The effect of infliximab dose escalation in inflammatory bowel disease patients with antibodies to infliximab.

BACKGROUND: Infliximab dose escalation (DE) can be used in inflammatory bowel disease patient; however, the long-term benefit remains unclear, especially in those with antibodies to infliximab (ATI). The aim was to assess the effect of DE in patients with ATI on drug level, clinical response and ATI status. METHODS: All patients undergoing infliximab DE (a reduction in dose interval between infusions <8 weeks ± an increase in dose up to 10 mg/kg) at a referral centre between April 2016 and August 2019 were included. RESULTS: Ninety-two patients were DE: 51 were men, 50 had CD and 63 were receiving immunosuppression. A total of 87 people received DE for a median of 44 weeks (range 4-176). Five stopped infliximab after 1 dose of DE: 2 for loss of response and 3 for infusion reaction. In patients with ATI ≤10 vs. >10 AU/mL, DE significantly increased drug levels: median infliximab levels of 1.4 and 0.9 at baseline, respectively, to 3.2 and 3.5 at week 24. After DE, 21/35 ATI-positive patients had a fall in ATI ≤10 AU/mL. At week 24 following DE 62/92 patients were in clinical remission. Duration of clinical remission was shorter in those with ATI >10 AU/mL (median 24 weeks, range 0-88) than in those with transient/ATI ≤10 AU/mL (median 36 weeks, range 0-126, P = 0.06). CONCLUSIONS: A strategy of DE for selected patients receiving infliximab is associated with an increase in drug levels and reduced ATI positivity. This is associated with clinical remission in approximately 70% of patients at 6 months.

Magnetically assisted capsule endoscopy in suspected acute upper GI bleeding versus esophagogastroduodenoscopy in detecting focal lesions.

BACKGROUND AND AIMS: Acute upper GI bleeding is common and requires investigation with EGD, but endotherapy is not always necessary. Magnetically assisted capsule endoscopy (MACE) uses a capsule steerable by an external magnet and allows examination of the upper GI tract and small bowel, but its role in acute upper GI bleeding has not been assessed. METHODS: We conducted a prospective cohort study comparing the diagnostic yield of MACE and EGD in patients with suspected acute upper GI bleeding. Patient tolerance, mucosal visibility by MACE, and frequency of small-bowel bleeding were assessed. Whether or not MACE could safely predict discharge of patients was also determined. RESULTS: Thirty-three patients were included for analysis (median age, 60 years; 75.8% male). MACE detected more focal lesions (peptic, vascular, and fresh/altered blood without a clear source) than EGD (40 versus 25, respectively, P = .02) but statistical significance was not reached for significant lesions (considered to be the bleeding source; 14 vs 13, respectively, P = 1). Capsule endoscopy identified an additional cause for bleeding in the small bowel in 18%. Visualization by MACE was excellent in most areas; views of the esophagus, gastroesophageal junction, fundus, and duodenal bulb were suboptimal. MACE was better tolerated than unsedated EGD and correctly identified patients who were safe for discharge. CONCLUSIONS: MACE had higher diagnostic yield for focal lesions and was better tolerated than EGD. It also correctly predicted safe discharge for patients with acute upper GI bleeding. (Clinical trials registration number: NCT02690376.).

Polymerase chain reaction for detection of mucosal cytomegalovirus infection in patients with acute ulcerative colitis.

BACKGROUND: Cytomegalovirus (CMV) infection is associated with acute exacerbations of ulcerative colitis (UC) but its clinical relevance remains uncertain. The primary aim of this study was to assess the prevalence of CMV infection in UC patients using viral polymerase chain reaction (PCR) analysis of mucosal biopsy samples. Secondary aims were to establish whether the disease was due to a primary infection or reactivation and to note associated risk factors and clinical outcomes. METHODS: Since 2011, a policy of biopsy for CMV infection was adopted for severe UC patients in a large tertiary center. A retrospective review was undertaken to identify patients with mucosal biopsies for exacerbations of UC from October 2011 through January 2014. RESULTS: Sixty biopsies for CMV PCR were obtained from 52 patients, 15 of whom were positive. In these patients, 9/9 tested were seropositive for anti-CMV IgG, while none were seropositive for anti-CMV IgM. Steroid refractory disease was a significant predictor of CMV positivity; however, there was no difference between the CMV-positive and -negative groups in rates of immunosuppression, or clinical and endoscopic severity. Six patients in the CMV-positive group received infliximab; all received concurrent antiviral therapy and did not require surgery. CONCLUSIONS: PCR of mucosal biopsies detected CMV infection due to viral reactivation in almost a third of patients with deteriorating or acute severe UC. Steroid refractory disease was significantly associated with CMV positivity, but no significant relationship was demonstrated with either disease severity or immunosuppression in our cohort. Treatment with anti-tumor necrosis factor agents was administered safely in combination with antiviral drugs.

