Mapping the distribution of small bowel angioectasias.

Background: Angioectasias are a prominent cause of small bowel (SB) bleeding frequently identified during capsule endoscopy (CE). Subsequent management depends upon grade/severity and location. There is increasing evidence that the location of SB angioectasias is not random. We aimed to map the distribution of SB angioectasias, and assess whether this impacted clinical outcomes. Materials and methods: Retrospective study examining CEs performed over a 10-year period at a tertiary referral centre. Information regarding number, location, and Saurin classification (P0-2) of SB angioectasias was collected. Clinically significant angioectasias (P1/P2) and active SB bleeding were analysed further. Outcomes of patients with P2 angioectasias or active SB bleeding were recorded. Results: 164 SBCE examinations reported angioectasias. 554 P1-2 angioectasias and active bleeds were seen, 435 (78.52%) within the first tertile of SB transit time (SBTT). 277 (50%) angioectasias were identified within the first 10% of SBTT. 40/75 (53.3%) patients with >1 P2 angioectasia and/or active bleed were referred for intervention. Of initial interventions, 24 patients underwent upper GI endoscopy; 13 underwent double balloon enteroscopy (DBE). 9/37(24.3%) had no identifiable angioectasias on endoscopy. Of those receiving ablative therapy, 20/28 (71.4%) re-presented with iron-deficiency anaemia or bleeding. In this group, average angioectasia position was 15.6% of SBTT, compared with 7.9% in those who did not re-represent (p = 0.344). Patients who re-presented had an average 1.6 additional P1 angioectasias, compared with 7.6 amongst those who did not return (p = 0.017). Conclusions: Clinically significant angioectasias are overwhelmingly located within the proximal SB. The majority are within reach of conventional endoscopy. However, AEs are often multiple and many patients re-present following intervention.

Clinical outcomes of negative small-bowel capsule endoscopy for small-bowel bleeding: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Small-bowel bleeding is the primary indication for capsule endoscopy (CE). Many experts advocate a "watch-and-wait" policy in negative CE. This meta-analysis examines the odds of rebleeding after negative index CE and the impact on long-term follow-up. METHODS: A comprehensive literature search identified articles examining the rebleeding rate after negative CE. Demographic and clinical information with emphasis on outcomes was retrieved, pooled, and analyzed. Heterogeneity among studies was assessed using the I2 statistic. A random effects model was used as the pooling method because of high heterogeneity. Risk of bias was assessed using the quality assessment of diagnostic accuracy studies (QUADAS-2) tool. The primary outcome evaluated was the pooled odds ratios (ORs) for rebleeding after a negative CE for obscure GI bleeding (OGIB). RESULTS: Twenty-six studies with 3657 patients were included. The pooled rate of rebleeding after negative CE was .19 (95% CI, .14-.25; P < .0001). The pooled OR of rebleeding was .59 (95% CI, .37-.95; P < .001). The effect was more pronounced in studies with a short follow-up (OR, .47; 95% CI, .24-.94; P < .001). There was no statistically significant difference in rebleeding after CE for occult and overt OGIB. Prospective studies showed a lower OR of rebleeding of .24 (95% CI, .08-.73; P = .01). Most studies were high quality. CONCLUSIONS: Our analysis shows that negative CE provides adequate evidence of a subsequently low risk of rebleeding. Such patients can therefore be safely managed with watchful waiting. However, patients who rebleed after 2 years may need to be investigated for a new source of blood loss.

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.

Chromoendoscopy, Narrow-Band Imaging or White Light Endoscopy for Neoplasia Detection in Inflammatory Bowel Diseases.

