1. BANFF SCHEMA FOR GRADING PANCREAS ALLOGRAFT REJECTION
Meeting Summary

2. Pancreas Tx are only performed in selected centers and pancreas biopsies are few in comparison to those of other organs.
Progress has been slow
Immunosuppression has improved
Indications have been re- and re-evaluated
Ongoing need for beta cell replacement

3. Overall the number of whole pancreas tx has stabilized
New pancreas transplant programs continue to be established (explosive growth in some regions)

4. Banff 2007
Pre-meeting discussions were concluded in the formal and “working lunch” sessions.
Consensus agreement
Definitions of the histological lesions
“cell mediated” grading schema
General histopathology guidelines including adequacy, recommendations for reporting, etc

5. Completion of consensus manuscript through group e-mail discussions.

7. Banff 2009 Pancreas Session
Session Chairs:
Edward Kraus
Brian Nankivell
Additional working breakfast the following morning

8. Banff 2009 Pancreas Session
1. Gene expression based categorization of pancreas transplant biopsies
Fu Luan
First attempt to correlate histological rejection with gene expression by using techniques and gene selection that has been used in the kidney
Demonstrated differential expression of a variety of genes that correlated with histological rejection grades and graft outcome.

9. Banff 2009 Pancreas Session
AMR in pancreas allografts
3.Ingeborg Bajema
4.Jose Torrealba
5.Erika Bevilaqua Rangel

10. Banff 2009 Pancreas Session
AMR in pancreas allografts
Ingeborg Bajema: Retrospective experience on C4d IHC. A combination of DSA+ and C4d+ correlate with worse graft outcome.
Jose Torrealba: Summarized their large experience with AMR in pancreas tx /SPK. Pattern of C4d staining.
Erika Bevilaqua Rangel: AMR in a cohort of patients transplanted in San Paulo (Brazil). Largest experience with IF C4d. DSA available on few pts.

11. Banff 2009 Pancreas Session
6. Lois Arend: Controversial lesions in pancreas biopsy grading.
Drug toxicity, acinar inflammation.
Discussed experience with AMR cases and confirmed findings in previous presentations.

12. Proposal for Diagnosis of Acute Antibody Mediated Rejection
Consensus discussion
Importance of defining AMR in the pancreas.
Recommendation to evaluate C4d staining in all biopsies
Both IHC and IF work well: comparison between methods to be performed in the future.
Interacinar staining pattern strongly correlates with AMR (in contrast to other staining patterns).

13. Proposal for Diagnosis of Acute Antibody Mediated Rejection
Focal staining for C4d appears to be important:
Agreement to recommend guidelines for reporting C4d as in the kidney schema.

14. 2007 Proposed Banff Schema

15. 2009 Proposal for Diagnosis of Acute Antibody Mediated Rejection
Remove requirement for “graft dysfunction”
for the pathology diagnosis of acute AMR.

16. Working Proposal for diagnosis of AMR
Acute antibody mediated rejection
1.C4d+
2.Morphologic evidence of chronic tissue injury (margination of inflammatory cells in interacinar capillaries (capillaritis), acinar cell damage, arteritis, etc).
3.DSA/HLA confirmatory testing
Two of 3 criteria necessary for diagnosis

17. Rule out AMR
C4d+ with no tissue injury
?Recommendation to do CD68 stain pending further discussions

18. Chronic Active antibody mediated rejection category remains
Chronic Active antibody mediated rejection category remains. Final wording will be discussed.

19. Acute
AMR
C4d+

20. 2. Erica Bracamonte Preliminary results: Reproducibility of Banff schema for grading of acute pancreas rejection.

21. Reproducibility Study Materials
12 Digital whole slides (Aperio system)
Only one case had C4d stain.

24. Participants Lois Arend Ingeborg Bajema Jan Bruijn Helen Cathro
Billie Fyfe-Kirschner
Lillian Gaber
Julio Goldberg
Danielle Hollanda
Ramesh Nair
Jean Olson
John Papadimitriou
Lorraine Racusen
Karine Renaudin-Autain
Finn P Reinholt
Monica Patricia Revelo
Phillip Ruiz
Edward B Stelow
Jose Torrealba
Megan Troxell
Matthew Turner
Ludek Voska
Matthew Yeh

25. Participants 22, from 19 institutions
Level of experience (self reported)
Novice: <2 yrs experience (n=5)
Competent: 2-5 yrs experience (n=12)
Expert: >5 yrs experience (n=4)

26. Preliminary Results Reproducibility study (E.Bracamonte)
Data still being collected
Rejection vs no rejection Kappa score 0.55

27. Further studies of Banff Schema Reproducibility (E.Bracamonte)
First Phase: Better Define Morphologic Features
Recognition of histological features should be tested.
Wording in schema should be simplified. Lesions grouped in categories for easier understanding.

28. Specific plan:
Images for each of the morphologic features to be posted at the University of Pittsburg website.
The selection of images will be done by “consensus” agreement with the goal of making more uniform the diagnostic interpretation of the cases.

29.  The images and web site will be also used for discussion of Banff scoring categories similar to kidney .
The material will be used for “training” of interested pathologists and clinicians (overlapping with the current didactic plan of the ASTS).

30. Second Phase – Retest Scoring of Cases
By consensus , another set of test cases should be passed around for restudy after the addition discussion of the morphologic features.
 All cases will include a C4d Stain and more cases of humoral rejection will be included.
 The biopsy worksheet will be revised and simplified (? online responses) 

31. “Gold standard” diagnoses to be defined
“Gold standard” diagnoses to be defined. Probably by using a small panel of two or three pathologists who come to a consensus.
All agreement statistics will be re-run based on the second set of testing, and compared to the prior set already performed.

32. Main goal of the study Assess reproducibility of the schema.
Ultimately, improve the Banff schema by decreasing complexity and increasing applicability for the average practicing pathologist.

33. Many thanks to the Banff Conference Organizing committee that provided excellent support for the Pancreas sessions.