National young GI sections and the ECYG

Ivana Mikolasevic talks about the European Conference of Young Gastroenterologists

The GI Hive is a brand-new blog from the UEG Young Talent Group (YTG) that covers the most up-to-date information about life, career development, education and opportunities for young gastroenterologist in Europe. Interviews, infographics, WhatsApp conversations and videos with both junior and renowned gastroenterologists will all be published in the GI Hive on a regular basis.

Our latest guest in the GI Hive is Ivana Mikolasevic, a member of the UEG YTG and an associate professor in Rijeka, Croatia. In December 2018, Ivana and a group of young gastroenterologists from the Croatian Young GI section (Tomislav Bokun, Maja Mijić, Sanja Stojsavljević, Nadija Skenderević, Ana Ostojić, Viktor Domislović, Ivan Jakopčić, Petra Puž) are holding the first European Conference of Young Gastroenterologists in Zagreb, Croatia. Ivana is president of the organizing committee and shared a few words with us about the conference and the Croatian Young GI Section.

There are still countries in Europe without a young GI section and the YTG has published a paper on how to start one. Could you tell us how everything started in your country and about the organisation of the Croatian Young GI section and its activities?

We revived the inactive youth section of our national society of gastroenterology in 2013. We first started having meetings during national society meetings/congresses, following the organisation of dedicated sessions for young gastroenterologists when they presented their best scientific work. Then we took over the administration of our society's webpage and gradually the idea of having our own meeting grew. At the beginning of 2017 we organised the first three-day symposium dedicated to members of the youth section: it was a great success and was repeated early this year. To be honest, as we are a rather small community, we were sceptical about having our own meeting, but it eventually appeared to become almost like a necessity and the occasion all young members eagerly awaited—to meet each other and be able to discuss common interests and problems. Our senior colleagues have been extremely supportive of all our activities, so we would suggest that young gastroenterologists start activities for themselves in their own countries without fear, and that they ask for support of any kind from senior colleagues.

How did you decide to organise the first European Conference of Young Gastroenterologists (ECYG)?

So, I talked in front of our small ECYG team—Tomislav Bokun, Maja Mijić, Sanja Stojsavljević, Nadija Skenderević, Ana Ostojić, Viktor Domislović, Ivan Jakopčić, Petra Puž and me. The idea for the conference organisation was born within the Youth Section of the Croatian Society of Gastroenterology, with a desire to stimulate and strengthen international cooperation.  We already have annual meetings of the youth section when we discuss how to improve our education; we hold lectures about specific topics in digestive health and so on. We wanted to do the same thing with this conference but on a European level, because we have all had such good experiences making contact with colleagues from other countries who we met on courses and congresses we have attended during our education. Therefore, we wanted to create something that would be focused on young gastroenterologists and their networking, under the supervision of senior experts established in specific fields of gastroenterology. The idea of gathering together as many young GIs as possible so that we can make new contacts and share experiences made us enthusiastic, although, at first, none of us were probably aware of exactly what we were getting ourselves into. Then, once we put down all the assignments on paper, we rolled up our sleeves and started working.

What can young GIs learn by attending the ECYC?

This is the first conference targeting young gastroenterologist from all over Europe with the purpose of exchanging experience, knowledge and ideas with eminent professors and researchers. The main idea of the conference is for us, young gastroenterologists, to have a chance to present our most challenging clinical cases and discuss them with our peers and acknowledged experts in the field. Furthermore, ECYG gives us the opportunity to present our clinical and scientific work in a poster presentation form. Not only that, during hands-on sessions young delegates will be able to improve their manual skills in abdominal ultrasound, Colour Doppler, elastography and endoscopy. Moreover, this conference will enable us to initiate constructive and productive dialogues and to create a network for future collaboration with colleagues all over Europe. Finally, to enable us to achieve this goal, interaction will be encouraged and stimulated throughout the conference.

What are the most important messages from the conference?

Learn. Connect. Grow. It doesn’t matter if you come from a big or small country, region or hospital—if you try to give the best of yourself, as we, people from a small country, are trying to do by organising this conference, you can succeed in anything. Finally, our wish is that this project stimulates the awareness of young people about the need for teamwork, co-operation and education, both within their own centre and among other centres. Our small team wants to stress the importance of teamwork and collaboration needed in everyday practice to succeed.  Another important point is the apparent need for organising events and programs dedicated to young GIs. This conference is another 'proof of concept' for gathering young GIs in youth GI sections and organising events for them. We believe that every nation should have their own young GI section and all their own meetings, and we also call for close collaboration in organising hopefully future ECYGs. We invite you to view the YTG section of the UEG webpage for more information on activities for young GIs within UEG and to get into contact with the YTG and also Friends of YTG countries around Europe. We also invite you to share your experience about organizing events for young GIs as this could help us to improve the quality of ECYG. Fresh ideas are also warmly welcomed! To improve our knowledge, we have to work together and exchange our ideas, so we can approach complex medical problems from every angle. The future of the field lies with young gastroenterologists, but the knowledge lies with those who are less young. We want to transfer knowledge into the future.

What are your insights for the future of the conference?

Well, we want to do it all over again! Call us crazy, but so far this has been such a great experience and we are sure it will continue this way until and during the conference.  We hope that we will get good feedback and reviews, so we can show that a small country like Croatia can do something big as this when people work together.

Interviewer: Radislav Nakov

GI Hive, a brand new blog by the UEG Young Talent Group

Yasmijn van Herwaarden reveals more about the activities of young GIs within UEG. 

GI Hive is a brand new blog edited by UEG Young Talent Group that combines the most up-to-date information about life, career development, education and opportunities for young GI specialists in Europe. Interviews, infographics, WhatsApp conversations and videos with both junior and renowned specialists will be regularly published in GI Hive.

The first bee in the GI Hive is Yasmijn van Herwaarden – UEG Young Talent Group (YTG) chair. Yasmijn is a resident at the Rijnstate hospital in Arnhem, the Netherlands and tries to finish her PhD thesis at the Radboud university hospital in Nijmegen. She is a 30-year old Sagittarius and loves painting, pilates and plants. 


Yasmijn, could you explain what is exactly Young Talent Group? What are the activities of the young GIs within UEG?

The Young Talent Group (YTG) was formed under the umbrella of the National Societies Committee to make the UEG and especially UEG Week more accessible and attractive for young specialists, residents, PhD students and post-docs working in digestive diseases. 
Within the YTG we are a group of nine from all over Europe who meet twice a year to plan our activities. We have a young representative in all other UEG committees to give the young perspective on all UEG activities. Next to the YTG we try to have a “friend of the YTG” in each national society connected to UEG. These Friends are our ambassadors and inform us on issues and activities from their country and they spread the word about our activities in each country. 
An important part of our activities take place during the UEG Week. We try to help guide first time visitors to the congress with for example the Young GI track in the congress app and the popular mentoring program. 
We try to facilitate informal networking in the young GI lounge were everyone under 40 is welcome for coffee and power outlets during the whole week and by organizing the Let’s Meet event on Sunday night each year. We also organize special sessions for young GI’s, for example this years “How to prepare a presentation” and the “Check your CV” informal meeting in the lounge. 

Among the most popular opportunities provided by YTG are the clinical and research fellowship programmes. Could you share with us a little bit more about them?

These fellowships were started to give young clinicians and researchers an opportunity to visit another European centre. We award € 1250 to spend at least two weeks in one of the participating centers. 
When rating the applications for this fellowship we are looking for young people with a specific plan of what they want to learn from the centre they will be visiting. So if you want to apply please make a good plan of what you want to learn and carefully pick the center you want to visit to match your plan. 
This year we completely changed the research fellowship compared to the previous years. We will be awarding more money, € 50.000, to spend 12 months with a European principal investigator to work on a research project. We want to support new and longer lasting research collaborations with this fellowship. 
You have to propose a plan of what you want to do and choose the principal investigator you want to visit. Of course you can draw inspiration from the list of centers participating in the clinical fellowships.

The YTG published a paper on the needs of young GI sections in UEG Journal. Can you explain what are the needs of young sections belonging to UEG National Societies?

We circulated a questionnaire among our Friends of the Young Talent Group to make an overview of the situation of young GI’s in each country. We learned that in many countries the young GI’s/residents are not organized and represented at a national level. We believe that it is important for young professionals to be represented and actually have a say in decisions that are made about their daily work and their future workplace. 
We are trying to help the young GI’s in different countries to get organized and have a young representative in the National Society. We already have some success stories, for example the newly formed young GI sections in Bulgaria and Spain. 

Why it is important for a young GI to send an abstract to UEG Week? 

For me submitting an abstract as a young researcher was always important because it was the opportunity to visit a conference and travel. I was fortunate that if the abstract was accepted for poster or oral presentation my department would pay for the travel costs and the conference fee. 
I always get new inspiration and also motivation to continue my research after a conference. Even during a poster presentation I have gotten tips from the audience that would make it into the final manuscript. But it is also just a lot of fun to visit another country with colleagues and make new friends. 

How can a young GI get involved with Young Talent Group and what is Young GI Network?

An easy way to stay in touch and hear about all our offers is to like the Young GI Network Facebook page. You can also subscribe to our mailing list and visit the UEG website to hear about the open calls we post. All the calls for the fellowships, other awards and grants and open calls for new positions in the YTG will be posted there. 
Very soon we will start offering a new way to get involved in the UEG: it will become possible to actively apply for our new UEG Talent Pool. From this pool we will actively promote young talents to all the UEG committees. 
The last two years we did a pilot for the talent pool with the Scientific Committee where young researchers could volunteer to chair a UEG Week session together with a senior chair. The reactions from both the junior chairs and the Scientific Committee were very positive seeing this as an excellent opportunity. We will post more information shortly and open the application on the UEG website.

Interviewer: Radislav Nakov

Personalised nutrition - food for thought

Developing tailored eating advice based on individual nutritional needs

‘Personalised nutrition’ represents any attempt to provide tailor-made healthy eating advice based on the nutritional needs of an individual, as dictated by their behaviour, phenotype and/or genotype and their interactions. Increasing evidence has shown the potential for integrating lifestyle habits, physiology, nutraceuticals, the gut microbiome and genetics into nutritional solutions, specific to the needs of each individual, for maintaining health and preventing disease. 

