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BACKGROUND ON PANCREAS HISTOLOGICAL FINDINGS: University of Maryland experience

BACKGROUND ON PANCREAS HISTOLOGICAL FINDINGS: University of Maryland experience. John C. Papadimitriou, M.D.,Ph.D. Professor of Pathology. Experimental models of acute pancreas allograft rejection. SEPTAL INFLAMMATION VENOUS ENDOTHELIITIS AND INFLAMMATION OF DUCTS ACINAR INFLAMMATION

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BACKGROUND ON PANCREAS HISTOLOGICAL FINDINGS: University of Maryland experience

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  1. BACKGROUND ON PANCREAS HISTOLOGICAL FINDINGS: University of Maryland experience John C. Papadimitriou, M.D.,Ph.D. Professor of Pathology

  2. Experimental models of acute pancreas allograft rejection • SEPTAL INFLAMMATION • VENOUS ENDOTHELIITIS AND INFLAMMATION OF DUCTS • ACINAR INFLAMMATION • INFLAMMATION OF ARTERIAL BRANCHES Allen et al: Am J Pathol 1991,138:303 Schulak et al: Surgery 1995,98:330. Steineger et al: Am J Pathol 1986,124:253. Carpenter et al: Transplantation 1989,48:764.

  3. GRADING ACUTE REJECTION 0 No inflammation I Minimal septal inflammation II Venous, ductal, focal acinar inflammation III Multifocal acinar inflammation IV Intimal arteritis/ transmural arteritis V Parenchymal necrosis (Drachenberg et al.: Transplantation 1997;63:1579-86)

  4. Background Histologic grading of acute allograft rejection in pancreas needle biopsy: correlation to serum enzymes, glycemia, and response to immunosuppressive treatment. (Papadimitriou JC et al.:Transplantation. 1998 Dec 27;66(12):1741-5. )

  5. Background • Progressive graft sclerosis/chronic rejection (CR) determines the useful lifespan of technically successful pancreas allografts. • Episodes of acute rejection are suspected to result in accelerated graft sclerosis.

  6. Chronic rejection/graft sclerosis • Histological correlate: Increasing fibrosis • Clinical correlate: Progressive deterioration of glucose metabolism requiring return to insulin dependence (graft loss).

  7. March 2002 April 2002 May 2002

  8. Objective of the current study • To understand better the relationship between histological features of acute rejection and the development of graft sclerosis.

  9. Materials and Methods Comparison of biopsy findings • Pancreas tx functioning >36 months (n=33) • Pancreas tx with histological and clinical chronic rejection leading to graft failure (n=27)

  10. Materials and Methods • Included patients with > 3 months of function (technically succesful) • Excluded • technical complications • pancreatic or abdominal infection at the time of biopsy • lymphoproliferative disorder • recurrence of original disease • lack of biopsy material • All bx were done for allograft dysfunction

  11. Materials and Methods:Biopsy Evaluation • Grading of acute rejection (Grades 0-V) • Mean rejection grade • Individual histological findings • Acinar inflammation (focal vs diffuse) • Venulitis • Ductal inflammation • Eosinophils • Arterial inflammation

  12. Comparison of Groups I and II

  13. RESULTS Mean grade of acute rejection (0-V) All bx with preserved function: 1.61 (± 1.64) All bx with chronic rejection: 2.55 (± .8) p=.0000 Patients with preserved function: 1.32 (± 0.9) Patients with chronic rejection: 2.57 (± .66) p=.0000

  14. FOCAL ACINAR INFLAMMATION DIFFUSE ACINAR INFLAMMATION

  15. Conclusions • Histological findings in bx for graft dysfunction strongly correlate with long-term outcome. • Diffuse acinar inflammation is the most common finding associated with chronic rejection.

  16. Conclusions (Cont….) • Inflammation involving only fibrous septa (sparing acini and arteries) may be responsive to antirejection treatment and/or may not lead to graft sclerosis.

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