A prospective study of fecal calprotectin and lactoferrin as predictors of small bowel Crohn's disease in patients undergoing capsule endoscopy.

BACKGROUND: Capsule endoscopy (CE) is often used to investigate small bowel Crohn's disease (CD). AIM: The aim of this study is to prospectively assess the value of fecal calprotectin and lactoferrin to predict CE findings. PATIENTS AND METHODS: Sixty-eight consecutive patients that were referred for CE were included. Stool samples for calprotectin and lactoferrin and blood samples were collected for relevant parameters. Correlation between fecal markers and CE findings was assessed and receiver operating characteristic (ROC) curves were built to determine the predictive values of fecal markers for the diagnosis of CD. RESULTS: Fecal calprotectin data was available for all the patients and lactoferrin data for 38. CE findings compatible with CD were found in 23 (33%) patients and 45 (67%) were negative for CD. The average age of the CD group was 34 compared to 46 in the non-CD group (p = .048). Median calprotectin and lactoferrin in the CD group and in the control group were 169 mg/kg vs. 40 (p = .004) and 6.6 mg/kg vs. 1 (p = .051), respectively. The area under the ROC curve was 0.767 for calprotectin and 0.70 for lactoferrin. A fecal calprotectin concentration of 95 mg/kg and fecal lactoferrin of 1.05 mg/kg had a sensitivity, specificity, positive predictive value and negative predictive value of 77 and 73%, 60 and 65%, 50 and 50%, and 84 and 84% in predicting CE findings compatible with CD. CONCLUSIONS: Fecal markers are simple and noninvasive surrogates for predicting CE findings compatible with CD. Fecal markers can help determine which patients should be referred for CE. ClinicalTrials.gov Identifier: NCT01266629.

Accuracy of capsule colonoscopy in detecting colorectal polyps in a screening population.

BACKGROUND & AIMS: Capsule colonoscopy is a minimally invasive imaging method. We measured the accuracy of this technology in detecting polyps 6 mm or larger in an average-risk screening population. METHODS: In a prospective study, asymptomatic subjects (n = 884) underwent capsule colonoscopy followed by conventional colonoscopy (the reference) several weeks later, with an endoscopist blinded to capsule results, at 10 centers in the United States and 6 centers in Israel from June 2011 through April 2012. An unblinded colonoscopy was performed on subjects found to have lesions 6 mm or larger by capsule but not conventional colonoscopy. RESULTS: Among the 884 subjects enrolled, 695 (79%) were included in the analysis of capsule performance for all polyps. There were 77 exclusions (9%) for inadequate cleansing and whole-colon capsule transit time fewer than 40 minutes, 45 exclusions (5%) before capsule ingestion, 15 exclusions (2%) after ingestion and before colonoscopy, and 15 exclusions (2%) for site termination. Capsule colonoscopy identified subjects with 1 or more polyps 6 mm or larger with 81% sensitivity (95% confidence interval [CI], 77%-84%) and 93% specificity (95% CI, 91%-95%), and polyps 10 mm or larger with 80% sensitivity (95% CI, 74%-86%) and 97% specificity (95% CI, 96%-98%). Capsule colonoscopy identified subjects with 1 or more conventional adenomas 6 mm or larger with 88% sensitivity (95% CI, 82%-93) and 82% specificity (95% CI, 80%-83%), and 10 mm or larger with 92% sensitivity (95% CI, 82%-97%) and 95% specificity (95% CI, 94%-95%). Sessile serrated polyps and hyperplastic polyps accounted for 26% and 37%, respectively, of false-negative findings from capsule analyses. CONCLUSIONS: In an average-risk screening population, technically adequate capsule colonoscopy identified individuals with 1 or more conventional adenomas 6 mm or larger with 88% sensitivity and 82% specificity. Capsule performance seems adequate for patients who cannot undergo colonoscopy or who had incomplete colonoscopies. Additional studies are needed to improve capsule detection of serrated lesions. Clinicaltrials.gov number: NCT01372878.

Small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline.