One area that has been gaining attention among both health professionals and the general public is nutrigenomics - the role of nutrients in gene expression. On a molecular level, nutrients work as messengers, transmitting signals that can be translated into changes in gene, protein, and metabolite expression and function, which may ultimately affect health outcomes. By employing molecular tools, nutrigenomics research identifies how nutrients and bioactive food compounds may alter gene expression, ultimately helping us to understand why people respond differently to the same diet and how genes and diet interact and predispose us to disease. 
Advances in nutrigenetics - how genes impact nutrient metabolism - and nutrigenomics do seem to encourage more personalised advice when it comes to food intake and nutritional supplements.1 
We are used to receiving generalized dietary guidelines and specific recommendations on food intake and nutrient supplements, based on age, gender and other requirements (e.g. during pregnancy or times of illness). For instance, many people will - at least intuitively - be familiar with some of the following daily nutritional recommendations for adults2:
  • 200 µg folic acid
  • 40 mg vitamin C
  • No more than 6 g salt
  • At least five portions of a variety of fruit and vegetables
  • No more than 11% of energy from saturated fat
Deficiencies in calcium, potassium, dietary fibre and vitamin D are also generally considered a public health concern.3 Some supplementation can be recommended. For example, folic acid taken during pregnancy to reduce the risk of malformations developing in the brain and spinal cord of the unborn child.  
By using information obtained from whole genome analysis, an individual’s genome can be scanned for polymorphisms (usually referred to as single nucleotide polymorphisms [SNPs]) in genes related to nutrient metabolism and disease development. For example, the methylenetetrahydrofolate reductase gene is associated with folate metabolism. If the common 677C-->T mutation (also known as the A222V mutation) is present in the methylenetetrahydrofolate reductase gene, it can result in an enzyme that has reduced activity. Should a person’s diet be low in folate, the presence of the 677C-->T mutation may lead to an increased risk of elevated homocysteine levels and a further moderate risk of cardiovascular disease.4,5 On a similar note, genetic variation may, at least in part, explain interindividual differences in plasma triacylglycerol concentrations on administration of polyunsatuared fatty acids, such as those found in fish oil,6 and it may also help explain why vitamin D might confer an increased risk of cancer development in some, while decreasing the risk in others.7 
So, is the future of gut (and general) health in personalised nutrition? How can we test it? Evidence-based medicine (EBM) relies on findings from randomized controlled trials to identify whether or not a given treatment or behaviour leads to a certain outcome. We have become used to EBM being critical to medical decision-making. A one-size-fits-all approach may appear inherently incompatible with the concept of personalised nutrition, and challenges arise when agreeing on the extent, quality and interpretation of evidence and consequent implications for dietary recommendations, particularly within the nutrigenomics arena. 
When will nutritional research be ready to be translated into public health action? Will personalized nutrition produce greater behaviour change and gains in health and wellbeing than can be achieved by conventional dietary advice?6 Although lowering the levels of dietary salt and saturated fats has had a positive effect on hypertension and lipid profiles, as demonstrated in clinical trials in healthy populations, limited trial data exist that prove a cause–effect relationship and a consequent reduction in disease by these dietary interventions.6 We also need to keep in mind that genes work together and not in isolation. This means that the presence of one SNP needs to be interpreted in the context of a person’s overall biochemistry, nutrition, and other lifestyle factors, such as activity, sleep and stress.
With advances in genetic testing, public awareness of personal genome testing and its potential is increasing. Companies are now offering affordable genetic testing options directly to the public. While there may be benefits to having your genetic information available, including the potential for personalised nutrition, there are also many risks and limitations that need to be highlighted and considered. These include, but are not limited to, whether there are sufficient regulations imposed on companies who perform genetic testing, interpretation and delivery of genetic information (via guidance of a health professional), ethical and social concerns, and privacy in terms of how DNA information is stored and used. 
Nutrigenomics and nutrigenetics, albeit an exciting area, is still relatively young and has not advanced enough to allow us to develop a diet based on a person’s entire genome–much more work is required before this can happen. Nonetheless, these tools have developed enough to highlight some nutrient–gene (and environment) interactions. So, for now, our advice is to watch this space as the field of personalised nutrition research continues to develop - who knows where we will find ourselves in the years to come!
Before you go, we would also like to guide your attention to the nutrition guidelines that are available in the UEG Standards & Guidelines Repository, including many from ESPEN and ESPGHAN! 
References 
  1. Fenech M, El-Sohemy A, Cahill L, et al. Nutrigenetics and nutrigenomics: Viewpoints on the current status and applications in nutrition research and practice. J Nutrigenet Nutrigenom 2011; 4: 69–89.
  2. Food Standards Agency. Nutrient and food based guidelines for UK institutions. https://www.ptdirect.com/training-design/nutrition/national-nutrition-guidelines-united-kingdom. (2007, revised October 2007, accessed 11 May 2018).
  3. Blumeberg JF, Bailey RL, Sesso HD, et al. The evolving role of multivitamin/multimineral supplement use among adults in the age of personalized nutrition. Nutrients 2018; 10: 248. 
  4. Kohlmeier M, De Caterina R, Ferguson LR, et al. Guide and position of the International Society of Nutrigenetics/Nutrigenomics on personalized nutrition: Part 2 – Ethics, challenges and endeavors of Precision Nutrition. J Nutrigenet Nutrigenom 2016; 9: 28–46.
  5. Liew SC and Gupta ED. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: Epidemiology, metabolism and the associated diseases. Eur J Med Genet 2015; 58: 1–10.
  6. Görman U, Mathers JC, Grimaldi KA, et al. Do we know enough? A scientific and ethical analysis of the basis for genetic-based personalized nutrition. Genes Nutr 2013; 8: 373–381.
  7. Davis CD and Milner JA. Nutrigenomics, vitamin D and cancer prevention. J Nutrigenet Nutrigenom 2011; 4: 1–11.

Thank you from UEG E-learning!

We wouldn’t be able to provide high-quality, valued content if not for our contributors.

This month has seen UEG E-learning reach a wonderful landmark, with 3,000 learners actively taking a UEG online course. Added to this are the thousands of pageviews attracted by our Mistakes in… series—more than 38,000 so far this year alone! Given UEG’s aim to enhance the education of young professionals in the field, we’re delighted that our content is being so well used.

Of course, we wouldn’t be in the position to provide such high-quality, valued content were it not for our contributors. Now, therefore, seems an appropriate time to say a big thank you to all our authors for their time, expertise and enthusiasm. Here, you’ll find a few UEG E-learning facts, figures and thoughts that demonstrate just how far the project has come in the past few years (since January 2014). At the end of this blog, you’ll find a list of the UEG E-learning content that’s currently available and the names of all our fantastic contributors. If you haven’t had a chance to look at our content then I recommend looking at the list and visiting the UEG Education website. Thank you, once more, to all our contributors—we truly appreciate your generosity and investment in UEG E-learning and look forward to working with you again in the future! Download the infographic

Alcohol, GI cancer and microbiota

To what extent might alcohol consumption drive or modify the relationship between gut microbiota and GI cancer?

In the ‘European Code Against Cancer', the International Agency for Research on Cancer (IARC) identify 12 ways to reduce the risk of developing cancer, one of which has to do with alcohol consumption.1 Indeed, the Code advises “If you drink alcohol of any type, limit your intake. Not drinking alcohol is better for cancer prevention.” This recommendation is perhaps not surprising given that alcohol has been identified as a cause of at least seven types of cancer, most of which are gastrointestinal (i.e. cancer of the mouth, pharynx, oesophagus, liver, colon and rectum).1

Working with clinical microbiology and microbiome analysis on a daily basis, I’m interested in the use of gut microbiota profiling for predicting human health and disease, including relationships between microbes and cancer. Dysbiosis and predominance of particular gut microbiota communities are thought to be involved in the development of, for example, colorectal cancer (CRC).2–4 But to what extent might alcohol consumption drive or modify such relationships? There may be several answers to this question, and, as exemplified by a recent study, they may not be black and white…5 In their study, Tsuruya et al. investigated the ecophysiological consequences of alcoholism on human gut microbiota.5 Detailing and corroborating the findings of others,6 they found that the gut microbiota of alcoholics were depleted in dominant obligate anaerobes (e.g. Ruminococcus) and enriched in aerotolerant (facultative anaerobic) groups, including Streptococcus and other minor species. That the distribution is skewed towards facultative anaerobes in alcoholics reflects—at least in part—the influence of oxidative stress due to ethanol-induced formation of reactive oxygen species by, for example, gut mucosal cells. The team go on to explain how the different major groups of bacteria metabolize ethanol under different ecological circumstances, which includes the production of acetaldehyde (the carcinogenic metabolite derived from alcohol that is thought to be critical to the development of ethanol-related CRC). While I strongly encourage you to acknowledge the complexity of these intricate relationships, what I find particularly intriguing is the extent to which it is possible to predict gut ecology (e.g. the level of oxidative stress) by microbiota profiling, since this could impact the way we manage and prevent cancers such as CRC. Strong epidemiological data suggest there is a dose–response relationship between alcohol consumption and the risk of CRC.7–10 And when it comes to alcohol (ab)use and the risk of developing and dying from CRC, it might be useful to look not only at the gut bacteria that are present and what they do, but also at those bacteria that are absent. For instance, the diet of individuals who consume excessive amounts of alcohol might favour gut microbiota changes that increase susceptibility to cancer development. Some bacteria produce short-chain fatty acids (SCFAs), which are most likely protective against the development of CRC.4,11 Such bacteria are established in the gut typically in relation to a diet rich in fibre. If the overall diet of alcoholics promotes (e.g. via malnutrition) a reduction in bacteria producing SCFAs, this could indirectly lead to an increased CRC risk. The possible opportunities here are manifold, but I will end by mentioning what I consider the two most important ones. First, microbiota profiling can be used as a noninvasive diagnostic/prognostic marker for various aspects of health and disease; stool analysis might in the future enable us to tell if a patient is an alcoholic, what type of food they eat (if you include profiling of eukaryotic cells in stool as well), and what the likelihood of, for example, CRC is in this patient. Second, microbiota manipulation—through diet, antibiotics, or gut microbiota transplantation—may be used with a view to reducing morbidity and mortality from cancer, not only CRC, but possibly also other types of cancer. References
  1. International Agency for Research on Cancer.  European Code Against Cancer (https://cancer-code-europe.iarc.fr/index.php/en/) [accessed March 21, 2017].
  2. Gagnière J, Raisch J, Veziant J, et al. Gut microbiota imbalance and colorectal cancer. World J Gastroenterol 2016; 22: 501–518.  
  3. Dulal S and Keku TO. Gut microbiome and colorectal adenomas. Cancer J 2014; 20: 225–231. 
  4. Vipperla K and O’Keefe SJ. Diet, microbiota, and dysbiosis: a ‘recipe’ for colorectal cancer. Food Funct 2016; 7: 1731–1740. 
  5. Tsuruya A, Kuwahara A, Saito Y, et al. Ecophysiological consequences of alcoholism on human gut microbiota: implications for ethanol-related pathogenesis of colon cancer. Sci Rep 2016; 6: 27923. 
  6. Mutlu EA, Gillevet PM, Rangwala H, et al. Colonic microbiome is altered in alcoholism. Am J Physiol Gastrointest Liver Physiol 2012; 302: G966–978. 
  7. Bailie L, Loughrey MB and Coleman HG. Lifestyle risk factors for serrated colorectal polyps: a systematic review and meta-analysis. Gastroenterology 2017; 152: 92–104.  
  8. Wang YM, Zhou QY, Zhu JZ, et al. Systematic review with meta-analyses: alcohol consumption and risk of colorectal serrated polyp. Dig Dis Sci 2015; 60: 1889–1902. 
  9. Bagnardi V, Rota M, Botteri E, et al. Alcohol consumption and site-specific cancer risk: a comprehensive dose-response meta-analysis. Br J Cancer 2015; 112: 580–593. 
  10. Cai S, Li Y, Ding Y, et al. Alcohol drinking and the risk of colorectal cancer death: a meta-analysis. Eur J Cancer Prev 2014; 23: 532-539. 
  11. Bultman SJ. Interplay between diet, gut microbiota, epigenetic events, and colorectal cancer. Mol Nutr Food Res 2017; 61. 
P.S. CRC awareness month takes place every March. Visit the Publications section [https://www.ueg.eu/publications/] of the UEG website to view several infographics on CRC, including one on ‘Alcohol and colorectal cancer’, or read the press release ‘Change through concrete policies: the case of EU alcohol policies and subsequent healthcare savings’ to find out more about the mortality attributable to major alcohol-attributable diseases, such as cancer and liver cirrhosis, and the strategy developed by the EU with a view to reducing alcohol-related morbidity and mortality.

Jointly organised by ESDO and ESGE

Early-bird registration for this UEG supported event is open until March 30, 2017.

Advice on Christmas Dinners...

A factual but fun article for the festive period from Mark Fox based on a Q&A session for his local newspaper

Advice on Christmas Dinners and its after effects

 “A factual but fun article for the festive period from Mark Fox based on a Q&A session for his local newspaper. Merry Christmas!”          

Nurse endoscopists

How have nurse endoscopists benefitted endoscopy services?

I remember the incredulity on the faces on my European colleagues 20 years ago when I told them that the UK was to start training nurse endoscopists. They doubted that it was desirable (or even possible!) to train nurses. Of course, by then the American Society for Gastrointestinal Endoscopy (ASGE) had for many years endorsed flexible sigmoidoscopy by ‘nonspecialists,’1,2 but little evidence of their effectiveness had been published.3

