Mike Thomson

An Antibody Against IL-5 Reduces Numbers of Esophageal Intraepithelial Eosinophils in Children With Eosinophilic Esophagitis

BACKGROUND & AIMSnThe role of interleukin (IL)-5 in the pathogenesis of eosinophilic esophagitis (EoE) has been established in animal models; anti-IL-5 therapy has been reported to be effective in adults. We investigated whether IL-5 has a role in accumulation of esophageal eosinophils in children with EoE and whether therapy with mepolizumab, an antibody against IL-5, reduces the number of esophageal intraepithelial eosinophils in children with EoE.nnnMETHODSnWe performed an international, multicenter, double-blind, randomized, prospective study of 59 children with EoE, defined as baseline peak count of esophageal intraepithelial eosinophils of ≥ 20 in at least 1 high-power field (hpf). Patients received an infusion every 4 weeks (a total of 3 infusions) of 0.55, 2.5, or 10 mg/kg mepolizumab. No placebo group was used.nnnRESULTSnBaseline peak and mean esophageal intraepithelial eosinophil counts were (mean ± SE) 122.5 ± 8.78 and 39.1 ± 3.63 per hpf, respectively. Four weeks after the third infusion, peak eosinophil counts were <5 per hpf in 5 of 57 children (8.8%); we did not observe differences among groups given different doses of mepolizumab. Reduced peak and mean eosinophil counts, to <20 per hpf, were observed in 18 of 57 (31.6%) and 51 of 57 (89.5%) children, respectively. Peak and mean esophageal intraepithelial eosinophil counts decreased significantly to 40.2 ± 5.17 and 9.3 ± 1.25 per hpf, respectively (P < .0001). An analysis to evaluate predictors of response associated a higher mean baseline esophageal intraepithelial eosinophil count with a greater reduction in mean count (P < .0001).nnnCONCLUSIONSnIL-5 is involved in the pathogenesis of EoE in children. Mepolizumab, an antibody against IL-5, reduces esophageal eosinophilic inflammation in these patients.

Achieving R0 resection in the colorectum using endoscopic submucosal dissection.

Endoscopic mucosal resection is established for the removal of non‐invasive colorectal tumours smaller than 20 mm but is unsatisfactory for larger lesions. Endoscopic submucosal dissection (ESD) enables en bloc resection of lesions larger than 20 mm. A UK‐based prospective feasibility study of ESD for colorectal tumours was undertaken; primary endpoints were R0 resection, safety and recurrence.

Endoscopic mucosal resection for flat neoplasia in chronic ulcerative colitis: can we change the endoscopic management paradigm?

Background: The potential of endoscopic mucosal resection (EMR) for treating flat dysplastic lesions in chronic ulcerative colitis (CUC) has not been addressed so far. Historically, such lesions were referred for colectomy. Furthermore, there are only limited data to support endoscopic resection of exophytic adenoma-like mass (ALM) lesions in colitis. Aims: To evaluate the safety and clinical outcomes of patients with colitis undergoing EMR for Paris class 0–II and class I ALM compared with sporadic controls. Secondary aims were to re-evaluate the prevalence, anatomical “mapping” and histopathological characteristics of both Paris class 0–II and class I lesions in the context of CUC. Methods: Prospective clinical, pathological and outcome data of patients with colitis-associated Paris class 0–II and Paris class I ALM treated with EMR (primary end points being colorectal cancer development, resection efficacy, metachronous lesion rates and post-resection recurrence rates) were compared with those of sporadic controls. Results: 204 lesions were diagnosed in 169 patients during the study period: 167 (82%) diagnosed at “entry” colonoscopy, and 36 (18%) diagnosed at follow-up. 170 ALMs, 18 dysplasia-associated lesion masses (DALMs) and 16 cancers were diagnosed. A total of 4316 colonoscopies were performed throughout the study period (median per patient: 6; range: 1–8). The median follow-up period for the complete cohort was 4.1 years (range: 3.6–5.21). 1675 controls were included from our prospective database of patients without CUC who had undergone EMR for sporadic Paris class 0–II and snare polypectomy of Paris type I lesions from 1998 onwards, and were considered to be at moderate to high lifetime risk of colorectal cancer. 3792 colonoscopies were performed throughout the study period in this group (median per patient: 4; range: 1–7). The median follow-up period was 4.8 years (range: 2.9–5.2). No statistically significant differences were observed between the CUC study group and controls with respect to age, sex, median number of colonoscopies per patient, median follow-up duration, post-resection complications, median lesional diameter or interval cancer rates. However, there was a significant between-group difference regarding the prevalence of Paris class 0–II lesions in the CUC group (82/155 (61%)) compared with controls (285/801 (35%); χ2u200a=u200a31.13; p<0.001). Furthermore, recurrence rates of lateral spreading tumours were higher in the colitis cohort (1/7 (14%)) than among controls (0/10 (0%); pu200a=u200a0.048 (95% CI 11.64% to 40.21%)). Conclusions: Flat DALM, similarly to Paris class I ALM, can be managed safely by EMR in CUC. A change in management paradigm to include EMR for the resection of flat dysplastic lesions in selected cases is proposed.

