James East Senior Scientist, Consultant Physician and Member of congregation

Research Area: Imaging (macro)
Technology Exchange: Cellular immunology, In vivo imaging and SNP typing
Scientific Themes: Cancer Biology and Clinical Trials & Epidemiology

Clinical and Translational Endoscopic Research

James East is a Consultant Gastroenterologist & Endoscopist and Honorary Senior Clinical Lecturer specializing in advanced luminal GI endoscopy. He is the Endoscopy Research Lead for the Translational Gastroenterology Unit, Clinical Lead for Endoscopy at the John Radcliffe Hospital, and Clinical Director for Bowel Cancer Screening Oxfordshire.

Gastrointestinal cancer cancer prevention is his core research focus, primarily though improving endoscopic strategies to halt development of pre-malignant lesions, through clinical and translational studies.

Key themes

Early detection and differentiation of colonic pre-malignant lesions

Current population based strategies to prevent bowel cancer rely on low efficacy screening test (faecal occult blood testing) and sigmoidoscopy or colonoscopy. We need to improve screening tests through development of better biomarkers and patient risk stratification, and the detection, characterisation [http://www.ncbi.nlm.nih.gov/pubmed/24239209], and effective resection of pre-malignant lesions (advanced endoscopic imaging). Surveillance strategies also need to be made more clinically and cost effective with stratification based on molecular markers.

Serrated pathway to colorectal cancer

Rare familial syndromes can give insights into some specific problems faced at a population level, particularly for the new "serrated pathways" to colorectal cancer, such as hereditary mixed polyposis syndrome and its gene GREM-1 [http://www.ncbi.nlm.nih.gov/pubmed/22561515]. Serrated polyps, and the associated Serrated Polyposis Syndrome, are now newly recognised as important pre-malignant lesions, distinct from the adenoma-carcinoma sequence, but their biology is poorly understood, and detection and safe resection are challenging. [http://www.nature.com/nrgastro/journal/v10/n2/pdf/nrgastro.2012.245.pdf]

Colitis (inflammation driven) associated colorectal cancer

Inflammation and cancer are also increasingly seen as linked. Colonoscopic surveillance for colitis associated cancer (CAC) is a particular clinical challenge where molecularly targeted endoscopic imaging could yield significant clinical benefit in the short term, as well as lead to insights into use the safe of immunosuppressants in the context of dysplasia. There is an inherent tension between inflammation driving dysplasia and cancer, where stopping inflammation can reverse dysplasia [IL-22 axis; http://jem.rupress.org/content/210/5/917.full.pdf+html]; conversely use of immunosuppressive agents (anti-TNFs) may lead to dangerous loss of immune surveillance against tumour growth.

Summary

Fundamentally we aim to translate advances in immunology and molecular genetics into clinically applicable endoscopic strategies to personalise care through patient stratification.

Name Department Institution Country
Simon Leedham Wellcome Trust Centre for Human Genetics Oxford University, Henry Wellcome Building of Genomic Medicine United Kingdom
Ian Tomlinson Wellcome Trust Centre for Human Genetics Oxford University, Henry Wellcome Building of Genomic Medicine United Kingdom
Xin Lu Oxford Ludwig Institute Oxford University, Old Road Campus Research Building United Kingdom
Alison Simmons Experimental Medicine Division Oxford University, Weatherall Institute of Molecular Medicine United Kingdom
Monahan KJ, Bradshaw N, Dolwani S, Desouza B, Dunlop MG, East JE, Ilyas M, Kaur A, Lalloo F, Latchford A et al. 2019. Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG). Gut, | Show Abstract | Read more

Heritable factors account for approximately 35% of colorectal cancer (CRC) risk, and almost 30% of the population in the UK have a family history of CRC. The quantification of an individual's lifetime risk of gastrointestinal cancer may incorporate clinical and molecular data, and depends on accurate phenotypic assessment and genetic diagnosis. In turn this may facilitate targeted risk-reducing interventions, including endoscopic surveillance, preventative surgery and chemoprophylaxis, which provide opportunities for cancer prevention. This guideline is an update from the 2010 British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland (BSG/ACPGBI) guidelines for colorectal screening and surveillance in moderate and high-risk groups; however, this guideline is concerned specifically with people who have increased lifetime risk of CRC due to hereditary factors, including those with Lynch syndrome, polyposis or a family history of CRC. On this occasion we invited the UK Cancer Genetics Group (UKCGG), a subgroup within the British Society of Genetic Medicine (BSGM), as a partner to BSG and ACPGBI in the multidisciplinary guideline development process. We also invited external review through the Delphi process by members of the public as well as the steering committees of the European Hereditary Tumour Group (EHTG) and the European Society of Gastrointestinal Endoscopy (ESGE). A systematic review of 10 189 publications was undertaken to develop 67 evidence and expert opinion-based recommendations for the management of hereditary CRC risk. Ten research recommendations are also prioritised to inform clinical management of people at hereditary CRC risk.

Rutter MD, East J, Rees CJ, Cripps N, Docherty J, Dolwani S, Kaye PV, Monahan KJ, Novelli MR, Plumb A et al. 2020. British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland/Public Health England post-polypectomy and post-colorectal cancer resection surveillance guidelines. Gut, 69 (2), pp. 201-223. | Show Abstract | Read more

These consensus guidelines were jointly commissioned by the British Society of Gastroenterology (BSG), the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and Public Health England (PHE). They provide an evidence-based framework for the use of surveillance colonoscopy and non-colonoscopic colorectal imaging in people aged 18 years and over. They are the first guidelines that take into account the introduction of national bowel cancer screening. For the first time, they also incorporate surveillance of patients following resection of either adenomatous or serrated polyps and also post-colorectal cancer resection. They are primarily aimed at healthcare professionals, and aim to address:Which patients should commence surveillance post-polypectomy and post-cancer resection?What is the appropriate surveillance interval?When can surveillance be stopped? two or more premalignant polyps including at least one advanced colorectal polyp (defined as a serrated polyp of at least 10 mm in size or containing any grade of dysplasia, or an adenoma of at least 10 mm in size or containing high-grade dysplasia); or five or more premalignant polyps The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument provided a methodological framework for the guidelines. The BSG's guideline development process was used, which is National Institute for Health and Care Excellence (NICE) compliant.two or more premalignant polyps including at least one advanced colorectal polyp (defined as a serrated polyp of at least 10 mm in size or containing any grade of dysplasia, or an adenoma of at least 10 mm in size or containing high-grade dysplasia); or five or more premalignant polyps The key recommendations are that the high-risk criteria for future colorectal cancer (CRC) following polypectomy comprise either:two or more premalignant polyps including at least one advanced colorectal polyp (defined as a serrated polyp of at least 10 mm in size or containing any grade of dysplasia, or an adenoma of at least 10 mm in size or containing high-grade dysplasia); or five or more premalignant polyps This cohort should undergo a one-off surveillance colonoscopy at 3 years. Post-CRC resection patients should undergo a 1 year clearance colonoscopy, then a surveillance colonoscopy after 3 more years.

Bisschops R, East JE, Hassan C, Hazewinkel Y, Kamiński MF, Neumann H, Pellisé M, Antonelli G, Bustamante Balen M, Coron E et al. 2019. Advanced imaging for detection and differentiation of colorectal neoplasia: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2019. Endoscopy, 51 (12), pp. 1155-1179. | Show Abstract | Read more

1:  ESGE suggests that high definition endoscopy, and dye or virtual chromoendoscopy, as well as add-on devices, can be used in average risk patients to increase the endoscopist's adenoma detection rate. However, their routine use must be balanced against costs and practical considerations.Weak recommendation, high quality evidence. 2:  ESGE recommends the routine use of high definition systems in individuals with Lynch syndrome.Strong recommendation, high quality evidence. 3:  ESGE recommends the routine use, with targeted biopsies, of dye-based pancolonic chromoendoscopy or virtual chromoendoscopy for neoplasia surveillance in patients with long-standing colitis.Strong recommendation, moderate quality evidence. 4:  ESGE suggests that virtual chromoendoscopy and dye-based chromoendoscopy can be used, under strictly controlled conditions, for real-time optical diagnosis of diminutive (≤ 5 mm) colorectal polyps and can replace histopathological diagnosis. The optical diagnosis has to be reported using validated scales, must be adequately photodocumented, and can be performed only by experienced endoscopists who are adequately trained, as defined in the ESGE curriculum, and audited.Weak recommendation, high quality evidence. 5:  ESGE recommends the use of high definition white-light endoscopy in combination with (virtual) chromoendoscopy to predict the presence and depth of any submucosal invasion in nonpedunculated colorectal polyps prior to any treatment. Strong recommendation, moderate quality evidence. 6:  ESGE recommends the use of virtual or dye-based chromoendoscopy in addition to white-light endoscopy for the detection of residual neoplasia at a piecemeal polypectomy scar site. Strong recommendation, moderate quality evidence. 7:  ESGE suggests the possible incorporation of computer-aided diagnosis (detection and characterization of lesions) to colonoscopy, if acceptable and reproducible accuracy for colorectal neoplasia is demonstrated in high quality multicenter in vivo clinical studies. Possible significant risks with implementation, specifically endoscopist deskilling and over-reliance on artificial intelligence, unrepresentative training datasets, and hacking, need to be considered. Weak recommendation, low quality evidence.

Spadaccini M, Frazzoni L, Vanella G, East J, Radaelli F, Spada C, Fuccio L, Benamouzig R, Bisschops R, Bretthauer M et al. 2019. Efficacy and Tolerability of High- vs Low-Volume Split-Dose Bowel Cleansing Regimens for Colonoscopy: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol, | Show Abstract | Read more

BACKGROUND & AIMS: Efficacy of bowel preparation is an important determinant of outcomes of colonoscopy. It is not clear whether approved low-volume polyethylene glycol (PEG) and non-PEG regimens are as effective as high-volume PEG regimens when taken in a split dose. METHODS: In a systematic review of multiple electronic databases through January 31, 2019 with a registered protocol (PROSPERO: CRD42019128067), we identified randomized controlled trials that compared low- vs high-volume bowel cleansing regimens, administered in a split dose, for colonoscopy. The primary efficacy outcome was rate of adequate bowel cleansing, and the secondary efficacy outcome was adenoma detection rate. Primary tolerability outcomes were compliance, tolerability, and willingness to repeat. We calculated relative risk (RR) and 95% CI values and assessed heterogeneity among studies by using the I2 statistic. The overall quality of evidence was assessed using the GRADE framework. RESULTS: In an analysis of data from 17 randomized controlled trials, comprising 7528 patients, we found no significant differences in adequacy of bowel cleansing between the low- vs high-volume split-dose regimens (86.1% vs 87.4%; RR, 1.00; 95% CI, 0.98-1.02) and there was minimal heterogeneity (I2 = 17%). There was no significant difference in adenoma detection rate (RR, 0.96; 95% CI, 0.87-1.08) among 4 randomized controlled trials. Compared with high-volume, split-dose regimens, low-volume split-dose regimens had higher odds for compliance or completion (RR, 1.06; 95% CI, 1.02-1.10), tolerability (RR, 1.39; 95% CI, 1.12-1.74), and willingness to repeat bowel preparation (RR, 1.41; 95% CI, 1.20-1.66). The overall quality of evidence was moderate. CONCLUSIONS: Based on a systematic review of 17 randomized controlled trials, low-volume, split-dose regimens appear to be as effective as high-volume, split-dose regimens in bowel cleansing and are better tolerated, with superior compliance.

Gupta V, East JE. 2019. Optimal Endoscopic Treatment and Surveillance of Serrated Polyps. Gut Liver, | Show Abstract | Read more

Serrated polyps are considered precursor lesions that account for 15% to 30% of colorectal cancers, and they are overrepresented as a cause of interval cancers. They are difficult to detect and resect comprehensively; however, recent data suggest that high definition endoscopy, chromoendoscopy (via spray catheter, pump or orally), narrow band imaging, split-dose bowel preparation and a slower withdrawal (>6 minutes) can all improve detection. Cold snare resection is effective and safe for these lesions, including cold snare piecemeal endoscopic mucosal resection, which is likely to become the standard of care for lesions >10 mm in size. Sessile serrated lesions ≥10 mm in size, those exhbiting dysplasia, or traditional serrated adenomas increase the chance of future advanced neoplasia. Thus, a consensus is emerging: a surveillance examination at 3 years should be recommended if these lesions are detected. Serrated lesions likely carry equivalent risk to adenomas, so future guidelines may consider serrated class lesions and adenomas together for risk stratification. Patients with serrated polyposis syndrome should undergo surveillance every 1 to 2 years once the colon is cleared of larger lesions, and their first degree relatives should undergo screening every 5 years starting at age 40.

Bisschops R, Dekker E, East JE, Johnson G, Pimentel-Nunes P, Sanders DS, Dinis-Ribeiro M, Ponchon T. 2019. European Society of Gastrointestinal Endoscopy (ESGE) curricula development for postgraduate training in advanced endoscopic procedures: rationale and methodology. Endoscopy, 51 (10), pp. 976-979. | Read more

Kleeman SO, Koelzer VH, Jones HJ, Vazquez EG, Davis H, East JE, Arnold R, Koppens MA, Blake A, Domingo E et al. 2019. Exploiting differential Wnt target gene expression to generate a molecular biomarker for colorectal cancer stratification. Gut, | Show Abstract | Read more

OBJECTIVE: Pathological Wnt pathway activation is a conserved hallmark of colorectal cancer. Wnt-activating mutations can be divided into: i) ligand-independent (LI) alterations in intracellular signal transduction proteins (Adenomatous polyposis coli, β-catenin), causing constitutive pathway activation and ii) ligand-dependent (LD) mutations affecting the synergistic R-Spondin axis (RNF43, RSPO-fusions) acting through amplification of endogenous Wnt signal transmembrane transduction. Our aim was to exploit differential Wnt target gene expression to generate a mutation-agnostic biomarker for LD tumours. DESIGN: We undertook harmonised multi-omic analysis of discovery (n=684) and validation cohorts (n=578) of colorectal tumours collated from publicly available data and the Stratification in Colorectal Cancer Consortium. We used mutation data to establish molecular ground truth and subdivide lesions into LI/LD tumour subsets. We contrasted transcriptional, methylation, morphological and clinical characteristics between groups. RESULTS: Wnt disrupting mutations were mutually exclusive. Desmoplastic stromal upregulation of RSPO may compensate for absence of epithelial mutation in a subset of stromal-rich tumours. Key Wnt negative regulator genes were differentially expressed between LD/LI tumours, with targeted hypermethylation of some genes (AXIN2, NKD1) occurring even in CIMP-negative LD cancers. AXIN2 mRNA expression was used as a discriminatory molecular biomarker to distinguish LD/LI tumours (area under the curve >0.93). CONCLUSIONS: Epigenetic suppression of appropriate Wnt negative feedback loops is selectively advantageous in LD tumours and differential AXIN2 expression in LD/LI lesions can be exploited as a molecular biomarker. Distinguishing between LD/LI tumour types is important; patients with LD tumours retain sensitivity to Wnt ligand inhibition and may be stratified at diagnosis to clinical trials of Porcupine inhibitors.

East JE. 2019. Can Colonoscopy Sow the Seeds of Colorectal Cancer? Gastroenterology, 157 (5), pp. 1192-1195. | Read more

Leng T, Akther HD, Hackstein C-P, Powell K, King T, Friedrich M, Christoforidou Z, McCuaig S, Neyazi M, Arancibia-Cárcamo CV et al. 2019. TCR and Inflammatory Signals Tune Human MAIT Cells to Exert Specific Tissue Repair and Effector Functions. Cell Rep, 28 (12), pp. 3077-3091.e5. | Show Abstract | Read more

MAIT cells are an unconventional T cell population that can be activated through both TCR-dependent and TCR-independent mechanisms. Here, we examined the impact of combinations of TCR-dependent and TCR-independent signals in human CD8+ MAIT cells. TCR-independent activation of these MAIT cells from blood and gut was maximized by extending the panel of cytokines to include TNF-superfamily member TL1A. RNA-seq experiments revealed that TCR-dependent and TCR-independent signals drive MAIT cells to exert overlapping and specific effector functions, affecting both host defense and tissue homeostasis. Although TCR triggering alone is insufficient to drive sustained activation, TCR-triggered MAIT cells showed specific enrichment of tissue-repair functions at the gene and protein levels and in in vitro assays. Altogether, these data indicate the blend of TCR-dependent and TCR-independent signaling to CD8+ MAIT cells may play a role in controlling the balance between healthy and pathological processes of tissue inflammation and repair.

Lahiff C, East JE. 2019. Distal attachments for adenoma detection go head-to-head: Cap or cuff? J Gastroenterol Hepatol, 34 (9), pp. 1471-1473. | Read more

Pimentel-Nunes P, Pioche M, Albéniz E, Berr F, Deprez P, Ebigbo A, Dewint P, Haji A, Panarese A, Weusten BLAM et al. 2019. Curriculum for endoscopic submucosal dissection training in Europe: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Endoscopy, 51 (10), pp. 980-992. | Show Abstract | Read more

There is a need for well-organized comprehensive strategies to achieve good training in ESD. In this context, the European Society of Gastrointestinal Endoscopy (ESGE) have developed a European core curriculum for ESD practice across Europe with the aim of high quality ESD training.Advanced endoscopy diagnostic practice is advised before initiating ESD training. Proficiency in endoscopic mucosal resection (EMR) and adverse event management is recommended before starting ESD trainingESGE discourages the starting of initial ESD training in humans. Practice on animal and/or ex vivo models is useful to gain the basic ESD skills. ESGE recommends performing at least 20 ESD procedures in these models before human practice, with the goal of at least eight en bloc complete resections in the last 10 training cases, with no perforation. ESGE recommends observation of experts performing ESD in tertiary referral centers. Performance of ESD in humans should start on carefully selected lesions, ideally small ( < 30 mm), located in the antrum or in the rectum for the first 20 procedures. Beginning human practice in the colon is not recommended. ESGE recommends that at least the first 10 human ESD procedures should be done under the supervision of an ESD-proficient endoscopist.Endoscopists performing ESD should be able to correctly estimate the probability of performing a curative resection based on the characteristics of the lesion and should know the benefit/risk relationship of ESD when compared with other therapeutic alternatives. Endoscopists performing ESD should know how to interpret the histopathology findings of the ESD specimen, namely the criteria for low risk resection ("curative"), local risk resection, and high risk resection ("non-curative"), as well as their implications. ESD should be performed only in a setting where early and delayed complications can be managed adequately, namely with the possibility of admitting patients to a ward, and access to appropriate emergency surgical teams for the organ being treated with ESD.

Hassan C, East J, Radaelli F, Spada C, Benamouzig R, Bisschops R, Bretthauer M, Dekker E, Dinis-Ribeiro M, Ferlitsch M et al. 2019. Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2019. Endoscopy, 51 (8), pp. 775-794. | Show Abstract | Read more

ESGE recommends a low fiber diet on the day preceding colonoscopy.Strong recommendation, moderate quality evidence.ESGE recommends the use of enhanced instructions for bowel preparation.Strong recommendation, moderate quality evidence.ESGE suggests adding oral simethicone to bowel preparation.Weak recommendation, moderate quality evidence.ESGE recommends split-dose bowel preparation for elective colonoscopy.Strong recommendation, high quality evidence.ESGE recommends, for patients undergoing afternoon colonoscopy, a same-day bowel preparation as an acceptable alternative to split dosing.Strong recommendation, high quality evidence.ESGE recommends to start the last dose of bowel preparation within 5 hours of colonoscopy, and to complete it at least 2 hours before the beginning of the procedure.Strong recommendation, moderate quality evidence.ESGE recommends the use of high volume or low volume PEG-based regimens as well as that of non-PEG-based agents that have been clinically validated for routine bowel preparation. In patients at risk for hydroelectrolyte disturbances, the choice of laxative should be individualized.Strong recommendation, moderate quality evidence.

Bolton C, Burch N, Morgan J, Harrison B, Pandey S, Pagnamenta AT, Oxford IBD cohort investigators, Taylor JC, Taylor JM, Marsh JCW et al. 2020. Remission of Inflammatory Bowel Disease in Glucose-6-Phosphatase 3 Deficiency by Allogeneic Haematopoietic Stem Cell Transplantation. J Crohns Colitis, 14 (1), pp. 142-147. | Show Abstract | Read more

Mendelian disorders in glucose-6-phosphate metabolism can present with inflammatory bowel disease [IBD]. Using whole genome sequencing we identified a homozygous variant in the glucose-6-phosphatase G6PC3 gene [c.911dupC; p.Q305fs*82] in an adult patient with congenital neutropenia, lymphopenia and childhood-onset, therapy-refractory Crohn's disease. Because G6PC3 is expressed in several haematopoietic and non-haematopoietic cells it was unclear whether allogeneic stem cell transplantation [HSCT] would benefit this patient with intestinal inflammation. We show that HSCT resolves G6PC3-associated immunodeficiency and the Crohn's disease phenotype. It illustrates how even in adulthood, next-generation sequencing can have a significant impact on clinical practice and healthcare utilization in patients with immunodeficiency and monogenic IBD.

Law PJ, Timofeeva M, Fernandez-Rozadilla C, Broderick P, Studd J, Fernandez-Tajes J, Farrington S, Svinti V, Palles C, Orlando G et al. 2019. Association analyses identify 31 new risk loci for colorectal cancer susceptibility. Nat Commun, 10 (1), pp. 2154. | Show Abstract | Read more

Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.

Vleugels JLA, van Neerven SM, van Leerdam ME, Wanders LK, de Wit M, Carvalho B, Delis-van Diemen PM, Kallenberg FGJ, Vermeulen L, Beliën JA et al. 2019. CD31-positive microvessel density within adenomas of Lynch Syndrome patients is similar compared to adenomas of non-Lynch patients. Endosc Int Open, 7 (5), pp. E701-E707. | Show Abstract | Read more

Background and study aims  Microsatellite instability accelerates colorectal cancer development in patients with Lynch syndrome (LS). Previous research showed that virtual chromoendoscopy increases detection of adenomas during colonoscopy surveillance of patients with LS. Because previous research revealed that Lynch patients have an increased vascular network in the oral mucosa, we hypothesized that increased vascularization of LS-associated adenomas is the cause of better detection with virtual chromoendoscopy. Patients and methods  In this pilot study, patients with LS having a proven germline mutation were selected from two tertiary referral hospitals and non-LS patients from an outpatient colonoscopy center. Adenomas from patients with LS were exactly matched in size and histology with adenomas from non-LS patients. Initial adenoma diagnosis was confirmed by a specialist pathologist. All adenomas were stained with CD31 and adenomatous tissue was annotated by the specialist pathologist. Image analysis of CD31-positive microvessel density was conducted using FIJI software. Results  Colonoscopy of 63 patients with LS and 24 non-LS patients provided 40 adenomas that could be exactly matched in size and histology. In image-analysis, the CD31-positive microvessel density (2.49 % vs. 2.47 %, P  = 0.96), the average size of CD31-positive structures (514 μm 2 vs. 523 μm 2 , P  = 0.26) nor the amount of vascular structures per mm 2 (183 vs. 176, P  = 0.50) differed between adenomas of LS patients and non-Lynch patients. Conclusion  The outcomes of this pilot case-control study did not provide further insights into the mechanism of increased adenoma detection in LS patients using virtual chromoendoscopy techniques.

Atkinson NSS, Ket S, Bassett P, Aponte D, De Aguiar S, Gupta N, Horimatsu T, Ikematsu H, Inoue T, Kaltenbach T et al. 2019. Narrow-Band Imaging for Detection of Neoplasia at Colonoscopy: A Meta-analysis of Data From Individual Patients in Randomized Controlled Trials. Gastroenterology, 157 (2), pp. 462-471. | Show Abstract | Read more

BACKGROUND & AIMS: Adenoma detection rate (ADR) is an important quality assurance measure for colonoscopy. Some studies suggest that narrow-band imaging (NBI) may be more effective at detecting adenomas than white-light endoscopy (WLE) when bowel preparation is optimal. We conducted a meta-analysis of data from individual patients in randomized controlled trials that compared the efficacy of NBI to WLE in detection of adenomas. METHODS: We searched MEDLINE, EMBASE, and Cochrane Library databases through April 2017 for randomized controlled trials that assessed detection of colon polyps by high-definition WLE vs NBI and from which data on individual patients were available. The primary outcome measure was ADR adjusted for bowel preparation quality. Multilevel regression models were used with patients nested within trials, and trial included as a random effect. RESULTS: We collected data from 11 trials, comprising 4491 patients and 6636 polyps detected. Adenomas were detected in 952 of 2251 (42.3%) participants examined by WLE vs 1011 of 2239 (45.2%) participants examined by NBI (unadjusted odds ratio [OR] for detection of adenoma by WLE vs NBI, 1.14; 95% CI, 1.01-1.29; P = .04). NBI outperformed WLE only when bowel preparation was best: adequate preparation OR, 1.07 (95% CI, 0.92-1.24; P = .38) vs best preparation OR, 1.30 (95% CI, 1.04-1.62; P = .02). Second-generation bright NBI had a better ADR than WLE (second-generation NBI OR, 1.28; 95% CI, 1.05-1.56; P = .02), whereas first-generation NBI did not. NBI detected more non-adenomatous polyps than WLE (OR, 1.24; 95% CI, 1.06-1.44; P = .008) and flat polyps than WLE (OR, 1.24; 95% CI, 1.02-1.51; P = .03). CONCLUSIONS: In a meta-analysis of data from individual patients in randomized controlled trials, we found NBI to have a higher ADR than WLE, and that this effect is greater when bowel preparation is optimal.

East JE, Bhandari P, Dolwani S, MacCarthy F, Rutter MD, Saunders BP. 2019. Endoscopic excision of significant polyp and early colorectal cancer lesions. Colorectal Dis, 21 Suppl 1 pp. 37-40. | Read more

Rutter MD, Dolwani S, East J, Beckett C, Bhandari P, McKaig B, Phull P, Ragunath K, Saunders B, O'Toole P. 2019. Defining, recognizing and describing significant polyp and early colorectal cancer lesions. Colorectal Dis, 21 Suppl 1 pp. 11-13. | Read more

Repici A, Wallace MB, East JE, Sharma P, Ramirez FC, Bruining DH, Young M, Gatof D, Irene Mimi Canto M, Marcon N et al. 2019. Efficacy of Per-oral Methylene Blue Formulation for Screening Colonoscopy. Gastroenterology, 156 (8), pp. 2198-2207.e1. | Show Abstract | Read more

BACKGROUND & AIMS: Topically applied methylene blue dye chromoendoscopy is effective in improving detection of colorectal neoplasia. When combined with a pH- and time-dependent multimatrix structure, a per-oral methylene blue formulation (MB-MMX) can be delivered directly to the colorectal mucosa. METHODS: We performed a phase 3 study of 1205 patients scheduled for colorectal cancer screening or surveillance colonoscopies (50-75 years old) at 20 sites in Europe and the United States, from December 2013 through October 2016. Patients were randomly assigned to groups given 200 mg MB-MMX, placebo, or 100 mg MB-MMX (ratio of 2:2:1). The 100-mg MB-MMX group was included for masking purposes. MB-MMX and placebo tablets were administered with a 4-L polyethylene glycol-based bowel preparation. The patients then underwent colonoscopy by an experienced endoscopist with centralized double-reading. The primary endpoint was the proportion of patients with 1 adenoma or carcinoma (adenoma detection rate [ADR]). We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for differences in detection between the 200-mg MB-MMX and placebo groups. False-positive (resection rate for non-neoplastic polyps) and adverse events were assessed as secondary endpoints. RESULTS: The ADR was higher for the MB-MMX group (273 of 485 patients, 56.29%) than the placebo group (229 of 479 patients, 47.81%) (OR 1.46; 95% CI 1.09-1.96). The proportion of patients with nonpolypoid lesions was higher in the MB-MMX group (213 of 485 patients, 43.92%) than the placebo group (168 of 479 patients, 35.07%) (OR 1.66; 95% CI 1.21-2.26). The proportion of patients with adenomas ≤5 mm was higher in the MB-MMX group (180 of 485 patients, 37.11%) than the placebo group (148 of 479 patients, 30.90%) (OR 1.36; 95% CI 1.01-1.83), but there was no difference between groups in detection of polypoid or larger lesions. The false-positive rate did not differ significantly between groups (83 [23.31%] of 356 patients with non-neoplastic lesions in the MB-MMX vs 97 [29.75%] of 326 patients with non-neoplastic lesions in the placebo group). Overall, 0.7% of patients had severe adverse events but there was no significant difference between groups. CONCLUSIONS: In a phase 3 trial of patients undergoing screening or surveillance colonoscopies, we found MB-MMX led to an absolute 8.5% increase in ADR, compared with placebo, without increasing the removal of non-neoplastic lesions. Clinicaltrials.gov no: NCT01694966.

