Polygenic risk score predicts risk of primary sclerosing cholangitis in inflammatory bowel disease.

BACKGROUND: Forty distinct primary sclerosing cholangitis (PSC) genomic loci have been identified through multiancestry meta-analyses. The polygenic risk score (PRS) could serve as a promising tool to discover unique disease behaviour, like PSC, underlying inflammatory bowel disease (IBD). AIM: To test whether PRS indicates PSC risk in patients with IBD. MATERIALS AND METHODS: Mayo Clinic and Washington University at St Louis IBD cohorts were used to test our hypothesis. PRS was modelled through the published PSC loci and weighted with their corresponding effect size. Logistic regression was applied to predict the PSC risk. RESULTS: In total, 63 (5.6%) among 1130 patients with IBD of European ancestry had PSC. Among 381 ulcerative colitis (UC), 12% had PSC; in contrast to 1.4% in 761 Crohn disease (CD). Compared with IBD alone, IBD-PSC had significantly higher PRS (PSC risk: 3.0% at the lowest PRS quartile vs 7.2% at the highest PRS quartile, Ptrend =.03). In IBD subphenotypes subgroup analysis, multivariate analysis shows that UC-PSC is associated with more extensive UC disease (OR, 5.60; p=0.002) and younger age at diagnosis (p=0.02). In CD, multivariate analysis suggests that CD-PSC is associated with colorectal cancer (OR, 50; p=0.005). CONCLUSIONS: We found evidence that patients with IBD with PSC presented with a clinical course difference from that of patients with IBD alone. PRS can influence PSC risk in patients with IBD. Once validated in an independent cohort, this may help identify patients with the highest likelihood of developing PSC.

Novel Genetic Risk Variants and Clinical Predictors Associated With Primary Sclerosing Cholangitis in Patients With Ulcerative Colitis.

INTRODUCTION: Patients with ulcerative colitis (UC) who are likely to have primary sclerosing cholangitis (PSC) should be identified because PSC can influence UC clinical behavior and outcomes.The aim of this study was to establish a model incorporating clinical and genetic risk predictors that identifies patients with UC at risk of developing PSC. METHODS: We conducted a retrospective case-control study. Inflammatory bowel disease cohorts from multiple institutions were used as discovery and replicate datasets. Quality control criteria, including minor allele frequency, call rates, Hardy-Weinberg equilibrium, cryptic relatedness, and population stratification (through principal components), were used. Discriminative accuracy was evaluated with area under the receiver operating characteristic curve. RESULTS: Fifty-seven of 581 patients (9.8%) with UC had PSC. Multivariate analysis showed that patients with UC-PSC had more extensive disease (odds ratio [OR], 5.42; P = 1.57E-04), younger diagnosis age (younger than 20 years; OR, 2.22; P = 0.02), and less smoking (OR, 0.42; P = 0.02) than those with UC. After linkage disequilibrium pruning and multivariate analyses, 3 SNPs (rs3131621 at 6p21.33; rs9275596 and rs11244 at 6p21.32) at the HLA region were found associated with a 2- to 3-fold increased risk of PSC. Our model demonstrated good discriminatory power (area under the receiver operating characteristic curve, 88%). DISCUSSION: Three variants in HLA (6p21.3) region significantly distinguished patients with UC-PSC from patients with UC alone. Once further validated in an independent large cohort, our model could be used to identify patients with UC at risk of PSC, and it could also help guide disease management.

Serological profiling of Crohn's disease and ulcerative colitis patients reveals anti-microbial antibody signatures.

