Digestive Disease Research Institute

1. Digestive Disease Research Institute Tehran University of Medical Sciences

2. History • 1974 • Establishment of the department of Gastroenterology and Hepatology of Shariati hospital • 1994 • Establishment of the Digestive Disease Research Center (DDRC) • 2007 • WHO collaborating center for research on gastrointestinal cancers • 2011 • Establishment of the Digestive Disease Research Institute (DDRI)

3. DDRC • Education • Medical students • Residents • GI fellows • 6-8 GI fellows each year • >100 gastroenterologists trained • Endoscopy training for Internists • Advanced courses for gastroenterologists • EUS • ERCP • DBE

4. DDRC • Patient care • Routine hospital load • OPD clinic • Research

6. Proposal Review Committee • Peer-review of proposals considering priorities • Help in improving research proposals • Collaborating with other associations and universities

7. Research Council • Final approval of proposals, progress reports, final reports. • Deciding on budget allocation to various research groups • Approving collaborations, sample transfer, etc. • Major decisions in research subjects

8. Collaborating Center for Ethics committee/IRB on Office for Human Research Protections (OHRP)

10. Collaborations • Many universities and centers in Iran • Collaborating with the 10 best world institutes and universities • IARC, WHO, NCI/NIH, Cambridge, John Hopkins, Harvard, Karolinska, Glasco, Leeds, CRUK

11. Collaboration with WHO • IARC is the arm of WHO researching on cancer • So our collaboration with WHO has been mainly through IARC • We have even managed to secure funding from IARC! • Over 20 high-impact papers each year closely related to problems in Iran, many of which have the potential to change health policies. • Many training opportunities for our researchers • Have returned to DDRI and help us here or … • Have moved to other research institutes abroad forming further opportunities for collaboration

12. Scopus

13. GI Cancer Research Center • Gastro-Esophageal Malignancy In Northern Iran (GEMINI) • Case control study • 300 cases of gastric cancer • 600 controls • In collaboration with NCI/NIH/IARC • Numerous studies published and still being published • Golestan Cohort Study

14. Collaborations in GEMINI • GEMINI was probably the one research project which boosted collaborations of DDRI with the world • We currently have collaborations in GEMINI with 10-20 internationally recognized centers and institutes

15. How to Make Collaborators Interested • It is not easy to draw attention of international organizations • Specially in a country so blackened by the media • Guidelines are needed!

16. Guidelines for Attracting Collaborators • Search for something of mutual interest for you and the international community. • Cancers • Cardiovascular mortality and it’s prevention • Choose a subject in which you have an advantage • High rate of ESCC in north Iran than most of the world • Referral center for Achalasea with over 800 samples • Very good infrastructure for population based rural studies

17. Guidelines for Attracting Collaborators • Search the literature to find centers/authors most interested in this subject with most publications • Identify authors with highest interest and key persons • Contact them • Emails • In person in meetings/congress/… • Through colleagues working in the same centers/city • Iranians abroad • Previous collaborators

18. Start the Collaboration • Invite them to Iran (congress, seminar, meeting, …) • Their view to Iran will suddenly change • You can discuss the basics of collaboration without distrations • Sometimes a PhD student can be assigned at the same time • Good proposal • It helps a lot if you can send a sharp PhD student to the collaborating center to work on the mutual project. • Much better communication • Training opportunity

21. The Golestan Cohort Study (GCS) • A cohort of 50,000 subjects, above 40 y/o started on 2005, now 9 Years old. A great deal of data collected including: • Detailed 30-page questionnaire (including FFQ) • Frozen samples of serum, whole blood, nails and hair. • Yearly follow-up of subjects • The cohort was originally designed to study ESCC, but many other studies are also on-going within this cohort.

24. Sub-Cohorts of GCS • Hepatitis B cohort • Approx. 5,000 subjects • All HBs Ag positives subjects of GCS (3500) and their positive family members (1500) • Ultrasound and Fibroscan available for those living in Gonbad (400) • Hepatitis C cohort • 350 subjects • Ultrasound and Fibroscanavailable • NAFLD …

25. Sub-Studies of GCS • Re-measurement • 20-25% of the GCS subjects were revisited after 5 Years and data/samples collected • PolyIran project • Interventional study • Aims at reducing cardiovascular mortality • PolyIran-Liverproject • Focusing on liver disease

26. The PolyIran Study • We observed that during the first 5 Years of GCS, the mortality from cancer was less than 20% whereas the mortality of CVD was over 50% • We started a CVD-prevention trial with a combination pill we call “PolyPill” • We have randomized all re-measurement subjects above 50 (8,500) to receive either polypill or minimal care

27. PolyPill • ASA: 81 mg • Atorvastatin: 20 mg • Hydrochlorthiazide: 12.5 mg • Enalapril: 5 mg or Valsartan: 80 mg Given daily for 5 years

28. The PolyIran-Liver Study • 1,500 of the PolyIran subjects live in the city of Gonbad where better facilities are available. • These subjects undergo some liver work-up too; we call them the PolyIran-Liver group • Ultrasound • Fibroscan • IMT, visceral fat measurement, MRI

30. Future and On-Going Activities • Identifying high risk groups for gastric and esophageal cancer • Preventive measures • Providing guidelines for early detection

31. Ardabil (prevalent gastric cancer) • Ten years ago, we performed1000 endoscopies on randomly selected volunteer subjects over 45 years of age • Chromoendoscopy (lugol staining) was carried out on all subjects and suspicious lesions were biopsied • In addition, biopsies were obtained from 10 predetermined sites in the stomach • Histology, blood, urine, nail, and hair samples plus an extensive questionnaire is available

32. Ardabil (prevalent gastric cancer) • We have identified over 900 of these subjects • 34 cases of cancer have been documented • We will compare initial data of subjects with progressed or new precancerous lesions with controls • We hope to find markers in their initial data (pathology, blood, questionnaire, …) which helps us identify high risk subjects

33. Gonbad (prevalent esophageal cancer) • We have already identified a few risk factors during our studies in Gonbad • In the case control study (GEMINI), we compared 300 cases of esophageal cancer with 600 controls • In the cohort (GCS), we have followed 50,000 subjects and so far over 50 have developed esophageal cancers

34. Gonbad (prevalent esophageal cancer) • During these studies we have already identified 7 risk factors • We will use these factors to create a model for prediction of esophageal cancer • High-risk subjects can then be screened by endoscopy

35. GE Cancer Screening Project (GESP) • Finding an efficient screening method for esophageal Ca • Most screening protocols are not really cost-effective • Endoscopy for all is definitely not an option • Evaluating serologic tests, sponge cytology, …