Bhandari P, Subramaniam S, East JE. 2019. British Society of Gastroenterology Endoscopy Quality Improvement Programme (BSG EQIP): Implementing new endoscopic techniques and technologies into clinical practice. Frontline Gastroenterol, 10 (2), pp. 155-159. | Show Abstract | Read more

Endoscopy has rapidly evolved from a diagnostic modality to a therapeutic tool with the advent of new technologies (medical devices or imaging) and techniques (types of procedures). Although the rapid advancement of technology is welcomed, this can pose its own problems if there is no robust system in place to assess the safety and efficacy of new endoscopic devices or practices or guide its use among clinicians prior to adoption. This is unlike the rigorous process that medical drugs need to go through from preclinical to clinical phases of development, often with controlled trials being conducted prior to integration of a new drug into clinical practice. In this review, we will identify the problems related to implementation of new technologies and techniques as well as propose solutions. We will outline the use of comparative effectiveness studies as a model for assessing new technologies and provide a structured pathway to support clinicians in their endeavour to introduce new devices or procedures in their clinical practice safely. We will also discuss the role of the British Society of Gastroenterology in risk stratifying new techniques and supporting clinicians in setting up national registries, training and business case development. This review will provide a framework for improving the quality and safety of our current practice of implementing new endoscopic technologies and techniques in the National Health Service.

East JE, Boyapati RK, Torres J, Parker CE, MacDonald JK, Chande N, Feagan BG. 2019. Controversies in Inflammatory Bowel Disease: Exploring Clinical Dilemmas Using Cochrane Reviews. Inflamm Bowel Dis, 25 (3), pp. 472-478. | Show Abstract | Read more

A symposium organized by the Cochrane IBD Group and presented at the 2017 Digestive Disease Week annual meeting reviewed the recent literature on several controversial topics in inflammatory bowel disease (IBD) management including the efficacy of oral aminosalicylates for induction and maintenance of Crohn's disease (CD), the feasibility of drug withdrawal in patients with quiescent CD, and strategies for detecting colon cancer in patients with IBD. This article summarizes the data presented at that session.

Wu HHL, East JE. 2019. Will endoscopic submucosal dissection (ESD) become the gold standard for laterally spreading tumors (LST)? Endosc Int Open, 7 (2), pp. E260-E263. | Read more

Rees CJ, Koo S, Anderson J, McAlindon M, Veitch AM, Morris AJ, Bhandari P, East JE, Webster G, Oppong KW, Penman ID. 2019. British society of gastroenterology Endoscopy Quality Improvement Programme (EQIP): overview and progress. Frontline Gastroenterol, 10 (2), pp. 148-153. | Show Abstract | Read more

High quality gastrointestinal (GI) endoscopy improves patient care. Raising standards in endoscopy improves diagnostic accuracy, management of pathology and ultimately improves outcomes. Historical identification of significant variation in colonoscopy quality led to the development of the Joint Advisory Group (JAG) on GI Endoscopy, the Global Rating Scale (GRS), JAG Endoscopy Training System (JETS) training and certification. These measures led to major improvements in UK endoscopy but significant variation in practice still exists. To improve quality further the British Society of Gastroenterology Endoscopy Quality Improvement (EQIP) has been established with the aim of raising quality and reducing variation in the quality of UK endoscopy. A multifaceted approach to quality improvement (QI) will be undertaken and is described in this manuscript. Upper GI EQIP will support adoption of standards alongside regional upskilling courses. Lower GI EQIP will focus on supporting endoscopists to achieve current standards alongside approaches to reducing postcolonoscopy colorectal cancer rates. Endoscopic retrograde cholangiopancreatography EQIP will adopt a regional approach of using local data to support network-based QI. Newer areas of endoscopy practice such as small bowel endoscopy and endoscopic ultrasound will focus on identifying key performance indicators as well as standardising training and accreditation pathways. EQIP will also support QI in management of GI bleeding as well as standardising the approach to new techniques and technologies. Where evidence is lacking, approaches to gather new evidence and support the translation into clinical practice will be supported.

Stockenhuber K, East JE. 2019. Colorectal cancer: prevention and early diagnosis Medicine (United Kingdom), 47 (7), pp. 395-399. | Show Abstract | Read more

© 2019 Elsevier Ltd Colorectal cancer (CRC) is one of the leading causes of cancer deaths worldwide. This article reviews the aetiology and risk factors for CRC and focuses on strategies for prevention and early diagnosis. Prevention involves identifying and optimizing modifiable risk factors through public health awareness as well as population screening, for example using detection of occult blood in stool. Endoscopic surveillance in the UK is currently performed on a population basis with the bowel scope programme and faecal immunochemical testing, with colonoscopy reserved for patients known to be at higher risk of developing CRC. These include individuals with genetic predisposition or long-standing inflammatory bowel disease. Population screening for CRC is well established in clinical practice as an effective method for early cancer detection and prevention through polypectomy. It is effective at improving disease stage at diagnosis and thus reducing CRC-specific mortality. Recent changes to the NHS screening programmes and advances in the understanding of the serrated pathway for CRC development are highlighted and their respective roles for cancer prevention discussed. Finally, future directions in technology and research for prevention and early diagnosis of CRC, including computer-aided diagnosis (deep learning), are explored.

Oakland K, Chadwick G, East JE, Guy R, Humphries A, Jairath V, McPherson S, Metzner M, Morris AJ, Murphy MF et al. 2019. Diagnosis and management of acute lower gastrointestinal bleeding: guidelines from the British Society of Gastroenterology. Gut, 68 (5), pp. 776-789. | Show Abstract | Read more

This is the first UK national guideline to concentrate on acute lower gastrointestinal bleeding (LGIB) and has been commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG). The Guidelines Development Group consisted of representatives from the BSG Endoscopy Committee, the Association of Coloproctology of Great Britain and Ireland, the British Society of Interventional Radiology, the Royal College of Radiologists, NHS Blood and Transplant and a patient representative. A systematic search of the literature was undertaken and the quality of evidence and grading of recommendations appraised according to the GRADE(Grading of Recommendations Assessment, Development and Evaluation) methodology. These guidelines focus on the diagnosis and management of acute LGIB in adults, including methods of risk assessment and interventions to diagnose and treat bleeding (colonoscopy, computed tomography, mesenteric angiography, endoscopic therapy, embolisation and surgery). Recommendations are included on the management of patients who develop LGIB while receiving anticoagulants (including direct oral anticoagulants) or antiplatelet drugs. The appropriate use of blood transfusion is also discussed, including haemoglobin triggers and targets.

Bye WA, Ma C, Nguyen TM, Parker CE, Jairath V, East JE. 2018. Strategies for Detecting Colorectal Cancer in Patients with Inflammatory Bowel Disease: A Cochrane Systematic Review and Meta-Analysis. Am J Gastroenterol, 113 (12), pp. 1801-1809. | Show Abstract | Read more

OBJECTIVES: Patients with longstanding ulcerative colitis (UC) and colonic Crohn's disease (CD) have an increased risk of colorectal cancer (CRC). We assess the effectiveness of endoscopic surveillance in patients with inflammatory bowel disease (IBD) for diagnosing CRC and reducing CRC-related mortality. METHODS: MEDLINE, EMBASE, and CENTRAL were searched from inception to 19 September 2016. Randomized controlled trials (RCTs), observational cohorts, or case-control studies assessing any form of endoscopic surveillance for early CRC detection were eligible for inclusion; studies without a comparison non-surveillance group were excluded. The primary outcome was rate of CRC detection. Secondary outcomes were rate of early (Duke stage A and B) versus late (Duke stage C & D) CRC detection and rate of CRC-related death. Data were pooled using fixed or random effects models based on the degree of heterogeneity; pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the Mantel-Haenszel method. RESULTS: Five observational studies evaluating 7199 IBD patients were included; no RCTs met criteria for inclusion. There are limited new studies evaluating this clinical question (last included study published 2014). There was a significantly higher rate of cancer detection in the non-surveillance group (3.2%, 135/4256) compared to the surveillance group (1.8%, 53/2895) (OR 0.58 (95% CI: 0.42-0.80), p < 0.001). In four pooled studies, there was a significantly lower rate of CRC-associated death in the surveillance group (8.5%, 15/176) compared to the non-surveillance group (22.3%, 79/354) (OR 0.36 (95% CI: 0.19-0.69), p = 0.002). In two pooled studies, there was a significantly higher rate of early-stage CRC detection in the surveillance group (15.5%, 17/110) compared to the non-surveillance group (7.7%, 9/117) (OR 5.40 (95% CI: 1.51-19.30), p = 0.009). CONCLUSIONS: Colonoscopic surveillance in IBD is associated with a reduction in CRC development and CRC-associated death, as well as increased detection of early-stage CRC.

Nicholson BD, James T, East JE, Grimshaw D, Paddon M, Justice S, Oke JL, Shine B. 2019. Experience of adopting faecal immunochemical testing to meet the NICE colorectal cancer referral criteria for low-risk symptomatic primary care patients in Oxfordshire, UK. Frontline Gastroenterol, 10 (4), pp. 347-355. | Show Abstract | Read more

Objective: To compare the diagnostic performance of guaiac faecal occult blood (gFOB) testing with faecal immunochemical test (FIT) in a low-risk symptomatic primary care population to provide objective data on which to base local referral guidelines. Design: Stool samples from routine primary care practice sent for faecal occult blood testing were analysed by a standard gFOB method and the HM-JACKarc FIT between January and March 2016. Symptoms described on the test request were recorded. Patients were followed up over 21 months for evidence of serious gastrointestinal pathology including colorectal adenocarcinoma. Results: In 238 patients, the sensitivity and specificity for colorectal adenocarcinoma detection using gFOB were 85.7% and 65.8%, respectively, compared with 85.7% and 89.2% for FIT. The positive predictive value (PPV) for gFOB was 7.1% and negative predictive value (NPV) was 99.3%. Comparatively, the PPV for FIT was 19.4% and NPV 99.5%. The improved performance of FIT over gFOB was due to a lower false positive rate (10.8 vs 34.2, p≤0.01) with no increase in the false negatives rate. For any significant colorectal disease, the PPV for FIT increased to 35.5% with a reduction in NPV to 95.7%. Conclusion: In this low-risk symptomatic patient group, the proportion of samples considered positive by FIT was considerably lower than gFOB with the same rate of colorectal adenocarcinoma detection. One in three of those with positive FIT had a significant colorectal disease. This supports National Institute of Health and Care Excellence recommendation that FIT can be reliably used as a triage test in primary care without overburdening endoscopy resources.

Lahiff C, Wang LM, Travis SPL, East JE. 2018. Polyp-adjacent biopsies no longer required in inflammatory bowel disease. Gastrointest Endosc, 88 (4), pp. 782-783. | Read more

Vleugels JLA, Rutter MD, Ragunath K, Rees CJ, Ponsioen CY, Lahiff C, Ket SN, Wanders LK, Samuel S, Butt F et al. 2018. Diagnostic Accuracy of Endoscopic Trimodal Imaging and Chromoendoscopy for Lesion Characterization in Ulcerative Colitis. J Crohns Colitis, 12 (12), pp. 1438-1447. | Show Abstract | Read more

Background: During surveillance colonoscopy of patients with long-standing ulcerative colitis [UC], a variety of dysplastic and non-dysplastic lesions are detected. The aim of this study was to address the diagnostic accuracy of endoscopic characterization of endoscopic trimodal imaging [ETMI] and chromoendoscopy [CE]. ETMI includes the combination of autofluorescence imaging [AFI], narrow band imaging [NBI] and white light endoscopy [WLE]. Methods: This is a pre-specified additional analysis of a multi-centre, randomized controlled trial that compared AFI with CE for dysplasia detection in 210 patients with long-standing UC [FIND-UC trial]. In the AFI arm, endoscopists used the ETMI system to record AFI colour, Kudo pit pattern using NBI and WLE for lesion characterization. For AFI, purple colour and ambiguous colour combined with pit pattern type III-V on NBI was considered dysplastic. Kudo pit pattern was described in the CE arm. For pit pattern description using NBI and CE, type III-V was considered dysplastic. Histology was the reference standard. Results: In total, 52 dysplastic and 255 non-dysplastic lesions were detected. Overall sensitivity for real-time prediction of dysplasia was 76.9% (95% confidence interval [CI] 46.2-95.0) for ETMI, and 81.6% [95% CI 65.7-92.3] for CE. Overall negative predictive value [NPV] for ETMI was 96.9% [95% CI 92.0-98.8] and 94.7% [90.2-97.2] for CE. Conclusions: Sensitivity for endoscopic differentiation of dysplastic lesions detected during surveillance of patients with long-standing UC seems limited using ETMI and CE. Future research is warranted as the high NPV indicates that these techniques are valuable for the exclusion of dysplastic lesions [NTR4062].

Cross W, Kovac M, Mustonen V, Temko D, Davis H, Baker A-M, Biswas S, Arnold R, Chegwidden L, Gatenbee C et al. 2018. The evolutionary landscape of colorectal tumorigenesis. Nat Ecol Evol, 2 (10), pp. 1661-1672. | Show Abstract | Read more

The evolutionary events that cause colorectal adenomas (benign) to progress to carcinomas (malignant) remain largely undetermined. Using multi-region genome and exome sequencing of 24 benign and malignant colorectal tumours, we investigate the evolutionary fitness landscape occupied by these neoplasms. Unlike carcinomas, advanced adenomas frequently harbour sub-clonal driver mutations-considered to be functionally important in the carcinogenic process-that have not swept to fixation, and have relatively high genetic heterogeneity. Carcinomas are distinguished from adenomas by widespread aneusomies that are usually clonal and often accrue in a 'punctuated' fashion. We conclude that adenomas evolve across an undulating fitness landscape, whereas carcinomas occupy a sharper fitness peak, probably owing to stabilizing selection.

Sharma S, Momose K, Hara H, East J, Sumiyama K, Nakajima K, Silbehumer G, Milsom J. 2019. Facilitating endoscopic submucosal dissection: double balloon endolumenal platform significantly improves dissection time compared with conventional technique (with video). Surg Endosc, 33 (1), pp. 315-321. | Show Abstract | Read more

BACKGROUND: Flexible endoscopes ability to manipulate the intestinal environment is limited. As a result, complex endolumenal procedures are often technically demanding and result in long procedure times, impacting institutional resources. Single- and double-balloon add-on endoscopic devices have been employed throughout the GI tract to facilitate tissue control e.g., small bowel enteroscopy, with recent reports suggesting a possible colonic utility for complex procedures e.g., ESD. Our objective was to objectively analyze the efficacy of a new double-balloon device in performing ESD. METHODS: Ex vivo-12 simulated colonic lesions were created in porcine rectum using a standard 40 mm diameter template. Two categories were evaluated, standard cap technique ESD and double-balloon assisted ESD with retraction (ESD-R). Cases were performed sequentially. In vivo-Six, 40 mm lesion ESD-R's were performed in a porcine model. The primary outcomes of this study were total procedure and dissection times. RESULTS: In ex vivo studies, the median total procedure time with the double-balloon platform was significantly shorter than the traditional ESD technique (29 ± 18 vs. 57 ± 21 min, p = 0.03). In the in vivo studies, lesions were successfully removed in a mean time of 48 min, with a dissection time of 20 min with no significant complications. Balloon-clip retraction and specimen retrieval capabilities were used in all double-balloon assisted cases. After 6 cases, times were significantly shorter (ex vivo 47 vs. 17 min; in vivo 57 vs. 27 min). CONCLUSIONS: We have demonstrated the development of a unique technical ESD method facilitated by a new double-balloon device. Ex and in vivo investigation demonstrated superiority of ESD-R over the conventional ex vivo method. The DB device provided increased stability, improved visualization and tissue traction, which significantly reduced dissection time. Such an approach may increase safety, improve patient outcomes, and may prevent unnecessary surgeries for benign conditions.

Baker A-M, Cross W, Curtius K, Al Bakir I, Choi C-HR, Davis HL, Temko D, Biswas S, Martinez P, Williams MJ et al. 2019. Evolutionary history of human colitis-associated colorectal cancer. Gut, 68 (6), pp. 985-995. | Show Abstract | Read more

OBJECTIVE: IBD confers an increased lifetime risk of developing colorectal cancer (CRC), and colitis-associated CRC (CA-CRC) is molecularly distinct from sporadic CRC (S-CRC). Here we have dissected the evolutionary history of CA-CRC using multiregion sequencing. DESIGN: Exome sequencing was performed on fresh-frozen multiple regions of carcinoma, adjacent non-cancerous mucosa and blood from 12 patients with CA-CRC (n=55 exomes), and key variants were validated with orthogonal methods. Genome-wide copy number profiling was performed using single nucleotide polymorphism arrays and low-pass whole genome sequencing on archival non-dysplastic mucosa (n=9), low-grade dysplasia (LGD; n=30), high-grade dysplasia (HGD; n=13), mixed LGD/HGD (n=7) and CA-CRC (n=19). Phylogenetic trees were reconstructed, and evolutionary analysis used to reveal the temporal sequence of events leading to CA-CRC. RESULTS: 10/12 tumours were microsatellite stable with a median mutation burden of 3.0 single nucleotide alterations (SNA) per Mb, ~20% higher than S-CRC (2.5 SNAs/Mb), and consistent with elevated ageing-associated mutational processes. Non-dysplastic mucosa had considerable mutation burden (median 47 SNAs), including mutations shared with the neighbouring CA-CRC, indicating a precancer mutational field. CA-CRCs were often near triploid (40%) or near tetraploid (20%) and phylogenetic analysis revealed that copy number alterations (CNAs) began to accrue in non-dysplastic bowel, but the LGD/HGD transition often involved a punctuated 'catastrophic' CNA increase. CONCLUSIONS: Evolutionary genomic analysis revealed precancer clones bearing extensive SNAs and CNAs, with progression to cancer involving a dramatic accrual of CNAs at HGD. Detection of the cancerised field is an encouraging prospect for surveillance, but punctuated evolution may limit the window for early detection.

Fernandez-Rozadilla C, Kartsonaki C, Woolley C, McClellan M, Whittington D, Horgan G, Leedham S, Kriaucionis S, East JE, Tomlinson I. 2018. Author Correction: Telomere length and genetics are independent colorectal tumour risk factors in an evaluation of biomarkers in normal bowel. Br J Cancer, 118 (12), pp. 1683. | Show Abstract | Read more

Since the publication of this paper, the authors noticed that James E. East was assigned to the incorrect affiliation. The affiliation information is provided correctly, above.

Kurioka A, Cosgrove C, Simoni Y, van Wilgenburg B, Geremia A, Björkander S, Sverremark-Ekström E, Thurnheer C, Günthard HF, Khanna N et al. 2018. CD161 Defines a Functionally Distinct Subset of Pro-Inflammatory Natural Killer Cells. Front Immunol, 9 (APR), pp. 486. | Show Abstract | Read more

CD161 is a C-type lectin-like receptor expressed on the majority of natural killer (NK) cells; however, the significance of CD161 expression on NK cells has not been comprehensively investigated. Recently, we found that CD161 expression identifies a transcriptional and innate functional phenotype that is shared across various T cell populations. Using mass cytometry and microarray experiments, we demonstrate that this functional phenotype extends to NK cells. CD161 marks NK cells that have retained the ability to respond to innate cytokines during their differentiation, and is lost upon cytomegalovirus-induced maturation in both healthy and human immunodeficiency virus (HIV)-infected patients. These pro-inflammatory NK cells are present in the inflamed lamina propria where they are enriched for integrin CD103 expression. Thus, CD161 expression identifies NK cells that may contribute to inflammatory disease pathogenesis and correlates with an innate responsiveness to cytokines in both T and NK cells.

Tan M, East JE. 2018. Fitting Balloon Overtube-Assisted Colonoscopy (BOAC) Into the Difficult or Failed Colonoscopy Algorithm. Clin Gastroenterol Hepatol, 16 (4), pp. 594-595. | Read more

Soetikno R, East J, Suzuki N, Uedo N, Matsumoto T, Watanabe K, Sanduleanu S, Sanchez-Yague A, Kaltenbach T. 2018. Endoscopic submucosal dissection for nonpolypoid colorectal dysplasia in patients with inflammatory bowel disease: in medias res. Gastrointest Endosc, 87 (4), pp. 1085-1094. | Read more

Vleugels JLA, Rutter MD, Ragunath K, Rees CJ, Ponsioen CY, Lahiff C, Ket SN, Wanders LK, Samuel S, Butt F et al. 2018. Chromoendoscopy versus autofluorescence imaging for neoplasia detection in patients with longstanding ulcerative colitis (FIND-UC): an international, multicentre, randomised controlled trial. Lancet Gastroenterol Hepatol, 3 (5), pp. 305-316. | Show Abstract | Read more

BACKGROUND: Patients with longstanding ulcerative colitis undergo regular dysplasia surveillance because they have an increased colorectal cancer risk. Autofluorescence imaging and chromoendoscopy improve dysplasia detection. The aim of this study was to determine whether autofluorescence imaging should be further studied as an alternative method for dysplasia surveillance in patients with longstanding ulcerative colitis. METHODS: This prospective, international, randomised controlled trial included patients from an ulcerative colitis-dysplasia surveillance cohort from five centres in the Netherlands and the UK. Eligible patients were aged 18 years or older who were undergoing dysplasia surveillance after being diagnosed with extensive colitis (Montreal E3) at least 8 years before study start or with left-sided colitis (Montreal E2) at least 15 years before study start. Randomisation (1:1) was minimised for a previous personal history of histologically proven dysplasia and concomitant primary sclerosing cholangitis. The coprimary outcomes were the proportion of patients in whom at least one dysplastic lesion was detected and the mean number of dysplastic lesions per patient. The relative dysplasia detection rate, calculated as the ratio of the detection rates by autofluorescence imaging and chromoendoscopy, needed to be more than 0·67 (using an 80% CI) for both primary outcomes to support a subsequent large non-inferiority trial. Outcomes were analysed on a per-protocol basis. The trial is registered at the Netherlands Trial Register, number NTR4062. FINDINGS: Between Aug 1, 2013, and March 10, 2017, 210 patients undergoing colonoscopy surveillance for longstanding ulcerative colitis were randomised for inspection with either autofluorescence imaging (n=105) or chromoendoscopy (n=105). Dysplasia was detected in 13 (12%) patients by autofluorescence imaging and in 20 patients (19%) by chromoendoscopy. The relative dysplasia detection rate of autofluorescence imaging versus chromoendoscopy for the proportion of patients with ulcerative colitis with at least one dysplastic lesion was 0·65 (80% CI 0·43-0·99). The mean number of detected dysplastic lesions per patient was 0·13 (SD 0·37) for autofluorescence imaging and 0·37 (1·02) for chromoendoscopy (relative dysplasia detection rate 0·36, 80% CI 0·21-0·61). Adverse events were reported for two patients in the autofluorescence imaging group (one patient had intraprocedural mild bleeding, and one patient had abdominal pain) and for three patients in the chromoendoscopy group (two patients had intraprocedural mild bleeding, and one patient had perforation). INTERPRETATION: Autofluorescence imaging did not meet criteria for proceeding to a large non-inferiority trial. Therefore, existing autofluorescence imaging technology should not be further investigated as an alternative dysplasia surveillance method. FUNDING: Olympus Europe and Olympus Keymed.

Bird-Lieberman E, East JE. 2018. Diminutive polyps and future colorectal cancer risk perception: how low do we need to go? Endoscopy, 50 (3), pp. 197-199. | Read more

Fernandez-Rozadilla C, Kartsonaki C, Woolley C, McClellan M, Whittington D, Horgan G, Leedham S, Kriaucionis S, East J, Tomlinson I. 2018. Telomere length and genetics are independent colorectal tumour risk factors in an evaluation of biomarkers in normal bowel. Br J Cancer, 118 (5), pp. 727-732. | Show Abstract | Read more

BACKGROUND: Colorectal cancer (CRC) screening might be improved by using a measure of prior risk to modulate screening intensity or the faecal immunochemical test threshold. Intermediate molecular biomarkers could aid risk prediction by capturing both known and unknown risk factors. METHODS: We sampled normal bowel mucosa from the proximal colon, distal colon and rectum of 317 individuals undergoing colonoscopy. We defined cases as having a personal history of colorectal polyp(s)/cancer, and controls as having no history of colorectal neoplasia. Molecular analyses were performed for: telomere length (TL); global methylation; and the expression of genes in molecular pathways associated with colorectal tumourigenesis. We also calculated a polygenic risk score (PRS) based on CRC susceptibility polymorphisms. RESULTS: Bowel TL was significantly longer in cases than controls, but was not associated with blood TL. PRS was significantly and independently higher in cases. Hypermethylation showed a suggestive association with case:control status. No gene or pathway was differentially expressed between cases and controls. Gene expression often varied considerably between bowel locations. CONCLUSIONS: PRS and bowel TL (but not blood TL) may be clinically-useful predictors of CRC risk. Sample collection to assess these biomarkers is feasible in clinical practice, especially where population screening uses flexible sigmoidoscopy or colonoscopy.

Lahiff C, Mun Wang L, Travis SPL, East JE. 2018. Diagnostic Yield of Dysplasia in Polyp-adjacent Biopsies for Patients with Inflammatory Bowel Disease: A Cross-sectional Study. J Crohns Colitis, 12 (6), pp. 670-676. | Show Abstract | Read more

Introduction: Patients with inflammatory bowel disease (IBD) undergoing polypectomy are recommended by current guidelines to have biopsies taken from adjacent mucosa to determine whether there is dysplasia present. With improvements in endoscopic imaging, it is now possible to characterize colonic lesions with higher levels of confidence than previously. We have reviewed the diagnostic yield of polyp-adjacent biopsies in IBD. Materials and Methods: A systematic search of our histopathology database revealed cases in which polyps had been endoscopically resected or biopsied in patients with IBD. Endoscopy reports and medical records were reviewed, and patient demographic and disease-specific details were recorded, along with details of polyp characteristics and histopathology outcomes. Results: Three hundred and two polyps were biopsied or resected in 131 patients undergoing 178 colonoscopies. The median polyp size was 4 mm (range 1-45), and the predominant morphology was Paris 0-Is (n = 98, 32%). The histology was tubular adenoma in 76 (25%), tubulovillous adenoma in 14 (5%), hyperplastic in 112 (37%), post-inflammatory in 32 (11%), sessile serrated polyp in 31 (10%), traditional serrated adenoma in 2 (0.7%), flat high-grade dysplasia or cancer in 2 (0.7%) and other in 33 (11%). Dysplasia in adjacent biopsies was detected in 2 patients (0.7%), and was endoscopically visible in both cases. The proportion of endoscopically unsuspected dysplasia was 0/300 (0%, 95% CI 0-1.6%). Conclusion: The diagnostic yield for polyp-adjacent biopsies in patients with IBD is negligible. With high-definition technology and chromoendoscopy, it may no longer be necessary to biopsy endoscopically normal adjacent tissue to detect invisible dysplasia.