BACKGROUND: Studies have confirmed an increased risk of colorectal cancer in patients with ulcerative colitis; hence, surveillance is recommended. Optional modalities include white light endoscopy (WLE) or dye-spray chromoendoscopy. However, narrow-band imaging (NBI) is still not considered comparable to chromoendoscopy. AIM: The aim of this study was to compare the diagnostic yield (DY) of WLE, chromoendoscopy, NBI for detection of neoplasia in patients with inflammatory bowel disease (IBD) by performing a meta-analysis of the existing literature. METHODS: We searched databases for prospective studies. For each modality, we performed comparative per-lesion analysis (any neoplasia detection) and per-patient analysis (patient with neoplastic lesions). Meta-analysis was performed using fixed-effect model unless heterogeneity was high. Odds ratios (ORs) with 95% CIs were calculated and pooled. RESULTS: Five studies compared chromoendoscopy to WLE. Chromoendoscopy (n = 361) was superior to WLE (n = 358) with per-patient analysis OR 2.05 (95% CI 1.26, 3.35) and per-lesion analysis OR 2.79 (95% CI 2.08, 3.73). High-definition (HD) chromoendoscopy was superior to HD-WLE with per-lesion analysis OR 2.48 (95% CI 1.55, 3.97). In four studies comparing NBI to WLE (n = 305), no difference was found in per-patient analysis OR 0.97 (95% CI 0.62, 1.53) and per-lesion analysis OR 0.94 (95% CI 0.63, 1.4). In two studies comparing CE to NBI (n = 104), no difference was found in per-patient analysis OR 1.0 (95% CI 0.51, 1.95) and per-lesion analysis OR 1.29 (95% CI 0.69, 2.41). CONCLUSION: Chromoendoscopy is superior to WLE for detection of dysplasia in IBD, even with HD endoscopy. No difference in DY could be demonstrated for NBI in comparison with other modalities.

Association Between Fecal Calprotectin Levels and Small-bowel Inflammation Score in Capsule Endoscopy: A Multicenter Retrospective Study.

BACKGROUND: Accurate inflammation reporting in capsule endoscopy (CE) is important for diagnosis and monitoring of treatment of inflammatory bowel disease (IBD). Fecal calprotectin (FC) is a highly specific biomarker of gut inflammation. Lewis score (LS) was developed to standardize quantification of inflammation in small-bowel (SB) CE images. GOALS: Multicenter retrospective study aiming to investigate correlation between LS and FC in a large group of patients undergoing CE for suspected or known small-bowel IBD, and to develop a model for prediction of CE results (LS) based on FC levels. STUDY: Five academic centers and a district general hospital offering CE in UK, Finland, Sweden, Canada, and Israel. In total, 333 patients were recruited. They had small-bowel CE and FC done within 3 months. RESULTS: Overall, correlation between FC and LS was weak (r s: 0.232, P < 0.001). When two clinically significant FC thresholds (100 and 250 µg/g) were examined, the r s between FC and LS was 0.247 (weak) and 0.337 (moderate), respectively (P = 0.307). For clinically significant (LS ≥ 135) or negative (LS < 135) for SB inflammation, ROC curves gave an optimum cutoff point of FC 76 µg/g with sensitivity 0.59 and specificity 0.41. LIMITATIONS: Retrospective design. CONCLUSIONS: LS appears to show low correlation with FC as well as other serology markers of inflammation. FC does not appear to be a reliable biomarker for significant small-bowel inflammation. Nevertheless, FC level ≥ 76 µg/g may be associated with appreciable visual inflammation on small-bowel CE in patients with negative prior diagnostic workup.

Small bowel capsule endoscopy and portal hypertensive enteropathy in cirrhotic patients: results from a tertiary referral centre.

BACKGROUND AND RATIONALE: Portal hypertensive enteropathy (PHE) remains difficult to diagnose in patients with cirrhosis and portal hypertension. Limited test choices exist for the inspection of the small bowel in these patients. Small bowel capsule endoscopy (SBCE) is ideal in this situation but rarely performed. We aimed to determine the prevalence of PHE using SBCE in a cirrhotic patient population and correlate its presence with clinical and CT imaging findings. MATERIAL AND METHODS: We retrospectively analysed data from cirrhotic patients who underwent SBCE at our unit. Studies were evaluated for the presence of cirrhosis-related findings in the oesophagus, stomach and small-bowel. The relationships between PHE and patients' clinical characteristics were evaluated. RESULTS: 53 patients with cirrhosis underwent SCBE. We used PillCam®SB on 36 patients and MiroCam® capsule on 17. Thirty patients were referred for iron deficiency anaemia, 15 for obscure gastrointestinal bleeding, and 4 for other indications. Four data sets were not available for review, leaving 49 patients. Mean age was 61.19 ± 14.54 years (M/F = 27/22). Six SBCE examinations were incomplete. Thirty three patients had evidence of portal hypertensive gastropathy (PHG) and 17 had evidence of oesophageal varices. In total, 29 patients had SCBE evidence of PHE (57%). 28/29 (96.5%) patients with PHE had also evidence of PHG. 13/17 (76.4%) patients with oesophageal varices had also evidence of PHE. CONCLUSIONS: The prevalence of PHE in our study was 57%. SBCE is a useful tool in evaluating PHE in cirrhotic patients irrespective of aetiology.