Unsurprisingly, it was the relentlessly increasing demand for endoscopy that made the introduction of nurse endoscopists necessary in the UK.  Some 20 years ago, the demand for gastroscopy approached 10 per 1,000 population per year and the demand for colonoscopy was expected to increase from an average of 2.5 to 10 colonoscopies per 1,000 population per year.4 In addition, the implementation of the NHS National Bowel Cancer Screening programme would further inflate the demand for endoscopy. For this reason, a British Society of Gastroenterology (BSG) Working Party5 gave the green light for nurse endoscopy, together with the United Kingdom Central Council (UKCC)6 and the General Medical Council (GMC). However, it was a cautious start because endoscopy was seen as a risky procedure that was associated with a 1:2,000 risk of death.7 The BSG, GMC and UKCC all agreed that nurse endoscopists were only to act as “technicians”. The responsibility for the patient’s management remained with “the supervising doctor” who had to be “immediately available within the hospital” (an oxymoron of course) in the event of complications or to give advice. Now we know that they were wrong and that the “interpretation of findings does not rely on the experience and training of an appropriately qualified doctor.”5 Endoscopy can be taught! Indeed, throughout the UK, nurse endoscopists now work independently, interpreting findings without the immediate supervision of a clinician. The uptake of nurse endoscopy has been steady in the past 20 years. In Leeds we have seven nurse endoscopists who undertake about 22% of our gastroscopies, 27% of our colonoscopies and all of our flexible sigmoidoscopies. ERCP, enteroscopy, EUS and most therapeutic endoscopy procedures that pose a significant risk of complications are carried out by consultants who are increasingly dedicating their time purely to endoscopy. Now we know more about the performance of nurse endoscopists. There is irrefutable evidence that the caecal intubation rate, adenoma detection rate, complication rate and patient satisfaction scores are comparable among nurses and doctors.8–10 In Leeds, the ‘raw’ caecal intubation rate for both our nurse endoscopists and consultants is 92% and the average polyp detection index (total number of polyps found/total number of patients) is also virtually identical (34.5 for nurses and 33.5 for consultants). In view of the reassuring published literature that has become available over the years, I was bemused to read a recent survey from New Zealand in which only 30% of doctors welcomed the introduction of nurse endoscopists.11 A huge majority believed that doctors would always deliver a better quality of endoscopy and that overall costs would spiral out of control if nurses were to be trained in endoscopy. Of course, endoscopy is a valued source of extra income for gastroenterologists in New Zealand, which makes me wonder if this may have had an influence on the outcome of the survey. Nevertheless, the statistics, reassuring as the may be, do not do nurse endoscopists justice. As a lead endoscopist, it is a relief to have a stable workforce that is fully committed to endoscopy. Most of my gastroenterology colleagues rush between ward rounds and outpatient clinics, phoning patients and their relatives in between. They have little time and energy to invest in endoscopy. By contrast, if an endoscopy list needs back filling, one of our nurse endoscopists will take it on. If an endoscopy audit is required, a nurse endoscopist can make the time. If there is an endoscopy-related problem, a nurse endoscopist will be willing to get involved. The truth is that without nurse endoscopists, endoscopy services will not be able to make the quantum leap from ‘Cinderella speciality’ to a core hospital service that is on an equal footing with radiology. My advice to any anxious colleagues who worry about the emergence of the nurse endoscopist is to welcome them, because with their help we can make endoscopy bloom! References 
  1. Maule WF. Screening for colorectal cancer by nurse endoscopist. NEJM 1994; 330(3):183–187. 
  2. DiSario JA and Sanowski RA. Sigmoidoscopy training for nurses and resident physicians. Gastrointest Endosc 1993; 39(1):29–32. 
  3. Committee on Training, Gross GWW, Bozymski EM, et al. Guidelines for training non-specialists in screening flexible sigmoidoscopy. Gastrointest Endosc 2000;51(6):783–785. 
  4. Barrison IG, Bramble MG, Wilkinson M, et al. Provision of endoscopy related services in district general hospitals: BSG Working Party Report 2001.
  5. British Society of Gastroenterology. Report of the British Society of Gastroenterology Working Party—The nurse endoscopist. 1994. 
  6. UKCC. The Scope Of Professional Practice. London UKCC 1992.
  7. Quine MA, Bell GD, McCloy RF, et al. Prospective audit of upper gastrointestinal endoscopy in two regions of England: safety, staffing, and sedation methods. Gut 1995; 36(3):462–467.
  8. Hui AJ, Lau JY, Lam PPY, et al. Comparison of colonoscopic performance between medical and nurse endoscopists: a non-inferiority randomised controlled study in Asia. Gut 2015; 64(7): 1058–1062. 
  9. Massl R, van Putten PG, Steyerberg EW, et al. Comparing quality, safety, and costs of colonoscopies performed by nurse vs physician trainees. Clin Gastroenterol Hepatol 2014; 12(3): 470–477. 
  10. Schoenfeld P; Lipscomb S; Crook J; et al. Accuracy of polyp detection by gastroenterologists and nurse endoscopists during flexible sigmoidoscopy: a randomized trial. Gastroenterology 1999; 117(2): 312–318. 
  11. Khan MI, Khan R and Owen W. Doctors and the nurse endoscopist issue in New Zealand. NZ Med J 2012; 125(1357): 88–97. 

Early Detection of Pancreatic Cancer—How?

What's the outlook for the development of biomarkers?

World Pancreatic Cancer Day is being held on November 13. It is estimated that 367,000 new cases of pancreatic cancer will be diagnosed worldwide in 2015 and the dismal survival rate means that only 2–10% of patients will be alive 5 years after diagnosis.

Globally, pancreatic cancer is the seventh most common cause of cancer-related death, and while death rates for many cancers are dropping, the death rate for pancreatic cancer is rising in Europe and the United States.1 The mortality of pancreatic cancer may, at least in part, be explained by the fact that early diagnosis is challenging. However, advances in the development of various biomarkers appear to hold promise for future screening of high-risk individuals, which—according to Cancer Research UK—includes patients with hereditary pancreatitis, a high incidence of pancreatic cancer in their family or a family history of at least one person with pancreatic cancer plus a linked cancer syndrome (e.g. a BRCA2 mutation).2 It has been reported that levels of serum cancer antigen 19-9 (CA19-9) are elevated in approximately 80% of patients with pancreatic cancer,3 and CA19-9 has been useful for therapeutic monitoring and early detection of recurrent disease after treatment in patients with known pancreatic cancer.4 However, CA19-9 is not a specific biomarker for pancreatic cancer. Moreover, patients who are negative for Lewis antigen a or b (approximately 10% of patients with pancreatic cancer) are unable to synthesize CA19-9. Although measurement of serum CA 19-9 levels is useful in patients with known pancreatic cancer, the use of this biomarker as a screening tool has yielded disappointing results.4 In addition to genetic alterations, dysregulation of specific epigenetic mechanisms is critical to tumour development. Comparing patients who have pancreatic cancer with healthy individuals and patients with chronic pancreatitis, Schultz et al. described differences in microRNA expression in whole blood with a view to identifying microRNA panels (classifiers) for diagnosing pancreatic cancer.3 microRNAs—non-coding 17–25-nucleotide-long RNAs that regulate gene expression—play important roles in tumour development and metastasis, and several have been described as specific to pancreatic cancer. Schultz and colleagues validated microRNA panels against CA19-9 sero-status and disease, and identified two panels for diagnosing pancreatic cancer using combinations of four and ten microRNAs in whole blood, respectively. The investigators call for further studies that could validate the use of these biomarkers as a screening tool for early-stage pancreatic cancer detection. More on the role of microRNAs in pancreatic tumour growth and progression can be found in a paper by Frampton and colleagues that was published in The Lancet in February 2015.5 Even more recently, in an article in Nature, Melo and colleagues6 suggested the use of a proteoglycan molecule (glypican-1 [GPC1]) anchored in the membrane of extracellular vesicles—exosomes—circulating in the bloodstream as a cancer biomarker. In particular, the team claimed that detection of GPC1+ exosomes in the blood could distinguish patients with early-stage and late-stage pancreatic cancer from patients with benign pancreatic disease and healthy individuals. The assay appeared more reliable than that based on CA19-9 detection. Compared with healthy donors, serum CA19-9 levels were increased in patients with cancer, but CA19-9 levels were also significantly increased in the serum of patients with benign pancreatic disease. Moreover, CA19-9 levels failed to distinguish patients with pancreatic cancer precursor lesions from healthy donors. An expanded interpretation of this important study, including a discussion of semantic issues, can be found in an accompanying News & Views article by Clotilde Théry.7 Apart from microRNAs, epigenetic features such as DNA methylation, satellite repeats and histone modifications might serve as biomarkers for early diagnosis of pancreatic cancer.8 Reviewing genes aberrantly methylated in pancreatic cancer, Henriksen and her team concluded that investigations into hypermethylated markers in cell-free DNA in plasma or serum are still limited by the availability of only a handful of small studies, which lack well-defined control groups, and that no single gene has been identified as a diagnostic marker.9 To read more about the many challenges related to identifying biomarkers for early diagnosis of pancreatic cancer, I recommend looking up a review by Jenkinson and colleagues.10 There are also a couple of interesting sessions from the recently concluded UEG Week 2015 in Barcelona that I’d like to highlight—all are available online. To learn more about ‘liquid biopsies’, including cell-free DNA, exosomes, and circulating tumour cells, you could look up the talk delivered by Aldo Scarpa, “Molecular diagnostics: From tissue biomarkers to liquid biopsies, single genes and panels”, which was part of the session “Pancreatic cancer: Where are we and what is the future?”11 There’s also an update session on therapy, including talks on chemotherapy, surgical resection, preoperative and palliative treatment, and neoadjuvant and adjuvant treatment.12 Finally, I would like to direct your attention to a talk that was given by Jean-Luc van Laethem, entitled “Pancreatic cancer in annual review”.13 Challenges aside, sensitive and specific biomarkers of early pancreatic cancer that can be obtained non-invasively appear critical to reducing the morbidity and mortality associated with pancreatic cancer. As we mark the 2015 World Pancreatic Cancer Day, we should set our hopes on it not being too long until one or more biomarkers prove valid for use in screening. References
  1. http://www.worldpancreaticcancerday.org/about/
  2. http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/pancreatic-cancer/risk-factors#heading-Eightteen
  3. Schultz NA, Dehlendorff C, Jensen BV, et al. MicroRNA biomarkers in whole blood for detection of pancreatic cancer. JAMA 2015; 311: 392–404.
  4. Hidalgo M. Pancreatic cancer. N Eng J Med 2010; 362: 1605–1617. 
  5. Frampton AE, Castellano L, Colombo T. Integrated molecular analysis to investigate the role of microRNAs in pancreatic tumour growth and progression. Lancet 2015; 385 Suppl 1: S37. 
  6. Melo SA, Luecke LB, Kahlert C, et al. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature 2015; 523: 177–182. 
  7. Théry C. Cancer: Diagnosis by extracellular vesicles. Nature 2015; 523: 161–162. 
  8. Fukushige S, Horii A. Road to early detection of pancreatic cancer: Attempts to utilize epigenetic biomarkers. Cancer Lett 2014; 342: 231–237. 
  9. Henriksen SD, Madsen PH, Krarup H, et al. DNA hypermethylation as a blood-based marker for pancreatic cancer: A literature review. Pancreas 2015; 44: 1036–1045. 
  10. Jenkinson C, Earl J, Ghaneh P, et al. Biomarkers for early diagnosis of pancreatic cancer. Expert Rev Gastroenterol Hepatol 2015; 9: 309—315. 
  11. Pancreatic cancer: Where are we and what is the future? Session at UEG Week 2015. 
  12. Therapy update: Pancreatic cancer Session at UEG Week 2015.
  13. Pancreatic cancer in annual review Presentation by Jean-Luc van Laetham in the Pancreas: What’s new in 2015? Session at UEG Week 2015.

Small things, vast impact: gut microbiota in health & disease

All things microbiota related at UEG Week 2015!

The relevance of manipulating gut microbiota—that is using gut microbiota (e.g. faecal microbiota transplantation [FMT]), components thereof, or diet (including probiotics)—with a view to ameliorating or potentially treating diseases and syndromes is currently subject to intense scrutiny.

The number of conditions that could potentially benefit from gut microbiota manipulation is vast, ranging from autoimmune diseases, such as inflammatory bowel disease (IBD) and multiple sclerosis, to functional bowel diseases (e.g. irritable bowel syndrome [IBS]), antibiotic-induced gut dysbiosis (e.g. recurrent Clostridium difficile infection) and metabolic syndrome. Others include mental health diseases/personality disorders, including anxiety, depression, autism, and schizophrenia. Through my own research, I have discovered that some intestinal microbes are much more common in healthy individuals than in patients with infectious diarrhoea, functional or inflammatory bowel diseases. Just to be clear, I’m not talking about Akkermansia muciniphila or Faecalibacterium prausnitzii, in fact, I’m not even talking about bacteria! I’m referring to a couple of intestinal protists (Blastocystis sp. and Dientamoeba fragilis) that once were thought by many to be gut pathogens. Well, a lot of recent data not only suggest that they are not gut pathogens, but that they also appear to be much more common than previously anticipated. At our lab, we have developed and are currently validating a gut microbiota profiling tool that enables unprecedented and exhaustive interrogation of ribosomal genes from bacteria, yeasts, moulds, and parasites (protists and helminths) in complex samples, such as stool samples. In other words, we will be able to identify all gut colonising/infecting organisms present in a stool sample to at least genus level, and very often to species level. Given my background and interests, I was very pleased to learn that UEG Week 2015 has a specific “Gut Microbiota” pathway. I’m going to adhere to it as much as I can! Not only am I interested in being able to pin down every single organism squatting our guts, I also want to know what they do! You’ll definitely find me in Room E2 at the “From omics to better understanding of pathogenesis” session, which is being chaired by my fellow Web Editor, Rui Castro. Here, Loris Lopetuso will present and compare data on gut microbiota composition (16S NGS data) in patients with IBD, IBS, diverticular disease and healthy controls. If you’re new to research into gut microbiota, you’d do well to attend the talk by Paul O’Toole on “Microbiota: What gastroenterologists should know.” This talk is part of the symposium “Microbiota: Evolving concepts in GI disorders” that takes place in Room F1 on Tuesday 27 October (14:00–15:30). Also in this session, you’ll be able to listen to Patricia Lepage discussing the fundamental issue of causation versus correlation in research into IBD-associated microbiota. Harry Sokol will reveal whether FMT for non-infectious GI diseases is “ready for prime time”, and Gerardo Nardone will deliver a talk with the title, “Microbiota and upper GI diseases: What is the clinical relevance?”  “Brain–gut interactions in health and disease” is the title of a Round Table Discussion taking place in Room E4 on Tuesday 27 October (14:00–15:30). As Peter Andrey Smith says, referring to the gut-brain axis, “…the mechanisms by which gut microbes and the brain might communicate are unclear, but there are several tantalising leads for researchers to follow.” In a recent News Feature in Nature, he provides some examples as to how differences in gut microbiota may lead to differences in brain development and behaviour. Butyrate, one of the short-chain fatty acids apparently produced by gut bacteria in those of us who are not on the FODMAP diet (for more information, see my previous blog), fortifies the blood–brain barrier by tightening connections between cells, hence influencing the basic physiology of the blood–brain barrier. I’m also really looking forward to the “Abstracts on Fire: Gut microbiota in lower GI diseases” session, which will be chaired by Antonio Gasbarrini and Herbert Tilg, and takes place at the UEG Hotspot on Wednesday 28 October (8:30–10:30). This free paper session provides us with no less than 12 talks, focusing on topics such as recurrent C. difficile infection and FMT. Among these, we will be spoiled with two talks from Gianluca Ianiro, who is going to try to convince us that surgery is no longer required in patients with C. difficile infection after FMT performed in an academic tertiary care centre. If you’d like to come and talk to me about gut microbiota in health and disease in general, research communication, or about UEG E-learning, I’ll be at the Young GI Network “Let’s Meet” event on Sunday evening and at the UEG Booth on Monday (13:00–14:00) and Tuesday (15:30–15:45). See you there!