BACKGROUND: The healthcare burden of inflammatory bowel disease (IBD) is rising globally and there are limited non-invasive biomarkers for accurate and early diagnosis. AIM: To understand the important role that intestinal microbiota play in IBD pathogenesis and identify anti-microbial antibody signatures that benefit clinical management of IBD patients. METHODS: We performed serological profiling of 100 Crohn's disease (CD) patients, 100 ulcerative colitis (UC) patients and 100 healthy controls against 1173 bacterial and 397 viral proteins from 50 bacteria and 33 viruses on protein microarrays. The study subjects were randomly divided into discovery (n = 150) and validation (n = 150) sets. Statistical analysis was performed using R packages. RESULTS: Anti-bacterial antibody responses showed greater differential prevalence among the three subject groups than anti-viral antibody responses. We identified novel antibodies against the antigens of Bacteroidetes vulgatus (BVU_0562) and Streptococcus pneumoniae (SP_1992) showing higher prevalence in CD patients relative to healthy controls. We also identified antibodies against the antigen of Streptococcus pyogenes (SPy_2009) showing higher prevalence in healthy controls relative to UC patients. Using these novel antibodies, we built biomarker panels with area under the curve (AUC) of 0.81, 0.87, and 0.82 distinguishing CD vs control, UC vs control, and CD vs UC, respectively. Subgroup analysis revealed that penetrating CD behavior, colonic CD location, CD patients with a history of surgery, and extensive UC exhibited highest antibody prevalence among all patients. We demonstrated that autoantibodies and anti-microbial antibodies in CD patients had minimal correlation. CONCLUSION: We have identified antibody signatures for CD and UC using a comprehensive analysis of anti-microbial antibody response in IBD. These antibodies and the source microorganisms of their target antigens improve our understanding of the role of specific microorganisms in IBD pathogenesis and, after future validation, should aid early and accurate diagnosis of IBD.

Clinical Course and Impact of Immune Checkpoint Inhibitor Colitis Resembling Microscopic Colitis.

Background: Microscopic colitis (MC) is suspected to result from increased immune activity in gut mucosa. Immune checkpoint inhibitors (ICIs) treat cancer by activating the immune system, and further investigation is needed regarding their role in the development of MC. Methods: A retrospective case series investigated cases of endoscopically and histologically confirmed MC developing after administration of ICIs. Clinical notes and medication administration records were reviewed for demographics, symptom duration, and treatment response. Results: Nineteen cases of de novo MC were identified, with 95% of cases requiring steroid treatment, 53% presenting with hospitalization, and colitis-related mortality in 1 individual. Symptom onset occurred a median of 160 days after initiation of ICI therapy and 53 days after their most recent dose of therapy. Patients had a median of 125 days of symptoms, and ICI therapy was held in 70% of individuals due for treatment. Conclusions: MC can develop after ICI administration, and presents with severe symptoms, often requiring hospitalization and steroid treatment. In certain individuals this can require a prolonged treatment course of steroid therapy or immunomodulators. Individuals developing diarrhea after ICI therapy warrant thorough workup including endoscopy and rapid treatment initiation given the disease severity observed in this series.

Utilizing Deep Learning to Analyze Whole Slide Images of Colonic Biopsies for Associations Between Eosinophil Density and Clinicopathologic Features in Active Ulcerative Colitis.

BACKGROUND: Eosinophils have been implicated in the pathogenesis of ulcerative colitis and have been associated with disease course and therapeutic response. However, associations between eosinophil density, histologic activity, and clinical features have not been rigorously studied. METHODS: A deep learning algorithm was trained to identify eosinophils in colonic biopsies and validated against pathologists' interpretations. The algorithm was applied to sigmoid colon biopsies from a cross-sectional cohort of 88 ulcerative colitis patients with histologically active disease as measured by the Geboes score and Robarts histopathology index (RHI). Associations between eosinophil density, histologic activity, and clinical features were determined. RESULTS: The eosinophil deep learning algorithm demonstrated almost perfect agreement with manual eosinophil counts determined by 4 pathologists (interclass correlation coefficients: 0.805-0.917). Eosinophil density varied widely across patients (median 113.5 cells per mm2, interquartile range 108.9). There was no association between eosinophil density and RHI (P = 0.5). Significant differences in eosinophil density were seen between patients with Montreal E3 vs E2 disease (146.2 cells per mm2 vs 88.2 cells per mm2, P = 0.005). Patients on corticosteroids had significantly lower eosinophil density (62.9 cells per mm2 vs 124.1 cells per mm2, P = 0.006). No association between eosinophil density and biologic use was observed (P = 0.5). CONCLUSIONS: We developed a deep learning algorithm to quantify eosinophils in colonic biopsies. Eosinophil density did not correlate with histologic activity but did correlate with disease extent and corticosteroid use. Future studies applying this algorithm in larger cohorts with longitudinal follow-up are needed to further elucidate the role of eosinophils in ulcerative colitis.

