Skip to main content

Anjan Dhar

Followers

0

Following

1

Public Views

Carolyn R Hastie

Griffith University

Toronto Metropolitan University

The University of Birmingham

New York University

Viacheslav Kuleshov

Stockholm University

Menoufiya University

Sucipto Syarifuddin

Brawijaya University

St John Simpson

The British Museum

Universidad del Desarrollo (UDD)

Abdolhalim Rajabi

Golestan University Of Medical Sciences

Interests

Uploads

Papers by Anjan Dhar

Curriculum review : investigation and management of dysphagia

Frontline Gastroenterology, 2021

Dysphagia is a common presentation in gastroenterology practice and the diagnosis and management ... more Dysphagia is a common presentation in gastroenterology practice and the diagnosis and management requires a comprehensive knowledge of diverse range of aetiologies, with a systematic approach for assessment of symptoms, selection of investigations and appropriate treatment to relieve symptoms. In this curriculum review, the suggested diagnostic approach highlights the importance of thorough clinical assessment in order to guide the selection of investigations. This article discusses the utility of endoscopic, histopathology, fluoroscopic and motility investigations for dysphagia, and their interpretation, in order to guide targeted treatments ranging from dietary, pharmacological, endoscopic and surgical interventions.

PWE-016 Delivering parenteral nutrition– real world challenges

Posters, 2019

On review of the patients whose cause of death were attributed to cancer, 12 did not have maligna... more On review of the patients whose cause of death were attributed to cancer, 12 did not have malignancy as initial HPN indication. Regarding mortality not linked to HPN, respiratory complications including pneumonia were the commonest causative factor (8/29, 28%). Conclusions This study showed that mortality was associated with the underlying disease condition resulting in the need for HPN or other co-morbidities rather than direct complications of HPN itself. REFERENCE 1. Pironi L, Joly F, Forbes A, et al. Long-term follow-up of patients on home parenteral nutrition in Europe: implications for intestinal transplantation. Gut 2011;60:1-5.

$Research paper thumbnail of P381 Infliximab induction regimes in steroid refractory acute severe colitis: a multi-centre retrospective cohort study with propensity score analysis$

P381 Infliximab induction regimes in steroid refractory acute severe colitis: a multi-centre retrospective cohort study with propensity score analysis

Journal of Crohn's and Colitis, 2019

16/32 patients (50.0%). 24.1% (n = 84) of patients reported at least one adverse event. Fifty pat... more 16/32 patients (50.0%). 24.1% (n = 84) of patients reported at least one adverse event. Fifty patients (14.3%) discontinued Budesonide MMX® for adverse events; 17.5% of patients (n = 61) reported at least one adverse event related to the study drug. Nine patients had worsening of the underlying colitis (3%). All the other adverse events were reported in <1% of patients. Table 1. Baseline characteristics of the study population. Conclusions: This large real-life cohort study demonstrates for the first time that Budesonide MMX® is effective in about two-thirds of UC patients, and that Budesonide MMX® was safe and well tolerated.

PWE-077 Residual Intestinal Metaplasia after Successful Endoscopic Therapy for Barrett’s Related Neoplasia Confers Higher Long Term Risk for Disease Recurrence, on Behalf of The UK RFA Registry

Gut, 2016

143 at medium volume (n = 4) & 118 at low volume centres (n = 15). There was no difference in ent... more 143 at medium volume (n = 4) & 118 at low volume centres (n = 15). There was no difference in entry criteria or demographics between groups. CR-D & CR-IM at 12 months are no different between the groups (CR-D 86-90%, CR-IM 74-81%). IM recurrence is significantly lower in high volume centres (16.1% vs 20.3% and 19.2%, Log Rank p < 0.001) but dysplasia recurrence is no different (Log Rank p = 0.12). Rescue EMR was performed less frequently in medium volume centres (0% vs high 5.3% and low volume 10%, p = 001). Conclusion Endotherapy for Barrett's dysplasia is highly effective whatever the centre volume. The rescue EMR rate in medium volume centres is unexplained. Despite lower IM recurrence in high volume centres, dysplasia recurrence rates are not significantly different. Caseload volume of a centre in the UK Registry does not appear to affect outcome.

PWE-087 Endoscopic Non-Ablative Radio Frequency Energy Treatment (Stretta®) for Gastro-Oesophageal Reflux Disease – The First UK Single Centre Experience: Abstract PWE-087 Table 1

Gut, 2016

Mercaptopurine versus placebo to prevent recurrence of Crohn's disease after surgical resection (TOPPIC): a multicentre, double-blind, randomised controlled trial