E-learning adventures at UEG Week 2015

Getting ready for a busy few days in Barcelona!

UEG Week 2015 is just around the corner and the UEG E-learning team is getting ready for a busy few days in Barcelona! As well as meeting to plan future UEG Education online courses and content, we’ll be spending time at the UEG Booth and the Young GI Lounge in Hall 8.0 during many of the session breaks on Monday, Tuesday and Wednesday. We’ll also be attending the “Young GI Network—Let’s Meet” reception on Sunday evening. If you’d like to meet the team to find out more about what we do, discuss how we can best serve you and how you might be able to get involved, then please do come and say hello!

Tomer, Rui and Bjorn will also be chairing sessions and, as one of this year’s UEG Rising Stars, Rui will be presenting his work on microRNAs in NASH in Room E1 during the first session on Wednesday morning. The team will also be attending many of the sessions to get their annual updates across the breadth of the field, and below are a few highlights that everyone is looking forward to. Charlie’s choice: As usual there is so much excellent content that the problem will be fitting it all in. I'll certainly be attending the Rising Stars session, highlighting the best of our researchers from Europe and the USA—this is always an inspiring session. I'll also be playing close attention to the IBD free paper sessions. Like Rune, I'm looking forward to attending the microbiota-focused sessions. And for all the rest there is UEG Week Live! Bjorn’s choice: My pick of the sessions would be “Endoscopic management of benign oesophageal strictures.” I am convinced that in treatment-resistant cases a “stricturoplasty”—whereby the stricture is cut with an endoscopic knife—can turn failure into victory. I would like to discuss this option with the presenters! Tomer’s choice: There are many attractive learning options at the upcoming UEG Week, ranging from basic science to practical patient management. I am looking forward to “Introducing the omics: A guide for clinicians” on Monday morning, as part of the Today’s Science; Tomorrow’s Medicine lectures. This field has evolved greatly and I am looking to hear an update on the implications for clinicians.  I am also glad the Postgraduate Teaching Programme has a session dedicated to lower GI bleeding, a topic that applies to our everyday practice. Rui’s choice: I am particularly interested in the hepatobiliary pathway, featuring different session formats on liver cirrhosis and cholestasis. And I always love the Today’s Science; Tomorrow’s Medicine sessions, showing just how much can be achieved from a well-sustained and rational basic-to-translational/clinical research plan. And speaking of research, I am also looking forward to a great panel discussion at the “How to do research?” Hotspot Symposia! Rune’s choice: The impact of the intestinal microbiota on human health and disease is something that never ceases to fascinate me, and of course, I’ll be giving priority to the gut microbiota pathway. I’m especially looking forward to the session chaired by my colleague Mirjana Rajilic-Stojanovic and Giovanni Barbara on evolving microbiota concepts in GI disorders on Tuesday. Here, Paul O'Toole will deliver a talk with the title “Microbiota: What gastroenterologists should know.” Natalie’s choice: I love a bit of controversy, so I’m really looking forward to visiting the UEG Week Hotspot to see some of the new session formats—Abstracts on Fire, Clinical Trials Revisited and Hotspot Symposia—in action! Coming from a basic research background, I’m also particularly interested in the sessions on the ‘omics’ and learning more about what difference they are making to practical patient care and what they might allow us to achieve in the future. Don’t forget to look out for tweets from all of the team (@CharlieMuz, @Bjorn_Rembacken, @Eukaryotes, @RuiCastroHD, @adartom and @nataliewood06) during UEG Week (#uegweek)! Why not join the dialogue and tell us what’s got your attention? And if you like twitter debates then make sure you’re online for the #WeekChat on Sunday with Mark Hull (@mark_tbh; Diet, microbiota and colonic disease) and on Tuesday with Chris Hawkey (@chrishawkey; Updates on stem cell research in gastroenterology). There will also be three Decide on the Spot cases published in the UEG Week News and online during UEG Week (on Saturday, Monday and Tuesday)—the answer and explanation for each case will be posted online the following day. Those of you who view the case online, sign in to myUEG and post a comment or answer in the comments section will qualify for a complimentary UEG Education Power Bank, which is perfect for charging your mobile devices on the go! To receive your UEG Education Power Bank, simply come and show us your post on the laptop at the UEG booth in Hall 8.0. Please note that comments on social media don’t count, participants are entitled to a maximum of one Power Bank and the number of Power Banks available each day is limited! Wishing you all an enjoyable and productive time in Barcelona! 

Time to change a treatment paradigm

Models of care and malnourished patients

In the past 10 years we have seen the expansion of a cadre of gastroenterologists who have a sub-specialty interest in nutrition. As a result, we have seen nutrition rightfully taking centre stage in our hospitals. Indeed, in the UK hospital mealtimes are now ‘protected’ and malnourished patients have their food served on red trays.

Our nutrition experts have more directly been involved in a transformation of the care of patients who have short bowels. This group of patients is a complex mix, in which every patient is different depending on how much small bowel is left, what type of anastomosis was constructed and the underlying disease. Such patients may suffer high morbidity and mortality because the malabsorption of macronutrients, micronutrients, electrolytes and water can result in impaired growth, premature aging, sudden hypotension, renal failure, arrhythmias, fits, infections, liver failure and impaired healing. The increased survival of these desperately ill patients has been achieved by meticulous attention to detail. A tiny shift in a patient’s serum magnesium level triggers an adjustment. As the 2003 AGA review put it: “Vitamin and mineral status should be monitored regularly, and supplementation should be customized for each patient.”1 Of course, it takes a particular type of meticulous doctor to tirelessly manage a patient’s micronutrient intake. I am not sure that I could manage to pay such careful daily attention to every patient’s zinc, copper, magnesium and selenium levels. Luckily, gastroenterologists with a specialist interest in nutrition are self-selected, thorough doctors and their patients with intestinal failure benefit greatly. Most UK hospitals now have a nutrition team, which is headed up by a gastroenterologist with a specialist interest in nutrition. Initially these teams only cared for patients with intestinal failure. Subsequently their remit enlarged to include patients with malabsorption and more recently came to include all those who are malnourished. The most severely malnourished patients in our hospitals are those with anorexia nervosa. The nutrition of these patients is now often looked after by gastroenterologists with an expertise in intestinal failure. Just as intestinal failure is at the sharp end of gastroenterology, anorexia nervosa is at the sharp end of psychiatry. Not only does the condition have the highest mortality rate of any mental illness,2 the management is complicated by a lack of reliably successful treatments. The National Institute for Health and Care Excellence (NICE) has reviewed the therapies available and awarded only “grade C level evidence” for 74 of the 75 therapies for eating disorders.3 As we start to see severely malnourished patients who have eating disorders on our gastroenterology wards, it is becoming apparent that simply focusing on a patient’s nutritional needs does not work. Care may be reduced to a battle of wills in which patients pull out their feeding tubes as quickly as doctors put them back down. Furthermore, in spite of opiates, botox injections, naso-gastric feeding, venting PEGs, gastric pacemakers and parenteral nutrition, many patients remain just as debilitated. Personally, I believe that the key to understanding why many patients with the most severe eating disorders do not seem to be greatly improved by pipes and pills is because we practise the “Medical Model” of care. This model focuses on ‘curing’ patients, whereby ‘cure’ is defined by the absence of symptoms and a return to normal, pre-morbid health.4 Of course, such a model is entirely appropriate for treating reflux oesophagitis, a peptic ulcer or an exacerbation of colitis. However, when managing patients who have functional bowel disease, alcohol addiction or eating disorders this model of care may be less helpful. In all areas of psychiatry, the Medical Model of care is being superseded by the “Recovery Model”. Indeed, the Recovery Model of care has been integrated into public mental health policy in many countries, including Australia, New Zealand, USA, Canada, Ireland and the UK.5 The Recovery Model emphasises the personal experience of recovery, involving hope, rebuilding connections with family, friends and supporting patients in rebuilding a fulfilling life in spite of ongoing illness. In contrast to the Medical Model, this model aims for ‘recovery’, defined as enabling a return of hope, personal responsibility, control and empowerment.6 Supporting patients with functional bowel disease, alcohol addiction and eating disorders on their journey towards recovery involves understanding their agenda, active listening, empathy and the setting of realistic goals in equal partnership with patients and their families. Unfortunately, this model of care is unfamiliar to many gastroenterologists, and perhaps particularly to those with a sub-speciality interest in intestinal failure. For this reason we may have to train a new cadre of gastroenterologists with particular expertise in functional disease. This new gastroenterological subspeciality would protect vulnerable patients against repeated cycles of inappropriate investigations and increasingly invasive interventions and instead focus on supporting them on a road towards recovery and a living a fulfilling life. References
  1. Buchman AL, Scolapio J and Fryer J. AGA technical review on short bowel syndrome and intestinal transplantation. Gastroenterology 2003; 124: 1111–1134. 
  2. Beumont PJ and Touyz SW. What kind of illness is anorexia nervosa? European Child and Adolescent Psychiatry 2003; 12: i20–i24. 
  3. National Institute for Health and Clinical Excellence. Eating disorders. NICE clinical guideline 9. January 2004.
  4. Roberts G and Wolfson P. The rediscovery of recovery: open to all. Advances in Psychiatric Treatment 2004; 10: 37–49.
  5. Andresen R, Oades LG and Caputi P. Psychological Recovery: Beyond Mental Illness. Chichester, UK: Wiley-Blackwell 2011 
  6. Schrank B and Slade M. Recovery in psychiatry. Psychiatric Bulletin 2007; 31: 321–325.

Ruminations on gut fermentation—any link to IBS?

Diet, gut microbiota, fermentation and IBS

The aetiology of irritable bowel syndrome (IBS), a disease that may affect at least 10% of the general population, continues to puzzle gastroenterologists and other scientists. While there is some evidence of perturbed gut microbiota in patients with IBS, microbiota profiles reliably linked to IBS remain to be identified. Meanwhile, studies of intestinal fermentation might hold the key to expanding our knowledge on the aetiology and management of IBS.