East JE, Rees CJ. 2018. Making optical biopsy a clinical reality in colonoscopy. Lancet Gastroenterol Hepatol, 3 (1), pp. 10-12. | Read more

Suzuki N, Toyonaga T, East JE. 2017. Endoscopic submucosal dissection of colitis-related dysplasia. Endoscopy, 49 (12), pp. 1237-1242. | Show Abstract | Read more

Background and study aims Endoscopic submucosal dissection (ESD) offers en bloc resection of lesions, allowing precise pathological assessment. Although possible in ulcerative colitis (UC) patients, the chronic inflammation may increase the procedural risks and reduce the complete resection rate. The aim of this study was to assess the feasibility of ESD for UC and to consider the factors contributing to its technical difficulty. Patients and methods Multicenter experiences of ESD for UC were retrospectively analyzed by reviewing endoscopic videos, pictures, reports, and clinical notes. Results A total of 32 dysplastic lesions were included (23 in British patients, 9 in Japanese patients). The lesions were macroscopically flat or with subtle extension macroscopically in 30 patients (94 %), with a median size of 33 mm (range 12 - 73 mm), and were located in the distal colon, including one on a pouch anastomosis. Submucosal fibrosis and adipose deposition were observed in 31 (97 %) and 13 lesions (41 %), respectively. En bloc resection was possible in 29/32 lesions (91 %). One patient had delayed bleeding. Advanced pathology was observed in 11 lesions (35 %). Recurrence was observed in only one patient (after a median of 33 months [range 6 - 76 months]); however, three patients developed metachronous lesions. Conclusions ESD is feasible for UC dysplasia without an increased rate of complications. Submucosal fibrosis and fat deposition were frequently observed and contributed to the technical complexity. Careful and intensive follow-up should be organized to detect metachronous lesions.

Parker B, Buchanan J, Wordsworth S, Keshav S, George B, East JE. 2017. Surgery versus surveillance in ulcerative colitis patients with endoscopically invisible low-grade dysplasia: a cost-effectiveness analysis. Gastrointest Endosc, 86 (6), pp. 1088-1099.e5. | Show Abstract | Read more

BACKGROUND AND AIMS: There is uncertainty regarding the optimal management of endoscopically invisible (flat) low-grade dysplasia in ulcerative colitis. Such a finding does not currently provide an automatic indication for colectomy; however, a recommendation of surveillance instead of surgery is controversial. The aim of this study was to determine the clinical and cost-effectiveness of colonoscopic surveillance versus colectomy for endoscopically invisible low-grade dysplasia of the colon in ulcerative colitis. METHODS: A Markov model was used to evaluate the costs and health outcomes of surveillance and surgery over a 20-year timeframe. Outcomes evaluated were life years gained and quality-adjusted life years (QALYs). Cohorts of patients aged 25 to 75 were modeled, including estimates from a validated surgical risk calculator and considering none, 1, or both of 2 key comorbidities: heart failure and obstructive airway disease. RESULTS: Surveillance is associated with more life years and QALYs compared with surgery from age 61 for those with no comorbidities, age 51 for those with 1 comorbidity and age 25 for those with 2 comorbidities. At the current United Kingdom National Institute for Health and Care Excellence threshold of $25,800 per QALY, ongoing surveillance was cost-effective at age 65 in those without comorbidities and at age 60 in those with either 1 or more comorbidities. CONCLUSIONS: Surveillance can be recommended from age 65 for those with no comorbidities; however, in younger patients with typical postsurgical quality of life, colectomy may be more effective clinically and more cost-effective. The results were sensitive to the colorectal cancer incidence rate in patients under surveillance and to quality of life after surgery.

Schwerd T, Bryant RV, Pandey S, Capitani M, Meran L, Cazier J-B, Jung J, Mondal K, Parkes M, Mathew CG et al. 2018. NOX1 loss-of-function genetic variants in patients with inflammatory bowel disease. Mucosal Immunol, 11 (2), pp. 562-574. | Show Abstract | Read more

Genetic defects that affect intestinal epithelial barrier function can present with very early-onset inflammatory bowel disease (VEOIBD). Using whole-genome sequencing, a novel hemizygous defect in NOX1 encoding NAPDH oxidase 1 was identified in a patient with ulcerative colitis-like VEOIBD. Exome screening of 1,878 pediatric patients identified further seven male inflammatory bowel disease (IBD) patients with rare NOX1 mutations. Loss-of-function was validated in p.N122H and p.T497A, and to a lesser degree in p.Y470H, p.R287Q, p.I67M, p.Q293R as well as the previously described p.P330S, and the common NOX1 SNP p.D360N (rs34688635) variant. The missense mutation p.N122H abrogated reactive oxygen species (ROS) production in cell lines, ex vivo colonic explants, and patient-derived colonic organoid cultures. Within colonic crypts, NOX1 constitutively generates a high level of ROS in the crypt lumen. Analysis of 9,513 controls and 11,140 IBD patients of non-Jewish European ancestry did not reveal an association between p.D360N and IBD. Our data suggest that loss-of-function variants in NOX1 do not cause a Mendelian disorder of high penetrance but are a context-specific modifier. Our results implicate that variants in NOX1 change brush border ROS within colonic crypts at the interface between the epithelium and luminal microbes.

Bisschops R, Bessissow T, Dekker E, East JE, Para-Blanco A, Ragunath K, Bhandari P, Rutter M, Schoon E, Wilson A et al. 2017. Pit pattern analysis with high-definition chromoendoscopy and narrow-band imaging for optical diagnosis of dysplasia in patients with ulcerative colitis. Gastrointest Endosc, 86 (6), pp. 1100-1106.e1. | Show Abstract | Read more

BACKGROUND AND AIMS: Patients with longstanding ulcerative colitis (UC) are at increased risk of developing colorectal neoplasia. Chromoendoscopy (CE) increases detection of lesions, and Kudo pit pattern classification I and II have been suggested to be predictive of benign polyps in UC. Little is known on the use of this classification in nonmagnified high-definition (HD) (virtual) CE and narrow-band Imaging (NBI) or on the interobserver agreement. The aim of this pilot study was to assess the diagnostic accuracy and the interobserver agreement of the Kudo pit pattern classification in UC patients undergoing surveillance with methylene blue CE or NBI in a multicenter study. METHODS: Fifty images of lesions identified in 27 UC patients (13 neoplastic) either with classical CE (methylene blue .1%; n = 24) or NBI (n = 26) were selected by an independent investigator. Images were selected from a randomized controlled trial to compare CE and NBI. All nonmagnified images were obtained with a processor and mounted in a PowerPoint file in a standardized way (same size; black background). Ten endoscopists with extensive experience in NBI/CE were asked to assess the lesions for the predominant Kudo pit pattern (I, II, IIIL, IIIS, IV, and V) to indicate if they believed the lesion was neoplastic and how confident they were about the diagnosis. Histology was used as the criterion standard. RESULTS: Median sensitivity, specificity, negative predictive value, and positive predictive value for diagnosing neoplasia based on the presence of pit pattern other than I or II was 77%, 68%, 88%, and 46%, respectively. Diagnostic accuracy was significantly higher when a diagnosis was made with a high level of confidence (77% vs 21%, P < .001). The overall interobserver agreement for any pit pattern was only fair (κ = .282), with CE being significantly better than NBI (.322 vs .224, P < .001). From a clinical viewpoint the difference between neoplastic and non-neoplastic lesions is important. The agreement for differentiation between non-neoplastic patterns (I, II) and neoplastic patterns (IIIL, IIIS, IV, or V) was moderate (κ = .587) and even significantly better for NBI in comparison with CE (κ = .653 vs .495, P < .001). CONCLUSIONS: Differentiation between non-neoplastic and neoplastic pit patterns in UC lesions shows a moderate to substantial agreement among expert endoscopists. The agreement for differentiating neoplastic from non-neoplastic lesions is significantly better for NBI in comparison with HD CE. The assessment of pit pattern I or II with nonmagnified HD CE or NBI has a high negative predictive value to rule out neoplasia. (Clinical trial registration number: NCT01882205.).

Oakland K, Isherwood J, Lahiff C, Goldsmith P, Desborough M, Colman KS, Guy R, Uberoi R, Murphy MF, East JE et al. 2017. Diagnostic and therapeutic treatment modalities for acute lower gastrointestinal bleeding: a systematic review. Endosc Int Open, 5 (10), pp. E959-E973. | Show Abstract | Read more

BACKGROUND AND STUDY AIMS:  Investigations for lower gastrointestinal bleeding (LGIB) include flexible sigmoidoscopy, colonoscopy, computed tomographic angiography (CTA), and angiography. All may be used to direct endoscopic, radiological or surgical treatment, although their optimal use is unknown. The aims of this study were to determine the diagnostic and therapeutic yields of endoscopy, CTA, and angiography for managing LGIB, and their influence on rebleeding, transfusion, and hospital stay. PATIENTS AND METHODS:  A systematic search of MEDLINE, PubMed, EMBASE, and CENTRAL was undertaken to identify randomized controlled trials (RCTs) and nonrandomized studies of intervention (NRSIs) published between 2000 and 12 November 2015 in patients hospitalized with LGIB. Separate meta-analyses were conducted, presented as pooled odds (ORs) or risk ratios (RR) with 95 % confidence intervals (CIs). RESULTS:  Two RCTs and 13 NRSIs were included, none of which examined flexible sigmoidoscopy, or compared endotherapy with embolization, or investigated the timing of CTA or angiography. Two NRSIs (57 - 223 participants) comparing colonoscopy and CTA were of insufficient quality for synthesis but showed no difference in diagnostic yields between the two interventions. One RCT and 4 NRSIs (779 participants) compared early colonoscopy (< 24 hours) with colonoscopy performed later; meta-analysis of the NRSIs demonstrated higher diagnostic and therapeutic yields with early colonoscopy (OR 1.86, 95 %CI 1.12 to 2.86, P  = 0.004 and OR 3.08, 95 %CI 1.93 to 4.90, P  < 0.001, respectively) and reduced length of stay (mean difference 2.64 days, 95 %CI 1.54 to 3.73), but no difference in transfusion or rebleeding. CONCLUSIONS:  In LGIB there is a paucity of high-quality evidence, although the limited studies on the timing of colonoscopy suggest increased rates of diagnosis and therapy with early colonoscopy.

Bye WA, Nguyen TM, Parker CE, Jairath V, East JE. 2017. Strategies for detecting colon cancer in patients with inflammatory bowel disease. Cochrane Database Syst Rev, 9 (9), pp. CD000279. | Show Abstract | Read more

BACKGROUND: Patients with longstanding ulcerative colitis and colonic Crohn's disease have an increased risk of colorectal cancer (CRC) compared with the general population. This review assessed the evidence that endoscopic surveillance may prolong life by allowing earlier detection of CRC or its pre-cursor lesion, dysplasia, in patients with inflammatory bowel disease (IBD). OBJECTIVES: To assess the effectiveness of cancer surveillance programs for diagnosis of IBD-associated colorectal cancer and in reducing the mortality rate from colorectal cancer in patients with IBD. SEARCH METHODS: We searched MEDLINE, EMBASE, CENTRAL and clinical clinicaltrials.gov from inception to 19 September 2016. We also searched conference abstracts and reference lists to identify additional studies. SELECTION CRITERIA: Potentially relevant articles were reviewed independently and unblinded by two authors to determine eligibility. Randomised controlled trials (RCTs) or observational studies (cohort or case control) assessing any form of endoscopic surveillance aimed at early detection of CRC were considered for inclusion. Studies had to have a no surveillance comparison group to be eligible for inclusion. DATA COLLECTION AND ANALYSIS: Eligible studies were reviewed in duplicate and the results of the primary research trials were independently extracted by two authors. The primary outcome was detection of CRC. Secondary outcomes included death from CRC, time to cancer detection, time to death and adverse events. Deaths from CRC were derived from life tables, survival curves or where possible, by calculating life tables from the data provided. The presence of significant heterogeneity among studies was tested by the chi-square test. Because this is a relatively insensitive test, a P value of less than 0.1 was considered statistically significant. Provided statistical heterogeneity was not present, the fixed effects model was used for the pooling of data. The 2x2 tables were combined into a summary test statistic using the pooled odds ratio (OR) and 95% confidence intervals as described by Cochrane and Mantel and Haenszel. The methodological quality of the included studies was assessed using the Newcastle-Ottawa scale for non-randomised studies The overall quality of the evidence supporting the primary and selected secondary outcomes was assessed using the GRADE criteria. MAIN RESULTS: No RCTs were identified. Five observational studies (N = 7199) met the inclusion criteria. The studies scored well on the Newcastle-Ottawa scale, but due to the nature of observational studies, a high risk of bias was assigned to all the studies. Three studies were pooled to assess the rate of cancer detected in the surveillance group compared to the non-surveillance group. The studies found a significantly higher rate of cancer detection in the non surveillance group compared to the surveillance group. CRC was detected in 1.83% (53/2895) of patients in the surveillance group compared to 3.17% (135/4256) of patients in the non-surveillance group (OR 0.58, 95% CI 0.42 to 0.80; P = 0.0009). Four studies were pooled to assess the death rate associated with CRC in patients who underwent surveillance compared to patients who did not undergo surveillance. There was a significantly lower death rate associated with CRC in the surveillance group compared to the non-surveillance group. Eight per cent (15/176) of patients in the surveillance group died from CRC compared to 22% (79/354) of patients in the non-surveillance group (OR 0.36, 95% CI 0.19 to 0.69, P=0.002). Data were pooled from two studies to examine the rate of early stage versus late stage colorectal cancer (Duke stages A & B compared to Duke stages C & D) in patients who underwent surveillance compared to patients who do not undergo surveillance. A significantly higher rate of early stage CRC (Duke A & B) was detected in the surveillance group compared to the non-surveillance group. Sixteen per cent (17/110) of patients in the surveillance group had early stage CRC compared to 8% (9/117) of patients in the non-surveillance group (OR 5.40, 95% CI 1.51 to 19.30; P = 0.009). A higher rate of late stage CRC (Duke C & D) was observed in the non-surveillance group compared to the surveillance group. Nine per cent (10/110) of patients in the surveillance group had late stage CRC compared to 16% (19/117) of patients in the non-surveillance group (OR 0.46, 95% CI 0.08 to 2.51; P = 0.37). A GRADE analysis indicated that the quality of the data was very low for all of these outcomes. The included studies did not report on the other pre-specified outcomes including time to cancer detection, time to death and adverse events. AUTHORS' CONCLUSIONS: The current data suggest that colonoscopic surveillance in IBD may reduce the development of both CRC and the rate of CRC-associated death through early detection, although the quality of the evidence is very low. The detection of earlier stage CRC in the surveillance group may explain some of the survival benefit observed. RCTs assessing the efficacy of endoscopic surveillance in people with IBD are unlikely to be undertaken due to ethical considerations.

Irshad S, Bansal M, Guarnieri P, Davis H, Zen AAH, Baran B, Pinna CMA, Rahman H, Biswas S, Bardella C et al. 2017. Bone morphogenetic protein and Notch signalling crosstalk in poor-prognosis, mesenchymal-subtype colorectal cancer JOURNAL OF PATHOLOGY, 242 (2), pp. 178-192. | Show Abstract | Read more

© 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. The functional role of bone morphogenetic protein (BMP) signalling in colorectal cancer (CRC) is poorly defined, with contradictory results in cancer cell line models reflecting the inherent difficulties of assessing a signalling pathway that is context-dependent and subject to genetic constraints. By assessing the transcriptional response of a diploid human colonic epithelial cell line to BMP ligand stimulation, we generated a prognostic BMP signalling signature, which was applied to multiple CRC datasets to investigate BMP heterogeneity across CRC molecular subtypes. We linked BMP and Notch signalling pathway activity and function in human colonic epithelial cells, and normal and neoplastic tissue. BMP induced Notch through a γ-secretase-independent interaction, regulated by the SMAD proteins. In homeostasis, BMP/Notch co-localization was restricted to cells at the top of the intestinal crypt, with more widespread interaction in some human CRC samples. BMP signalling was downregulated in the majority of CRCs, but was conserved specifically in mesenchymal-subtype tumours, where it interacts with Notch to induce an epithelial–mesenchymal transition (EMT) phenotype. In intestinal homeostasis, BMP–Notch pathway crosstalk is restricted to differentiating cells through stringent pathway segregation. Conserved BMP activity and loss of signalling stringency in mesenchymal-subtype tumours promotes a synergistic BMP–Notch interaction, and this correlates with poor patient prognosis. BMP signalling heterogeneity across CRC subtypes and cell lines can account for previous experimental contradictions. Crosstalk between the BMP and Notch pathways will render mesenchymal-subtype CRC insensitive to γ-secretase inhibition unless BMP activation is concomitantly addressed. © 2017 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

East JE, Atkin WS, Bateman AC, Clark SK, Dolwani S, Ket SN, Leedham SJ, Phull PS, Rutter MD, Shepherd NA et al. 2017. British Society of Gastroenterology position statement on serrated polyps in the colon and rectum. Gut, 66 (7), pp. 1181-1196. | Show Abstract | Read more

Serrated polyps have been recognised in the last decade as important premalignant lesions accounting for between 15% and 30% of colorectal cancers. There is therefore a clinical need for guidance on how to manage these lesions; however, the evidence base is limited. A working group was commission by the British Society of Gastroenterology (BSG) Endoscopy section to review the available evidence and develop a position statement to provide clinical guidance until the evidence becomes available to support a formal guideline. The scope of the position statement was wide-ranging and included: evidence that serrated lesions have premalignant potential; detection and resection of serrated lesions; surveillance strategies after detection of serrated lesions; special situations-serrated polyposis syndrome (including surgery) and serrated lesions in colitis; education, audit and benchmarks and research questions. Statements on these issues were proposed where the evidence was deemed sufficient, and re-evaluated modified via a Delphi process until >80% agreement was reached. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool was used to assess the strength of evidence and strength of recommendation for finalised statements. Key recommendation: we suggest that until further evidence on the efficacy or otherwise of surveillance are published, patients with sessile serrated lesions (SSLs) that appear associated with a higher risk of future neoplasia or colorectal cancer (SSLs ≥10 mm or serrated lesions harbouring dysplasia including traditional serrated adenomas) should be offered a one-off colonoscopic surveillance examination at 3 years (weak recommendation, low quality evidence, 90% agreement).

Tan M, Lahiff C, Bassett P, Bailey AA, East JE. 2017. Efficacy of Balloon Overtube-Assisted Colonoscopy in Patients With Incomplete or Previous Difficult Colonoscopies: A Meta-analysis. Clin Gastroenterol Hepatol, 15 (10), pp. 1628-1630. | Read more

West NR, Hegazy AN, Owens BMJ, Bullers SJ, Linggi B, Buonocore S, Coccia M, Görtz D, This S, Stockenhuber K et al. 2017. Oncostatin M drives intestinal inflammation and predicts response to tumor necrosis factor-neutralizing therapy in patients with inflammatory bowel disease. Nat Med, 23 (5), pp. 579-589. | Show Abstract | Read more

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are complex chronic inflammatory conditions of the gastrointestinal tract that are driven by perturbed cytokine pathways. Anti-tumor necrosis factor-α (TNF) antibodies are mainstay therapies for IBD. However, up to 40% of patients are nonresponsive to anti-TNF agents, which makes the identification of alternative therapeutic targets a priority. Here we show that, relative to healthy controls, inflamed intestinal tissues from patients with IBD express high amounts of the cytokine oncostatin M (OSM) and its receptor (OSMR), which correlate closely with histopathological disease severity. The OSMR is expressed in nonhematopoietic, nonepithelial intestinal stromal cells, which respond to OSM by producing various proinflammatory molecules, including interleukin (IL)-6, the leukocyte adhesion factor ICAM1, and chemokines that attract neutrophils, monocytes, and T cells. In an animal model of anti-TNF-resistant intestinal inflammation, genetic deletion or pharmacological blockade of OSM significantly attenuates colitis. Furthermore, according to an analysis of more than 200 patients with IBD, including two cohorts from phase 3 clinical trials of infliximab and golimumab, high pretreatment expression of OSM is strongly associated with failure of anti-TNF therapy. OSM is thus a potential biomarker and therapeutic target for IBD, and has particular relevance for anti-TNF-resistant patients.

Kaminski MF, Thomas-Gibson S, Bugajski M, Bretthauer M, Rees CJ, Dekker E, Hoff G, Jover R, Suchanek S, Ferlitsch M et al. 2017. Performance measures for lower gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative. Endoscopy, 49 (4), pp. 378-397. | Show Abstract | Read more

The European Society of Gastrointestinal Endoscopy and United European Gastroenterology present a short list of key performance measures for lower gastrointestinal endoscopy. We recommend that endoscopy services across Europe adopt the following seven key performance measures for lower gastrointestinal endoscopy for measurement and evaluation in daily practice at a center and endoscopist level: 1 Rate of adequate bowel preparation (minimum standard 90 %); 2 Cecal intubation rate (minimum standard 90 %); 3 Adenoma detection rate (minimum standard 25 %); 4 Appropriate polypectomy technique (minimum standard 80 %); 5 Complication rate (minimum standard not set); 6 Patient experience (minimum standard not set); 7 Appropriate post-polypectomy surveillance recommendations (minimum standard not set). Other identified performance measures have been listed as less relevant based on an assessment of their importance, scientific acceptability, feasibility, usability, and comparison to competing measures.

Kaminski MF, Thomas-Gibson S, Bugajski M, Bretthauer M, Rees CJ, Dekker E, Hoff G, Jover R, Suchanek S, Ferlitsch M et al. 2017. Performance measures for lower gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy (ESGE) quality improvement initiative. United European Gastroenterol J, 5 (3), pp. 309-334. | Show Abstract | Read more

The European Society of Gastrointestinal Endoscopy and United European Gastroenterology present a short list of key performance measures for lower gastrointestinal endoscopy. We recommend that endoscopy services across Europe adopt the following seven key performance measures for lower gastrointestinal endoscopy for measurement and evaluation in daily practice at a center and endoscopist level: 1 rate of adequate bowel preparation (minimum standard 90%); 2 cecal intubation rate (minimum standard 90%); 3 adenoma detection rate (minimum standard 25%); 4 appropriate polypectomy technique (minimum standard 80%); 5 complication rate (minimum standard not set); 6 patient experience (minimum standard not set); 7 appropriate post-polypectomy surveillance recommendations (minimum standard not set). Other identified performance measures have been listed as less relevant based on an assessment of their importance, scientific acceptability, feasibility, usability, and comparison to competing measures.

Lahiff C, East JE. 2017. Endoscopic approach to polyp recognition. Frontline Gastroenterol, 8 (2), pp. 98-103. | Show Abstract | Read more

Identification and complete resection of colorectal polyps provide a significant mortality benefit from colorectal cancer. With improvements in colonoscopic techniques and advanced endoscopic imaging techniques, polyp detection has taken on greater complexity since the establishment of bowel cancer screening programmes internationally. All endoscopists operating within symptomatic and screening populations should be aware of endoscopic features associated with advanced neoplasia. Chromoendoscopy and advanced imaging techniques, such as narrow spectrum technologies (narrow band imaging, flexible spectral imaging colour enhancement (FICE) and i-Scan digital contrast (iSCAN)), have specific classification systems to support accurate lesion characterisation. This review summarises the evidence in relation to polyp detection, recognition and characterisation as well as the identification of features of invasion. Future areas of interest include optimal management of large polyps, incorporation of a 'detect, resect and discard' strategy for small and diminutive polyps, expected wider use of computer decision support tools (artificial intelligence and deep learning) and the use of fluorescently labelled molecular probes to improve detection and assessment of neoplasia.

Monahan KJ, Alsina D, Bach S, Buchanan J, Burn J, Clark S, Dawson P, De Souza B, Din FVN, Dolwani S et al. 2017. Urgent improvements needed to diagnose and manage Lynch syndrome. BMJ, 356 pp. j1388. | Read more

Irshad S, Bansal M, Guarnieri P, Davis H, Al Haj Zen A, Baran B, Pinna CMA, Rahman H, Biswas S, Bardella C et al. 2017. Bone morphogenetic protein and Notch signalling crosstalk in poor-prognosis, mesenchymal-subtype colorectal cancer. J Pathol, 242 (2), pp. 178-192. | Show Abstract | Read more

The functional role of bone morphogenetic protein (BMP) signalling in colorectal cancer (CRC) is poorly defined, with contradictory results in cancer cell line models reflecting the inherent difficulties of assessing a signalling pathway that is context-dependent and subject to genetic constraints. By assessing the transcriptional response of a diploid human colonic epithelial cell line to BMP ligand stimulation, we generated a prognostic BMP signalling signature, which was applied to multiple CRC datasets to investigate BMP heterogeneity across CRC molecular subtypes. We linked BMP and Notch signalling pathway activity and function in human colonic epithelial cells, and normal and neoplastic tissue. BMP induced Notch through a γ-secretase-independent interaction, regulated by the SMAD proteins. In homeostasis, BMP/Notch co-localization was restricted to cells at the top of the intestinal crypt, with more widespread interaction in some human CRC samples. BMP signalling was downregulated in the majority of CRCs, but was conserved specifically in mesenchymal-subtype tumours, where it interacts with Notch to induce an epithelial-mesenchymal transition (EMT) phenotype. In intestinal homeostasis, BMP-Notch pathway crosstalk is restricted to differentiating cells through stringent pathway segregation. Conserved BMP activity and loss of signalling stringency in mesenchymal-subtype tumours promotes a synergistic BMP-Notch interaction, and this correlates with poor patient prognosis. BMP signalling heterogeneity across CRC subtypes and cell lines can account for previous experimental contradictions. Crosstalk between the BMP and Notch pathways will render mesenchymal-subtype CRC insensitive to γ-secretase inhibition unless BMP activation is concomitantly addressed. © 2017 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Lahiff C, Wang LM, Travis SPL, East JE. 2017. Zero diagnostic yield of dysplasia in polyp adjacent biopsies for patients with inflammatory bowel disease JOURNAL OF CROHNS & COLITIS, 11 pp. S16-S16.

Hartery K, Williamson K, Chapman R, Atkinson N, East J. 2017. Use of chromoendoscopy versus white light endoscopy for colorectal cancer surveillance in inflammatory bowel disease patients with primary sclerosing cholangitis; a six year experience JOURNAL OF CROHNS & COLITIS, 11 pp. S64-S64.

Thompson AG, Blackwell V, Marsden R, Millard E, Lawson C, Nickol AH, East JE, Talbot K, Allan PJ, Turner MR. 2017. A risk stratifying tool to facilitate safe late-stage percutaneous endoscopic gastrostomy in ALS. Amyotroph Lateral Scler Frontotemporal Degener, 18 (3-4), pp. 243-248. | Show Abstract | Read more

BACKGROUND: The safety of percutaneous endoscopic gastrostomy (PEG) insertion in amyotrophic lateral sclerosis (ALS) patients with significant respiratory compromise has been questioned. OBJECTIVES: To review the characteristics of an ALS clinic patient cohort undergoing PEG, and the introduction of a risk stratification tool with procedural adaptations for higher-risk individuals. METHODS: Patients undergoing PEG insertion were analysed (n = 107). Cases stratified as higher-risk underwent insertion in a semi-recumbent position, minimising sedation, with the option of nasal non-invasive ventilation. RESULTS: All underwent successful PEG. One-third had pre-procedure FVC ≤50% (mean, 64 ± 22%). Of those who underwent PEG insertion after introduction of risk stratification (n = 58), 39 (67%) met criteria for being higher risk, 16 (41%) of whom had FVC ≤50% (p = 0.005). High-risk patients received lower sedative doses vs. the low-risk group (midazolam 2.1 ± 1.1 vs.2.8 ± 0.95mg, p = 0.021; fentanyl 42 ± 16 vs. 60 ± 21μg, p = 0.015). Four deaths occurred within one month of insertion (attributable to the natural disease course). CONCLUSIONS: Risk stratification identified a greater number of patients with evidence of respiratory compromise than using the sole criterion of FVC ≤50%. A modified PEG procedure enabled safe insertion despite respiratory compromise, in those who might not have tolerated attempted insertion by alternative means such as radiologically-inserted gastrostomy.

Yu JX, East JE, Kaltenbach T. 2016. Surveillance of patients with inflammatory bowel disease. Best Pract Res Clin Gastroenterol, 30 (6), pp. 949-958. | Show Abstract | Read more

Patients with inflammatory bowel disease involving the colon are at increased risk for developing colorectal cancer. Colonoscopy surveillance is important to identify and treat IBD associated dysplasia. The SCENIC consensus provides evidence-based recommendations for optimal surveillance and management of dysplasia in IBD. Chromoendoscopy, with the surface application of dyes to enhance mucosal visualization, is the superior endoscopic surveillance strategy to detect dysplasia. Most dysplasia is visible, and can be endoscopically resected. Future studies should determine the effect of new surveillance strategies on the incidence of CRC and mortality in patients with IBD.