Confocal chromoscopic endomicroscopy is superior to chromoscopy alone for the detection and characterisation of intraepithelial neoplasia in chronic ulcerative colitis

BACKGROUNDnThe diagnosis of intraepithelial neoplasia is pivotal for ongoing clinical management decisions in ulcerative colitis. Previous studies have compared the diagnostic yield of endomicroscopy with conventional white light endoscopy and hence the overall objective increase of endomicroscopy targeted biopsies as compared to chromoscopy guided alone is not apparent.nnnAIMSnWe performed a prospective randomised controlled study to compare the diagnostic yield of intraepithelial neoplasia and cancer in patients undergoing ulcerative colitis screening using chromoscopy assisted endomicroscopy (group A) versus pan-colonic chromoscopy assisted colonoscopy (group B).nnnMETHODSnPatients were randomised in a 1:1 ratio to undergo screening colonoscopy using either chromoscopic endomicroscopy or chromoscopy alone with targeted biopsies. Circumscribed lesions were characterised using endomicroscopy and chromoscopy with pit pattern analysis. Targeted biopsies in addition to conventional 10 cm quadrantic biopsies were taken. Primary outcome addressed the number of intraepithelial neoplasias detected in each group.nnnRESULTSnEndomicroscopy targeted biopsies significantly increased the yield of intraepithelial neoplasia as compared to pan-chromoscopy and biopsy alone (p<0.001) and also increased the yield of high-grade dysplastic lesions (p<0.001). Endomicroscopy targeted biopsies increased the diagnostic yield of intraepithelial neoplasia as compared to chromoscopy guided biopsies alone by 2.5-fold.nnnCONCLUSIONSnThis is the first randomised controlled study to show the true clinical benefit of endomicroscopy for the in vivo detection and characterisation of intraepithelial neoplasia in chronic ulcerative colitis surveillance colonoscopy. Endomicroscopy with targeted biopsy may potentially be the gold standard for the detection of intraepithelial neoplasia in ulcerative colitis.

EMR using dextrose solution versus sodium hyaluronate for colorectal Paris type I and 0-II lesions: a randomized endoscopist-blinded study.

BACKGROUND AND AIMSnLoss of mucosal lift prior to submucosal dissection or endoscopic mucosal resection (EMR) increases the risk of complications. We conducted a randomized controlled trial comparing dextrose solution with sodium hyaluronic acid (SHA) for the EN BLOC resection of Paris type I/0-II and lateral spreading lesions of the colorectum.nnnPATIENTS AND METHODSnPatients with Paris type I/0-II or lateral spreading tumor lesions of < 30 mm were randomized in a 1 : 1 ratio to undergo EMR using either dextrose solution or SHA. The primary study outcome was complete resection. Secondary outcomes were endoscopic complications (i. e. perforation or bleeding) and polyp recurrence rates.nnnRESULTSnA total of 174 patients were randomized. R0 resection was achieved in 59 of the 82 lesions (72 %) in the dextrose group and 56 of the 81 lesions (69 %) in the SHA group ( P > 0.1), with no significant difference in median lesion diameter ( P > 0.1). The median number of post resection surveillance colonoscopies was 3 (range 2 - 7) in the dextrose group and 4 (range 2 - 6) in the SHA group ( P = NS). The median post index EMR resection follow-up period was 20 months (range 4 - 26) in the DS group and 18 months (range 3 - 22) in the SHA group ( P = NS). Recurrence rates were 1/82 (1.21 %) in the dextrose group and 1/81 (1.23 %) in the SHA group ( P = NS).nnnCONCLUSIONSnEMR using dextrose solution is as effective as SHA in terms of resection completion, recurrence rates, and complications.

Infliximab delays but does not avoid the need for surgery in treatment-resistant pediatric Crohn' disease.