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). The Guideline was also reviewed and endorsed by the British Society of Gastroenterology (BSG). It addresses the roles of small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders. Main recommendations 1 ESGE recommends small-bowel video capsule endoscopy as the first-line investigation in patients with obscure gastrointestinal bleeding (strong recommendation, moderate quality evidence). 2 In patients with overt obscure gastrointestinal bleeding, ESGE recommends performing small-bowel capsule endoscopy as soon as possible after the bleeding episode, optimally within 14 days, in order to maximize the diagnostic yield (strong recommendation, moderate quality evidence). 3 ESGE does not recommend the routine performance of second-look endoscopy prior to small-bowel capsule endoscopy; however whether to perform second-look endoscopy before capsule endoscopy in patients with obscure gastrointestinal bleeding or iron-deficiency anaemia should be decided on a case-by-case basis (strong recommendation, low quality evidence). 4 In patients with positive findings at small-bowel capsule endoscopy, ESGE recommends device-assisted enteroscopy to confirm and possibly treat lesions identified by capsule endoscopy (strong recommendation, high quality evidence). 5 ESGE recommends ileocolonoscopy as the first endoscopic examination for investigating patients with suspected Crohn's disease (strong recommendation, high quality evidence). In patients with suspected Crohn's disease and negative ileocolonoscopy findings, ESGE recommends small-bowel capsule endoscopy as the initial diagnostic modality for investigating the small bowel, in the absence of obstructive symptoms or known stenosis (strong recommendation, moderate quality evidence).ESGE does not recommend routine small-bowel imaging or the use of the PillCam patency capsule prior to capsule endoscopy in these patients (strong recommendation, low quality evidence). In the presence of obstructive symptoms or known stenosis, ESGE recommends that dedicated small bowel cross-sectional imaging modalities such as magnetic resonance enterography/enteroclysis or computed tomography enterography/enteroclysis should be used first (strong recommendation, low quality evidence). 6 In patients with established Crohn's disease, based on ileocolonoscopy findings, ESGE recommends dedicated cross-sectional imaging for small-bowel evaluation since this has the potential to assess extent and location of any Crohn's disease lesions, to identify strictures, and to assess for extraluminal disease (strong recommendation, low quality evidence). In patients with unremarkable or nondiagnostic findings from such cross-sectional imaging of the small bowel, ESGE recommends small-bowel capsule endoscopy as a subsequent investigation, if deemed to influence patient management (strong recommendation, low quality evidence). When capsule endoscopy is indicated, ESGE recommends use of the PillCam patency capsule to confirm functional patency of the small bowel (strong recommendation, low quality evidence). 7 ESGE strongly recommends against the use of small-bowel capsule endoscopy for suspected coeliac disease but suggests that capsule endoscopy could be used in patients unwilling or unable to undergo conventional endoscopy (strong recommendation, low quality evidence).

Colon PillCam: why not just take a pill?

This review article deals with the clinical value of capsule endoscopy for visualization of the colon. Since its introduction in 2006, the colon capsule endoscopy underwent major technological improvements. The improved performance of colon capsule endoscopy is reviewed based on three multicenter prospective studies. Screening patients for colonic adenomatous polyps is reasonable in patients who are unwilling to undergo conventional colonoscopy. Another prospective study proved that colon capsule endoscopy is effective in incomplete colonoscopy. Colon capsule endoscopy was shown to be superior to virtual colonography in the evaluation of patients with incomplete colonoscopy. Further improvements are expected in colon capsule endoscopy.

Comparison of small-bowel colon capsule endoscopy system to conventional colonoscopy for the evaluation of ulcerative colitis activity.

Background and aims Diagnosis and monitoring of ulcerative colitis (UC) includes conventional colonoscopy. This procedure is invasive and does not exclude small-bowel Crohn's disease (CD). Current therapeutic goals include mucosal healing which may lead to an increased number of endoscopic procedures in many patients. The small-bowel colon capsule endoscopy (SBC-CE) system visualizes the small bowel and colon. The aim of this study was to evaluate the performance and adverse events of SBC-CE in patients with UC. Methods This was a prospective, feasibility study involving two study sites. Patients with active UC underwent SBC-CE and colonoscopy. Kappa statistics were performed to assess the agreement between SBC-CE and colonoscopy. Adverse events (AEs) data were collected throughout and following the procedure. Results In total, 30 consecutive patients were recruited, and 23 of those were included in the final analysis. For the primary end point, evaluation of the extent of UC disease in the colon, the percent agreement between SBC-CE and colonoscopy was moderate (56.5 %); kappa coefficient 0.42. The percent agreement between SBC-CE and colonoscopy for UC disease activity, based on Mayo endoscopic sub-score, was 95.7 %; kappa coefficient 0.86. Disease activity in the more proximal small bowel was detected in two patients with SBC-CE. No SBC-CE device-related AEs were reported. Conclusions When comparing SBC-CE to conventional colonoscopy, there was a moderate agreement for the extent of UC disease and a very good overall agreement between the two modalities for UC disease activity.

Cystic fibrosis transmembrane conductance regulator ion channel function testing in recurrent acute pancreatitis.

