Cinthia Drachenberg Pancreas Summary Banff 2013 Meeting in Brazil

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PANCREAS ALLOGRAFTS SESSION: SUMMARY

• Jon Odorico

Pancreatic AMR – Clinicopathological correlations and experience at Wisconsin-Madison.

Study Design

• Single center, retrospective study of “for-cause” pancreas

allograft biopsies• 94 Bx from 49 patients

• 162 Pancreas Transplants 2006-09 All biopsies had C4d staining – IHC on paraffin sections• Majority (79/94) of bx had DSA data – Luminex SAB

assay

Niederhaus et al. AJT, in press

Summary Acute AMR of the Pancreas Transplant

• Acute AMR Occurs in ~10% of patients in the first year

• Risk Factors: Solitary pancreas transplant, Non-primary SPK transplant, Donor/recipient race mismatch, Female recipient

• Patients having AMR did not have worse graft survival than patients having AMR/ACR or ACR, but do have worse outcomes than patients having no rejection

• DSA+C4d- rejection is uncommon but does occur, C4d+DSA- rejection occurs; DSA alone is not diagnostic Niederhaus et al. AJT in press

• Surya Seshan

Summary and Conclusions• Routine C4d staining on all pancreas allograft

biopsies is the current practice.• C4d staining along with detectable DSA remain

the best method to diagnose AbMR in pancreas transplants.

• Typical morphologic findings may not be apparent in early or late AbMR cases.

• Further studies to examine all aspects of C4d staining and its relationship to DSA and morphological findings in the diagnosis of AbMR is needed.

• Further develop and define criteria for chronic (active) AbMR.

• Hanneke de Kort

Banff 2013 9

1. Biopsy data: Leiden + Maryland

de Kort et al, 2010 AJT

Banff 2013 10

2. Tq data: Leiden

26 2 d not tested 1 0 0 1 0 0 0 0 0 0 n

27 3 f class II 1 0 0 1 0 0 0 0 0 0 n28 3 f class II 1 1 1 1 0 1 3 1 1 0 d29 3 f class I&II 1 - 0 2 1 1 3 2 1 0 f30 3 d class II 1 1 0 2 1 1 3 2 1 0 n/a31 3 d class I&II 1 - 0 0 0 1 3 2 0 0 n/a32 3 d class II 1 0 1 1 0 1 0 0 1 0 d33 3 d class I&II 0 - 0 0 0 1 3 2 1 0 n

26 2 d not tested 1 0 0 1 0 0 0 0 0 0 n


26 2 d not tested 1 0 0 1 0 0 0 0 0 0 n


26 2 d not tested 1 0 0 1 0 0 0 0 0 0 n


18 1 n not tested 0 0 0 0 0 0 0 0 0 0 n

19 2 n class II 1 1 0 0 0 1 3 1 1 0 n/a20 2 f n 0 0 0 0 0 0 0 2 0 0 n21 2 f n 0 0 0 1 0 1 0 2 0 1 n22 2 d n 1 1 1 1 1 0 2 2 0 0 n/a23 2 d n 0 0 1 0 0 0 0 2 0 0 n24 2 d n 1 0 1 0 0 1 3 0 0 0 n/a25 2 f not tested 1 1 0 0 0 0 1 0 0 1 f26 2 d not tested 1 0 0 1 0 0 0 0 0 0 n

18 1 n not tested 0 0 0 0 0 0 0 0 0 0 n


18 1 n not tested 0 0 0 0 0 0 0 0 0 0 n


18 1 n not tested 0 0 0 0 0 0 0 0 0 0 n


1 1 n n 0 0 0 0 0 0 1 2 - 0 n/a2 1 n n 0 1 0 0 0 0 0 2 0 3 n3 1 n n 0 0 0 0 0 0 0 0 0 0 n4 1 n n 0 0 0 0 0 0 0 0 0 0 f5 1 n n 1 1 1 0 0 0 2 2 0 0 n6 1 n n 1 1 0 1 0 0 3 1 1 0 n7 1 n n 1 - 1 1 0 0 2 0 1 0 n8 1 n n 0 0 0 0 0 0 0 0 0 0 n/a9 1 n n 1 - 1 0 0 0 3 2 1 0 n10 1 n n 0 0 0 1 0 0 0 2 0 0 f11 1 n n 1 1 1 2 0 1 3 2 0 0 n12 1 n n 1 - 1 0 0 0 1 0 0 0 n/a13 1 n n 0 0 1 0 0 0 0 0 0 0 n14 1 n n 1 1 1 0 0 0 1 0 0 0 n/a15 1 n not tested 1 1 0 0 0 0 2 0 0 0 n/a16 1 n not tested 0 0 0 0 0 0 0 0 0 0 n17 1 n not tested 0 0 1 0 0 0 0 0 0 0 f18 1 n not tested 0 0 0 0 0 0 0 0 0 0 n




AMR negative

Suspicious for AMR

Acute AMR

Banff 2013 11

3. Data: London

• All 17 Tq; DSA and C4d negative

• 58 bx; – 8 Bx had no arteries sampled– Includes PAK and PTA

Banff 2013 12

Conclusion

Consistency with kidney so far

For pancreas allografts intimal arteritis can be indicative of ACMR as well as AMR, regardless of the severity

Immunophenotypical studies on pancreas tx inflammation

Erika Rangel (15 bx, CD68)

John Papadimitriou (46 bx, CD3,CD20,CD68)

Discussion (Erika Rangel)

Macrophage infiltration in pancreas graft:

Occurs in both acute AMR and TCMR

Is associated with the severity of the TCMR

Has negative impact on pancreas graft survival

Does not occur in significant numbers in the later

fibrosing stages

Conclusions (John Papadimitriou)

CD3 increase proportionally with grades of ACMR, AMR and stage.

CD20 increase proportionally with ACMR and AMR and stage.

CD68 increase proportionally with ACMR and AMR, but not stage.

CD3 CD3

CD20 CD20

ACMR I-IIStage I-II

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Diagnosis of rejection in grafted duodenal cuff

Determine if a biopsy of the grafted duodenal cuff can be a surrogate for a pancreas biopsy

Erik Larsson and team – Ongoing prospective studies

Uppsala University, Sweden

•Approximately 200 samples in 50 patients

•Have used these biopsies for clinical monitoring and guidance of therapeutic decisions

•Excellent graft outcomes

Danniele Holanda – Pilot retrospective studies on archival material of 21 pancreas samples incidentally containing duodenal tissue, to evaluate the degree of concordance of pathological findings in each pair.

There was >70% full concordance in the diagnosis and grade of rejection.

The rest of the sampled were discordant but the disagreement was of no more than 1 grade (i.e. indeterminate vs grade 1)

Myriam Leon Fradejas (Malaga, Spain)

Graft failure due to deposition of islet amyloid

Under recognition of Islet processes

• The Banff pancreas group started working on a set of recommendations for a diagnostic algorithm of late hyperglycemia in order to aid in the identification of islet pathology: recurrent autoimmune DM and islet amyloidosis.

• Topic of extensive discussions on 2011 Banff meeting.

Issues with diagnostic criteria and grading schema

• “capillaritis” • Vascular lesions• etc

• Hanneke de Kort and Candice Roufosse have made a preliminary analysis of the most important issues that need attention and this will be the basis to proceed with group discussions.

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Good bye Comandatuba…

Cinthia Drachenberg Pancreas Summary Banff 2013 Meeting in Brazil

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