The Lancet Gastroenterology & Hepatology, 2016

Background Up to 60% of patients with Crohn's disease need intestinal resection within the fi rst... more Background Up to 60% of patients with Crohn's disease need intestinal resection within the fi rst 10 years of diagnosis, and postoperative recurrence is common. We investigated whether mercaptopurine can prevent or delay postoperative clinical recurrence of Crohn's disease. We did a randomised, placebo-controlled, double-blind trial at 29 UK secondary and tertiary hospitals of patients (aged >16 years in Scotland or >18 years in England and Wales) who had a confi rmed diagnosis of Crohn's disease and had undergone intestinal resection. Patients were randomly assigned (1:1) by a computer-generated web-based randomisation system to oral daily mercaptopurine at a dose of 1 mg/kg bodyweight rounded to the nearest 25 mg or placebo; patients with low thiopurine methyltransferase activity received half the normal dose. Patients and their carers and physicians were masked to the treatment allocation. Patients were followed up for 3 years. The primary endpoint was clinical recurrence of Crohn's disease (Crohn's Disease Activity Index >150 plus 100-point increase in score) and the need for anti-infl ammatory rescue treatment or primary surgical intervention. Primary and safety analyses were by intention to treat. Subgroup analyses by smoking status, previous thiopurines, previous infl iximab or methotrexate, previous surgery, duration of disease, or age at diagnosis were also done. This trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN89489788) and the European Clinical Trials Database (EudraCT number 2006-005800-15).

Faecal calprotectin—ready for prime time?

Frontline Gastroenterology, 2014

841 Residual Intestinal Metaplasia After Successful Endoscopic Therapy for Barrett's Related Neoplasia Confers Higher Long Term Risk for Disease Recurrence, on Behalf of the UK RFA Registry

Gastroenterology, 2016

that none of the patients with BE < 1 cm (irregular -z line developed HGD or cancer during follow... more

Optic neuritis and TNF antagonists in IBD

Journal of Crohn's & colitis, Jan 12, 2016

Background and AimsAcute optic neuritis (ON) is an inflammatory condition affecting the optic ner... more Background and AimsAcute optic neuritis (ON) is an inflammatory condition affecting the optic nerve. Clinicians should suspect optic neuritis in cases of painful and rapidly progressive loss of central visual field. This condi-tion may be associated with a multitude of diseases, and mostly with multiple sclerosis (MS) where may present as an initial symptom. The literature reports that optic neuritis and MS occur in patients with inflammatory bowel disease (IBD) before and after the era of anti-tumor necrosis factor-α (TNF-α) drugs. At the present moment, there is little consensus for managing this complication, currently treated with corticosteroids and discontinuation of the causative agents.MethodsWe collected cases through a retrospective multicenter European Crohn's and Colitis Organization CONFER (Collaborative Network For Exceptionally Rare case reports) project. We also performed a comprehensive retrospective search of the available litterature on this topic.ResultWe rep...

Reply to Kristo et al

Endoscopy, 2016

We thank you for your observations and comments about the role of surgical treatment for acid ref... more We thank you for your observations and comments about the role of surgical treatment for acid reflux in maintaining long-term disease remission after successful endoscopic therapy. We share your observations that although, in most patents, with combined endoscopic resection and radiofrequency ablation (RFA), we are able to clear the mucosal neoplasia and intestinal metaplasia that is Barrett’s esophagus, we do not reverse the persisting reflux insult that drives the biological transformation to Barrett’s esophagus and neoplasia. The ongoing requirement for acid suppression after successful endoscopic treatment may well reduce the quantity of acid exposure to the distal esophagus but this has little impact on the number of reflux events overall [1]. Toxic compounds within the refluxate that can lead to persistent damage to squamous mucosa include duodenogastric contents such as bile, pepsin, and pancreatic proteolytic enzymes [2]. Furthermore, the mechanical clearance of refluxate after endotherapy might also be impaired as has been shown in patients with mucosal esophagitis when compared to those with endoscopy-negative reflux disease [3], a concept yet to be explored in the context of refractory Barrett’s esophagus. Shaheen at al. [4] showed from data derived from the US registry that in patients undergoing endoscopic therapy for Barrett’s neoplasia prior antireflux surgery made no difference to the outcome. The authors examined 5537 patients undergoing RFA, of which 301 (5.4 %) had had a prior fundoplication. Complete eradication of intestinal metaplasia and dysplasia were achieved in 71 % and 87 %, respectively, of patients with a fundoplication, and 73 % and 87 %, respectively, of patients without a fundoplication (P = non-significant for both). Therefore the authors concluded that prior antireflux surgery made no difference to the outcome. However, there was little emphasis on the selection criteria for antireflux surgery or on the manometric and reflux characteristics that led to the surgical decision-making. The role of surgery after successful endoscopic treatment has yet to be examined and may well find a place in carefully selected patients in whom significant reflux is more likely after successful therapy – for example those with a large hiatus hernia and significant exposure to acid (or exposure to weak acid/non-acids such as bile) despite maximum medical therapy.

Oesophageal stenting for benign and malignant strictures: a systematic approach

Frontline Gastroenterology, 2015

Oesophageal stenting is now standard treatment for managing both benign and malignant stenosis of... more Oesophageal stenting is now standard treatment for managing both benign and malignant stenosis of the oesophagus. There is a wide choice in oesophageal stents currently available on the market, with variations in the stent material, size and design. Most oesophageal stents are made from metal alloy compounds for use in malignant strictures, although there are stents made of durable polymers, and now of biodegradable (BD) material, for use in both benign and malignant strictures. With the development of self-expanding plastic stents, self-expanding metal stents and BD stents, stent placement for oesophageal pathologies can be safe and cost-effective. Oesophageal stenting has several challenges for a therapeutic endoscopist which is determined by the location of stricture or tumour, the anatomy of the stenosis and the nature of stent selected. Strictures that have narrow or tortuous lumens can be particularly difficult to stent as the luminal diameter must allow access of at least a 0.035 inch guide wire. This review covers the indications and outcomes of different stents in clinical situations to help rational decisionmaking. Benign oesophageal strictures include most commonly peptic strictures, corrosive, postsurgical anastomotic strictures and radiation-induced inflammatory strictures. Less common causes include tracheooesophageal fistulae, iatrogenic perforation and leaks and external compression.