In a recent article in the American Journal of Gastroenterology, Rajilić-Stojanović et al. reviewed data on the impact of diet and the intestinal microbiota on IBS symptoms.1 One of their important conclusions was that powerful interactions between distinct dietary patterns and intestinal microbial communities may—at least in part—be responsible for the fact that IBS has not yet been shown to be defined by certain microbiota profiles. As a lot of data going into studies exploring associations between microbiota profiles and disease conditions are cross-sectional, what we need to know much more about is how, including how quickly, changes in diet influences our gut microbiota, and therefore how resilient gut microbiota are to dietary changes. A study that appeared in Gut earlier in 2015 was looking into just that issue. In their study, Halmos et al. considered whether differences in dietary FODMAP (fermentable oligo-, di-, monosaccharides and polyols) content reflect differences in the colonic luminal microenvironment.2 Study participants (IBS patients and healthy controls) consumed their habitual diets for 1 week, but were subsequently switched to one of two challenge diets for 3 weeks (i.e. either a diet low in FODMAPs or a typical Australian diet). They were then allowed a wash-out period of 5 days, during which they consumed their habitual diets, and then later allocated to the alternative challenge diet for a further 3 weeks. Halmos et al. found that the higher FODMAP content of the Australian diet compared with that of the low FODMAP or habitual diets was associated with specific stimulation of the growth of bacterial groups with putative health benefits, including butyrate-producers and mucus-associated Akkermansia muciniphila. This finding made the team speculate that long-term use of low-FODMAP diets should be used with caution, at least until the long-term effects of such diets on intestinal microbiota have been fully elucidated. To this end, a recent randomized controlled trial by Böhn et al. compared the effects of a diet low in FODMAPs with traditional dietary advice in patients with IBS. The findings of this study suggest that traditional IBS dietary advice is just as effective in terms of reducing IBS symptoms as adhering to a diet low in FODMAPs.3 In the study by Halmos et al., the concentration of short-chain fatty acids (SCFAs) in stool, which was used as a colonic health index, was independent of diet type.2 The SCFAs acetate, propionate, and butyrate are produced primarily by bacterial fermentation of undigested carbohydrates (primarily dietary fibre aka ‘resistant starch’). The relevance of using the faecal SCFA concentration as a biomarker has, however, been questioned. Ringel–Kulka et al. looked into altered intestinal bacterial fermentation in the setting of IBS with regard to bowel characteristics and gastrointestinal symptoms.4 In their study, the primary aim was not merely to look at the distribution and composition of the microbiota, but to look at what the bacteria were actually doing. For this purpose, they looked at surrogate markers of gut bacterial fermentation, namely intestinal intraluminal pH and faecal SCFAs. Faecal SCFAs are naturally acidic and therefore cause a drop in the pH of the intestinal lumen. Compared with healthy controls, patients with IBS—independent of subtype—exhibited a significantly lower mean total colonic pH level, which could indicate higher intraluminal bacterial fermentation in this cohort. Of note, small-intestine pH levels did not differ between IBS patients and healthy controls, which suggests that bacterial fermentation is not increased in the small intestine of IBS patients. This finding may have important implications for understanding the contribution of small intestinal bacterial overgrowth (SIBO) in the pathophysiology of IBS. The SCFA levels in stool from IBS patients and healthy controls did not differ. Although this could be due to a number of circumstances, including differences in the absorption of SCFAs and colonic transit time, the authors do not recommend using faecal SCFAs as a marker for estimating intraluminal bacterial fermentation. There seems to be an emerging focus on the role of SCFAs in intestinal health and disease. While the low-FODMAP diet used by some IBS patients is associated with reduced SCFA production, these fermented substances appear to have a central role in the prevention of colon cancer and possibly other diseases. The use of surrogate markers of fermentation may have taken us some way already in our search for aetiological factors, but we need to know more about the direct impact of changes in intestinal fermentation and the various molecules generated by these processes on the development and course of IBS. I look forward to discussing the impact on SCFAs on intestinal homeostasis specifically and public health in general in one or more future blog posts. References
  1. Rajilić-Stojanović M, Jonkers DM, Salonen A, et al. Intestinal microbiota and diet in IBS: causes, consequences, or epiphenomena? Am J Gastroenterol 2015; 110: 278–287. 
  2. Halmos EP, Christophersen CT, Bird AR, et al. Diets that differ in their FODMAP content alter the colonic lumincal microenvironment. Gut Epub ahead of print 12 July 2015 doi: 10.1136/gutjnl-2014-307264.
  3. Böhn L, Störsrud S, Liljebo T, et al. Diet low in FODMAPs reduces symptoms of irritable bowel syndrome as well as traditional dietary advice: A randomized controlled trial. Gastroenterology Epub ahead of print 5 August 2015. DOI: 10.1053/j.gastro.2015.07.054.
  4. Ringel-Kulka T, Choi CH, Temas D, et al. Altered colonic bacterial fermentation as a potential pathophysiological factor in irritable bowel syndrome. Am J Gastroenterol 2015; 110: 1339–1346. 

Gastric balloons join the fight against obesity 

How can we tackle obesity?

Obesity is one of today’s most worrying public health problems; it strongly correlates with cardiovascular disease, diabetes, cancer and non-alcoholic fatty liver disease, among other pathologies associated with metabolic syndrome.

According to the World Health Organization (WHO),1 the worldwide prevalence of obesity has more than doubled since 1980; in 2014, a whopping 39% of adults aged 18 years and older were overweight and 13% were obese. The culprits? Ever-increasing sedentary lifestyles and overconsumption of high-fat/high-sugar foods. Which means that the solution should be very easy—to move more and eat less of the wrong foods—right? Unfortunately, there is no simple solution/easy answer. Obesity encompasses many social and psychological layers, which are difficult to get past. Children and adults are constantly exposed to advertisements on how tasty and delicious sugary drinks or high-fat/high-sugar foods are, not to mention the fun and approval associated with sharing them with friends. At the same time, kids will play on their videogame consoles or chat with friends online, rather than going outside and doing the exact same things… for real. Not that I am against any of those things, but a knowledge-based balance is essential. Healthy lifestyles are now being heavily promoted at the societal level, starting from a very early age; as an example, the WHO has created a commission on ending childhood obesity, taking into account the different economic and cultural contexts of each region of the world. The medical community itself has been changing gears in the fight against obesity. Several recent clinical guidelines advise doctors to think of obesity as a disease and to have a more active role in treating obese patients to help them achieve weight loss.2 As a result, most medical practitioners now require that their patients engage in healthy lifestyles before any medical or surgical procedure is considered. In particular, gastroenterologists are stepping up their game. As stated by Professor Mathus-Vliegen, Gastroenterologist and Professor in Clinical Nutrition at the Academic Medical Centre, University of Amsterdam, there are several natural reasons why gastroenterologists should take care of obese patients: many obesity-associated diseases develop in the gastrointestinal tract; patients with complications arising from bariatric surgery can be managed using minimally invasive endoscopic techniques; and the gastrointestinal tract is also the target for other forms of treatment, like endoscopic therapy.3 Indeed, endoscopic bariatric treatment of obesity has recently jumped into the spotlight since the US Food and Drug Administration (FDA) approved the use of two different inflatable medical devices, which are delivered to the stomach via a quick and minimally invasive endoscopic procedure and that trigger a feeling of fullness to help with weight loss. The ReShape™ Integrated Dual Balloon System consists of two attached balloons that are filled and sealed separately in the stomach of the patient during an endoscopic procedure. 326 obese patients (BMI 30–40 kg/m2), who had at least one obesity-related health condition, participated in the clinical study that led to the FDA approval.4 Individuals who received the device lost an average of 6.8% of their total body weight at the time of removal (6 months after placement) compared with an average of 3.3% in the control group. The ORBERA™ Intragastric Balloon System uses a single balloon that can be filled with different amounts of saline. In the pivotal ORBERA™ clinical trial in the US, 255 obese patients (BMI 30–40 kg/m2) were randomly allocated to the treatment and control groups.5 The treatment group lost 3.1 times as much weight as the control group at 6 months. Gastric balloons have been around for years outside the US and are not without controversy. Both of the obesity devices approved by the FDA are temporary and should be removed after 6 months. As such, are they effective in the long term? The clinical trials showed that patients were able to keep off most of the weight they had lost 6 months after removal of the device. But whether the same is true for longer periods of time is not clear. It is also important to note that both trials used obesity devices as adjuncts to lifestyle modification and it would be interesting to see their effect in isolation, for patients unable to diet and exercise. Whatever the case might be, it is clear that gastroenterologists are on the look out for obesity, which is also reflected by the increasing discussion of this topic at speciality meetings. At UEG Week 2015, for instance, you can expect to hear all about potential novel solutions for obesity, new developments in our knowledge on the gut-brain axis and cancer as they relate to obesity, as well as a dedicated symposium on its epidemiology, treatment and management. I am curious to see what gastroenterologists will bring to the table this time around! References
  1. World Health Organization. Obesity and overweight. Fact Sheet No 311 (January 2015) http://www.who.int/mediacentre/factsheets/fs311/en/.
  2. Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol 2014; 63: 2985–3023. 
  3. Mathus-Vliegen EM. Endoscopic treatment: the past, the present and the future. Best Pract Res Clin Gastroenterol 2014; 28: 685–702. 
  4. Ponce J, Woodman G, Swain J, et al. The REDUCE pivotal trial: a prospective, randomized controlled pivotal trial of a dual intragastric balloon for the treatment of obesity. Surg Obes Relat Dis 2015; 11: 874–881. 
  5. Abu Dayyeh BK, Eaton LL, Woodman G, et al. 444. A randomized, multi-center study to evaluate the safety and effectiveness of an intragastric balloon as an adjunct to a behavioral modification program, in comparison with a behavioral modification program alone in the weight management of obese subjects. Gastrointest Endosc 2015; 81: Supplement, Page AB147.
Further UEG Resources Invasive management of obesity Session at UEG Week 2014. Obesity and the digestive tract Session at EAGEN Obesity Conference 2013. Obesity: Causes and consequences for the digestive system Session at EAGEN Obesity Conference 2013.

IBD: Musings on models and methods

A snapshot of current developments!

From July 9–11, the UEG Basic Science Course 'IBD: Models and Methods' took place in the Netherlands. A total of 41 delegates had the opportunity to engage in lectures on models of inflammatory bowel disease (IBD)—mouse, rat and organoid cultures. Delegates also participated in hands-on training in the laboratory, which involved a 2D in vitro barrier function model and a 3D in vitro gut model amongst other things. Here, to follow this up, we highlight a newly published method for 3D-pattern profiling of mouse and human phenotypes of intestinal inflammation and give a snapshot of some of the current developments within gut experimental models.

IBD is a complex of diseases, mainly involving Crohn’s disease and ulcerative colitis, which differ in terms of intestinal involvement and other specific macroscopic and microscopic features. The distinction between macroscopic intestinal disease phenotypes has traditionally relied on macroscopic assessment of lesions by trained pathologists, along with histological characterisation of inflammatory processes using 2D sections from which inflammatory cell counts are calculated by analysis of a very limited amount of tissue. Rodriguez-Palacios et al. recently took a microscopic approach to comprehensively examining the integrity of the entire intestinal tract, with a view to characterising disease biology based on 3D-structural patterns.1 Realising that the different types of IBD are often histologically indistinguishable on the basis of mucosal biopsy samples and discovering that stereomicroscopy (SM) has great potential as a routine diagnostic tool for real-time topographical analysis of the gastrointestinal tract at the villous level, this team developed a method using SM to rapidly profile the entire intestinal topography (3D-structure patterns) in mouse models of colitis/ileitis and human IBD. After creating a comprehensive SM catalogue of histologically and scanning electron microscopy (SEM)-validated 3D-intestinal abnormalities (comprising 4,700 mice, 416 inbred strains, and various mouse models of acute/chronic intestinal inflammation and infection), they designed the ‘3D-SM Assessment and Pattern Profiling (3D-SMAPgut)’ system and a registration form to capture qualitative and quantitative data—cm by cm—in order to determine lesion co-occurrence and spatial distribution patterns. Introducing the concept of ‘stereroenterotypes’, which are subclusters of 3D-structure-patterns of IBD pathology that are histologically indistinguishable, the authors found that spontaneous ileitis led to the ‘cobblestone’ steroenterotype in some mouse lines, while the ‘villous mini-aggregation’ stereoenterotype was identified in others. This finding suggests that host genetics drive unique and divergent inflammatory 3D-structural patterns in the gut. To this end, on the basis of the 3D-stereoenterotype, SM correctly predicted with 100% accuracy whether a mouse ileum belonged to SAMP mice or TNFARE mice (strains that have different genetic backgrounds but that both develop spontaneous ileitis) or to a control (ileitis-free) strain. The authors believe that the use of SM will improve our understanding of human IBD by facilitating SM-target analysis of intestinal specimens from animals and IBD patients. This analysis is critical to intestinal phenotyping of genetically diverse mouse and human populations and for preclinical drug testing. The use of animal models has been indispensable in IBD research. These models can be chemically induced, genetically engineered, immunologically mediated or spontaneous. There are also other types of animal models, and the choice of which model to use relies on the specific hypothesis/question that is being addressed.2 The panel of mouse colitis models is vast;3 the oxazolone colitis model in particular appears relevant for studying human ulcerative colitis due to its close resemblance not only with respect to morphology, but also with respect to immunopathogenesis. Another model, the widely applied DSS colitis model, has proven useful for studies on innate immune mechanisms involved in the development of intestinal inflammation. This model has also been used to study the development of colon cancer in relation to colonic inflammation, such as that occurring in patients with long-standing ulcerative colitis. However, mouse models are intrinsically low throughput and sometimes do not adequately mimic human physiology.3,4 The development of ‘organoids’,4-6 including ‘enteroids’ and ‘colonoids’, by ex vivo culture of intestinal epithelial cells may soon enable a marked reduction in the animals used for experimental purposes and allow for more precise and targeted studies of human intestinal disease phenotypes. Indeed, it appears that there is immense potential for this culture system in gastrointestinal research, particularly to model diseases such as graft-versus-host-disease and IBD.7 As an example, Rodansky et al. have taken advantage of advances in stem-cell-derived human intestinal organoids by developing a new human model of fibrosis in Crohn’s disease.8 To find out more on the use of intestinal and hepatic organoids, please sign in to myUEG and search the UEG Education Library! To learn more about general advances in, and the outlook for, organoid technologies in terms of disease modelling, I’d suggest looking up the 2014 review by Lancaster and Knoblich.9
References
  1. Rodriguez-Palacios A, et al. Stereomicroscopic 3D-pattern profiling of murine and human intestinal inflammation reveals unique structural phenotypes. Nat Commun 2015; 6: 7577 doi: 10.1038/ncomms8577
  2. Pizarro T. Intestinal fibrosis (IBD) including models. Presentation in the "GI organ-specific fibrosis" session at UEGF Teaching Activity on Basic Science 2011. 
  3. Kiesler P, et al. Experimental models of inflammatory bowel diseases. Cell Mol Gastroenterol Hepatol 2015; 1: 154–170. 
  4. Wells JM, and Spence JR. How to make an intestine. Development 2014; 141: 752–760. 
  5. Sato T, et al. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Battett’s epithelium. Gastroenterology 2011; 141: 1762–1772. 
  6. Watson CL, et al. An in vivo model of human small intestine using pluripotent stem cells. Nat Med 2014; 20: 1310–1314. 
  7. Hartman KG, et al. Modeling inflammation and oxidative stress in gastrointestinal disease development using novel organotypic culture systems. Stem Cell Res Ther 2013; 4 Suppl. 1: S5. 
  8. Rodansky ES, et al. Intestinal organoids: a model of intestinal fibrosis for evaluating anti-fibrotic drugs. Exp Mol Pathol 2015; 98: 346–351. 
  9. Lancaster MA and Knoblich JA. Organogenesis in a dish: modelling development and disease using organoid technologies. Science 2014; 345: 1247125.  

