Reena Sidhu

Is there an association between coeliac disease and inflammatory bowel diseases? A study of relative prevalence in comparison with population controls

Objective. The relationship between coeliac disease and inflammatory bowel disease (IBD) is controversial. The aim of this study was to determine the prevalence of coeliac disease in IBD and the prevalence of IBD in coeliac disease. Material and methods. Patients were enrolled from specialist IBD and coeliac clinics. Antigliadins, endomysial, tissue transglutaminase antibody and total IgA levels were measured in IBD patients. Patients with positive antibodies were offered a duodenal biopsy. The notes on coeliac patients were reviewed for colonoscopic and biopsy findings. Controls were recruited from the local population. Results. The study included 305 patients with coeliac disease, 354 with IBD and 601 healthy controls. The IBD group comprised 154 ulcerative colitis (UC) cases, 173 Crohns disease, 18 indeterminate colitis and 9 cases of microscopic colitis. Forty-seven patients had positive antibodies and 3 had villous atrophy on biopsy. All three patients had positive anti-tissue transglutaminase antibodies but only two were endomysial antibody (EMA) positive. Ten coeliac patients had IBD (5 UC and 5 lymphocytic colitis). Five controls had coeliac disease and 2 had IBD (1 Crohns disease and 1 UC). Stepwise multiple logistic regression showed only antibody positivity as being significant (p<0.0001). Conclusions. The prevalence of IBD in coeliac disease was increased 10-fold compared with that in controls (odds ratio 9.98, 95% CI 2.8–45.9, p=0.0006), while the prevalence of coeliac disease in IBD was comparable with that in controls (odds ratio 1.02, 95% CI, 0.24–4.29, p=1.0).

Capsule endoscopy in adult celiac disease: a potential role in equivocal cases of celiac disease?

BACKGROUND There have been limited studies evaluating capsule endoscopy (CE) in equivocal celiac disease (CD). OBJECTIVE To determine the role CE may have in equivocal CD cases, compared with patients with biopsy-proven and serology-proven CD who have persisting symptoms. DESIGN Prospective cohort study. SETTING University hospital. PATIENTS A total of 62 patients with equivocal CD and 69 patients with nonresponsive CD. INTERVENTION CE. MAIN OUTCOME MEASUREMENTS Diagnostic yield of CE in equivocal cases and accuracy of mucosal abnormality detection in patients with nonresponsive CD. RESULTS Equivocal cases (n = 62) were divided into two subgroups: group A (antibody-negative villous atrophy, n = 32) and group B (Marsh 1-2 changes, n = 30). In group A, CE secured a diagnosis of CD or Crohns disease in 28% (9/32), significantly higher than the diagnostic yield in group B (7%; P = .044). In patients with CD with persisting symptoms, significant CE findings were identified in 12% (8/69), including 2 cases of enteropathy-associated lymphoma, 4 type 1 refractory disease cases, 1 polypoidal mass histologically confirmed to be a fibroepithelial polyp, and 1 case of ulcerative jejunitis. This outcome was significantly lower than the diagnostic yield of CE in antibody-negative villous atrophy (P = .048). LIMITATIONS Single center. CONCLUSION There have been no previous reports systematically evaluating equivocal CD by using CE. The diagnostic yield of CE in patients with antibody-negative villous atrophy is better than that of CE in patients with CD with persisting symptoms. We advocate the use of CE in equivocal cases, particularly in patients with antibody-negative villous atrophy.

Is formal training necessary for capsule endoscopy?: The largest gastroenterology trainee study with controls