East JE, Vleugels JL, Roelandt P, Bhandari P, Bisschops R, Dekker E, Hassan C, Horgan G, Kiesslich R, Longcroft-Wheaton G et al. 2016. Advanced endoscopic imaging: European Society of Gastrointestinal Endoscopy (ESGE) Technology Review. Endoscopy, 48 (11), pp. 1029-1045. | Show Abstract | Read more

Background and aim: This technical review is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the utilization of advanced endoscopic imaging in gastrointestinal (GI) endoscopy. Methods: This technical review is based on a systematic literature search to evaluate the evidence supporting the use of advanced endoscopic imaging throughout the GI tract. Technologies considered include narrowed-spectrum endoscopy (narrow band imaging [NBI]; flexible spectral imaging color enhancement [FICE]; i-Scan digital contrast [I-SCAN]), autofluorescence imaging (AFI), and confocal laser endomicroscopy (CLE). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendation and the quality of evidence. Main recommendations:1. We suggest advanced endoscopic imaging technologies improve mucosal visualization and enhance fine structural and microvascular detail. Expert endoscopic diagnosis may be improved by advanced imaging, but as yet in community-based practice no technology has been shown consistently to be diagnostically superior to current practice with high definition white light. (Low quality evidence.) 2. We recommend the use of validated classification systems to support the use of optical diagnosis with advanced endoscopic imaging in the upper and lower GI tracts (strong recommendation, moderate quality evidence). 3. We suggest that training improves performance in the use of advanced endoscopic imaging techniques and that it is a prerequisite for use in clinical practice. A learning curve exists and training alone does not guarantee sustained high performances in clinical practice. (Weak recommendation, low quality evidence.) Conclusion: Advanced endoscopic imaging can improve mucosal visualization and endoscopic diagnosis; however it requires training and the use of validated classification systems.

Marsden R, Allan P, Blackwell V, East J, Lawson C, Nickol AH, Millard E, Talbot K, Thompson AG, Turner MR. 2016. Nutritional pathway for people with motor neurone disease. Br J Community Nurs, 21 (7), pp. 360-363. | Show Abstract | Read more

This paper provides an overview of the nutritional management and care of people living with motor neurone disease (MND) in a specialist nutrition clinic. A specialist pathway of care has been developed to enable people living with MND to undergo a percutaneous endoscopic gastrostomy (PEG) procedure in a safe way; the pathway incorporates attendance at a dedicated nutrition clinic, a stratification tool to identify patients with a high periprocedural risk and a PEG insertion team with significant experience in the MND population. Since this pathway has been in place, gastrostomies have been successfully placed in patients with a forced vital capacity (FVC) of less than 50%; previously, this would not have been possible.

Rees CJ, Rajasekhar PT, Wilson A, Close H, Rutter MD, Saunders BP, East JE, Maier R, Moorghen M, Muhammad U et al. 2017. Narrow band imaging optical diagnosis of small colorectal polyps in routine clinical practice: the Detect Inspect Characterise Resect and Discard 2 (DISCARD 2) study. Gut, 66 (5), pp. 887-895. | Show Abstract | Read more

BACKGROUND: Accurate optical characterisation and removal of small adenomas (<10 mm) at colonoscopy would allow hyperplastic polyps to be left in situ and surveillance intervals to be determined without the need for histopathology. Although accurate in specialist practice the performance of narrow band imaging (NBI), colonoscopy in routine clinical practice is poorly understood. METHODS: NBI-assisted optical diagnosis was compared with reference standard histopathological findings in a prospective, blinded study, which recruited adults undergoing routine colonoscopy in six general hospitals in the UK. Participating colonoscopists (N=28) were trained using the NBI International Colorectal Endoscopic (NICE) classification (relating to colour, vessel structure and surface pattern). By comparing the optical and histological findings in patients with only small polyps, test sensitivity was determined at the patient level using two thresholds: presence of adenoma and need for surveillance. Accuracy of identifying adenomatous polyps <10 mm was compared at the polyp level using hierarchical models, allowing determinants of accuracy to be explored. FINDINGS: Of 1688 patients recruited, 722 (42.8%) had polyps <10 mm with 567 (78.5%) having only polyps <10 mm. Test sensitivity (presence of adenoma, N=499 patients) by NBI optical diagnosis was 83.4% (95% CI 79.6% to 86.9%), significantly less than the 95% sensitivity (p<0.001) this study was powered to detect. Test sensitivity (need for surveillance) was 73.0% (95% CI 66.5% to 79.9%). Analysed at the polyp level, test sensitivity (presence of adenoma, N=1620 polyps) was 76.1% (95% CI 72.8% to 79.1%). In fully adjusted analyses, test sensitivity was 99.4% (95% CI 98.2% to 99.8%) if two or more NICE adenoma characteristics were identified. Neither colonoscopist expertise, confidence in diagnosis nor use of high definition colonoscopy independently improved test accuracy. INTERPRETATION: This large multicentre study demonstrates that NBI optical diagnosis cannot currently be recommended for application in routine clinical practice. Further work is required to evaluate whether variation in test accuracy is related to polyp characteristics or colonoscopist training. TRIAL REGISTRATION NUMBER: The study was registered with clinicaltrials.gov (NCT01603927).

East JE, Wang LM. 2016. Response. Gastrointest Endosc, 83 (3), pp. 675-676. | Read more

Rajasekhar PT, Rees CJ, Nixon C, East JE, Brown S. 2016. Factors influencing change in clinical practice: A qualitative evaluation of the implementation of the quality improvement in colonoscopy study. Int J Health Care Qual Assur, 29 (1), pp. 5-15. | Show Abstract | Read more

PURPOSE: The quality improvement in colonoscopy study was a region wide service improvement study to improve adenoma detection rate at colonoscopy by implementing evidence into routine colonoscopy practice. Implementing evidence into clinical practice can be challenging. The purpose of this paper is to perform a qualitative interview study to evaluate factors that influenced implementation within the study. DESIGN/METHODOLOGY/APPROACH: Semi-structured interviews were conducted with staff in endoscopy units taking part in the quality improvement in colonoscopy study, after study completion. Units and interviewees were purposefully sampled to ensure a range of experiences was represented. Interviews were conducted with 11 participants. FINDINGS: Key themes influencing uptake of the quality improvement in colonoscopy evidence bundle included time, study promotion, training, engagement, positive outcomes and modifications. Areas within themes were increased awareness of quality in colonoscopy (QIC), emphasis on withdrawal time and empowerment of endoscopy nurses to encourage the use of quality measures were positive outcomes of the study. The simple, visible study posters were reported as useful in aiding study promotion. Feedback sessions improved engagement. Challenges included difficulty arranging set-up meetings and engaging certain speciality groups. ORIGINALITY/VALUE: This evaluation suggests that methods to implement evidence into clinical practice should include identification and empowerment of team members who can positively influence engagement, simple, visible reminders and feedback. Emphasis on timing of meetings and strategies to engage speciality groups should also be given consideration. Qualitative evaluations can provide important insights into why quality improvement initiatives are successful or not, across different sites.

Koutsoumpas A, East JE. 2016. What can we learn from publishing endoscopy trial protocols? Endosc Int Open, 4 (2), pp. E213-E214. | Read more

East JE, Saunders BP, Burling D, Tam E, Boone D, Halligan S, Taylor SA. 2015. Mechanisms of hyoscine butylbromide to improve adenoma detection: A case-control study of surface visualization at simulated colonoscope withdrawal. Endosc Int Open, 3 (6), pp. E636-E641. | Show Abstract | Read more

BACKGROUND AND STUDY AIMS: Antispasmodics may improve mucosal visualization during colonoscope withdrawal, potentially improving polyp and adenoma detection. Meta-analysis and case-control studies suggest a 9 % to 13 % relative increase in adenoma and polyp detection. We aimed to assess the impact of hyoscine butylbromide on the expected visualization during colonoscope withdrawal using a CT colonography (CTC) simulation. PATIENTS AND METHODS: Datasets from a previous CTC study examining the effect of antispasmodic were re-analyzed with customised CTC software, adjusted to simulate a standard colonoscopic view. Eighty-six patients received intravenous (IV) hyoscine butylbromide 20 mg, 40 mg or no antispasmodic. Main outcome measurements at unidirectional flythrough, simulating colonoscope withdrawal, were percentage colonic surface visualization, numbers and sizes of unseen areas, and colonic length. RESULTS: Use of antispasmodic was associated with a significant relative increase in percentage surface visualization of 2.6 % to 3.9 %, compared with no antispasmodic, P < 0.006. Total numbers of missed areas and intermediate sized (300 - 1000 mm(2)) missed areas were significantly decreased, by approximately 20 %. There were no differences between the 20-mg and 40-mg doses. Mean colonic length (161 - 169 cm) was unchanged by antispasmodic. CONCLUSIONS: IV hyoscine butylbromide at simulated colonoscope withdrawal was associated with significant increases in surface visualization, which might explain up to half the improvement in adenoma detection seen in clinical studies.

IJspeert JEG, Rana SAQ, Atkinson NSS, van Herwaarden YJ, Bastiaansen BAJ, van Leerdam ME, Sanduleanu S, Bisseling TM, Spaander MCW, Clark SK et al. 2017. Clinical risk factors of colorectal cancer in patients with serrated polyposis syndrome: a multicentre cohort analysis. Gut, 66 (2), pp. 278-284. | Show Abstract | Read more

OBJECTIVE: Serrated polyposis syndrome (SPS) is accompanied by an increased risk of colorectal cancer (CRC). Patients fulfilling the clinical criteria, as defined by the WHO, have a wide variation in CRC risk. We aimed to assess risk factors for CRC in a large cohort of patients with SPS and to evaluate the risk of CRC during surveillance. DESIGN: In this retrospective cohort analysis, all patients with SPS from seven centres in the Netherlands and two in the UK were enrolled. WHO criteria were used to diagnose SPS. Patients who only fulfilled WHO criterion-2, with IBD and/or a known hereditary CRC syndrome were excluded. RESULTS: In total, 434 patients with SPS were included for analysis; 127 (29.3%) were diagnosed with CRC. In a per-patient analysis ≥1 serrated polyp (SP) with dysplasia (OR 2.07; 95% CI 1.28 to 3.33), ≥1 advanced adenoma (OR 2.30; 95% CI 1.47 to 3.67) and the fulfilment of both WHO criteria 1 and 3 (OR 1.60; 95% CI 1.04 to 2.51) were associated with CRC, while a history of smoking was inversely associated with CRC (OR 0.36; 95% CI 0.23 to 0.56). Overall, 260 patients underwent surveillance after clearing of all relevant lesions, during which two patients were diagnosed with CRC, corresponding to 1.9 events/1000 person-years surveillance (95% CI 0.3 to 6.4). CONCLUSION: The presence of SPs containing dysplasia, advanced adenomas and/or combined WHO criteria 1 and 3 phenotype is associated with CRC in patients with SPS. Patients with a history of smoking show a lower risk of CRC, possibly due to a different pathogenesis of disease. The risk of developing CRC during surveillance is lower than previously reported in literature, which may reflect a more mature multicentre cohort with less selection bias.

Veitch AM, Uedo N, Yao K, East JE. 2015. Optimizing early upper gastrointestinal cancer detection at endoscopy. Nat Rev Gastroenterol Hepatol, 12 (11), pp. 660-667. | Show Abstract | Read more

Survival rates for upper gastrointestinal cancers are poor and oesophageal cancer incidence is increasing. Upper gastrointestinal cancer is also often missed during examinations; a predicament that has not yet been sufficiently addressed. Improvements in the detection of premalignant lesions, early oesophageal and gastric cancers will enable organ-preserving endoscopic therapy, potentially reducing the number of advanced upper gastrointestinal cancers and resulting in improved prognosis. Japan is a world leader in high-quality diagnostic upper gastrointestinal endoscopy and the clinical routine in this country differs substantially from Western practice. In this Perspectives article, we review lessons learnt from Japanese gastroscopy technique, training and screening for risk stratification. We suggest a key performance indicator for upper gastrointestinal endoscopy with a minimum total procedure time of 8 min, and examine how quality assurance concepts in bowel cancer screening in the UK could be applied to upper gastrointestinal endoscopy and improve clinical practice.

Luzzatto L, Pandolfi PP. 2015. Causality and Chance in the Development of Cancer. N Engl J Med, 373 (16), pp. 1579. | Read more

East JE, Travis SPL, Leedham SJ. 2015. Causality and Chance in the Development of Cancer. N Engl J Med, 373 (16), pp. 1578-1579. | Read more

Wang LM, East JE. 2015. Diminutive polyp cancers and the DISCARD strategy: Much ado about nothing or the end of the affair? GASTROINTESTINAL ENDOSCOPY, 82 (3), pp. 589-592. | Read more

Wang LM, East JE. 2015. Diminutive polyp cancers and the DISCARD strategy: Much ado about nothing or the end of the affair? Gastrointest Endosc, 82 (2), pp. 385-388. | Read more

Colling R, Church DN, Carmichael J, Murphy L, East J, Risby P, Kerr R, Chetty R, Wang LM. 2015. Screening for Lynch syndrome and referral to clinical genetics by selective mismatch repair protein immunohistochemistry testing: an audit and cost analysis. J Clin Pathol, 68 (12), pp. 1036-1039. | Show Abstract | Read more

Lynch syndrome (LS) accounts for around 3% of colorectal cancers (CRCs) and is caused by germline mutations in mismatch repair (MMR) genes. Recently, screening strategies to identify patients with LS have become popular. We audited CRCs screened with MMR immunohistochemistry (IHC) in 2013. 209 tumours had MMR IHC performed at a cost of £12 540. 47/209 (21%) cases showed IHC loss of expression in at least one MMR protein. 28/44 cases with loss of MLH1 had additional BRAF V600E testing, at a cost of £5040. MMR IHC reduced the number of potential clinical genetics referrals from 209 to 47. BRAF mutation testing, performed in a subset of cases with MLH1 loss, further reduced this to 21. At a cost of £1340 per referral, this model of LS screening for clinical genetics referral had significant potential savings (£234 340) and can be easily implemented in parallel with MMR IHC done for prognostication in CRCs.

Atkinson NS, East JE. 2015. Optical biopsy and sessile serrated polyps: Is DISCARD dead? Long live DISCARD-lite! Gastrointest Endosc, 82 (1), pp. 118-121. | Read more

Bhat SK, East JE. 2015. Colorectal cancer: prevention and early diagnosis Medicine, 43 (6), pp. 295-298. | Show Abstract | Read more

© 2015 Elsevier Ltd. All rights reserved. Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. This article examines strategies for the prevention and early diagnosis of CRC, and reviews the aetiology and risk factors for CRC. Preventative strategies involve improving modifiable risk factors through public health awareness. Patients known to be at higher risk of CRC development, such as those with a genetic predisposition or long-standing inflammatory bowel disease, should undergo endoscopic surveillance in order to detect early cancer or polyps. Population screening for CRC is now strongly established as an effective method for the early detection of CRC and prevention through polypectomy. Screening has been shown to improve the stage of disease at diagnosis and CRC-specific mortality. This article will highlight recent developments in the understanding of the serrated pathway for CRC development and discuss the clinical relevance of this in terms of cancer prevention, as well as exploring future directions for research into the prevention and early diagnosis of CRC.

East JE, Vieth M, Rex DK. 2015. Serrated lesions in colorectal cancer screening: detection, resection, pathology and surveillance. Gut, 64 (6), pp. 991-1000. | Read more

Toyonaga T, Tanaka S, Man-I M, East J, Ono W, Nishino E, Ishida T, Hoshi N, Morita Y, Azuma T. 2015. Clinical significance of the muscle-retracting sign during colorectal endoscopic submucosal dissection. Endosc Int Open, 3 (3), pp. E246-E251. | Show Abstract | Read more

BACKGROUND AND STUDY AIMS: During colorectal endoscopic submucosal dissection (ESD), the feature of a muscle layer being pulled toward a neoplastic tumor is sometimes detected. We call this feature the muscle-retracting sign (MR sign). The aim of this study was to evaluate whether the MR sign is associated with particular types of neoplastic lesions and whether it has any clinical significance for ESD sessions. PATIENTS AND METHODS: A total of 329 patients underwent ESD for 357 colorectal neoplasms. The frequency of positivity for the MR sign was evaluated in different morphologic and histopathologic types of neoplasm. The success rate of complete resection and the incidence of complications were also evaluated according to whether lesions were positive or negative for the MR sign. RESULTS: The rates of positivity for the MR sign in the various lesion types were as follows: laterally spreading tumor - granular nodular mixed type (LST-G-M), 9.6 %; laterally spreading tumor - granular homogeneous type (LST-G-H) and laterally spreading tumor - nongranular type (LST-NG), 0 %; sessile type, 41.2 %. The resection rate was 100 % (329 /329) in lesions negative for the MR sign; however, it was 64.3 % (18 /28) in lesions positive for the MR sign, which was significantly lower (P < 0.001). CONCLUSIONS: The MR sign was present only in some protruding lesions, and more importantly, it was associated with a high risk of incomplete tumor removal by ESD. Our data indicate that lesions positive for the MR sign lesions should be dissected with great caution; alternatively, based on the features of the individual case, a switch to surgery should be considered for the benefit of the patient.

Ket SN, Bird-Lieberman E, East JE. 2015. Electronic imaging to enhance lesion detection at colonoscopy. Gastrointest Endosc Clin N Am, 25 (2), pp. 227-242. | Show Abstract | Read more

Adenoma removal prevents colorectal cancer (CRC) development. Lower adenoma detection rates correlate with increased postcolonoscopy CRC. Chromoendoscopy it is not practical for routine use. It was hoped that electronic imaging techniques would offer effective alternatives to improve detection; however, meta-analyses in average-risk patients indicate no benefit. Narrow band imaging may be of benefit for high-risk surveillance. Combining electronic imaging techniques with molecular imaging probes may highlight dysplasia at a molecular level. In future colonoscopy is likely to rely on sensitive and specific, labeled molecular probes detected by electronic endoscopic imaging to enhance detection and reduce miss rates for premalignant lesions.

Ket SN, Bird-Lieberman E, East JE. 2015. Electronic imaging to enhance lesion detection at colonoscopy Gastrointestinal Endoscopy Clinics of North America, 25 (2), pp. 227-242. | Show Abstract | Read more

© 2015 Elsevier Inc. Adenoma removal prevents colorectal cancer (CRC) development. Lower adenoma detection rates correlate with increased postcolonoscopy CRC. Chromoendoscopy it is not practical for routine use. It was hoped that electronic imaging techniques would offer effective alternatives to improve detection; however, meta-analyses in average-risk patients indicate no benefit. Narrow band imaging may be of benefit for high-risk surveillance. Combining electronic imaging techniques with molecular imaging probes may highlight dysplasia at a molecular level. In future colonoscopy is likely to rely on sensitive and specific, labeled molecular probes detected by electronic endoscopic imaging to enhance detection and reduce miss rates for premalignant lesions.

East JE, Vieth M, Rex DK. 2015. Serrated lesions in colorectal cancer screening: Detection, resection, pathology and surveillance Gut, | Read more

Rajasekhar PT, Rees CJ, Bramble MG, Wilson DW, Rutter MD, Saunders BP, Hungin APS, East JE. 2015. A multicenter pragmatic study of an evidence-based intervention to improve adenoma detection: the Quality Improvement in Colonoscopy (QIC) study. Endoscopy, 47 (3), pp. 217-224. | Show Abstract | Read more

BACKGROUND AND STUDY AIMS: Low adenoma detection rates (ADRs) at colonoscopy are linked to significantly higher interval cancer rates, and vary between colonoscopists. Studies demonstrate that lesion detection is improved by: withdrawal time of ≥ 6 minutes; use of hyoscine butylbromide; position change; and rectal retroflexion. We evaluated the feasibility of implementing the above "bundle" of interventions into colonoscopy practice, and the effect on ADR. MATERIALS AND METHODS: A longitudinal cohort design was used. Implementation combined central training, local promotion, and feedback. The uptake marker was change in hyoscine butylbromide use. Comparisons were between the 3 months before and the 9 months after the implementation phase, globally, by endoscopy unit and by quartile when colonoscopists were ranked according to baseline ADR. Chi-squared or Fisher's tests were used to evaluate significance. RESULTS: 12 units participated. Global and quartile analyses included data from 118 and 68 colonoscopists and 17 508 and 14 193 procedures respectively. A significant increase in hyoscine butylbromide use was observed globally (54.4 % vs. 15.8 %, P < 0.001), in all endoscopy units (P < 0.001) and quartiles (P < 0.001). A significant increase in ADR was observed globally (18.1 % vs. 16.0 %, P = 0.002) and in the lower two colonoscopist quartiles (P < 0.001), with a nonsignificant increase in the upper middle quartile and a significant fall to 21.5 %. in the upper quartile. The significant variations in ADR among the upper three quartiles disappeared. CONCLUSION: In routine clinical practice, introduction of a simple, inexpensive, evidence-based "bundle" of measures is feasible and is associated with higher global ADR, driven by improvements amongst the poorest performing colonoscopists.

East JE. 2015. How to treat diminutive polyps? Do we need more evidence? Endosc Int Open, 3 (1), pp. E81-E82. | Read more

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Davis H, Irshad S, Bansal M, Rafferty H, Boitsova T, Bardella C, Jaeger E, Lewis A, Freeman-Mills L, Giner FC et al. 2015. Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche Nature Medicine, 21 (1), pp. 62-70. | Show Abstract | Read more

© 2014 Nature America, Inc. All rights reserved. Hereditary mixed polyposis syndrome (HMPS) is characterized by the development of mixed-morphology colorectal tumors and is caused by a 40-kb genetic duplication that results in aberrant epithelial expression of the gene encoding mesenchymal bone morphogenetic protein antagonist, GREM1. Here we use HMPS tissue and a mouse model of the disease to show that epithelial GREM1 disrupts homeostatic intestinal morphogen gradients, altering cell fate that is normally determined by position along the vertical epithelial axis. This promotes the persistence and/or reacquisition of stem cell properties in Lgr5-negative progenitor cells that have exited the stem cell niche. These cells form ectopic crypts, proliferate, accumulate somatic mutations and can initiate intestinal neoplasia, indicating that the crypt base stem cell is not the sole cell of origin of colorectal cancer. Furthermore, we show that epithelial expression of GREM1 also occurs in traditional serrated adenomas, sporadic premalignant lesions with a hitherto unknown pathogenesis, and these lesions can be considered the sporadic equivalents of HMPS polyps.

Bhat SK, East JE. 2015. Colorectal cancer: Prevention and early diagnosis Medicine (United Kingdom), | Show Abstract | Read more

© 2015 Elsevier Ltd.Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. This article examines strategies for the prevention and early diagnosis of CRC, and reviews the aetiology and risk factors for CRC. Preventative strategies involve improving modifiable risk factors through public health awareness. Patients known to be at higher risk of CRC development, such as those with a genetic predisposition or longstanding inflammatory bowel disease, should undergo endoscopic surveillance in order to detect early cancer or polyps. Population screening for CRC is now strongly established as an effective method for the early detection of CRC and prevention through polypectomy. Screening has been shown to improve the stage of disease at diagnosis and CRC-specific mortality. This article will highlight recent developments in the understanding of the serrated pathway for CRC development and discuss the clinical relevance of this in terms of cancer prevention, as well as exploring future directions for research into the prevention and early diagnosis of CRC.

van Doorn SC, Hazewinkel Y, East JE, van Leerdam ME, Rastogi A, Pellisé M, Sanduleanu-Dascalescu S, Bastiaansen BAJ, Fockens P, Dekker E. 2015. Polyp morphology: an interobserver evaluation for the Paris classification among international experts. Am J Gastroenterol, 110 (1), pp. 180-187. | Show Abstract | Read more

OBJECTIVES: The Paris classification is an international classification system for describing polyp morphology. Thus far, the validity and reproducibility of this classification have not been assessed. We aimed to determine the interobserver agreement for the Paris classification among seven Western expert endoscopists. METHODS: A total of 85 short endoscopic video clips depicting polyps were created and assessed by seven expert endoscopists according to the Paris classification. After a digital training module, the same 85 polyps were assessed again. We calculated the interobserver agreement with a Fleiss kappa and as the proportion of pairwise agreement. RESULTS: The interobserver agreement of the Paris classification among seven experts was moderate with a Fleiss kappa of 0.42 and a mean pairwise agreement of 67%. The proportion of lesions assessed as "flat" by the experts ranged between 13 and 40% (P<0.001). After the digital training, the interobserver agreement did not change (kappa 0.38, pairwise agreement 60%). CONCLUSIONS: Our study is the first to validate the Paris classification for polyp morphology. We demonstrated only a moderate interobserver agreement among international Western experts for this classification system. Our data suggest that, in its current version, the use of this classification system in daily practice is questionable and it is unsuitable for comparative endoscopic research. We therefore suggest introduction of a simplification of the classification system.

Davis H, Irshad S, Bansal M, Rafferty H, Boitsova T, Bardella C, Jaeger E, Lewis A, Freeman-Mills L, Giner FC et al. 2015. Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche. Nat Med, 21 (1), pp. 62-70. | Show Abstract | Read more

Hereditary mixed polyposis syndrome (HMPS) is characterized by the development of mixed-morphology colorectal tumors and is caused by a 40-kb genetic duplication that results in aberrant epithelial expression of the gene encoding mesenchymal bone morphogenetic protein antagonist, GREM1. Here we use HMPS tissue and a mouse model of the disease to show that epithelial GREM1 disrupts homeostatic intestinal morphogen gradients, altering cell fate that is normally determined by position along the vertical epithelial axis. This promotes the persistence and/or reacquisition of stem cell properties in Lgr5-negative progenitor cells that have exited the stem cell niche. These cells form ectopic crypts, proliferate, accumulate somatic mutations and can initiate intestinal neoplasia, indicating that the crypt base stem cell is not the sole cell of origin of colorectal cancer. Furthermore, we show that epithelial expression of GREM1 also occurs in traditional serrated adenomas, sporadic premalignant lesions with a hitherto unknown pathogenesis, and these lesions can be considered the sporadic equivalents of HMPS polyps.

Pullens B, Dekker E, Ellis AJ, Guy R, Madronal K, Chetty R, East JE. 2014. Impact of the consideration of serrated polyps to the interval of colonoscopic surveillance in the NHS Bowel Cancer Screening Programme. Colorectal Dis, 16 (9), pp. O320-O326. | Show Abstract | Read more

AIM: Most international post polypectomy surveillance guidelines do not recommend surveillance for serrated polyps. In the present study the additional impact of serrated polyps on surveillance intervals from international adenoma surveillance guidelines was investigated. METHOD: Endoscopic and pathology records were audited of participants in the NHS Bowel Cancer Screening Programme (guaiac faecal occult blood test, gFOBT) in 2011. Surveillance intervals were calculated for current guidelines and also for serrated polyps based on previously described aggressive and conservative strategies. RESULTS: In total, 389 patients were included of whom 141 (36.2%) were high risk (advanced adenoma: adenoma ≥ 10 mm, villous elements, high grade dysplasia, or adenoma ≥ 3 in number) needing surveillance at ≤ 3 years. Thirty-three (8.5%) had significant serrated polyps, of whom 18 (4.6% of the total) had significant serrated lesions and simultaneous advanced adenoma or ≥ 3 adenomas. Adopting an aggressive surveillance strategy, the mean overall absolute additional proportion of all such patients in the surveillance group at 3 years or less was 4.0% (3.9% - 4.1%; 4.2% women; 3.8% men). These proportions varied according to endoscopist from 2.3% to 4.7%. For more conservative strategies the increase was only 1%. CONCLUSION: The impact of including serrated polyps in current guidelines would result in a small increase in surveillance intervals for FOBT based bowel cancer screening. About half of those who might need surveillance for serrated polyps would already receive surveillance for being in a high risk adenoma group.