Validated Indices for Histopathologic Activity Predict Development of Colorectal Neoplasia in Ulcerative Colitis.

BACKGROUND AND AIMS: To correlate histologic activity in surveillance colonoscopies with the development of colorectal neoplasia in ulcerative colitis [UC]. METHODS: Colorectal biopsies during surveillance [N = 764] from 52 UC patients with colorectal neoplasia were compared to 122 patients without neoplasia enrolled in a prospective natural history registry. All biopsies were scored using validated histologic scoring systems (Geboes score, Nancy histopathologic index [NHI], and Robarts histopathologic index [RHI]). Clinical, endoscopic, and histologic data were correlated with the development of colorectal neoplasia. RESULTS: In multivariable analysis, mean RHI (hazard ratio [HR] 1.07 for each 1-unit increase in RHI, 95% confidence interval [CI] 1.03-1.12, p = 0.002) and mean NHI [HR 1.89 for each 1-unit increase in NHI, 95% CI 1.34-2.67, p = 0.002] for the entire surveillance period were significantly associated with colorectal neoplasia development. Shorter surveillance interval and increasing age were associated with increased risk of neoplasia development whereas mean Mayo endoscopic score was not significant. To generate a clinically useful measure of neoplasia risk, mean histologic activity in the preceding 5 years before the study endpoint was correlated with neoplasia development. In the preceding 5 years of surveillance, a mean RHI ≥ 8 had a 7.53-fold increased risk [95% CI 2.56-12.16, p < 0.001] and mean NHI ≥ 1.9 had a 5.89-fold increased risk [95% CI 2.18-15.92, p < 0.001] of developing colorectal neoplasia. CONCLUSIONS: Persistent histologic activity during multiple surveillance episodes is an independent predictor of colorectal neoplasia. Mean RHI and mean NHI during a 5-year colonoscopic surveillance period can be used to assess risk for colorectal neoplasia and optimize UC surveillance.

Novel Genetic Variant Predicts Surgical Recurrence Risk in Crohn's Disease Patients.

BACKGROUND: We aimed to identify a model of clinical and genetic risk factors through hypothesis-free search across genome that can predict the surgical recurrence risk after the first abdominal surgery in CD patients. MATERIALS AND METHODS: Two independent inflammatory bowel disease (IBD) cohort studies were used to derive and validate the genetic risk profile. The study subjects were genotyped using Illumina Immunochip custom genotyping array. Surgical recurrence was defined as having the second or more abdominal bowel resections after the first abdominal surgery at the time of study enrollment; nonsurgical recurrence was defined as having no further abdominal resection after the first abdominal surgery. RESULTS: Among 372 CD patients who had at least 1 abdominal surgery at the study enrollment, 132 (35.5%) had subsequent surgical recurrence after their first abdominal surgery, and 240 (64.5%) required no subsequent abdominal surgery at the end of follow up. Among clinical factors, multivariable analysis showed that history of immunomodulatory use (odds ratio [OR], 3.96; P = 0.002) and early era of CD first surgery (OR, 1.12; P = 1.01E-04) remained significant. Genotypic association tests identified a genome-wide significant locus rs2060886 in TCF4 at chr18q21.2 associated with surgical recurrence risk (OR, dom, 4.10 [2.37-7.11]; P = 4.58E-08). CONCLUSIONS: Novel genetic locus rs2060886 in TCF4 was associated with surgical recurrence risk at genome-wide significance level among CD patients after their first abdominal surgery. Early era of CD first intestinal surgery predicts higher surgical recurrence risk. These results suggest that genetic variants may help guide the CD management strategy in patients at the highest risk of repeated abdominal surgeries.

Role of Capsule Endoscopy in Inflammatory Bowel Disease.

