PostScript transcript remains to be validated in other independent series of HCC. Qian Cao,1,2,3,4 Sandrine Imbeaud,1,2,3,4 Shalini Datta,1,2,3,4 Jessica Zucman-Rossi1,2,3,4,5 1
Inserm, UMR-1162, Génomique fonctionnelle des tumeurs solides, IUH, Paris, France 2 Faculté de Médecine, Université Paris Descartes, Labex Immuno-oncology, Sorbonne Paris Cité, Paris, France 3 Université Paris 13, Sorbonne Paris Cité, UFR SMBH, Bobigny, France 4 Université Paris Diderot, Paris, France 5 Assistance Publique-Hôpitaux de Paris, Hopital Europeen Georges Pompidou, Paris, France Correspondence to Professor Jessica Zucman-Rossi, Inserm U1162, Génomique fonctionnelle des tumeurs solides, 27 rue Juliette Dodu, Paris 75010, France; [email protected] Contributors All authors performed the experiments, analyses and have written the letter. Competing interests None. Patient consent Obtained. Provenance and peer review Not commissioned; internally peer reviewed.
To cite Cao Q, Imbeaud S, Datta S, et al. Gut 2015;64:853–854. Received 22 September 2014 Accepted 25 September 2014 Published Online First 20 October 2014
▸ http://dx.doi.org/10.1136/gutjnl-2014-308283 ▸ http://dx.doi.org/10.1136/gutjnl-2014-306228 Gut 2015;64:853–854. doi:10.1136/gutjnl-2014-308482
REFERENCES 1
2
3
Cao W, Peppelenbosch MP, Pan Q. Virus-host interactions in HBV-related hepatocellular carcinoma: more to be revealed? Gut 2015;64:852–3. Amaddeo G, Cao Q, Ladeiro Y, et al. Integration of tumour and viral genomic characterisations in HBV-related hepatocellular carcinomas. Gut 2015;64: 820–9. Lau CC, Sun T, Ching AK, et al. Viral-human chimeric transcript predisposes risk to liver cancer development and progression. Cancer Cell 2014;25: 335–49.
Author response: oral contraceptives and Crohn’s disease We appreciate the suggestion by Dr Rhodes to further evaluate the link between oral contraceptive (OC) use and risk of Crohn’s disease according to the anatomical location of disease involvement.1 We agree that a plausible 854
mechanism for the link between OC use and risk of Crohn’s disease may be through the effect of oestrogen on subacute thrombosis, leading to the development of multifocal ischaemia and infarction of the colon that manifests as colitis. In our study,2 we documented 315 incident cases of Crohn’s disease through 2007 in Nurses’ Health Study II (NHS II) and 2008 in NHS I. Among these cases, 141 (45%) were isolated colonic disease and 82 (26%) were ileal Crohn’s disease. Compared with never users of OC, the multivariate-adjusted HRs of Crohn’s disease confined to the ileum were 2.99 (95% CI 1.06 to 8.49) for current OC use and 1.46 (95% CI 0.86 to 2.50) for past use. Similarly, compared with never users, the multivariate-adjusted HRs for isolated colonic Crohn’s disease were 4.13 (95% CI 1.77 to 9.68) for current OC users and 1.88 (95% CI 1.22 to 2.88) for past use. Thus, these data do not support a preferential association of OC use with isolated colonic Crohn’s disease. Nonetheless, as we noted in our original manuscript, several other plausible mechanisms exist. First, oral oestrogen has been shown to modify intestinal permeability,3 4 a critical step in the pathophysiology of IBD. Second, OC use through its effect on endogenous levels of hormones may enhance the development of Th1mediated and Th2- mediated inflammatory diseases.5 Lastly, recent data have linked modification in the gut microbiome to endogenous levels of androgens,6 which are also known to be altered with OC use and influence the development of autoimmune diseases. This supports the intriguing hypothesis that the gut microbiome lies at the crossroads of pathways linking exogenous hormone use with innate and adaptive immunity. Hamed Khalili,1 Andrew T Chan1,2 1 Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA 2 Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
Correspondence to Dr Hamed Khalili, Gastrointestinal Unit, Massachusetts General Hospital, 165 Cambridge St., 9th floor, Boston, MA 02114, USA; [email protected] Competing interests None. Provenance and peer review Not commissioned; internally peer reviewed.
