Background Total-pancreatectomy (TP) with intraportal-islet-auto-transplantation (IAT) can relieve pain and preserve beta-cell-mass in patients with chronic-pancreatitis (CP) when other-therapies fail. Reported is a >30-year-single-center-series. Study Design 409 patients (53 children, 5–18 yrs) with CP underwent TP-IAT from Feb/1977–Sept/2011; (etiology idiopathic-41%; SOD/biliary-9%; genetic-14%; divisum-17%; alcohol-7%; other-12%); mean age-35.3 yrs,); 74% female; prior-surgeries 21%--Puestow procedure 9%, Whipple 6%, distal pancreatectomy 7%; other 2%). Islet-function was classified as insulin-independent for those on no insulin; partial if known C-peptide positive or euglycemic on once-daily-insulin; and insulin-dependent if on standard basal–bolus diabetic regimen. An SF-36-survey for Quality-of-Life (QOL)) was completed before and in serial follow-up by patients done since 2007 with an integrated-survey that added in 2008. Results Actuarial-patient-survival post-TP-IAT was 96% in adults and 98% in children (1-year) and; 89% and 98% (5-years). Complications requiring relaparotomy occurred in 15.9%, bleeding (9.5%) being most common. IAT-function is achieved in 90% (C-peptide >0.6 ng/ml). At 3 years, 30% were insulin-independent (25% in adults, 55% in children) and 33% had partial-function. Mean HbA1C was <7.0% in 82%. Prior pancreas surgery lowered islet-yield (2712vs4077/kg, p=.003). Islet yield [<2500/kg (36%); 2501–5000/kg (39%); >5000/kg (24%)] correlated with degree of function with insulin-independent rates at 3 yrs of 12, 22 and 72%, partial function 33, 62 and 24%. All patients had pain before TP-IAT and nearly all were on daily-narcotics. After TP-IAT, 85% had pain-improvement. By two years 59% had ceased-narcotics. All children were on narcotics before, 39% at follow-up; pain improved in 94%; 67% became pain-free. In the SF-36 survey, there was significant improvement from baseline in all dimensions including the Physical and Mental Component Summaries (P<0.01), whether on narcotics or not. Conclusions TP can ameliorate pain and improve QOL in otherwise-refractory-CP-patients, even if narcotic-withdrawal is delayed or incomplete because of prior long-term use. IAT preserves meaningful islet function in most patients and substantial islet function in >2/3 of patients with insulin-independence occurring in one-quarter of adults and half the children.

The seemingly inexorable decline in insulin independence after islet transplant alone (ITA) has raised concern about its clinical utility. We hypothesized that induction immunosuppression therapy determines durability of insulin independence. We analyzed the proportion of insulin independent patients following final islet infusion in four groups of ITA recipients according to induction immunotherapy: University of Minnesota recipients given FcR nonbinding anti-CD3 antibody alone or T cell depleting antibodies (TCDAb) and TNF-α inhibition (TNF-α-i) (Group 1;n=29); recipients reported to the Collaborative Islet Transplant Registry (CITR) given TCDAb+TNF-α-i (Group 2; n=20); CITR recipients given TCDAb without TNF-α-i (Group 3;n=43); and CITR recipients given IL-2 receptor antibodies (IL-2RAb) alone (Group 4,n=177). Results were compared with outcomes in pancreas transplant alone (PTA) recipients reported to the Scientific Registry of Transplant Recipients (Group 5;n=677). 5-yr insulin independence rates in Group 1 (50%) and Group 2 (50%) were comparable to outcomes in PTA (Group 5: 52%; p>>0.05) but significantly higher than in Group 3 (0%; p=0.001) and Group 4 (20%; p=0.02). Induction immunosuppression was significantly associated with 5-year insulin independence (p=0.03), regardless of maintenance immunosuppression or other factors. These findings support potential for long-term insulin independence after ITA using potent induction therapy, with anti-CD3 Ab or TCDAb+TNF-α-i.

No abstract

Islet function is more resilient in autografts than allografts. Indeed, the 5-year insulin-independence persistence rate for IATs is similar to the 2-year rate for allografts. Several factors unique to allocases are likely responsible for the differences, including donor brain death, longer cold ischemia time, diabetogenic immunosuppression, and auto- and alloimmunity. IAT outcomes provide a minimum theoretical standard to work toward in allotransplantation.