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Journal ArticleDOI

A Few Spanish Pearls for the American Journal of Gastroenterology.

07 Nov 2017-The American Journal of Gastroenterology (Nature Publishing Group)-Vol. 112, Iss: 12, pp 1759-1760

TL;DR: How “cost-zero” research in Spain combined with international competitive pressure created a strong collaboration of independent support networks through researcher associations and societies is described, and how this collaboration has become one of the most important contributors to Spanish Gastroenterology.

AbstractIn the Red Section of this issue of the American Journal of Gastroenterology , well-known specialists in their respective fi elds present highlights from gastroenterology research in Spain. Th ese reports illustrate how well-organized network collaborations could impact the scientifi c literature worldwide, as these collaborations are positioned at the frontier of knowledge and could reveal innovative approaches to the diagnosis and treatment of patients with digestive diseases. Th ese achievements are especially notable, given that they occurred during a serious worldwide economic crisis that aff ected research in many countries, especially those that do not generally prioritize science ( 1,2 ). Most of the successes presented here were obtained under the umbrella of two national organizations. One is the CIBERehd, an acronym of the Spanish name “Centro de Investigation Biomédica en Red para Enfermedades Hepáticas y Digestivas” or “Biomedical Research Networking Center Consortium in Hepatic and Digestive Diseases” in English. Th e CIBERehd ( http://www.ciberehd. org ) is part of a larger entity known as “CIBER”, which has additional areas of interest focused on a variety of human diseases. Th e CIBER was initiated and organized by the National Institute of Health Carlos III ( http://www.eng.isciii.es ), in charge of coordinating Spanish biomedical research. Th e CIBERehd is a “virtual” center, combining the eff orts of the best research groups in gastroenterology and hepatology across the country, and it funds, awards, and prioritizes collaborative research among the groups. Th e second organization may have even greater merit in this context, and is known as the Asociación Española de Gastro enterología (AEG) ( http://www.aegastro.es ), also known as the “Spanish Association of Gastroenterology” in English. Th e AEG has promoted important network research collaborations joining the eff orts of many clinical research groups of diff erent sizes and capacities. Many of these groups are not yet included in the CIBERehd, which limits their capacity for funding. Th e AEG has several working groups (Esophagus-Stomach-Duodenum, GI Oncology, Endoscopy, Neuro-gastroenterology and Motility, Infl ammatory Bowel Diseases, Pancreas and Biliary Tree) and platforms and collaborates closely with other scientifi c organizations, including the Spanish Working Group on Crohn’s Disease and Ulcerative Colitis (GETECCU) with its registries and methodological unit, as well as the Spanish Pancreatic Club. In just 10 years, CIBER investigators have published >7200 articles in the top medical journals, and almost 2600 of them were related to CIBERehd. Th e AEG groups have published almost 300 studies over the same period, fi ft y of which have been published in Th e American Journal of Gastroenterology ( 3,4 ). One of the fi ve reports published in this special section illustrates two of the tools enabling this small miracle, the ENEIDA (Estudio Nacional en Enfermedad Infl amatoria intestinal sobre Determinantes genéticos y Ambientales) and the AEG-REDCap platforms. Adrian G. McNicholl and Javier P. Gisbert describe how “cost-zero” research in Spain combined with international competitive pressure created a strong collaboration of independent support networks through researcher associations and societies, and how this collaboration has become one of the most important contributors to Spanish Gastroenterology. ENEIDA, created by GETECCU, is a nationwide, hospital-based registry and biobank of Infl ammatory Bowel Disease patients from 100 Spanish hospitals. Th is database provides an infrastructure for the development of multicenter studies of all types. Th e impact and success of ENEIDA has grown exponentially and has become an inspiration for other European organizations replicating this model. Th e other major platform is the AEG-REDCap, created by AEG within a consortium agreement with Vanderbilt University ( 5 ). AEG-REDCap provides scientifi c methodological support and online data capture/management tools to over 50 projects, including more than 200 databases and 1300 researchers. Th e success of this initiative inspired participation by many European researchers in this local Spanish platform. Th e European Registry on Helicobacter pylori management is the best example of this success as well as the largest international project, with over 25,000 cases already registered. In the pages that follow, Enrique Quintero and Antonio GimenoGarcía off er a perspective on colorectal cancer screening based on studies conducted in Europe in general, and Spain in particular. Much of that knowledge was again obtained within the collaborative network of the GI Oncology group of AEG. Th is AEG working group has effi ciently and successfully generated ongoing projects, A Few Spanish Pearls for the American Journal of Gastroenterology