To cite Khalili H, Chan AT. Gut 2015;64:854.
Received 23 September 2014 Revised 29 September 2014 Accepted 30 September 2014 Published Online First 20 October 2014
▸ http://dx.doi.org/10.1136/gutjnl-2014-305972 ▸ http://dx.doi.org/10.1136/gutjnl-2012-302362 Gut 2015;64:854. doi:10.1136/gutjnl-2014-308509
REFERENCES 1 2
3
4
5
6
Rhodes JM. Oral contraceptives and Crohn’s disease. Gut 2014;63:863. Khalili H, Higuchi LM, Ananthakrishnan AN, et al. Oral contraceptives, reproductive factors and risk of inflammatory bowel disease. Gut 2013;62:1153–9. Braniste V, Jouault A, Gaultier E, et al. Impact of oral bisphenol A at reference doses on intestinal barrier function and sex differences after perinatal exposure in rats. Proc Natl Acad Sci USA 2010;107:448–53. Looijer-van Langen M, Hotte N, Dieleman LA, et al. Estrogen receptor-beta signaling modulates epithelial barrier function. Am J Physiol Gastrointest Liver Physiol 2011;300:G621–6. Cutolo M, Capellino S, Straub RH. Oestrogens in rheumatic diseases: friend or foe? Rheumatology 2008;47(Suppl 3):iii2–5. Markle JG, Frank DN, Mortin-Toth S, et al. Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science 2013;339:1084–8.
Successful delivery of clinical gastroenterology studies in the UK Recent publications in Gut1 2 have highlighted the beneficial role of the National Institute for Health Research (NIHR) Clinical Research Network in supporting clinical gastroenterology research in the UK.3 On an European level, the European Clinical Research Infrastructures Network provides integrated support to multinational clinical research projects in partner countries. The overarching aim of the NIHR Clinical Research Network is to maximise clinical research delivery by providing the infrastructure that allows high-quality studies to be undertaken in the NHS. The support available encompasses many aspects of the study life-cycle, including study set-up, researcher training and aiding study delivery, for example by providing protected clinician research time and research nurse support at individual study sites in NHS institutions. All clinical gastroenterology research studies entered onto the NIHR Clinical Research Network Portfolio are eligible for support.3 The performance of the NIHR Clinical Research Network Portfolio is closely Gut May 2015 Vol 64 No 5
PostScript monitored using several High Level Objectives, one of which is increasing the proportion of studies that deliver in line with their planned delivery time and patient recruitment targets. The progress of each study during the recruitment phase is rated on a BRAG (black/red/ amber/green) system, with studies deemed to be on target (‘green’) if recruitment is running at least 80% of that expected according to each study’s self-determined recruitment schedule.4 Upon closure, studies which successfully recruited to their target within the specified time are rated ‘green’ and those which either over-ran their time or failed to recruit to plan are rated ‘red’. One can immediately see that when bodies such as the NIHR and the research charities are making funding decisions, they might be very interested in the proportion of ‘green’ studies on the Gastroenterology Portfolio as an indicator of the future ability of gastroenterologists to deliver successful research projects in the NHS. The same could be said of potential commercial trial sponsors, who approach the NIHR Clinical Research Network to use a number of services, including identification of research sites for multicentre studies. It is, therefore, in the gastroenterology research community’s best interests, and the interests of patients, to maximise the number of studies on the portfolio which deliver to time and target. However, although study delivery has improved significantly over the last few years, only 55% of gastroenterology studies closed ‘green’ in 2013/2014 compared with the national target of 80%, and currently, for this financial year, a similar proportion (53%) of open studies are recruiting to time and target (data accessed 25 July 2014). There are obviously many reasons why research projects do not proceed to plan and participant recruitment is lower than expected, some of which may be beyond the investigators’ control. However, there are also several ‘investigator factors’ that probably contribute to poor study performance and that can be addressed relatively easily by gastroenterology researchers: 1. Investigators should carefully consider and state a realistic, achievable sample size target for their study, along with an appropriate start date and study duration, during the Integrated Research Application System (application process for study approvals. Targets set during the approvals
