Introduction: Eighth Banff Introduction: Eighth Banff Conference on Allograft Conference on Allograft

Pathology - Edmonton, AB Pathology - Edmonton, AB

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

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

““Kicking the CAN” - Coming to grips Kicking the CAN” - Coming to grips with the morphologic counterparts of with the morphologic counterparts of chronic graft failure - getting away chronic graft failure - getting away from the nonspecificity of “CAN”.from the nonspecificity of “CAN”.

““Banff on a chip” - The emerging role of gene chip Banff on a chip” - The emerging role of gene chip microarray results. microarray results.

““Rules for the masses” - Revisiting Rules for the masses” - Revisiting clinical practice guidelines, C4d, clinical practice guidelines, C4d, new lesion scores.new lesion scores.

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

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

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

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The Banff Schema was first developed by a The Banff Schema was first developed by a group of pathologists, nephrologists, and group of pathologists, nephrologists, and transplant surgeons at a meeting in Banff Canada transplant surgeons at a meeting in Banff Canada August 2-4, 1991.August 2-4, 1991.

The Banff Schema was first developed by a The Banff Schema was first developed by a group of pathologists, nephrologists, and group of pathologists, nephrologists, and transplant surgeons at a meeting in Banff Canada transplant surgeons at a meeting in Banff Canada August 2-4, 1991.August 2-4, 1991.

The Banff Schema was first developed by a The Banff Schema was first developed by a group of pathologists, nephrologists, and group of pathologists, nephrologists, and transplant surgeons at a meeting in Banff Canada transplant surgeons at a meeting in Banff Canada August 2-4, 1991.August 2-4, 1991.

The Banff Schema was first developed by a The Banff Schema was first developed by a group of pathologists, nephrologists, and group of pathologists, nephrologists, and transplant surgeons at a meeting in Banff Canada transplant surgeons at a meeting in Banff Canada August 2-4, 1991.August 2-4, 1991.

It has continued to evolve through It has continued to evolve through meetings every two years and has meetings every two years and has become the worldwide standard for become the worldwide standard for interpretation of transplant biopsies.interpretation of transplant biopsies.

It has continued to evolve through It has continued to evolve through meetings every two years and has meetings every two years and has become the worldwide standard for become the worldwide standard for interpretation of transplant biopsies.interpretation of transplant biopsies.

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Banff Classification: Milestones Banff Classification: Milestones

1991 First Conference1991 First Conference

1993 First Kidney International publication1993 First Kidney International publication

1995 Integration with CADI 1995 Integration with CADI

1997 Integration with CCTT classification1997 Integration with CCTT classification

1999 Second KI paper. Clinical practice guidelines. 1999 Second KI paper. Clinical practice guidelines. Implantation biopsies, microwave.Implantation biopsies, microwave.

2001 Classification of antibody-mediated rejection2001 Classification of antibody-mediated rejection

Regulatory agencies participatingRegulatory agencies participating

2003 Genomics focus, ptc cell accumulation scoring, 2003 Genomics focus, ptc cell accumulation scoring, macrophages.macrophages.

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Banff Classification - Subjects in Banff Classification - Subjects in Edmonton meeting July 15-21, 2005Edmonton meeting July 15-21, 2005 Updates on Schemas for Diagnosis of RejectionUpdates on Schemas for Diagnosis of Rejection

Transcriptome Gene Chip DiagnosesTranscriptome Gene Chip Diagnoses

Emerging TechnologiesEmerging Technologies

Antibody-mediated rejection/C4d Antibody-mediated rejection/C4d

Special PopulationsSpecial Populations

Revisiting Clinical Practice GuidelinesRevisiting Clinical Practice Guidelines

Histologic hallmarks of sclerosing rejection: Histologic hallmarks of sclerosing rejection: Strategies to establish diagnoses other than CAN. Strategies to establish diagnoses other than CAN.

Heart, lung, pancreas, and liver sessions in addition.Heart, lung, pancreas, and liver sessions in addition.

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Much important work being Much important work being presented in poster session!presented in poster session!

Poster session Monday, July 18thPoster session Monday, July 18th

5:30 - 7:305:30 - 7:30

Poster Viewing SessionPoster Viewing Session

Wine & Cheese EventWine & Cheese Event

Posters can be put up during the breaks or 7-Posters can be put up during the breaks or 7-8 AM tomorrow or Monday8 AM tomorrow or Monday

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

Calcineurin inhibitor toxicity most common Calcineurin inhibitor toxicity most common entity. entity.