BACKGROUND Little is known about the infrastructure to train gastroenterologists in capsule endoscopy. The level of capsule endoscopy exposure among trainees in the United Kingdom or Europe has also not been quantified. AIMS AND METHODS To assess the ability of 10 gastroenterology trainees with endoscopy experience to interpret 10 capsule endoscopy videos against five medical students, with an expert in capsule endoscopy as the gold standard. Parameters assessed included gastric emptying time, small bowel transit and the diagnosis made. A questionnaire survey assessed the level of capsule endoscopy exposure among United Kingdom trainees. RESULTS Trainees were better at determining the gastric emptying time (p=0.013) and more likely to record true positives compared to the students (p=0.037). They were also less likely to record false positives (p=0.005) and more likely to reach the correct diagnosis (p=0.001, OR 3.6, CI 1.8-7.4). Our survey found that, 65% of trainees had prior exposure to capsule endoscopy but only 13% had done capsule endoscopy reporting. Sixty seven percent felt capsule endoscopy should be incorporated into their training. CONCLUSION This study has shown that prior endoscopic experience enables trainees to interpret capsule endoscopy more accurately than medical students. However, there is a demand for focussed training which would enable trainees to reliably interpret pathology on capsule endoscopy.

Gastrointestinal capsule endoscopy: from tertiary centres to primary care.

The first endoscope introduced by Bruening in 1907 was a rigid instrument that allowed inspection of the upper gastrointestinal tract under a general anaesthetic.w1 Forty years later the first flexible fibreoptic instrument allowed procedures to be done under local anaesthetic or light sedation. It took a further 20 years for the technological evolution of the first colonoscope. A major advance occurred in 1999, when capsule endoscopy enabled complete visualisation of the small bowel.w2 A capsule is swallowed and propelled through the gastrointestinal tract by the action of peristalsis. It contains an imaging device, which transmits images of the intestine to sensors on the abdominal wall. Fig 1 A capsule endoscope Historically the small bowel was considered technically difficult to examine because of its length (3-5 metres), location, and tortuosity.w3 Previously the small bowel could be partly assessed by a push enteroscope, which is longer (about 2 metres) than a standard gastroscope and therefore allows examination of up to 80-120 cm beyond the ligament of Treitz (anatomically the duodenojejunal flexure), while intraoperative enteroscopy required a general anaesthetic and laparotomy. Barium follow through (small bowel meal) and enteroclysis (double contrast small bowel follow through) allow indirect examination of the small bowel but have a low diagnosis rate.1 w4 w5 Given the limitations of these other tests, there has been a surge in investigations on the practical diagnostic ability and clinical utility of capsule endoscopy. #### Summary points Capsule endoscopy—a novel method of imaging the small bowel—is safe and can be performed on an outpatient basis in both primary and secondary care It has a higher positive diagnosis rate in the detection of small bowel pathology than conventional small bowel investigations Capsule endoscopy can be used to investigate patients with obscure gastrointestinal bleeding and negative results on upper and lower gastrointestinal endoscopy We performed …

Evaluating the role of small-bowel endoscopy in clinical practice: the largest single-centre experience.

Objective There are few centres that offer all forms of small-bowel endoscopic modalities [capsule endoscopy (CE), push enteroscopy (PE), double-balloon enteroscopy (DBE) or single-balloon enteroscopy and intraoperative enteroscopy (IOE)]. Previous investigators have suggested that DBE may be more cost-effective as the first-line investigation. We evaluated the relationship among four modalities of small-bowel endoscopy in terms of demand, diagnostic yield, patient management and tolerability. Methods Data were collected on patients who underwent PE and IOE since January 2002, CE since June 2002 and DBE since July 2006. These included age, sex, indication of referral, comorbidity, previous investigations and diagnosis obtained, including subsequent management change. Results Demand for CE and DBE increased every year. A total of 1431 CEs, 247 PEs, 102 DBEs and 17 IOEs were performed over 93 months. The diagnostic yield was 88% for IOE compared with 34.6% for CE, 34.5% for PE and 43% for DBE (P<0.001). Management was altered by CE in 25%, by PE in 19% and by DBE in 33% of patients. However, 44% of patients who underwent DBE found the procedure difficult to tolerate. In 2009, for every 17 CEs performed, one patient underwent DBE locally. Conclusion This is the first series to report the clinical experience of four modalities of small-bowel endoscopy from a single centre. The use of CE as first-line investigation, followed by PE/DBE or IOE, is potentially both less invasive and tolerable.

