Total pancreatectomy with islet autotransplantation in diabetic and pre-diabetic patients with intractable chronic pancreatitis

Abstract

Total pancreatectomy with islet autotransplantation (TPIAT) is an effective treatment option for non-diabetic patients with intractable chronic pancreatitis. The outcome and potential benefits for pre-diabetic and diabetic patients are less well established. Thirty-four patients underwent TPIAT were retrospectively divided into 3 groups according to pre-operative glycemic control: diabetes mellitus (DM) (n=5, 15%), pre-DM (n=11, 32%) and non-DM (n=18, 54%). Pre-operative fasting c-peptide was detectable and similar in all 3 groups. Islet yield in the DM group was comparable to pre-DM and non-DM groups (median islet equivalents [IEQ] was 191,800, 111,800, and 232,000IEQ, respectively). Patients received islet mass of over the target level of 2000IEQ/kg in pre-DM and DM at lower but clinically meaningful rates compared to the non-DM group: 45% (5/11) and 60% (3/5) for a combined 50% (8/16) rate, respectively, compared to 83% (15/18) for the non-DM group. At 1 year, fasting c-peptide and HbA1c did not differ between DM and pre-DM groups but c-peptide was significantly higher in non-DM. Islet transplantation failed (negative c-peptide) only in 1 patient. Pre-operatively, all patients experienced pancreatic pain with daily opioid dependence in 60% to 70%. Pancreatic-type pain gradually subsided completely in all groups with no differences in other painful somatic symptoms. Diabetic patients with measurable pre-operative c-peptide can achieve similar benefit from TPIAT, with comparable outcomes to pre-diabetic and non-diabetic patients including pain relief and the metabolic benefit of transplanted islets. Not surprisingly, endocrine outcomes for diabetic and pre-diabetics patients are substantially worse than in those with normal pre-operative glucose control.

Keywords: Autotransplantation; Islets; Outcomes; Pancreatectomy; Pre-diabetes.

Figure 1.

Islet mass retrieved and transplanted from diabetic, pre-diabetic, and non-diabetic patients. (A) Islet mass expressed in islet IEQ isolated and transplanted in the DM group did not differ significantly from that in the pre-DM and non-DM groups (NS). However, islet mass in the pre-DM group was significantly lower than that in the non-DM group (P=.03)*. (B) Islet mass transplanted per patient body weight in kilograms (IEQ/kg) did not differ significantly between the DM and pre-DM groups. However, it was significantly higher in the non-DM group than both other groups (P<.05). DM = diabetes mellitus, IEQ = islet equivalents, NS = not significant.

Figure 2.

Rate of patients receiving a transplanted islet mass of over 2000IEQ/kg. A similar proportion of patients received a clinically relevant islet mass of over 2000IEQ/kg during the transplantation in the DM and non-DM groups: 60% (3/5) and 83% (15/18) (83.3%) (NS), respectively. Of note, significantly fewer patients received such an islet mass in the pre-DM group (45% [5/11]) as compared to the non-DM group (P=.04). DM = diabetes mellitus, IEQ = islet equivalents, NS = not significant.

Figure 3.

Insulin independence rate during the follow-up. None of the 5 diabetic patients (DM group) became insulin independent. Only 1 out of 8 (12.5%) patients from the pre-DM group was insulin-free at 1-year and later postprocedure. The rate of insulin-independence at 1-year in the non-DM group was 53% and remained in the range of 40% to 60% afterward. DM = diabetes mellitus.

Figure 4.

Metabolic outcome: HbA1c at 1-year follow-up. Nearly 80% of patients from the non-DM group had optimal glucose control with HbA1c<6%. Interestingly, 50% of patients from the DM group and 37% from the pre-DM group had such an outcome. DM = diabetes mellitus.

Figure 5.

Pain required opioids. (A) All patients required opioid-based therapy due to pancreatic pain before TPIAT. The majority of the patients (60%–70%) required opioids on a daily basis in all 3 groups. (B) Pancreatic pain gradually subsided completely, within 1 year in all patients in the DM group, within 2 years in all the non-DM group and by 3 years in the pre-DM group. The percentage of patients requiring prolonged opioid therapy, periodically or daily, during follow-up due to incisional or hernia-related pain (or other medical problems) did not differ statistically between the groups. DM = diabetes mellitus, TPIAT = total pancreatectomy with islet autotransplantation.