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INTERNATIONAL DATELINE

  • Including the EPICOLON (estudio de la EPIdemiologia del cáncer de COLON) I and II as well as COLONPREV (COLON PREVention study), which have already resulted in important reports.
  • Th e COLONPREV project ( 6 ) will be the fi rst RCT to provide 10-year mortality data, comparing colonoscopy and biennial FIT, as screening methods for intermediate risk populations over the age of 50.
  • Th e EST-CPRE study, a retrospective analysis of consecutive patients undergoing Endoscopic Retrograde Cholangiopancreatography (ERCP) in four centers in Spain, found that patients consuming statins had a 70% lower risk of post-ERCP acute pancreatitis.
  • Crucially, these studies have advanced the understanding that GERD and EoE are not mutually exclusive disorders, and that there is a clear EoE phenotype with complete remission on PPIs, with or without GERD.

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1
© 2017 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
THE RED SECTION
INTERNATIONAL DATELINE
In the Red Section of this issue of the American Journal of
Gastroenterology , well-known specialists in their respective  elds
present highlights from gastroenterology research in Spain.  ese
reports illustrate how well-organized network collaborations
could impact the scienti c literature worldwide, as these col-
laborations are positioned at the frontier of knowledge and could
reveal innovative approaches to the diagnosis and treatment of
patients with digestive diseases.  ese achievements are especially
notable, given that they occurred during a serious worldwide eco-
nomic crisis that a ected research in many countries, especially
those that do not generally prioritize science ( 1,2 ).
Most of the successes presented here were obtained under the
umbrella of two national organizations. One is the CIBERehd, an
acronym of the Spanish name “Centro de Investigation Biomédica
en Red para Enfermedades Hepáticas y Digestivas” or “Biomedical
Research Networking Center Consortium in Hepatic and Diges-
tive Diseases” in English.  e CIBERehd ( http://www.ciberehd.
org ) is part of a larger entity known as “CIBER, which has addi-
tional areas of interest focused on a variety of human diseases.
e CIBER was initiated and organized by the National Institute
of Health Carlos III ( http://www.eng.isciii.es ), in charge of coordi-
nating Spanish biomedical research.  e CIBERehd is a “virtual”
center, combining the e orts of the best research groups in gastro-
enterology and hepatology across the country, and it funds, awards,
and prioritizes collaborative research among the groups.
e second organization may have even greater merit in this con-
text, and is known as the Asociación Española de Gastro enterología
(AEG) ( http://www.aegastro.es ), also known as the “Spanish Asso-
ciation of Gastroenterology” in English.  e AEG has promoted
important network research collaborations joining the e orts
of many clinical research groups of di erent sizes and capaci-
ties. Many of these groups are not yet included in the CIBERehd,
which limits their capacity for funding.  e AEG has several
working groups (Esophagus-Stomach-Duodenum, GI Oncology,
Endoscopy, Neuro-gastroenterology and Motility, In ammatory
Bowel Diseases, Pancreas and Biliary Tree) and platforms and col-
laborates closely with other scienti c organizations, including the
Spanish Working Group on Crohns Disease and Ulcerative Colitis
(GETECCU) with its registries and methodological unit, as well
as the Spanish Pancreatic Club. In just 10 years, CIBER investiga-
tors have published >7200 articles in the top medical journals, and
almost 2600 of them were related to CIBERehd.  e AEG groups
have published almost 300 studies over the same period,  y
of which have been published in  e American Journal of Gastro-
enterology ( 3,4 ).
One of the ve reports published in this special section illus-
trates two of the tools enabling this small miracle, the ENEIDA
(Estudio Nacional en Enfermedad In amatoria intestinal sobre
Determinantes genéticos y Ambientales) and the AEG-REDCap
platforms. Adrian G. McNicholl and Javier P. Gisbert describe how
cost-zero” research in Spain combined with international com-
petitive pressure created a strong collaboration of independent
support networks through researcher associations and societies,
and how this collaboration has become one of the most important
contributors to Spanish Gastroenterology. ENEIDA, created by
GETECCU, is a nationwide, hospital-based registry and biobank
of In ammatory Bowel Disease patients from 100 Spanish hos-
pitals.  is database provides an infrastructure for the develop-
ment of multicenter studies of all types.  e impact and success of
ENEIDA has grown exponentially and has become an inspiration
for other European organizations replicating this model.  e other
major platform is the AEG-REDCap, created by AEG within a con-
sortium agreement with Vanderbilt University ( 5 ). AEG-REDCap
provides scienti c methodological support and online data cap-
ture/management tools to over 50 projects, including more than
200 databases and 1300 researchers.  e success of this initiative
inspired participation by many European researchers in this local
Spanish platform.  e European Registry on Helicobacter pylori
management is the best example of this success as well as the larg-
est international project, with over 25,000 cases already registered.
In the pages that follow, Enrique Quintero and Antonio Gimeno-
García o er a perspective on colorectal cancer screening based on
studies conducted in Europe in general, and Spain in particular.
Much of that knowledge was again obtained within the collabora-
tive network of the GI Oncology group of AEG.  is AEG working
group has e ciently and successfully generated ongoing projects,
A Few Spanish Pearls for the American Journal
of Gastroenterology
A n g e l L a n a s , M D , P h D
1
,
2
,
3
Am J Gastroenterol advance online publication, 7 November 2017; doi: 10.1038/ajg.2017.410
1
Service of Digestive Diseases, University Clinic Hospital Lozano Blesa, University of Zaragoza , Zargoza , Spain ;
2
Instituto de Investigación Sanitaria Aragón ,
Zargoza , Spain ;
3
Centro de Investigation Biomédica en Red para Enfermedades Hepáticas y Digestivas (CIBERehd) , Madrid , Spain . Correspondence:
Angel Lanas, MD, PhD, Servicio de Aparato Digestivo, Hospital Clínico Universitario , C/ San Juan Bosco 15 , Zaragoza 50009 , Spain . E-mail: alanas@unizar.es