Microscopic colitis: a misnomer for a clearly defined entity?

In recent years, several endoscopic features of microscopic colitis have been noted. The pickup of these on colonoscopy depends on local expertise, endoscopic technology, and case volume. As the incidence of microscopic colitis has increased, we wanted to draw attention to endoscopists' ability to recognize such findings. We present eight cases of biopsy-proven microscopic colitis which demonstrate the spectrum of endoscopic findings. Endoscopists should actively search for such findings and target their biopsies, as new high-definition colonoscopes with sharper images, zoom capabilities, and high resolution allow a new vision into this syndrome.

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

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.

Thrombin Is an Effective and Safe Therapy in the Management of Bleeding Gastric Varices. A Real-World Experience.

Variceal haemorrhage is a severe complication of liver disease with high mortality. Human recombinant thrombin has gained popularity in the management of variceal haemorrhage. We report on the use of thrombin for gastric and ectopic varices at a regional tertiary care centre. This was a retrospective observational study. Patients with portal hypertension who received endoscopic injection of recombinant thrombin were identified and data collected on haemostasis and rebleeding rates, complications and mortality. Patients were grouped by indication for thrombin injection: gastric/oesophageal/ectopic varices and endoscopic band ligation (EBL)-induced ulceration. 155 patients (96M/59F, mean age 58.3 years) received endoscopic thrombin injection. Mean volume of thrombin injected at index endoscopy was 9.5 ml/2375IU. Initial haemostasis was achieved in 144 patients (92.9%). Rebleeding occurred in a total of 53 patients (36.8%) divided as follows: early rebleeding (<5 days from index endoscopy)-26 patients (18%); rebleeding within 30 days-42 patients (29.1%); delayed rebleeding (> 30 days)-11 patients (7.6%). There was statistically significant difference in rate of initial haemostasis between Child-Pugh A/B patients vs Child-Pugh C (p = 0.046). There was no significant difference in rebleeding rates between different indication groups (p = 0.78), by presence of cirrhosis or by Child-Pugh Score. All-cause mortality at 6 weeks was 18.7%; 1-year mortality 37.4% (median follow-up 48 months). There was no significant difference in mortality between groups (p = 0.37). No significant adverse events or complications were reported. Thrombin is effective and safe for gastric varices and other portal-hypertension-related bleeding including oesophageal varices, ulcers secondary to EBL and ectopic varices.

Conventional cardiac risk factors associated with trastuzumab-induced cardiotoxicity in breast cancer: Systematic review and meta-analysis.

BACKGROUND: Trastuzumab has had a major impact on the treatment of human epidermal growth factor receptor 2 (HER2) positive breast cancer patients. However, it is associated with cardiotoxicity, expressed as an asymptomatic decrease in left ventricular ejection fraction (LVEF) and less often as clinical HF. The aim of this meta-analysis is to identify the association of conventional cardiovascular risk factors with the development of trastuzumab-induced cardiotoxicity (TIC). METHODS: A literature search of PubMed was conducted to identify studies examining the association between cardiovascular risk factors and TIC. Data were extracted and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated examining the odds of developing TIC for each of the risk factors. RESULTS: A total of 35 studies were included in the analysis. Age (OR:0.7; 95%CI 0.318-1.09; P= 0.0004), hypertension (OR:0.69; 95%CI 0.26-1.12; P = 0.001), smoking(OR:0.35; 95%CI 0.01- 0.69; P = 0.038), diabetes mellitus (OR:0.44; 95%CI 0.24- 0.68; P = 0.0001) and family history of CAD (OR:5.51, 95%CI 1.76-17.25; P< 0.00001)were significantly associated with the development of cardiotoxicity. Known history of CAD (OR: 3.72; 95%CI 2.11-6.57; P = 0.0005) was also associated with the development of TIC. CONCLUSION(S): Identifying women at risk for TIC have several important potential applications. Clinicians may decide to assess LVEF more frequently in patients at highest risk for TIC in order to detect LV systolic dysfunction earlier. Additionally, this could help identify patients who would benefit most from prophylactic therapy for preventing TIC.

