Total Pancreatectomy With Islet Autotransplantation Resolves Pain in Young Children With Severe Chronic Pancreatitis.

OBJECTIVES: Fear of diabetes and major surgery may prohibit referral of young children severely affected by pancreatitis for total pancreatectomy with islet autotransplant (TPIAT). We evaluated outcomes in our youngest TPIAT recipients, 3 to 8 years of age at surgery. METHODS: Medical records were reviewed for 17 children (9 girls) ages 8 years or younger undergoing TPIAT from 2000 to 2014. Most (14/17) had genetic risk factors for pancreatitis. Since 2006, TPIAT recipients were followed prospectively with health questionnaires including assessments of pain and narcotic use, and scheduled hemoglobin A1c (HbA1c) and mixed-meal tolerance tests (6 mL/kg Boost HP) before surgery, and at regular intervals after. Patients are 1 to 11 years post-TPIAT (median 2.2 years). Data are reported as median (25th, 75th percentile). RESULTS: All had relief of pain, with all 17 patients off narcotics at most recent follow-up. Hospitalization rates decreased from 5.0 hospitalization episodes per person-year of follow-up before TPIAT, to 0.35 episodes per person-year of follow-up after TPIAT. Fourteen (82%) discontinued insulin, higher than the observed insulin independence rate of 41% in 399 patients older than 8 years of age undergoing TPIAT over the same interval (P = 0.004). Median post-TPIAT HbA1c was 5.9% (5.6%, 6.3%), and within patient post-TPIAT mean HbA1c was ≤6.5% for all but 2 patients. CONCLUSIONS: Young children with severe refractory chronic pancreatitis may be good candidates for TPIAT, with high rates of pain relief and insulin independence, and excellent glycemic control in the majority.

Update on pancreas and islet cell transplantation - abstract

The purpose of both pancreas and islet transplantation is to improve the quality of life in diabetic patients by establishing an insulin-independent, constant normoglycaemic state. They are the only treatments that can do so. Currently, pancreas transplantation is much more successful but requires a major operation. Islet transplantation is simpler for the recipient but islet preparation is complicated and isolated islets may be more vulnerable to rejection than an intact organ. Generalized immunosuppression is required in recipients of either pancreas or islet transplants. Thus, most are performed in patients with advanced diabetic nephropathy who recieve kidney transplants to treat uraemia and who are obligated to immunosuppression for this reason. Of more than 6000 pancreas transplants reported to the International Pancreas Transplant Registry from 1966 to 1994, approximately 85 per cent were in diabetic renal allograft recipients. Pancreas transplants alone are primarily performed in highly selected patients with extremely labile diabetes mellitus. Since 1986, success rates (insulin-independence for o 1 year) as calculated by the Pancreas Transplant Registry have been approximately 75 per cent for pancreas transplants performed simultaneously with kidney transplants and approximately 50 per cent when performed as a solitary procedure. With good HLA matches, however, the success rate with solitary pancreas transplants is also over 70 per cent. Another goal is to ameliorate or prevent secondary complications of diabetes mellitus. Most recipients have had diabetes mellitus for many years with complications already at an advanced stage, and so the effect of a successful transplant on secondary lesions is mixed. Clinical neuropathy and early, but not advanced, neuropathy appear to be favourably influenced but advanced retinopathy is not. Nevertheless, several studies show most recipients rate their quality of life as higher post-pancreas transplant. Type I diabetes mellitus is an autoimmune disease directed against pancreatic beta cells and recurrence of disease in the absence of rejection has been observed in some grafts placed in non- or minimally immunosuppressed recipients of segmental grafts from non-diabetic identical twin or HLA-identical non-twin sibling donors. However, many grafts from related donors have functioned long-term without evidence of disease (graft isletitis) in immunosuppressed recipients and recurrence of disease in the absence of rejection has never been observed in the relatively heavily immunosuppressed recipients of cadaveric grafts. Pancreas transplantation has evolved into a very routine method of beta cell replacement in many centres when performed in conjunction with renal allografts for treatment of uraemia. As a solitary procedure, it has a role in treatment of highly selected patients with extremely labile diabetes mellitus not well served by the alternatives. Ultimately, pancreas transplantation will probably be superseded by islet transplantation. Islet isolation is complex and prevention of rejection is difficult but islet transplantation remains an attractive goal because of the simplicity of the implantation procedure; sustained insulin-independence has been achieved in a few recipients. Approximately 200 cases have been reported to the Islet Transplant Registry. Of those done in the last few years, 40 per cent have had C-peptide levels above baseline at 1 year, but less than 10 per cent have been insulin-independent. Work in this area continues. For the moment, however, only pancreas transplantation can be offered with a probability of success similar to that of other solid organ transplants. In diabetic uraemia recipients of kidney transplants, the addition of a pancreas is routine in many centres. For selected patients with labile diabetes mellitus and hypoglycaemia unawareness, a successful pancreas transplant can dramatically improve quality of life (AU)