INTERNATIONAL DATELINE
The American Journal of GASTROENTEROLOGY www.nature.com/ajg
2
THE RED SECTION
INTERNATIONAL DATELINE
including the EPICOLON (estudio de la EPIdemiologia del cáncer
de COLON) I and II as well as COLONPREV (COLON PREVen-
tion study), which have already resulted in important reports.  e
COLONPREV project ( 6 ) will be the  rst RCT to provide 10-year
mortality data, comparing colonoscopy and biennial FIT, as screen-
ing methods for intermediate risk populations over the age of 50.
On the basis of the local and regional studies summarized in their
report, Quintero and Gimeno–García conclude that under condi-
tions of universal access to our National public Health System and
coming from a Spanish perspective, the current recommendations
for colorectal cancer screening of  rst-degree relatives of patients
with colorectal cancer should be revised for individuals with only
one index case in the family. In their view, the evidence currently
supports that these patients should follow a similar screening strat-
egy as those classi ed within the average-risk population, and that
fecal immunological tests (FIT) should be o ered as an alternative
to colonoscopy screening in this population.
Enrique de Madaria reports another exciting outcome of net-
work collaboration for the study of pancreatic diseases in Spain. He
presents four clinical multicenter studies based on basic research
addressing the e ect of statins in experimental pancreatitis, and
suggests a potential role for these drugs in improving the disease
course as well as several outcomes.  e EST-CPRE study, a retro-
spective analysis of consecutive patients undergoing Endoscopic
Retrograde Cholangiopancreatography (ERCP) in four centers
in Spain, found that patients consuming statins had a 70% lower
risk of post-ERCP acute pancreatitis.  is result prompted the
initiation of a pan-European prospective cohort study involving
centers from Spain, Italy, Finland, Croatia, Sweden, and Roma-
nia to con rm these results with the STARK study ( STA tins and
R is K of post-ERCP acute pancreatitis).  e STAR-TREC trial is
another collaborative study, involving centers from Spain, Peru,
and Bolivia, aiming to investigate whether atorvastatin will be
useful in the prevention of acute pancreatitis a er ERCP. Finally,
Madaria presents the SIMBA trial, ( SIM vastatin in the prevention
of recurrent acute pancreatitis, a triple- B lind, r A ndomized con-
trolled trial) designed to investigate the e ectiveness of simvasta-
tin (40 mg daily) in decreasing the incidence of new episodes of
AP in recurrent cases.  is multicenter, randomized, triple-blind,
placebo-controlled trial is focused on adult patients with at least
2 episodes of AP. Fi een centers from Spain have joined SIMBA,
and recruitment has already started ( 7 ).
e European and especially the Spanish contribution to our
understanding of Eosino lic Esophagitis (EoE), a relatively new
diagnosis, has been notable over the last 5 years. Javier Molina
and Alfredo Lucendo are two of the most important researchers in
this area ( 8 ).  eir studies have been conducted in Spain, and are
now being projected within the United European Gastroentero-
logy (UEG) organization. Crucially, these studies have advanced
the understanding that GERD and EoE are not mutually exclusive
disorders, and that there is a clear EoE phenotype with complete
remission on PPIs, with or without GERD. European studies have
demonstrated that phenotypic, molecular, and mechanistic fea-
tures cannot distinguish between patients with EoE that do or do
not respond to PPI.  erefore, Molina and Lucendo conclude that
PPI therapy responders should be included within the spectrum of