The aim of this study was to review the impact of infliximab therapy on children with treatment-resistant Crohn’s disease. Treatment resistance was defined as clinically active disease despite > 4 months of immunosuppressive therapy. The outcome variables were time to first remission, duration of remission and the need for surgery. 24 children received 90 infusions of infliximab (16 boys; median 10.3y, range 1.0–14.4y); all had three infusions as an induction course. 17 (70.8%) achieved clinical remission, with 14/17 (82.3%) relapsing within 4 months of the third infusion. 6/7 in the non-responding group and 8/17 of the responders required surgery with an insignificant difference in the median time to surgery (p = 0.49). Four remain dependent on regular infliximab. Infliximab is well-tolerated and highly effective in achieving clinical remission in children with refractory Crohn’s disease but may only delay and not avoid the need for surgery. Failure to achieve clinical remission by the 3rd infusion significantly increases the risk of surgery.

In vivo confocal laser scanning chromo‐endomicroscopy of colorectal neoplasia: changing the technological paradigm

Recently, miniaturization of a novel confocal laser endomicroscope (Optiscan Pty, Notting Hill, Victoria, Australia) has permitted functional integration into the distal tip of a conventional video colonoscope (Pentax EC3870K; Pentax, Tokyo, Japan) enabling imaging of the surface epithelium and the underlying lamina propria during ongoing video endoscopy. Using endomicroscopy and intravenous sodium fluorescein as a contrast agent, ‘virtual histology’ can be created, which allows visualization of both the surface epithelium, and some of the lamina propria (down to a quarter of a millimetre), including the microvasculature. Confocal endomicroscopy may have major implications in the future of colonoscopy as uniquely it allows in vivo diagnosis of colonic intraepithelial neoplasia and carcinoma enabling ‘smart’ biopsy targeting and hence potentially influencing ‘on table’ management decisions. Initial pilot data have now shown that confocal imaging in vivo using the newly developed EC3870K has high overall accuracy for the immediate diagnosis of intraepithelial neoplasia and carcinoma in sporadic screened cohorts, but also has a role in the detection of intraepithelial neoplasia detection in chronic ulcerative colitis cancer screening when used in conjunction with methylene blue chromoscopy. We discuss the current evidence in support of confocal endomicroscopy in the colorectum and explore the new diagnostic possibilities for this technology.

Pediatric gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) and European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) Guideline Executive summary

This Executive summary of the Guideline on pediatric gastrointestinal endoscopy from the European Society of Gastrointestinal Endoscopy (ESGE) and the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) refers to infants, children, and adolescents aged 0u200a-u200a18 years. The areas covered include: indications for diagnostic and therapeutic esophagogastroduodenoscopy and ileocolonoscopy; endoscopy for foreign body ingestion; endoscopic management of corrosive ingestion and stricture/stenosis; upper and lower gastrointestinal bleeding; endoscopic retrograde cholangiopancreatography, and endoscopic ultrasonography. Percutaneous endoscopic gastrostomy and endoscopy specific to inflammatory bowel disease (IBD) have been dealt with in other Guidelines and are therefore not mentioned in this Guideline. Training and ongoing skill maintenance will be addressed in an imminent sister publication.

20 mm lithium button battery causing an oesophageal perforation in a toddler: lessons in diagnosis and treatment

Swallowed button batteries (BB) which remain lodged in the oesophagus are at risk of serious complications, particularly in young children. The authors report a 3-year-old child, who rapidly developed an oesophageal perforation, following the ingestion of a 20-mm lithium BB which was initially mistaken for a coin. A thoracotomy and T-tube management of the perforation led to a positive outcome. BBs (20 mm) in children should be removed quickly and close observation is required as the damage initiated by the battery can lead to a significant injury within a few hours.

Defining esophageal landmarks, gastroesophageal reflux disease, and Barrett's esophagus

The following paper on gastroesophageal reflux disease (GERD) and Barretts esophagus (BE) includes commentaries on defining esophageal landmarks; new techniques for evaluating upper esophageal sphincter (UES) tone; differential diagnosis of GERD, BE, and hiatal hernia (HH); the use of high‐resolution manometry for evaluation of reflux; the role of fundic relaxation in reflux; the use of 24‐h esophageal pH–impedance testing in differentiating acid from nonacid reflux and its potential inclusion in future Rome criteria; classification of endoscopic findings in GERD; the search for the cell origin that generates BE; and the relationship between BE, Barretts carcinoma, and obesity.