Gut May 2015 Vol 64 No 5
process are used to populate the NIHR Clinical Research Network Portfolio entry. One might expect that basing the time and target metric on the predictions of the Investigator would give a study the best possible opportunity to recruit to time and target. However, many Investigators still underestimate the time taken to gain regulatory approvals during study set-up and overestimate recruitment potential. Realistic targets compatible with the funding provided for a study are more likely to be achievable. 2. Investigators should realise that if unexpected delays are encountered, the date and recruitment targets set on the NIHR Clinical Research Network Portfolio may be altered, in agreement with the study funder. This can make a huge difference to an individual study’s BRAG rating. The key action is to inform Clinical Research Network Portfolio staff through the national gastroenterology team (see below), who can then help the investigator gain the necessary evidence of a study extension with which to change the entry on the Portfolio database. 3. Investigators need to update their study entry on the Portfolio on a regular basis. Portfolio data are published every month and it is expected that each study team will provide a monthly recruitment figure. This is, in fact, another metric—so-called ‘recruitment upload engagement’ or the % number of occasions when monthly recruitment data are reported. Currently ( July 2014), recruitment data is missing for nearly 10% of gastroenterology studies and one can easily imagine the effect of inaccurate recruitment data on individual study and overall gastroenterology BRAG ratings. One factor which has hampered the ability of investigators to fully engage with the NIHR Clinical Research Network Portfolio and study performance has been the lack of a simple means by which to communicate with Portfolio staff in the NIHR Clinical Research Network Coordinating Centre. Recently this has changed with the appointment of a dedicated Gastroenterology Portfolio Coordinator, whose role is to ensure that individual non-commercial study data entries are as up-to-date and accurate as possible. We are convinced that the Gastroenterology Specialty’s performance against the High Level Objectives will improve significantly if all investigators
respond in a timely and positive manner to requests from the coordinator for information regarding individual studies that are supported by NIHR Clinical Research Network infrastructure locally. The situation is slightly different regarding commercially sponsored studies, but the same strategy applies; maximal engagement with the NIHR Clinical Research Network Commercial team will reap dividends for improved performance. The Gastroenterology Portfolio Coordinator and Specialty National Lead can be contacted at [email protected]. The NIHR Clinical Research Network has recently undergone reconfiguration such that gastroenterology research takes place across England in 15 Local Clinical Research Networks.5 Each Local Clinical Research Network has a Gastroenterology Lead, who is well-placed to help any investigator deliver their study successfully, and communicate through the NIHR Clinical Research Network Coordinating Centre to affect any necessary changes to their study record. If a gastroenterologist is unclear who his or her Regional Lead is, this can easily be determined by contacting their Local Clinical Research Network,5 checking on the NIHR Clinical Research Network’s website6 or checking with the British Society of Gastroenterology.7 In summary, we believe that the above simple measures based around improved communication with the Gastroenterology Portfolio Coordinator and more realistic targets can improve individual study and overall gastroenterology performance, with consequent benefits for gastroenterology research, in general, by persuading funders of the feasibility of noncommercial gastroenterology studies and attracting more commercially sponsored gastroenterology research to the UK. Mark A Hull,1 John T McLaughlin2 1
Leeds Institute of Biomedical & Clinical Sciences, St James’s University Hospital, Leeds, UK 2 Department of GI Sciences, University of Manchester, Salford, UK Correspondence to Professor Mark A Hull, Leeds Institute of Biomedical & Clinical Sciences, St James’s University Hospital, Wellcome Trust Brenner Building, Leeds LS9 7TF, UK; [email protected] Acknowledgements MAH is the Specialty National Lead, NIHR Clinical Research Network: Gastroenterology and the Specialty Local Lead, NIHR Clinical Research Network: Yorkshire and Humber (Gastroenterology), and JTM is the Chair of British Society of Gastroenterology Research Committee. Competing interests None.