Diagnostic yield of magnetically assisted capsule endoscopy versus gastroscopy in recurrent and refractory iron deficiency anemia.

BACKGROUND: Small-bowel capsule endoscopy is advocated and repeat upper gastrointestinal (GI) endoscopy should be considered for evaluation of recurrent or refractory iron deficiency anemia (IDA). A new device that allows magnetic steering of the capsule around the stomach (magnetically assisted capsule endoscopy [MACE]), followed by passive small-bowel examination might satisfy both requirements in a single procedure. METHODS: In this prospective cohort study, MACE and esophagogastroduodenoscopy (EGD) were performed in patients with recurrent or refractory IDA. Comparisons of total (upper GI and small bowel) and upper GI diagnostic yields, gastric mucosal visibility, and patient comfort scores were the primary end points. RESULTS: 49 patients were recruited (median age 64 years; 39 % male). Combined upper and small-bowel examination using the new capsule yielded more pathology than EGD alone (113 vs. 52; P < 0.001). In upper GI examination (proximal to the second part of the duodenum, D2), MACE identified more total lesions than EGD (88 vs. 52; P < 0.001). There was also a difference if only IDA-associated lesions (esophagitis, altered/fresh blood, angioectasia, ulcers, and villous atrophy) were included (20 vs. 10; P = 0.04). Pathology distal to D2 was identified in 17 patients (34.7 %). Median scores (0 - 10 for none - extreme) for pain (0 vs. 2), discomfort (0 vs. 3), and distress (0 vs. 4) were lower for MACE than for EGD (P < 0.001). CONCLUSION: Combined examination of the upper GI tract and small bowel using the MACE capsule detected more pathology than EGD alone in patients with recurrent or refractory IDA. MACE also had a higher diagnostic yield than EGD in the upper GI tract and was better tolerated by patients.

Upper gastrointestinal tract capsule endoscopy using a nurse-led protocol: First reported experience.

AIM: To test the feasibility and performance of a novel upper gastrointestinal (GI) capsule endoscope using a nurse-led protocol. METHODS: We conducted a prospective cohort analysis of patients who declined gastroscopy (oesophagogastroduodenoscopy, OGD) but who consented to upper GI capsule endoscopy. Patients swallowed the upper GI capsule following ingestion of 1 liter of water (containing simethicone). A series of positional changes were used to exploit the effects of water flow and move the upper GI capsule from one gravity-dependent area to another using a nurse-led protocol. Capsule transit time, video reading time, mucosal visualisation, pathology detection and patient tolerance was evaluated. RESULTS: Fifty patients were included in the study. The mean capsule transit times in the oesophagus and stomach were 28 s and 68 min respectively. Visualisation of the following major anatomical landmarks was achieved (graded 1-5: Poor to excellent): Oesophagus, 4.8 (± 0.5); gastro-oesophageal junction (GOJ), 4.8 (± 0.8); cardia, 4.8 (± 0.8); fundus, 3.8 (± 1.2); body, 4.5 (± 1); antrum, 4.5 (± 1); pylorus, 4.7 (± 0.8); duodenal bulb, 4.7 (± 0.7); second part of the duodenum (D2), 4.7 (± 1). The upper GI capsule reached D2 in 64% of patients. The mean video reading time was 48 min with standard playback mode and 20 min using Quickview (P = 0.0001). No pathology was missed using Quickview. Procedural tolerance was excellent. No complications were seen with the upper GI capsule. CONCLUSION: The upper GI capsule achieved excellent views of the upper GI tract. Future studies should compare the diagnostic accuracy between upper GI capsule and OGD.

