title: Long-term outcomes of total pancreatectomy and islet auto transplantation for hereditary/genetic pancreatitis.
abstract: BACKGROUND
  Chronic pancreatitis is a debilitating disease resulting from many causes. The subset with hereditary/genetic pancreatitis (HGP) not only has chronic pain, but also an increased risk for pancreatic cancer. Long-term outcomes of total pancreatectomy (TP) and islet autogeneic transplantation (IAT) for chronic pancreatitis due to HGP are not clear.
  
  
  METHODS
  We reviewed a prospectively maintained database of 484 TP-IATs from 1977 to 2012 at a single center. The outcomes (eg, pain relief, narcotic use, β-cell function, health-related quality of life measures) of patients who received TP-IAT for HGP (protease trypsin 1, n = 38; serine protease inhibitor Kazal type 1, n = 9; cystic fibrosis transmembrane conductance regulator, n = 14; and familial, n = 19) were evaluated and compared with those with non-hereditary/nongenetic causes.
  
  
  RESULTS
  All 80 patients with HGP were narcotic dependent and failed endoscopic management or direct pancreatic surgery. Post TP-IAT, 90% of the patients were pancreatitis pain free with sustained pain relief; >65% had partial or full β-cell function. Compared with nonhereditary causes, HGP patients were younger (22 years old vs 38 years old; p ≤ 0.001), had pancreatitis pain of longer duration (11.6 ± 1.1 years vs 9.0 ± 0.4 years; p = 0.016), had a higher pancreas fibrosis score (7 ± 0.2 vs 4.8 ± 0.1; p ≤ 0.001), and trended toward lower islet yield (3,435 ± 361 islet cell equivalent vs 3,850 ± 128 islet cell equivalent; p = 0.28). Using multivariate logistic regression, patients with non-HGP causes (p = 0.019); lower severity of pancreas fibrosis (p < 0.001); shorter duration of years with pancreatitis (p = 0.008); and higher transplant islet cell equivalent per kilogram body weight (p ≤ 0.001) were more likely to achieve insulin independence (p < 0.001). There was a significant improvement in health-related quality of life from baseline by RAND 36-Item Short Form Health Survey and in physical and mental component health-related quality of life scores (p < 0.001). None of the patients in the entire cohort had cancer of pancreatic origin in the liver or elsewhere develop during 2,936 person-years of follow-up.
  
  
  CONCLUSIONS
  Total pancreatectomy and IAT in patients with chronic pancreatitis due to HGP cause provide long-term pain relief (90%) and preservation of β-cell function. Patients with chronic painful pancreatitis due to HGP with a high lifetime risk of pancreatic cancer should be considered earlier for TP-IAT before pancreatic inflammation results in a higher degree of pancreatic fibrosis and islet cell function loss.
authors.affiliation: Department of Surgery, University of Minnesota School of Medicine, Minneapolis, MN; Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, MN. Electronic address: chinni@umn.edu.
authors.forename: Srinath
authors.initials: S
authors.lastname: Chinnakotla
authors.affiliation: Department of Surgery, University of Minnesota School of Medicine, Minneapolis, MN.
authors.forename: David M
authors.initials: DM
authors.lastname: Radosevich
authors.affiliation: Department of Surgery, University of Minnesota School of Medicine, Minneapolis, MN.
authors.forename: Ty B
authors.initials: TB
authors.lastname: Dunn
authors.affiliation: Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, MN; Schulze Diabetes Institute, University of Minnesota School of Medicine, Minneapolis, MN.
authors.forename: Melena D
authors.initials: MD
authors.lastname: Bellin
authors.affiliation: Department of Medicine, University of Minnesota School of Medicine, Minneapolis, MN.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Freeman
authors.affiliation: Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, MN.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Schwarzenberg
authors.affiliation: Department of Surgery, University of Minnesota School of Medicine, Minneapolis, MN.
authors.forename: A N
authors.initials: AN
authors.lastname: Balamurugan
authors.affiliation: Schulze Diabetes Institute, University of Minnesota School of Medicine, Minneapolis, MN.
authors.forename: Josh
authors.initials: J
authors.lastname: Wilhelm
authors.affiliation: Department of Surgery, University of Minnesota School of Medicine, Minneapolis, MN.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bland
authors.affiliation: Department of Surgery, University of Minnesota School of Medicine, Minneapolis, MN.
authors.forename: Selwyn M
authors.initials: SM
authors.lastname: Vickers
authors.affiliation: Department of Surgery, University of Minnesota School of Medicine, Minneapolis, MN.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Beilman
authors.affiliation: Department of Surgery, University of Minnesota School of Medicine, Minneapolis, MN; Schulze Diabetes Institute, University of Minnesota School of Medicine, Minneapolis, MN.
authors.forename: David E R
authors.initials: DE
authors.lastname: Sutherland
authors.affiliation: Department of Surgery, University of Minnesota School of Medicine, Minneapolis, MN.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Pruett
mesh_terms: D000328:Adult; D059350:Chronic Pain / Q000209:etiology; D016208:Databases, Factual; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016381:Islets of Langerhans Transplantation / Q000379:methods; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D010180:Pancreatectomy / Q000379:methods; D050500:Pancreatitis, Chronic / Q000150:complications / Q000235:genetics / Q000601:surgery*; D011788:Quality of Life; D014182:Transplantation, Autologous; D016896:Treatment Outcome