Imperial College London

Professor Julian Teare

Faculty of MedicineDepartment of Surgery & Cancer

Emeritus Professor
 
 
 
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Contact

 

+44 (0)20 3312 1072j.teare

 
 
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Location

 

CL3 026St Marys Multiple BuildingsSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

169 results found

Glover B, Teare J, Patel N, 2021, Assessment of H. pylori status by examination of gastric mucosal patterns: diagnostic accuracy of white-light endoscopy and narrow-band imaging, BMJ Open Gastroenterology, Vol: 8, Pages: 1-9, ISSN: 2054-4774

ObjectivesHelicobacter pylori infection is a common cause of chronic gastritis worldwide and an established risk factor for developing gastric malignancy. The endoscopic appearances predicting H. pylori status are an ongoing area of research, as are their diagnostic accuracies. This study aimed to establish the diagnostic accuracy of several mucosal features predictive of H. pylori negative status and formulate a simple prediction model for use at the time of endoscopy.DesignPatients undergoing high-definition upper GI endoscopy without magnification were recruited prospectively. During endoscopy, the presence or absence of specific endoscopic findings was noted. Sydney protocol biopsies were used as the diagnostic reference standard, and urease test if taken. The results informed a logistic regression model used to produce a simple diagnostic approach. This model was subsequently validated using a further cohort of 30 patients.Results153 patients were recruited and completed the study protocol. The prevalence of active H. pylori infection was 18.3% (28/153). The overall diagnostic accuracy of the simple prediction model was 80.0%, and 100% of patients with active H. pylori infection were correctly classified. Presence of regular arrangement of collecting venules (RAC) showed a positive predictive value for H. pylori naïve status of 90.7%, rising to 93.6% for patients under the age of 60.ConclusionA simple endoscopic model may be accurate for predicting H. pylori status of a patient, and the need for biopsy-based tests. The presence of RAC in the stomach is an accurate predictor of H. pylori negative status, particularly in patients under the age of 60.

Journal article

Nazarian S, Glover B, Ashrafian H, Darzi A, Teare Jet al., 2021, Diagnostic Accuracy of Artificial Intelligence and Computer-Aided Diagnosis for the Detection and Characterization of Colorectal Polyps: Systematic Review and Meta-analysis, JOURNAL OF MEDICAL INTERNET RESEARCH, Vol: 23, ISSN: 1438-8871

Journal article

Alexander J, Ibraheim H, Sheth B, Little J, Khan MS, Richards C, Hunter N, Chauhan D, Ratnakumaran R, McHugh K, Pinato DJ, Nathan P, Choy J, Cursz SM, Furness A, Turajlic S, Pickering L, Larkin J, Teare J, Papa S, Speight A, Powell Net al., 2021, Clinical outcomes of patients with corticosteroid refractory immune checkpoint inhibitor induced enterocolitis treated with infliximab, Journal for ImmunoTherapy of Cancer, Vol: 9, Pages: 1-9, ISSN: 2051-1426

IntroductionImmune Checkpoint Inhibitors (CPI) have changed the treatment landscape for many cancers, but also cause severe inflammatory side effects including enterocolitis. CPI-induced enterocolitis is treated empirically with corticosteroids, and infliximab (IFX) is used in corticosteroid-refractory cases. However, robust outcome data for these patients are scarce. MethodsWe conducted a multi-centre (six cancer centres), cohort study of outcomes in patients treated with IFX for corticosteroid-refractory CPI-induced enterocolitis between 2007 and 2020. The primary outcome was corticosteroid-free clinical remission (CFCR) with CTCAE grade 0 for diarrhoea at 12 weeks after IFX initiation. We also assessed cancer outcomes at one year using RECIST criteria.Results127 patients (73 male; median age 59 years) were treated with IFX for corticosteroid-refractory CPI-induced enterocolitis. Ninety-six (75.6%) patients had diarrhoea CTCAE grade >2 and 115 (90.6%) required hospitalisation for colitis. CFCR was 41.2% at 12 weeks and 50.9% at 26 weeks. In multivariable logistical regression, IFX-resistant enterocolitis was associated with rectal bleeding (OR 0.19; 95% CI 0.04-0.80; p=0.03) and absence of colonic crypt abscesses (OR 2.16; 95% CI 1.13-8.05; p=0.03). Cancer non-progression was significantly more common in patients with IFX-resistant enterocolitis (64.4%) as compared to patients with IFX-responsive enterocolitis (37.5%; p=0.013).ConclusionThis is the largest study to date reporting outcomes of IFX therapy in patients with corticosteroid-refractory CPI-induced enterocolitis. Utilizing pre-defined robust endpoints, we have demonstrated that fewer than half of patients achieved CFCR. Our data also indicate that cancer outcomes may be better in patients developing prolonged and severe inflammatory side effects of CPI-therapy.

