title: Proposed thresholds for pancreatic tissue volume for safe intraportal islet autotransplantation after total pancreatectomy.
abstract: The simple question of how much tissue volume (TV) is really safe to infuse in total pancreatectomy-islet autotransplantation (TP-IAT) for chronic pancreatitis (CP) precipitated this analysis. We examined a large cohort of CP patients (n = 233) to determine major risk factors for elevated portal pressure (PP) during islet infusion, using bivariate and multivariate regression modeling. Rates of bleeding requiring operative intervention and portal venous thrombosis (PVT) were evaluated. The total TV per kilogram body weight infused intraportally was the best independent predictor of change in PP (ΔPP) (p < 0.0001; R(2) = 0.566). Rates of bleeding and PVT were 7.73% and 3.43%, respectively. Both TV/kg and ΔPP are associated with increased complication rates, although ΔPP appears to be more directly relevant. Receiver operating characteristic analysis identified an increased risk of PVT above a suggested cut-point of 26 cmH2O (area under the curve = 0.759), which was also dependent on age. This ΔPP threshold was more likely to be exceeded in cases where the total TV was >0.25 cm(3)/kg. Based on this analysis, we have recommended targeting a TV of <0.25 cm(3)/kg during islet manufacturing and to halt intraportal infusion, at least temporarily, if the ΔPP exceeds 25 cmH2O. These models can be used to guide islet manufacturing and clinical decision making to minimize risks in TP-IAT recipients.
authors.affiliation: Department of Surgery, Schulze Diabetes Institute, University of Minnesota, St. Paul, MN.
authors.forename: J J
authors.initials: JJ
authors.lastname: Wilhelm
authors.forename: M D
authors.initials: MD
authors.lastname: Bellin
authors.forename: T B
authors.initials: TB
authors.lastname: Dunn
authors.forename: A N
authors.initials: AN
authors.lastname: Balamurugan
authors.forename: T L
authors.initials: TL
authors.lastname: Pruett
authors.forename: D M
authors.initials: DM
authors.lastname: Radosevich
authors.forename: S
authors.initials: S
authors.lastname: Chinnakotla
authors.forename: S J
authors.initials: SJ
authors.lastname: Schwarzenberg
authors.forename: M L
authors.initials: ML
authors.lastname: Freeman
authors.forename: B J
authors.initials: BJ
authors.lastname: Hering
authors.forename: D E R
authors.initials: DE
authors.lastname: Sutherland
authors.forename: G J
authors.initials: GJ
authors.lastname: Beilman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010179:Pancreas / Q000601:surgery*; D010180:Pancreatectomy / Q000379:methods*; D010195:Pancreatitis; D050500:Pancreatitis, Chronic / Q000628:therapy*; D011169:Portal Vein / Q000473:pathology; D012372:ROC Curve; D012307:Risk Factors; D013927:Thrombosis; D016896:Treatment Outcome; D055815:Young Adult
keywords: Bleeding; chronic pancreatitis; intraportal infusion; islet autotransplantation; portal hypertension; portal vein thrombosis; postoperative complications