Al-Mammari S, Selvarajah U, East JE, Bailey AA, Braden B. 2014. Narrow band imaging facilitates detection of inlet patches in the cervical oesophagus. Dig Liver Dis, 46 (8), pp. 716-719. | Show Abstract | Read more

BACKGROUND: Proximal esophageal heterotopic gastric mucosa or so-called inlet patch in the cervical oesophagus is easily missed on endoscopic examination because of its localisation, usually just below the upper oesophageal sphincter. We evaluated the clinical use of narrow band imaging for detection of inlet patches. METHODS: In this prospective, controlled observational study, 1407 subsequent patients underwent oesophagogastroduodenoscopy with or without narrow band imaging on withdrawal of the endoscope in the cervical oesophagus. RESULTS: One endoscopist who was not aware of the prospective observation documented 6 (1.17%) cases of inlet patches in 515 oesophagogastroduodenoscopies compared to 4 cases out of 382 (1.05%) performed by the endoscopist who paid special attention to the presence of inlet patches but did not routinely apply narrow band imaging (OR 0.89, CI 95% 0.25-3.20, p=0.85). In comparison, 17 cases of inlet patches out of 510 (3.33%) were detected by the endoscopist who routinely applied narrow band imaging. The detection rate of proximal oesophageal heterotopic gastric mucosa using narrow band imaging was significantly higher compared to white light endoscopy only (OR 3.06, CI 95% 1.39-6.73, p=0.005). CONCLUSIONS: Withdrawal of the endoscope from the cervical oesophagus using narrow band imaging increased the detection of inlet patches about three-fold compared to standard white light endoscopy.

East JE, Toyonaga T, Suzuki N. 2014. Endoscopic management of nonpolypoid colorectal lesions in colonic IBD. Gastrointest Endosc Clin N Am, 24 (3), pp. 435-445. | Show Abstract | Read more

Much of the flat or biopsy-only detected dysplasia in inflammatory bowel disease (IBD) that had historically warranted a colectomy can now be shown to be circumscribed lesions with dye-spray or advanced endoscopic imaging. These lesions are therefore amenable to endoscopic excision with close endoscopic follow-up, though are technically very challenging. This review discusses preresection assessment of nonpolypoid or flat (Paris 0-II) lesions in colitis; lifting with colloids or hyaluronate; endoscopic mucosal resection (EMR) with spiral or flat ribbon snares; or simplified, hybrid, and full endoscopic submucosal dissection (ESD); as well as mucosal ablation. Close follow-up postresection is mandatory.

Wanders LK, Dekker E, Pullens B, Bassett P, Travis SPL, East JE. 2014. Cancer risk after resection of polypoid dysplasia in patients with longstanding ulcerative colitis: a meta-analysis. Clin Gastroenterol Hepatol, 12 (5), pp. 756-764. | Show Abstract | Read more

BACKGROUND & AIMS: American and European guidelines propose complete endoscopic resection of polypoid dysplasia (adenomas or adenoma-like masses) in patients with longstanding colitis, with close endoscopic follow-up. The incidence of cancer after detection of flat low-grade dysplasia or dysplasia-associated lesion or mass is estimated at 14 cases/1000 years of patient follow-up. However, the risk for polypoid dysplasia has not been determined with precision. We investigated the risk of cancer after endoscopic resection of polypoid dysplasia in patients with ulcerative colitis. METHODS: MEDLINE, EMBASE, PubMed, and the Cochrane library were searched for studies of patients with colitis and resected polypoid dysplasia, with reports of colonoscopic follow-up and data on cancers detected. Outcomes from included articles were pooled to provide a single combined estimate of outcomes by using Poisson regression. RESULTS: Of 425 articles retrieved, we analyzed data from 10 studies, comprising 376 patients with colitis and polypoid dysplasia with a combined 1704 years of follow-up. A mean of 2.8 colonoscopies were performed for each patient after the index procedure (range, 0-15 colonoscopies). The pooled incidence of cancer was 5.3 cases (95% confidence interval, 2.7-10.1 cases)/1000 years of patient follow-up. There was no evidence of heterogeneity or publication bias. The pooled rate of any dysplasia was 65 cases (95% confidence interval, 54-78 cases)/1000 patient years. CONCLUSION: Patients with colitis have a low risk of colorectal cancer after resection of polypoid dysplasia; these findings support the current strategy of resection and surveillance. However, these patients have a 10-fold greater risk of developing any dysplasia than colorectal cancer and should undergo close endoscopic follow-up.

Cited:

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Wanders LK, Dekker E, Pullens B, Bassett P, Travis SPL, East JE. 2014. Cancer risk after resection of polypoid dysplasia in patients with longstanding ulcerative colitis: A meta-analysis Clinical Gastroenterology and Hepatology, 12 (5), pp. 756-764. | Show Abstract | Read more

Background & Aims: American and European guidelines propose complete endoscopic resection of polypoid dysplasia (adenomas or adenoma-like masses) in patients with longstanding colitis, with close endoscopic follow-up. The incidence of cancer after detection of flat low-grade dysplasia or dysplasia-associated lesion or mass is estimated at 14 cases/1000 years of patient follow-up. However, the risk for polypoid dysplasia has not been determined with precision. We investigated the risk of cancer after endoscopic resection of polypoid dysplasia in patients with ulcerative colitis. Methods: MEDLINE, EMBASE, PubMed, and the Cochrane library were searched for studies of patients with colitis and resected polypoid dysplasia, with reports of colonoscopic follow-up and data on cancers detected. Outcomes from included articles were pooled to provide a single combined estimate of outcomes by using Poisson regression. Results: Of 425 articles retrieved, we analyzed data from 10 studies, comprising 376 patients with colitis and polypoid dysplasia with a combined 1704 years of follow-up. A mean of 2.8 colonoscopies were performed for each patient after the index procedure (range, 0-15 colonoscopies). The pooled incidence of cancer was 5.3 cases (95% confidence interval, 2.7-10.1 cases)/1000 years of patient follow-up. There was no evidence of heterogeneity or publication bias. The pooled rate of any dysplasia was 65 cases (95% confidence interval, 54-78 cases)/1000 patient years. Conclusion: Patients with colitis have a low risk of colorectal cancer after resection of polypoid dysplasia; these findings support the current strategy of resection and surveillance. However, these patients have a 10-fold greater risk of developing any dysplasia than colorectal cancer and should undergo close endoscopic follow-up. © 2014 AGA Institute.

Kamiński MF, Hassan C, Bisschops R, Pohl J, Pellisé M, Dekker E, Ignjatovic-Wilson A, Hoffman A, Longcroft-Wheaton G, Heresbach D et al. 2014. Advanced imaging for detection and differentiation of colorectal neoplasia: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy, 46 (5), pp. 435-449. | Show Abstract | Read more

MAIN RECOMMENDATIONS: 1 ESGE suggests the routine use of high definition white-light endoscopy systems for detecting colorectal neoplasia in average risk populations (weak recommendation, moderate quality evidence). 2 ESGE recommends the routine use of high definition systems and pancolonic conventional or virtual (narrow band imaging [NBI], i-SCAN) chromoendoscopy in patients with known or suspected Lynch syndrome (strong recommendation, low quality evidence). 2b ESGE recommends the routine use of high definition systems and pancolonic conventional or virtual (NBI) chromoendoscopy in patients with known or suspected serrated polyposis syndrome (strong recommendation, low quality evidence). 3 ESGE recommends the routine use of 0.1 % methylene blue or 0.1 % - 0.5 % indigo carmine pancolonic chromoendoscopy with targeted biopsies for neoplasia surveillance in patients with long-standing colitis. In appropriately trained hands, in the situation of quiescent disease activity and adequate bowel preparation, nontargeted, four-quadrant biopsies can be abandoned (strong recommendation, high quality evidence). 4 ESGE suggests that virtual chromoendoscopy (NBI, FICE, i-SCAN) and conventional chromoendoscopy can be used, under strictly controlled conditions, for real-time optical diagnosis of diminutive (≤ 5 mm) colorectal polyps to replace histopathological diagnosis. The optical diagnosis has to be reported using validated scales, must be adequately photodocumented, and can be performed only by experienced endoscopists who are adequately trained and audited (weak recommendation, high quality evidence). 5 ESGE suggests the use of conventional or virtual (NBI) magnified chromoendoscopy to predict the risk of invasive cancer and deep submucosal invasion in lesions such as those with a depressed component (0-IIc according to the Paris classification) or nongranular or mixed-type laterally spreading tumors (weak recommendation, moderate quality evidence). CONCLUSION: Advanced imaging techniques will need to be applied in specific patient groups in routine clinical practice and to be taught in endoscopic training programs.

East JE, Leedham SJ. 2014. Colonoscopy, tumors. Endoscopy, 46 (4), pp. 318-321. | Read more

East J, Leedham S. 2014. Colonoscopy, tumors Endoscopy, 46 (04), pp. 318-321. | Read more

Corte CJ, Burger DC, Horgan G, Bailey AA, East JE. 2014. Postpolypectomy haemorrhage following removal of large polyps using mechanical haemostasis or epinephrine: a meta-analysis. United European Gastroenterol J, 2 (2), pp. 123-130. | Show Abstract | Read more

BACKGROUND AND AIM: Postpolypectomy haemorrhage (PPH) is a known adverse event that can occur following polypectomy, occurring in 0.3-6.1% of cases. Previous meta-analysis has included small polyps, which are less likely to bleed, and less amenable to some methods of mechanical haemostasis. No comprehensive cost-benefit analysis of this topic is available. The aim of this study was to perform a meta-analysis of randomized trials and a cost-benefit analysis of prophylactic haemostasis in PPH. METHODS: A total of 3092 abstracts from prospective trials conducted in human colonoscopic polypectomy were screened. Outpatients undergoing polypectomy in seven suitable studies (1426 episodes), without polyposis syndromes or bleeding diathesis, were identified. The interventions of prophylactic haemostatic measures (clips, loops, and/or adrenaline injection) to prevent PPH were assessed. The main outcome measurements were PPH measured by haematochezia or drop in haematocrit >10% or haemoglobin >1 g/dl. Risk ratio and number needed to treat (NNT) were generated using meta-analysis. RESULTS: Comparing any prophylactic haemostasis to none, the pooled risk ratio for PPH was 0.35 (0.21-0.57; p < 0.0001), NNT was 13.6, and cost to prevent one PPH was USD652. Using adrenaline alone vs. no prophylactic haemostasis revealed a pooled risk ratio of 0.37 (0.20-0.66; p = 0.001), NNT 14.0, cost to prevent one PPH USD382. Any prophylactic mechanical haemostasis compared to adrenaline produced a RR for PPH of 0.28 (0.14-0.57; p < 0.0001), NNT 12.3, and cost to prevent one PPH USD1368. CONCLUSIONS: Adrenaline injection or mechanical haemostasis reduces the risk of PPH. Routine prophylactic measures to reduce PPH for polyps larger than 10 mm are potentially cost effective, although more thorough cost-benefit modelling is required.

Rastogi A, Rao DS, Gupta N, Grisolano SW, Buckles DC, Sidorenko E, Bonino J, Matsuda T, Dekker E, Kaltenbach T et al. 2014. Impact of a computer-based teaching module on characterization of diminutive colon polyps by using narrow-band imaging by non-experts in academic and community practice: a video-based study. Gastrointest Endosc, 79 (3), pp. 390-398. | Show Abstract | Read more

BACKGROUND: Experts can accurately characterize the histology of diminutive polyps with narrow-band imaging (NBI). There are limited data on the performance of non-experts. OBJECTIVE: To assess the impact of a computer-based teaching module on the accuracy of predicting polyp histology with NBI by non-experts (in academics and community practice) by using video clips. DESIGN: Prospective, observational study. SETTING: Academic and community practice. PARTICIPANTS: A total of 15 gastroenterologists participated-5 experts in NBI, 5 non-experts in academic practice, and 5 non-experts in community practice. INTERVENTION: Participants reviewed a 20-minute, computer-based teaching module outlining the different NBI features for hyperplastic and adenomatous polyps. MAIN OUTCOME MEASUREMENTS: Performance characteristics in characterizing the histology of diminutive polyps with NBI by using short video clips before (pretest) and after (posttest) reviewing the teaching module. RESULTS: Non-experts in academic practice showed a significant improvement in the sensitivity (54% vs 79%; P < .001), accuracy (64% vs 81%; P < .001), and proportion of high-confidence diagnoses (49% vs 69%; P < .001) in the posttest. Non-experts in community practice had significantly higher sensitivity (58% vs 75%; P = .004), specificity (76% vs 90%; P = .04), accuracy (64% vs 81%; P < .001), and proportion of high-confidence diagnoses (49% vs 72%; P < .001) in the posttest. Performance of experts in NBI was significantly better than non-experts in both academic and community practice. LIMITATIONS: Selection bias in selecting good quality videos. Performance not assessed during live colonoscopy. CONCLUSION: Academic and community gastroenterologists without prior experience in NBI can achieve significant improvements in characterizing diminutive polyp histology after a brief computer-based training. The durability of these results and applicability in everyday practice are uncertain.

Hazewinkel Y, East JE, Dekker E. 2014. Response. Gastrointest Endosc, 79 (1), pp. 184. | Read more

Adelson M, Pannick S, East JE, Risby P, Dawson P, Monahan KJ. 2014. UK colorectal cancer patients are inadequately assessed for Lynch syndrome. Frontline Gastroenterol, 5 (1), pp. 31-35. | Show Abstract | Read more

OBJECTIVE: To establish whether colorectal cancer patients in two centres in the UK are screened appropriately for Lynch syndrome, in accordance with current international guidance. DESIGN: Patients newly diagnosed with colorectal cancer over an 18-month period were identified from the UK National Bowel Cancer Audit Programme. Their records and management were reviewed retrospectively. SETTING: Two university teaching hospitals, Imperial College Healthcare and Oxford Radcliffe Hospitals NHS Trusts. OUTCOMES MEASURED: Whether patients were screened for Lynch syndrome-and the outcome of that evaluation, if it took place-were assessed from patients' clinical records. The age, tumour location and family history of screened patients were compared to those of unscreened patients. RESULTS: Five hundred and fifty three patients with newly diagnosed colorectal cancer were identified. Of these, 97 (17.5%) satisfied the revised Bethesda criteria, and should have undergone further assessment. There was no evidence that those guidelines had been contemporaneously applied to any patient. In practice, only 22 of the 97 (22.7%) eligible patients underwent evaluation. The results for 14 of those 22 (63.6%) supported a diagnosis of Lynch syndrome, but only nine of the 14 (64.3%) were referred for formal mismatch repair gene testing. No factors reliably predicted whether or not a patient would undergo Lynch syndrome screening. CONCLUSIONS: Colorectal teams in the UK do not follow international guidance identifying the patients who should be screened for Lynch syndrome. Patients and their families are consequently excluded from programmes reducing colorectal cancer incidence and mortality. Multidisciplinary teams should work with their local genetics services to develop reliable algorithms for patient screening and referral.

Annese V, Daperno M, Rutter MD, Amiot A, Bossuyt P, East J, Ferrante M, Götz M, Katsanos KH, Kießlich R et al. 2013. European evidence based consensus for endoscopy in inflammatory bowel disease. J Crohns Colitis, 7 (12), pp. 982-1018. | Read more

Gill P, Rafferty H, Munday D, Bailey A, Wang LM, East JE, Chetty R, Leedham SJ. 2013. Proximal colon cancer and serrated adenomas - hunting the missing 10%. Clin Med (Lond), 13 (6), pp. 557-561. | Show Abstract | Read more

There is a 10% shortfall in the number of proximal colorectal cancer cases detected by the UK Bowel Cancer Screening Programme and the actual number of UK-registered proximal colorectal cancers. Sessile serrated adenomas/polyps (SSA/P) are common premalignant lesions in the proximal colon and are notoriously difficult to spot endoscopically. Missed or dismissed SSA/Ps might contribute to this UK proximal colon cancer detection disparity. In Oxfordshire, a service evaluation audit and histological review has shown a linear increase in the detection rate of these lesions over the past 4 years. This is the result of increased endoscopist and pathologist awareness of these lesions and improved interdisciplinary communication. This is the result of increased endoscopist and pathologist awareness of these lesions, together with improved interdisciplinary communication, and we predict that this will lead to a comparable detection increase nationwide. Ongoing surveillance of an increasing number of these premalignant lesions could become a significant endoscopic resource requirement once UK guidelines on serrated lesion follow up are established.

Wanders LK, East JE, Uitentuis SE, Leeflang MMG, Dekker E. 2013. Diagnostic performance of narrowed spectrum endoscopy, autofluorescence imaging, and confocal laser endomicroscopy for optical diagnosis of colonic polyps: a meta-analysis. Lancet Oncol, 14 (13), pp. 1337-1347. | Show Abstract | Read more

BACKGROUND: Novel endoscopic technologies could allow optical diagnosis and resection of colonic polyps without histopathological testing. Our aim was to establish the sensitivity, specificity, and real-time negative predictive value of three types of narrowed spectrum endoscopy (narrow-band imaging [NBI], image-enhanced endoscopy [i-scan], and Fujinon intelligent chromoendoscopy [FICE]), confocal laser endomicroscopy (CLE), and autofluorescence imaging for differentiation between neoplastic and non-neoplastic colonic lesions. METHODS: We identified relevant studies through a search of Medline, Embase, PubMed, and the Cochrane Library. Clinical trials and observational studies were eligible for inclusion when the diagnostic performance of NBI, i-scan, FICE, autofluorescence imaging, or CLE had been assessed for differentiation, with histopathology as the reference standard, and for which a 2 × 2 contingency table of lesion diagnosis could be constructed. We did a random-effects bivariate meta-analysis using a non-linear mixed model approach to calculate summary estimates of sensitivity and specificity, and plotted estimates in a summary receiver-operating characteristic curve. FINDINGS: We included 91 studies in our analysis: 56 were of NBI, ten of i-scan, 14 of FICE, 11 of CLE, and 11 of autofluorescence imaging (more than one of the investigated modalities assessed in eight studies). For NBI, overall sensitivity was 91·0% (95% CI 88·6-93·0), specificity 85·6% (81·3-89·0), and real-time negative predictive value 82·5% (75·4-87·9). For i-scan, overall sensitivity was 89·3% (83·3-93·3), specificity 88·2% (80·3-93·2), and real-time negative predictive value 86·5% (78·0-92·1). For FICE, overall sensitivity was 91·8% (87·1-94·9), specificity 83·5% (77·2-88·3), and real-time negative predictive value 83·7% (77·5-88·4). For autofluorescence imaging, overall sensitivity was 86·7% (79·5-91·6), specificity 65·9% (50·9-78·2), and real-time negative predictive value 81·5% (54·0-94·3). For CLE, overall sensitivity was 93·3% (88·4-96·2), specificity 89·9% (81·8-94·6), and real-time negative predictive value 94·8% (86·6-98·1). INTERPRETATION: All endoscopic imaging techniques other than autofluorescence imaging could be used by appropriately trained endoscopists to make a reliable optical diagnosis for colonic lesions in daily practice. Further research should be focused on whether training could help to improve negative predictive values. FUNDING: None.

East JE. 2013. Resection Techniques for Small Colonic Polyps: Cold Forceps Polypectomy, Hot Biopsy, Cold Snare and Hot Snare Video Journal and Encyclopedia of GI Endoscopy, 1 (2), pp. 401-402. | Show Abstract | Read more

The majority of polyps encountered at colonoscopy are less than 10 mm in diameter. A range of techniques for resecting these small lesions are described in this article. Cold forceps polypectomy can be used for diminutive lesions less than 3 mm in size. Hot biopsy is also demonstrated; however, it is no longer recommended as a resection technique for small polyps. Cold snaring including a small rim of normal tissue is shown. Hot snare can be applied to lesions larger than 7 mm in size. Cold snaring has become the standard technique for most small lesions due to speed, comprehensive resection, and safety. This article is part of an expert video encyclopedia. © 2013 Elsevier GmbH.

East JE. 2013. En Bloc Endoscopic Mucosal Resection of a Large Right Colonic Serrated Lesion Video Journal and Encyclopedia of GI Endoscopy, 1 (2), pp. 321-322. | Show Abstract | Read more

Sessile serrated lesions (sessile serrated adenomas or polyps), particularly in the proximal colon, are increasingly recognized as premalignant lesions, which require removal; however, to remove these flat and indistinct lesions in the thin-walled right colon can be technically demanding. In this article, en bloc endoscopic mucosal resection technique is demonstrated for a 12-mm sessile serrated lesion in the proximal colon. This article is part of an expert video encyclopedia. © 2013 Elsevier GmbH.

East JE. 2013. Resection of Large Pedunculated Rectal Polyp with Preinjection and Clips Followed by Roth Net Retrieval Video Journal and Encyclopedia of GI Endoscopy, 1 (2), pp. 399-400. | Show Abstract | Read more

Large pedunculated polyps in the colon and rectum represent a challenge to the endoscopist to resect in a controlled and safe manner. How stalk preinjection with epinephrine (adrenaline) can help avoiding immediate postpolypectomy bleeding has been demonstrated in the given video. Endoscopic clips are applied to the polyp base following polypectomy to reduce the risk of delayed bleeding. Retrieval with a Roth net is also demonstrated. This article is part of an expert video encyclopedia. © 2013 Elsevier GmbH.

Chetty R, Wang LM, Gill P, East JE, Leedham S. 2013. Left-sided sessile serrated polyps/adenomas. Hum Pathol, 44 (9), pp. 1959-1960. | Read more

Cited:

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Gill P, Wang LM, Bailey A, East JE, Leedham S, Chetty R. 2013. Reporting trends of right-sided hyperplastic and sessile serrated polyps in a large teaching hospital over a 4-year period (2009-2012) Journal of Clinical Pathology, 66 (8), pp. 655-658. | Show Abstract | Read more

Aim An audit of serrated polyps diagnosed over a 4-year period: 2009 to 2012 was undertaken to ascertain the reporting trends of sessile serrated polyps (SSP). Methods All right sided hyperplastic polyps (HP) proximal to the splenic flexure and all polyps designated SSP were retrieved from the study period. Three pathologists blinded to the original diagnosis re-examined the slides. Recent American College of Gastroenterology guidelines for the diagnosis of SSP was utilised. Results No cases of SSP were diagnosed in 2009. In 2010, 32 right-sided cases were encountered, 83 confirmed in 2011 and 134 confirmed in 2012. The vast majority of these were right-sided. With regards to right-sided HP that were re-classified as SSP the data is as follows: 20 of 66 in 2009 (30%); 58 of 91 in 2010 (64%); 42 of 106 (40%) in 2011 and 69 of 206 in 2012 (33%). Conclusions This study has demonstrated an almost exponential increase in the diagnosis of SSP over a 4-year period. In addition, 30 to 64% of right-sided HP were re-classified as SSP over the 4-year period suggesting that greater awareness of the diagnostic criteria for SSP is required. SSP is an important precursor lesion in the serrated pathway of colorectal cancer. Its recognition is important for surveillance and therapeutic strategies.

Hassan C, East JE. 2013. Can high resolution microendoscopy improve the resect and discard strategy? Endoscopy, 45 (7), pp. 513-515. | Read more

Rafferty H, Gill P, Davis H, Bailey A, East J, Chetty R, Leedham S. 2013. SESSILE SERRATED ADENOMAS, UNDER-RECOGNISED ENDOSCOPICALLY AND UNDER DIAGNOSED PATHOLOGICALLY GUT, 62 (Suppl 1), pp. A196-A196. | Read more

Boitsova T, Rafferty H, Davis H, Bardella C, Gill P, East J, Tomlinson I, Chetty R, Silver A, Leedham S. 2013. BONE MORPHOGENETIC PROTEIN (BMP) PATHWAY DYSREGULATION SUBVERTS ONCOGENE INDUCED SENESCENCE MECHANISMS IN THE SERRATED PATHWAY OF TUMOURIGENESIS GUT, 62 (Suppl 1), pp. A200-A200. | Read more

Hazewinkel Y, López-Cerón M, East JE, Rastogi A, Pellisé M, Nakajima T, van Eeden S, Tytgat KMAJ, Fockens P, Dekker E. 2013. Endoscopic features of sessile serrated adenomas: validation by international experts using high-resolution white-light endoscopy and narrow-band imaging. Gastrointest Endosc, 77 (6), pp. 916-924. | Show Abstract | Read more

BACKGROUND: Sessile serrated adenomas/polyps (SSAs/Ps) are premalignant lesions susceptible to being easily overlooked by endoscopists. A detailed description of the endoscopic appearance of SSAs/Ps might help endoscopists to recognize these lesions to improve the effectiveness of colonoscopy. OBJECTIVE: To identify various endoscopic features of SSAs/Ps using high-resolution white-light endoscopy (HR-WLE) and narrow-band imaging (NBI). DESIGN: Retrospective image evaluation study. SETTING: Single tertiary referral center. PATIENTS: Forty-5 patients with serrated polyposis syndrome undergoing surveillance colonoscopies. INTERVENTION: HR-WLE and NBI images of 150 polyps (50 SSAs/Ps, 50 hyperplastic polyps [HPs], and 50 adenomas) were systematically assessed by 5 experts using various endoscopic descriptors. MAIN OUTCOME MEASUREMENTS: The prevalence of specific endoscopic features observed in SSAs/Ps versus HPs. RESULTS: Multivariate analysis demonstrated that indistinct borders (OR, 3.11; 95% CI, 1.57-6.15) and a cloud-like surface (OR, 2.65; 95% CI, 1.21-5.78) were associated with SSA/P histology on HR-WLE. On NBI, a cloud-like surface (OR, 4.91; 95% CI, 2.42-9.97), indistinct borders (OR, 2.38; 95% CI, 1.14-4.96), irregular shape (OR, 3.17; 95% CI, 1.59-6.29), and dark spots inside the crypts (OR, 2.05; 95% CI, 1.02-4.11) were found to be endoscopic predictors of SSA/P histology. The sensitivity, specificity, and accuracy of NBI for differentiating serrated polyps containing either none or all 4 endoscopic SSA/P features were, respectively, 89%, 96%, and 93%. LIMITATIONS: Retrospective, image evaluation analysis. CONCLUSIONS: The current study demonstrates that SSAs/Ps possess several specific endoscopic features compared with HPs. Recognition of these characteristics might assist endoscopists in the differentiation of these lesions and could possibly facilitate endoscopic detection of these rather subtle lesions.

Gill P, Wang LM, Bailey A, East JE, Leedham S, Chetty R. 2013. Reporting trends of right-sided hyperplastic and sessile serrated polyps in a large teaching hospital over a 4-year period (2009-2012). J Clin Pathol, 66 (8), pp. 655-658. | Show Abstract | Read more

AIM: An audit of serrated polyps diagnosed over a 4-year period: 2009 to 2012 was undertaken to ascertain the reporting trends of sessile serrated polyps (SSP). METHODS: All right sided hyperplastic polyps (HP) proximal to the splenic flexure and all polyps designated SSP were retrieved from the study period. Three pathologists blinded to the original diagnosis re-examined the slides. Recent American College of Gastroenterology guidelines for the diagnosis of SSP was utilised. RESULTS: No cases of SSP were diagnosed in 2009. In 2010, 32 right-sided cases were encountered, 83 confirmed in 2011 and 134 confirmed in 2012. The vast majority of these were right-sided. With regards to right-sided HP that were re-classified as SSP the data is as follows: 20 of 66 in 2009 (30%); 58 of 91 in 2010 (64%); 42 of 106 (40%) in 2011 and 69 of 206 in 2012 (33%). CONCLUSIONS: This study has demonstrated an almost exponential increase in the diagnosis of SSP over a 4-year period. In addition, 30 to 64% of right-sided HP were re-classified as SSP over the 4-year period suggesting that greater awareness of the diagnostic criteria for SSP is required. SSP is an important precursor lesion in the serrated pathway of colorectal cancer. Its recognition is important for surveillance and therapeutic strategies.

Leedham S, East JE, Chetty R. 2013. Diagnosis of sessile serrated polyps/adenomas: What does this mean for the pathologist, gastroenterologist and patient Journal of Clinical Pathology, 66 (4), pp. 265-268. | Read more

Horgan G, East JE, Saunders BP. 2013. Malignant polyp Techniques in Gastrointestinal Endoscopy, 15 (2), pp. 106-112. | Show Abstract | Read more

Malignant polyps are now being encountered more frequently because of increased colorectal cancer screening. Endoscopy offers a minimally invasive option for treating some malignant polyps thus reducing surgical morbidity and mortality. This chapter reviews the endoscopic assessment of colorectal polypoid lesions and risk stratification using gross polyp morphology (Paris classification), lesion surface appearance (Kudo pit pattern and mucosal microvessel appearance, via high-magnification chromoendoscopy and narrow-band imaging), and by the lesion's lifting characteristics ("nonlifting sign"). In combination, these features allow an assessment of the potential for malignancy as well as the likely depth of submucosal invasion, so as to guide appropriate management. We also consider possible adjunct assessment modalities, such as endoscopic ultrasound, and discuss postpolypectomy histologic classification, including Haggitt staging for pedunculated lesions and Kikuchi staging for sessile lesions or laterally spreading tumors. Finally, we describe endoscopic resection techniques for removal of malignant polyps, including endoscopic mucosal resection and endoscopic submucosal dissection, and compare these with surgical management options. © 2013 Elsevier Inc.

