grading of rejection in pancreas allografts are changes needed? cinthia b. drachenberg, m.d....
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GRADING OF REJECTION IN PANCREAS ALLOGRAFTS Are changes needed?
Cinthia B. Drachenberg, M.D.University of Maryland School of
MedicineBaltimore MD
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PANCREAS TRANSPLANTATIONBACKGROUND
Insulin dependent diabetics (low C-peptide).
13,000 pancreas transplants (1966-99).
1200 in the USA in 1998.
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PANCREAS TRANSPLANTATIONBACKGROUND
1y patient survival 95%
1y pancreas graft function 85%
1y kidney graft function (SPK) 91%
Gruessner and Sutherland in: Clinical Transplants 1999, Cecka and Terasaki Eds. UCLA Immunogenetics Center, Los Angeles CA.
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PANCREAS TX NEEDLE BX BACKGROUND
10 years since Allen et al.
described the percutaneous
biopsy technique
(Transplantation 1991;51:1213).
> 550 done at the Univ. of MD Complications 2-3%.
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PANCREAS TX NEEDLE BX:INDICATIONS
INCREASE IN SERUM AMYLASE/ LIPASE
HYPERGLYCEMIA UNEXPLAINED FEVER
(DECREASE IN URINARY AMYLASE)
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PANCREAS TX NEEDLE BX BACKGROUND
Minimum tissue amount adequate for diagnosis in a needle biopsy:
Two lobules with associated septal tissue (arteries,veins, ducts).
H&E stained sections x3 Unstained slides
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GRADING: ACUTE REJECTION Acute rejection starts in the septal
area with venous endotheliitis. Vessels, acini and ducts are typically involved.
(Carpenter et al. Sequential histopathologic changes in pancreaticoduodenal allograft rejection in dogs. Transplantation 1989; 48:764)
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GRADING: ACUTE REJECTION
0 No inflammationI Minimal septal inflammationII Venous endotheliitisIII Acinar inflammationIV Arterial endotheliitisV Transmural arteritis
Drachenberg et al.: Transplantation 1997;63:1579.
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GRADING OF REJECTION IN PANCREAS ALLOGRAFTS
Are changes needed?
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Are changes needed? Grade I is non-specific with equal
significance as grade 0.
Simplification of the 5 grade system is desirable.
The findings in pancreas rejection appear to be analogous to rejection Types I, II and III in the kidney.
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PROPOSED GRADING SCHEME
0 No inflammation No rejection
I Minimal septal infl.
II Venous endotheliitis Type IAIII Acinar inflammation Type IB
IV Arterial endotheliitis Type II
V Transmural arteritis Type III
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Correlation with response to treatment: 212 bx, 100 pt
TYPE # Treated CS CS/AL
0 90 42 39/13 (33%) 4/1(25%)
I A 51 47 34 (94%) 13 (85%) B 48 48 10 (80%) 38 (74%)
II A 15 14 2 (0%) 12 (78%)
III 8 8 - 8 (12.5%)
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PANCREAS NEEDLE BIOPSIESDifferential Diagnosis Acute rejection Hyperacute rejection Pancreatitis – peripancreatitis Ischemia - thrombosis Viral infections (CMV, EBV-PTLD) Drug toxicity Recurrence of autoimmune disease Chronic rejection
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GRADING OF CHRONIC REJECTION IN NEEDLE BIOPSIES
We had previously proposed a 5 point histological grading scheme for the diagnosis of CR in pancreas transplant needle biopsies.
(Papadimitriou et al.Trans. Pro. 1999, 31,614)
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GRADING OF CHRONIC REJECTION IN NEEDLE BIOPSIES
PROGRESSIVE FIBROSIS.
PROPORTIONAL ACINAR ATROPHY
TRANSPLANT ARTERIOPATHY*
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UPDATED CR GRADING SCHEME CR 0: No fibrosis CR I: Mild, Septal fibrosis in <30% of
core surface. CR II: Moderate, Fibrosis in 30-60% of
core surface. CR III: Severe, Fibrosis in >60% of core
surface.
Acinar atrophy is proportional to fibrosis.Transplant arteriopathy depending on sample.
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UPDATED CR SCHEME:CLINICAL CORRELATION
The average time from Bx to graft failure per grade:
CR 0: 41 months CRI: 22.3 months CII: 10.8 months CIII: 1.2 m (p=.0001).
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UPDATED CR SCHEME:REPRODUCIBILITY
130 biopsies (Bx) from 36 randomly selected patients were analyzed blindly by 3 pathologists
CR 0: k=.94 (p.0001) CRI: k=.79 (p.0001) CII: k=.85 (p.0001) CIII: k=.94 (p.0001)
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UPDATED CR GRADING SCHEME
The proposed scheme correlates well with graft outcome and predicts to a large extent the remaining time of graft function.
The system is based on easily reproducible criteria.
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