EoE, suggesting novel questions requiring investigation with new
compounds such as vonoprazan, the  rst agent of a new class of
potassium-competitive acid blockers.
e last report comes from one of our most relevant investigators
on functional disorders. Fermin Mearín provides a provocatively
titled report on the speci cally Spanish view of IBS. Fermín Mearin
has conducted several studies within the AEG working group, and
is one of the researchers most familiar with the perception of this
disease by Spanish and European gastroenterologists ( 9 ). Despite
living in a Mediterranean country and consuming a Mediterranean
diet, Spanish people are not “immune” to IBS. We appear to have
similar IBS subtypes as patients from other parts of the world, with
small di erences relative to Northern European Countries and the
USA. Mearin also points out that Spanish IBS patients seek medi-
cal attention more frequently than patients from other countries.
is may be due to our public and open access universal health
systems, and could have a tremendous impact on costs. Clearly, the
regional IBS perspective described by Dr. Mearin will be crucial for
an improved understanding of this disease, and will open areas of
research for those interested in functional disorders.
ese are just some examples of the excellent research currently
performed in Spain, and re ected the experiences of hardworking
doctors and scientists in harsh economic environments. One could
imagine what they would accomplish under a better support from
our national and regional institutions.
CONFLICT OF INTEREST
Guarantor of article: Angel Lanas, MD, PhD.
Speci c author contributions: Angel Lanas wrote the manuscript.
Financial support: is report was partially funded by a grant from
“Instituto de Salud Carlos III (ISCIII) (PI14/01218).
Competing interests: None.
REFERENCES
1. Pain E . European debt crisis. Research cuts will cause 'exodus' from Spain .
Science 2012 ; 336 : 139 – 40 .
2. Torjesen I . Funding crisis forces Cancer Research UK to cut spending by
10% . BMJ 2011 ; 343 : d8068 .
3. Lanas A , García-Rodríguez LA , Arroyo MT et al. E ect of antisecretory
drugs and nitrates on the risk of ulcer bleeding associated with nonsteroidal
anti-in ammatory drugs, antiplatelet agents, and anticoagulants . Am J
Gastroenterol 2007 ; 102 : 507 – 15 .
4. Gisbert JP , Calvet X , Cosme A et al. Long-term follow-up of 1,000 patients
cured of Helicobacter pylori infection following an episode of peptic ulcer
bleeding . Am J Gastroenterol 2012 ; 107 : 1197 – 204 .
5 . H a r r i s P A , T a y l o r R , ielke R et al. Research electronic data capture (REDCap)-
-a metadata-driven methodology and work ow process for providing transla-
tional research informatics support . J Biomed Inform 2009 ; 42 : 377 – 81 .
6 . Q u i n t e r o E , C a s t e l l s A , B u j a n d a L et al. Colonoscopy versus fecal immuno-
chemical testing in colorectal-cancer screening . N Engl J Med 2012 ; 366 : 697 – 706
7. SIMBA trial: Simvastatin in the prevention of recurrent acute pancreatitis, a
Triple Blind Randomized Controlled Trial EU Clinical Trials Register2016;
updated 08-05-2016. Available at https://www.clinicaltrialsregister.eu/
ctr-search/trial/2016-002445-31/ES
8. Lucendo AJ , Molina-Infante J , Arias A et al. Guidelines on eosinophilic
esophagitis: evidence-based statements and recommendations for diagnosis
and management in children and adults . United Eur Gastroenterol J 2017
2017 ; 5 : 335 – 58 .
9. Mearin F . Editorial: From the acute infection to the chronic disorder "Don't
worry it's just a viral gastroenteritis" . Am J Gastroenterol 2012 ; 107 : 900 – 1 .
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