855
PostScript Provenance and peer review Not commissioned; internally peer reviewed.
Accepted 18 October 2014 Published Online First 6 November 2014 Gut 2015;64:854–856. doi:10.1136/gutjnl-2014-308348
To cite Hull MA, McLaughlin JT. Gut 2015;64:854– 856. Received 29 August 2014 Revised 13 October 2014
REFERENCES 1
Cockbain AJ, Volpato M, Race AD, et al. Anticolorectal cancer activity of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid. Gut 2014;63:1760–8.
EDITOR’S QUIZ: GI SNAPSHOT
Unusual cause of a giant antral ulcer See page 730 for question
ANSWER White cell and eosinophil counts were 22 690/mm3 and 59.7%, respectively. Histological examination of gastric antrum (figure 3A) and random colon biopsies (figure 3B) revealed heavy eosinophilic infiltration. Oral prednisone (30 mg qd) was started. The patient’s epigastric pain and diarrhoea resolved and eosinophil count normalised rapidly. A month later, imaging studies revealed antral and colonic ulcer healing, a normal gallbladder wall and disappearance of the low-density area around the portal vein. Treatment was stopped after 6 months, and the patient was doing well. Eosinophilic gastroenteritis (EG) was finally diagnosed. EG is a rare disease characterised by eosinophilic infiltration of the GI tract, with reports of cholangitis-associated EG. Allergic response may play a central role. Diagnostic criteria include recurrent GI symptoms, predominant eosinophilic infiltration (eosinophil sheets on histopathology) and no parasitic or extraintestinal disease.1 2 Idiopathic hypereosinophilic syndrome, a heterogeneous collection of disorders marked by hypereosinophilia and organ damage, is a differential diagnosis,3 but was ruled out because our patient had a history of asthma and eczema and no organ involvement except for the digestive system.
2
3 4 5 6 7
Garsed K, Chernova J, Hastings M, et al. A randomised trial of ondansetron for the treatment of irritable bowel syndrome with diarrhoea. Gut 2014;63:1617–25. http://www.crn.nihr.ac.uk/ http://www.crn.nihr.ac.uk/about-crn/our-performance/ http://www.crn.nihr.ac.uk/networks/ http://www.crn.nihr.ac.uk/gastroenterology/ about-gastroenterology-research/specialty-leads/ http://www.bsg.org.uk/research/using_ccrn/index.html
To our knowledge, this is the first reported case of EG presenting with a giant gastric ulcer, colonic ulcer, cholecystitis and portal area inflammation. Xiang-Yang Wang,1 Ying-Huan Dai,2 Yu-Ming Yang1 1
Department of Gastroenterology, Hunan Provincial People’s Hospital, Hunan Normal University, Changsha, Hunan, China 2 Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China Correspondence to Dr Xiang-Yang Wang, Department of Gastroenterology, Hunan Provincial People’s Hospital, Hunan Normal University, Changsha, Hunan 410005, China; [email protected] Competing interests None. Patient consent Obtained. Provenance and peer review Not commissioned; externally peer reviewed.
To cite Wang X-Y, Dai Y-H, Yang Y-M. Gut 2015;64:856. Received 23 October 2014 Revised 29 October 2014 Accepted 18 November 2014 Published Online First 5 December 2014 Gut 2015;64:856. doi:10.1136/gutjnl-2014-308699
REFERENCES 1 2
3
Schoonbroodt D, Horsmans Y, Laka A, et al. Eosinophilic gastroenteritis presenting with colitis and cholangitis. Dig Dis Sci 1995;40:308–14. Chang JY, Choung RS, Lee RM, et al. A shift in the clinical spectrum of eosinophilic gastroenteritis toward the mucosal disease type. Clin Gastroenterol Hepatol 2010;8:669–75. Weller PF, Bubley GJ. The idiopathic hypereosinophilic syndrome. Blood 1994;83:2759–79.