Su1181 Point-of-Contact Faecal Calprotectin (FC) Testing in Diarrhoea Helps Decision Making for Referral to Gastroenterologists: A Primary Care Pilot Study in North East England

Gastroenterology, 2013

Introduction Faecal Calprotectin (FC) is a cytosolic protein belonging to the S-100 family of cal... more Introduction Faecal Calprotectin (FC) is a cytosolic protein belonging to the S-100 family of calcium binding proteins found in neutrophils. It is excreted in the intestinal lumen in inflammatory conditions of the gut and can be used to distinguish irritable bowel syndrome (IBS) from other inflammatory bowel conditions such as colitis, diverticulosis, etc. Point-of-contact qualitative FC tests are now available and can be used in primary care to aid decision making for referrals to gastroenterologists for young patients presenting with chronic diarrhoea. Methods Aims To assess the feasibility and cost effectiveness of a primary care Pathway using a point-of-contact FC Test (Caldetect®) to aid decision making for referrals to gastroenterology in young patients presenting to their primary physicians with chronic diarrhoea. Methods: Primary Care data indicated that approximately 253 referrals are made annually to gastroenterologists from Primary Care to assess patients 60 ug/g. Patients with FC results of 15–60 and >60 were deemed to have an inflammatory process and referred to Gastroenterology Clinics. Cost analysis was carried out using the 2010–11 tariffs for the NHS. Results 142 Caldetect® tests were carried out in Primary Care during this pilot phase. Of these, a negative result ( 60 ug/g. 3 tests were at the intermediate level and 14 tests could not be accurately reported. Negative results were managed in primary care as IBS. A monthly cost savings of £6100 was calculated taking consultation and endoscopy tariffs into account. Conclusion This pilot study demonstrates the feasibility and cost effectiveness of a Pathway for decision making and a point-of-care faecal calprotectin test in rationalising referrals to Gastroenterologists for chronic diarrhoea. Disclosure of Interest A. Dhar Speaker bureau with: Shire Pharamceuticals, Warner Chilcott UK, S. Lee: None Declared, H. Borthwick: None Declared, P. Nair: None Declared, C. White: None Declared

Azathioprine paper RCPE Apr 2009

Comparing outcome of radiofrequency ablation in Barrett's with high grade dysplasia and intramucosal carcinoma: a prospective multicenter UK registry

Endoscopy, Jan 30, 2015

Background and study aim: Mucosal neoplasia arising in Barrett's esophagus can be successfull... more Background and study aim: Mucosal neoplasia arising in Barrett's esophagus can be successfully treated with endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA). The aim of the study was to compare clinical outcomes of patients with high grade dysplasia (HGD) or intramucosal cancer (IMC) at baseline from the United Kingdom RFA registry. Patients and methods: Prior to RFA, visible lesions and nodularity were removed entirely by EMR. Thereafter, patients underwent RFA every 3 months until all visible Barrett's mucosa was ablated or cancer developed (end points). Biopsies were taken at 12 months or when end points were reached. Results: A total of 515 patients, 384 with HGD and 131 with IMC, completed treatment. Prior to RFA, EMR was performed for visible lesions more frequently in the IMC cohort than in HGD patients (77 % vs. 47 %;…

Pancrease divisum: five years' experience in a teaching hospital

Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology, 1996

To study the frequency and significance of pancreas divisum. Retrospective analysis of all pancre... more To study the frequency and significance of pancreas divisum. Retrospective analysis of all pancreatograms carried out between July 1989 and June 1994. The 809 pancreatograms performed included 207 in patients with pancreatitis (acute 74, chronic 133), 330 with biliary disease, 238 with obscure abdominal pain and 34 with pancreatic malignancy. Of these, 30 patients (3.7%) were diagnosed to have pancreas divisum - 26 had type I variant, one had type II variant and three had type III variant. Accessory papillary cannulation was attempted in 10 patients; 8 were successful, with dorsal ductography confirming pancreas divisum in all of them. Two of these 8 patients had changes of chronic pancreatitis in the dorsal duct. The frequency of pancreas divisum in patients with pancreatitis (19 of 207, 9.2%) was significantly higher than in patients with biliary diseases and those with obscure abdominal pain (11 of 568, 1.9%; p < 0.001). Pancreas divisum is not an uncommon condition in India a...