Journal article

Ruban A, Miras AD, Glaysher MA, Goldstone AP, Prechtl CG, Johnson N, Chhina N, Al-Najim W, Aldhwayan M, Klimowska-Nassar N, Smith C, Lord J, Li JV, Flores L, Al-Lababidi M, Dimitriadis G, Patel M, Moore M, Chahal H, Ahmed AR, Cousins J, Aldubaikhi G, Glover B, Falaschetti E, Ashrafian H, Roux PCWL, Darzi A, Byrne JP, Teare JPet al., 2021, Duodenal-Jejunal Bypass Liner for the management of Type 2 Diabetes Mellitus and Obesity, Annals of Surgery, Vol: Publish Ahead of Print, ISSN: 0003-4932

Journal article

Ruban A, Miras A, glaysher M, Goldstone A, Teare Jet al., 2021, Duodenal-jejunal bypass liner for the management of Type 2 diabetes and obesity: a multicenter randomized controlled trial, Annals of Surgery, ISSN: 0003-4932

ObjectiveTo examine the clinical efficacy and safety of the duodenal-jejunal bypass liner (DJBL) whilstin situ for 12 months and for 12 months after explantation.Summary Background Data:This is the largest randomized controlled trial (RCT) of the DJBL, a medical device used forthe treatment of people with type 2 diabetes mellitus (T2DM) and obesity. Endoscopicinterventions have been developed as potential alternatives to those not eligible or fearful ofthe risks of metabolic surgery.MethodsIn this multicenter open-label RCT, 170 adults with inadequately controlled T2DM andobesity were randomized to intensive medical care with or without the DJBL. Primaryoutcome was the percentage of participants achieving a glycated hemoglobin reduction of≥20% at 12 months. Secondary outcomes included weight loss and cardiometabolic riskfactors at 12 and 24 months.ResultsThere were no significant differences in the percentage of patients achieving the primaryoutcome between both groups at 12 months (DJBL 54.6% [n=30] vs. control 55.2% [n=32];OR 0.93, 95% CI: 0.44, 2.0; p=.85). 24% (n=16) patients achieved ≥15% weight loss in theDJBL group compared to 4% (n=2) in the controls at 12 months (OR 8.3, 95% CI: 1.8, 39;p=.007). The DJBL group experienced superior reductions in systolic blood pressure, serumStructured Abstractcholesterol and alanine transaminase at 12months. There were more adverse events in theDJBL group.ConclusionThe addition of the DJBL to intensive medical care was associated with superior weightloss, improvements in cardiometabolic risk factors and fatty liver disease markers, butnot glycaemia, only whilst the device was in situ. The benefits of the devices need to bebalanced against the higher rate of adverse events when making clinical decisions.

Journal article

Nazarian S, Glover B, Ashrafian H, Darzi A, Teare Jet al., 2021, The diagnostic accuracy of artificial intelligence and computer-aided diagnosis for the detection and characterisation of colorectal polyps: A systematic review and meta-analysis., Journal of Medical Internet Research, ISSN: 1438-8871

AimsColonoscopy reduces the incidence of colorectal cancer by allowing detection and resection of neoplastic polyps. Evidence shows that many small polyps are missed on a single colonoscopy. There has been a successful adoption of AI technologies to tackle the issues around missed polyps and as a tool to increase adenoma detection rate (ADR). The aim of this review was to examine the diagnostic accuracy of AI-based technologies in assessing colorectal polyps.MethodA comprehensive literature search was undertaken using the databases of EMBASE, Medline and the Cochrane Library. PRISMA guidelines were followed. Studies reporting use of computer-aided diagnosis for polyp detection or characterisation during colonoscopy were included. Independent proportion and their differences were calculated and pooled through DerSimonian and Laird random-effects modelling. ResultsA total of 48 studies were included. The meta-analysis showed a significant increase in pooled PDR in patients with the use of AI for polyp detection during colonoscopy compared with patients who had standard colonoscopy (OR 1.75; 95% CI 1.56-1.96; p= 0.0005). When comparing patients undergoing colonoscopy with the use of AI to those without, there was also a significant increase in ADR (OR 1.53; 95% CI 1.32-1.77; p= 0005). ConclusionWith the aid of machine learning, there is potential to improve ADR and consequently reduce the incidence of CRC. The current generation of AI-based systems demonstrate impressive accuracy for the detection and characterisation of colorectal polyps. However, this is an evolving field and before its adoption into a clinical setting, AI systems must prove worthy to patients and clinicians.