Leedham S, East JE, Chetty R. 2013. Diagnosis of sessile serrated polyps/adenomas: what does this mean for the pathologist, gastroenterologist and patient? J Clin Pathol, 66 (4), pp. 265-268. | Read more

East JE, Dekker E. 2013. Colorectal cancer diagnosis in 2012: A new focus for CRC prevention--more serration, less inflammation. Nat Rev Gastroenterol Hepatol, 10 (2), pp. 69-70. | Read more

Cited:

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Leedham SJ, Rodenas-Cuadrado P, Howarth K, Lewis A, Mallappa S, Segditsas S, Davis H, Jeffery R, Rodriguez-Justo M, Keshav S et al. 2013. A basal gradient of Wnt and stem-cell number influences regional tumour distribution in human and mouse intestinal tracts Gut, 62 (1), pp. 83-93. | Show Abstract | Read more

Objective: Wnt signalling is critical for normal intestinal development and homeostasis. Wnt dysregulation occurs in almost all human and murine intestinal tumours and an optimal but not excessive level of Wnt activation is considered favourable for tumourigenesis. The authors assessed effects of pan-intestinal Wnt activation on tissue homeostasis, taking into account underlying physiological Wnt activity and stem-cell number in each region of the bowel. Design: The authors generated mice that expressed temporally controlled, stabilised β-catenin along the crypt-villus axis throughout the intestines. Physiological Wnt target gene activity was assessed in different regions of normal mouse and human tissue. Human intestinal tumour mutation spectra were analysed. Results: In the mouse, β-catenin stabilisation resulted in a graduated neoplastic response, ranging from dysplastic transformation of the entire epithelium in the proximal small bowel to slightly enlarged crypts of non-dysplastic morphology in the colorectum. In contrast, stem and proliferating cell numbers were increased in all intestinal regions. In the normal mouse and human intestines, stem-cell and Wnt gradients were non-identical, but higher in the small bowel than large bowel in both species. There was also variation in the expression of some Wnt modulators. Human tumour analysis confirmed that different APC mutation spectra are selected in different regions of the bowel. Conclusions: There are variable gradients in stem-cell number, physiological Wnt activity and response to pathologically increased Wnt signalling along the cryptvillus axis and throughout the length of the intestinal tract. The authors propose that this variation influences regional mutation spectra, tumour susceptibility and lesion distribution in mice and humans.

Man-i M, Morita Y, Fujita T, East JE, Tanaka S, Wakahara C, Yoshida M, Hayakumo T, Kutsumi H, Inokuchi H et al. 2013. Endoscopic submucosal dissection for gastric neoplasm in patients with co-morbidities categorized according to the ASA Physical Status Classification. Gastric Cancer, 16 (1), pp. 56-66. | Show Abstract | Read more

BACKGROUND: Endoscopic submucosal dissection (ESD) has come to be widely performed for reduced invasiveness; however, its safety in patients with co-morbidities is not fully examined. We aimed to evaluate the safety and efficacy of gastric ESD with co-morbidities categorized according to ASA Physical Status Classification. METHODS: Two hundred and forty patients of ASA 1 (no co-morbidities), 268 of ASA 2 (mild), and 19 of ASA 3 (severe) were treated by ESD for gastric neoplasms. We retrospectively compared clinicopathological features and treatment results of these three groups. RESULTS: Cases (by percent) treated with anticoagulant/platelet agents were more common in the higher ASA grades (ASA 1, 5.8%; ASA 2, 29.1%; ASA 3, 31.6%; P < 0.0001). There were no significant differences in case numbers treated under guideline criteria, curative resection (ASA 1, 79.6%; ASA 2, 79.9%; ASA 3, 78.9%), or complications related to the ESD procedure (e.g., postoperative bleeding, perforation, thermal injury). By a patient risk prediction model on surgery, i.e., P-POSSUM, morbidity was halved, and no patients died compared to a predicted death rate of 0.5-2%; however, total and complications unrelated to ESD procedure (e.g., aspiration pneumonia, ischemic heat attack) were more common in higher ASA grades (ASA 1, ASA 2, ASA 3: 15.4, 23.9, 26.3%, respectively, P = 0.014; 0.4, 7.1, 0%, respectively, P = 0.00087). Deviation rates from clinical pathway were more frequent and hospital stay (days) longer in higher ASA grades (ASA 1, ASA 2, ASA 3: 11.3, 17.9, 26.3%, respectively, P = 0.014; 8, 8, 9%, respectively, P = 0.0053). CONCLUSIONS: ESD is an efficient treatment for gastric neoplasms with co-morbidities. However, additional caution is required because co-morbidity is a risk factor for both total complications and complications unrelated to the ESD procedure, and may cause deviations in the clinical course and prolonged hospital stay.

Rajasekhar PT, Rutter MD, Bramble MG, Wilson DW, East JE, Greenaway JR, Saunders BP, Lee TJW, Barton R, Hungin APS, Rees CJ. 2012. Achieving high quality colonoscopy: using graphical representation to measure performance and reset standards. Colorectal Dis, 14 (12), pp. 1538-1545. | Show Abstract | Read more

AIM: Completeness and thoroughness of colonoscopy are measured by the caecal intubation rate (CIR) and the adenoma detection rate (ADR). National standards are ≥ 90% and ≥ 10% respectively. Variability in CIR and ADR have been demonstrated but comparison between individuals and units is difficult. We aimed to assess the performance of colonoscopy in endoscopy units in the northeast of England. METHOD: Data on colonoscopy performance and sedation use were collected over 3 months from 12 units. Colonoscopies performed by screening colonoscopists were included for the CIR only. Funnel plots with upper and lower 95% confidence limits for CIR and ADR were created. RESULTS: CIR was 92.5% (n = 5720) and ADR 15.9% (n = 4748). All units and 128 (99.2%) colonoscopists were above the lower limit for CIR. All units achieved the ADR standard with 10 above the upper limit. Ninety-nine (76.7%) colonoscopists were above 10%, 16 (12.4%) above the upper limit and 7 (5.4%) below the lower limit. Median medication doses were 2.2 mg midazolam, 29.4 mg pethidine and 83.3 μg fentanyl. In all, 15.1% of colonoscopies were unsedated. Complications were bleeding (0.10%) and perforation (0.02%). There was one death possibly related to bowel preparation. CONCLUSION: Results indicate that colonoscopies are performed safely and to a high standard. Funnel plots can highlight variability and areas for improvement. Analyses of ADR presented graphically around the global mean suggest that the national standard should be reset at 15%.

East JE, Ignjatovic A, Suzuki N, Guenther T, Bassett P, Tekkis PP, Saunders BP. 2012. A randomized, controlled trial of narrow-band imaging vs high-definition white light for adenoma detection in patients at high risk of adenomas. Colorectal Dis, 14 (11), pp. e771-e778. | Show Abstract | Read more

AIM: The study aimed to investigate whether narrow-band imaging (NBI) can enhance adenoma detection in patients at high risk for adenomas compared with high-definition white-light endoscopy (WLE). High risk was defined as three or more adenomas at last colonoscopy, history of colorectal cancer and positive faecal occult blood test. METHOD: Two hundred and fourteen patients were randomized 1:1 to examination with NBI or WLE. The primary outcome measure was the proportion of patients with at least one adenoma detected. Secondary outcomes included total adenomas and polyps, flat adenomas, nonadenomatous polyps, advanced adenomas and patients with three or five or more adenomas. A post hoc analysis to examine the effect of endoscopist and bowel preparation was performed. RESULTS: There was no significant difference in the proportion of patients with at least one adenoma: NBI 73%vs WLE 66%, odds ratio 1.40 (95% CI 0.78-2.52), P = 0.26. There was no significant difference for any secondary outcome measure except for the number of flat adenomas which was significantly greater with NBI [comparison ratio 2.66 (95% CI 1.52-4.63), P = 0.001]. Post hoc analysis indicated that one of three endoscopists performed significantly better for adenoma detection with NBI than WLE [comparison ratio 1.92 (95% CI 1.07-3.44), P = 0.03]. Good bowel preparation was associated with significantly improved adenoma detection with NBI [comparison ratio 1.55 (95% CI 1.01-2.22), P = 0.04] but not with fair preparation. CONCLUSION: Overall NBI did not improve detection compared with WLE in a group of patients at high risk for colorectal adenomas, but specific subgroups might benefit.

East JE. 2012. Colonoscopic Cancer Surveillance in Inflammatory Bowel Disease: What's New Beyond Random Biopsy? Clin Endosc, 45 (3), pp. 274-277. | Show Abstract | Read more

Colonoscopy based colitis surveillance is widely accepted to try to prevent development of and ensure early detection of colitis-associated colorectal cancer. Traditionally this has been performed with quadrantic random biopsies throughout the colon. Chromoendoscopy "dye-spray" with targeted biopsies only has been shown to increase dysplasia detection 4 to 5 fold on a per lesion basis. It has therefore been suggested that random biopsies should be abandoned as they do not increase dysplasia detection nor change patient clinical course. Recent British guidelines for colitis surveillance have strongly endorsed chromoendoscopy. This short review summarizes current international guidelines and looks at how to optimize white light colonoscopy in colitis considering: bowel preparation, withdrawal time, high definition, and structure enhancement. Data for advanced imaging techniques are reviewed including positive evidence in favor of chromoendoscopy, and limited data suggesting autofluoresence imaging may be promising. Narrow band imaging does not increase dysplasia detection in colitis. Confocal endomicroscopy might potentially reduce biopsies beyond that of chromoendoscopy but does not offer a clear detection advantage. Pan-colonic chromoendoscopy with targeted biopsies increases dysplasia detection and is the standard of care in the United Kingdom. It is likely that the use of chromoendoscopy for colitis surveillance will become widely accepted internationally.

Biswas S, Ellis AJ, Guy R, Savage H, Madronal K, East JE. 2013. High prevalence of hyperplastic polyposis syndrome (serrated polyposis) in the NHS bowel cancer screening programme. Gut, 62 (3), pp. 475. | Read more

Biswas S, Ellis AJ, Guy R, Chetty R, Madronal K, Savage H, East JE. 2012. HIGH PREVALENCE OF HYPERPLASTIC POLYPOSIS SYNDROME IN THE NHS BOWEL CANCER SCREENING PROGRAMME GUT, 61 (Suppl 2), pp. A382-A382. | Read more

Rajasekhar PT, Rutter MD, Bramble MG, Wilson DW, East JE, Greenaway JR, Saunders BP, Lee TJ, Barton R, Hungin P et al. 2012. ACHIEVING HIGH QUALITY COLONOSCOPY: USING GRAPHICAL REPRESENTATION TO MEASURE PERFORMANCE AND RESET STANDARDS GUT, 61 (Suppl 2), pp. A373-A373. | Read more

Rajasekhar PT, Lee TJ, Rutter MD, Bramble MG, Wilson DW, East JE, Saunders BP, Hungin P, Rees CJ. 2012. USING A "CONVERSION FACTOR" TO ESTIMATE ADENOMA DETECTION RATE GUT, 61 (Suppl 2), pp. A372-A373. | Read more

Siersema PD, Rastogi A, Leufkens AM, Akerman PA, Azzouzi K, Rothstein RI, Vleggaar FP, Repici A, Rando G, Okolo PI et al. 2012. Retrograde-viewing device improves adenoma detection rate in colonoscopies for surveillance and diagnostic workup. World J Gastroenterol, 18 (26), pp. 3400-3408. | Show Abstract | Read more

AIM: To determine which patients might benefit most from retrograde viewing during colonoscopy through subset analysis of randomized, controlled trial data. METHODS: The Third Eye® Retroscope® Randomized Clinical Evaluation (TERRACE) was a randomized, controlled, multicenter trial designed to evaluate the efficacy of a retrograde-viewing auxiliary imaging device that is used during colonoscopy to provide a second video image which allows viewing of areas on the proximal aspect of haustral folds and flexures that are difficult to see with the colonoscope's forward view. We performed a post-hoc analysis of the TERRACE data to determine whether certain subsets of the patient population would gain more benefit than others from use of the device. Subjects were patients scheduled for colonoscopy for screening, surveillance or diagnostic workup, and each underwent same-day tandem examinations with standard colonoscopy (SC) and Third Eye colonoscopy (TEC), randomized to SC followed by TEC or vice versa. RESULTS: Indication for colonoscopy was screening in 176/345 subjects (51.0%), surveillance after previous polypectomy in 87 (25.2%) and diagnostic workup in 82 (23.8%). In 4 subjects no indication was specified. Previously reported overall results had shown a net additional adenoma detection rate (ADR) with TEC of 23.2% compared to SC. Relative risk (RR) of missing adenomas with SC vs TEC as the initial procedure was 1.92 (P = 0.029). Post-hoc subset analysis shows additional ADRs for TEC compared to SC were 4.4% for screening, 35.7% for surveillance, 55.4% for diagnostic and 40.7% for surveillance and diagnostic combined. The RR of missing adenomas with SC vs TEC was 1.11 (P = 0.815) for screening, 3.15 (P = 0.014) for surveillance, 8.64 (P = 0.039) for diagnostic and 3.34 (P = 0.003) for surveillance and diagnostic combined. Although a multivariate Poisson regression suggested gender as a possibly significant factor, subset analysis showed that the difference between genders was not statistically significant. Age, bowel prep quality and withdrawal time did not significantly affect the RR of missing adenomas with SC vs TEC. Mean sizes of adenomas detected with TEC and SC were similar at 0.59 cm and 0.56 cm, respectively (P = NS). CONCLUSION: TEC allows detection of significantly more adenomas compared to SC in patients undergoing surveillance or diagnostic workup, but not in screening patients (ClinicalTrials.gov Identifier: NCT01044732).

Jaeger E, Leedham S, Lewis A, Segditsas S, Becker M, Cuadrado PR, Davis H, Kaur K, Heinimann K, Howarth K et al. 2012. Hereditary mixed polyposis syndrome is caused by a 40-kb upstream duplication that leads to increased and ectopic expression of the BMP antagonist GREM1. Nat Genet, 44 (6), pp. 699-703. | Show Abstract | Read more

Hereditary mixed polyposis syndrome (HMPS) is characterized by apparent autosomal dominant inheritance of multiple types of colorectal polyp, with colorectal carcinoma occurring in a high proportion of affected individuals. Here, we use genetic mapping, copy-number analysis, exclusion of mutations by high-throughput sequencing, gene expression analysis and functional assays to show that HMPS is caused by a duplication spanning the 3' end of the SCG5 gene and a region upstream of the GREM1 locus. This unusual mutation is associated with increased allele-specific GREM1 expression. Whereas GREM1 is expressed in intestinal subepithelial myofibroblasts in controls, GREM1 is predominantly expressed in the epithelium of the large bowel in individuals with HMPS. The HMPS duplication contains predicted enhancer elements; some of these interact with the GREM1 promoter and can drive gene expression in vitro. Increased GREM1 expression is predicted to cause reduced bone morphogenetic protein (BMP) pathway activity, a mechanism that also underlies tumorigenesis in juvenile polyposis of the large bowel.

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Jaeger E, Leedham S, Lewis A, Segditsas S, Becker M, Cuadrado PR, Davis H, Kaur K, Heinimann K, Howarth K et al. 2012. Hereditary mixed polyposis syndrome is caused by a 40-kb upstream duplication that leads to increased and ectopic expression of the BMP antagonist GREM1 Nature Genetics, 44 (6), pp. 699-703. | Show Abstract | Read more

Hereditary mixed polyposis syndrome (HMPS) is characterized by apparent autosomal dominant inheritance of multiple types of colorectal polyp, with colorectal carcinoma occurring in a high proportion of affected individuals. Here, we use genetic mapping, copy-number analysis, exclusion of mutations by high-throughput sequencing, gene expression analysis and functional assays to show that HMPS is caused by a duplication spanning the 3′ end of the SCG5 gene and a region upstream of the GREM1 locus. This unusual mutation is associated with increased allele-specific GREM1 expression. Whereas GREM1 is expressed in intestinal subepithelial myofibroblasts in controls, GREM1 is predominantly expressed in the epithelium of the large bowel in individuals with HMPS. The HMPS duplication contains predicted enhancer elements; some of these interact with the GREM1 promoter and can drive gene expression in vitro. Increased GREM1 expression is predicted to cause reduced bone morphogenetic protein (BMP) pathway activity, a mechanism that also underlies tumorigenesis in juvenile polyposis of the large bowel. © 2012 Nature America, Inc. All rights reserved.

Ignjatovic A, East JE, Subramanian V, Suzuki N, Guenther T, Palmer N, Bassett P, Ragunath K, Saunders BP. 2012. Narrow band imaging for detection of dysplasia in colitis: a randomized controlled trial. Am J Gastroenterol, 107 (6), pp. 885-890. | Show Abstract | Read more

OBJECTIVES: In ulcerative colitis surveillance, chromoendoscopy improves dysplasia detection 3 – 5-fold compared with white light endoscopy (WLE). The aim of this study was to investigate whether narrow band imaging (NBI) can improve dysplasia detection compared with WLE. METHODS: This was a randomized, parallel-group trial. A total of 220 patients were needed to be recruited to detect a threefold increase in dysplasia detection. In all, 112 patients with long-standing ulcerative colitis were randomized to colonoscopic extubation with NBI (56) or WLE (56) (1:1 ratio) at two tertiary endoscopy units in the United Kingdom. Targeted biopsies of suspicious areas and quadrantic random biopsies every 10 cm were taken in both groups. The primary outcome measure was the proportion of patients with at least one area of dysplasia detected. In a prespecified mid-point analysis, the criteria for trial discontinuation were met and the trial was stopped and analyzed at this point. RESULTS: There was no difference in the primary outcome between the two groups, with 5 patients having at least one dysplastic lesion in each group (odds ratio (OR) 1.00, 95 % confidence interval (95 % CI) 0.27 – 3.67, P = 1.00). This remained unchanged when adjusted for other variables (OR 0.69, 95 % CI 0.16 – 2.96, P = 0.62). Overall, dysplasia detection was 9 % in each arm. Yield of dysplasia from random nontargeted biopsies was 1 / 2,707 (0.04 % ). CONCLUSIONS: Overall, in this multicenter parallel-group trial, there was no difference in dysplasia detection when using NBI compared with high-definition WLE colonoscopy. Random background biopsies were ineffective in detecting dysplasia.

East JE. 2012. Proximal serrated polyp detection at colonoscopy: the best of times ...the worst of times? Gastrointest Endosc, 75 (3), pp. 521-524. | Read more

Leedham SJ, Rodenas-Cuadrado P, Howarth K, Lewis A, Mallappa S, Segditsas S, Davis H, Jeffery R, Rodriguez-Justo M, Keshav S et al. 2013. A basal gradient of Wnt and stem-cell number influences regional tumour distribution in human and mouse intestinal tracts. Gut, 62 (1), pp. 83-93. | Show Abstract | Read more

OBJECTIVE: Wnt signalling is critical for normal intestinal development and homeostasis. Wnt dysregulation occurs in almost all human and murine intestinal tumours and an optimal but not excessive level of Wnt activation is considered favourable for tumourigenesis. The authors assessed effects of pan-intestinal Wnt activation on tissue homeostasis, taking into account underlying physiological Wnt activity and stem-cell number in each region of the bowel. DESIGN: The authors generated mice that expressed temporally controlled, stabilised β-catenin along the crypt-villus axis throughout the intestines. Physiological Wnt target gene activity was assessed in different regions of normal mouse and human tissue. Human intestinal tumour mutation spectra were analysed. RESULTS: In the mouse, β-catenin stabilisation resulted in a graduated neoplastic response, ranging from dysplastic transformation of the entire epithelium in the proximal small bowel to slightly enlarged crypts of non-dysplastic morphology in the colorectum. In contrast, stem and proliferating cell numbers were increased in all intestinal regions. In the normal mouse and human intestines, stem-cell and Wnt gradients were non-identical, but higher in the small bowel than large bowel in both species. There was also variation in the expression of some Wnt modulators. Human tumour analysis confirmed that different APC mutation spectra are selected in different regions of the bowel. CONCLUSIONS: There are variable gradients in stem-cell number, physiological Wnt activity and response to pathologically increased Wnt signalling along the crypt-villus axis and throughout the length of the intestinal tract. The authors propose that this variation influences regional mutation spectra, tumour susceptibility and lesion distribution in mice and humans.

Rajasekhar PT, Rees CJ, Rutter MD, Saunders BP, Bramble MG, Hungin P, East JE, Quality Improvement in Colonoscopy Study Group. 2012. Improving the quality of colonoscopy. Gastrointest Endosc, 75 (1), pp. 229-230. | Read more

Rey J-F, Lambert R, Aabakken L, Dekker E, East JE, Kaltenbach T, Kato M, Sharma P, Tanaka S. 2011. Proceedings of a preliminary workshop at Gastro 2009--narrow banding imaging in digestive endoscopy: clinical outcome of classification (Omed-Jges Educational Meeting held on 22 November, 2009). Dig Endosc, 23 (3), pp. 251-266. | Show Abstract | Read more

This publication reports the proceedings of the preliminary meeting of the working party that met at Gastro 2009 during the World Congress in London. The purpose of the preliminary meeting was to consider the areas that require attention, to discuss some of the findings that have already been published and to agree on the way forward. Our reason for publishing these proceedings is to stimulate interest in this venture and to provide the opportunity for input from the endoscopy community worldwide. The next meeting of the working party will be at the JGES Society meeting in Aomori in April 2011 when we hope to prepare a preliminary classification. This will be presented for general discussion and debate at the International Congress of Endoscopy (ICE) in Los Angeles in September 2011.

Leufkens AM, DeMarco DC, Rastogi A, Akerman PA, Azzouzi K, Rothstein RI, Vleggaar FP, Repici A, Rando G, Okolo PI et al. 2011. Effect of a retrograde-viewing device on adenoma detection rate during colonoscopy: the TERRACE study. Gastrointest Endosc, 73 (3), pp. 480-489. | Show Abstract | Read more

BACKGROUND: Although colonoscopy is currently the optimal method for detecting colorectal polyps, some are missed. The Third Eye Retroscope provides an additional retrograde view that may detect polyps behind folds. OBJECTIVE: To determine whether the addition of the Third Eye Retroscope to colonoscopy improves the adenoma detection rate. DESIGN: Prospective, multicenter, randomized, controlled trial. SETTING: Nine European and U.S. centers. PATIENTS: Of 448 enrolled subjects, 395 had data for 2 procedures. INTERVENTIONS: Subjects underwent same-day tandem examinations with standard colonoscopy (SC) and Third Eye colonoscopy (TEC). Subjects were randomized to SC followed by TEC or TEC followed by SC. MAIN OUTCOME MEASUREMENTS: Detection rates for all polyps and adenomas with each method. RESULTS: In the per-protocol population, 173 subjects underwent SC and then TEC, and TEC yielded 78 additional polyps (48.8%), including 49 adenomas (45.8%). In 176 subjects undergoing TEC and then SC, SC yielded 31 additional polyps (19.0%), including 26 adenomas (22.6%). Net additional detection rates with TEC were 29.8% for polyps and 23.2% for adenomas. The relative risk of missing with SC compared with TEC was 2.56 for polyps (P < .001) and 1.92 for adenomas (P = .029). Mean withdrawal times for SC and TEC were 7.58 and 9.52 minutes, respectively (P < .001). The median difference in withdrawal times was 1 minute (P < .001). The mean total procedure times for SC and TEC were 16.97 and 20.87 minutes, respectively (P < .001). LIMITATIONS: Despite randomization and a large cohort, there was disparity in polyp prevalence between the 2 groups of subjects. CONCLUSION: The Third Eye Retroscope increases adenoma detection rate by visualizing areas behind folds. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01044732.).

Elsadani NN, East JE, Walters JRF. 2011. New 2010 British Society of Gastroenterology colitis surveillance guidelines: costs and surveillance intervals. Gut, 60 (2), pp. 282-283. | Read more

Ignjatovic A, East JE, Guenther T, Hoare J, Morris J, Ragunath K, Shonde A, Simmons J, Suzuki N, Thomas-Gibson S, Saunders BP. 2011. What is the most reliable imaging modality for small colonic polyp characterization? Study of white-light, autofluorescence, and narrow-band imaging. Endoscopy, 43 (2), pp. 94-99. | Show Abstract | Read more

BACKGROUND AND STUDY AIMS: In vivo optical diagnosis of small colorectal polyps has potential clinical and cost advantages, but requires accuracy and high interobserver agreement for clinically acceptability. We aimed to assess interobserver variability and diagnostic performance of endoscopic imaging modalities in characterizing small colonic polyps. METHODS: High quality still images of 80 polyps < 1 cm were recorded using white-light endoscopy (WLE), autofluorescence imaging (AFI) and narrow-band imaging with and without magnification (NBI and NBImag). All images were assessed for quality, prediction of polyp histology, and vascular pattern intensity (with NBI) by nine experienced colonoscopists (four experts in advanced imaging) from five UK centers. Interobserver agreement (kappa statistic), sensitivity, specificity, and accuracy were calculated compared with histopathological findings. RESULTS: Interobserver agreement for predicting polyp histology using NBImag was significantly better for experts (κ = 0.63, substantial) compared with nonexperts (κ = 0.30, fair; P < 0.001), and was moderate for all colonoscopists with WLE, AFI and NBI. Interobserver agreement for vascular pattern intensity using NBI was 0.69 (substantial) for experts and 0.57 (good) for nonexperts. NBImag had higher sensitivity than WLE (experts, 0.93 vs. 0.68, P < 0.001; nonexperts, 0.90 vs. 0.52, P < 0.001) and higher overall accuracy (experts, 0.76 vs. 0.64, P = 0.003; nonexperts 0.61 vs. 0.40, P < 0.001). AFI had worse accuracy than WLE for both expert colonoscopists (0.53 vs. 0.64, P = 0.02) and nonexperts (0.32 vs. 0.40, P = 0.04). CONCLUSIONS: Of the imaging modalities tested, NBImag appeared to have the best overall accuracy and interobserver agreement, although not adequate for in vivo diagnosis. NBI and AFI did not have better sensitivity, specificity, or accuracy compared with WLE.

Ignjatovic A, Thomas-Gibson S, East JE, Haycock A, Bassett P, Bhandari P, Man R, Suzuki N, Saunders BP. 2011. Development and validation of a training module on the use of narrow-band imaging in differentiation of small adenomas from hyperplastic colorectal polyps. Gastrointest Endosc, 73 (1), pp. 128-133. | Show Abstract | Read more

BACKGROUND: Experts are accurate in differentiating small adenomas from hyperplastic polyps at colonoscopy by using narrow-band imaging (NBI). OBJECTIVE: To prospectively evaluate the effectiveness of an NBI training module on individuals with varying colonoscopy experience. DESIGN: Prospective educational evaluation study. SETTING: Academic endoscopy unit. PARTICIPANTS: Twenty-one participants of varying colonoscopy experience (novices, trainees, and experienced gastroenterologists) and 5 experts in NBI. INTERVENTION: Participants completed a computer-based test module consisting of 30 NBI polyp images. No feedback was given. They then completed a computer-based training module on the use of NBI in the differentiation of adenomas and hyperplastic polyps. The test module was then completed a second time. MAIN OUTCOME MEASUREMENTS: Construct validity (the difference in baseline accuracy on the test module between different groups of participants) and content validity (difference in accuracy achieved on the test module before and after training) of the training module. RESULTS: There was a significant difference in the baseline accuracy (P < .001) between experts (0.95; 95% confidence interval [CI], 0.92-0.97), experienced colonoscopists (0.68; 95% CI, 0.68-0.74), trainees (0.75; 95% CI, 0.67-0.82), and novices (0.62; 95% CI, 0.46-0.77). Accuracy increased significantly (P < .001) for all 3 groups after training (novices 0.84; 95% CI, 0.78-0.88, trainees 0.90; 95% CI, 0.84-0.93, and experienced colonoscopists 0.84; 95% CI, 0.76-0.89). After training, the agreement was moderate at least (κ = 0.56 for novices, κ = 0.70 for trainees, and κ = 0.54 for experienced colonoscopists). LIMITATIONS: This study did not assess the accuracy of optical diagnosis in routine clinical practice. CONCLUSION: A short, computer-based training module can improve the diagnostic accuracy and interobserver agreement for the use of NBI to differentiate adenomas from hyperplastic polyps and could be used for the initial training in optical diagnosis.

