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Meniscal Allograft Transplantation

PRAGUE June 2007. Meniscal Allograft Transplantation. CARTILAGE PROTECTION ????. René Verdonk Peter Verdonk F. Almqvist. Department of Orthopaedic Surgery Director: Prof. Dr. R. Verdonk Ghent University Hospital Belgium. Meniscus lesions. After resection

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Meniscal Allograft Transplantation

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  1. PRAGUE June 2007 Meniscal Allograft Transplantation CARTILAGE PROTECTION ???? René Verdonk Peter Verdonk F. Almqvist Department of Orthopaedic Surgery Director: Prof. Dr. R. Verdonk Ghent University Hospital Belgium P. VERDONK M.D.

  2. Meniscus lesions • After resection  decreased capacity to distribute load  higher peak stress on cartilage  cartilage degeneration • APPROX 4% CARTILAGE VOLUME LOSS PER YEAR1 • MORE LOSS LATERAL THAN MEDIAL² 1.Cicuttini FM J Rheumatol. 2002 Sep;29(9):1954-6. 2.Chatain F et al Arthroscopy. 2003 Oct;19(8):842-9

  3. The ultimate goal is to prevent cartilage degeneration relieve painimprove functionby a meniscus substitute P. VERDONK M.D.

  4. Preservation techniques for meniscal allografts Cells Mechanics Logistics • Lyophilisation • Deep-freezing • Cryopreservation • cultured ‘VIABLE’ ACELLULAR OK! ACELLULAR OK! OK! OK! 10-40% OK! OK!

  5. Viable meniscal allografts • Allograft harvested < 24 h postmortem • Culture medium: DMEM + antibiotics + L-Glut + 20 % acceptor serum • In vitro culture for approx. 2 weeks • Screening of donor for transmissible diseases Verbruggen G, Verdonk R, et al. Human meniscal proteoglycan metabolism in long-term tissue culture. Knee Surg Sports Traumatol Arthrosc. 1996;4:57-63. Verdonk R, et al. Viable meniscus transplantation. Orthopäde. 1994;23:153-9.

  6. Indication • Younger patient • Previous total meniscectomy • Moderate to severe postmeniscectomy pain • Cartilage status ideally limited degeneration • Not old enough to be considered for TKA • Good alignment corrective osteotomy • Stable joint ligament repair

  7. Surgical Technique Verdonk P et al. Surgical Technique: Viable Meniscal allograft Transplantation. JBJS Am 2006 Illustrations courtesy of JBJS Am and Harderer & Muller

  8. Transplantation ofViable Meniscal AllograftSURVIVORSHIP ANALYSIS AND CLINICAL OUTCOME OF ONE HUNDRED CASESJBJS Am. 2005 April Mean follow-up 7.2 years BY PETER C.M. VERDONK, MD, ALEX DEMURIE, MD, KARL FREDRIK ALMQVIST, MD, PHD, ERIC M. VEYS, MD, PHD, GUST VERBRUGGEN, MD, PHD, AND RENÉ VERDONK, MD, PHD Investigation performed at the Departments of Orthopaedic Surgery and Rheumatology, Ghent University Hospital, Ghent, Belgium P. VERDONK M.D.

  9. MEDIAL LATERAL Patients Mean age at transplantation: 35 years (range 16-47) Mean follow-up 7.2 years (range 2-14.5) 61 39 TOTAL NUMBER = 100 allografts

  10. Associated Procedures Medial meniscal allografts Lateral meniscal allografts TOTAL NUMBER = 39 medial allografts TOTAL NUMBER = 61 lateral allografts = analyzed seperately

  11. Clinical Outcome & Survival analysis • Based on modified Knee Society Score (KSS) • Failure was defined as • Moderate to severe pain (pain score < 30/50) • Poor function (functional score < 80/100) Including conversion to TKA (N=9), capsular resuture (N=2)

