Samuel N. Adler

Prospective multicenter performance evaluation of the second-generation colon capsule compared with colonoscopy

BACKGROUND AND STUDY AIMS A second-generation capsule endoscopy system, using the PillCam Colon 2, was developed to increase sensitivity for colorectal polyp detection compared with the first-generation system. The performance of this new system is reported. PATIENTS AND METHODS In a five-center feasibility study, second-generation capsule endoscopy was prospectively compared with conventional colonoscopy as gold standard for the detection of colorectal polyps and other colonic disease, in a cohort of patients scheduled for colonoscopy and having known or suspected colonic disease. Colonoscopy was independently performed within 10 hours after capsule ingestion. Capsule-positive but colonoscopy-negative cases were counted as false-positive. RESULTS 104 patients (mean age 49.8 years) were enrolled; data from 98 were analyzed. Patient rate for polyps of any size was 44 %, 53 % of these patients having adenomas. No adverse events related to either procedure were reported. The capsule sensitivity for the detection of patients with polyps >or= 6 mm was 89 % (95 % confidence interval [CI] 70 - 97) and for those with polyps >or= 10 mm it was 88 % (95 %CI 56 - 98), with specificities of 76 % (95 %CI 72 - 78) and 89 % (95 %CI 86 - 90), respectively. Both polyps missed by colonoscopy and mismatch in polyp size by study definition lowered specificity. Overall colon cleanliness for capsule endoscopy was adequate in 78 % of patients (95 %CI 68 - 86). CONCLUSIONS The new second-generation colon capsule endoscopy is a safe and effective method for visualizing the colon and detecting colonic lesions. Sensitivity and specificity for detecting colorectal polyps appear to be very good, suggesting a potential for improved accuracy compared with the first-generation system. Further prospective and comparative studies are needed.

Colon capsule endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

PillCam colon capsule endoscopy (CCE) is an innovative noninvasive, and painless ingestible capsule technique that allows exploration of the colon without the need for sedation and gas insufflation. Although it is already available in European and other countries, the clinical indications for CCE as well as the reporting and work-up of detected findings have not yet been standardized. The aim of this evidence-based and consensus-based guideline, commissioned by the European Society of Gastrointestinal Endoscopy (ESGE) is to furnish healthcare providers with a comprehensive framework for potential implementation of this technique in a clinical setting.

Detecting esophageal disease with second-generation capsule endoscopy: initial evaluation of the PillCam ESO 2.

BACKGROUND AND STUDY AIM Esophageal capsule endoscopy (ECE) provides an alternative, minimally invasive modality for evaluating the esophagus. This study evaluates the performance and test characteristics of a second-generation esophageal capsule endoscope, the PillCam ESO 2. METHODS Adults with known or suspected esophageal disease were included. Using the simplified ingestion procedure, each patient underwent capsule endoscopy with the PillCam ESO 2. Following ECE, esophagogastroduodenoscopy (EGD) was performed on the same day by an investigator who was blinded to the results of the ECE. In random order, capsule endoscopy videos were read and interpreted by the study investigator blinded to EGD results. RESULTS 28 patients (19 men, 9 women; mean age 53.3 years) were included. In 82 % of the patients, at least 75 % of the Z line was visualized by the PillCam ESO 2. A per-lesion analysis demonstrated that the PillCam ESO 2 had definitive results in 30/43 lesions (69.8 %) and EGD in 29/43 (67.4 %), P value = 0.41. Compared with EGD for detecting suspected Barretts esophagus and esophagitis, the PillCam ESO 2 had a sensitivity of 100 % and a specificity of 74 %, and a sensitivity of 80 % and a specificity of 87 %, respectively. The PillCam ESO 2 demonstrated 86 % agreement with EGD in describing the Z line (kappa statistic 0.68). The modified ingestion protocol provided excellent cleansing, with bubbles/saliva having no or only a minor effect on Z line images in 86 % of cases. CONCLUSIONS The PillCam ESO 2 demonstrated excellent visualization of the Z line. Compared with standard EGD, the PillCam ESO 2 had good test characteristics with high rates of detection of suspected Barretts esophagus and esophagitis. This study provides indirect validation of the simplified ingestion procedure. The PillCam ESO 2 acquires high quality esophageal images, performs safely, and should be able to replace the current PillCam ESO.

