Diana E. Yung

Do prokinetics influence the completion rate in small-bowel capsule endoscopy? A systematic review and meta-analysis

Abstract Background: The use of purging for bowel cleansing prior to small-bowel capsule endoscopy (SBCE) has now been established in clinical practice. Despite that, the number of incomplete SBCEs is still around 15–20%. To date, the use of prokinetics in SBCE – aiming to improve completion rate (CR) – remains a contentious issue resulting in lack of consensus among capsule experts. Methods: Extensive medical literature searches were conducted (to November 2012), using suitable MeSH terms and keywords, in search of studies that compared capsule ingestion with prokinetic agents vs. controls or placebo. We examined the effects of prokinetic administration on SBCE CR (primary end point), as well as on the following secondary end points: diagnostic yield (DY), gastric transit time (GTT) and small-bowel transit time (SBTT) by meta-analysis of all relevant studies. Results: A total of 17 eligible studies (14 prospective, 3 retrospective) were identified, including 1028 individuals who ingested the capsule with no prokinetic vs. 876 who received a prokinetic. Overall, there was a higher CR in patients who ingested the capsule with prokinetics vs. controls (OR [95% CI]: 1.96 [1.38–2.78]). Of the two most readily available prokinetics, metoclopramide was associated with superior SBCE CR vs. control (OR [95% CI]: 2.8 [1.35–3.21]), while erythromycin showed no benefit (OR [95% CI]: 1.36 [0.61–3.03]). Where prokinetics were used alone, neither metoclopramide nor erythromycin showed any benefit on CR. There was no benefit of prokinetics (over controls) on DY. However, metoclopramide had a significant effect on GTT and SBTT. Limitations: The majority of the included studies were heterogeneous, and the effect of prokinetics on image quality and mucosal visualization was not examined. Conclusion: Our pooled data shows that the use of prokinetics for capsule ingestion improves CR in SBCE. This effect appears to be particularly evident with metoclopramide, when used concurrently with purging and/or use of real-time monitoring. In a small number of studies, erythromycin showed – through its gastrokinetic effect – marginal benefit. No prokinetic has a beneficial effect on SBCE DY.

The use of small-bowel capsule endoscopy in iron-deficiency anemia alone; be aware of the young anemic patient.

Abstract Background & aim. The role of Small-Bowel Capsule Endoscopy (SBCE) in Iron Deficiency Anemia (IDA) alone is still under validation. We aim to assess the usefulness of SBCE in patients with IDA alone; Methods. Retrospective study; patients with IDA (no GI symptoms or known previous diagnosis), who underwent SBCE were included. SBCE findings were classified as clinically significant/sinister (small-bowel malignancy, significant/sinister inflammation and/or strictures and coeliac disease) or vascular, i.e., signifcant/angioectasias (P1/P2 lesions); Results. A total of 221 (151F/70M) patients had SBCE for IDA as the sole indication. The diagnostic yield (DY) was 30.7% (68/221). The DY for significant/sinister pathology and significant/angioectasias was 9% and 21.7%, respectively. In those ≤40 years (20; 13F/7M), significant pathology was found in 25% (5/20); in the >40-year group (201; 138F/63M), significant/sinister pathology was found in 7.5% (15/201), p = 0.0231. None of the patients ≤40 years had angioectasias, such lesions were found in 48/201 (21.7%) of those >40 years, p = 0.009. Fifty percent of those >80 years (16; 12F/4M) had angioectasias, but none had significant/sinister pathology (p = 0.0126). On multiple regression analysis, only prior blood transfusion was predictive of higher DY in SBCE; Conclusions. IDA alone is one of the main indications (27%) for referral to SBCE; the majority of patients are >40 years. In our cohort, the DY of SBCE for IDA was 30.7% and the commonest finding was angioectasias. The detection rate of sinister small-bowel pathology for those >40 years is low decreasing to zero in the >80 age group. In contrast, 25% of those ≤40 years had a sinister diagnosis.