Wadsworth CA, East JE, Hoare JM. 2010. Early covered-stent fracture after placement for a benign esophageal stricture. Gastrointest Endosc, 72 (6), pp. 1260-1261. | Read more

Ignjatovic A, Burling D, Ilangovan R, Clark SK, Taylor SA, East JE, Saunders BP. 2010. Flat colon polyps: what should radiologists know? Clin Radiol, 65 (12), pp. 958-966. | Show Abstract | Read more

With the recent publication of international computed tomography (CT) colonography standards, which aim to improve quality of examinations, this review informs radiologists about the significance of flat polyps (adenomas and hyperplastic polyps) in colorectal cancer pathways. We describe flat polyp classification systems and propose how flat polyps should be reported to ensure patient management strategies are based on polyp morphology as well as size. Indeed, consistency when describing flat polyps is of increasing importance given the strengthening links between CT colonography and endoscopy.

Dekker E, East JE. 2010. Does advanced endoscopic imaging increase the efficacy of surveillance colonoscopy? Endoscopy, 42 (10), pp. 866-869. | Read more

Toyonaga T, Man-i M, Fujita T, East JE, Nishino E, Ono W, Morita Y, Sanuki T, Yoshida M, Kutsumi H et al. 2010. Retrospective study of technical aspects and complications of endoscopic submucosal dissection for laterally spreading tumors of the colorectum. Endoscopy, 42 (9), pp. 714-722. | Show Abstract | Read more

BACKGROUND AND STUDY AIMS: Laterally spreading tumors - non granular type (LST-NG) are more often considered candidates for endoscopic submucosal dissection (ESD) than laterally spreading tumors - granular type (LST-G), because of their higher potential for submucosal invasion. However, ESD for LST-NG can be technically difficult. The aim of our study was to compare our ESD results for LST-NG and for LST-G. PATIENTS AND METHODS: Ninety-nine LST-NG and 169 LST-G measuring 20 mm in size or more were removed by ESD. We retrospectively evaluated the clinicopathological features of the tumors and treatment results (en bloc resection rate, procedure time and speed, rate of use of ancillary devices, and complication and recurrence rates). RESULTS: Histopathology revealed that there were more submucosally invasive lesions in the LST-NG than in the LST-G group (28 % vs. 9 %; P < 0.0001). The en bloc resection rate, en bloc R0 resection rate, and en bloc curative resection rate of LST-NG were similar to those of LST-G (LST-NG: 99 %, 98 %, and 88 %; LST-G: 99 %, 98 %, and 91 %). In LST-NG, the median procedure time tended to be longer (LST-NG: 69 min; LST-G: 60 min) and the median procedure speed was slower (LST-NG: 0.15 cm (2)/min; LST-G: 0.25 cm (2)/min; P < 0.0001). Use of ancillary devices was higher for LST-NG (38 % vs. 15 % for LST-G; P < 0.0001), as was the perforation rate (5.1 % vs. 0.6 % for LST-G; P = 0.027). No recurrence was seen in either group. CONCLUSIONS: ESD was an effective treatment method for both LST-NG and LST-G. However, the degree of technical difficulty appears higher for LST-NG than for LST-G lesions, as shown by the lower dissection speed and higher perforation rate. ESD for LST-NG should probably be performed by those with significant experience of colorectal ESD.

East JE. 2010. Commentary: surveillance colonoscopy: the long and the short of it. Colorectal Dis, 12 (7), pp. 639-641. | Read more

Tanaka S, Toyonaga T, East J, Obata D, Fujiwara S, Wakahara C, Masuda A, Man-i M, Morita Y, Sanuki T et al. 2010. Endoscopic retrieval method using a small grip-seal plastic bag for large colorectal resection specimens after endoscopic submucosal dissection. Endoscopy, 42 Suppl 2 (S 02), pp. E186-E187. | Read more

East JE, Westaby D, Rastogi A. 2010. Management of varices in cirrhosis. N Engl J Med, 362 (24), pp. 2331-2332. | Read more

Haycock AV, East JE, Swain D, Thomas-Gibson S. 2010. Development of a novel esophageal stricture simulation. Dig Dis Sci, 55 (2), pp. 321-327. | Show Abstract | Read more

BACKGROUND AND STUDY AIMS: Esophageal stricture dilatation has a significant morbidity and mortality and training can be difficult to obtain. The aim of the study was to investigate the face validity of a novel stricture simulation and evaluate its utility for training in balloon-dilatation technique. METHODS: Single-use stricture simulations were used to adapt a mechanical model for use in esophageal stricture dilatation. Face validity was evaluated using a questionnaire survey following a 40-min hands-on training session. Performance improvement was evaluated as part of a randomized blinded controlled trial. RESULTS: Face validity was established, with all trainees and instructors rating it as good or excellent overall and as adequately realistic or better in appearance. About 74% found it fairly or very realistic to dilate and 91% found it fairly or very useful for learning balloon-dilatation technique. Significant improvements in performance compared with controls were found following use of the simulation in a training episode. CONCLUSIONS: The novel esophageal stricture simulation had good face validity and has been shown to improve performance when used for training in balloon-dilatation technique. Its use allows practice without risk to patients or the need for animal cadavers.

Ignjatovic A, East JE, Suzuki N, Vance M, Guenther T, Saunders BP. 2009. Optical diagnosis of small colorectal polyps at routine colonoscopy (Detect InSpect ChAracterise Resect and Discard; DISCARD trial): a prospective cohort study. Lancet Oncol, 10 (12), pp. 1171-1178. | Show Abstract | Read more

BACKGROUND: Accurate optical diagnosis of small (<10 mm) colorectal polyps in vivo, without formal histopathology, could make colonoscopy more efficient and cost effective. The aim of this study was to assess whether optical diagnosis of small polyps is feasible and safe in routine clinical practice. METHODS: Consecutive patients with a positive faecal occult blood test or previous adenomas undergoing surveillance at St Mark's Hospital (London, UK), from June 19, 2008, to June 16, 2009, were included in this prospective study. Four colonoscopists with different levels of experience predicted polyp histology using optical diagnosis with high-definition white light, followed by narrow-band imaging without magnification and chromoendoscopy, as required. The primary outcome was accuracy of polyp characterisation using optical diagnosis compared with histopathology, the current gold standard. Accuracy of optical diagnosis to predict the next surveillance interval was also assessed and compared with surveillance intervals predicted by current guidelines using histopathology. This study is registered with ClinicalTrials.gov, NCT00888771. FINDINGS: 363 polyps smaller than 10 mm were detected in 130 patients, of which 278 polyps had both optical and histopathological diagnosis. By histology, 198 of these polyps were adenomas and 80 were non-neoplastic lesions (of which 62 were hyperplastic). Optical diagnosis accurately diagnosed 186 of 198 adenomas (sensitivity 0.94; 95% CI 0.90-0.97) and 55 of 62 hyperplastic polyps (specificity 0.89; 0.78-0.95), with an overall accuracy of 241 of 260 (0.93, 0.89-0.96) for polyp characterisation. Using optical diagnosis alone, 82 of 130 patients could be given a surveillance interval immediately after colonoscopy, and the same interval was found after formal histopathology in 80 patients (98%) using British guidelines and in 78 patients (95%) using US multisociety guidelines. INTERPRETATION: For polyps less than 10 mm in size, in-vivo optical diagnosis seems to be an acceptable strategy to assess polyp histopathology and future surveillance intervals. Dispensing with formal histopathology for most small polyps found at colonoscopy could improve the efficiency of the procedure and lead to substantial savings in time and cost. FUNDING: Leigh Family Trust, London, UK.

East JE. 2009. Colonoscopy, tumors, and inflammatory bowel disease. Endoscopy, 41 (1), pp. 59-63. | Read more

Mavranezouli I, East JE, Taylor SA. 2008. CT colonography and cost-effectiveness. Eur Radiol, 18 (11), pp. 2485-2497. | Show Abstract | Read more

CT colonography (CTC) is increasingly advocated as an effective initial screening tool for colorectal cancer. Nowadays, policy-makers are increasingly interested in cost-effectiveness issues. A number of studies assessing the cost-effectiveness of CTC have been published to date. The majority of findings indicate that CTC is probably not cost-effective when colonoscopy is available, but this conclusion is sensitive to a number of key parameters. This review discusses the findings of these studies, and considers those factors which most influence final conclusions, notably intervention costs, compliance rates, effectiveness of colonoscopy, and the assumed prevalence and natural history of diminutive advanced polyps.

East JE, Suzuki N, Bassett P, Stavrinidis M, Thomas HJ, Guenther T, Tekkis PP, Saunders BP. 2008. Narrow band imaging with magnification for the characterization of small and diminutive colonic polyps: pit pattern and vascular pattern intensity. Endoscopy, 40 (10), pp. 811-817. | Show Abstract | Read more

BACKGROUND AND STUDY AIMS: Narrow band imaging (NBI) can accurately characterize colonic polyps using microvascular appearances. We aimed to assess whether the Kudo pit pattern classification is accurate when used with NBI (without dye-spray), and if microvascular appearances or NBI pit patterns maintain accuracy for polyp characterization at sizes < 10 mm. PATIENTS AND METHODS: 116 polyps < 10 mm in size were detected in 62 patients undergoing surveillance colonoscopy. The polyps were prospectively assessed using NBI and magnification for Kudo pit pattern (III-V neoplastic, I-II non-neoplastic) and vascular pattern intensity (VPI), a measure of microvascular density (strong VPI, neoplastic; normal or weak VPI, non-neoplastic). Sensitivity, specificity, and accuracy were calculated and compared with results from histopathology. RESULTS: The mean polyp size was 3.4 mm (range 1 - 9 mm). Overall, NBI pit pattern sensitivity, specificity, and accuracy were 0.88, 0.91, and 89.6 %, respectively. Equivalent values for VPI were 0.94, 0.89, and 91.4 %. Results were similar when polyps were subdivided into diminutive polyps (size <or= 5 mm) and flat polyps. Combining both pit pattern and VPI improved the sensitivity (0.98, P = 0.06 versus NBI pit pattern alone). There was very good agreement between NBI pit pattern and VPI for prediction of dysplasia (kappa = 0.83). No evidence of a learning curve for VPI was found. The NBI pit pattern was better than the VPI at subclassifying hyperplastic from other non-neoplastic polyps (sensitivity 0.79 versus 0.56, respectively, P = 0.02), but accuracy was poor. CONCLUSION: The NBI pit pattern and VPI are both highly accurate in characterizing neoplastic colonic polyps of < 10 mm, with VPI appearing to be simple to learn. NBI has the potential to replace conventional histology for small polyps.

East JE, Tan EK, Bergman JJ, Saunders BP, Tekkis PP. 2008. Meta-analysis: narrow band imaging for lesion characterization in the colon, oesophagus, duodenal ampulla and lung. Aliment Pharmacol Ther, 28 (7), pp. 854-867. | Show Abstract | Read more

BACKGROUND: Narrow band imaging is a new endoscopic technology that highlights mucosal surface structures and microcapillaries, which may be indicative of neoplastic change. AIM: To assess the diagnostic precision of narrow band imaging for the diagnosis of epithelial neoplasia compared to conventional histology both overall and in specific organs. METHODS: We performed a meta-analysis of studies which compared narow band imaging-based diagnosis of neoplasia with histopathology as the gold standard. Search terms: 'endoscopy' and 'narrow band imaging'. RESULTS: Five hundred and eighty-two patients and 1108 lesions in 11 studies were included. Overall, sensitivity was 0.94 (95% confidence interval 0.92-0.95), specificity 0.83 (0.80-0.86); weighted area under the curve was 0.96 (standard error 0.02), diagnostic odds ratio (DOR) 72.74 (34.11-155.15). DORs were 66.65 (25.84-171.90), 61.19 (7.09-527.97), 69.74 (8.04-605.24) for colon, oesophagus and lung respectively. Studies with more than 50 patients had higher diagnostic precision, relative DOR 4.96 (1.28-19.27), P = 0.022. There was no difference in accuracy between microvessel and mucosal (pit) pattern based measures, relative DOR 1.29 (0.05-35.16), P = 0.87. There was significant heterogeneity overall between studies, Q = 31.2, P = 0.003. CONCLUSION: Narrow band imaging is accurate with high diagnostic precision for in vivo diagnosis of neoplasia across a range of organs, using simple microvessel-based measures.

East JE, Stavrindis M, Thomas-Gibson S, Guenther T, Tekkis PP, Saunders BP. 2008. A comparative study of standard vs. high definition colonoscopy for adenoma and hyperplastic polyp detection with optimized withdrawal technique. Aliment Pharmacol Ther, 28 (6), pp. 768-776. | Show Abstract | Read more

BACKGROUND: Colonoscopy has a known miss rate for polyps and adenomas. High definition (HD) colonoscopes may allow detection of subtle mucosal change, potentially aiding detection of adenomas and hyperplastic polyps. AIM: To compare detection rates between HD and standard definition (SD) colonoscopy. METHODS: Prospective, cohort study with optimized withdrawal technique (withdrawal time >6 min, antispasmodic, position changes, re-examining flexures and folds). One hundred and thirty patients attending for routine colonoscopy were examined with either SD (n = 72) or HD (n = 58) colonoscopes. RESULTS: Groups were well matched. Sixty per cent of patients had at least one adenoma detected with SD vs. 71% with HD, P = 0.20, relative risk (benefit) 1.32 (95% CI 0.85-2.04). Eighty-eight adenomas (mean +/- standard deviation 1.2 +/- 1.4) were detected using SD vs. 93 (1.6 +/- 1.5) with HD, P = 0.12; however more nonflat, diminutive (<6 mm) adenomas were detected with HD, P = 0.03. Twenty-three proximal hyperplastic polyps (0.32 +/- 0.58) were detected with SD vs. 31 (0.53 +/- 0.86) with HD, P = 0.35. Overall prevalence of proximal large (>9 mm) hyperplastic polyps was 7% (0.09 +/- 0.36). CONCLUSIONS: High definition did not lead to a significant increase in adenoma or hyperplastic polyp detection, but may help where comprehensive lesion detection is paramount. High detection rates appear possible with either SD or HD, when using an optimized withdrawal technique.

East JE, Saunders BP, Boone D, Burling D, Halligan S, Taylor SA. 2008. Uni- and bidirectional wide angle CT colonography: effect on missed areas, surface visualization, viewing time and polyp conspicuity. Eur Radiol, 18 (9), pp. 1910-1917. | Show Abstract | Read more

The effect of field of view on mucosal visualisation and reader efficiency during three-dimensional endoluminal CT colonography (CTC) was investigated. Twenty CTC datasets were reviewed at standard 90-degree and "wide" 140-degree viewing angles using customised viewing software (V3D colon; Viatronix), which listed number and size of missed mucosal areas ("missed regions tool") and percentage mucosal visualisation. We compared: (1) unidirectional and bidirectional flythrough using 140- versus 90-degree viewing angles; (2) reader analysis time comparing unidirectional 140-degree flythrough versus bidirectional 90-degree flythrough; (3) paired image snapshots of 12 polyps taken at each field of view were reviewed to assess conspicuity. All patients underwent conventional colonoscopy. Bidirectional 140-degree review reduced the numbers of missed areas by between eight- and 40-fold depending on size category, including those >1,000 mm(2), compared with standard 90-degree bidirectional flythrough (P < 0.001). Combined prone-supine unidirectional 140-degree flythrough and missed area review was 3.8 min faster than 90-degree bidirectional review (9.3 versus 5.5 min, P < 0.0001) for the same surface visualisation. When viewed as pairs, polyps were rated more conspicuous with a 90-degree field of view, P = 0.03. Wide-angle (140-degree) CTC can reduce both numbers of missed areas and review times. However, this may be at the expense of polyp conspicuity.

Burling D, Moore A, Gupta A, East J, Tam E, Pickhardt PJ, Marshall M, Taylor SA. 2008. Effect of visualization display colour on polyp conspicuity at virtual colonoscopy. Clin Radiol, 63 (9), pp. 979-985. | Show Abstract | Read more

AIM: To investigate the effect of different colour three-dimensional (3D) displays on polyp detection at virtual colonoscopy (VC). METHODS: Five VC trained observers were shown "brief flashes" (lasting 0.2s) of 125 3D endoluminal image snap-shots, repeated for each of six display colours (750 images total). One hundred images contained a single polyp (diameter range 5-42 mm) and 25 contained no polyp ("normal"). Images were reviewed in random order over five reading sessions, readers recording either normality or presence and location of a polyp. Multilevel logistic regression was used to examine any influence of colour on polyp detection stratified according to polyp size (medium 5-9 mm/large >or=10mm). The kappa statistic was used to assess effect of colour on observer agreement. RESULTS: Individual reader polyp detection rates ranged between 75-94%. Compared to the default pink "soft tissue" display, the odds of polyp detection were 0.65 (CI 0.41,1.01) for green, 0.82 (0.53,1.30) for blue, 1 (0.63,1.59) for red, 1.12 (0.7,1.79) for monochrome, and 1.15 for yellow (0.72,1.84). Overall, there was no significant difference between the displays (p=0.11). Including normal cases, there was no overall difference in correct case classification between the six colours (p=0.44). The odds of detecting large versus medium polyps was significantly greater for 3/5 observers; odds ratio (OR) 2.84-10.1, although unaffected by display colour (p=0.3). CONCLUSION: The background colour display generally has a minimal effect on polyp detection at VC, although green should be avoided.

East JE, Suzuki N, Stavrinidis M, Guenther T, Thomas HJW, Saunders BP. 2008. Authors' response Gut, 57 (8), pp. 1177-1178.

East JE, Suzuki N, Stavrinidis M, Guenther T, Thomas HJW, Saunders BP. 2008. "A brownish depressed area'': a novel narrow band imaging colonoscopic finding of a depressed adenoma - Reply GUT, 57 (8), pp. 1177-1178.

Malik AH, East JE, Buchanan GN, Kennedy RH. 2008. Endoscopic haemostasis of staple-line haemorrhage following colorectal resection. Colorectal Dis, 10 (6), pp. 616-618. | Show Abstract | Read more

OBJECTIVE: Bleeding from stapled colonic stapled anastomoses is rare, but occasionally may be severe enough to require re-operation, with associated morbidity. Endoscopic therapy is a potential alternative. METHOD: We examined a large 15-year prospective series of patients who had undergone colorectal resection with stapled anastomosis. We reviewed the management of cases where severe postoperative rectal bleeding had occurred. RESULTS: In six of 777 (0.8%) patients, bleeding occurred that was severe enough to require intervention. In the first three cases, conventional re-operation was performed. In the latter three cases, endoscopic therapy (adrenaline injection, diathermy or endoscopic clipping) was used to control the bleeding. No complications occurred as a result of endoscopic therapy, either patient or anastomosis related. CONCLUSION: Endoscopic management using standard endoscopic techniques appears safe and effective for haemostasis in colorectal stapled anastomotic bleeding. Endoscopic therapy should probably be attempted before re-operation is considered.

East JE, Saunders BP, Burling D, Boone D, Halligan S, Taylor SA. 2008. New colonoscopic technology or back-to-basic techniques? AMERICAN JOURNAL OF GASTROENTEROLOGY, 103 (6), pp. 1568-1569. | Read more

East JE, Saunders BP, Jass JR. 2008. Sporadic and syndromic hyperplastic polyps and serrated adenomas of the colon: classification, molecular genetics, natural history, and clinical management. Gastroenterol Clin North Am, 37 (1), pp. 25-v. | Show Abstract | Read more

There is now strong evidence for an alternative pathway of colorectal carcinogenesis implicating hyperplastic polyps and serrated adenomas. This article briefly reviews the evidence for this serrated pathway, provides diagnostic criteria for clinically significant hyperplastic polyps and allied serrated polyps, and suggests how this information may be translated into safe, effective guidelines for colonoscopy-based colon cancer prevention. Consideration also is given to the definition and management of hyperplastic polyposis syndrome. The currently proposed management plan for serrated polyps is tentative because of incomplete knowledge of the nature and behavior of these polyps. This article highlights key areas warranting further research.

East JE, Saunders BP. 2008. Narrow band imaging at colonoscopy: seeing through a glass darkly or the light of a new dawn? Expert Rev Gastroenterol Hepatol, 2 (1), pp. 1-4. | Read more

East JE, Guenther T, Saunders BP. 2008. Novel approaches in colorectal endoscopy: what do we need biopsies for? Pathol Res Pract, 204 (7), pp. 459-467. | Show Abstract | Read more

Magnification chromoendoscopy, narrow band imaging (NBI) and confocal endomicroscopy can all provide accurate assessment of small and diminutive colonic lesions for neoplastic change that approaches the accuracy of standard histopathology. It is likely that there will be a move to use these techniques in clinical practice for small and particularly diminutive, non-depressed lesions in the near future. Non-neoplastic lesions would be left in situ, and neoplastic lesions resected and disposed of without histopathological assessment. Histopathology would be reserved for larger lesions, indeterminate lesions or lesions where invasion was suspected. There are potentially significant cost savings and patient benefits, with a focussing of histopathological expertise on higher risk lesions, particularly in the era of bowel cancer screening. These techniques may also help target biopsies in colitis surveillance, removing the need for large numbers of random samples. However, in order to convince patients, histopathologists and those funding healthcare of the validity of this approach, further trial data will be needed, with an accreditation process for endoscopists wishing to take on this responsibility.

Saunders BP, East JE. 2008. What are the benefits of the variable-stiffness colonoscope? Nat Clin Pract Gastroenterol Hepatol, 5 (1), pp. 8-9. | Read more

East JE, Suzuki N, Stavrinidis M, Guenther T, Thomas HJW, Saunders BP. 2008. Narrow band imaging for colonoscopic surveillance in hereditary non-polyposis colorectal cancer. Gut, 57 (1), pp. 65-70. | Show Abstract | Read more

BACKGROUND: Colonoscopic surveillance for hereditary non-polyposis colorectal cancer (HNPCC) reduces death rates, but early interval cancers still occur, probably due to missed small, aggressive adenomas. Narrow band imaging (NBI), a novel endoscopic technology, highlights superficial mucosal capillaries and improves contrast for adenomas. This study examined whether a second pass with NBI in the proximal colon helped detect additional adenomas in patients with HNPCC. METHODS: 62 patients from HNPCC families (Amsterdam II or genetic criteria) attending for colonoscopic surveillance were examined twice from caecum to sigmoid-descending junction, first with high definition white light and then a second pass with NBI in a back-to-back fashion. All polyps detected were removed for histopathological analysis. RESULTS: At least one adenoma in the proximal colon was detected during the initial white light pass in 17/62 (27%). NBI detected additional adenomas in 17/62 (27%). 26/62 (42%) patients had at least one adenoma detected after both white light and NBI; absolute difference 15% (95% CI 4-25%), p = 0.004 versus white light alone. The total number of adenomas increased from 25 before NBI to 46 after NBI examination, p<0.001. The proportion of flat adenomas detected in the NBI pass, 9/21 (45%), was higher than in the white light pass, 3/25 (12%), p = 0.03. Including white light examination of the sigmoid and rectum, overall 28/62 (45%) patients had at least one adenoma detected. CONCLUSIONS: Use of NBI in the proximal colon for patients undergoing HNPCC surveillance appears to improve adenoma detection, particularly those with a flat morphology. NBI could help reduce interval cancer rates.

East JE, Tan E, Bergman JJ, Saunders BP, Tekkis PP. 2008. Narrow band imaging for lesion characterisation in the colon, oesophagus, duodenal ampulla and lung: A meta-analysis GUT, 57 pp. A29-A30.

Burling D, East JE, Taylor SA. 2007. Investigating rectal bleeding. BMJ, 335 (7632), pp. 1260-1262. | Read more

East JE, Saunders BP, Burling D, Boone D, Halligan S, Taylor SA. 2007. Surface visualization at CT colonography simulated colonoscopy: effect of varying field of view and retrograde view. Am J Gastroenterol, 102 (11), pp. 2529-2535. | Show Abstract | Read more

OBJECTIVES: Colonoscopy is the gold standard for diagnosis of mucosal disease, but has a recognized "miss rate" for polyps probably because some lesions lie in areas of the colonic surface that do not enter the field of view. Using CT colonography (CTC) simulation this pilot study aimed to determine how much colonic surface is visualized with a standard, modern optical colonoscope (field of view 140 degrees ) with or without the addition of a retrograde viewing auxiliary imaging device (RVAID; 135 degrees ) and of a wide-angle (170 degrees ) colonoscope. METHODS: Supine CTC datasets for 20 patients were reviewed with customized CTC software that calculated the percentage of colonic surface seen and number and area of nonvisualized "missed" areas at a unidirectional three-dimensional (3D) endoluminal flythrough, approximating the view obtained at optical colonoscopy. The field of view could be varied from 0-180 degrees . The combination of a colonoscope with RVAID was simulated by an additional flythrough facing the rectum. RESULTS: Mean colonic surface area was 2,743 +/- 759 cm2. Percentage colonic surface visualized at simulated optical colonoscopy with a 90 degrees , 140 degrees , and 170 degrees field of view was 68.0 +/- 5.2%, 86.6 +/- 3.3%, and 92.2 +/- 3.3%, respectively, P < 0.001. Simulation of a 140 degrees colonoscope with an RVAID resulted in almost complete surface visualization, 98.7 +/- 0.5%, with total missed area reduced 10-fold compared with a 170 degrees colonoscope, P < 0.001. CONCLUSION: CTC simulated 140 degrees optical colonoscopy visualizes over 85% of the colonic surface. 170 degrees colonoscopy provides a modest reduction in missed surface and the simulated addition of RVAIDs appears beneficial.

East JE, Saunders BP. 2007. Look, remove, and discard: can narrow-band imaging replace histopathology for small colorectal polyps? It is time to push the button! Gastrointest Endosc, 66 (5), pp. 953-956. | Read more

East JE, Brooker JC, Rutter MD, Saunders BP. 2007. A pilot study of intrastricture steroid versus placebo injection after balloon dilatation of Crohn's strictures. Clin Gastroenterol Hepatol, 5 (9), pp. 1065-1069. | Show Abstract | Read more

BACKGROUND & AIMS: Restricturing after ileocolonic resection for Crohn's disease is common. Colonoscopic balloon dilatation is effective but repeated dilatations often are required. Intrastricture steroid injection after balloon dilatation has been reported to reduce the need for repeat dilatation in retrospective series, but no randomized data are available. METHODS: We performed a pilot study comparing local quadrantic injection of triamcinolone (40 mg total dose) after endoscopic balloon dilatation of Crohn's ileocolonic anastomotic strictures vs saline placebo. The primary end point was time to redilatation or surgery. Patients were followed up for 52 weeks. RESULTS: Thirteen patients were randomized, 7 to steroid and 6 to placebo. Groups were well matched for baseline and dilatation characteristics. In the intention-to-treat analysis, 1 of 6 patients in the placebo group and 5 of 7 patients in the steroid group needed redilatation (log rank test P = .06; Cox regression P = .10; hazard ratio, 6.1; 95% confidence interval, 0.7-53.0). In the per-protocol analysis the differences were more significant (log rank test P = .03; Cox regression P = .07; hazard ratio, 7.7; 95% confidence interval, 0.9-67.9). CONCLUSIONS: A single treatment of intrastricture triamcinolone injection did not reduce the time to redilatation after balloon dilatation of Crohn's ileocolonic anastomotic strictures and there was a trend toward a worse outcome. The use of this technique in clinical practice should be considered carefully until more data are available.

East JE, Guenther T, Kennedy RH, Saunders BP. 2007. Narrow band imaging avoids potential chromoendoscopy risks. Gut, 56 (8), pp. 1168-1169.