Figure 3 Biopsy from the gastric antrum (A) and colon (B).
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Copyright of Gut is the property of BMJ Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Inserm, UMR-1162, Génomique fonctionnelle des tumeurs solides, IUH, Paris, France 2 Faculté de Médecine, Université Paris Descartes, Labex Immuno-oncology, Sorbonne Paris Cité, Paris, France 3 Université Paris 13, Sorbonne Paris Cité, UFR SMBH, Bobigny, France 4 Université Paris Diderot, Paris, France 5 Assistance Publique-Hôpitaux de Paris, Hopital Europeen Georges Pompidou, Paris, France Correspondence to Professor Jessica Zucman-Rossi, Inserm U1162, Génomique fonctionnelle des tumeurs solides, 27 rue Juliette Dodu, Paris 75010, France; [email protected] Contributors All authors performed the experiments, analyses and have written the letter. Competing interests None. Patient consent Obtained. Provenance and peer review Not commissioned; internally peer reviewed.
To cite Cao Q, Imbeaud S, Datta S, et al. Gut 2015;64:853–854. Received 22 September 2014 Accepted 25 September 2014 Published Online First 20 October 2014
▸ http://dx.doi.org/10.1136/gutjnl-2014-308283 ▸ http://dx.doi.org/10.1136/gutjnl-2014-306228 Gut 2015;64:853–854. doi:10.1136/gutjnl-2014-308482
REFERENCES 1
2
3
Cao W, Peppelenbosch MP, Pan Q. Virus-host interactions in HBV-related hepatocellular carcinoma: more to be revealed? Gut 2015;64:852–3. Amaddeo G, Cao Q, Ladeiro Y, et al. Integration of tumour and viral genomic characterisations in HBV-related hepatocellular carcinomas. Gut 2015;64: 820–9. Lau CC, Sun T, Ching AK, et al. Viral-human chimeric transcript predisposes risk to liver cancer development and progression. Cancer Cell 2014;25: 335–49.
Author response: oral contraceptives and Crohn’s disease We appreciate the suggestion by Dr Rhodes to further evaluate the link between oral contraceptive (OC) use and risk of Crohn’s disease according to the anatomical location of disease involvement.1 We agree that a plausible 854
mechanism for the link between OC use and risk of Crohn’s disease may be through the effect of oestrogen on subacute thrombosis, leading to the development of multifocal ischaemia and infarction of the colon that manifests as colitis. In our study,2 we documented 315 incident cases of Crohn’s disease through 2007 in Nurses’ Health Study II (NHS II) and 2008 in NHS I. Among these cases, 141 (45%) were isolated colonic disease and 82 (26%) were ileal Crohn’s disease. Compared with never users of OC, the multivariate-adjusted HRs of Crohn’s disease confined to the ileum were 2.99 (95% CI 1.06 to 8.49) for current OC use and 1.46 (95% CI 0.86 to 2.50) for past use. Similarly, compared with never users, the multivariate-adjusted HRs for isolated colonic Crohn’s disease were 4.13 (95% CI 1.77 to 9.68) for current OC users and 1.88 (95% CI 1.22 to 2.88) for past use. Thus, these data do not support a preferential association of OC use with isolated colonic Crohn’s disease. Nonetheless, as we noted in our original manuscript, several other plausible mechanisms exist. First, oral oestrogen has been shown to modify intestinal permeability,3 4 a critical step in the pathophysiology of IBD. Second, OC use through its effect on endogenous levels of hormones may enhance the development of Th1mediated and Th2- mediated inflammatory diseases.5 Lastly, recent data have linked modification in the gut microbiome to endogenous levels of androgens,6 which are also known to be altered with OC use and influence the development of autoimmune diseases. This supports the intriguing hypothesis that the gut microbiome lies at the crossroads of pathways linking exogenous hormone use with innate and adaptive immunity. Hamed Khalili,1 Andrew T Chan1,2 1 Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA 2 Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
Correspondence to Dr Hamed Khalili, Gastrointestinal Unit, Massachusetts General Hospital, 165 Cambridge St., 9th floor, Boston, MA 02114, USA; [email protected] Competing interests None. Provenance and peer review Not commissioned; internally peer reviewed.