Fecal calprotectin for the prediction of small-bowel Crohn's disease by capsule endoscopy: a systematic review and meta-analysis.

Background and aims Fecal calprotectin is a well-established marker of mucosal inflammation. Although the correlation of elevated calprotectin levels with colonic inflammation has been confirmed repeatedly, it is less established for the small bowel. The aim of the current study was to assess the diagnostic accuracy of calprotectin for the prediction of active small-bowel disease on capsule endoscopy by performing a diagnostic test meta-analysis. Materials and methods A comprehensive search was performed using PubMed/Embase. Studies addressing patients with suspected/established Crohn’s disease (CD) evaluated with calprotectin and videocapsule were included. A diagnostic meta-analysis was carried out; pooled diagnostic sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated for each cut-off. Results Seven studies (463 patients) were entered into the final analysis. The DOR was significant for all the evaluated FC cut-offs (50 &mgr;g/g: sensitivity 0.83, specificity 0.53, DOR-5.64; 100 &mgr;g/g: sensitivity 0.68, specificity 0.71, DOR-5.01; 200 &mgr;g/g: sensitivity 0.42, specificity 0.94, DOR-13.64). On sensitivity analyses, when only studies addressing suspected Crohn’s or retrospective studies were included, the results did not change significantly. For studies including patients with suspected CD only, the overall accuracy for FC cut-off 50 &mgr;g/g was further increased (sensitivity 0.89, specificity 0.55, DOR-10.3), with a negative predictive value of 91.8%. Summary and conclusion Fecal calprotectin has a significant diagnostic accuracy for the detection of small-bowel CD. Our results suggest that in patients with suspected CD with calprotectin <50 &mgr;g/g, the likelihood of positive diagnosis is very low.

Vedolizumab in IBD–Lessons From Real-world Experience; A Systematic Review and Pooled Analysis

Background Vedolizumab [VDZ] is an anti-integrin monoclonal antibody effective in ulcerative colitis [UC] and Crohns disease [CD]. Several real-world experience [RWE] studies with VDZ have been published to date. The aim of this systematic review was to summarise the available real-life experience with VDZ. Methods We performed a systematic review of the available RWE studies of VDZ in CD and UC. We performed a pooled analysis of the available efficacy and safety data for induction and maintenance treatment in adult cohorts. A narrative review of VDZ use in special clinical settings was also performed. Results Nine studies including 1565 [571 UC, 994 CD] adult patients were identified. In CD, clinical response and remission were achieved in 54% (95% confidence interval [CI] 41-66%) and 22% [95% CI 13-35%] by Week 6 and in 49% [95% CI 37-51%] and 32% [95% CI 23-42%] by Week 14; at Week 52, 45% [95% CI 28-64%] and 32% [95% CI 12-62] of the patients responded, and were in clinical remission, respectively. In UC, clinical response and remission were achieved in 43% [95% CI 37-49] and 25% [95% CI 12-45] by Week 6, respectively, and in 51% [95% CI 43-61%]and 30% [95% CI 24-36%] by Week 14/22, respectively; at week 52, clinical response and remission were achieved in 48% and 39% of the patients, respectively. Adverse effects were mostly minor and occurred in 30.6% of the patients; infections were reported in 3.4% of the patients. Conclusions VDZ is efficacious in CD and UC and has a favourable safety profile in RWE studies.

Diagnostic yield of capsule endoscopy versus magnetic resonance enterography and small bowel contrast ultrasound in the evaluation of small bowel Crohn’s disease: Systematic review and meta-analysis