Reassessing the value of gastroscopy for the investigation of dyspepsia.

OBJECTIVE: To evaluate the diagnostic yield of investigating dyspepsia with oesophagogastroduodenoscopy (OGD) with or without mucosal biopsy. DESIGN: Retrospective service evaluation study. SETTING: Two teaching hospitals: The Royal Hallamshire Hospital and Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, UK. PATIENTS: 500 patients, 55 years of age and over, who underwent OGD to investigate dyspepsia were included. The study period included a 3-month window. All OGDs were performed on an outpatient basis. INTERVENTIONS: Data were extracted from electronic OGD records within the study period. MAIN OUTCOME MEASURES: Diagnostic yield provided by endoscopic examination and histological assessment. RESULTS: 378 patients (75.6%) were reported to have some form of endoscopic abnormality, and 417 patients (83.4%) had biopsies taken. The most common findings at OGD were gastritis (47.2%) and oesophagitis (24.4%). Oesophagogastric malignancy was seen in 1%. Diagnoses made endoscopically or histologically that would not have been appropriately managed by empirical therapies were seen in 16.2%. CONCLUSION: OGD in dyspepsia influences patient management in approximately one-sixth of cases. However, the majority of patients are sufficiently managed with Helicobacter pylori testing and eradication and/or a trial of proton pump inhibitor therapy. Further non-invasive approaches are needed to identify patients who need endoscopy for biopsy or therapy.

Unrestricted faecal calprotectin testing performs poorly in the diagnosis of inflammatory bowel disease in patients in primary care.

BACKGROUND: Faecal calprotectin (FC) measurement distinguishes patients with inflammatory bowel disease (IBD) from those with irritable bowel syndrome but evidence of its performance in primary care is limited. AIMS: To assess the yield of IBD from FC testing in primary care. METHODS: Retrospective review of hospital records to assess the outcome following FC testing in primary care. Investigations for all patients undergoing FC testing in a single laboratory for 6 months from 1 October 2013 to 28 February 2014 were reviewed. RESULTS: 410 patients (162 male; median age 42; range 16-91) were included. FC>50 µg/g was considered positive (FC+). 148/410 (36.1%; median age 44 (17-91)) were FC+ (median FC 116.5 µg/g (51-1770)). 122/148 FC-positive patients (82.4%) underwent further investigation. 97 (65.5%) underwent lower gastrointestinal endoscopy (LGIE), of which 7 (7.2%) had IBD. 49/262 (18.7%) FC-negative (FC-) patients (FC ≤50 µg/g) (median age 47 (19-76)) also underwent LGIE, of whom 3 (6.1%) had IBD.IBD was diagnosed in 11/410 (2.7%; 4 ulcerative colitis, 3 Crohn's disease, 4 microscopic colitis). 8/11 were FC+ (range 67-1170) and 3 FC-. At a 50 µg/g threshold, sensitivity for detecting IBD was 72.7%, specificity 64.9%, positive predictive value (PPV) 5.41% and negative predictive value 98.9%. Increasing the threshold to 100 µg/g reduced the sensitivity of the test for detecting IBD to 54.6%. CONCLUSIONS: FC testing in primary care has low sensitivity and specificity with poor PPV for diagnosing IBD. Its use needs to be directed to those with a higher pretest probability of disease. Local services and laboratories should advise general practitioners accordingly.

The diagnostic accuracy of faecal calprotectin and small bowel capsule endoscopy and their correlation in suspected isolated small bowel Crohn's disease.

