Introduction: Eighth Banff Conference on Allograft Pathology Edmonton, AB

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Introduction Eighth Banff Conference on
Allograft Pathology - Edmonton, AB

• Kim Solez, M.D. and Lorraine C. Racusen

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Making Banff into a verb! Banff it 2005 most
important meeting yet.

• Kicking the CAN - Coming to grips
  with the morphologic counterparts of
  chronic graft failure - getting
  away from the
  nonspecificity of CAN.
• Banff on a chip - The emerging role of gene
  chip microarray results.
  
• Rules for the masses - Revisiting
  clinical practice guidelines, C4d,
  new lesion scores.

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Edmonton, where the Banff Meetings have been
organized from since 1991!

• Largest metropolitan center between Toronto and
  Vancouver, and Canada's fifth-largest city.
• 2,263.7 hours of sunlight in the average year -
  more than any other major city in Canada.
• Average of 17 hours of daylight per day in June.
• Edmontons River Valley is the largest stretch
  of urban parkland in North America with 7400
  hectares this vast parkland is approximately 12
  times larger than Central Park in New York City.

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The Banff Schema was first developed by a group
of pathologists, nephrologists, and transplant
surgeons at a meeting in Banff Canada August
2-4, 1991.
The Banff Schema was first developed by a group
of pathologists, nephrologists, and transplant
surgeons at a meeting in Banff Canada August
2-4, 1991.
It has continued to evolve through meetings
every two years and has become the worldwide
standard for interpretation of transplant
biopsies.
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Banff Classification Milestones

• 1991 First Conference
• 1993 First Kidney International publication
• 1995 Integration with CADI
• 1997 Integration with CCTT classification
• 1999 Second KI paper. Clinical practice
  guidelines. Implantation biopsies, microwave.
• 2001 Classification of antibody-mediated
  rejection
• Regulatory agencies participating
• 2003 Genomics focus, ptc cell accumulation
  scoring, macrophages.

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Banff Classification - Subjects in Edmonton
meeting July 15-21, 2005

• Updates on Schemas for Diagnosis of Rejection
• Transcriptome Gene Chip Diagnoses
• Emerging Technologies
• Antibody-mediated rejection/C4d
• Special Populations
• Revisiting Clinical Practice Guidelines
• Histologic hallmarks of sclerosing rejection
  Strategies to establish diagnoses other than CAN.
  
• Heart, lung, pancreas, and liver sessions in
  addition.

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Much important work being presented in poster
session!

• Poster session Monday, July 18th
• 530 - 730
• Poster Viewing Session
• Wine Cheese Event
• Posters can be put up during the breaks or 7-8 AM
  tomorrow or Monday

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More than half of transplant biopsies in 2005 do
not show rejection!

• Calcineurin inhibitor toxicity most common
  entity.
• Scoring/classification system must deal with all
  entities, not just rejection!
• New onset hyaline arteriolar thickening (ah) a
  sign of calcineurin inhibitor toxicity.

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Non- Circumferential vs. Circumferential
hyalinosis
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Quantitative Criteria for Arteriolar Hyaline
Thickening Current scoring.

• 0 No PAS-positive hyaline thickening
• 1 Mild-to-moderate PAS-positive hyaline
  thickening in at least one arteriole
• 2 Moderate-to-severe PAS-positive hyaline
  thickening in more than one arteriole
• 3 Severe PAS-positive hyaline thickening in
  many arterioles

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Quantitative Criteria for Arteriolar Hyaline
Thickening Proposed new scoring - Mihatsch

• 0 No PAS-positive hyaline thickening
• 1 PAS-positive hyaline thickening present in
  only one arteriole, no circular involvement
• 2 PAS-positive hyaline thickening present in
  more than one arteriole, but no circular
  involvement
• 3 PAS-positive hyaline thickening with circular
  involvement, independent of the number of
  arterioles involved

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Quantitative Criteria for Arteriolar Hyaline
Thickening Study of Sis et al. (Banff 05)

• The severity of ah scored by both criteria, was
  significantly correlated with serum creatinine at
  biopsy (plt0.05). Using Banff criteria, the mean
  rate of pairwise agreement was 57.8 with an
  overall kappa value of 0.39. With the newly
  proposed criteria, the mean rate of pairwise
  agreement was 70 and the overall kappa value was
  0.51. The mean interslide variation rates using
  Banff criteria and the new criterion were 30.7
  and 36.7, respectively.
• Conclusion While Banff and the recently proposed
  criteria for ah scoring resulted in fair to
  moderate interobserver agreement, the new
  criterion seems to be more objective and results
  in better interobserver reproducibility. There is
  a substantial variation in the distribution and
  severity of arteriolar lesions in an individual
  biopsy, therefore, evaluation of more than one
  section is crucial to determine the severity of
  arteriolar damage more accurately.

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Intimal elastosis found to correlated with
antibody mediated rejection! Sis, Hunter et al.

• Intimal elastosis - the deposition of elastic
  fibers in intima - significant association with
  class II antibodies in our study may suggest that
  antibody mediated injury could be one of the
  mechanisms leading to arterial injury and
  subsequent formation of neo-intima rich in
  elastic fibers.

173 posttransplant biopsies from 127 patients
with available anti-HLA Ab analysis Jan. 2002 to
March 2004
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Moving from semiquantitative scoring to
quantitative scoring by morphometry!

• Despite all the praise we have received for the
  Banff scoring system, a truly quantitative system
  would obviously be better if practical, so we are
  only half way there!
• Howie AJ The Problems with BANFF,
  Transplantation 731383, 2002 other approaches
  should be tried such as morphometry
  
  
• Financially and technically impractical for most
  centers right now, but possibly doable in the
  near future.
• Banff classification is based on semiquantitative
  assessment. Quantitative assessment would
  ultimately be better, just as the molecular
  biology/genomics alternative would be. But they
  must be made practical!

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New Developments in Morphometry - Birk et al.
(2005 Banff meeting)

• Used hue saturation intensity (HSI) image
  analysis software to quantify renal allograft
  interstitial fibrosis in pediatric protocol
  biopsies, significant correlation with Banff ci
  score and with decreased GFR and other clinical
  parameters.

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Clinical practice guidelines, new lesion scoring
etc.

• Revisiting 1999 guidelines.
• Methods review for C4d as a marker for antibody
  mediated rejection.
• Peritubular capillary cell accumulation scoring.

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Polys in peritubular capillaries in
antibody-mediated rejection.
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1999 - Agreed upon clinical practice guidelines
that need buy-in generally

• Implantation biopsies
• Rapid paraffin (microwave) processing for rapid
  reading rather than frozen sections
• Routine (protocol) biopsies
• HE, PAS (/o silver), and trichrome or Sirius
  red stains

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Schedule of the Meeting
Saturday, 16 July 2005 800 - 820 Welcome,
Opening Remarks - Kim Solez and Lorraine
Racusen Plenary session 820 - 920 Keynote
Address  Future directions in organ replacement.
- Jeffrey Platt Transcriptome Gene
Chip Moderator  Philip F. Halloran 920-1150 12
00 - 100Lunch (Wedgwood Room)Lunch (Empire
Terrace) PMEmpire Ballroom  100 -
130Experimental heart transplantation.  - Thomas
Mueller Emerging Technologies Moderator  Philip
F. Halloran 130-430