY (PYY) which act on appetite control centres in the brainstem through an endocrine or paracrine pathway. Recent animal research has suggested that immune-regulated upregulation of proximal CCK-secreting EEC plays a mechanistic role in the appetite and feeding disturbance observed during gut inflammation. We have studied whether distal ileal EEC are perturbed in ileocolonic Crohn9s disease. Methods Patients with active intestinal inflammation were studied: active small and large bowel (SB and LB, respectively) CD and age/sex matched controls. Patient symptoms were assessed using a validated visual analogue score (VAS). At tissue level EEC markers and transcription factors have been studied through immunohistochemistry and quantitative polymerase chain reaction. Gut hormone responses to a test meal (PYY and GLP-1) were studied using a multiplex-ELISA technique. Results CD patients with active inflammation displayed a ∼6-fold significant reduction in appetite parameters as measured by VAS (p Conclusion Measurable changes were observed in distal small intestinal EEC markers in active CD, including elements of both GLP-1 and PYY. These data support a potential role of EEC in appetite dysregulation in intestinal inflammation. Measurements of gut hormones in peripheral blood may not adequately reflect biologically important changes occurring at the epithelial level. Enhanced EEC responses to nutrients may adversely affect appetite through increased gut-brain signalling, and provide novel therapeutic targets. Further work is underway to further dissect this neuroendocrine circuitry.

Enteroendocrine cells and appetite dysregulation in Crohn's disease

IntroductionLoss of appetite and malnutrition in active Crohn's disease (CD) are important problems. The biological mechanisms underpinning appetite loss are unclear. Enteroendocrine cells (EEC) form a pivotal part of the...

Dipeptidyl peptidase IV expression in a cellular and human model of intestinal inflammation

IntroductionDipeptidyl peptidase IV (DP IV) is a serine protease. It modulates the physiological activity of satiety inducing hormones such as glucagon like peptide 1 (GLP-1) and polypeptide YY (PYY). It...

Impact of capsule endoscopy on management in patients with established crohn's disease-experience from a single tertiary centre

IntroductionCapsule endoscopy (CE) has developed a pertinent role in the management of patients with Crohn's disease, however there is a paucity of literature assessing the long term impact of CE....

Active Crohn's Disease in the small bowel: Evaluation by diffusion weighted imaging and quantitative dynamic contrast enhanced MR imaging

To determine relative diagnostic value of MR diffusion and perfusion parameters in detection of active small bowel inflammation in patients with Crohn's disease (CD). We reviewed 18 patients with active CD of terminal ileum (TI) who underwent MR enterography (MRE; including dynamic contrast enhanced MRI and diffusion-weighted MRI). Conventional MRI findings of TI were recorded. Regions of interest were drawn over TI and normal ileum to calculate apparent diffusion coefficient (ADC), the volume transfer constant (K(trans)) and the contrast media distribution volume (v(e)). Receiver operating characteristic analysis was used to determine their diagnostic performance. Among conventional MR findings, mural thickening and increased enhancement were present in all actively inflamed small bowel. K(trans), v(e), and ADC values differed significantly between actively inflamed TI and normal ileum (0.92 s(-1) versus 0.36 s(-1); 0.31 versus 0.15 ± 0.08; 0.00198 mm(2)/s versus 0.00311 mm(2)/s; P < 0.001). Area under the curve (AUC) for K(trans), v(e), and ADC values ranged from 0.88 to 0.92 for detection of active inflammation. Combining K(trans) and ADC data provided an AUC value of 0.95. Dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) provide quantitative measures of small bowel inflammation that can differentiate actively inflamed small bowel segments from normal small bowel in CD. DWI provides better sensitivity compared with DCE-MRI and combination of ADC and K(trans) parameters for analysis can potentially improve specificity.

Benefit of Computed Tomography Enterography in Crohnʼs Disease: Effects on Patient Management and Physician Level of Confidence§†

Computed tomographic enterography (CTE) has been shown to have a high sensitivity and specificity for active small bowel inflammation. There are only sparse data on the effect of CTE results on Crohn's disease (CD) patient care. We prospectively assessed 273 patients with established or suspected CD undergoing a clinically indicated CTE. Providers were asked to complete pre- and postimaging questionnaires regarding proposed clinical management plans and physician level of confidence (LOC) for the presence or absence of active small bowel disease, fistula(s), abscess(es), or stricturing disease. Correlative clinical, serologic, and histologic data were recorded. Following revelation of CTE results, providers were questioned if CTE altered their management plans, and whether LOC changes were due to CTE findings (on a 5-point scale). CTE altered management plans in 139 cases (51%). CTE changed management in 70 (48%) of those with established disease, prompting medication changes in 35 (24%). Management changes were made post-CTE in 69 (54%) of those with suspected CD, predominantly due to excluding CD (36%). CTE-perceived changes in management were independent of clinical, serologic, and histologic findings (P < 0.0001). Clinically meaningful LOC changes (2 or more points) were observed in 212 (78%). CTE is a clinically useful examination, altering management plans in nearly half of patients with CD, while increasing physician LOC for the detection of small bowel inflammation and penetrating disease. These findings further support the use of CTE in CD management algorithms.