Journal article

Glaysher M, Ward J, Aldhwayan M, Ruban A, Prechtl CG, Fisk HL, Chhina N, Al-Najim W, Smith C, Klimowska-Nassar N, Johnson N, Falaschetti E, Goldstone AP, Miras AD, Byrne JP, Calder PC, Teare Jet al., 2021, The effect of a duodenal-jejunal bypass liner on lipid profile and blood concentrations of long chain polyunsaturated fatty acids, Clinical Nutrition, Vol: 40, Pages: 2343-2354, ISSN: 0261-5614

Background & aimsDuodenal-jejunal bypass liners (DJBLs) prevent absorption in the proximal small intestine, the site of fatty acid absorption. We sought to investigate the effects of a DJBL on blood concentrations of essential fatty acids (EFAs) and bioactive polyunsaturated fatty acids (PUFAs).MethodsSub-study of a multicentre, randomised, controlled trial with two treatment groups. Patients aged 18–65 years with type-2 diabetes mellitus and body mass index 30–50 kg/m2 were randomised to receive a DJBL for 12 months or best medical therapy, diet and exercise. Whole plasma PUFA concentrations were determined at baseline, 10 days, 6 and 11.5 months; data were available for n = 70 patients per group.ResultsWeight loss was significantly greater in the DJBL group compared to controls after 11.5 months: total body weight loss 11.3 ± 5.3% versus 6.0 ± 5.7% (mean difference [95% CI] = 5.27% [3.75, 6.80], p < 0.001). Absolute concentrations of both EFAs, linoleic acid and α-linolenic acid, and their bioactive derivatives, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid, were significantly lower in the DJBL group than in the control group at 6 and 11.5 months follow-up. Total serum cholesterol, LDL-cholesterol and HDL-cholesterol were also significantly lower in the DJBL group.ConclusionOne year of DJBL therapy is associated with superior weight loss and greater reductions in total serum cholesterol and LDL-cholesterol, but also depletion of EFAs and their longer chain derivatives. DJBL therapy may need to be offset by maintaining an adequate dietary intake of PUFAs or by supplementation.

Journal article

Kohoutova D, Worku D, Aziz H, Teare J, Weir J, Larkin Jet al., 2021, Malignant melanoma of the gastrointestinal tract: symptoms, diagnosis, and current treatment options., Cells, Vol: 10, ISSN: 2073-4409

Malignant melanoma (MM) has become the fifth most frequent cancer in the UK. It is the most common carcinoma to metastasize to the gastrointestinal (GI) tract. MM particularly has an affinity to spread to the small bowel, which is followed by the involvement of the stomach and large intestine. Excellent endoscopic options including video capsule endoscopy and enteroscopy are available for a precise diagnosis of GI involvement by a metastatic MM. The complete surgical resection of GI metastatic MM in carefully selected patients not only provides symptom control, but has also been associated with an increase in overall survival. The approval of BRAF-targeted therapies and immune checkpoint inhibitors has transformed therapeutic approaches for patients with metastatic MM over the past decade. Currently, the overall survival of patients with advanced metastatic MM who have been treated with a combination of immunotherapeutic agents reaches 52% at five years. The role of surgery for patients with the metastatic involvement of the GI tract with MM is evolving in the era of effective systemic treatments.

Journal article

Awasthi A, Barbour J, Beggs A, Bhandari P, Blakeway D, Brookes M, Brown J, Brown M, Caldwell G, Clokie S, Colleypriest B, Conlin A, de Silva S, de Caestecker J, Deeks J, Dhar A, Dilworth M, Fogden E, Foley S, Ghosh D, Grellier L, Hart A, Hoque SS, Iacucci M, Iqbal T, James J, Jarvis M, Jayaprakash A, Keshav S, Magill L, Matthews G, Mawdsley J, McLaughlin S, Mehta S, Monahan K, Morton D, Murugesan S, Parkes M, Pestinger V, Probert C, Ramadas A, Rettino A, Sebastian S, Sharma N, Griffiths M, Stockton J, Subramanian V, Suggett N, Taniere P, Teare J, Verma AM, Wallis Yet al., 2021, Enhanced neoplasia detection in chronic ulcerative colitis: the ENDCaP-C diagnostic accuracy study, Efficacy and Mechanism Evaluation, Vol: 8, Pages: 1-88, ISSN: 2050-4365

BackgroundChronic ulcerative colitis is a large bowel inflammatory condition associated with increased colorectal cancer risk over time, resulting in 1000 colectomies per year in the UK. Despite intensive colonoscopic surveillance, 50% of cases progress to invasive cancer before detection. Detecting early (precancer) molecular changes by analysing biopsies from routine colonoscopy should increase neoplasia detection.ObjectivesTo establish a deoxyribonucleic acid (DNA) marker panel associated with early neoplastic changes in ulcerative colitis patients. To develop the DNA methylation test for high-throughput analysis within the NHS. To prospectively evaluate the test within the existing colonoscopy surveillance programme.DesignModule 1 analysed 569 stored biopsies from neoplastic and non-neoplastic sites/patients using pyrosequencing for 11 genes that were previously reported to have altered promoter methylation associated with colitis-associated neoplasia. Classifiers were constructed to predict neoplasia based on gene combinations. Module 2 translated analysis to a NHS laboratory, assessing next-generation sequencing to increase speed and reduce cost. Module 3 applied the molecular classifiers within a prospective diagnostic accuracy study, in the existing ulcerative colitis surveillance programme. Comparisons were made between baseline and reference colonoscopies undertaken in a stratified patient sample 6–12 months later.SettingThirty-one UK hospitals.ParticipantsPatients with chronic ulcerative colitis, either for at least 10 years and extensive disease, or with primary sclerosing cholangitis.InterventionsAn optimised DNA methylation classifier tested on routine mucosal biopsies taken during colonoscopy.Main outcomeIdentifying ulcerative colitis patients with neoplasia.ResultsModule 1 selected five genes with specificity for neoplasia. The optimism-adjusted area under the receiver operating characteristic curve for neoplasia was 0.83 (95% confidence interv