Push Enteroscopy in the Era of Capsule Endoscopy

Goals To evaluate the diagnostic yield of push enteroscopy in relation to indication and compare the yield in patients who had capsule endoscopy followed by push enteroscopy against capsule endoscopy naive patients. Background With the advent of capsule endoscopy the role of push enteroscopy needs to be reevaluated. Study Patients who underwent push enteroscopy from January 2002 to May 2006 were included. Results One hundred fifty-five patients underwent push enteroscopy: 93 females, average age 55 years. There were 74 cases where both push enteroscopy (PE) and capsule endoscopy (CE) were performed. Indications for PE were iron deficiency anemia (n=51), overt bleeding (n=31), suspected celiac disease (n=32), refractory celiac disease (n=19), assessment for Crohns disease (n=10), and miscellaneous (n=12). In 148 patients, an average length of 70 cm of small bowel was examined (range 30 to 130 cm). PE was unsuccessful in 7 patients due to anatomic strictures or patient distress. The overall diagnostic yield was 30% with the highest yield in overt bleeding when compared with other subgroups (P<0.001). Nine percent of lesions were within the reach of a standard endoscope. Comparison of the diagnostic yield in patients who had CE followed by PE against CE naive patients was 41% versus 47%, respectively (P<1). There were no cases where push enteroscopy recognized a lesion that had not been already detected by capsule endoscopy. Conclusions Push enteroscopy has the greatest diagnostic yield in patients with overt bleeding when compared with other referral indications. PE should be used as an adjuvant to CE for therapeutic intervention.

Capsule endoscopy: is there a role for nurses as physician extenders?

Capsule endoscopy is a novel technique for examining the small bowel; however, data interpretation is time consuming and requires expertise. This study aimed to compare the interpretation of capsule endoscopy between an experienced gastroenterologist and a nurse. A total of 50 consecutive videos were viewed independently by a nurse and a physician, both blinded to the referral indications. The nurse had no prior experience with capsule endoscopy. Possible pathology was graded in a pre-agreed standardized manner, with findings described as “relevant,” “uncertain,” or “irrelevant.” Another gastroenterologist, who had knowledge of all the cases including follow-up data and clinical outcomes, independently arbitrated. Findings showed no difference in the number of relevant or uncertain pathologies identified. The nurse reader was more likely to record irrelevant findings (4.7 vs. 2.0 lesions; p < .01) and required more time to read the videos than the physician (mean = 73 vs. 58 min; p < .01). This study shows that a nurse capsule endoscopy reader is as capable as an experienced physician in identifying small bowel mucosal abnormalities on capsule endoscopy. Capsule endoscopy is an area in which nurses could develop as physician extenders.

Elevated serum chromogranin A in irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD): A shared model for pathogenesis?

To the Editor: Sciola et al have demonstrated that plasma chromogranin A levels are elevated in patients with inflammatory bowel disease (IBD), suggesting neuroendocrine system activation in response to inflammation. We would like to share our observations in this area. We studied the prevalence of elevated serum chromogranin A levels in patients with IBD and diarrhea predominant irritable bowel syndrome (D-IBS who fulfilled Rome II criteria). This study measured CgA levels in 39 patients with IBD and 87 patients with D-IBS. We used the new competitive radioimmunoassay that uses antibodies against human CgA (EURO-DIAGNOSTICA, normal values <4 nmol/L). Patients with serially elevated CgA levels were requested to have fasting gut hormones and urinary 5-hydroxyindole acetic acid. CgA levels were elevated in 30.8% (n 1⁄4 12) of patients with IBD and 50.6% (n 1⁄4 44) of patients with D-IBS (P 1⁄4 0.04). The mean CgA levels in the IBD and IBS groups were 6.4 nmol/L and 7.2 nmol/L, respectively. Within the IBD group with elevated CgA (n 1⁄4 12/39), levels returned to normal in 2 patients on repeat testing. 8/12 had persistently elevated CgA but at a level less than 10 u/L. For the 2 patients who had a CgA >10 u/L, 1 patient had a normal octreoscan and computed tomography (CT) scan while the other patient declined repeat levels. In the D-IBS group, of the 44/87 who had CgA levels that were elevated, in 19/44 the CgA level normalized on repeat testing. Fifteen had repeat levels <10 nmol/L but with normal fasting gut hormones and urinary 5HIAA. In the 10/ 44 with levels >10 nmol/L subsequent carcinoid investigations were normal. Our study supports the observation of Sciola et al of elevated serum chromogranin A in IBD but also demonstrates that elevated levels occur more frequently in D-IBS patients. Could the unifying hypothesis be enterochromaffin cell hyperplasia resulting in elevated serum chromogranin A levels? The differential replication of the enterochromaffin cells in IBS patients could also explain why elevated levels are only found in a proportion of patients and levels decline with time. Further studies of serial serum chromogranin A measurements in both of these conditions would strengthen our understanding of the plausible mechanisms behind these observations.