Clinical Efficacy of MR Enterography in the Diagnosis and Management of Crohnʼs Disease

Purpose: Background: Assessing small bowel Crohn's disease (CD) activity is challenging as direct visualization is difficult and traditional radiographic studies can result in large cumulative radiation doses. MR enterography (MRE) is a rapidly evolving diagnostic technique performed without ionizing radiation. While prior studies evaluate the technical aspects of MRE, few address its clinical utility. Aim: To evaluate the clinical utility of MRE in patients with known or suspected CD at a single institution. Methods: Consecutive MRE performed between 1/1/09 and 9/30/09 were reviewed. All imaging was performed on a 1.5T clinical scanner with an 8-channel phased array body coil. Patients were scanned after ingestion of hyperosmolar oral contrast. High resolution T2 and T1 weighted pre- and post-contrast images were obtained. Studies performed for reasons other than known or suspected CD were excluded. Patient data including clinical course prior to MRE and subsequent management was abstracted from the medical record and a clinical disease activity score was derived. Each MRE was scored on a 4-point scale (1: active small bowel inflammation definitely absent, 2: probably absent, 3: probably present, 4: definitely present). A clinical efficacy score (CES) was also assigned to each MRE (range 0-3, from 0: not helpful, 1: confirmatory only, 2: contributory, led to change in management/diagnosis, 3: determined diagnosis/directly led to management change). Comparisons were made between groups to the correlation between MRE findings and clinical activity and impact of the MRE on management. Results: 50 of 57 MREs met inclusion criteria. MRE was ordered in 1 patient in clinical remission and showed no activity. 57% of clinically severe cases had MRE scores of 3 or 4 and 75% had definite activity. In mild to moderate cases by symptoms, MRE was unlikely to show active disease with 68% having MRE scores of 1 or 2. With regard to clinical efficacy, CES >2 in 74% while MRE was considered not helpful once. MRE had the greatest impact when it was employed to differentiate active CD from other non-functional diagnoses. In this group, CES =3 in 60%. In the group with established CD where MRE was used to assess activity, CES = 3 in 29%. Conclusion: MRE findings correlate well with clinical activity in patients with severe CD and those in remission. Most patients with clinically mild to moderate disease activity did not have active disease by MRE. In these patients, MRE prevented escalation of therapy and led to the work-up of alternate diagnoses. Overall, MRE was a useful tool in this clinical setting, leading to management change in 66% of cases without use of ionizing radiation.

Validation of a lower radiation computed tomography enterography imaging protocol to detect Crohnʼs disease in the small bowel

The purpose was to validate a lower radiation dose computed tomography enterography (CTE) imaging protocol to detect the presence of Crohn's disease (CD) in the small bowel using two different reference standards and to identify a prediction model based on CTE signs for the presence of active CD. This retrospective study included patients with known or suspected CD who underwent CTE between January and October 2006 according to a lower radiation dose protocol. Two gastrointestinal radiologists blindly and independently classified each CTE as being active or inactive. Reference standards included ileocolonoscopy ± biopsy and a comprehensive clinical reference standard (retrospectively created by a gastroenterologist, also including history, physical, follow-up course, and subsequent endoscopy, imaging, or surgery). Logistic regression was used to identify CTE findings that predicted the presence of active CD based on the combined clinical reference standard. In all, 137 patients underwent CTE and ileocolonoscopy. Using an endoscopic reference standard, the sensitivity of CTE to detect active CD for the two readers was 81% and 89%, respectively. Using the clinical reference standard, the sensitivity of CTE to detect active CD was 89% and 98%, respectively. For both readers the sensitivity of CTE increased by 8%-9% when using the comprehensive reference standard. Multivariate analysis showed that a combination of mural thickness and hyperenhancement best predicted active CD (area under the curve [AUC] = 0.92-0.93, P < 0.0001). Lower radiation dose CTE exams are sensitive for the detection of active small bowel CD. The combination of mural thickness and hyperenhancement are the best radiologic predictors of active CD.

