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 INFLAMMATION OF ARTERIAL

BRANCHES

Allen et al: Am J Pathol 1991,138:303Schulak et al: Surgery 1995,98:330.Steineger et al: Am J Pathol 1986,124:253.Carpenter et al: Transplantation 1989,48:764.

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)

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. )

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.

Chronic rejection/graft sclerosis

Histological correlate: Increasing fibrosis Clinical correlate: Progressive

deterioration of glucose metabolism requiring return to insulin dependence (graft loss).

March 2002

April 2002

May 2002

Objective of the current study

To understand better the relationship between histological features of acute rejection and the development of graft sclerosis.

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)

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

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

Comparison of Groups I and II

Group I, n=33

(function)

Group II, n=27

(chronic rejection)

Transplant type 8 PAK, 9 PTA, 16 SPK 7 PAK, 7 PTA, 13 SPK (NS)

Transplanted before 1996

33.3 % 37.0 % (NS)

Mean (median) tx life Mean 2736 (±301.5) days

1333 (±1167) days (p=.0000)

Number of biopsies/

Time biopsy

n=71 (2.15/pt)

mean -13 months

n=91 mean 3.37/pt (p=.0027)

18 months - NS

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

RESULTS

Grading of Acute Rejection by group

0

10

20

30

40

50

60

0 (.0002) I (.005) II (NS) III (.0000) IV (.008)

AR Grade

Preserved function

Chronic rejection

FOCAL ACINAR INFLAMMATION DIFFUSE ACINAR INFLAMMATION

Focal vs. Diffuse Acinar Inflammation by group

0

5

10

15

20

25

30

35

40

Focal Acinar Inflammation (NS) Diffuse Acinar Inflammation (.0000)

% o

f b

iop

sie

s

Preserved function

Chronic rejection

SPECIFIC HISTOLOGICAL FEATURES BY GROUP

0

5

10

15

20

25

30

Venulitis (NS) DuctalInflammation

(NS)

Arteritis (.008) Eosinophils (.01)

% o

f b

iop

sie

s

Preserved function

Chronic rejection

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.

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.