David H. Bruining

Clinical utility of measuring infliximab and human anti-chimeric antibody concentrations in patients with inflammatory bowel disease.

OBJECTIVES:Human anti-chimeric antibodies (HACAs) and subtherapeutic infliximab concentrations are associated with decreased duration of response. We evaluated the clinical utility of measuring HACA and infliximab concentrations.METHODS:The medical records of patients with inflammatory bowel disease (IBD) who had HACA and infliximab concentrations measured were reviewed to determine whether the result affected clinical management.RESULTS:One hundred fifty-five patients had HACA and infliximab concentrations measured. The main indications for testing were loss of response to infliximab (49%), partial response after initiation of infliximab (22%), and possible autoimmune/delayed hypersensitivity reaction (10%). HACAs were identified in 35 patients (23%) and therapeutic infliximab concentrations in 51 patients (33%). Of 177 tests assessed, the results impacted treatment decisions in 73%. In HACA-positive patients, change to another anti-tumor necrosis factor (TNF) agent was associated with a complete or partial response in 92% of patients, whereas dose escalation had a response of 17%. In patients with subtherapeutic infliximab concentrations, dose escalation was associated with complete or partial clinical response in 86% of patients whereas changing to another anti-TNF agent had a response of 33%. Patients with clinical symptoms and therapeutic infliximab concentrations were continued at the same dose 76% of the time and had no evidence of active inflammation by endoscopic/radiographic assessment 62% of the time.CONCLUSIONS:Measurement of HACA and infliximab concentration impacts management and is clinically useful. Increasing the infliximab dose in patients who have HACAs is ineffective, whereas in patients with subtherapeutic infliximab concentrations, this strategy may be a good alternative to changing to another anti-TNF agent.

Prospective Comparison of State-of-the-Art MR Enterography and CT Enterography in Small-Bowel Crohn's Disease

OBJECTIVE The objective of our study was to prospectively obtain pilot data on the accuracy of MR enterography for detecting small-bowel Crohns disease compared with CT enterography and with a clinical reference standard based on imaging, clinical information, and ileocolonoscopy. SUBJECTS AND METHODS The study group for this blinded prospective study was composed of 33 patients with suspected active Crohns ileal inflammation who were scheduled for clinical CT enterography and ileocolonoscopy and had consented to also undergo MR enterography. The MR enterography and CT enterography examinations were each interpreted by two radiologists with disagreements resolved by consensus. The reports from ileocolonoscopy with or without mucosal biopsy were interpreted by a gastroenterologist. The reference standard for the presence of small-bowel Crohns disease was based on the final clinical diagnosis by the referring gastroenterologist after reviewing all of the available information. RESULTS All 33 patients underwent CT enterography and ileocolonoscopy, 30 of whom also underwent MR enterography. The sensitivities of MR enterography and CT enterography for detecting active small-bowel Crohns disease were similar (90.5% vs 95.2%, respectively; p = 0.32). The image quality scores for MR enterography examinations were significantly lower than those for CT enterography (p = 0.005). MR enterography and CT enterography identified eight cases (24%) with a final diagnosis of active small-bowel inflammation in which the ileal mucosa appeared normal at ileocolonoscopy. Furthermore, enterography provided the only available imaging in three additional patients who did not have ileal intubation. CONCLUSION MR enterography and CT enterography have similar sensitivities for detecting active small-bowel inflammation, but image quality across the study cohort was better with CT. Cross-sectional enterography provides complementary information to ileocolonoscopy.

Prevalence of penetrating disease and extraintestinal manifestations of Crohn's disease detected with CT enterography

Background: This study was conducted to determine the prevalence of penetrating disease and extraintestinal manifestations of Crohns disease (CD) identified by computed tomography enterography (CTE). We also sought to examine the percentage of clinically significant new noninflammatory bowel disease (IBD) related findings in these patients. Methods: We analyzed the records of 357 consecutive patients with previously diagnosed CD evaluated at our institution who underwent a CTE between August 2004 and October 2005. Radiology reports were reviewed for the presence of penetrating disease (abscess, fistula, or phlegmon) or extraintestinal IBD manifestations (nephrolithiasis, cholelithiasis, sacroiliitis, avascular necrosis, deep vein thrombosis, or primary sclerosing cholangitis). Additional non‐IBD‐related abnormalities were also recorded, including any mass or cystic lesion. Urgent findings were defined as those that were deemed by the radiologist or ordering physician to require medical follow‐up within 3 months. Results: Of 357 patients identified (51% female) the median age was 41.6 years and median disease duration was 9.9 years. Of this cohort, 20.7% had penetrating disease (new finding in 58.1%) and 18.8% had extraintestinal IBD manifestations (new finding in 67.2%). Six patients had primary sclerosing cholangitis and portal/mesenteric vein thrombosis, respectively. In addition, 45.1% had non‐IBD findings including 2 unsuspected malignancies. Most of these extraenteric non‐IBD abnormalities were benign, with only 13.0% requiring urgent follow‐up. Conclusions: CT enterography is a valuable diagnostic modality for detecting both penetrating disease and extraintestinal IBD manifestations. These data add to a growing body of evidence that supports the use of CTE in CD diagnostic and management algorithms.