BACKGROUND AND AIMS Capsule endoscopy (CE), magnetic resonance enterography (MRE) and small bowel (SB) intestinal contrast ultrasound (SICUS) are the modalities of choice for SB evaluation. This study aimed to compare the diagnostic yield (DY) of CE to MRE and SICUS in detection and monitoring of SB CD through meta-analysis of the available literature. METHODS We performed a systematic literature search for trials comparing the accuracy of CE, MRE and SICUS for detection of active SB inflammation in patients with suspected and/or established CD. Only prospective studies comparing CE with another additional diagnostic modality were included in the final analysis. Pooled odds ratios (ORs) for the DY of the three modalities were calculated. RESULTS A total of 112 studies were retrieved; following selection, 13 studies were eligible for analysis. The DY of CE for detection of active SB CD was similar to that of MRE (10 studies, 400 patients, OR 1.17; 95% CI 0.83-1.67) and SICUS (5 studies, 142 patients, OR 0.88; 95% CI 0.51-1.53). The outcomes were similar for the subgroups of suspected versus established CD and adult versus pediatric patients. CE was superior to MRE for proximal SB CD (7 studies, 251 patients, OR 2.79; 95% CI 1.2-6.48); the difference vs SICUS was not significant. CONCLUSION CE, MRE and SICUS have similar DY for detection of SB CD in both suspected and established CD. CE is superior to MRE for detection of proximal SB disease, however the risk of capsule retention should be considered.

Systematic review and meta-analysis: is bowel preparation still necessary in small bowel capsule endoscopy?

ABSTRACT Introduction: Optimal bowel preparation for small bowel capsule endoscopy(SBCE) is controversial. This meta-analysis aimed to investigate the effects of laxatives in SBCE. Methods: A comprehensive literature search was conducted for studies investigating the use of laxatives in SBCE. The primary outcome was diagnostic yield(DY) for SB findings; secondary outcomes SB visualization quality(SBVQ) and completion rate(CR). Pooled odds ratios(ORs) with 95% confidence intervals(CIs) and number needed to treat(NNT) were calculated. Results: Forty studies (4380 patients with laxatives, 2185 without) were included. Laxative use did not improve DY of SB findings overall (OR 1.11 (95%CI 0.85–1.44)) or for significant SB findings (OR 1.10 (95%CI 0.76–1.60)). However, SBVQ improved with the use of laxatives (OR 1.60 (95%CI 1.08–2.06)), NNT 14. The OR for completed SBCE was 1.30 (95%CI 0.95–1.78). Patients given polyethylene glycol(PEG) had lower DY than sodium phosphate(NaP). SBVQ improved more with NaP (NNT 7) than PEG (NNT 53). Conclusions: Laxatives do not significantly improve DY or CR in SBCE, but do improve SBQV. The use of laxatives may be beneficial in patients likely to have subtle findings. There are significant differences in methodology/definitions between studies, hence the need for standardized visualization scoring and recording of SBCE findings.

Clinical validity of flexible spectral imaging color enhancement (FICE) in small-bowel capsule endoscopy: a systematic review and meta-analysis

Patients and methods A comprehensive literature search was conducted. We measured pooled rate of lesion visualization improvement and improvement in lesion detection comparing FICE settings 1 - 3 and WLE, for angioectasias and ulcers/erosions. Pooled results were derived using the random-effects model because of high heterogeneity as measured by I2. Repeated-measures analysis of variance (ANOVA) was used to measure differences in lesion detection between WLE and the three FICE modes. Results 13 studies were analyzed. All studies used the PillCam SB 1 and/or SB 2 devices. Most used experienced readers. Improvement in delineation had been investigated in 4 studies; in the 3 studies entered into the meta-analysis, using FICE setting 1, 89 % of angioectasias and 45 % of ulcer/erosions were considered to show improved delineation. For FICE settings 2 and 3, small proportions of images showed improved delineation. Heterogeneity of studies was high with I2 > 90 % in 4/6 analyses. Lesion detection had been investigated in 10 studies; meta-analysis included 5 studies. Lesion detection did not differ significantly between any of the FICE modes and WLE. Conclusions Overall, the use of the three FICE modes did not significantly improve delineation or detection rate in SBCE. In pigmented lesions, FICE setting 1 performed better in lesion delineation and detection.