Biodegradable stent or balloon dilatation for benign oesophageal stricture: pilot randomised controlled trial

World journal of gastroenterology : WJG, Jan 28, 2014

To undertake a randomised pilot study comparing biodegradable stents and endoscopic dilatation in... more To undertake a randomised pilot study comparing biodegradable stents and endoscopic dilatation in patients with strictures. This British multi-site study recruited seventeen symptomatic adult patients with refractory strictures. Patients were randomised using a multicentre, blinded assessor design, comparing a biodegradable stent (BS) with endoscopic dilatation (ED). The primary endpoint was the average dysphagia score during the first 6 mo. Secondary endpoints included repeat endoscopic procedures, quality of life, and adverse events. Secondary analysis included follow-up to 12 mo. Sensitivity analyses explored alternative estimation methods for dysphagia and multiple imputation of missing values. Nonparametric tests were used. Although both groups improved, the average dysphagia scores for patients receiving stents were higher after 6 mo: BS-ED 1.17 (95%CI: 0.63-1.78) P = 0.029. The finding was robust under different estimation methods. Use of additional endoscopic procedures and ...

Coeliac disease and granulomatous ileocolitis: an association or chance occurrence?

The Journal of the Royal College of Physicians of Edinburgh, 2011

Enteric granulomatous inflammation can be caused by a number of conditions including Crohn's dise... more Enteric granulomatous inflammation can be caused by a number of conditions including Crohn's disease, sarcoidosis, enteric infections, chronic granulomatous disease and also by drug reactions. Granulomas have also been described in microscopic colitis associated with certain medications and autoimmune diseases. The association of granulomatous ileocolitis with coeliac disease is not common. We present a case of coeliac disease with granulomatous ileocolitis with follow-up and repeat histology on a gluten-free diet. We discuss the pathological mechanisms leading to the association of granulomatous ileocolitis with coeliac disease as well as other conditions.

Polymorphisms Near TBX5 and GDF7 Are Associated With Increased Risk for Barrett's Esophagus

Gastroenterology, 2015

Barrett&amp…

Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus

Nature Genetics, 2012

Barrett's Esophagus is an increasingly common disease that is strongly associated with reflux of ... more Barrett's Esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia. Barrett's Esophagus strongly predisposes to esophageal adenocarcinoma (EAC), a tumour with a very poor prognosis. We have undertaken the first genome-wide association study on Barrett's Esophagus, comprising 1,852 UK cases and 5,172 UK controls in discovery and 5,986 cases and 12,825 controls in the replication. Two regions were associated with disease risk: chromosome 6p21, rs9257809 (P combined =4.09×10 -9 , OR(95%CI) =1.21(1.13-1.28)) and chromosome 16q24, rs9936833 (P combined =2.74×10 -10 , OR(95%CI) =1.14(1.10-1.19)). The top SNP on chromosome 6p21 is within the major histocompatibility complex, and the closest protein-coding gene to rs9936833 on chromosome 16q24 is FOXF1, which is implicated in esophageal development and structure. We found evidence that the genetic component of Barrett's Esophagus is mediated by many common variants of small effect and that SNP alleles predisposing to obesity also increase risk for Barrett's Esophagus.

Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial

The Lancet, 2013

Background Antibiotic-associated diarrhoea (AAD) occurs most frequently in older (≥65 years) inpa... more Background Antibiotic-associated diarrhoea (AAD) occurs most frequently in older (≥65 years) inpatients exposed to broad-spectrum antibiotics. When caused by Clostridium diffi cile, AAD can result in life-threatening illness. Although underlying disease mechanisms are not well understood, microbial preparations have been assessed in the prevention of AAD. However, studies have been mostly small single-centre trials with varying quality, providing insuffi cient data to reliably assess eff ectiveness. We aimed to do a pragmatic effi cacy trial in older inpatients who would be representative of those admitted to National Health Service (NHS) and similar secondary care institutions and to recruit a suffi cient number of patients to generate a defi nitive result. Methods We did a multicentre, randomised, double-blind, placebo-controlled, pragmatic, effi cacy trial of inpatients aged 65 years and older and exposed to one or more oral or parenteral antibiotics. A computer-generated randomisation scheme was used to allocate participants (in a 1:1 ratio) to receive either a multistrain preparation of lactobacilli and bifi dobacteria, with a total of 6 × 10¹⁰ organisms, one per day for 21 days, or an identical placebo. Patients, study staff , and specimen and data analysts were masked to assignment. The primary outcomes were occurrence of AAD within 8 weeks and C diffi cile diarrhoea (CDD) within 12 weeks of recruitment. Analysis was by modifi ed intention-totreat. This trial is registered, number ISRCTN70017204. Of 17 420 patients screened, 1493 were randomly assigned to the microbial preparation group and 1488 to the placebo group. 1470 and 1471, respectively, were included in the analyses of the primary endpoints. AAD (including CDD) occurred in 159 (10•8%) participants in the microbial preparation group and 153 (10•4%) participants in the placebo group (relative risk [RR] 1•04; 95% CI 0•84-1•28; p=0•71). CDD was an uncommon cause of AAD and occurred in 12 (0•8%) participants in the microbial preparation group and 17 (1•2%) participants in the placebo group (RR 0•71; 95% CI 0•34-1•47; p=0•35). 578 (19•7%) participants had one or more serious adverse event; the frequency of serious adverse events was much the same in the two study groups and none was attributed to participation in the trial. Interpretation We identifi ed no evidence that a multistrain preparation of lactobacilli and bifi dobacteria was eff ective in prevention of AAD or CDD. An improved understanding of the pathophysiology of AAD is needed to guide future studies.

