Correlation of histopathology, islet yield, and islet graft function after islet autotransplantation in chronic pancreatitis.

OBJECTIVE: The number of islets available (yield) is an important predictor of insulin independence after islet autotransplantation (IAT) done at the time of total pancreatectomy to treat painful chronic pancreatitis. The aim of this study was to correlate histopathologic findings with islet yield and graft function. METHODS: Pancreatic histopathology was examined in 105 adults who underwent pancreatectomy and IAT; postoperative insulin use was known in 53 cases. Histologic degree of fibrosis, acinar atrophy, inflammation, and nesidioblastosis were scored by a surgical pathologist. The correlation of histopathology with islet yield and graft function was evaluated. RESULTS: Patients received a median of 2968 islet equivalents per kilogram. Fibrosis and acinar atrophy correlated negatively with islet yield (P < G 0.001, r =0.67), as did inflammation (P < G 0.001, r =0.43). There was a positive correlation of islet yield (P < G 0.0001, r = 0.64) and a negative correlation of fibrosis (P = 0.006, r = 0.43) and acinar atrophy (P = 0.006, r = 0.42) with islet graft function. CONCLUSION: More severe histopathologic changes were associated with a lower islet yield and lower likelihood of insulin independence. Total pancreatectomy and IAT should not be delayed in patients with painful chronic pancreatitis refractory to medical therapy; otherwise progressive damage to the pancreas may limit islet yield and increase the risk of diabetes.

Correlation of pancreatic histopathologic findings and islet yield in children with chronic pancreatitis undergoing total pancreatectomy and islet autotransplantation.

OBJECTIVES: The probability of insulin independence after intraportal islet autotransplantation (IAT) for chronic pancreatitis (CP) treated by total pancreatectomy (TP) relates to the number of islets isolated from the excised pancreas. Our goal was to correlate the islet yield with the histopathologic findings and the clinical parameters in pediatric (age, <19 years) CP patients undergoing TP-IAT. METHODS: Eighteen pediatric CP patients aged 5 to 18 years (median, 15.6 years) who underwent TP-IAT were studied. Demographics and clinical history came from medical records. Histopathologic specimens from the pancreas were evaluated for presence and severity of fibrosis, acinar cell atrophy, inflammation, and nesidioblastosis by a surgical pathologist blinded to clinical information. RESULTS: Fibrosis and acinar atrophy negatively correlated with islet yield (P = 0.02, r = -0.50), particularly in hereditary CP (P = 0.01). Previous duct drainage surgeries also had a strong negative correlation (P = 0.01). Islet yield was better in younger (preteen) children (P = 0.02, r = -0.61) and in those with pancreatitis of shorter duration (P = 0.04, r = -0.39). CONCLUSIONS: For preserving beta cell mass, it is best to perform TP-IAT early in the course of CP in children, and prior drainage procedures should be avoided to maximize the number of islets available, especially in hereditary disease.

Islet autotransplant outcomes after total pancreatectomy: a contrast to islet allograft outcomes.

INTRODUCTION: Islet allografts are currently associated with a high rate of early insulin independence, but after 1 year insulin-independence rates rapidly decline for unclear reasons. In contrast, as shown here, islet autotransplants (IATs) show durable function and extended insulin-independence rates, despite a lower beta-cell mass. METHODS: IAT function was determined in 173 patients after total pancreatectomy at our center. Islet function was considered full in insulin-independent patients, partial when euglycemic on once-daily long-acting insulin (all tested were C-peptide positive), and failed if on a standard diabetic regimen. Outcomes for autoislet recipients by Kaplan-Meier survival analysis were compared with those of alloislet recipients in the Collaborative Islet Transplant Registry. RESULTS: IAT function (full/partial combined) and insulin independence correlated with islet yield. Overall only 65% functioned within the first year, and only 32% were insulin independent, but of IATs that functioned initially (n=112), 85% remained so 2-years later, in contrast to 66% of allografts (n=262). Of IAT recipients who became insulin independent (n=55), 74% remained so 2-years later versus 45% of initially insulin-independent allograft recipients (n=154). Of IATs that functioned or induced insulin independence, the rates at 5 years were 69% and 47%, respectively. CONCLUSION: 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.

