Pancreas Transplantation. Sonia Clarke-Swaby Recipient Kidney/pancreas Transplant Co-ordinator Guy s Hospital

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1 Pancreas Transplantation Sonia Clarke-Swaby Recipient Kidney/pancreas Transplant Co-ordinator Guy s Hospital

2 Introduction Selection criteria, New innovation Complications, Success rates, Life expectancy Rejection Immune suppressant medication

3 Transplantation Implanting in one part a tissue or organ taken from another part or from another individual Clinically, used to replace the function of a failed organ Renal transplant for ESRD +/- dialysis Pancreas transplantation

4 Pancreas The pancreas is an organ located in the abdomen. It plays an essential role in converting the food we eat into fuel for the body's cells. The pancreas has two main functions: an exocrine function that helps in digestion and an endocrine function that regulates blood sugar

5 Discovery of Insulin 1922 Banting and Best (Nobel Prize) isolated an extract from a dog pancreas which was able to control or lower blood glucose level of diabetic patients. In January 1922, Leonard Thompson, a 14-year-old boy dying from diabetes in a Toronto hospital, became the first person to receive an injection of insulin. Within 24 hours, Leonard s dangerously high blood glucose levels dropped to near-normal levels Banting FG & Best CH, Collip JB, cambell WR, Fletcher AA. Pancreatic extract in the treatment of diabetes mellitus. Preliminary report. CMAJ 1922:12:141-6

6 Discovery of Insulin Left starvation method: Right, Insulin treatment method (Yuwiler 22)

7 Diabetes Leading cause of blindness in year olds Leading cause in lower extremity, vascular disease and amputation Diabetic neuropathy affects approx 50% of patients. Life expectancy is = 1/3 less than that of the general population

8 Diabetes can be treated with transplantation Kelly, W. Lillehei, R. Merkel, F. Idezuki, Y. Goetz, F: Allotransplantation of the pancreas and duodenum along with the kidney in diabetic nephropathy. Surgery 61: , 1967.

9 The first kidney/pancreas transplant 1966 Richard Lellehei and Dr William D Kelly university on Minnesota 28 year old woman diabetic age 10 with renal failure She had normal blood sugar following the procedure, but died at 2 months later from rejection and sepsis. The procedure was considered experimental. Now it is a widely accepted as a therapeutic modality for patients needing pancreas transplantation.

10 The Purpose of pancreas transplantation Improve quality of life by establishing insulindependent, normoglycaemic state Prevent and ameliorate secondary complications of diabetes

11 Selection Category Combined Simultaneous Pancreas and kidney (SPK) transplantation Pancreas After Kidney Transplantation (PAK) Pancreas Transplant Alone (PTA) Improved microvascular outcomes and lipids, outcome

12 Selection Criteria SPK: Renal failure, defined as egfr 20 or on dialysis. Insulin-dependent Diabetes Mellitus Recipient. Age < 65 Body Mass Index (BMI) < 30 kg/m2 if type 2 DM Require < 100 units insulin per week SPK Characteristics More involved technically Easier to detect rejection Higher risk patients ESRD- longer waiting time

13 Contd. PAT: Presence of Insulin-dependent Type I Diabetes Mellitus egfr > 70 ml/min/1.73 m2. The following is recommended: Hypoglycaemic unawareness Diabetology referral with brittle diabetes with frequent or severe episodes of hypoglycaemia Disabling recurrent, severe hypoglycaemia despite evidence of compliance with expert medical advice Preservation of Kidney function Improve quality of and life expectancy

14 Contd. PAK Prior functioning kidney transplant with sufficient renal reserve to tolerate pancreatic transplantation with the extra immunosuppressive burden, e.g. patients with stable function of a previous renal allograft (egfr > 40 ml/min/1.73 m2) who meet criteria for SPK Benefit of LDKTx Shorter operation Not drain on DD pool list Decreased waiting time 2 operations Guidelines Relevant to Pancreas Transplantation Effective January 2016 January 2018

15 Pancreas Transplant About 75% of pancreas transplantations are performed with kidney transplantation (both organs from the same donor) in patients with renal failure who are diabetic (SPK transplant). About 15% of pancreas transplantations are performed after a previously successful kidney transplantation, (PAK). The remaining 10% of cases are performed as pancreas transplantation alone in patients (PAT) with unstable and/ or problematic diabetes. An alternative new therapy that may also ameliorate diabetes is islet transplantation, which is not yet as effective as pancreas transplantation.

16 Bladder Drainage with Systemic Venous Anastomosis Advantage: Monitoring of urine amylase Disadvantage Alkalinization of urine infections Irritation by enzymes infection Loss of bicard acidosis & dehydration Urine in the pancreas - pancreatitis Enteric Drainage with Portal Venous Anastomosis Advantages: Avoid metabolic complications Avoid infections complications Avoid bladder dysfunction Lower re-operation rate Lower leak rate

17 Surgery Midline incision Intra-abdominal Placement Graft to duodenum to bladder or small intestine

18 Complications, Complications Return to theatre (30-40%) Bleeding Leaks Bowel or bladder complications Pancreas loss Blood clots (5-10%), leaks (5-10%), rejection Heart attack, stroke Other complications as for kidney transplantation Lifelong Immunosuppressant

19 Contd. Transplants are not a cure Not all kidney/pancreas transplants are the same Other donor issues Transmitted diseases: infection, cancer Age: the average age of deceased donors is increasing

20 Pancreas Graft Survival Based on Type of Transplant 1 Transplant Type 1 year 5 years 10 years 15 years Simultaneous pancreas kidney 85-90% 69% 51% 33% Pancreas after kidney 74-80% 45% 24% 13% Pancreas alone 78-80% 54% 28% 9% Transplant Type 1 year 5 years 10 years 15 years Waki K, Kadowaki T. An analysis of long-term survival from the OPTN/UNOS Transplant Registry. Clin Transplant. 2007:9-17 Ryan EA, Paty BW, Senior PA, et al. Five year follow-up after clinical islet transplantation. Diabetes. 2005;54:

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23 Immunosuppressant medication -Our Unit We have many years experience of our regimen and we have found it to be highly effective. Each immunosuppressant has its own side effects that tend to be dose related, so we give a combination of 3 drugs allowing lower doses of each thus reduces the side effects.

24 Immunosuppressant's What are they used for? When your body detects foreign tissue it attacks it. The result of this is rejection. We want to PREVENT rejection Immunosuppressant's dampen down the immune system to reduce risks of rejection but in doing so your body isn t as effective at fighting infection or unusual cells

25 Our regimen Long Term Tacrolimus (Adoport / Advagraf / Prograf ) Immunosuppressant Long Term Mycophenolate Immunosuppressant Long Term Prednisolone (Steroid) Immunosuppressant?Long Term Aspirin Prevents Blood clots 1 month Nystatin Liquid Oral Thrush 12 months Co-trimoxazole PCP Prevention 3 months Ranitidine Stomach Acid 3 months? Valganciclovir CMV prevention 6 months?

26 In Conclusion Pancreatic transplantation is believe to offer potential for normalisation of blood sugar levels in diabetic patients. This is done in the context of patients receiving immunosuppressant Despite the requirement for an abdominal surgical procedure and lifelong immunosuppressant, currently the most reliable way to provide long term glucose control in patient with diabetes with the appropriate indications.

27 Contd. Currently Guy s kidney-pancreas transplant centre ranks among the most prestigious transplant programs in the country It has one of the best outcome post SPK transplant SPK/PAT remains and the best option intervention for patient with type 1 diabetes and some type two s

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29 Slide 28 G2 Any Questions GSTT, 10/05/2016