Capsule endoscopy:Current practice and future directions

Capsule endoscopy (CE) has transformed investigation of the small bowel providing a non-invasive, well tolerated means of accurately visualising the distal duodenum, jejunum and ileum. Since the introduction of small bowel CE thirteen years ago a high volume of literature on indications, diagnostic yields and safety profile has been presented. Inclusion in national and international guidelines has placed small bowel capsule endoscopy at the forefront of investigation into suspected diseases of the small bowel. Most commonly, small bowel CE is used in patients with suspected bleeding or to identify evidence of active Crohns disease (CD) (in patients with or without a prior history of CD). Typically, CE is undertaken after upper and lower gastrointestinal flexible endoscopy has failed to identify a diagnosis. Small bowel radiology or a patency capsule test should be considered prior to CE in those at high risk of strictures (such as patients known to have CD or presenting with obstructive symptoms) to reduce the risk of capsule retention. CE also has a role in patients with coeliac disease, suspected small bowel tumours and other small bowel disorders. Since the advent of small bowel CE, dedicated oesophageal and colon capsule endoscopes have expanded the fields of application to include the investigation of upper and lower gastrointestinal disorders. Oesophageal CE may be used to diagnose oesophagitis, Barretts oesophagus and varices but reliability in identifying gastroduodenal pathology is unknown and it does not have biopsy capability. Colon CE provides an alternative to conventional colonoscopy for symptomatic patients, while a possible role in colorectal cancer screening is a fascinating prospect. Current research is already addressing the possibility of controlling capsule movement and developing capsules which allow tissue sampling and the administration of therapy.

Undisclosed Use of Nonsteroidal Anti-Inflammatory Drugs May Underlie Small-Bowel Injury Observed by Capsule Endoscopy

BACKGROUND & AIMS Findings from capsule endoscopies (CEs) of patients with enteropathy from nonsteroidal anti-inflammatory drugs (NSAIDs) may be indistinguishable from those with Crohns disease, making medication history crucial to image interpretation. Undeclared NSAID use has been proposed to cause unexplained peptic ulcers; we investigated whether it is also an issue among patients referred for small-bowel CE. METHODS We collected demographic data, indications for CE, and medication history prospectively. A salicylate spot test and gas chromatography-mass spectrometry were performed for NSAID metabolites in urine samples of patients undergoing routine CE. Videos were analyzed by a gastroenterologist who was blinded to the urinalysis results. RESULTS Seventy-six patients (52 women; mean age, 50 y) underwent CE for suspected small-bowel pathology. Urinalysis was positive in 13.6% of patients (salicylates, n = 3; ibuprofen, n = 6; and ibuprofen and diclofenac, n = 1) although only 1 of these patients declared use of an NSAID (aspirin). Although 2 patients had normal CE results, 80% had positive results, including the presence of erosions (n = 5), ulceration (n = 2), and ulcers with early stricturing (n = 1, diagnosed with Crohns disease). A patient with small-bowel ulceration underwent surgery and was found to have NSAID-associated enteropathy, based on histologic analysis. CONCLUSIONS Of patients who undergo CE, 13.6% took NSAIDs or aspirin, but most did not declare using these medications. Small-bowel inflammation was common in this cohort and could be mistaken for Crohns disease. Patients should be questioned about use of over-the-counter medications, and routine urinalysis for NSAID metabolites may be helpful before interpretation of CE findings.