Outcome after pancreatectomy and islet autotransplantation in a pediatric population.

OBJECTIVES: Little is known regarding outcomes after pancreatectomy and islet autotransplantation for chronic pancreatitis in pediatric patients. In this study, we document pain control and metabolic course after this procedure in a pediatric population. MATERIALS AND METHODS: We reviewed medical records for 24 patients 18 years old or younger who underwent pancreatectomy with islet autotransplantation at the University of Minnesota from July 1989 through June 2006. Patients and/or their parents were invited to participate in a follow-up telephone survey. Primary outcome measures were narcotics and insulin use at follow-up. We compared outcomes in patients undergoing surgery as preadolescents (<13 years old) versus adolescents. RESULTS: Follow-up information was available on 18 of 24 patients. All of the patients required narcotics before surgery. Of the 18, only 7 (39%) were still taking narcotics at the time of the survey. At 1 year posttransplant, 78% of patients had islet graft function with full function (insulin independent) in 56% and partial function (once-daily insulin use only) in 22%. By Cox regression analysis, important predictors of insulin independence were islet yield >2000 islet equivalents per kilogram and lack of prior pancreatic surgery (P = 0.011). Preadolescents were less likely to require chronic narcotic therapy at follow-up (P = 0.05) and were more likely to maintain graft function (P = 0.02) compared with adolescents. CONCLUSIONS: Pancreatectomy can relieve pain in pediatric patients with chronic pancreatitis and the majority can withdraw from narcotics. Islet autotransplantation can prevent or reduce the severity of diabetes in about three fourths of patients. Outcome goals were reached in a higher proportion of younger than older children.

The role of total pancreatectomy and islet autotransplantation for chronic pancreatitis.

Total pancreatectomy and islet autotransplantation are done for chronic pancreatitis with intractable pain when other treatment measures have failed, allowing insulin secretory capacity to be preserved, minimizing or preventing diabetes, while at the same time removing the root cause of the pain. Since the first case in 1977, several series have been published. Pain relief is obtained in most patients, and insulin independence preserved long term in about a third, with another third having sufficient beta cell function so that the surgical diabetes is mild. Islet autotransplantation has been done with partial or total pancreatectomy for benign and premalignant conditions. Islet autotransplantation should be used more widely to preserve beta cell mass in major pancreatic resections.

Islet autotransplantation to prevent or minimize diabetes after pancreatectomy.

PURPOSE OF REVIEW: Islet autotransplantation can prevent or minimize diabetes following near or total pancreatectomy for chronic pancreatitis or other lesions. Since the first case nearly 30 years ago, islet autotransplantation has been performed at more than 20 centers. This review summarizes outcomes and factors that correlate with success or failure. The main criteria for success of an islet autotransplantation per se are whether insulin-independence was maintained or insulin-need minimized, but, for those with chronic pancreatitis, as important is the degree of pain reduction, narcotic withdrawal, and quality of life improvement. RECENT FINDINGS: Total pancreatectomy/islet autotransplantation for chronic pancreatitis usually ameliorates pain and improves quality of life. The higher the islet yield, the more likely is the patient to be insulin-independent or metabolically stable. A prior Puestow procedure or distal pancreatectomy, or long-standing disease with severe pancreatic fibrosis, predisposes to poor islet yield. In recipients who require insulin, ß cell function facilitates glycemic control. Islet autotransplantation function for more than a decade has been documented, but more studies are needed to determine durability. SUMMARY: Islet autotransplantation preserves ß cell function after total pancreatectomy. Future studies comparing function of islet autografts and allografts matched for initial ß cell mass may help determine the immunological and nonimmunological factors that influence long-term islet survival.