Curriculum review : investigation and management of dysphagia

Frontline Gastroenterology, 2021

Dysphagia is a common presentation in gastroenterology practice and the diagnosis and management ... more Dysphagia is a common presentation in gastroenterology practice and the diagnosis and management requires a comprehensive knowledge of diverse range of aetiologies, with a systematic approach for assessment of symptoms, selection of investigations and appropriate treatment to relieve symptoms. In this curriculum review, the suggested diagnostic approach highlights the importance of thorough clinical assessment in order to guide the selection of investigations. This article discusses the utility of endoscopic, histopathology, fluoroscopic and motility investigations for dysphagia, and their interpretation, in order to guide targeted treatments ranging from dietary, pharmacological, endoscopic and surgical interventions.

PWE-016 Delivering parenteral nutrition– real world challenges

Posters, 2019

On review of the patients whose cause of death were attributed to cancer, 12 did not have maligna... more On review of the patients whose cause of death were attributed to cancer, 12 did not have malignancy as initial HPN indication. Regarding mortality not linked to HPN, respiratory complications including pneumonia were the commonest causative factor (8/29, 28%). Conclusions This study showed that mortality was associated with the underlying disease condition resulting in the need for HPN or other co-morbidities rather than direct complications of HPN itself. REFERENCE 1. Pironi L, Joly F, Forbes A, et al. Long-term follow-up of patients on home parenteral nutrition in Europe: implications for intestinal transplantation. Gut 2011;60:1-5.

$Research paper thumbnail of P381 Infliximab induction regimes in steroid refractory acute severe colitis: a multi-centre retrospective cohort study with propensity score analysis$

P381 Infliximab induction regimes in steroid refractory acute severe colitis: a multi-centre retrospective cohort study with propensity score analysis

Journal of Crohn's and Colitis, 2019

16/32 patients (50.0%). 24.1% (n = 84) of patients reported at least one adverse event. Fifty pat... more 16/32 patients (50.0%). 24.1% (n = 84) of patients reported at least one adverse event. Fifty patients (14.3%) discontinued Budesonide MMX® for adverse events; 17.5% of patients (n = 61) reported at least one adverse event related to the study drug. Nine patients had worsening of the underlying colitis (3%). All the other adverse events were reported in <1% of patients. Table 1. Baseline characteristics of the study population. Conclusions: This large real-life cohort study demonstrates for the first time that Budesonide MMX® is effective in about two-thirds of UC patients, and that Budesonide MMX® was safe and well tolerated.

PWE-077 Residual Intestinal Metaplasia after Successful Endoscopic Therapy for Barrett’s Related Neoplasia Confers Higher Long Term Risk for Disease Recurrence, on Behalf of The UK RFA Registry

Gut, 2016

143 at medium volume (n = 4) & 118 at low volume centres (n = 15). There was no difference in ent... more 143 at medium volume (n = 4) & 118 at low volume centres (n = 15). There was no difference in entry criteria or demographics between groups. CR-D & CR-IM at 12 months are no different between the groups (CR-D 86-90%, CR-IM 74-81%). IM recurrence is significantly lower in high volume centres (16.1% vs 20.3% and 19.2%, Log Rank p < 0.001) but dysplasia recurrence is no different (Log Rank p = 0.12). Rescue EMR was performed less frequently in medium volume centres (0% vs high 5.3% and low volume 10%, p = 001). Conclusion Endotherapy for Barrett's dysplasia is highly effective whatever the centre volume. The rescue EMR rate in medium volume centres is unexplained. Despite lower IM recurrence in high volume centres, dysplasia recurrence rates are not significantly different. Caseload volume of a centre in the UK Registry does not appear to affect outcome.

PWE-087 Endoscopic Non-Ablative Radio Frequency Energy Treatment (Stretta®) for Gastro-Oesophageal Reflux Disease – The First UK Single Centre Experience: Abstract PWE-087 Table 1

Gut, 2016

Mercaptopurine versus placebo to prevent recurrence of Crohn's disease after surgical resection (TOPPIC): a multicentre, double-blind, randomised controlled trial

The Lancet Gastroenterology & Hepatology, 2016

Background Up to 60% of patients with Crohn's disease need intestinal resection within the fi rst... more Background Up to 60% of patients with Crohn's disease need intestinal resection within the fi rst 10 years of diagnosis, and postoperative recurrence is common. We investigated whether mercaptopurine can prevent or delay postoperative clinical recurrence of Crohn's disease. We did a randomised, placebo-controlled, double-blind trial at 29 UK secondary and tertiary hospitals of patients (aged >16 years in Scotland or >18 years in England and Wales) who had a confi rmed diagnosis of Crohn's disease and had undergone intestinal resection. Patients were randomly assigned (1:1) by a computer-generated web-based randomisation system to oral daily mercaptopurine at a dose of 1 mg/kg bodyweight rounded to the nearest 25 mg or placebo; patients with low thiopurine methyltransferase activity received half the normal dose. Patients and their carers and physicians were masked to the treatment allocation. Patients were followed up for 3 years. The primary endpoint was clinical recurrence of Crohn's disease (Crohn's Disease Activity Index >150 plus 100-point increase in score) and the need for anti-infl ammatory rescue treatment or primary surgical intervention. Primary and safety analyses were by intention to treat. Subgroup analyses by smoking status, previous thiopurines, previous infl iximab or methotrexate, previous surgery, duration of disease, or age at diagnosis were also done. This trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN89489788) and the European Clinical Trials Database (EudraCT number 2006-005800-15).