Quality, clinical influence and tolerance of computed tomography enteroclysis in patients with suspected small bowel disease

Computed tomography enteroclysis (CTE) may be superior to other small bowel imaging techniques, detecting subtle mucosal lesions and extraluminal pathology. This study aimed to define the technical success, clinical influence and tolerance of CTE in patients with suspected small bowel disease. CTE scans of 42 consecutive patients (aged 21-78 years, 12 men) were reviewed by a single radiologist for technical adequacy and diagnosis. A panel of gastroenterologists reviewed clinical information. At a telephone interview, tolerance of CTE was graded numerically from 1 (unbearable) to 10 (excellent) and descriptively as unbearable, fair, good or excellent. Good or optimal distension of small bowel was achieved in 98%. The entire small bowel was imaged in 88%. Eighteen patients had a normal small bowel, whereas 12 (29%) had active small bowel Crohn disease, 4 intussusception, 3 small bowel diverticula and 7 having other diagnoses. Mesenteric lymphadenopathy was evident in 11 and fat stranding in 5. CTE resulted in a new or altered diagnosis in 13 (31%) patients and identified more extensive Crohn disease in a further 8 (19%). A change in management plan was instituted in 18 (43%) patients, with subsequent clinically significant improvement in 12. 33 (85%) described the procedure as 'fair' or 'unbearable' rather than 'good' or 'excellent'. The median tolerance score was 3 out of 10. CTE provided high-quality images in nearly all patients and had an effect on diagnosis, management or outcome in most, but was not well tolerated.

Double-balloon enteroscopy in Crohn’s disease patients suspected of small bowel activity: findings and clinical impact

It is estimated that 10-30% of patients with Crohn's disease (CD) have small bowel (SB) involvement, but the exact frequency and clinical relevance of these findings is unknown. Double-balloon enteroscopy (DBE) enables endoscopic visualization of the SB. In this study we evaluated whether DBE is a feasible technique for detection of CD localized in the SB in CD patients with clinical suspicion of SB lesions and whether these findings have clinical impact. Retrospectively we analyzed 52 DBE procedures in 40 CD patients (16 males, mean age 40 years, mean duration of CD 15 years). Included patients had clinical suspicion of small bowel CD activity, including persistent abdominal discomfort (n = 27), iron deficiency anemia (n = 9) and/or hypomagnesemia (n = 4). Active small bowel CD was found in 24 (60%) patients, leading to a change in therapy in 18 patients (75%). After a mean follow-up of 13 months, 15 (83%) had persistent clinical improvement with a significant drop of mean CDAI from 178 to 90, after a mean follow-up of 13 months. DBE is a useful diagnostic tool for the evaluation of SB lesions in CD patients. The significance of these findings is emphasized by the fact that adjustment of therapy in the majority of these patients leads to significant and sustained clinical improvement.

163. Adaptive Growth Following Ileocecal Resection (ICR) in a Murine Model of Active Small Intestinal Inflammatory Bowel Disease (IBD)

163. Adaptive Growth Following Ileocecal Resection (ICR) in a Murine Model of Active Small Intestinal Inflammatory Bowel Disease (IBD)

Role of capsule endoscopy in inflammatory bowel disease

Capsule endoscopy (CE) is an innovative technological breakthrough that for the first time provides a noninvasive method to obtain high-resolution imaging of the entire small bowel. Since its recent inception, the diagnostic utility of CE has become well established for the evaluation of diverse ulcerative and inflammatory disorders of the jejunum and ileum. The incredible resolution of its lens (0.1 mm) detects focal villous edema or atrophy, denuded, as well as ulcerated mucosal lesions missed by other imaging techniques. CE has been shown by meta-analysis to be a more sensitive method to investigate patients for small bowel Crohn's disease, with an incremental yield above 30% versus other imaging modalities. In patients with indeterminate colitis, CE is useful in distinguishing between ulcerative and Crohn's colitis. Among patients with established Crohn's disease, CE may be employed to determine: (1) the extent and severity of small bowel involvement, (2) postoperative recurrence, (3) post-therapy mucosal healing, and (4) whether active small bowel inflammatory lesions exist in the clinical setting of functional bowel disorder. Complications are rare and include capsule retention at stricture sites. The new patency capsule can diminish the risk of the latter problem in at-risk patients. CE can also serve as a guide to sites that require biopsies or dilatation by push or double-balloon enteroscopy. However, other causes of small bowel lesions may mimic Crohn's disease. A standard terminology system has thus been developed, and a CE Crohn's disease severity scoring index is currently undergoing validation studies.

