1. Islet cell transplantation Rob Crookston. Advanced Nurse Practitioner. Oxford University Hospitals NHS Foundation Trust.

2. Islet Cell Transplantation Allo-Transplantation Auto-Transplantation (following total pancreatectomy for non malignant conditions)

3. Newcastle (Bristol) Manchester Royal Free Oxford Kings NCG Consortium

4. Oxford Islet Transplant Network

5. Aims of Islet transplant A successful Islet transplant would prevent hypoglycaemia, reverse hypoglycaemic unawareness and achieve Insulin Independence. This in turn may prevent the long term complications of diabetes To improve the quality of life of patients with Type 1 DM who suffer severe potentially life threatening problems with blood sugar control Not Insulin Independence!!

6. Inclusion Criteria Type 1 diabetes of >5 years duration. Age 18 with no upper age limit. C-peptide 4 mmol/L. Recurrent hypoglycaemia of at least one year’s duration, with at least 2 episodes of severe hypoglycaemia (defined by coma, seizure, or requiring third party assistance) in the last 24 months. Failure to optimise glycaemic control by conventional insulin replacement. No or minimal renal impairment. Normal liver function tests. Evidence of the use of a reliable method of contraception in women of child-bearing age.

7. Waiting List Shared with whole pancreas and SPK All offers come from NHSBT Algorithm allocates points based on 8 criteria Algorithm altered in 2010 to give equal weighting for islet transplant

8. Total Points Score (TPS) Example routine islet patient: 2 mm: -150 300 days:247 15% cRF: 3 On dialysis: 180 DBD ‘local’: 365 BMI of 29: 365 Age diff of 5: -2 Total points: 1008

9. Donors DBD/DCD BMI <40 DBD 25-60, DCD 25-50 No history of diabetes or pancreatitis Cold Ischaemia time DBD 6 hrs

10. 2 stages : Collagenase Digestion (releasing islets) Density-Gradient Purification (separating islets) Human Islet Isolation

11. Islet Isolation and Islet Transplantation

12. Dissection

13. Collagenase Infusion (1) Bacterial Collagenase and Neutral Protease enzyme mixture – critical for successful islet isolation

14. Collagenase Infusion (2)

15. Digestion

16. Monitoring Digestion

17. Optimal Digestion

18. Density-Gradient Purification

19. 20 – 50 ml < 5 ml Why purify?

20. Culture Logistics Quality testing Patient pre-treatment

21. Percutaneous transhepatic approach via portal vein (or laparoscopic / mini-lap.) Antibiotic and Heparin cover Infuse over 15-20 minutes Monitor portal pressure throughout Islet Transplant (1)

22. Islet Transplant Islet Transplant (2)

23. Sliding scale insulin / dextrose for first 48 hours Daily C-peptide levels Liver ultrasound at 24 hours Transfer back to pre-Tx insulin regime and titrate insulin requirements Intensive outpatient follow-up Post Transplant

24. Outcomes Outcomes in 24 UK patients in first 3 years of NHS funded programme (April 2008 to March 2011) Brooks et al., Diabetic Medicine

25. Patient RML after 12 months HbA1c 7.0% HbA1c 5.1% 100% Insulin Reduction

26. Transplant Numbers 2014-15 = 23 transplants 2015-16 = 20 transplants

27. Patient testimonials RML Islet transplant 09/02/2010. “Increased confidence allows me to go out and live my life” “I’ve also noticed the change in other people and their confidence towards me allowing me to be less of a worry to my friends and family” “Has allowed me to regain my independence both with the confidence to go out and getting my driving licence back” TC Islet transplant 29/09/2009. “The transplant has improved my quality of life a hell of a lot” “Having no fear of hypos and not having to take insulin has really improved my life” “I have the independence to go away for a weekend and forget my glucometer and not have to worry”

28. Patient Video https://www.youtube.com/watch?v=CbzUbrpF3KQ

29. Aims of the project Develop knowledge of islet cell transplant across the Thames Valley Develop relationships with local centres to prevent unnecessary travel Facilitate increasing referrals To reduce travel time and costs for patients post transplant

30. Current Progress 1.Introduction to medical and nursing staff 2.Evening meeting for stakeholders to introduce program 3.Electronic referral form 4.Patient experience video 5.Virtual clinics

31. Current progress (cont) Referrals from Thames Valley 2008-2014 = 3 Referrals from Thames Valley 2014-2015 = 14

32. Future Plans Further develop e-referrals – Developing a true e-referral – Uploading blood glucose data remotely – Transferring images from referring hospitals

33. Future Plans (cont) Virtual clinics – Post transplant clinics – Pre transplant visits – Remote requesting of blood tests – Online/virtual monitoring of blood sugars

34. Future plans (cont) Developing patient information – PPI – Interactive media – Social media integration

35. Acknowledgements Professor Paul Johnson Professor Stephen Gough Dr Alistair Lumb Dr Chitra Ballav Islet isolation lab team Transplant ward Team RTC team Patients

36. Thank you for listening. Questions?