Journal article

Ruban A, Glaysher MA, Miras AD, Goldstone AP, Prechtl CG, Johnson N, Li J, Aldhwayan M, Aldubaikhi G, Glover B, Lord J, Onyimadu O, Falaschetti E, Klimowska-Nassar N, Ashrafian H, Byrne J, Teare JPet al., 2020, A duodenal sleeve bypass device added to intensive medical therapy for obesity with type 2 diabetes: a RCT, Efficacy and Mechanism Evaluation, Vol: 7, Pages: 1-130, ISSN: 2050-4365

BackgroundThe EndoBarrier® (GI Dynamics Inc., Boston, MA, USA) is an endoluminal duodenal–jejunal bypass liner developed for the treatment of patients with obesity and type 2 diabetes mellitus. Meta-analyses of its effects on glycaemia and weight have called for larger randomised controlled trials with longer follow-up.ObjectivesThe primary objective was to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level reduction of ≥ 20%. The secondary objectives were to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level of < 42 mmol/mol, blood pressure of < 135/85 mmHg, and the effectiveness on total body weight loss. Additional secondary outcomes were to investigate the cost-effectiveness and mechanism of action of the effect of a duodenal–jejunal bypass liner on brain reward system responses, insulin sensitivity, eating behaviour and metabonomics.DesignA multicentre, open-label, randomised controlled trial.SettingImperial College Healthcare NHS Trust and University Hospital Southampton NHS Foundation Trust.ParticipantsPatients aged 18–65 years with a body mass index of 30–50 kg/m2 and with inadequately controlled type 2 diabetes mellitus who were on oral glucose-lowering medications.InterventionsParticipants were randomised equally to receive intensive medical therapy alongside a duodenal–jejunal bypass liner device (n = 85) or intensive medical therapy alone for 12 months (n = 85), and were followed up

Journal article

Glover B, Teare J, Patel N, 2020, The endoscopic predictors of H. pylori status: a meta-analysis of diagnostic performance., Therapeutic Advances in Gastrointestinal Endoscopy, Vol: 13, Pages: 1-19, ISSN: 1179-5522

ObjectiveThe endoscopic findings associated with H. pylori naïve status, current infection or past infection is an area of ongoing interest. Previous studies have investigated parameters with potential diagnostic value. The aim of this study was to perform meta-analysis of the available literature to validate the diagnostic accuracy of mucosal features proposed in the Kyoto classification.Data SourcesThe databases of Medline and Embase, clinicaltrials.gov and the Cochrane library were systematically searched for relevant studies from October 1999 to October 2019.MethodsA bivariate random effects model was used to produce pooled diagnostic accuracy calculations for each of the studied endoscopic findings. Diagnostic odds ratios and sensitivity and specificity characteristics were calculated to identify significant predictors of H. pylori status.ResultsMeta-analysis included 4,380 patients in 15 studies. The most significant predictor of an H. pylori naïve status was a regular arrangement of collecting venules (RAC). (DOR 55.0, Sensitivity 78.3%, Specificity 93.8%) Predictors of active H. pylori infection were mucosal oedema (18.1, 63.7%, 91.1%) and diffuse redness (14.4, 66.5%, 89.0%). Map-like redness had high specificity for previous H. pylori eradication (99.0%), but poor specificity (13.0%).ConclusionsThe RAC, mucosal oedema, diffuse redness and map-like redness are important endoscopic findings for determining H. pylori status. This meta-analysis provides a tentative basis for developing future endoscopic classification systems.