GOALS: To understand the relationship between acute recurrent pancreatitis and cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. BACKGROUND: An emerging number of patients present with a nonclassic phenotype of cystic fibrosis (CF) with partial features or single-organ disease only. The association between the phenotype of recurrent pancreatitis CFTR dysfunction is unclear. METHODS: Patients with idiopathic recurrent pancreatitis were referred for electrophysiologic investigation. RESULTS: Thirty-three patients (18 males) aged 20+/-12 years with recurrent pancreatitis were studied. Three patients had mild asthma and 1 patient had mild ulcerative colitis. There was no family history of CF. All patients had normal imaging of the pancreatic duct by endoscopic retrograde cholangiopancreatography or magnetic resonance cholangiopancreatography. No patient was pancreatic insufficient. Mean sweat chloride values were 41+/-14 meq/L (range: 18 to 64). Nasal potential difference (NPD) measurement was pathologic in 7 patients. Mean basal potential difference in these 7 patients was -33+/-13 mV and there was an abnormal response to chloride-free and isoproterenol solutions. There was no difference in sweat chloride concentration between the 2 groups. Mutation analysis revealed W1282X/5T, D1152H/5T, and W1282X/- in 3 patients with abnormal NPD and 1 W1282X allele was found in 1 patient with normal NPD. CONCLUSIONS: In this series, 21% of patients with recurrent pancreatitis have abnormalities of CFTR function. Patients presenting with recurrent, "idiopathic" pancreatitis require CFTR function testing.

The history of time for capsule endoscopy.

Capsule endoscopy was conceived by inventive minds of good people. In the beginning there was a will to do something for medicine. The idea fomented after a discourse between the talented engineer with his physician friend. It took years to develop the concept. Then excellent engineers created de novo the necessary components to turn the capsule into a viable reality. The story is a tribute to human ingenuity.

A novel purgative protocol for capsule endoscopy of the small bowel produces better quality of visibility than 2 l of PEG: Timing is of the essence.

INTRODUCTION: The ideal way of preparing patients for small-bowel capsule endoscopy has been controversial. Previous studies have shown that ingestion of 2 l of polyethylenglycol (PEG) 12 hours prior to capsule ingestion leads to improved visibility in comparison to no preparation at all. We speculated that using a post-ingestion (PI), booster-based cleansing protocol might provide an alternative to the PEG cleansing protocol. METHODS: This randomized, blinded, prospective study enrolled 45 individuals. Patients were allocated to either of two groups. The PEG group ingested 2 l PEG 12 hours prior to the exam (n = 22) and the PI group ingested one sachet of Picolax® dissolved in 250 ml of water one hour after swallowing the capsule with 500 ml of water (n = 18). Primary endpoints were overall small bowel and distal third of small bowel cleansing levels. Secondary endpoints were average gastric and small-bowel transit time. RESULTS: Forty-five patients participated in this study. Five individuals were excluded because of incomplete study. Percentage of patients with adequate visibility in the distal third of the small bowel in the PEG group was 9% vs 72% in the PI group (p < 0.0001). Average gastric time and total transit time were shorter in the PI group vs the PEG group (p = 0.0065). CONCLUSION: Timing of ingestion of the Picolax® purgative 60 minutes after swallowing the capsule endoscopy delivers better visibility in the distal third of the small bowel than the accepted cleansing protocol of ingesting 2 l PEG 12 hours prior to the capsule endoscopy procedure.

New insights into the pathophysiology of gastrointestinal graft-versus-host disease using capsule endoscopy.

We investigated gastrointestinal graft-versus-host-disease using capsule endoscopy in patients with abdominal pain and/or diarrhea. We found severe pathology involving most of the gut including loss of villi, ulcerations, narrowing, bleeding and fistula formation. In 2 patients, capsule endoscopy alone established the diagnosis of graft-versus-host-disease. Some ulcerations were associated with cytomegalovirus infection.

Mutated MCM9 is associated with predisposition to hereditary mixed polyposis and colorectal cancer in addition to primary ovarian failure.

Mutations in MCM9, which encodes DNA helicase, were recently shown to cause a clinical phenotype of primary ovarian failure and chromosomal instability. MCM9 plays an essential role in homologous recombination-mediated double-strand break repair. We describe a multiplex family with early colorectal carcinoma and mixed polyposis associated with primary hypergonadotropic hypogonadism. A combination of whole genome homozygosity mapping as well as exome sequencing and targeted gene sequencing identified a homozygous c.672_673delGGinsC mutation that predicts a truncated protein, p.Glu225Lysfs*4. Our data expand the phenotypic spectrum of MCM9 mutations and suggest a link between MCM9 and inherited predisposition to mixed polyposis and early-onset colorectal cancer.