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 3

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

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

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 7

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

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 10

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

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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. 21

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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 Fibroscan available NAFLD … 24

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-Liver project Focusing on liver disease 25

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 26

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

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 28

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

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 31

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 32

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 33

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 34

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, …

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