Journal article

Ruban A, Glaysher M, Miras A, Prechtl CG, Goldstone AP, Johnson NA, Aldhwayan M, Chhina N, Al-Najim W, Ashrafian H, Patel M, Byrne J, Teare JPet al., 2020, ONE YEAR OF DUODENAL-JEJUNAL BYPASS LINER THERAPY (ENDOBARRIER (R)) LEADS TO SIGNIFICANT CHANGES IN LIVER BIOCHEMISTRY ASSOCIATED WITH NON-ALCOHOLIC FATTY LIVER DISEASE, GI Fellows Sessions at Digestive Disease Week / 61st Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract, Publisher: MOSBY-ELSEVIER, Pages: AB225-AB226, ISSN: 0016-5107

Conference paper

Glaysher M, Ward J, Aldhwayan M, Ruban A, Prechtl C, Fisk H, Gelauf C, Chhina N, Al-Najim W, Smith C, Klimowska-Nassar N, Johnson N, Goldstone A, Miras A, Patel M, Byrne J, Calder P, Teare Jet al., 2020, The effect of a duodenal-jejunal bypass liner device (Endobarrier (R)) on lipid profile and blood concentrations of long chain polyunsaturated fatty acids, 11th Annual Scientific Meeting of the British-Obesity-and-Metabolic-Surgery-Society (BOMSS), Publisher: SPRINGER, Pages: S16-S17, ISSN: 0960-8923

Conference paper

Ruban A, Liu Z, Glaysher M, Ashrafian H, Miras A, Prechtl C, Goldstone A, Aldhwayan M, Chhina N, Al-Najim W, Johnson N, Patel M, Li J, Byrne J, Teare Jet al., 2020, One year of duodenal-jejunal bypass liner therapy (Endobarrier (R)) leads to perturbations in the metabolic profile of urine, plasma and stool of obese diabetic patients., 11th Annual Scientific Meeting of the British-Obesity-and-Metabolic-Surgery-Society (BOMSS), Publisher: SPRINGER, Pages: S10-S10, ISSN: 0960-8923

Conference paper

Glaysher M, Miras A, Ruban A, Prechtl C, Shojaee-Moradie F, Jackson N, Coppin L, Aldhwayan M, Johnson N, Chhina N, Al-Najim W, Smith C, Klimowska-Nassar N, Goldstone A, Patel M, Le Roux C, Umpleby M, Byrne J, Teare Jet al., 2020, The effect of a duodenal-jejunal bypass liner device (Endobarrier (R)) on insulin sensitivity, 11th Annual Scientific Meeting of the British-Obesity-and-Metabolic-Surgery-Society (BOMSS), Publisher: SPRINGER, Pages: S25-S26, ISSN: 0960-8923

Conference paper

Glover B, Teare J, Patel N, 2020, The status of advanced imaging techniques for ‘optical biopsy’ of colonic polyps, Clinical and Translational Gastroenterology, Vol: 11, Pages: 1-11, ISSN: 2155-384X

Introduction: The progressive miniaturisation of photonics components presents the opportunity to obtain unprecedented microscopic images of colonic polyps in real-time, during endoscopy. This information has the potential to act as an ‘optical biopsy’ to aid clinical decision making, including the possibility of adopting new paradigms such as a ‘resect and discard’ approach for low-risk lesions. The technologies discussed in this review include Confocal Laser Endomicroscopy, Optical Coherence Tomography, Multiphoton Microscopy, Raman Spectroscopy and Hyperspectral Imaging. These are in different stages of development and clinical readiness, but all show the potential to produce reliable in-vivo discrimination of different tissue types.Methods:A structured literature search of the imaging techniques for colorectal polyps has been conducted. The significant developments in endoscopic imaging was identified for each modality, and the status of current development was discussed.Conclusions:Of the advanced imaging techniques discussed, Confocal Laser Endomicroscopy is in clinical use, and under optimal conditions with an experienced operator, can provide accurate histological assessment of tissue. The remaining techniques show potential for incorporation into endoscopic equipment and practice, although further component development is needed, followed by robust prospective validation of accuracy. Optical Coherence Tomography illustrates tissue ‘texture’ well and gives good assessment of mucosal thickness and layers. Multiphoton Microscopy produces high resolution images at a subcellular resolution. Raman Spectroscopy and Hyperspectral Imaging are less developed endoscopically but provide a tissue ‘fingerprint’ which can distinguish between tissue types. Molecular Imaging may become a powerful adjunct to other techniques, with its ability to precisely label specific molecules within tissue and thereby enhance imaging.

Journal article

Glover B, Teare J, Patel N, 2020, A systematic review of the role of non-magnified endoscopy for the assessment of H. pylori infection., Endoscopy International Open, Vol: 8, Pages: E105-E114, ISSN: 2196-9736

BackgroundThere is growing interest in the endoscopic recognition of H. pylori infection, and application to routine practice. We present a systematic review of the current literature regarding diagnosis of H. pylori during standard (non-magnified) endoscopy, including adjuncts such as image enhancement and computer-aided diagnosis.MethodThe Medline and Cochrane databases were searched for studies investigating the performance of non-magnified optical diagnosis for H. pylori, or those which characterised mucosal features associated with H. pylori infection. Studies were preferred with a validated reference test as the comparator, although were included if at least one validated reference test was used.Results20 suitable studies were identified and included for analysis. In total, 4,703 patients underwent investigation including white light endoscopy, narrow band imaging, i-scan, blue-laser imaging, and computer-aided diagnostic techniques. The endoscopic features of H. pylori infection observed using each modality are discussed and diagnostic accuracies reported. The Regular Arrangement of Collecting Venules (RAC) is an important predictor of the H. pylori naïve stomach. ‘Mosaic’ and ‘Mottled’ patterns have a positive association with H. pylori infection. The ‘Cracked’ pattern may be a predictor of an H. pylori negative stomach following eradication.ConclusionsThis review summarises the current progress made in endoscopic diagnosis of H. pylori infection. At present there is no single diagnostic approach that provides validated diagnostic accuracy. Further prospective studies are required, as is the development of a validated classification system. Early studies in Computer-Aided Diagnosis suggest potential for a high level of accuracy but real-time results are awaited.