Faecal calprotectin—ready for prime time?

Frontline Gastroenterology, 2014

841 Residual Intestinal Metaplasia After Successful Endoscopic Therapy for Barrett's Related Neoplasia Confers Higher Long Term Risk for Disease Recurrence, on Behalf of the UK RFA Registry

Gastroenterology, 2016

that none of the patients with BE < 1 cm (irregular -z line developed HGD or cancer during follow... more

Optic neuritis and TNF antagonists in IBD

Journal of Crohn's & colitis, Jan 12, 2016

Background and AimsAcute optic neuritis (ON) is an inflammatory condition affecting the optic ner... more Background and AimsAcute optic neuritis (ON) is an inflammatory condition affecting the optic nerve. Clinicians should suspect optic neuritis in cases of painful and rapidly progressive loss of central visual field. This condi-tion may be associated with a multitude of diseases, and mostly with multiple sclerosis (MS) where may present as an initial symptom. The literature reports that optic neuritis and MS occur in patients with inflammatory bowel disease (IBD) before and after the era of anti-tumor necrosis factor-α (TNF-α) drugs. At the present moment, there is little consensus for managing this complication, currently treated with corticosteroids and discontinuation of the causative agents.MethodsWe collected cases through a retrospective multicenter European Crohn's and Colitis Organization CONFER (Collaborative Network For Exceptionally Rare case reports) project. We also performed a comprehensive retrospective search of the available litterature on this topic.ResultWe rep...

Reply to Kristo et al

Endoscopy, 2016

We thank you for your observations and comments about the role of surgical treatment for acid ref... more We thank you for your observations and comments about the role of surgical treatment for acid reflux in maintaining long-term disease remission after successful endoscopic therapy. We share your observations that although, in most patents, with combined endoscopic resection and radiofrequency ablation (RFA), we are able to clear the mucosal neoplasia and intestinal metaplasia that is Barrett’s esophagus, we do not reverse the persisting reflux insult that drives the biological transformation to Barrett’s esophagus and neoplasia. The ongoing requirement for acid suppression after successful endoscopic treatment may well reduce the quantity of acid exposure to the distal esophagus but this has little impact on the number of reflux events overall [1]. Toxic compounds within the refluxate that can lead to persistent damage to squamous mucosa include duodenogastric contents such as bile, pepsin, and pancreatic proteolytic enzymes [2]. Furthermore, the mechanical clearance of refluxate after endotherapy might also be impaired as has been shown in patients with mucosal esophagitis when compared to those with endoscopy-negative reflux disease [3], a concept yet to be explored in the context of refractory Barrett’s esophagus. Shaheen at al. [4] showed from data derived from the US registry that in patients undergoing endoscopic therapy for Barrett’s neoplasia prior antireflux surgery made no difference to the outcome. The authors examined 5537 patients undergoing RFA, of which 301 (5.4 %) had had a prior fundoplication. Complete eradication of intestinal metaplasia and dysplasia were achieved in 71 % and 87 %, respectively, of patients with a fundoplication, and 73 % and 87 %, respectively, of patients without a fundoplication (P = non-significant for both). Therefore the authors concluded that prior antireflux surgery made no difference to the outcome. However, there was little emphasis on the selection criteria for antireflux surgery or on the manometric and reflux characteristics that led to the surgical decision-making. The role of surgery after successful endoscopic treatment has yet to be examined and may well find a place in carefully selected patients in whom significant reflux is more likely after successful therapy – for example those with a large hiatus hernia and significant exposure to acid (or exposure to weak acid/non-acids such as bile) despite maximum medical therapy.

Oesophageal stenting for benign and malignant strictures: a systematic approach

Frontline Gastroenterology, 2015

Oesophageal stenting is now standard treatment for managing both benign and malignant stenosis of... more Oesophageal stenting is now standard treatment for managing both benign and malignant stenosis of the oesophagus. There is a wide choice in oesophageal stents currently available on the market, with variations in the stent material, size and design. Most oesophageal stents are made from metal alloy compounds for use in malignant strictures, although there are stents made of durable polymers, and now of biodegradable (BD) material, for use in both benign and malignant strictures. With the development of self-expanding plastic stents, self-expanding metal stents and BD stents, stent placement for oesophageal pathologies can be safe and cost-effective. Oesophageal stenting has several challenges for a therapeutic endoscopist which is determined by the location of stricture or tumour, the anatomy of the stenosis and the nature of stent selected. Strictures that have narrow or tortuous lumens can be particularly difficult to stent as the luminal diameter must allow access of at least a 0.035 inch guide wire. This review covers the indications and outcomes of different stents in clinical situations to help rational decisionmaking. Benign oesophageal strictures include most commonly peptic strictures, corrosive, postsurgical anastomotic strictures and radiation-induced inflammatory strictures. Less common causes include tracheooesophageal fistulae, iatrogenic perforation and leaks and external compression.