Capsule endoscopy in young patients with iron deficiency anaemia and negative bidirectional gastrointestinal endoscopy

Background Recent data imply young patients (age ≤50 years) undergoing small-bowel (SB) capsule endoscopy (CE) for iron deficiency anaemia (IDA) show higher diagnostic yield (DY) for sinister pathology. We aimed to investigate DY of CE in a large cohort of young IDA patients, and evaluate factors predicting significant SB pathology. Materials and methods This was a retrospective, multicentre study (2010–2015) in consecutive, young patients (≤50 years) from 18 centres/12 countries, with negative bidirectional gastrointestinal (GI) endoscopy undergoing SBCE for IDA. Exclusion criteria: previous/ongoing obscure-overt GI bleeding; age <19 or >50 years; comorbidities associated with IDA. Data retrieved: SBCE indications; prior investigations; medications; SBCE findings; final diagnosis. Clinical and laboratory data were analysed by multivariate logistic regression. Results Data on 389 young IDA patients were retrieved. In total, 169 (43.4%) were excluded due to incomplete clinical data; data from 220 (122F/98M; mean age 40.5 ± 8.6 years) patients were analysed. Some 71 patients had at least one clinically significant SBCE finding (DY: 32.3%). They were divided into two groups: neoplastic pathology (10/220; 4.5%), and non-neoplastic but clinically significant pathology (61/220; 27.7%). The most common significant but non-neoplastic pathologies were angioectasias (22/61) and Crohn’s disease (15/61). On multivariate analysis, weight loss and lower mean corpuscular volume(MCV) were associated with significant SB pathology (OR: 3.87; 95%CI: 1.3–11.3; p = 0.01; and OR: 0.96; 95%CI: 0.92–0.99; p = 0.03; respectively). Our model also demonstrates association between use of antiplatelets and significant SB pathology, although due to the small number of patients, definitive conclusions cannot be drawn. Conclusion In IDA patients ≤50 years with negative bidirectional GI endoscopy, overall DY of SBCE for clinically significant findings was 32.3%. Some 5% of our cohort was diagnosed with SB neoplasia; lower MCV or weight loss were associated with higher DY for SB pathology.

The validity of suspected blood indicator software in capsule endoscopy: a systematic review and meta-analysis

ABSTRACT Introduction: Software tools have been developed as capsule endoscopy (CE) reading aids. The suspected blood indicator (SBI) tags possible areas of haemorrhage in the gastrointestinal (GI) tract. This meta-analysis aims to investigate the diagnostic accuracy of SBI in CE. Areas covered: A systematic literature search was conducted for studies on the use of SBI in CE. Sensitivity, specificity and diagnostic odds ratio (DOR) of SBI in diagnosing GI bleeding was evaluated. 2040 patients from 16 studies underwent 2049 CE examinations. The overall sensitivity of SBI for bleeding or potentially bleeding lesions was 0.553, specificity 0.578, DOR 12.354. The sensitivity of SBI for active bleeding was 0.988, specificity 0.646, DOR 229.89. Expert commentary: Currently, SBI has limited validity in CE reading. However, in active GI bleeding, it has good sensitivity, supporting its use in the acute setting.

From clinical uncertainties to precision medicine: the emerging role of the gut barrier and microbiome in small bowel functional diseases

ABSTRACT Introduction: Over the last decade, remarkable progress has been made in the understanding of disease pathophysiology. Many new theories expound on the importance of emerging factors such as microbiome influences, genomics/omics, stem cells, innate intestinal immunity or mucosal barrier complexities. This has introduced a further dimension of uncertainty into clinical decision-making, but equally, may shed some light on less well-understood and difficult to manage conditions. Areas covered: Comprehensive review of the literature on gut barrier and microbiome relevant to small bowel pathology. A PubMed/Medline search from 1990 to April 2017 was undertaken and papers from this range were included. Expert commentary: The scenario of clinical uncertainty is well-illustrated by functional gastrointestinal disorders (FGIDs). The movement towards achieving a better understanding of FGIDs is expressed in the Rome IV guidelines. Novel diagnostic and therapeutic protocols focused on the GB and SB microbiome can facilitate diagnosis, management and improve our understanding of the underlying pathological mechanisms in FGIDs.