To cite Khalili H, Chan AT. Gut 2015;64:854.
Received 23 September 2014 Revised 29 September 2014 Accepted 30 September 2014 Published Online First 20 October 2014
▸ http://dx.doi.org/10.1136/gutjnl-2014-305972 ▸ http://dx.doi.org/10.1136/gutjnl-2012-302362 Gut 2015;64:854. doi:10.1136/gutjnl-2014-308509
REFERENCES 1 2
3
4
5
6
Rhodes JM. Oral contraceptives and Crohn’s disease. Gut 2014;63:863. Khalili H, Higuchi LM, Ananthakrishnan AN, et al. Oral contraceptives, reproductive factors and risk of inflammatory bowel disease. Gut 2013;62:1153–9. Braniste V, Jouault A, Gaultier E, et al. Impact of oral bisphenol A at reference doses on intestinal barrier function and sex differences after perinatal exposure in rats. Proc Natl Acad Sci USA 2010;107:448–53. Looijer-van Langen M, Hotte N, Dieleman LA, et al. Estrogen receptor-beta signaling modulates epithelial barrier function. Am J Physiol Gastrointest Liver Physiol 2011;300:G621–6. Cutolo M, Capellino S, Straub RH. Oestrogens in rheumatic diseases: friend or foe? Rheumatology 2008;47(Suppl 3):iii2–5. Markle JG, Frank DN, Mortin-Toth S, et al. Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science 2013;339:1084–8.
Successful delivery of clinical gastroenterology studies in the UK Recent publications in Gut1 2 have highlighted the beneficial role of the National Institute for Health Research (NIHR) Clinical Research Network in supporting clinical gastroenterology research in the UK.3 On an European level, the European Clinical Research Infrastructures Network provides integrated support to multinational clinical research projects in partner countries. The overarching aim of the NIHR Clinical Research Network is to maximise clinical research delivery by providing the infrastructure that allows high-quality studies to be undertaken in the NHS. The support available encompasses many aspects of the study life-cycle, including study set-up, researcher training and aiding study delivery, for example by providing protected clinician research time and research nurse support at individual study sites in NHS institutions. All clinical gastroenterology research studies entered onto the NIHR Clinical Research Network Portfolio are eligible for support.3 The performance of the NIHR Clinical Research Network Portfolio is closely Gut May 2015 Vol 64 No 5
PostScript monitored using several High Level Objectives, one of which is increasing the proportion of studies that deliver in line with their planned delivery time and patient recruitment targets. The progress of each study during the recruitment phase is rated on a BRAG (black/red/ amber/green) system, with studies deemed to be on target (‘green’) if recruitment is running at least 80% of that expected according to each study’s self-determined recruitment schedule.4 Upon closure, studies which successfully recruited to their target within the specified time are rated ‘green’ and those which either over-ran their time or failed to recruit to plan are rated ‘red’. One can immediately see that when bodies such as the NIHR and the research charities are making funding decisions, they might be very interested in the proportion of ‘green’ studies on the Gastroenterology Portfolio as an indicator of the future ability of gastroenterologists to deliver successful research projects in the NHS. The same could be said of potential commercial trial sponsors, who approach the NIHR Clinical Research Network to use a number of services, including identification of research sites for multicentre studies. It is, therefore, in the gastroenterology research community’s best interests, and the interests of patients, to maximise the number of studies on the portfolio which deliver to time and target. However, although study delivery has improved significantly over the last few years, only 55% of gastroenterology studies closed ‘green’ in 2013/2014 compared with the national target of 80%, and currently, for this financial year, a similar proportion (53%) of open studies are recruiting to time and target (data accessed 25 July 2014). There are obviously many reasons why research projects do not proceed to plan and participant recruitment is lower than expected, some of which may be beyond the investigators’ control. However, there are also several ‘investigator factors’ that probably contribute to poor study performance and that can be addressed relatively easily by gastroenterology researchers: 1. Investigators should carefully consider and state a realistic, achievable sample size target for their study, along with an appropriate start date and study duration, during the Integrated Research Application System (application process for study approvals. Targets set during the approvals