Let’s get physical: Listen to your liver talk! 

Does exercise benefit NAFLD patients?

Summer is just around the corner and I’ve been hitting the gym more often to get ready for the beach (and by more often I mean I actually started going to the gym)! But there are many more important reasons why you should work out and your liver’s health is a major one, particularly concerning non-alcoholic fatty liver disease (NAFLD).

NAFLD consists of a spectrum of histopathological changes that range in severity from simple steatosis to non-alcoholic steatohepatitis (NASH). Although simple steatosis is characterized by a relatively favourable clinical outcome, NASH can progress to cirrhosis and hepatocellular carcinoma, leading to liver-related morbidity and mortality. Largely considered a manifestation of obesity and the metabolic syndrome, NAFLD is becoming the most common cause of chronic liver disease worldwide. Indeed, NAFLD is found in almost 70% of the adult obese population and in more than 90% of morbidly obese individuals.1 NAFLD is also highly prevalent in children and its incidence appears to be increasing in Europe, with 2–12.5% of children and early adolescents presenting with NAFLD, a number that rises to 36–44% in obese children.2 Of note, the risk factors for paediatric NAFLD mirror those for adult NAFLD and further correlate with an increasingly sedentary lifestyle, coupled with unbalanced dietary habits, where changes in macronutrients, increased calorie intake and decreased physical activity negatively influence NAFLD pathogenesis. There is no current pharmacological treatment for NAFLD, although several clinical trials are ongoing, with promising results reported so far. As a consequence, lifestyle interventions remain the cornerstone of NAFLD treatment; in parallel with healthier and smarter eating choices, the benefit of physical activity for NAFLD patients has recently been expounded. Originally thought to be effective only when combined with the introduction of a healthy diet in obese patients, it is now apparent that different exercise regimens can benefit NAFLD, even without dietary restriction and/or in the absence of significant weight loss. For instance, aerobic exercise alone has been shown to be able to decrease visceral adipose tissue volume and liver fat content in sedentary obese individuals by 12% and 21%, respectively.3 Similarly, Oh and co-workers showed that increased physical exercise with or without dieting significantly reduced hepatic inflammation and associated oxidative stress in obese men.4 More recently, Oh and colleagues have suggested that at least 250 minutes of moderate to vigorous intensity physical exercise per week was required to reduce liver fat in obese men as part of lifestyle management.5 In other words, this is more or less equivalent to 50 minutes of moderate (dancing, gardening, housework/domestic chores, walking domestic animals) to vigorous (walking, running, fast cycling/swimming, aerobics, competitive sports/games) intensity physical activity, 5 times per week. Not bad at all! But it gets even better. In April 2015, Keating et al. showed that inactive and overweight/obese adults placed under different aerobic exercise regimens reduce their liver fat and visceral adipose tissue, irrespective of exercise volume or intensity and in the absence of clinically significant weight loss!6 In my opinion, these findings suggest that regular exercise may also greatly benefit non-obese NAFLD patients, despite there being no expectation that these patients will lose a significant amount of weight (they are lean!). Although it might be surprising for some to learn that NAFLD is not solely a disease of the obese population, the prevalence of NAFLD in lean individuals is increasing. This increase in prevalence is particularly noticeable in the Asia-Pacific region, due to diverse environmental and genetic factors.7 As such, if you think you have ‘good genes’ because you look lean and healthy despite not working out much and/or eating junk food all the time, you might want to think twice, listen to your liver talk and get physical! If nothing else, individuals who exercise regularly might be, perhaps unknowingly, actively lowering their risk of developing fatty liver or even cardiometabolic disease, as the latter correlates with excess liver fat, even in the absence of NASH. However, the key word here is ‘regularly’; if you are a seasonal gym member like me, I would encourage you (and myself) to find other parallel and fun exercise activities and to stick to them. This might be difficult for some, but the sustainability of any intervention is the key to success. This is why—despite believing that specialized and personalized exercise prescription, in parallel with dietary advice, should continue to represent the main line of treatment for NAFLD patients—I think that the use of pharmacological agents on their own or as adjunctive therapies to lifestyle modification will remain desirable. When exercising, the old saying, “Feel good on the inside and look good on the outside,” usually crosses my mind. Now, I can also almost picture my liver shouting “I feel good, na na, na na, na na, na…” References: 
  1. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002; 346: 1221–12231.
  2. Durmaz O. Metabolic liver disease in the adolescent. Presentation in the Non-alcoholic fatty liver disease (NAFLD): any news? session at UEG Week 2014.
  3. Johnson NA, et al. Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss. Hepatology 2009; 50: 1105–1112.
  4. Oh S, et al. Exercise reduces inflammation and oxidative stress in obesity-related liver diseases. Med Sci Sports Exerc 2013; 45: 2214–2222.
  5. Oh S, et al. Moderate to vigorous physical activity volume is an important factor for managing nonalcoholic fatty liver disease: a retrospective study. Hepatology 2015; 61: 1205–1215.
  6. Keating SE, et al. Effect of aerobic exercise training dose on liver fat and visceral adiposity. J Hepatol Epub ahead of print 1 April 2015. DOI: 10.1016/j.jhep.2015.02.022.
  7. Bugianesi E. Non-obese patients with NAFLD. Presentation in the Non-alcoholic fatty liver disease (NAFLD): any news? session at UEG Week 2014.
Further UEG Resources: Bellentani, S. How frequent is NAFLD in Europe and in the world? Presentation in the Update on non-alcoholic fatty liver disease session at UEG Week 2013 Dufour J-F. Impact of lifestyle and diet on disease progression. Presentation in the Non-alcoholic fatty liver  disease (NAFLD): any news? session at UEG Week 2014. Ratziu, V.  Medical treatment. Presentation in the Non-alcoholic fatty liver disease (NAFLD): any news? session at UEG Week 2014. Ratziu, V. Treatment modalities for non-alcoholic steatohepatitis. Presentation in the Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease in 2014 session at UEG Week 2014. 

Wake up Europe—it’s World IBD Day!

World IBD Day is observed on May 19.

World IBD Day (#worldIBDday) is observed on May 19 every year. This is the day for the millions of patients with IBD (inflammatory bowel disease), their supporters and IBD organizations worldwide to raise awareness, advance the understanding of the impact of IBD on human health and highlight the large number of people affected.

Ulcerative colitis and Crohn’s disease, the major types of IBD, are autoimmune diseases, the etiology of which appears multifactorial, involving both genetic and environmental factors. A study in the American Journal of Gastroenterology mapped the risk of acquiring IBD in relatives of patients with IBD.1 The study was based on data in the Danish National Patient Register, which included the 45,857 Danes who were diagnosed with IBD between 1977 and 2011. The team identified that the children, siblings or parents of individuals with IBD had an eightfold increased risk of developing IBD. For grandparents, uncles, aunts, nephews and nieces, the risk was increased by 2.5-fold. Among the younger siblings of patients with Crohn’s disease who were aged 20–25 years, the risk of developing IBD over the following 10 years was as high as 2%. First author on the paper, Frederik Trier Møller, says “Our results can be used in the counselling of relatives of IBD patients and maybe in the long run to identify persons, who could benefit from future available preventive measures.” Moving on to environmental factors, the intestinal microbiota is thought also to have a key role in the development of IBD. Books, such as ‘An Epidemic of Absence,’2 sum up some of the hypotheses on the etiology of allergic and autoimmune diseases. Intestinal parasites—protists and worms—are eukaryotic symbionts associated with the human intestine that have co-evolved with humans over thousands of years. These symbionts are still almost obligate findings in citizens in some regions of the world where IBD appears to be a very limited problem (e.g. Sub-Saharan Africa). Such organisms tend to establish stable communities in the human gut, but their role in human health and disease remains relatively unexplored. However, there is some evidence that the defaunation of the human gut seen in many countries with a Westernized lifestyle is associated with an increased incidence of immune-mediated and inflammatory diseases.2–5 Hence, while busy ridding ourselves of bugs, maybe particularly so those of our children, we may have inflicted new diseases on ourselves, including IBD. And so, in efforts to ‘dirty up’ our diets again, potential alleviation of IBD using concoctions of microscopic helminth eggs (Trichuris suis) is currently being investigated, the rationale being that helminth therapy will favorably modulate pro-inflammatory cytokine responses associated with intestinal inflammation. Indeed, IBD patients appear much less prone to being hosts of parasites than healthy individuals,6 but until now, only mere associations have been identified, not mechanistic understandings. Not only parasites—or the lack thereof—but also bacteria may have crucial roles in the etiology of IBD. It’s difficult not to think of peptic ulcers and gastric cancer when the word falls on Helicobacter pylori. Meanwhile, performing a meta-analysis of 33 available studies, comprising 4,400 IBD patients and 4,763 controls, to explore the association between H. pylori infection and IBD, Rokkas and colleagues7 found that 26.5% of IBD patients tested positive for H. pylori infection, compared with 44.7% of individuals in the control group. The significant negative association between H. pylori infection and IBD supports the hypothesis that H. pylori infection protects against the development of IBD. This conclusion is backed up by data in a recent study that was not included in the meta-analysis. Roka et al. found that the occurrence of H. pylori gastritis was less frequent in children with newly diagnosed IBD compared with controls.8 However, the team calls for studies that enable the distinction between a true protective role of H. pylori and a confounding effect due to, for instance, previous use of antibiotics in children with IBD. The fact that patients with IBD may have a slightly higher risk of developing small bowel cancer and colorectal cancer than individuals without the disease may now be quite well established, but how about the treatment offered to IBD patients? For example, what are the side effects of biologics and how severe are they? A study published in JAMA aimed to investigate whether patients with IBD who were exposed to TNF-α antagonists were at increased risk of developing cancer.9 Exposure to TNF-α antagonists (e.g. infliximab, adalimumab, and certolizumab pegol) among patients with IBD was not associated with an increased risk of cancer over a median follow-up of 3.7 years; an increased risk associated with longer-term accumulated doses and follow-up, however, could not be excluded. With regard to anti-TNF treatment and beyond, the ‘Therapy update: Best use of biologics in IBD in 2014’ session at UEG Week 2014 is available in the UEG Education Library. In the presentation, Professor Séverine Vermeire uses the ECCO guidelines and her experience to advise on when to use anti-TNF agents.10 Dr Silvio Danese then talks us through emerging therapeutic monoclonal antibodies, such as vedolizumab, golimumab, etrolizumab, tofacitinib, including their mechanisms of action.11 Dr Alessandro Armuzzi reviews the efficacy of drugs used for prevention of postoperative recurrence of Crohn’s disease recurrence, distinguishing between endoscopic and clinical recurrence, and highlights the importance of revisiting strategies to managing postoperative Crohn’s disease.12 In the final presentation from the session, Professor Gils highlights the importance of using pharmacokinetics to guide anti-TNF treatment in clinical practice.13 For more on the same topic, I guide your attention to the ‘How to manage IBD in 2014’ session from UEG Week 2014. Professor Maria Abreu brings you the best on IBD from Digestive Disease Week 201414 and also provides a strategy for how to make a confident diagnosis of IBD15 in the collection of presentations from the postgraduate course ‘What is important when diagnosing IBD?’ This collection also includes Dr Shomron Ben-Horin asking the question ‘Do characteristics at diagnosis predict disease outcome and complications?’,16 something which is also to some extent taken up by Dr Geert D’Haens in a very ‘good-for-teaching’ talk that aims to answer the question ‘Is differentiating ulcerative colitis from Crohn’s disease important?’17 The IBD material available in the UEG Education Library is vast, and I can only encourage you to mark #worldIBDday2015 by listening to some of these presentations. Also, if you want to know more about the activities related to World IBD Day, you may want to visit the World IBD events page. Finally, perhaps it is worth suggesting that World IBD Day should receive special attention on the Faroe Islands. This North-Atlantic archipelago has the highest incidence of IBD in the world, going from 8 per 100,000 person years in 1960–1979 to 75 per 100,000 person years in 2010–2014.18 Such a rapid change is most likely linked not only to increased diagnostic awareness but also to so-far-unidentified environmental factors. References
  1. Moller FT, et al. Familial risk of inflammatory bowel disease: a population-based cohort study 1977–2011. Am J Gastroenterol 2015; 110: 564–571.
  2. Velasquez-Manoff M. An Epidemic of Absence: A New Way of Understanding Allergies and Autoimmune Diseases. New York: Scribner, 2013.
  3. Elliot DE, and Weinstock JV. Where are we on worms? Curr Opin Gastroenterol 2012; 28: 551–556.
  4. Wiria AE, et al. Helminth infection in populations undergoing epidemiological transition: a friend or foe? Semin Immunopathol 2012; 34: 889–901.
  5. Rook GA, et al. Microbial ’Old Friends’, immunoregulation and stress resilience. Evol Med Public Health 2013; 2013: 46–64. 
  6. Petersen AM et al. Active ulcerative colitis associated with low prevalence of Blastocystis and Dientamoeba fragilis infection. Scand J Gastroenterol 2013; 48: 638–639. 
  7. Rokkas T, et al. The association between Helicobacter pylori infection and inflammatory bowel disease based on meta-analysis. United European Gastroenterology Journal Epub ahead of print April 9 2015. DOI:10.1177/2050640615580889. 
  8. Roka K, et al. The prevalence of Helicobacter pylori gastritis in newly diagnosed children with inflammatory bowel disease. Helicobacter 2014; 19: 400–405.
  9. Nyboe Andersen N, et al. Association between tumor necrosis factor-α antagonists and risk of cancer in patients with inflammatory bowel disease. JAMA 2014; 311: 2406–2413.
  10. Vermeire S. When should we start anti-TNF in IBD? Presentation in the “Therapy update: Best use of biologics in IBD in 2014” session at UEG Week 2014. 
  11. Danese S. Looking beyond anti-TNF in IBD: Vedolizumab, tofacitinib, etc. Presentation in the “Therapy update: Best use of biologics in IBD in 2014” session at UEG Week 2014. 
  12. Armuzzi A. Anti-TNF to prevent and treat postoperative recurrence of Crohn’s disease. Presentation in the “Therapy update: Best use of biologics in IBD in 2014” session at UEG Week 2014. 
  13. Gils A. Use of pharmacokinetics to guide anti-TNF treatment in clinical practice. Presentation in the “Therapy update: Best use of biologics in IBD in 2014” session at UEG Week 2014.
  14. Abreu MT. Inflammatory bowel disease. Presentation in the “Best of DDW” session at UEG Week 2014.
  15. Abreu MT. Diagnostic strategy to make a confident diagnosis of IBD. Presentation at UEG Week 2014. Presentation in the Postgraduate Teaching Programme at UEG Week 2014. 
  16. Ben-Horin S. Do characteristics at diagnosis predict disease outcome and complications? Presentation in the Postgraduate Teaching Programme at UEG Week 2014.
  17. d’Haens G. Is differentiating UC from CD important? Presentation in the Postgraduate Teaching Programme at UEG Week 2014.
  18. Hammer T et al. DOP010 Incidence of inflammatory bowel diseases in the Faroe Islands from 1960–2014: a 54-year overview from a population-based cohort. Presentation in “DOP Session 2 – Epidemiology of IBD" at ECCO Congress 2015.