Scoring/classification system must deal with Scoring/classification system must deal with all entities, not just rejection!all entities, not just rejection!

New onset hyaline arteriolar thickening (ah) a New onset hyaline arteriolar thickening (ah) a sign of calcineurin inhibitor toxicity.sign of calcineurin inhibitor toxicity.

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Non- Circumferential vs. Circumferential hyalinosisNon- Circumferential vs. Circumferential hyalinosisNon- Circumferential vs. Circumferential hyalinosisNon- Circumferential vs. Circumferential hyalinosis

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Quantitative Criteria for Arteriolar Hyaline Quantitative Criteria for Arteriolar Hyaline Thickening – Current scoring.Thickening – Current scoring.

0 = No PAS-positive hyaline thickening0 = No PAS-positive hyaline thickening

1 = Mild-to-moderate PAS-positive hyaline thickening in 1 = Mild-to-moderate PAS-positive hyaline thickening in at least one arterioleat least one arteriole

2 = Moderate-to-severe PAS-positive hyaline thickening 2 = Moderate-to-severe PAS-positive hyaline thickening in more than one arteriolein more than one arteriole

3 = Severe PAS-positive hyaline thickening in many 3 = Severe PAS-positive hyaline thickening in many arteriolesarterioles

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Quantitative Criteria for Arteriolar Hyaline Quantitative Criteria for Arteriolar Hyaline Thickening – Proposed new scoring - MihatschThickening – Proposed new scoring - Mihatsch

0 = No PAS-positive hyaline thickening0 = No PAS-positive hyaline thickening

1 = PAS-positive hyaline thickening1 = PAS-positive hyaline thickening present in only one present in only one arteriole, no circular involvement arteriole, no circular involvement

2 = PAS-positive hyaline thickening 2 = PAS-positive hyaline thickening present in more present in more than one arteriole, but no circular involvementthan one arteriole, but no circular involvement

3 = PAS-positive hyaline thickening 3 = PAS-positive hyaline thickening with circular with circular involvement, independent of the number of arterioles involvement, independent of the number of arterioles involved involved

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

The severity of ah scored by both criteria, was significantly correlated The severity of ah scored by both criteria, was significantly correlated with serum creatinine at biopsy (p<0.05). Using Banff criteria, the with serum creatinine at biopsy (p<0.05). Using Banff criteria, the mean rate of pairwise agreement was 57.8% with an overall kappa 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 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. pairwise agreement was 70% and the overall kappa value was 0.51. The mean interslide variation rates using Banff criteria and the new The mean interslide variation rates using Banff criteria and the new criterion were 30.7% and 36.7%, respectively.criterion were 30.7% and 36.7%, respectively.

Conclusion:Conclusion: While Banff and the recently proposed criteria for ah While Banff and the recently proposed criteria for ah scoring resulted in fair to moderate interobserver agreement, the new scoring resulted in fair to moderate interobserver agreement, the new criterion seems to be more objective and results in better criterion seems to be more objective and results in better interobserver reproducibility. There is a substantial variation in the interobserver reproducibility. There is a substantial variation in the distribution and severity of arteriolar lesions in an individual biopsy, distribution and severity of arteriolar lesions in an individual biopsy, therefore, evaluation of more than one section is crucial to determine therefore, evaluation of more than one section is crucial to determine the severity of arteriolar damage more accurately.the severity of arteriolar damage more accurately.

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

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

CAN

REC/DN DZ

ACUTE VASC

ACUTE TI

CNI

TGP

BRDLN

AB MED

BK Virus

MIN CHANGES

MIS

173 posttransplant biopsies from 127 173 posttransplant biopsies from 127 patients with available anti-HLA Ab analysispatients with available anti-HLA Ab analysis

Jan. 2002 to March 2004Jan. 2002 to March 2004

173 posttransplant biopsies from 127 173 posttransplant biopsies from 127 patients with available anti-HLA Ab analysispatients with available anti-HLA Ab analysis

Jan. 2002 to March 2004Jan. 2002 to March 2004

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Moving from semiquantitative scoring to Moving from semiquantitative scoring to quantitative scoring by morphometry!quantitative scoring by morphometry!

Despite all the praise we have received for the Banff scoring Despite all the praise we have received for the Banff scoring system, a truly quantitative system would obviously be better system, a truly quantitative system would obviously be better if practical, so we are only half way there!if practical, so we are only half way there!