In Crohn disease (CD), the use of capsule endoscopy (CE) for suspected versus established disease is very different. Most patients with CD are diagnosed with ileocolonoscopy. In patients with a negative ileocolonoscopy, CE is the next best test in suspected CD. In patients with established CD, the potential benefits of CE are rating severity of disease, establishing extent and distribution, and following mucosal healing in a treat to target strategy. In those with proximal small bowel disease, CE can help in diagnosis and prognostication. In ulcerative colitis, CE has a limited role, but that may change with evolving technology.

Coccidioidomycosis in patients with various inflammatory disorders treated with tumor necrosis factor α inhibitors.

Coccidioides fungi are found primarily in the southwestern United States and are the cause of coccidioidomycosis. Tumor necrosis factor α inhibitors (TNFIs) are therapies for autoimmune and inflammatory conditions; their association with coccidioidomycosis is not well characterized. We aimed to determine the prevalence and characteristics of coccidioidomycosis among TNFI recipients with different inflammatory disorders at a tertiary care center. We retrospectively reviewed the electronic health records of patients at our institution from April 4, 2010 to December 17, 2017, who received TNFIs (infliximab, etanercept, adalimumab, certolizumab pegol, or golimumab) and had positive culture, pathologic, and/or serologic results for coccidioidomycosis. Among 1770 patients identified who received TNFIs, 49 (2.8%) had proven or probable coccidioidomycosis. Of these 49, 28 (57%) were men, 47 (96%) were White, and 42 (86%) had pulmonary coccidioidomycosis. The most common TNFIs used were adalimumab, infliximab, and etanercept. Coccidioidomycosis was identified in 25 of 794 patients with rheumatologic disorders (3.1%), 18 of 783 patients with inflammatory bowel disease (IBD) (2.3%), and six of 193 patients with dermatologic disorders (3.1%) (P = .34). There was no difference in coccidioidal infections among recipients of any particular TNFI agents. A minority of patients (7/49, 14%) had an extrapulmonary infection, and the majority of these (6/7) had IBD. Our study shows a low prevalence of coccidioidomycosis in TNFI recipients, even within the Coccidioides-endemic area. Persons with IBD were disproportionately represented among those with extrapulmonary coccidioidomycosis. Treatment with azoles was effective. LAY SUMMARY: Among 1770 patients who received tumor necrosis factor α inhibitors, 49 (2.8%) had newly acquired coccidioidomycosis over a 7-year period. Dissemination occurred in 14.3%, but disproportionately among those with underlying inflammatory bowel disease. All patients recovered with medical management.

Unique Phenotypic Characteristics and Clinical Course in Patients With Ulcerative Colitis and Primary Sclerosing Cholangitis: A Multicenter US Experience.

INTRODUCTION: Ulcerative colitis (UC) associated with primary sclerosing cholangitis (PSC) is a rare phenotype. We aimed to assess patients with UC-PSC or UC alone and describe differences in clinical and phenotypic characteristics, antitumor necrosis factor (TNF) therapy, and long-term clinical outcomes. METHODS: This retrospective multicenter cohort study included patients who received a diagnosis of UC from 1962 through 2015. We evaluated clinical factors associated with UC-PSC vs UC alone and assessed associations by using multivariable logistic regression models. RESULTS: Among 522 patients with UC, 56 (10.7%) had PSC. Compared with UC alone, patients with UC-PSC were younger (younger than 20 years) at diagnosis (odds ratios [OR], 2.35; adjusted P = 0.02) and had milder UC severity (adjusted P = 0.05), despite having pancolonic involvement (OR, 7.01; adjusted P < 0.001). In the biologics era (calendar year 2005 to 2015), patients with UC-PSC less commonly received anti-TNF therapy compared with patients with UC (OR, 0.38; adjusted P = 0.009), but their response rates were similar. Fewer patients with UC-PSC received corticosteroids (OR, 0.24; adjusted P = 0.005) or rectal 5-aminosalicyte acid (OR, 0.26; adjusted P < 0.001). Other differences were identified that were not statistically significant in a multivariable model: patients with UC-PSC more commonly were male, had lower rates of smoking, and had higher rates of colorectal cancer and colectomy. DISCUSSION: This study identified a unique phenotype of UC with concurrent PSC, which had different clinical behavior compared with UC only. These phenotypic characteristics can help identify high-risk patients with UC before PSC is diagnosed and guide different management and monitoring strategies.