Poor Quality of Small Bowel Capsule Endoscopy Images Has a Significant Negative Effect in the Diagnosis of Small Bowel Malignancy.

BACKGROUND AND AIMS: Capsule endoscopy (CE) is a visual modality; hence, diagnosis relies on image quality. We studied the contribution of image parameters to visualization quality and their effect on diagnostic certainty of small bowel (SB) lesions. METHODS: Five clear CE images of common SB pathology - two vascular lesions, two inflammatory, one polyp - were processed for three image parameters to simulate poor SB conditions: opacity (color-matched to luminal content; 10-90%, 10% increments); blurriness (radius 1-10 pixels; one pixel increments); and contrast (-50-50%; 10% increments). Nine expert readers evaluated whether images were adequate for diagnosis. Points where perception of image quality changed significantly were determined for each parameter. Three further sets of SBCE images (vascular, inflammatory, and neoplastic lesions; nine images/set) were processed for four points/parameters. Twenty experienced/expert CE readers reviewed these images. RESULTS: The negative effects of opacity in diagnostic certainty were mostly evident in images of neoplasia; images of vascular and inflammatory lesions were less affected. Similar results were observed with increasing blur radius, simulating movement, and poor focus. The proportions of readers finding vascular and inflammatory images adequate for diagnosis did not drop significantly at wider blur radii, while images of neoplasia were quickly deemed inadequate. Low contrast had a greater negative effect than high, most consistently in neoplastic lesions. CONCLUSION: Poor visualization quality in all parameters affected mostly neoplastic lesions. Software to increase contrast and sharpen images can improve visualization quality; smart frame rate adaptation could improve the number of high-quality frames obtained. Thoroughness in SB cleansing is most important when there is a suspicion of neoplasia.

Balloon-Assisted Colonoscopy after Incomplete Conventional Colonoscopy-Experience from Two European Centres with A Comprehensive Review of the Literature.

BACKGROUND: Conventional colonoscopy (CC) allows access for colonic investigation and intervention; in the small group in whom CC is unsuccessful alternative imaging is often sufficient. There remains a subset, however, requiring full colonic visualisation or intervention. Balloon-assisted colonoscopy (BAC) gives a further option when access is difficult. Aims: This study aims to present the experience with BAC of two European tertiary referral centres. Methods: Procedures were carried out under local protocol over 15-years (2006-2020). Markers of procedural quality such as caecal intubation, complications and comfort were retrospectively compiled and analysed. Published evidence was summarised for comparison. Results: 122 procedures were undertaken, with polyps the most frequent indication and 90.2% having at least one previously incomplete CC. Features associated with difficult colonoscopy were common, including intraabdominal surgery (32.0%). 92.6% reached the caecum; completion was higher (96.3%) in those failing CC due to discomfort and lower in those failing due to anatomical difficulties (90.7%) or previous surgery (84.6%). Mean time to the caecum was 20.9 minutes and mean midazolam and fentanyl doses were 2.6 mg and 49.9 µg with low discomfort scores. Conclusion(s): Balloon-assisted colonoscopy is successful in >90% of patients, is well-tolerated, and is safe.

Nomenclature and semantic descriptions of ulcerative and inflammatory lesions seen in Crohn's disease in small bowel capsule endoscopy: An international Delphi consensus statement.