Journal article

Ruban A, Prechtl C, Glaysher M, Chhina N, Al-Najim W, Miras A, smith C, Goldstone A, Patel M, Moore M, Ashrafian H, Byrne J, Teare Jet al., 2019, Effectiveness of different recruitment strategies in an RCT of a surgical device:;Experience from the Endobarrier trial, BMJ Open, Vol: 9, ISSN: 2044-6055

Recruiting participants into clinical trials is notoriously difficult and poses the greatest challenge when planning any investigative study. Poor recruitment may not only have financial ramifications owing to increased time and resources being spent but could adversely influence the clinical impact of a study if it becomes underpowered. Herein we present our own experience of recruiting into a nationally funded, multi-centre, randomised controlled trial (RCT) of the Endobarrier vs. standard medical therapy in obese patients with type 2 diabetes. Despite these both being highly prevalent conditions, there were considerable barriers to the effectiveness of different recruitment strategies across each study site. Although recruitment from primary care proved extremely successful at one study site, this largely failed at another site prompting the implementation of multimodal recruitment strategies including a successful media campaign to ensure sufficient participants were enrolled and the study was adequately powered. From this experience we propose where appropriate the early engagement and investment in media campaigns to enhance recruitment into clinical trials.

Journal article

Cameron SJS, Alexander JL, Bolt F, Burke A, Ashrafian H, Teare J, Marchesi JR, Kinross J, Li JV, Takats Zet al., 2019, Evaluation of direct from sample metabolomics of human feces using rapid evaporative ionization mass spectrometry, Analytical Chemistry, Vol: 91, Pages: 13448-13457, ISSN: 0003-2700

Mass spectrometry is a powerful tool in the investigation of the human fecal metabolome. However, current approaches require time-consuming sample preparation, chromatographic separations, and consequently long analytical run times. Rapid evaporative ionization mass spectrometry (REIMS) is a method of ambient ionization mass spectrometry and has been utilized in the metabolic profiling of a diverse range of biological materials, including human tissue, cell culture lines, and microorganisms. Here, we describe the use of an automated, high-throughput REIMS robotic platform for direct analysis of human feces. Through the analysis of fecal samples from five healthy male participants, REIMS analytical parameters were optimized and used to assess the chemical information obtainable using REIMS. Within the fecal samples analyzed, bile acids, including primary, secondary, and conjugate species, were identified, and phospholipids of possible bacterial origin were detected. In addition, the effect of storage conditions and consecutive freeze/thaw cycles was determined. Within the REIMS mass spectra, the lower molecular weight metabolites, such as fatty acids, were shown to be significantly affected by storage conditions for prolonged periods at temperatures above −80 °C and consecutive freeze/thaw cycles. However, the complex lipid region was shown to be unaffected by these conditions. A further cohort of 50 fecal samples, collected from patients undergoing bariatric surgery, were analyzed using the optimized REIMS parameters and the complex lipid region mass spectra used for multivariate modeling. This analysis showed a predicted separation between pre- and post-surgery specimens, suggesting that REIMS analysis can detect biological differences, such as microbiome-level differences, which have traditionally been reliant upon methods utilizing extensive sample preparations and chromatographic separations and/or DNA sequencing.

Journal article

Turkes FS, Crux R, Cunningham D, Athauda A, Kalaitzaki E, Musallam A, Begum R, De Paepe K, Fotiadis N, Riddell A, Von Loga K, Kinross J, Marchesi JR, Teare J, Morganstein D, Rao S, Watkins D, Chau I, Gerlinger M, Starling Net al., 2019, iSCORE: Immunotherapy sequencing in colon and rectal cancer, 44th Congress of the European-Society-for-Medical-Oncology (ESMO), Publisher: OXFORD UNIV PRESS, ISSN: 0923-7534

Conference paper

Ruban A, Doshi A, Lam E, Teare JPet al., 2019, Medical devices in obesity treatment, Current Diabetes Reports, Vol: 19, Pages: 1-6, ISSN: 1534-4827

PURPOSE OF REVIEW: Obesity is increasing at an alarming rate and now poses a global threat to humankind. In recent years, we have seen the emergence of medical devices to combat the obesity epidemic. These therapeutic strategies are discussed in this review dividing them into gastric and duodenal therapies. RECENT FINDINGS: Traditionally, medical devices for obesity such as the intragastric balloon have focused on reducing gastric size, but more recently there has been a shift towards developing devices that modulate neural and hormonal responses to induce early satiety thus reducing oral intake. Medical devices for obesity treatment may have a role in those patients who are struggling to control their weight despite significant lifestyle modifications such as diet and exercise and who decline or are unfit for bariatric surgery. For the wider adoption and integration of these devices in the obesity treatment paradigm, more long-term efficacy and safety data from randomised controlled trials are required.