INTRODUCTION: Faecal calprotectin (FC) is less accurate at identifying inflammation in the small bowel than in the colon. Small bowel capsule endoscopy (SBCE) is a useful tool to detect small bowel inflammation. We investigated the diagnostic accuracy of FC and SBCE and their correlation in patients with suspected isolated small bowel Crohn's disease. PATIENTS AND METHODS: This was performed as a prospective single centre study including patients attending for SBCE with suspected small bowel Crohn's disease. Patient demographics, symptoms, medications and blood parameters were collected. Capsule endoscopy findings were analysed against calprotectin values, final diagnosis and blood parameters. RESULTS: A total of 146 patients were included (99 females and 47 males) with a mean age of 38±14 years. FC of more than 50 mg/kg was not significantly associated with clinically relevant capsule endoscopy findings (P=0.25), correlation coefficient was 0.11. Sensitivity, specificity, positive and negative predictive values for FC at a cut-off of more than 50 mg/kg were 88.9% [95% confidence interval (CI): 65.3-98.6], 25.0% (95% CI: 17.8-33.4), 14.3 (95% CI: 8.4-22.2) and 94.1% (95% CI: 80.3-99.3), respectively. A raised FC was not significantly associated with an elevated C-reactive protein or the presence of anaemia (P=0.19 and 0.10, respectively). CONCLUSION: FC performs modestly as a screening test to exclude small bowel inflammation. However, we recommend interpretation within the overall clinical context to avoid overlooking the infrequent patient with small bowel inflammation and a negative FC.

Does magnetically assisted capsule endoscopy improve small bowel capsule endoscopy completion rate? A randomised controlled trial.

BACKGROUND AND STUDY AIMS: Delayed gastric emptying is a significant factor in incomplete small bowel capsule examinations. Gastric transit could be hastened by external magnetic control of the capsule. We studied the feasibility of this approach to improve capsule endoscopy completion rates. PATIENTS AND METHODS: Prospective, single-center, randomized controlled trial involving 122 patients attending for small bowel capsule endoscopy using MiroCam Navi. Patients were randomized to either the control group (mobilisation for 30 minutes after capsule ingestion, followed by intramuscular metoclopramide 10 mg if the capsule failed to enter the small bowel) or the intervention group (1000 mL of water prior to capsule ingestion, followed by positional change and magnetic steering). Outcome measures were capsule endoscopy completion rate, gastric clarity and distention, relationship of body habitus to capsule endoscopy completion rate (CECR), and patient comfort scores. RESULTS: 122 patients were recruited (61 each to the control and intervention groups: mean age 49 years [range 21 - 85], 61 females). There was no significant difference in CECR between the two groups (P = 0.39). Time to first pyloric image was significantly shorter in the intervention group (P = 0.03) but there was no difference in gastric transit times (P = 0.12), suggesting that magnetic control hastens capsular transit to the gastric antrum but does not influence duodenal passage. Gastric clarity and distention were significantly better in the intervention group (P < 0.0001 and P < 0.0001 respectively). CONCLUSIONS: Magnetic steering of a small bowel capsule is unable to overcome pyloric contractions to enhance gastric emptying and improve capsule endoscope completion rate. Excellent mucosal visualisation within the gastric cavity suggests this technique could be harnessed for capsule examination of the stomach.

Magnetically steerable gastric capsule endoscopy is equivalent to flexible endoscopy in the detection of markers in an excised porcine stomach model: results of a randomized trial.

BACKGROUND AND STUDY AIMS: Capsule endoscopy is well tolerated but control of its movement is needed in order to visualize the whole gastric surface. Technological developments have produced an external magnet to allow manipulation of the capsule within the gastric cavity. The aim of this study was to compare magnetically steerable gastric capsule endoscopy (MSGCE) with flexible endoscopy for the detection of beads in a porcine stomach. MATERIALS AND METHODS: Beads were sewn onto the mucosal surface of 12 ex vivo porcine stomachs. Each model was examined by flexible endoscopy and MSGCE by two blinded investigators. MSGCE was performed according to a protocol using positional changes and magnetic steering. Outcome measures were number and location of beads identified, and duration of procedure. RESULTS: Flexible endoscopy identified 79 /90 beads (88 %), and MSGCE identified 80 /90 (89 %). The difference in sensitivities was 1.11 (95 % confidence interval 0.06 - 28.26). Thus, MSGCE was noninferior to flexible endoscopy. Mean examination times for flexible endoscopy and MSGCE were 3.34 minutes and 9.90 minutes, respectively. CONCLUSION: MSGCE was equivalent to conventional flexible endoscopy in the detection of beads in a porcine stomach model.

Practical aspects of delivering a small bowel endoscopy service in the UK.