Su1181 Point-of-Contact Faecal Calprotectin (FC) Testing in Diarrhoea Helps Decision Making for Referral to Gastroenterologists: A Primary Care Pilot Study in North East England

Gastroenterology, 2013

Introduction Faecal Calprotectin (FC) is a cytosolic protein belonging to the S-100 family of cal... more Introduction Faecal Calprotectin (FC) is a cytosolic protein belonging to the S-100 family of calcium binding proteins found in neutrophils. It is excreted in the intestinal lumen in inflammatory conditions of the gut and can be used to distinguish irritable bowel syndrome (IBS) from other inflammatory bowel conditions such as colitis, diverticulosis, etc. Point-of-contact qualitative FC tests are now available and can be used in primary care to aid decision making for referrals to gastroenterologists for young patients presenting with chronic diarrhoea. Methods Aims To assess the feasibility and cost effectiveness of a primary care Pathway using a point-of-contact FC Test (Caldetect®) to aid decision making for referrals to gastroenterology in young patients presenting to their primary physicians with chronic diarrhoea. Methods: Primary Care data indicated that approximately 253 referrals are made annually to gastroenterologists from Primary Care to assess patients 60 ug/g. Patients with FC results of 15–60 and >60 were deemed to have an inflammatory process and referred to Gastroenterology Clinics. Cost analysis was carried out using the 2010–11 tariffs for the NHS. Results 142 Caldetect® tests were carried out in Primary Care during this pilot phase. Of these, a negative result ( 60 ug/g. 3 tests were at the intermediate level and 14 tests could not be accurately reported. Negative results were managed in primary care as IBS. A monthly cost savings of £6100 was calculated taking consultation and endoscopy tariffs into account. Conclusion This pilot study demonstrates the feasibility and cost effectiveness of a Pathway for decision making and a point-of-care faecal calprotectin test in rationalising referrals to Gastroenterologists for chronic diarrhoea. Disclosure of Interest A. Dhar Speaker bureau with: Shire Pharamceuticals, Warner Chilcott UK, S. Lee: None Declared, H. Borthwick: None Declared, P. Nair: None Declared, C. White: None Declared

Azathioprine paper RCPE Apr 2009

Comparing outcome of radiofrequency ablation in Barrett's with high grade dysplasia and intramucosal carcinoma: a prospective multicenter UK registry

Endoscopy, Jan 30, 2015

Background and study aim: Mucosal neoplasia arising in Barrett's esophagus can be successfull... more Background and study aim: Mucosal neoplasia arising in Barrett's esophagus can be successfully treated with endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA). The aim of the study was to compare clinical outcomes of patients with high grade dysplasia (HGD) or intramucosal cancer (IMC) at baseline from the United Kingdom RFA registry. Patients and methods: Prior to RFA, visible lesions and nodularity were removed entirely by EMR. Thereafter, patients underwent RFA every 3 months until all visible Barrett's mucosa was ablated or cancer developed (end points). Biopsies were taken at 12 months or when end points were reached. Results: A total of 515 patients, 384 with HGD and 131 with IMC, completed treatment. Prior to RFA, EMR was performed for visible lesions more frequently in the IMC cohort than in HGD patients (77 % vs. 47 %;…

Pancrease divisum: five years' experience in a teaching hospital

Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology, 1996

To study the frequency and significance of pancreas divisum. Retrospective analysis of all pancre... more To study the frequency and significance of pancreas divisum. Retrospective analysis of all pancreatograms carried out between July 1989 and June 1994. The 809 pancreatograms performed included 207 in patients with pancreatitis (acute 74, chronic 133), 330 with biliary disease, 238 with obscure abdominal pain and 34 with pancreatic malignancy. Of these, 30 patients (3.7%) were diagnosed to have pancreas divisum - 26 had type I variant, one had type II variant and three had type III variant. Accessory papillary cannulation was attempted in 10 patients; 8 were successful, with dorsal ductography confirming pancreas divisum in all of them. Two of these 8 patients had changes of chronic pancreatitis in the dorsal duct. The frequency of pancreas divisum in patients with pancreatitis (19 of 207, 9.2%) was significantly higher than in patients with biliary diseases and those with obscure abdominal pain (11 of 568, 1.9%; p < 0.001). Pancreas divisum is not an uncommon condition in India a...