The G.U.T. of gut

One of the most ambitious objectives of physics has been to formulate a Grand Unified Theory (G.U.T.) whose ultimate goal is to conceptualize, unite and express the behaviour of particles and forces of nature into a framework that allows it to be expressed in a single mathematical equation (1). Although falling somewhat short of this goal, current cosmological G.U.T.s endeavour to describe the earliest events in the formation of the universe. If successful, this has the potential to elucidate the evolution of the fundamental forces (or matter) that span the micro-cosmos realm of bosons, fermions, gluons, gravitons, etc., to that which integrates the movement of the estimated 250 billion galaxies of the macro-cosmos. At present the big bang theory is the favoured explanation for the creation of the universe, a phenomenon possibly followed by a state of exponential expansion (Guth’s inflation theory) or even Linde’s chaotic inflation (2). The latter proposes that universes are constantly popping in and out of existence (as a part of a multi-universe system). The ekpyrotic universe theory is an example of a different G.U.T. whereby it is postulated that the universe began when two gigantic membranes collided (2). This idea encompasses the M-theory, which is a composite of the superstring theories (whereby it is suggested that the smallest building blocks of matter are loops of string and oscillating globules that undergo extreme contortions with spontaneous breaks and repair) (3). The strength of the M-theory is that it unites all the four forces (i.e. gravity, electromagnetism, the weak and strong electric force), but this requires calculations that span 11 space–time dimensions that entwine as a singularity at the moment of creation, assuming that there was a beginning (1, 3). However difficult it is to imagine what state of reality existed before the cosmos came into existence, the aim of a G.U.T. is to unite the extravagantly complex physical phenomena into a framework whereby individual components yield themselves for experimentation, verification or rejection. Whether a particular G.U.T. is legitimate or not is, of course, important but not crucially so, as its cardinal purpose is to facilitate and encourage research. G.U.T.s are therefore continually amended and updated to accommodate new emerging data. Unlike physicists who observe and marvel at objects in excess of 12 billion light years away, many medical researchers are, by comparison, restrained and inward looking and avoid extrapolating data outside their experimental settings. This may reflect the orthodox medical school curriculum and training, which uncompromisingly individualizes diseases, emphasizing diagnosis as obligatory for implementation of standardized treatment. Furthermore, the scientific funding system, whereby politically Machiavellian armchair speculators advocate exclusive funding for selfserving, myopic, reductionist research that misses the whole by concentrating exclusively on the minuscule, may also be at fault. Even if these factors were unimportant, it would still be matter of considerable conjecture whether a G.U.T. could be applied in the biological sciences. However, if the affirmative, it would not take an astute allegorist to conclude that a biological G.U.T. would ‘nemine contradicente’ pertain to the pathogenesis of gut disorders. Indeed, by considering some of the unique characteristic features of the gastrointestinal tract and consolidating much experimental evidence from different sources in man, we propose and set out to justify the basis of a G.U.T. of the pathogenesis of gut disorders, i.e. disease of the small intestine.

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.

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

Abstract Background: Capsule endoscopy (CE) is often used to investigate small bowel Crohns 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

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.

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.

Evaluation of a new pan-enteric video capsule endoscopy system in patients with suspected or established inflammatory bowel disease – feasibility study

Background and study aims  Inflammatory bowel disease (IBD) affects the small bowel and colon. Endoscopic evaluation of these organs is essential. The new pan-enteric Crohn’s capsule (PCC) system is customized for complete coverage of IBD lesions in the entire bowel, allowing assessment and follow-up of disease severity and extent. The aim of this study was to evaluate the functionality of the PCC system in patients with suspected or established IBD. Patients and methods  This was a prospective five-center feasibility study assessing the performance of PCC. Subjects ingested PCC after patency assurance with standard bowel preparation plus boosts. The primary endpoint was successful procedure, that is, video creation and report generation in accordance with methodology. Secondary endpoints were subjective coverage of the entire bowel, duration of reading time, video quality and occurrence of adverse events. Results  Forty-one patients were included in the study with a mean age of 40.8 years ± 15.5, 46 % of whom were males. Seventy-one percent of patients had established Crohn’s disease (CD) and 53 % had active disease. Cleansing was graded good/excellent in 95 %. All 41 videos met the primary endpoint. There was no retention, 83 % reached the toilet while still recording. Thirty-one percent of patients with CD had proximal disease. Bowel coverage was graded 6.7 ± 0.6 and 6.1 ± 1.3 (1 – 7, unconfident – confident), image quality 6.1 ± 0.8 (1 – 7, poor – excellent), and reading time 3.7 ± 1.4 (1 – 7, very short to very long). Conclusions  The PCC system is a minimally invasive system allowing extensive evaluation of the entire bowel in patients with IBD.

Tricyclic antidepressants for the treatment of tenesmus associated with rectal prolapse.

Tenesmus in rectal prolapse leads to a vicious circle of straining with deterioration of prolapse. The primary phenomenon triggering this may be rectal hypersensitivity. We aimed to assess whether treatment with tricyclic antidepressants (TCAs) may break the vicious circle and improve tenesmus.