East JE, Suzuki N, Saunders BP. 2007. Comparison of magnified pit pattern interpretation with narrow band imaging versus chromoendoscopy for diminutive colonic polyps: a pilot study. Gastrointest Endosc, 66 (2), pp. 310-316. | Show Abstract | Read more

BACKGROUND: Chromoendoscopy can accurately differentiate neoplastic from nonneoplastic polyps in the colon. Narrow band imaging (NBI) has been described as "electronic chromoendoscopy," but it is unclear whether pit patterns seen with chromoendoscopy are identical to those with NBI. OBJECTIVE: Pilot study to compare features of diminutive polyps assessed with magnification NBI and chromoendoscopy. DESIGN: Prospective polyp series. SETTING: Single tertiary referral center in the United Kingdom. PATIENTS: Twenty patients seen for routine colonoscopy. INTERVENTION: Digital images of each polyp recorded with NBI and chromoendoscopy were subsequently assessed as single images in a random order and as paired polyp images by experienced European- and Japanese-trained endoscopists. MAIN OUTCOME MEASUREMENTS: Pit pattern (Kudo classification); vascular pattern intensity (weak, normal, strong); predicted histology; pit pattern and vessel network clarity (scale 1-3, 1 poor, 3 excellent). RESULTS: A total of 33 polyps <or=6 mm were assessed. Chromoendoscopic and NBI pit patterns were different for 12 and 20 of 33 polyps (Japanese and European, respectively), combined kappa 0.23, P < .001 compared with published intraobsever variation. Sensitivity, specificity, and accuracy for neoplasia were comparable for chromoendoscopic and NBI pit patterns and vascular pattern intensity for both observers. Vessel network clarity was better with NBI, P < .001 (both), as was pit pattern clarity, P = .04 (European). LIMITATIONS: Small sample size; pilot study. CONCLUSIONS: Pit patterns were not always identical with NBI and chromoendoscopy. The Kudo classification may need to be modified and revalidated before it can be used with confidence with NBI. Vascular pattern intensity, a simple color change, appears as accurate as pit pattern.

East JE, Kamm MA, Bassett P, Saunders BP. 2007. Magnification pan-chromoendoscopy remains the mainstay for colitis dysplasia detection and differentiation. Gastroenterology, 133 (1), pp. 366-367. | Read more

East JE, Suzuki N, Arebi N, Bassett P, Saunders BP. 2007. Position changes improve visibility during colonoscope withdrawal: a randomized, blinded, crossover trial. Gastrointest Endosc, 65 (2), pp. 263-269. | Show Abstract | Read more

BACKGROUND: Adequate distension is essential to maximize neoplasia detection during colonoscope withdrawal. Position changes may improve distension but are often not performed in routine practice. OBJECTIVE: To assess whether routine position changes improve luminal distension during colonoscope withdrawal. DESIGN: Randomized, blinded, crossover trial. SETTING: Single tertiary-referral center, United Kingdom. PATIENTS: Fourteen patients attending for routine colonoscopy. INTERVENTIONS: Videotaped, back-to-back examination of colon proximal to rectosigmoid junction in left lateral position only, then with position changes: left lateral for the cecum to the hepatic flexure, supine for the transverse colon, and right lateral for the splenic flexure and the descending colon, or vice versa. MAIN OUTCOME MEASUREMENTS: Luminal distension as scored by a blinded video reviewer. Luminal distension was scored on a scale of 1 to 5 for each colonic area: 1, complete collapse; 5, widely distended to limit of view. A score of 2 or less was considered inadequate for diagnosis. RESULTS: Scores for the 2 examinations from the blinded video reviewer were significantly higher in the transverse, the splenic flexure, and the descending colon, P = .02, .002, and <.001, respectively. Without position changes, 6 of 14 of patients (43%) would have had a nondiagnostic distension score (1 or 2) in at least 1 colonic area, P = .03. LIMITATIONS: Nonvalidated scoring system for luminal distension, however, good agreement between endoscopist and blinded reviewer, weighted kappa 0.53, 95% confidence interval 0.38-0.69. CONCLUSIONS: Position change, a cost-neutral intervention, during colonoscope withdrawal improved luminal distension between hepatic flexure and sigmoid-descending junction and has the potential to reduce adenoma and early cancer miss rates.

East JE. 2006. Statin Therapy after Stroke or Transient Ischemic Attack New England Journal of Medicine, 355 (22), pp. 2368-2371. | Read more

East JE, Suzuki N, von Herbay A, Saunders BP. 2006. Narrow band imaging with magnification for dysplasia detection and pit pattern assessment in ulcerative colitis surveillance: a case with multiple dysplasia associated lesions or masses. Gut, 55 (10), pp. 1432-1435. | Show Abstract | Read more

A 62 year old man with longstanding ulcerative colitis and previous endoscopic excision of two dysplasia associated lesions or masses (DALMs) was admitted to our endoscopy unit for evaluation and resection of other possible DALMs. He had previously been offered and refused colectomy because of comorbidity from Parkinson's disease. He had multiple polypoid and sessile lesions which were assessed using a third generation prototype narrow band imaging (NBI) colonoscope with magnification. Selected lesions were either biopsied or resected with a combination of endoscopic submucosal dissection and endoscopic mucosal resection techniques. We correlated the pit pattern and vascular pattern intensity seen with magnification NBI with histology of both inflammatory and dysplastic lesions. Dysplastic areas showed Kudo pit patterns II, IIIL, and IV and high vascular pattern intensity. Non-dysplastic and dysplastic areas of recurrence immediately adjacent to the scar from a previous endoscopic mucosal resection site were also assessed. This is the first case report where NBI has been shown to help in DALM detection and to distinguish dysplastic from non-dysplastic mucosa in ulcerative colitis.

East JE, Saunders BP, Boone D, Halligan S, Taylor SA. 2006. Comprehensive mucosal visualization at optical colonoscopy: Technique remains the key. Gastroenterology, 131 (3), pp. 975-976. | Read more

East JE, Foweraker JE, Murgatroyd FD. 2005. Gentamicin induced ototoxicity during treatment of enterococcal endocarditis: resolution with substitution by netilmicin. Heart, 91 (5), pp. e32. | Show Abstract | Read more

Enterococcal endocarditis can be very difficult to eradicate, requiring prolonged treatment with a combination of a penicillin and an aminoglycoside. In this patient with a pacemaker associated enterococcal endocarditis, ototoxicity occurred due to total gentamicin dose despite plasma concentrations consistently within the treatment range. Substitution with netilmicin, without a break in aminoglycoside treatment, resulted in a rapid improvement in hearing and allowed the required course of aminoglycoside to be completed. The risk factors for ototoxicity with gentamicin are reviewed, in particular the dangers of increasing age and of multiple and prolonged courses. Close treatment monitoring does not totally avoid this risk, especially when prolonged aminoglycoside treatment is required. This case emphasises the need for prompt investigation and adequate, definitive treatment of enterococcal endocarditis to avoid the increased risk consequent on repeated courses of antibiotics. The resolution of the ototoxicity with netilmicin is consistent with other reports of lower cochleotoxicity than with other aminoglycosides.

Mehta G, East J, Thoua N, Thillainayagam A, Bansi D. 2005. Prophylaxis and treatment of infective endocarditis in adults: a concise guide. Clin Med (Lond), 5 (2), pp. 183.

Vleugels JLA, Rutter MD, Ragunath K, Rees CJ, Ponsioen CY, Lahiff C, Ket SN, Wanders LK, Samuel S, Butt F et al. 2018. Chromoendoscopy versus autofluorescence imaging for neoplasia detection in patients with longstanding ulcerative colitis (FIND-UC): an international, multicentre, randomised controlled trial. Lancet Gastroenterol Hepatol, 3 (5), pp. 305-316. | Show Abstract | Read more

BACKGROUND: Patients with longstanding ulcerative colitis undergo regular dysplasia surveillance because they have an increased colorectal cancer risk. Autofluorescence imaging and chromoendoscopy improve dysplasia detection. The aim of this study was to determine whether autofluorescence imaging should be further studied as an alternative method for dysplasia surveillance in patients with longstanding ulcerative colitis. METHODS: This prospective, international, randomised controlled trial included patients from an ulcerative colitis-dysplasia surveillance cohort from five centres in the Netherlands and the UK. Eligible patients were aged 18 years or older who were undergoing dysplasia surveillance after being diagnosed with extensive colitis (Montreal E3) at least 8 years before study start or with left-sided colitis (Montreal E2) at least 15 years before study start. Randomisation (1:1) was minimised for a previous personal history of histologically proven dysplasia and concomitant primary sclerosing cholangitis. The coprimary outcomes were the proportion of patients in whom at least one dysplastic lesion was detected and the mean number of dysplastic lesions per patient. The relative dysplasia detection rate, calculated as the ratio of the detection rates by autofluorescence imaging and chromoendoscopy, needed to be more than 0·67 (using an 80% CI) for both primary outcomes to support a subsequent large non-inferiority trial. Outcomes were analysed on a per-protocol basis. The trial is registered at the Netherlands Trial Register, number NTR4062. FINDINGS: Between Aug 1, 2013, and March 10, 2017, 210 patients undergoing colonoscopy surveillance for longstanding ulcerative colitis were randomised for inspection with either autofluorescence imaging (n=105) or chromoendoscopy (n=105). Dysplasia was detected in 13 (12%) patients by autofluorescence imaging and in 20 patients (19%) by chromoendoscopy. The relative dysplasia detection rate of autofluorescence imaging versus chromoendoscopy for the proportion of patients with ulcerative colitis with at least one dysplastic lesion was 0·65 (80% CI 0·43-0·99). The mean number of detected dysplastic lesions per patient was 0·13 (SD 0·37) for autofluorescence imaging and 0·37 (1·02) for chromoendoscopy (relative dysplasia detection rate 0·36, 80% CI 0·21-0·61). Adverse events were reported for two patients in the autofluorescence imaging group (one patient had intraprocedural mild bleeding, and one patient had abdominal pain) and for three patients in the chromoendoscopy group (two patients had intraprocedural mild bleeding, and one patient had perforation). INTERPRETATION: Autofluorescence imaging did not meet criteria for proceeding to a large non-inferiority trial. Therefore, existing autofluorescence imaging technology should not be further investigated as an alternative dysplasia surveillance method. FUNDING: Olympus Europe and Olympus Keymed.

East JE, Atkin WS, Bateman AC, Clark SK, Dolwani S, Ket SN, Leedham SJ, Phull PS, Rutter MD, Shepherd NA et al. 2017. British Society of Gastroenterology position statement on serrated polyps in the colon and rectum. Gut, 66 (7), pp. 1181-1196. | Show Abstract | Read more

Serrated polyps have been recognised in the last decade as important premalignant lesions accounting for between 15% and 30% of colorectal cancers. There is therefore a clinical need for guidance on how to manage these lesions; however, the evidence base is limited. A working group was commission by the British Society of Gastroenterology (BSG) Endoscopy section to review the available evidence and develop a position statement to provide clinical guidance until the evidence becomes available to support a formal guideline. The scope of the position statement was wide-ranging and included: evidence that serrated lesions have premalignant potential; detection and resection of serrated lesions; surveillance strategies after detection of serrated lesions; special situations-serrated polyposis syndrome (including surgery) and serrated lesions in colitis; education, audit and benchmarks and research questions. Statements on these issues were proposed where the evidence was deemed sufficient, and re-evaluated modified via a Delphi process until >80% agreement was reached. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool was used to assess the strength of evidence and strength of recommendation for finalised statements. Key recommendation: we suggest that until further evidence on the efficacy or otherwise of surveillance are published, patients with sessile serrated lesions (SSLs) that appear associated with a higher risk of future neoplasia or colorectal cancer (SSLs ≥10 mm or serrated lesions harbouring dysplasia including traditional serrated adenomas) should be offered a one-off colonoscopic surveillance examination at 3 years (weak recommendation, low quality evidence, 90% agreement).

East JE, Vleugels JL, Roelandt P, Bhandari P, Bisschops R, Dekker E, Hassan C, Horgan G, Kiesslich R, Longcroft-Wheaton G et al. 2016. Advanced endoscopic imaging: European Society of Gastrointestinal Endoscopy (ESGE) Technology Review. Endoscopy, 48 (11), pp. 1029-1045. | Show Abstract | Read more

Background and aim: This technical review is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the utilization of advanced endoscopic imaging in gastrointestinal (GI) endoscopy. Methods: This technical review is based on a systematic literature search to evaluate the evidence supporting the use of advanced endoscopic imaging throughout the GI tract. Technologies considered include narrowed-spectrum endoscopy (narrow band imaging [NBI]; flexible spectral imaging color enhancement [FICE]; i-Scan digital contrast [I-SCAN]), autofluorescence imaging (AFI), and confocal laser endomicroscopy (CLE). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendation and the quality of evidence. Main recommendations:1. We suggest advanced endoscopic imaging technologies improve mucosal visualization and enhance fine structural and microvascular detail. Expert endoscopic diagnosis may be improved by advanced imaging, but as yet in community-based practice no technology has been shown consistently to be diagnostically superior to current practice with high definition white light. (Low quality evidence.) 2. We recommend the use of validated classification systems to support the use of optical diagnosis with advanced endoscopic imaging in the upper and lower GI tracts (strong recommendation, moderate quality evidence). 3. We suggest that training improves performance in the use of advanced endoscopic imaging techniques and that it is a prerequisite for use in clinical practice. A learning curve exists and training alone does not guarantee sustained high performances in clinical practice. (Weak recommendation, low quality evidence.) Conclusion: Advanced endoscopic imaging can improve mucosal visualization and endoscopic diagnosis; however it requires training and the use of validated classification systems.

Veitch AM, Uedo N, Yao K, East JE. 2015. Optimizing early upper gastrointestinal cancer detection at endoscopy. Nat Rev Gastroenterol Hepatol, 12 (11), pp. 660-667. | Show Abstract | Read more

Survival rates for upper gastrointestinal cancers are poor and oesophageal cancer incidence is increasing. Upper gastrointestinal cancer is also often missed during examinations; a predicament that has not yet been sufficiently addressed. Improvements in the detection of premalignant lesions, early oesophageal and gastric cancers will enable organ-preserving endoscopic therapy, potentially reducing the number of advanced upper gastrointestinal cancers and resulting in improved prognosis. Japan is a world leader in high-quality diagnostic upper gastrointestinal endoscopy and the clinical routine in this country differs substantially from Western practice. In this Perspectives article, we review lessons learnt from Japanese gastroscopy technique, training and screening for risk stratification. We suggest a key performance indicator for upper gastrointestinal endoscopy with a minimum total procedure time of 8 min, and examine how quality assurance concepts in bowel cancer screening in the UK could be applied to upper gastrointestinal endoscopy and improve clinical practice.

East JE, Vieth M, Rex DK. 2015. Serrated lesions in colorectal cancer screening: detection, resection, pathology and surveillance. Gut, 64 (6), pp. 991-1000. | Read more

Rajasekhar PT, Rees CJ, Bramble MG, Wilson DW, Rutter MD, Saunders BP, Hungin APS, East JE. 2015. A multicenter pragmatic study of an evidence-based intervention to improve adenoma detection: the Quality Improvement in Colonoscopy (QIC) study. Endoscopy, 47 (3), pp. 217-224. | Show Abstract | Read more

BACKGROUND AND STUDY AIMS: Low adenoma detection rates (ADRs) at colonoscopy are linked to significantly higher interval cancer rates, and vary between colonoscopists. Studies demonstrate that lesion detection is improved by: withdrawal time of ≥ 6 minutes; use of hyoscine butylbromide; position change; and rectal retroflexion. We evaluated the feasibility of implementing the above "bundle" of interventions into colonoscopy practice, and the effect on ADR. MATERIALS AND METHODS: A longitudinal cohort design was used. Implementation combined central training, local promotion, and feedback. The uptake marker was change in hyoscine butylbromide use. Comparisons were between the 3 months before and the 9 months after the implementation phase, globally, by endoscopy unit and by quartile when colonoscopists were ranked according to baseline ADR. Chi-squared or Fisher's tests were used to evaluate significance. RESULTS: 12 units participated. Global and quartile analyses included data from 118 and 68 colonoscopists and 17 508 and 14 193 procedures respectively. A significant increase in hyoscine butylbromide use was observed globally (54.4 % vs. 15.8 %, P < 0.001), in all endoscopy units (P < 0.001) and quartiles (P < 0.001). A significant increase in ADR was observed globally (18.1 % vs. 16.0 %, P = 0.002) and in the lower two colonoscopist quartiles (P < 0.001), with a nonsignificant increase in the upper middle quartile and a significant fall to 21.5 %. in the upper quartile. The significant variations in ADR among the upper three quartiles disappeared. CONCLUSION: In routine clinical practice, introduction of a simple, inexpensive, evidence-based "bundle" of measures is feasible and is associated with higher global ADR, driven by improvements amongst the poorest performing colonoscopists.

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Davis H, Irshad S, Bansal M, Rafferty H, Boitsova T, Bardella C, Jaeger E, Lewis A, Freeman-Mills L, Giner FC et al. 2015. Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche Nature Medicine, 21 (1), pp. 62-70. | Show Abstract | Read more

© 2014 Nature America, Inc. All rights reserved. Hereditary mixed polyposis syndrome (HMPS) is characterized by the development of mixed-morphology colorectal tumors and is caused by a 40-kb genetic duplication that results in aberrant epithelial expression of the gene encoding mesenchymal bone morphogenetic protein antagonist, GREM1. Here we use HMPS tissue and a mouse model of the disease to show that epithelial GREM1 disrupts homeostatic intestinal morphogen gradients, altering cell fate that is normally determined by position along the vertical epithelial axis. This promotes the persistence and/or reacquisition of stem cell properties in Lgr5-negative progenitor cells that have exited the stem cell niche. These cells form ectopic crypts, proliferate, accumulate somatic mutations and can initiate intestinal neoplasia, indicating that the crypt base stem cell is not the sole cell of origin of colorectal cancer. Furthermore, we show that epithelial expression of GREM1 also occurs in traditional serrated adenomas, sporadic premalignant lesions with a hitherto unknown pathogenesis, and these lesions can be considered the sporadic equivalents of HMPS polyps.

van Doorn SC, Hazewinkel Y, East JE, van Leerdam ME, Rastogi A, Pellisé M, Sanduleanu-Dascalescu S, Bastiaansen BAJ, Fockens P, Dekker E. 2015. Polyp morphology: an interobserver evaluation for the Paris classification among international experts. Am J Gastroenterol, 110 (1), pp. 180-187. | Show Abstract | Read more

OBJECTIVES: The Paris classification is an international classification system for describing polyp morphology. Thus far, the validity and reproducibility of this classification have not been assessed. We aimed to determine the interobserver agreement for the Paris classification among seven Western expert endoscopists. METHODS: A total of 85 short endoscopic video clips depicting polyps were created and assessed by seven expert endoscopists according to the Paris classification. After a digital training module, the same 85 polyps were assessed again. We calculated the interobserver agreement with a Fleiss kappa and as the proportion of pairwise agreement. RESULTS: The interobserver agreement of the Paris classification among seven experts was moderate with a Fleiss kappa of 0.42 and a mean pairwise agreement of 67%. The proportion of lesions assessed as "flat" by the experts ranged between 13 and 40% (P<0.001). After the digital training, the interobserver agreement did not change (kappa 0.38, pairwise agreement 60%). CONCLUSIONS: Our study is the first to validate the Paris classification for polyp morphology. We demonstrated only a moderate interobserver agreement among international Western experts for this classification system. Our data suggest that, in its current version, the use of this classification system in daily practice is questionable and it is unsuitable for comparative endoscopic research. We therefore suggest introduction of a simplification of the classification system.

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Wanders LK, Dekker E, Pullens B, Bassett P, Travis SPL, East JE. 2014. Cancer risk after resection of polypoid dysplasia in patients with longstanding ulcerative colitis: A meta-analysis Clinical Gastroenterology and Hepatology, 12 (5), pp. 756-764. | Show Abstract | Read more

Background & Aims: American and European guidelines propose complete endoscopic resection of polypoid dysplasia (adenomas or adenoma-like masses) in patients with longstanding colitis, with close endoscopic follow-up. The incidence of cancer after detection of flat low-grade dysplasia or dysplasia-associated lesion or mass is estimated at 14 cases/1000 years of patient follow-up. However, the risk for polypoid dysplasia has not been determined with precision. We investigated the risk of cancer after endoscopic resection of polypoid dysplasia in patients with ulcerative colitis. Methods: MEDLINE, EMBASE, PubMed, and the Cochrane library were searched for studies of patients with colitis and resected polypoid dysplasia, with reports of colonoscopic follow-up and data on cancers detected. Outcomes from included articles were pooled to provide a single combined estimate of outcomes by using Poisson regression. Results: Of 425 articles retrieved, we analyzed data from 10 studies, comprising 376 patients with colitis and polypoid dysplasia with a combined 1704 years of follow-up. A mean of 2.8 colonoscopies were performed for each patient after the index procedure (range, 0-15 colonoscopies). The pooled incidence of cancer was 5.3 cases (95% confidence interval, 2.7-10.1 cases)/1000 years of patient follow-up. There was no evidence of heterogeneity or publication bias. The pooled rate of any dysplasia was 65 cases (95% confidence interval, 54-78 cases)/1000 patient years. Conclusion: Patients with colitis have a low risk of colorectal cancer after resection of polypoid dysplasia; these findings support the current strategy of resection and surveillance. However, these patients have a 10-fold greater risk of developing any dysplasia than colorectal cancer and should undergo close endoscopic follow-up. © 2014 AGA Institute.

Kamiński MF, Hassan C, Bisschops R, Pohl J, Pellisé M, Dekker E, Ignjatovic-Wilson A, Hoffman A, Longcroft-Wheaton G, Heresbach D et al. 2014. Advanced imaging for detection and differentiation of colorectal neoplasia: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy, 46 (5), pp. 435-449. | Show Abstract | Read more

MAIN RECOMMENDATIONS: 1 ESGE suggests the routine use of high definition white-light endoscopy systems for detecting colorectal neoplasia in average risk populations (weak recommendation, moderate quality evidence). 2 ESGE recommends the routine use of high definition systems and pancolonic conventional or virtual (narrow band imaging [NBI], i-SCAN) chromoendoscopy in patients with known or suspected Lynch syndrome (strong recommendation, low quality evidence). 2b ESGE recommends the routine use of high definition systems and pancolonic conventional or virtual (NBI) chromoendoscopy in patients with known or suspected serrated polyposis syndrome (strong recommendation, low quality evidence). 3 ESGE recommends the routine use of 0.1 % methylene blue or 0.1 % - 0.5 % indigo carmine pancolonic chromoendoscopy with targeted biopsies for neoplasia surveillance in patients with long-standing colitis. In appropriately trained hands, in the situation of quiescent disease activity and adequate bowel preparation, nontargeted, four-quadrant biopsies can be abandoned (strong recommendation, high quality evidence). 4 ESGE suggests that virtual chromoendoscopy (NBI, FICE, i-SCAN) and conventional chromoendoscopy can be used, under strictly controlled conditions, for real-time optical diagnosis of diminutive (≤ 5 mm) colorectal polyps to replace histopathological diagnosis. The optical diagnosis has to be reported using validated scales, must be adequately photodocumented, and can be performed only by experienced endoscopists who are adequately trained and audited (weak recommendation, high quality evidence). 5 ESGE suggests the use of conventional or virtual (NBI) magnified chromoendoscopy to predict the risk of invasive cancer and deep submucosal invasion in lesions such as those with a depressed component (0-IIc according to the Paris classification) or nongranular or mixed-type laterally spreading tumors (weak recommendation, moderate quality evidence). CONCLUSION: Advanced imaging techniques will need to be applied in specific patient groups in routine clinical practice and to be taught in endoscopic training programs.

Rastogi A, Rao DS, Gupta N, Grisolano SW, Buckles DC, Sidorenko E, Bonino J, Matsuda T, Dekker E, Kaltenbach T et al. 2014. Impact of a computer-based teaching module on characterization of diminutive colon polyps by using narrow-band imaging by non-experts in academic and community practice: a video-based study. Gastrointest Endosc, 79 (3), pp. 390-398. | Show Abstract | Read more

BACKGROUND: Experts can accurately characterize the histology of diminutive polyps with narrow-band imaging (NBI). There are limited data on the performance of non-experts. OBJECTIVE: To assess the impact of a computer-based teaching module on the accuracy of predicting polyp histology with NBI by non-experts (in academics and community practice) by using video clips. DESIGN: Prospective, observational study. SETTING: Academic and community practice. PARTICIPANTS: A total of 15 gastroenterologists participated-5 experts in NBI, 5 non-experts in academic practice, and 5 non-experts in community practice. INTERVENTION: Participants reviewed a 20-minute, computer-based teaching module outlining the different NBI features for hyperplastic and adenomatous polyps. MAIN OUTCOME MEASUREMENTS: Performance characteristics in characterizing the histology of diminutive polyps with NBI by using short video clips before (pretest) and after (posttest) reviewing the teaching module. RESULTS: Non-experts in academic practice showed a significant improvement in the sensitivity (54% vs 79%; P < .001), accuracy (64% vs 81%; P < .001), and proportion of high-confidence diagnoses (49% vs 69%; P < .001) in the posttest. Non-experts in community practice had significantly higher sensitivity (58% vs 75%; P = .004), specificity (76% vs 90%; P = .04), accuracy (64% vs 81%; P < .001), and proportion of high-confidence diagnoses (49% vs 72%; P < .001) in the posttest. Performance of experts in NBI was significantly better than non-experts in both academic and community practice. LIMITATIONS: Selection bias in selecting good quality videos. Performance not assessed during live colonoscopy. CONCLUSION: Academic and community gastroenterologists without prior experience in NBI can achieve significant improvements in characterizing diminutive polyp histology after a brief computer-based training. The durability of these results and applicability in everyday practice are uncertain.

Wanders LK, East JE, Uitentuis SE, Leeflang MMG, Dekker E. 2013. Diagnostic performance of narrowed spectrum endoscopy, autofluorescence imaging, and confocal laser endomicroscopy for optical diagnosis of colonic polyps: a meta-analysis. Lancet Oncol, 14 (13), pp. 1337-1347. | Show Abstract | Read more

BACKGROUND: Novel endoscopic technologies could allow optical diagnosis and resection of colonic polyps without histopathological testing. Our aim was to establish the sensitivity, specificity, and real-time negative predictive value of three types of narrowed spectrum endoscopy (narrow-band imaging [NBI], image-enhanced endoscopy [i-scan], and Fujinon intelligent chromoendoscopy [FICE]), confocal laser endomicroscopy (CLE), and autofluorescence imaging for differentiation between neoplastic and non-neoplastic colonic lesions. METHODS: We identified relevant studies through a search of Medline, Embase, PubMed, and the Cochrane Library. Clinical trials and observational studies were eligible for inclusion when the diagnostic performance of NBI, i-scan, FICE, autofluorescence imaging, or CLE had been assessed for differentiation, with histopathology as the reference standard, and for which a 2 × 2 contingency table of lesion diagnosis could be constructed. We did a random-effects bivariate meta-analysis using a non-linear mixed model approach to calculate summary estimates of sensitivity and specificity, and plotted estimates in a summary receiver-operating characteristic curve. FINDINGS: We included 91 studies in our analysis: 56 were of NBI, ten of i-scan, 14 of FICE, 11 of CLE, and 11 of autofluorescence imaging (more than one of the investigated modalities assessed in eight studies). For NBI, overall sensitivity was 91·0% (95% CI 88·6-93·0), specificity 85·6% (81·3-89·0), and real-time negative predictive value 82·5% (75·4-87·9). For i-scan, overall sensitivity was 89·3% (83·3-93·3), specificity 88·2% (80·3-93·2), and real-time negative predictive value 86·5% (78·0-92·1). For FICE, overall sensitivity was 91·8% (87·1-94·9), specificity 83·5% (77·2-88·3), and real-time negative predictive value 83·7% (77·5-88·4). For autofluorescence imaging, overall sensitivity was 86·7% (79·5-91·6), specificity 65·9% (50·9-78·2), and real-time negative predictive value 81·5% (54·0-94·3). For CLE, overall sensitivity was 93·3% (88·4-96·2), specificity 89·9% (81·8-94·6), and real-time negative predictive value 94·8% (86·6-98·1). INTERPRETATION: All endoscopic imaging techniques other than autofluorescence imaging could be used by appropriately trained endoscopists to make a reliable optical diagnosis for colonic lesions in daily practice. Further research should be focused on whether training could help to improve negative predictive values. FUNDING: None.

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