Journal article

Radhakrishnan ST, Ruban A, Uthayakumar AK, Cohen P, Levy J, Teare Jet al., 2019, Haemolytic Uraemic Syndrome - a rare case report of bloody diarrhoea in adults, BMC Gastroenterology, Vol: 19, Pages: 1-4, ISSN: 1471-230X

Background: Haemolytic uraemic syndrome is a rarely seen in adults often leading to critical illness.This case highlights how difficult it can be to establish a diagnosis and treat when a patient presentswith bloody diarrhoea.Case Presentation: A 17-year-old Iraqi man presented to the emergency department with abdominalpain and bloody diarrhoea. He was initially treated as acute appendicitis, undergoing anappendectomy but following a recurrence in his symptoms a colonoscopy was performed. Adiagnosis of shiga toxin-producing Escherichia coli leading to HUS was suspected following histologyobtained at colonoscopy and this was confirmed on antibody testing. Despite intravenous fluids andsupportive therapy the patient's symptoms and condition deteriorated. He developed seizures andacute renal failure requiring intubation and plasma exchange in the intensive care setting. Heeventually required treatment with ecluzimab therapy; a monoclonal antibody and subsequentlymade a full recovery.Conclusions: Haemolytic uraemic syndrome is a triad of progressive renal failure, thrombocytopeniaand haemolytic anaemia which is a condition rarely seen in adults. It is usually associated with an E.coli infection and supportive therapy remains the mainstay of treatment.

Journal article

Scott AJ, Alexander JL, Merrifield CA, Cunningham D, Jobin C, Brown R, Alverdy J, O'Keefe SJ, Gaskins HR, Teare J, Yu J, Hughes DJ, Verstraelen H, Burton J, O'Toole PW, Rosenberg DW, Marchesi JR, Kinross JMet al., 2019, International Cancer Microbiome Consortium consensus statement on the role of the human microbiome in carcinogenesis, Gut, Vol: 68, Pages: 1624-1632, ISSN: 0017-5749

Objective In this consensus statement, an international panel of experts deliver their opinions on key questions regarding the contribution of the human microbiome to carcinogenesis.Design International experts in oncology and/or microbiome research were approached by personal communication to form a panel. A structured, iterative, methodology based around a 1-day roundtable discussion was employed to derive expert consensus on key questions in microbiome-oncology research.Results Some 18 experts convened for the roundtable discussion and five key questions were identified regarding: (1) the relevance of dysbiosis/an altered gut microbiome to carcinogenesis; (2) potential mechanisms of microbiota-induced carcinogenesis; (3) conceptual frameworks describing how the human microbiome may drive carcinogenesis; (4) causation versus association; and (5) future directions for research in the field.The panel considered that, despite mechanistic and supporting evidence from animal and human studies, there is currently no direct evidence that the human commensal microbiome is a key determinant in the aetiopathogenesis of cancer. The panel cited the lack of large longitudinal, cohort studies as a principal deciding factor and agreed that this should be a future research priority. However, while acknowledging gaps in the evidence, expert opinion was that the microbiome, alongside environmental factors and an epigenetically/genetically vulnerable host, represents one apex of a tripartite, multidirectional interactome that drives carcinogenesis.Conclusion Data from longitudinal cohort studies are needed to confirm the role of the human microbiome as a key driver in the aetiopathogenesis of cancer.

Journal article

Glover B, Teare J, Patel N, 2019, A Review of New and Emerging Techniques For Optical Diagnosis of Colonic Polyps, JOURNAL OF CLINICAL GASTROENTEROLOGY, Vol: 53, Pages: 495-506, ISSN: 0192-0790

Journal article

Ruban A, Stoenchev K, Ashrafian H, Teare Jet al., 2019, Current treatments for obesity, Clinical Medicine, Vol: 19, Pages: 205-212, ISSN: 1470-2118

Obesity is a major health and economic crisis facing the modern world. It is associated with excess mortality and morbidity and is directly linked to common conditions such as type 2 diabetes mellitus, coronary heart disease and sleep apnoea. The management of obesity and its associated complications has evolved in recent years, with a shift towards more definitive strategies such as bariatric surgery. This review encompasses the dietary, pharmacological and surgical strategies currently available for the management of obesity.