Capsule Retention in Crohn's Disease: A Meta-analysis.

BACKGROUND: The main factor that limits wider utilization of capsule endoscopy (CE) in Crohn's disease (CD) is the potential risk of retention. The aim of this systematic review was to evaluate capsule retention rates in adult and pediatric CD and determine if retention risk is reduced in established CD (ECD) with patency capsule (PC) or magnetic resonance/computed tomography (MR/CT) enterography. METHODS: Studies of CD patients undergoing CE that reported retention were identified. Pooled estimates for retention rates and relative risk in ECD to suspected CD (SCD) were calculated. All hypothesis tests were 2-sided; statistical significance was set at a P value of <0.05. RESULTS: In the overall CD cohort, retention rates were 3.32% (95% confidence interval [CI], 2.62%-4.2%): 4.63% (95% CI, 3.42%-6.25%) and 2.35% (95% CI, 1.31%-4.19%) in ECD and SCD, respectively. Retention rates were 3.49% (95% CI, 2.73%-4.46%) and 1.64% (95% CI, 0.68%-3.89%) in adult and pediatric CD, respectively. Retention risk in adult ECD was 3.4 times higher than SCD, but there was no difference in retention risk in pediatric ECD compared with SCD. Retention rates in ECD were decreased after patency capsule (2.88%; 95% CI, 1.74%-4.74%) and MR/CT enterography (2.32%; 95% CI, 0.87%-6.03%). CONCLUSIONS: In comparison with older literature, this meta-analysis demonstrates lower CE retention rates in SCD and ECD. Retention rates in pediatric CD were lower than in adult CD. Retention rates in adult ECD were higher than SCD, but there were no differences between pediatric ECD and SCD. Retention rates in ECD were lower after negative PC or MR/CT enterography.

Prospective multicenter study to evaluate capsule endoscopy competency using a validated assessment tool.

BACKGROUND AND AIMS: Capsule endoscopy (CE) is an established, noninvasive modality for examining the small bowel. Minimum training requirements are based primarily on guidelines and expert opinion. A validated tool to assess the competence of CE is lacking. In this prospective, multicenter study, we determined the minimum number of CE procedures required to achieve competence during gastroenterology fellowship; validated a capsule competency test (CapCT); and evaluated any correlation between CE competence and endoscopy experience. METHODS: We included second- and third-year gastroenterology fellows from 3 institutions between 2013 and 2018 in a structured CE training program with supervised CE interpretation. Fellows completed the CapCT with a maximal score of 100. For comparison, expert faculty completed the same CapCT. Trainee competence was defined as a score ≥90% compared with the mean expert score. Fellows were tested after 15, 25, and 35 supervised CE interpretations. CapCT was validated using expert consensus and item analysis. Data were collected on the number of previous endoscopies. RESULTS: A total of 68 trainees completed 102 CapCTs. Fourteen CE experts completed the CapCT with a mean score of 94. Mean scores for fellows after 15, 25, and 35 cases were 83, 86, and 87, respectively. Fellows with at least 25 interpretations achieved a mean score ≥84 in all 3 institutions. CapCT item analysis showed high interobserver agreement among expert faculty (k = 0.85). There was no correlation between the scores and the number of endoscopies performed. CONCLUSION: After a structured CE training program, gastroenterology fellows should complete a minimum of 25 supervised CE interpretations before assessing competence using the validated CapCT, regardless of endoscopy experience.

The Clinician's Guide to Suspected Small Bowel Bleeding.

Small bowel bleeding accounts for 5-10% of gastrointestinal bleeding. With the advent of capsule endoscopy, device-assisted enteroscopy, and multiphase CT scanning, a small bowel source can now be found in many instances of what has previously been described as obscure gastrointestinal bleeding. We present a practical review on the evaluation and management of small bowel bleeding for the practicing clinician.