Gut May 2015 Vol 64 No 5
process are used to populate the NIHR Clinical Research Network Portfolio entry. One might expect that basing the time and target metric on the predictions of the Investigator would give a study the best possible opportunity to recruit to time and target. However, many Investigators still underestimate the time taken to gain regulatory approvals during study set-up and overestimate recruitment potential. Realistic targets compatible with the funding provided for a study are more likely to be achievable. 2. Investigators should realise that if unexpected delays are encountered, the date and recruitment targets set on the NIHR Clinical Research Network Portfolio may be altered, in agreement with the study funder. This can make a huge difference to an individual study’s BRAG rating. The key action is to inform Clinical Research Network Portfolio staff through the national gastroenterology team (see below), who can then help the investigator gain the necessary evidence of a study extension with which to change the entry on the Portfolio database. 3. Investigators need to update their study entry on the Portfolio on a regular basis. Portfolio data are published every month and it is expected that each study team will provide a monthly recruitment figure. This is, in fact, another metric—so-called ‘recruitment upload engagement’ or the % number of occasions when monthly recruitment data are reported. Currently ( July 2014), recruitment data is missing for nearly 10% of gastroenterology studies and one can easily imagine the effect of inaccurate recruitment data on individual study and overall gastroenterology BRAG ratings. One factor which has hampered the ability of investigators to fully engage with the NIHR Clinical Research Network Portfolio and study performance has been the lack of a simple means by which to communicate with Portfolio staff in the NIHR Clinical Research Network Coordinating Centre. Recently this has changed with the appointment of a dedicated Gastroenterology Portfolio Coordinator, whose role is to ensure that individual non-commercial study data entries are as up-to-date and accurate as possible. We are convinced that the Gastroenterology Specialty’s performance against the High Level Objectives will improve significantly if all investigators
respond in a timely and positive manner to requests from the coordinator for information regarding individual studies that are supported by NIHR Clinical Research Network infrastructure locally. The situation is slightly different regarding commercially sponsored studies, but the same strategy applies; maximal engagement with the NIHR Clinical Research Network Commercial team will reap dividends for improved performance. The Gastroenterology Portfolio Coordinator and Specialty National Lead can be contacted at [email protected]. The NIHR Clinical Research Network has recently undergone reconfiguration such that gastroenterology research takes place across England in 15 Local Clinical Research Networks.5 Each Local Clinical Research Network has a Gastroenterology Lead, who is well-placed to help any investigator deliver their study successfully, and communicate through the NIHR Clinical Research Network Coordinating Centre to affect any necessary changes to their study record. If a gastroenterologist is unclear who his or her Regional Lead is, this can easily be determined by contacting their Local Clinical Research Network,5 checking on the NIHR Clinical Research Network’s website6 or checking with the British Society of Gastroenterology.7 In summary, we believe that the above simple measures based around improved communication with the Gastroenterology Portfolio Coordinator and more realistic targets can improve individual study and overall gastroenterology performance, with consequent benefits for gastroenterology research, in general, by persuading funders of the feasibility of noncommercial gastroenterology studies and attracting more commercially sponsored gastroenterology research to the UK. Mark A Hull,1 John T McLaughlin2 1
Leeds Institute of Biomedical & Clinical Sciences, St James’s University Hospital, Leeds, UK 2 Department of GI Sciences, University of Manchester, Salford, UK Correspondence to Professor Mark A Hull, Leeds Institute of Biomedical & Clinical Sciences, St James’s University Hospital, Wellcome Trust Brenner Building, Leeds LS9 7TF, UK; [email protected] Acknowledgements MAH is the Specialty National Lead, NIHR Clinical Research Network: Gastroenterology and the Specialty Local Lead, NIHR Clinical Research Network: Yorkshire and Humber (Gastroenterology), and JTM is the Chair of British Society of Gastroenterology Research Committee. Competing interests None.