Strictureplasty for active Crohn's disease

Several studies over the last 20 years have confirmed the safety and efficacy of strictureplasty in the treatment of obstructive Crohn's disease. However, almost all of these studies use strictureplasty to treat fibrotic strictures: limited resection being preferred to treat active disease strictures. One study dating from 1986 used strictureplasty to treat purely active disease strictures, with disappointing results. No other similar studies have been published. We investigate the complication and recrudescence rates together with the intervention-free intervals in patients undergoing strictureplasty for active disease strictures. A retrospective review of 14 patients who underwent strictureplasty either in isolation or in combination with limited resection for active small bowel Crohn's disease between 1996 and 2004 was undertaken. A total of 73 strictureplasties were carried out. There was no operative mortality; however, one patient subsequently died from metastatic small bowel adenocarcinoma arising from existing Crohn's disease. One patient subsequently developed complications directly attributed to strictureplasty and required further surgery. Three patients developed recrudescent disease and required further surgery in the form of either strictureplasty, limited resection or both. All patients undergoing strictureplasty with resection and over 70% of patients undergoing strictureplasty alone were intervention-free at 41 months. With extended follow-up, the same proportion of patients would remain intervention-free at 70 months or longer. The use of strictureplasty in active disease strictures is well tolerated and has similar, if not better, recurrence and complication rates when compared with limited resection in patients with similar disease profiles.

Utility of Wireless Capsule Enteroscopy (WCE) in Evaluating Crohn's Disease Patients with Abdominal Symptoms

WCE is a new diagnostic modality for patients with suspected or known Crohn's disease (CD). Aim: To determine the frequency of small bowel (SB) disease and the distribution of SB lesions detected by WCE among symptomatic patients with known CD. Methods: Data of all established CD patients who underwent WCE between October 2001 and February of 2004 for symptoms suggestive of active disease were retrospectively reviewed. Symptoms included abdominal pain, gastrointestinal bleeding, diarrhea, and weight loss. All images were reviewed by a single experienced endoscopist and were analyzed with respect to type and location of SB lesions. The finding of multiple ulcerations (>3) on WCE was classified as active small bowel CD. The presence of ≤3 ulcerations was considered suggestive of active CD. Results: Ninety-seven WCE were performed on 88 symptomatic patients with documented CD. Forty-eight of 96 (50%) patients had findings diagnostic of active CD, and 10 (10%) patients had findings suggestive of active CD. Thirty-three (34%) patients had normal findings. Forty-four of 96 (46%) procedures showed lesions in more than one region of the SB. 23%, 34%, 42%, and 51% of the lesions were in the duodenum, jejunum, proximal ileum, and distal ileum, respectively. Only 5 cases showed lesions in the duodenum, jejunum, or proximal ileum without lesions in the distal ileum (Fisher's Exact p < 0.0001). The capsule reached the cecum in 64 of 96 (67%) procedures and showed active colonic ulcerations in 18 cases. Twenty-two patients had colonoscopy data within 90 days (mean 30 days) of WCE. While 55% had disease findings on WCE, only one patient (5%) had a single aphthous ulcer on colonoscopy. In 32 cases a small bowel follow through (SBFT) had been performed within 90 days of the WCE procedure (mean 30 days). WCE was superior to SBFT in detecting active Crohn's lesions (p = 0.05). Conclusion: WCE identified active SB lesions in half of CD patients experiencing abdominal symptoms. A surprisingly large number of lesions were seen in the more proximal parts of the SB, but they rarely existed in the absence of distal ileal lesions. Our limited data suggests that colonoscopy added little value to assess active disease in symptomatic patients. Therefore, WCE may be the preferred modality in evaluating CD patients presenting with symptoms. Prospective studies are needed to assess the utility of WCE as the primary tool for evaluating patients with symptomatic CD.

5 Current applicability of scintigraphic methods in gastroenterology

Patients are often referred for evaluation of a wide range of GI complaints including dysphagia, abdominal pain, bloating, nausea, constipation or diarrhoea. Many are diagnosed with ‘functional’ disease when endoscopy or conventional radiological studies fail to identify an anatomic cause for the patient's symptoms. In such cases nuclear medicine offers non-invasive methods for objectively demonstrating disease involving different areas of the gastrointestinal tract. Increasingly scintigraphy is playing a primary role in the evaluation of patients with suspected acute cholecystitis, active gastrointestinal bleeding, gastroparesis, and small and large bowel motility disorders. In addition, it supplements other studies when results are inconclusive in diagnosing oesophageal dysmotility, gastro-oesophageal reflux, acalculous cholecystitis, and postoperative complications of gastrointestinal surgery.