Procedure time and the determination of polypoid abnormalities with experience: Implementation of a chromoendoscopy program for surveillance colonoscopy for ulcerative colitis

Background:Procedure length and agreement in detection of abnormalities may limit implementation of chromoendoscopy (CE) for dysplasia surveillance in ulcerative colitis (UC). We investigated these factors among endoscopists inexperienced in this technique. Methods:Six investigators performed surveillance colonoscopy with white light endoscopy (WLE) followed by CE on 75 patients with long-standing UC. Interobserver agreement for WLE and CE images of polyps and nonpolypoid mucosa was determined. Withdrawal times from the cecum were compared based on number of colonoscopies performed. Dysplasia detection rate with WLE was compared with CE. Results:The analysis of 586 images (266 WLE and 320 CE) from 57 patients included images of 160 polyps (64 flat) with 29 dysplastic lesions. All investigators identified 10/11 WLE images of dysplasia and 4 identified all 18 CE dysplasia images, 1 missed 1 and 1 missed 3. Four dysplastic lesions were not identified by 1 or more investigators and all measured <5 mm. Interobserver agreement for lesions was high with kappa scores of 0.91 and 0.86 for WLE and CE, respectively. Among the 75 patients enrolled, dysplasia was found in 9.3% with WLE compared with 21.3% with WLE and CE (P = 0.007). Median colonoscopy withdrawal time improved from 31 minutes for endoscopists performing fewer than 5 procedures to 18 minutes for 5 to 14 and 19 minutes for more than 15 procedures. Conclusions:Indigo carmine CE for UC surveillance resulted in high rates of interobserver agreement for polyp detection, acceptable withdrawal times, and enhanced dysplasia detection. These results are encouraging for the implementation of CE programs for chronic UC.

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

Background: The purpose was to validate a lower radiation dose computed tomography enterography (CTE) imaging protocol to detect the presence of Crohns 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. Methods: 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. Results: 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). Conclusions: 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. (Inflamm Bowel Dis 2011;)

MR enterography in pediatric inflammatory bowel disease: retrospective assessment of patient tolerance, image quality, and initial performance estimates.

OBJECTIVE The purpose of this article was to evaluate image quality, oral contrast administration and bowel distention, side effects, and performance estimates of MR enterography in a large cohort of pediatric patients with inflammatory bowel disease (IBD). MATERIALS AND METHODS A retrospective analysis of the pediatric IBD clinic database (2007-2010) was performed. Eighty-five MR enterography studies in 70 patients were performed without sedation. All pediatric patients with the potential diagnosis of IBD were included, with the exception of studies performed on patients with ileoanal pouch anatomy. The quantity of ingested oral contrast material and number of adverse events were recorded. Retrospectively, image quality (including motion artifact and bowel distention) and enteric inflammation were assessed. Correlation between radiographic findings and endoscopic findings was tested by the Fisher exact test. RESULTS Eighty-five MR enterography studies were performed without sedation in 70 patients (mean age, 15.6 years; age range, 9-18 years) over 30 months. The mean image quality for unenhanced images was significantly higher than for contrast-enhanced images (4.7 vs 4.1, p < 0.0001), with unacceptable image quality occurring on both unenhanced and contrast-enhanced sequences in one patient. The amount of oral contrast material ingested correlated with patient age (p = 0.009), with acceptable bowel distention occurring in 93% (78/85). Two patients had nausea or emesis and one experienced a syncopal episode after MR enterography. Sensitivity and specificity of MR enterography for active disease of the terminal ileum, right colon, and left colon were 80% and 85.2%, 79.1% and 77.8%, and 90.3% and 63.6%, respectively. CONCLUSION MR enterography is feasible in patients 9 years old and older without sedation. Acceptable image quality can be achieved in nearly all patients, but a small minority will have suboptimal bowel distention or minor adverse events. Oral contrast ingestion regimes can be based on patient age. Performance estimates in children parallel reports in adults.

Guidelines for privileging, credentialing, and proctoring to perform GI endoscopy

Ashley L. Faulx, MD, FASGE, Jenifer R. Lightdale, MD, MPH, FASGE, NASPGHAN representative, Ruben D. Acosta, MD, Deepak Agrawal, MD, MPH, David H. Bruining, MD, Vinay Chandrasekhara, MD, Mohamad A. Eloubeidi, MD, MHS, FASGE, Suryakanth R. Gurudu, MD, FASGE, Loralee Kelsey, BSN, RN, CGRN, SGNA representative, Mouen A. Khashab, MD, Shivangi Kothari, MD, V. Raman Muthusamy, MD, FASGE, Bashar J. Qumseya, MD, MPH, Aasma Shaukat, MD, MPH, FASGE, Amy Wang, MD, FASGE, Sachin B. Wani, MD, Julie Yang, MD, John M. DeWitt, MD, FASGE, Chair