Capsule endoscopy remains at the forefront of small bowel investigation, offering the only non-invasive means of directly imaging the mucosa of the small bowel. Recommended for the investigation of obscure gastrointestinal bleeding, Crohn's disease, coeliac disease, small bowel tumours and hereditary polyposis syndromes, the uptake of small bowel capsule endoscopy has been widespread in the UK. However, despite a wealth of published literature supporting the utility of capsule endoscopy in clinical practice, there are limited data regarding the actual practical aspects of service delivery, training and quality assurance. In this article, we attempt to address this by considering specific factors that contribute to provision of a high-quality capsule service. The role of formal training, accreditation and quality assurance measures is also discussed.

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 Crohn's 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, Barrett's 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.

Point-of-care testing for celiac disease has a low sensitivity in endoscopy.

BACKGROUND: Celiac disease (CD) is a common but underdiagnosed condition. A rapid point-of-care test (POCT) could reduce lead times and missed diagnoses. OBJECTIVE: To assess the utility of an immunoglobulin (Ig) A tissue transglutaminase (TTG) antibody POCT in an endoscopic setting. DESIGN: Prospective observational study. SETTING: A single UK university hospital. PATIENTS: Patients presenting with suspected CD, known CD, and routine endoscopy for upper GI symptoms. INTERVENTIONS: All patients were tested with POCT, serum TTG, endomysial antibody (EMA), and upper GI endoscopy with duodenal biopsies at the same visit. MAIN OUTCOME MEASUREMENTS: Comparison was made with histology in all cases, with villous atrophy regarded as diagnostic of CD. RESULTS: A total of 576 patients (63.5% female, mean [± standard deviation] age 49.7 years [± 17.6 years]) were recruited. A total of 523 patients had no prior diagnosis of CD, and 53 patients had known CD coming for reassessment. A total of 117 patients were newly diagnosed with CD, and 82 were positively identified by the POCT. Sensitivity, specificity, positive predictive value, and negative predictive value were 70.1%, 96.6%, 85.4%, and 91.8%, respectively. In comparison, TTG and EMA both performed significantly better than the POCT. Sensitivity and specificity of TTG were 91.0% and 83.5%, respectively, and EMA were 83.8% and 97.5%, respectively. Of patients with known CD coming for reassessment, 26 had villous atrophy, and POCT results were positive in 16 (61.5%). There was poor agreement between POCT and standard serology. LIMITATIONS: High pre-test probability of CD. CONCLUSION: The performance of this POCT was disappointing compared with standard serology and cannot at present be recommended within the context of an endoscopy unit.

Duodenal bulb biopsies for diagnosing adult celiac disease: is there an optimal biopsy site?

BACKGROUND: Recent studies highlight the role of duodenal bulb biopsy in the diagnosis of celiac disease. OBJECTIVE: To determine whether a targeted duodenal bulb biopsy in addition to distal duodenal biopsies is the optimal strategy to identify villous atrophy. DESIGN: Prospective cohort study. SETTING: Tertiary-care referral center. PATIENTS: Seventy-seven patients undergoing clinically indicated EGD with duodenal biopsies were recruited. Of these, 28 had newly diagnosed celiac disease and 49 were controls. INTERVENTIONS: At endoscopy, 8 duodenal biopsy specimens were taken: 4 from the second part of the duodenum and 4 quadrantically from the bulb (at the 3-, 6-, 9-, and 12-o'clock positions). MAIN OUTCOME MEASUREMENTS: Increasing the diagnostic yield and detection of the most severe villous atrophy in celiac disease with the addition of a targeted duodenal bulb biopsy. RESULTS: The most severe degree of villous atrophy was detected when distal duodenal biopsy specimens were taken in addition to a duodenal bulb biopsy specimen from either the 9- or 12-o'clock position (96.4% sensitivity; 95% CI, 79.7%-100%). The difference between the 12-o'clock position biopsy and the 3-o'clock position biopsy in detecting the most severe villous atrophy was 92% (24/26) versus 65% (17/26) (P = .02). LIMITATIONS: Small sample and study performed in a tertiary referral center. CONCLUSIONS: This study demonstrates the patchy appearance of villous atrophy that occurs within the duodenum. A targeted duodenal bulb biopsy from either the 9- or 12-o'clock position in addition to distal duodenal biopsies may improve diagnostic yields by detecting the most severe villous atrophy within the duodenum.