855
PostScript Provenance and peer review Not commissioned; internally peer reviewed.
Accepted 18 October 2014 Published Online First 6 November 2014 Gut 2015;64:854–856. doi:10.1136/gutjnl-2014-308348
To cite Hull MA, McLaughlin JT. Gut 2015;64:854– 856. Received 29 August 2014 Revised 13 October 2014
REFERENCES 1
Cockbain AJ, Volpato M, Race AD, et al. Anticolorectal cancer activity of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid. Gut 2014;63:1760–8.
EDITOR’S QUIZ: GI SNAPSHOT
Unusual cause of a giant antral ulcer See page 730 for question
ANSWER White cell and eosinophil counts were 22 690/mm3 and 59.7%, respectively. Histological examination of gastric antrum (figure 3A) and random colon biopsies (figure 3B) revealed heavy eosinophilic infiltration. Oral prednisone (30 mg qd) was started. The patient’s epigastric pain and diarrhoea resolved and eosinophil count normalised rapidly. A month later, imaging studies revealed antral and colonic ulcer healing, a normal gallbladder wall and disappearance of the low-density area around the portal vein. Treatment was stopped after 6 months, and the patient was doing well. Eosinophilic gastroenteritis (EG) was finally diagnosed. EG is a rare disease characterised by eosinophilic infiltration of the GI tract, with reports of cholangitis-associated EG. Allergic response may play a central role. Diagnostic criteria include recurrent GI symptoms, predominant eosinophilic infiltration (eosinophil sheets on histopathology) and no parasitic or extraintestinal disease.1 2 Idiopathic hypereosinophilic syndrome, a heterogeneous collection of disorders marked by hypereosinophilia and organ damage, is a differential diagnosis,3 but was ruled out because our patient had a history of asthma and eczema and no organ involvement except for the digestive system.
2
3 4 5 6 7
Garsed K, Chernova J, Hastings M, et al. A randomised trial of ondansetron for the treatment of irritable bowel syndrome with diarrhoea. Gut 2014;63:1617–25. http://www.crn.nihr.ac.uk/ http://www.crn.nihr.ac.uk/about-crn/our-performance/ http://www.crn.nihr.ac.uk/networks/ http://www.crn.nihr.ac.uk/gastroenterology/ about-gastroenterology-research/specialty-leads/ http://www.bsg.org.uk/research/using_ccrn/index.html
To our knowledge, this is the first reported case of EG presenting with a giant gastric ulcer, colonic ulcer, cholecystitis and portal area inflammation. Xiang-Yang Wang,1 Ying-Huan Dai,2 Yu-Ming Yang1 1
Department of Gastroenterology, Hunan Provincial People’s Hospital, Hunan Normal University, Changsha, Hunan, China 2 Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China Correspondence to Dr Xiang-Yang Wang, Department of Gastroenterology, Hunan Provincial People’s Hospital, Hunan Normal University, Changsha, Hunan 410005, China; [email protected] Competing interests None. Patient consent Obtained. Provenance and peer review Not commissioned; externally peer reviewed.
To cite Wang X-Y, Dai Y-H, Yang Y-M. Gut 2015;64:856. Received 23 October 2014 Revised 29 October 2014 Accepted 18 November 2014 Published Online First 5 December 2014 Gut 2015;64:856. doi:10.1136/gutjnl-2014-308699
REFERENCES 1 2
3
Schoonbroodt D, Horsmans Y, Laka A, et al. Eosinophilic gastroenteritis presenting with colitis and cholangitis. Dig Dis Sci 1995;40:308–14. Chang JY, Choung RS, Lee RM, et al. A shift in the clinical spectrum of eosinophilic gastroenteritis toward the mucosal disease type. Clin Gastroenterol Hepatol 2010;8:669–75. Weller PF, Bubley GJ. The idiopathic hypereosinophilic syndrome. Blood 1994;83:2759–79.
Figure 3 Biopsy from the gastric antrum (A) and colon (B).
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Gut May 2015 Vol 64 No 5
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