The need for novel GORD diagnostic tools.

The need of noninvasive methods.

Gone are the days when a doctor would diagnose gastroesophageal reflux disease (GORD) simply by asking about symptoms and/or evaluating the response to acid suppression. Though this is still the case in many clinical practices, particularly for patients who have uncomplicated symptoms, a more accurate diagnosis usually involves undertaking invasive and expensive procedures that, nonetheless, are still claimed to have only moderate sensitivity and specificity. As such, more specific, noninvasive and cost-effective methods are needed for the diagnosis of GORD.

GORD is a common and chronic condition that has a significant impact on quality of life and confers a significant economic burden. It generally arises from the reflux of stomach contents into the oesophagus, thus leading to oesophageal injury and associated complications. The most common cause of GORD is the disrupted relaxation of the anti-reflux barrier, which is composed of the lower oesophageal sphincter and the diaphragmatic crura; when failing to respond to swallowing, these transient lower oesophageal relaxations result in reflux of gastric fluid through the oesophagogastric junction. Heartburn and acid regurgitation follow. Ultimately, in some patients acid reflux may damage the oesophageal squamous epithelium and lead to the development of Barrett oesophagus. Left untreated, Barret oesophagus can progress to oesophageal adenocarcinoma.1 The European Association of Endoscopic Surgery (EAES) states that the two main GORD diagnostic tools are upper endoscopy and long-term impedance esophageal pH monitoring. Indeed, the combined information obtained from clinical symptoms, endoscopy and pH testing is usually considered to be sufficient and specific for the diagnosis of GORD.  The EAES also highlight that “…further diagnostic investigations may be needed to verify functional abnormalities and establish the indication for surgery or other invasive therapies.”2 These additional diagnostic tools include high-resolution manometry (HRM), video-radiography and scintigraphy. For patients who have more severe symptoms, such as dysphagia and odynophagia, those who do not respond to acid suppression, or those in whom Barrett oesophagus is suspected, such additional diagnostic tools should be employed.3 Unfortunately, this comes at a sizeable financial cost. In Germany, the incidence of GORD is high and the associated healthcare costs have been estimated at €4.8 billion.4 In the United States, GORD represents the most common GI-related diagnosis; annually, GORD accounts for 8.9 million patient visits to the clinic and endoscopy exams cost $32.4 billion.5 These budgets emphasize the need for alternative, cheaper diagnostic methods for GORD and, ideally, noninvasive ones. Encouragingly, we might be on the right track with two recently published studies on novel GORD diagnostic tools, namely pepsin detection in saliva and minimally invasive oesophageal mucosal impedance testing. Several pathological settings may lead to pepsin being found in the laryngeal and paranasal sinus mucosa, saliva, middle ear effusion, tracheal secretions and bronchoalveolar lavage fluid. In their study, Hayat and co-workers sought to determine the value of salivary pepsin for discriminating patients with reflux-related symptoms from those with functional heartburn (FH).6 Pepsin was more likely to be detected in the saliva of patients with GORD and hypersensitive oesophagus (HO) and at higher concentrations than in the saliva of controls or FH patients. As such, the authors propose that salivary pepsin testing may complement GORD diagnosis.6 The fact that salivary pepsin can distinguish between GORD/HO and FH is extremely relevant, as most GORD patients benefit from pharmacological or surgical anti-reflux therapy, whereas FH patients do not. Interestingly, the detection of pepsin in saliva may also help in the diagnosis of laryngopharyngeal reflux (LPR).7 Despite the belief that LPR symptoms primarily result from GORD-related alterations of the laryngeal mucosa by gastric fluids, LPR differs from GORD in symptomatology and treatment modalities. A higher concentration of pepsin and bile acids has also been found in the saliva of patients with early laryngeal cancer than in the saliva of healthy volunteers, suggesting that LPR plays a role in the development of laryngeal carcinoma and might have utility as a disease biomarker.8 The question of how specific pepsin is for the diagnosis of GORD then arises. Indeed, is salivary pepsin diagnosing GORD, LPR or laryngeal carcinoma in development? As it currently stands, the measurement of salivary pepsin seems to represent a quick, cost-effective, noninvasive and simple 'office-based' method for GORD diagnosis, which I believe should be  followed or paralleled with other disease-specific methods. Nonetheless, it holds a great value on its own in pinpointing the next step; for instance, the absence of pepsin could be taken as a sign of null or low frequency reflux events. Ates and co-workers have developed a minimally invasive device to assess oesophageal mucosal impedance as a marker of chronic reflux in GORD, where impedance is measured close to the squamocolumnar junction.9 They found that the impedance values were significantly lower in patients with GORD, with mucosal impedance patterns being identified in patients with oesophagitis at higher levels of specificity and positive predictive values than wireless pH monitoring.9 Despite being a simple method that’s easy to use and provides immediate results, it is unlikely that mucosal impedance will fully replace current GORD diagnosis tools, as it is unable to distinguish between different GORD symptoms or even GORD-related disorders, which require different therapeutic approaches. Still, it represents an excellent strategy to differentiate between GORD and FH, much like salivary pepsin. Though measurement of mucosal impedance is still invasive, the procedure is quick, which makes it attractive for patients who cannot (or will not) tolerate a transnasal probe that must be in place for 24 hours.   Salivary pepsin levels and oesophageal mucosal impedance stand as two recent major breakthroughs in GORD diagnosis, but more are needed. I hope to see a lot of new and exciting discoveries on GORD diagnosis and management this October at UEG Week 2015! In the meantime, please feel free to browse the UEG Education Library for more resources. References:
  1. Subramanian CR and Triadafilopoulos G. Refractory gastroesophageal reflux disease. Gastroenterol Rep (Oxf) 2015; 3: 41–53.
  2. Fuchs KH, Babic B, Breithaupt W, et al. EAES recommendations for the management of gastroesophageal reflux disease. Surg Endosc 2014; 28: 1753–1773.
  3. Badillo R and Francis D. Diagnosis and treatment of gastroesophageal reflux disease. World J Gastrointest Pharmacol Ther 2014; 5: 105–112.
  4. UEG White Book Brochure [https://ueg.eu/epaper/WhiteBook.Brochure/index.html].
  5. Medical Economics. Treatment of GERD evolving [May 2013, accessed April 14, 2015].
  6. Hayat JO, Gabieta-Somnez S, Yazaki E, et al. Pepsin in saliva for the diagnosis of gastro-oesophageal reflux disease. Gut 2015; 64: 373–380.
  7. Ocak E, Kubat G and Yorulmaz I. Immunoserologic pepsin detection in the saliva as a non-invasive rapid diagnostic test for laryngopharyngeal reflux. Balkan Med J 2015; 32: 46–50.
  8. Sereg-Bahar M, Jerin A and Hocevar-Boltezar I. Higher levels of total pepsin and bile acids in the saliva as a possible risk factor for early laryngeal cancer. Radiol Oncol 2015; 49: 59–64.
  9. Ates F, Yuksel ES, Higginbotham T, et al. Mucosal impedance discriminates GERD from non-GERD conditions. Gastroenterology 2015; 148: 334–343.
Further UEG Resources “Challenges in GORD” Session at UEG Week 2014. “Therapy update: GORD” Session at UEG Week 2014. “New options in gastro-oesophageal reflux disease” Session at UEG Week 2014.

Is your ward happy?

All health services in Europe are under immense pressure …

I was woken up whilst on call recently by one of the staff nurses on our gastroenterology ward. It had been a busy day and, in addition to five new admissions, one patient—a withdrawing alcoholic—had become encephalopathic and was in the process of using a chair to try to smash through a window on the fifth floor. Earlier in the evening the same nurse had been hit in the mouth when she told another liver patient that he couldn’t go for a cigarette.