Novel Genetic Risk Variants Can Predict Anti-TNF Agent Response in Patients With Inflammatory Bowel Disease.

BACKGROUND: It is important to identify patients with inflammatory bowel disease [IBD] refractory to anti-tumour necrosis factor [TNF] therapy, to avoid potential adverse effects and to adopt different treatment strategies. We aimed to identify and validate clinical and genetic factors to predict anti-TNF response in patients with IBD. MATERIALS AND METHODS: Mayo Clinic and Washington University IBD genetic association study cohorts were used as discovery and replicate datasets, respectively. Clinical factors included sex, age at diagnosis, disease duration and phenotype, disease location, bowel resection, tobacco use, family history of IBD, extraintestinal manifestations, and response to anti-TNF therapy. RESULTS: Of 474 patients with IBD treated with anti-TNF therapy, 41 [8.7%] were refractory to therapy and 433 [91.3%] had response. Multivariate analysis showed history of immunomodulator use (odds ratio 10.2, p = 8.73E-4) and bowel resection (odds ratio 3.24, p = 4.38E-4) were associated with refractory response to anti-TNF agents. Among genetic loci, two [rs116724455 in TNFSF4/18, rs2228416 in PLIN2] were successfully replicated and another four [rs762787, rs9572250, rs144256942, rs523781] with suggestive evidence were found. An exploratory risk model predictability [area under the curve] increased from 0.72 [clinical predictors] to 0.89 after adding genetic predictors. Through identified clinical and genetic predictors, we constructed a preliminary anti-TNF refractory score to differentiate anti-TNF non-responders (mean [standard deviation] score, 5.49 [0.99]) from responders (2.65 [0.39]; p = 4.33E-23). CONCLUSIONS: Novel and validated genetic loci, including variants in TNFSF, were found associated with anti-TNF response in patients with IBD. Future validation of the exploratory risk model in a large prospective cohort is warranted.

The Utility of Screening for Coccidioidomycosis in Recipients of Inhibitors of Tumor Necrosis Factor α.

BACKGROUND: Tumor necrosis factor α inhibitors (TNFi) are commonly used to treat immune-mediated disorders, but they are associated with an increased risk of mycobacterial and fungal infections. We compared the outcomes of TNFi recipients screened for asymptomatic coccidioidomycosis with those of unscreened patients to compare the development of symptomatic coccidioidomycosis and to describe its outcomes for patients with abnormal coccidioidal screenings. METHODS: We searched electronic health records from 4 September 2010 through 26 September 2016 for all patients receiving a TNFi for dermatologic, rheumatologic, or gastroenterologic diagnoses, then categorized patients by whether or not they had undergone coccidioidal serologic testing for screening or diagnostic purposes. RESULTS: A total of 2793 patients had a TNFi prescribed. Of those, 1951 met the inclusion criteria: 1025/1951 (52.5%) never had coccidioidal screening; 925/1951 (47.4%) had serologic screening either before beginning TNFi therapy or annually, or both after beginning a TNFi. Symptomatic coccidioidomycosis developed in 35/1025 (3.4%) unscreened patients. Of those screened, 861/925 (93.1%) had negative serologic tests, of which 11/861 (1.3%) subsequently developed symptomatic coccidioidomycosis; 36/925 (3.9%) had coccidioidomycosis at screening (7, probable infection; 11, possible infection; 18, asymptomatic seropositive result); and 17 had only positive findings for immunoglobulin M antibodies and did not meet the definition for coccidioidomycosis. The unscreened cohort was more likely to have symptomatic coccidioidomycosis than the screened cohort (35/1025 vs 11/861, P < .01). CONCLUSIONS: Screening for asymptomatic coccidioidomycosis within a Coccidioides-endemic area allowed for identifying and managing asymptomatic coccidioidomycosis before patients began TNFi therapy. Less symptomatic infection developed in the screened than the unscreened cohort.

Utility of video capsule endoscopy for longitudinal monitoring of Crohn's disease activity in the small bowel: a prospective study.

