*Purpose: Total pancreatectomy with autologous islet transplantation (TPIAT) is a promising procedure for alleviating pain and maintaining glucose homeostasis in chronic pancreatitis (CP) patients. However, the progression of fibrosis in the pancreas and its degeneration affects the quality and yield of isolated islets and overall outcome of islet transplantation. In this study, we compared histological pancreatic sections from TPIAT patients from multiple etiological categories of CP to determine effects of fibrosis on TPIAT outcomes.

*Methods: A total of 150 patients undergoing TPIAT at our center were analyzed for effects of etiology on pancreatic fibrosis, islet isolation yield and quality, and post transplant outcomes. Collagen content and fibrosis in histological pancreatic sections were assessed and scored by H&E and picro-sirius red staining. Extracellular matrix proteins and markers of tissue repair including collagen VI, alpha laminin 5, desmin, P-Laminin, and perlecan were analyzed by immunohistochemistry. Islet transplant outcomes were measured by blood glucose and C-peptide levels.

*Results: Picro-sirius red staining of collagen strongly correlated with progression of fibrosis assessed in histological pancreatic sections. Among the major etiologies of CP at our center, patients with hereditary CP genes including PRSS1, CFTR and SPINK1 and excessive consumption of alcohol showed highest fibrosis by Picro-sirius red and H&E staining. Islet yields (IEQ/g) were significantly lower in the alcoholic (3153±3554, n=12) and hereditary (3303±2090, n=16) patients 30 years of age and over compared to psuedocyst (5952±3572, n=5), pancreatic divisum (5692±3291, n=17), Oddi dysfunction (5533±2798, n=10), and idiopathic (5108± 2624, n=61), and autoimmune (4424±2060, n=7) patients. Notably, hereditary patients undergoing TPAIT prior to the age of 30 had improved islet yields (4580±2787, n=14). Lower islet yield and islet doses for hereditary and alcoholic patients over 30 resulted in poor transplant outcomes. CP patients having advanced fibrosis had elevated blood glucose and progressive islet dysfunction at 6-month follow up.

*Conclusions: Picro-sirius red staining of clinical pancreas sections from CP patients can be used to assess fibrosis and predict islet yield and post-transplant function in TPIAT patients. Alcohol consumption and hereditary CP genes in patients 30 years and older were strong factors associated with pancreatic fibrosis. Early intervention of CP, especially in patients with hereditary CP genes, resulted in improved transplant outcomes.

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