Howie AJ: The Problems with BANFF, Transplantation Howie AJ: The Problems with BANFF, Transplantation 73:1383, 2002 “…other approaches should be tried such as 73:1383, 2002 “…other approaches should be tried such as morphometry” morphometry”

Financially and technically impractical for most centers right Financially and technically impractical for most centers right now, but possibly doable in the near future.now, but possibly doable in the near future.

Banff classification is based on semiquantitative Banff classification is based on semiquantitative assessment. Quantitative assessment would ultimately be assessment. Quantitative assessment would ultimately be better, just as the molecular biology/genomics alternative better, just as the molecular biology/genomics alternative would be. But they must be made practical!would be. But they must be made practical!

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

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

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Clinical practice guidelines, new Clinical practice guidelines, new lesion scoring etc.lesion scoring etc.

Revisiting 1999 guidelines.Revisiting 1999 guidelines.

Methods review for C4d as a marker for antibody Methods review for C4d as a marker for antibody mediated rejection.mediated rejection.

Peritubular capillary cell accumulation scoring.Peritubular capillary cell accumulation scoring.

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Polys in peritubular capillaries in antibody-mediated rejection.Polys in peritubular capillaries in antibody-mediated rejection.Polys in peritubular capillaries in antibody-mediated rejection.Polys in peritubular capillaries in antibody-mediated rejection.

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1999 - Agreed upon clinical practice 1999 - Agreed upon clinical practice guidelines that need buy-in generallyguidelines that need buy-in generally

Implantation biopsiesImplantation biopsies

Rapid paraffin (microwave) processing for rapid Rapid paraffin (microwave) processing for rapid reading rather than frozen sectionsreading rather than frozen sections

Routine (“protocol”) biopsiesRoutine (“protocol”) biopsies

H&E, PAS (+/o silver), and trichrome or Sirius red H&E, PAS (+/o silver), and trichrome or Sirius red stainsstains

Schedule of the MeetingSchedule of the MeetingSaturday, 16 July 2005Saturday, 16 July 20058:00 - 8:208:00 - 8:20Welcome, Opening Remarks - Welcome, Opening Remarks - Kim Solez and Lorraine RacusenKim Solez and Lorraine Racusen

Plenary sessionPlenary session8:20 - 9:208:20 - 9:20Keynote Address:  Future directions in organ replacement. - Keynote Address:  Future directions in organ replacement. - Jeffrey Jeffrey PlattPlatt

Transcriptome Gene ChipTranscriptome Gene ChipModerator:  Moderator:  Philip F. HalloranPhilip F. Halloran9:20-11:509:20-11:50

12:00 - 1:00Lunch (Wedgwood Room)Lunch (Empire Terrace) PMEmpire 12:00 - 1:00Lunch (Wedgwood Room)Lunch (Empire Terrace) PMEmpire Ballroom Ballroom 1:00 - 1:30Experimental heart transplantation.1:00 - 1:30Experimental heart transplantation.  - Thomas Mueller  - Thomas MuellerEmerging TechnologiesEmerging TechnologiesModerator:  Moderator:  Philip F. HalloranPhilip F. Halloran1:30-4:301:30-4:30

Saturday, 16 July 2005Saturday, 16 July 20058:00 - 8:208:00 - 8:20Welcome, Opening Remarks - Welcome, Opening Remarks - Kim Solez and Lorraine RacusenKim Solez and Lorraine Racusen

Plenary sessionPlenary session8:20 - 9:208:20 - 9:20Keynote Address:  Future directions in organ replacement. - Keynote Address:  Future directions in organ replacement. - Jeffrey Jeffrey PlattPlatt

Transcriptome Gene ChipTranscriptome Gene ChipModerator:  Moderator:  Philip F. HalloranPhilip F. Halloran9:20-11:509:20-11:50

12:00 - 1:00Lunch (Wedgwood Room)Lunch (Empire Terrace) PMEmpire 12:00 - 1:00Lunch (Wedgwood Room)Lunch (Empire Terrace) PMEmpire Ballroom Ballroom 1:00 - 1:30Experimental heart transplantation.1:00 - 1:30Experimental heart transplantation.  - Thomas Mueller  - Thomas MuellerEmerging TechnologiesEmerging TechnologiesModerator:  Moderator:  Philip F. HalloranPhilip F. Halloran1:30-4:301:30-4:30