Radiological Response Is Associated With Better Long-Term Outcomes and Is a Potential Treatment Target in Patients With Small Bowel Crohn's Disease

OBJECTIVES:Crohns disease (CD) management targets mucosal healing on ileocolonoscopy as a treatment goal. We hypothesized that radiologic response is also associated with better long-term outcomes.METHODS:Small bowel CD patients between 1 January 2002 and 31 October 2014 were identified. All patients had pre-therapy computed tomography enterography (CTE)/magnetic resonance enterography (MRE) with follow-up CTE or MRE after 6 months, or 2 CTE/MREs≥6 months apart while on maintenance therapy. Radiologists characterized inflammation in up to five small bowel lesions per patient. At second CTE/MRE, complete responders had all improved lesions, non-responders had worsening or new lesions, and partial responders had other scenarios. CD-related outcomes of corticosteroid usage, hospitalization, and surgery were assessed using Kaplan–Meier survival analysis and multivariable Cox models.RESULTS:CD patients (n=150), with a median disease duration of 9 years, had 223 inflamed small bowel segments (76 with strictures and 62 with penetrating, non-perianal disease), 49% having ileal distribution. Fifty-five patients (37%) were complete radiologic responders, 39 partial (26%), and 56 non-responders (37%). In multivariable Cox models, complete and partial response decreased risk for steroid usage by over 50% (hazard ratio (HR)s: 0.37 (95% confidence interval (CI), 0.21–0.64); 0.45 (95% CI, 0.26–0.79)), and complete response decreased the risk of subsequent hospitalizations and surgery by over two-thirds (HRs: HR, 0.28 (95% CI, 0.15–0.50); HR, 0.34 (95% CI, 0.18–0.63)).CONCLUSIONS:Radiological response to medical therapy is associated with significant reductions in long-term risk of hospitalization, surgery, or corticosteroid usage among small bowel CD patients. These findings suggest the significance of radiological response as a treatment target.

Validation of a CT-Derived Method for Osteoporosis Screening in IBD Patients Undergoing Contrast-Enhanced CT Enterography

OBJECTIVES:Osteoporosis and bone fractures are of particular concern in patients with inflammatory bowel disease (IBD). Biomechanical computed tomography (BCT) is an image-analysis technique that can measure bone strength and dual-energy X-ray absorptiometry (DXA)-equivalent bone mineral density (BMD) from noncontrast CT images. This study seeks to determine whether this advanced technology can be applied to patients with IBD undergoing CT enterography (CTE) with IV contrast.METHODS:Patients with IBD who underwent a CTE and DXA scan between 2007 and 2011 were retrospectively identified. Femoral neck BMD (g/cm2) and T-scores were measured and compared between DXA and BCT analysis of the CTE images. Femoral strength (Newtons) was also determined from BCT analysis.RESULTS:DXA- and CTE-generated BMD T-score values were highly correlated (R2=0.84, P<0.0001) in this patient cohort (n=136). CTE identified patients with both osteoporosis (sensitivity, 85.7%; 95% confidence interval (CI), 48.7–97.4 and specificity, 98.5%; 95% CI, 94.5–99.6) and osteopenia (sensitivity, 85.1%; 95% CI, 72.3–92.6 and specificity, 85.4%; 95% CI, 76.6–91.3). Of the 16 patients who had “fragile” bone strength by BCT (placing them at the equivalent high risk of fracture as for osteoporosis), 6 had osteoporosis and 10 had osteopenia by DXA.CONCLUSIONS:CTE scans can provide hip BMD, T-scores, and clinical classifications that are comparable to those obtained from DXA; when combined with BCT analysis, CTE can identify a subset of patients with osteopenia who have clinically relevant fragile bone strength. This technique could markedly increase bone health assessments in IBD patients already undergoing CTE to evaluate small bowel disease.

The role of endoscopy in the diagnosis and treatment of inflammatory pancreatic fluid collections

V. Raman Muthusamy, MD, FASGE, Vinay Chandrasekhara, MD, Ruben D. Acosta, MD, David H. Bruining, MD, Krishnavel V. Chathadi, MD, Mohamad A. Eloubeidi, MD, MHS, FASGE, Ashley L. Faulx, MD, FASGE, Lisa Fonkalsrud, BSN, RN, CGRN, SGNA representative, Suryakanth R. Gurudu, MD, FASGE, Mouen A. Khashab, MD, Shivangi Kothari, MD, Jenifer R. Lightdale, MD, MPH, FASGE, NASPGHAN representative, Shabana F. Pasha, MD, John R. Saltzman, MD, FASGE, Aasma Shaukat, MD, MPH, FASGE, Amy Wang, MD, Julie Yang, MD, Brooks D. Cash, MD, FASGE, Previous Committee Chair, John M. DeWitt, MD, FASGE, Chair