Journal article

Glover B, Patel N, Teare J, Ashrafian Het al., 2019, Diagnostic accuracy of i-scan image enhancement for real-time endoscopic diagnosis of small colorectal polyps: a meta-analysis, Therapeutic Advances in Gastroenterology, Vol: 11, ISSN: 1756-2848

Objective:i-Scan is a digital image enhancement technology, reported to improve diagnostic performance during endoscopy. Previous studies have investigated the accuracy of i-scan for distinguishing between neoplastic and non-neoplastic colonic polyps and suggested diagnostic accuracy close to that required for use in routine clinical practice. The aim of this study was to perform a meta-analysis of the available literature investigating diagnostic accuracy for i-scan optical diagnosis when made in real time for colorectal polyps <10 mm in size.

Journal article

Alexander JL, Scott AJ, Pouncey AL, Marchesi J, Kinross J, Teare Jet al., 2018, Colorectal carcinogenesis: an archetype of gut microbiota-host interaction, Ecancermedicalscience, Vol: 12, ISSN: 1754-6605

Sporadic colorectal cancer (CRC) remains a major cause of worldwide mortality. Epidemiological evidence of markedly increased risk in populations that migrate to Western countries, or adopt their lifestyle, suggests that CRC is a disease whose aetiology is defined primarily by interactions between the host and his environment. The gut microbiome sits directly at this interface and is now increasingly recognised as a modulator of colorectal carcinogenesis. Bacteria such as Fusobacterium nucleatum and Escherichia coli (E. Coli) are found in abundance in patients with CRC and have been shown in experimental studies to promote neoplasia. A whole armamentarium of bacteria-derived oncogenic mechanisms has been defined, including the subversion of apoptosis and the production of genotoxins and pro-inflammatory factors. But the microbiota may also be protective: for example, they are implicated in the metabolism of dietary fibre to produce butyrate, a short chain fatty acid, which is anti-inflammatory and anti-carcinogenic. Indeed, although our understanding of this immensely complex, highly individualised and multi-faceted relationship is expanding rapidly, many questions remain: Can we define friends and foes, and drivers and passengers? What are the critical functions of the microbiota in the context of colorectal neoplasia?

Journal article

Ruban A, Ashrafian H, Teare JP, 2018, The EndoBarrier: Duodenal-Jejunal Bypass Liner for Diabetes and Weight Loss, GASTROENTEROLOGY RESEARCH AND PRACTICE, Vol: 2018, ISSN: 1687-6121

The rapid rise of obesity and type 2 diabetes poses a global threat to healthcare and is a major cause of mortality and morbidity. Bariatric surgery has revolutionised the treatment of both these conditions but is invasive and associated with an increased risk of complications. The EndoBarrier is a device placed endoscopically in the duodenum, which is designed to mimic the effects of gastric bypass surgery with the aim of inducing weight loss and improving glycaemic control. This review outlines the current clinical evidence of the device, its efficacy, potential mechanisms of action, and utility in clinical practice.

Journal article

Patel N, Mohanaruban A, Ashrafian H, Le Roux C, Byrne J, Mason J, Hopkins J, Kelly J, Teare Jet al., 2018, EndoBarrier®: a safe and effective novel treatment for obesity and type 2 diabetes?, Obesity Surgery, Vol: 28, Pages: 1980-1989, ISSN: 0960-8923

BACKGROUND AND AIMS: Obesity associated with diabetes mellitus is a significant worldwide problem associated with considerable health care costs. Whilst surgical intervention is effective, it is invasive, costly and associated with complications. This study aims to evaluate the safety and efficacy of the EndoBarrier®, a duodenal-jejunal sleeve bypass as an alternative treatment of diabetes mellitus in obese patients. MATERIALS AND METHODS: This was a multi-centre, non-randomised trial recruiting obese patients with type 2 diabetes from three sites in the UK. Eligible participants had a BMI of 30-50 kg/m2and HbA1c levels of 7.5-10%. The study comprised a 12-month period with the EndoBarrier® inserted and a 6-month follow-up period after it had been explanted. The primary study outcomes were weight, BMI, HbA1c levels and fasting insulin and glucose levels. RESULTS: Forty-five patients were recruited and 31 patients (69%) completed the 12-month study period. Significant reductions in weight (95%CI 0.62-29.38; p < 0.05) and BMI (95%CI 1.1-8.7; p < 0.005) were documented 12 months after device insertion. The mean HbA1c was significantly reduced (95%CI 0.1-1.6; p < 0.05) after the device insertion period and reductions in metabolic parameters (fasting insulin and glucose levels) were also documented during the study. Adverse events were also assessed in all patients, the vast majority of which were reported as mild. CONCLUSIONS: The EndoBarrier® appears to be a safe and effective treatment strategy in overweight patients with poor glycaemic control despite medical therapy, or in those who are eligible but decline bariatric surgery.

Journal article

Ruban A, Uthayakumar A, Ashrafian H, Teare Jet al., 2018, Endoscopic interventions in the treatment of obesity and diabetes, Digestive Diseases and Sciences, ISSN: 1573-2568

Journal article

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