BACKGROUND AND AIMS: This prospective, multicenter study evaluated small-bowel capsule endoscopy (CE) for the longitudinal assessment of mucosal inflammation in subjects with Crohn's disease (CD). METHODS: Subjects with known CD underwent clinical evaluation with ileocolonoscopy and CE at baseline and 6-month follow-up. Small-bowel patency was confirmed before CE at both time points. The Simple Endoscopic Score for CD (SES-CD) was used for ileocolonoscopy, and the Lewis score and the CE CD Endoscopic Index of Severity (CECDEIS) were used for CE. Clinical scoring indices included the Physician Global Assessment (PGA), CD Activity Index (CDAI), and Harvey-Bradshaw Index (HBI). Laboratory markers including C-reactive protein, fecal calprotectin, and erythrocyte sedimentation rate were collected at baseline and follow-up. Correlation between endoscopic scores and clinical parameters were measured using Spearman tests. RESULTS: A total of 74 subjects were enrolled, of whom 53 (72%) completed endoscopic procedures at baseline and 6-month follow-up. The SES-CD ileocolonoscopy score correlated with the Lewis score (P < .001, ρ = .59) and CECDEIS capsule score (P = .002, ρ = .48). None of the 3 endoscopic scores correlated with PGA, CDAI, HBI, C-reactive protein, erythrocyte sedimentation rate, or fecal calprotectin. Approximately 85% of subjects had proximal small-bowel inflammation identified on CE. There were no CE-related adverse events. CONCLUSIONS: There was high correlation between CE and ileocolonoscopy scores for the assessment of mucosal disease activity over time; however, there were no correlations between endoscopic scores and clinical parameters. The use of serial CE for the assessment of small-bowel CD is feasible and valid. (Clinical trial registration number: NCT01942720.).

Applications of Colon Capsule Endoscopy.

PURPOSE OF REVIEW: This is a review of colon capsule endoscopy (CCE) with a focus on its recent developments, technological improvements, and current and potential future indications. RECENT FINDINGS: Based on the current literature, CCE II demonstrates comparable polyp detection rates as optical colonoscopy and CT colonography, and improved cost-effectiveness. The main limitation to patient acceptance is the requirement of a rigorous bowel preparation. Preliminary studies show good correlation between CCE and optical colonoscopy for assessment of colonic disease activity in inflammatory bowel disease (IBD). CCE II is currently FDA, approved as an adjunctive test in patients with prior incomplete colonoscopy, and in the evaluation of patients with suspected lower gastrointestinal bleeding. The test is approved in Europe as one of the options for average-risk colorectal cancer screening, and high-risk screening in patients with contraindications or unwilling to undergo colonoscopy. CCE has a potential role in the evaluation and monitoring of colonic disease activity in IBD. Future technological advances should focus on minimizing bowel preparation, improvement in reading times, and development of therapeutic capabilities. • With technological improvements, the second-generation colon capsule has a significantly higher sensitivity than the first-generation capsule for detection of colon polyps. • Colon capsule endoscopy has been approved in Europe as an option for average-risk colorectal cancer screening, and high-risk screening in patients with contraindications or unwilling to undergo colonoscopy. • Colon capsule endoscopy has received FDA approval as an option for colorectal cancer screening in patients with prior incomplete colonoscopy, and in evaluation of patients with suspected lower gastrointestinal bleeding. • Colon capsule endoscopy may have a role in evaluation and monitoring of inflammatory bowel disease. • Colon capsule endoscopy currently requires a bowel preparation that is more rigorous than colonoscopy.

Evidence-Based Guide on Capsule Endoscopy for Small Bowel Bleeding.

Capsule endoscopy is the diagnostic test of choice for the evaluation of overt and occult small bowel bleeding. Its yield is higher in patients presenting with overt bleeding. The yield is also improved if the capsule is performed soon after the presentation of bleeding. Capsule endoscopy has a complementary role with cross-sectional imaging to triage patients for appropriate management, including deep enteroscopy, surgery, or, if negative, conservative management. Although capsule endoscopy is useful to detect vascular and inflammatory lesions, it appears to have a significant miss rate for solitary small bowel lesions, including tumors. The main adverse event is capsule retention in patients with underlying small bowel obstruction.