BACKGROUND: In the medical literature, the nomenclature and descriptions (ND) of small bowel (SB) ulcerative and inflammatory (U-I) lesions in capsule endoscopy (CE) are scarce and inconsistent. Inter-observer variability in interpreting these findings remains a major limitation in the assessment of the severity of mucosal lesions, which can impact negatively on clinical care, training and research on SB-CE. OBJECTIVE: Focusing on SB-CE in Crohn's disease (CD), our aim is to establish a consensus on the ND of U-I lesions. METHODS: An international panel of experienced SB-CE readers was formed during the 2016 United European Gastroenterology Week meeting. A core group of five CE and inflammatory bowel disease (IBD) experts established an Internet-based, three-round Delphi consensus but did not participate in the voting process. The core group built illustrated questionnaires, including SB-CE still frames of U-I lesions from patients with documented CD. Twenty-seven other experts were asked to rate and comment on the different proposals for the ND of the most frequent SB U-I lesions. For each round, we used a 6-point rating scale (varying from 'strongly disagree' to 'strongly agree'). The consensus was reached when at least 80 % of the voting members scored the statement within the 'agree' or 'strongly agree' categories. RESULTS: A 100% participation rate was obtained for all the rounds. Consensual ND were reached for the following seven U-I lesions: aphthoid erosion, deep ulceration, superficial ulceration, stenosis, edema, hyperemia and denudation. CONCLUSION: Considering the most frequent SB U-I lesions seen in CE in CD, a consensual ND was reached by the international group of experts. These descriptions and names are useful not only for daily practice and medical education, but also for medical research.

Aortoenteric fistula: a rare but critical cause of small bowel bleeding discovered on capsule endoscopy.

A 78-year-old man attended for outpatient capsule endoscopy, to investigate a recent history of unexplained small bowel bleeding. His previous medical history included an abdominal aortic aneurysm repair 6 years ago. Soon after capsule ingestion, he experienced sudden onset abdominal pain and collapsed on hospital grounds. He was rapidly transferred to the emergency department as he was haemodynamically unstable, and a significant per rectum (PR) bleed was found on examination. The patient was quickly stabilised following fluid resuscitation. CT angiography was performed which did not show active bleeding. However, use of the real-time capsule viewer indicated a profuse active jejunal bleed originating from the aortic graft, suggestive of an aortoenteric fistula. The patient underwent emergency endovascular cuff placement, and subsequent endovascular abdominal aortic stent grafting, to good effect.

Follow-up on: optimizing lesion detection in small bowel capsule endoscopy and beyond: from present problems to future solutions.

INTRODUCTION: This review presents noteworthy advances in clinical and experimental Capsule Endoscopy (CE), focusing on the progress that has been reported over the last 5 years since our previous review on the subject. Areas covered: This study presents the commercially available CE platforms, as well as the advances made in optimizing the diagnostic capabilities of CE. The latter includes recent concept and prototype capsule endoscopes, medical approaches to improve diagnostic yield, and progress in software for enhancing visualization, abnormality detection, and lesion localization. Expert commentary: Currently, moving through the second decade of CE evolution, there are still several open issues and remarkable challenges to overcome.

Effectiveness and safety of Ustekinumab for Crohn's disease; systematic review and pooled analysis of real-world evidence.

BACKGROUND: Ustekinumab [UST] is effective in Crohn's disease (CD) in the UNITI studies. Several real-world experience (RWE) studies with UST have been published to date. Our aim was to summarize the available RWE data for UST effectiveness and safety. METHODS: A systematic review of the available RWE studies of UST for CD and pooled analysis of the available effectiveness and safety data was performed. RESULTS: Eight relevant studies of 6 RWE were included for analysis. Data from 578 patients were pooled for analysis. Most patients (97.7%) were anti-TNF experienced. Pooled clinical response rate was 60%, 62%, 49% at 12, 24 and 52 weeks respectively (95% CI (0.42-0.77), (0.48-0.75), (0.37-0.62)). Pooled remission rate was 39% (95% CI (0.18-0.65)) at 24 weeks and pooled endoscopic response rate was 63% (95% CI (0.53-0.72)) after approximately one year of UST; 134 adverse events (AE) were reported in total, pooled proportion 21% (95% CI (0.12-0.35)). Serious AE were reported in 19 patients, pooled proportion 5% (95% CI (0.03-0.08)). Infections were reported in 38, pooled proportion 6% (95% CI (0.04-0.11)). CONCLUSION: Pooled analysis of the RWE data suggests that the real-world effectiveness and safety are comparable to that reported in the randomized control trials.