The 50 inpatient beds in our ward are always occupied by a mixture of patients who have alcoholic liver disease, inflammatory bowel disease, emergency GI bleeding, infective diarrhoea, GI cancer or eating disorders of such severity that they are unable to maintain their weight let alone their electrolyte balance. In my opinion, gastroenterology wards are undoubtedly the most challenging in any hospital. No other hospital ward hosts such a wide-ranging mixture of disease, affecting patients of any age and with such severity! In spite of the state-of-the-art care that we provide, we have more deaths on our ward than any other ward in our hospital. This is because our patients are the sickest. Of course all health services in Europe are under immense pressure. In the UK, the number of patients presenting to GPs and Accident & Emergency departments is increasing, as is the number of patients admitted to hospital.1 As the workload increases, hospital cost cutting has led to a reduction the number of nurses and an increasing pressure to squeeze as much work as possible out of the existing workforce. In the NHS, 12-hour shifts are now the norm. I am sceptical that a 12-hour working day is compatible with the provision of compassionate, expert care to a complex GI patient and would like to see the evidence that this is achievable. The “Registered Nurse Forecast Study”, published in the Lancet in February 2014, looked at the impact of nursing numbers on patient mortality in 300 hospitals across Norway, Ireland, Netherlands, Finland, Sweden, Switzerland, England, Belgium and Spain.2 The authors found that hospitals in which trained nurses cared for an average of 6 patients had almost 30% lower mortality than in hospitals where nurses cared for an average of 8 patients. Similarly, a study by Rafferty et al.3 showed that in the UK “Patients and nurses in the quartile of hospitals with the best staffing levels had consistently better outcomes.” Mortality was 31% worse in hospitals where a single nurse cared for 8 patients compared with those hospitals where a single nurse cared for only 4 patients. Naturally, morale drops as workloads and stress increase. A study by Aiken et al.4 looked at staffing levels at Canadian, American, English and Scottish sites. Higher staffing levels led to higher nurse reported satisfaction with care given, resulting in better nurse retention and reduced burn out. Similarly a study of the safety and quality of hospital care across 12 European countries and the US concluded that better ratios of patients to nurses were associated with increased care quality and patient satisfaction.5 The UK nursing trade union UNISON conduct an annual survey of workload. In 2014, 51% of nurses said that they did not have sufficient staff numbers to deliver dignified, compassionate care.6 Furthermore, an astonishing 48% of respondents described their organisation as being at risk of a similar situation to "the Staffordshire Hospital". The Francis report7 into the Staffordshire Hospital scandal concluded that quality of care had become a secondary priority to financial savings. As a result, the Staffordshire Hospital failed in its duty of care to hundreds of patients and families. Patients died needlessly and loved ones were left in the dark without adequate answers or explanations. There are no European guidelines on minimum nurse staffing levels. In every country, it remains up to each institution to decide how many nurses it should employ. Unfortunately, many hospital managers seem to have no idea of the challenges faced on gastroenterology wards, which have to accommodate the widest range of the most complex conditions in patients aged anywhere between 15 and 115 years old (our oldest ever patient). Next time you do your ward round, make a note of the patient-to-staff ratio and ask yourself whether it is good enough. References
  1. The King’s Fund. What’s going on in A&E? The key questions answered, http://www.kingsfund.org.uk/projects/urgent-emergency-care/urgent-and-emergency-care-mythbusters (14 January 2015, accessed 7 May 2015)
  2. Aiken LH, et.al. Nurse Staffing and education and hospital mortality in nine European countries; a retrospective observational study. Lancet 2014; 383:1824–1830.
  3. Rafferty AM, et al. Outcomes of variation in hospital nurse staffing in English hospitals: cross-sectional analysis of survey data and discharge records, Int J Nursing Studies 2007; 44: 175–182. 
  4. Aiken LH, Clarke SP and Sloane DM. Hospital staffing, organization, and quality of care: cross-national findings, Int J Quality in Health Care 2002; 14: 5–13. 
  5. Aiken LH, et al. Patient safety, satisfaction, and quality of hospital care: cross sectional surveys of nurses and patients in 12 countries in Europe and the United States. BMJ 2012;344:e1717. 
  6. UNISON. Running on Empty—NHS staff stretched to the limit: UNISON’s staffing levels survey 2014, https://www.unison.org.uk/upload/sharepoint/On%20line%20Catalogue/22245.pdf (14 May 2014, accessed 7 May 2015).
  7. Francis R. Report of the Mid Staffordshire NHS Foundation Trust Public Inquiry Executive Summary, http://www.midstaffspublicinquiry.com/sites/default/files/report/Executive%20summary.pdf (6 February 2013, accessed 7 May 2015).

MicrObesity

To what extent do gut microbes contribute to obesity?

Obesity—morbid overweight—is usually defined by a body mass index (BMI) >30. The condition can develop into metabolic syndrome, a rapidly emerging global epidemic that is associated with the development of multiple gastrointestinal (GI) disorders, including GI cancer.

In one of the presentations now available for viewing from the "EAGEN Obesity Course—metabolic and nutritional problems in Western and Eastern Europe", which was held in October 2014, Professor Peter Malfertheiner dishes out quite a few disturbing facts.1 In 2005, 1 billion people worldwide were overweight and 300 million were obese. Ten years on and the numbers have risen to 2.3 billion overweight people and 700 million obese. This means that 14% of the world’s population is now pre-obese (7%) or obese (7%). One of the main concerns regarding obesity is the level of co-morbidity and reduction in life expectancy that is associated with it. Indeed, at the age of 40, the life expectancy of obese individuals is reduced by 7 years compared with that of non-obese individuals. However, it is not the actual BMI level per se, but the number of years living with obesity that is the stronger predictor of mortality, which is why strategies to delay the onset of obesity should be developed and implemented. Distinctions are also made between ‘benign’ and ‘malign’ obesity, the latter being synonymous with ‘visceral obesity’ (or ‘central obesity’), which is linked to inflammatory processes and insulin resistance, and which is labelled metabolic syndrome. Professor Malfertheiner explains how an inappropriate diet may lead to dysbiosis, increased gut permeability and gut bacterial lipopolysaccharide-associated metabolic endotoxaemia, with deterioration in gut, liver and endocrine functions. Professor Malfertheiner also discusses how obesity-associated non-alcoholic fatty liver disease (NAFLD) may develop into hepatocellular cancer (HCC) and underlines the fact that patients receiving insulin have a much higher risk of developing colorectal cancer (CRC). In general, the role of metabolic syndrome in cancer development is currently under intense scrutiny. In his talk ‘The link between obesity and lower GI tract diseases’, Dr Lazlo Herzeny mentions that 15% and 20% of cancer deaths in men and women, respectively, can be attributed to visceral/central obesity.2 Allegedly, 40%, 30% and 10% cases of oesophageal carcinoma, HCC and CRC, respectively, are associated with this type of obesity. In their study, Kang et al.3 showed that visceral obesity and insulin resistance are risk factors of colorectal adenoma, and Rampal et al.4 found an association between metabolic syndrome and colorectal adenoma. Be sure to look up Dr Herzeny’s talk to learn more about the factors potentially involved in obesity-related tumour development and progression. Incidentally, the EAGEN meeting included a pro-con debate on the role of obesity in GI cancers. Citing a study by Danaei et al.,5 Professor Borut Stabuc argues that obesity is on its way to outcompeting tobacco as the number one preventable cause of cancer.6 He talks us through reviews and meta-analyses that provide data evidencing links between metabolic syndrome and various types of cancer. However, gender differences are seen, and the relative risks associating metabolic syndrome with cancer are generally quite modest. As Professor Jaroslaw Regula points out in his talk,7 we are swamped with epidemiological data evidencing associations between metabolic syndrome and GI cancer, but these associations do not necessarily represent causal relationships. Professor Regula gives examples of some of the caveats when interpreting epidemiological data and calls into question the overall applicability of BMI in epidemiological studies, since BMI is not a direct indicator of visceral obesity. Moreover, there are few intervention studies and they do not necessarily show the same trends for men and women.8 The composition of the gut microbiota varies substantially among individuals, but within individuals it is also dynamic and susceptible to change by diet and administration of antimicrobial agents. The term ‘MicrObesity’ (microbes and obesity), coined by Drs Cani and Delzenne, is about deciphering the specific role of intestinal microbiota dysbiosis and its impact on host metabolism and energy storage.9 Microbes take up approximately 1 kg of our body weight, with most microbes being in the gut. Perturbations of the intestinal microbiota can have severe implications for our health, and several diseases appear to stem from intestinal dysbiosis. According to Lopez-Legarrea et al.,10 the majority of the bacterial phylotypes found in the intestine are members of two phyla: the Firmicutes (e.g. Clostridium, Enterococcus, Lactobacillus, Ruminococcus), which make up 60% of the gut microbiota, and the Bacteroidetes (e.g. Bacteroides, Prevotella), which account for about 15%. Other phyla include Actinobacteria (e.g. Bifidobacterium) and Proteobacteria (Helicobacter, Escherichia). In her talk, Dr Darij Vranesic Bender points out that a Mediterranean diet, which is high in polyphenols and polyunsaturated fatty acids, leads to increases in Prevotella, Enterococcus, Bifidobacteria, Latobacillus and Bacteroides, while a decrease in obesity-associated Clostridium is seen.11 Changes in the relative balance of bacterial groups may be directly associated with nutritional uptake, but the situation is complex and influenced by host factors such as genetics/co-evolution and physical activity. Also, one might ask how do changes in microbiota structure and function impact benign and malign (visceral/central) obesity? Data are still scarce, but a study recently published in Gut showed that cranberry extract administered to mice fed on a high-fat/high-sucrose (HFHS) diet reduced HFHS-induced weight gain and visceral obesity.12 Cranberry extract treatment markedly increased the proportion of the mucin-degrading bacterium Akkermansia muciniphila, which has previously been shown to be decreased in obese individuals, and which may be a bacterium actively fighting obesity and diabetes.13 As pointed out by Professor Krznaric in his talk “The role of microbiota in the pathophysiology of obesity”, imbalances in the relative proportion of Bacteroides to Firmicutes may lead to obesity.14 Of particular interest is the recognition of obesity-associated gut microbiomes with increased capacity for energy harvest, since the human microbiota—in this rising era of microbiota transplantation—can be remodelled in different cohorts (obese vs underweight) with a view to optimising nutritional intake. Part of the mechanism underlying this is the role of short-chain fatty acids that are not only a source of energy for the intestinal epithelium, but also act as signalling molecules with implications for fat metabolism. Professor Krznaric also underlines the possibility that long-term exposure to low-dose antibiotics, for instance through foods, may lead to intestinal dysbiosis and obesity. Moreover, as pointed out by Professor Malfertheiner, non-caloric artificial sweeteners—quite paradoxically—drive the development of glucose intolerance, which is associated with insulin resistance, due to alterations of the structure and function of the intestinal microbiota.2 Given this complex situation it will be challenging to come up with one-size-fits-all strategies for combatting obesity in the future. Nonetheless, Professors Petr Díte and Tomica Milosavljevic both attempt to do this. To learn about their thoughts and to update yourself with much more news in the field interfacing obesity and GI diseases, please do listen to their talks.15,16 Gut microbiota manipulation appears to be critical to future advances in preventing and treating obesity, and the effect of diet on gut microbiota structure and function is probably one of today’s hottest research areas. The collection of talks from the EAGEN meeting includes a variety of other obesity-associated topics, including endoscopic approaches to obesity, an update on bariatric surgery and epidemiology, clinical presentation and management of non-alcoholic steatohepatitis (NASH), to mention just some. Why not sit down with a nice cup of coffee and have a browse yourself, though you may want to try the coffee without the sugar or sweetener … and skip the biscuits! References
  1. Malfertheiner, P. Epidemiological trends of metabolic syndrome affecting GI diseases. Presentation at EAGEN Obesity Course - metabolic & nutritional problems in Western and Eastern Europe.
  2. Herzeny, L. The link between obesity and lower GI tract diseases. Presentation at EAGEN Obesity Course - metabolic & nutritional problems in Western and Eastern Europe.
  3. Kang HW, et al. Visceral Obesity and Insulin Resistance as Risk Factors for Colorectal Adenoma: A Cross-Sectional, Case–Control Study. Am J Gastroenterol 2010; 105: 178–187. 
  4. Rampal S, et al. Association Between Markers of Glucose Metabolism and Risk of Colorectal Adenoma. Gastroenterology 2014; 147: 78–87.
  5. Danaei G, et al. Causes of cancer in the world: comparative risk assessment of nine behavioural and environmental risk factors. Lancet 2005; 366: 1784–1793.
  6. Stabuc  B. Debate: Obesity and the risk of GI cancer – PRO. Presentation at EAGEN Obesity Course - metabolic & nutritional problems in Western and Eastern Europe.
  7. Regula J. Debate: Obesity and the risk of GI cancer – CONTRA. Presentation at EAGEN Obesity Course - metabolic & nutritional problems in Western and Eastern Europe. 
  8. Sjöström L. Review of the key results from the Swedish Obese Subjects (SOS) trial - a prospective controlled intervention study of bariatric surgery. J Intern Med 2013; 273: 219–234.
  9. Cani PD and Delzenne NM. The gut microbiome as therapeutic target. Pharmacol Ther 2011; 130: 202–212. 
  10. Lopez-Legarrea P, et al. The influence of Mediterranean, carbohydrate and high protein diets on gut microbiota composition in the treatment of obesity and associated inflammatory state. Asia Pac J Clin Nutr 2014; 23: 360–368. 
  11. Bender DV.  Protein, carbs and fats in personalised weight control - efficacy and safety. Presentation at EAGEN Obesity Course - metabolic & nutritional problems in Western and Eastern Europe. 
  12. Anhê FF et al. A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice. Gut (Epub ahead of print 30 July 2014) doi:10.1136/gutjnl-2014-307142.
  13. Everarda, A et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci 2013; 110: 9066–9071. 
  14. Krznarik Z. The role of microbiota in the pathophysiology of obesity. Presentation at EAGEN Obesity Course - metabolic & nutritional problems in Western and Eastern Europe. 
  15. Díte P. Health strategies to manage the epidemics of metabolic syndrome. Presentation at EAGEN Obesity Course - metabolic & nutritional problems in Western and Eastern Europe. 
  16. Milosavljevic T. Health strategies to manage the epidemics of metabolic syndrome. Presentation at EAGEN Obesity Course - metabolic & nutritional problems in Western and Eastern Europe.  
Further UEG Education Resources EAGEN Obesity Course—metabolic and nutritional problems in Western and Eastern Europe. Acknowledgements "Overweight and obesity tape measure" image: http://www.canstockphoto.com © Can Stock Photo / alexskopje.
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