Biodegradable stent or balloon dilatation for benign oesophageal stricture: pilot randomised controlled trial

World journal of gastroenterology : WJG, Jan 28, 2014

To undertake a randomised pilot study comparing biodegradable stents and endoscopic dilatation in... more To undertake a randomised pilot study comparing biodegradable stents and endoscopic dilatation in patients with strictures. This British multi-site study recruited seventeen symptomatic adult patients with refractory strictures. Patients were randomised using a multicentre, blinded assessor design, comparing a biodegradable stent (BS) with endoscopic dilatation (ED). The primary endpoint was the average dysphagia score during the first 6 mo. Secondary endpoints included repeat endoscopic procedures, quality of life, and adverse events. Secondary analysis included follow-up to 12 mo. Sensitivity analyses explored alternative estimation methods for dysphagia and multiple imputation of missing values. Nonparametric tests were used. Although both groups improved, the average dysphagia scores for patients receiving stents were higher after 6 mo: BS-ED 1.17 (95%CI: 0.63-1.78) P = 0.029. The finding was robust under different estimation methods. Use of additional endoscopic procedures and ...

Coeliac disease and granulomatous ileocolitis: an association or chance occurrence?

The Journal of the Royal College of Physicians of Edinburgh, 2011

Enteric granulomatous inflammation can be caused by a number of conditions including Crohn's dise... more Enteric granulomatous inflammation can be caused by a number of conditions including Crohn's disease, sarcoidosis, enteric infections, chronic granulomatous disease and also by drug reactions. Granulomas have also been described in microscopic colitis associated with certain medications and autoimmune diseases. The association of granulomatous ileocolitis with coeliac disease is not common. We present a case of coeliac disease with granulomatous ileocolitis with follow-up and repeat histology on a gluten-free diet. We discuss the pathological mechanisms leading to the association of granulomatous ileocolitis with coeliac disease as well as other conditions.

Polymorphisms Near TBX5 and GDF7 Are Associated With Increased Risk for Barrett's Esophagus

Gastroenterology, 2015

Barrett&amp…

Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus

Nature Genetics, 2012

Barrett's Esophagus is an increasingly common disease that is strongly associated with reflux of ... more Barrett's Esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia. Barrett's Esophagus strongly predisposes to esophageal adenocarcinoma (EAC), a tumour with a very poor prognosis. We have undertaken the first genome-wide association study on Barrett's Esophagus, comprising 1,852 UK cases and 5,172 UK controls in discovery and 5,986 cases and 12,825 controls in the replication. Two regions were associated with disease risk: chromosome 6p21, rs9257809 (P combined =4.09×10 -9 , OR(95%CI) =1.21(1.13-1.28)) and chromosome 16q24, rs9936833 (P combined =2.74×10 -10 , OR(95%CI) =1.14(1.10-1.19)). The top SNP on chromosome 6p21 is within the major histocompatibility complex, and the closest protein-coding gene to rs9936833 on chromosome 16q24 is FOXF1, which is implicated in esophageal development and structure. We found evidence that the genetic component of Barrett's Esophagus is mediated by many common variants of small effect and that SNP alleles predisposing to obesity also increase risk for Barrett's Esophagus.

Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial

The Lancet, 2013

Background Antibiotic-associated diarrhoea (AAD) occurs most frequently in older (≥65 years) inpa... more Background Antibiotic-associated diarrhoea (AAD) occurs most frequently in older (≥65 years) inpatients exposed to broad-spectrum antibiotics. When caused by Clostridium diffi cile, AAD can result in life-threatening illness. Although underlying disease mechanisms are not well understood, microbial preparations have been assessed in the prevention of AAD. However, studies have been mostly small single-centre trials with varying quality, providing insuffi cient data to reliably assess eff ectiveness. We aimed to do a pragmatic effi cacy trial in older inpatients who would be representative of those admitted to National Health Service (NHS) and similar secondary care institutions and to recruit a suffi cient number of patients to generate a defi nitive result. Methods We did a multicentre, randomised, double-blind, placebo-controlled, pragmatic, effi cacy trial of inpatients aged 65 years and older and exposed to one or more oral or parenteral antibiotics. A computer-generated randomisation scheme was used to allocate participants (in a 1:1 ratio) to receive either a multistrain preparation of lactobacilli and bifi dobacteria, with a total of 6 × 10¹⁰ organisms, one per day for 21 days, or an identical placebo. Patients, study staff , and specimen and data analysts were masked to assignment. The primary outcomes were occurrence of AAD within 8 weeks and C diffi cile diarrhoea (CDD) within 12 weeks of recruitment. Analysis was by modifi ed intention-totreat. This trial is registered, number ISRCTN70017204. Of 17 420 patients screened, 1493 were randomly assigned to the microbial preparation group and 1488 to the placebo group. 1470 and 1471, respectively, were included in the analyses of the primary endpoints. AAD (including CDD) occurred in 159 (10•8%) participants in the microbial preparation group and 153 (10•4%) participants in the placebo group (relative risk [RR] 1•04; 95% CI 0•84-1•28; p=0•71). CDD was an uncommon cause of AAD and occurred in 12 (0•8%) participants in the microbial preparation group and 17 (1•2%) participants in the placebo group (RR 0•71; 95% CI 0•34-1•47; p=0•35). 578 (19•7%) participants had one or more serious adverse event; the frequency of serious adverse events was much the same in the two study groups and none was attributed to participation in the trial. Interpretation We identifi ed no evidence that a multistrain preparation of lactobacilli and bifi dobacteria was eff ective in prevention of AAD or CDD. An improved understanding of the pathophysiology of AAD is needed to guide future studies.