  12. Only one true survival analysis available in the literature: • van Arkel ER, de Boer HH. Survival analysis of human meniscal transplantations. JBJS (B )2002 ;84(2):227-31. CRYOPRESERVED (mean follow-up 5 years) Mean Survival Time / Survival Rate at 10 y Medial allografts: 5.75 y / 50.6% Lateral allografts: 9.25 y / 76.54% Failure rate: 13/63 (21%) ACL deficient knees

  13. Clinical Outcome: PAIN Significantly improved at final follow-up

  14. Clinical Outcome: FUNCTION Significantly improved at final follow-up

  15. Failure rate Overall failure rate: 21/100

  16. – LMT LMT-censored – MMT MMT-censored 10 0 2 4 6 8 12 14 16 Overall Survivorship A Survival MMT vs. LMT 100 74.2% MMT 90 80 70 60 69.8% LMT Cumulative Survival (%) 50 40 30 20 10 p=0.733 (log rank test) 0 Follow-up (years)

  17. – Isol.LMT Isol.LMT-censored – Isol.MMT Isol.MMT-censored 0 2 4 6 8 10 12 14 16 Survivorship after isolated allografts transplantation B Survival of isol.MMT vs. isol.LMT 100 72.4% isol.MMT 90 80 70 60 66.8% isol.LMT Cumulative Survival (%) 50 40 30 20 10 p=0.680 (log rank test) 0 Follow-up (years)

  18. – MMT+HTO MMT+HTO-censored – Isol.MMT Isol.MMT-censored 0 2 4 6 8 10 12 14 16 Survivorship after isolated medial allografts vs. medial allografts combined with HTO C Survival of MMT+HTO vs. Isol.MMT 100 83.3% MMT+HTO 90 80 70 72.4% MMT 60 Cumulative Survival (%) 50 40 30 20 10 p=0.156 (log rank test) 0 Follow-up (years)

  19. Meniscal Allograft TransplantationLONG TERM CLINICAL FOLLOW-UP WITH RADIOLOGICAL AND MRI CORRELATIONSaccepted KSSTA 2006 Mean follow-up 12.1 years BY PETER C.M. VERDONK, MD, KOEN L VERSTRAETE, MD, PhD, KARL FREDRIK ALMQVIST, MD, PHD, KRISTOF DE CUYPER, MD, ERIC M. VEYS, MD, PHD, GUST VERBRUGGEN, MD, PHD, AND RENÉ VERDONK, MD, PHD Investigation performed at the Departments of Orthopaedic Surgery, Radiology and Rheumatology, Ghent University Hospital, Ghent, Belgium P. VERDONK M.D.

  20. Patients Mean age at transplantation: 35.2 years (range 16-47) Mean follow-up 12.1 years (range 10-14.8) 15 24 11/24 HTO 3/24 ACL TOTAL NUMBER = 39 allografts = analyzed seperately

  21. Clinical & Imagery outcome • Knee Society Score (KSS) • preop and postop (N=100%) • Knee Osteoarthritis Outcome Score (KOOS) • Postop (N=81%) • Standing X-rays • Baseline and postop (N=81%) • MRI • Baseline and postop (N=68%) Baseline= within 6mo (XR) to 1Y (MRI) after transplant

  22. Clinical outcome: KSS Mean values Significantly improved at final follow-up

  23. Clinical outcome: KOOS Mean values However, substantial disability and reduced QoL

  24. Radiological Outcome MMT MMT+HTO LMT JSN Fairbanks JSN Fairbanks JSN Fairbanks

  25. Radiological outcome preop FU > 10y LMT, no progression Patient D.L.

  26. Radiological outcome preop FU > 10y MMT+HTO, progression by 1 grade Patient V.W.

  27. Radiological outcome preop FU > 10y MMT+HTO, progression by 2 grades Patient B.J.

  28. Radiological outcome preop FU > 10y LMT, progression by 3 grades Patient V.C.

  29. OVERALL JSN, 52% NO PROGRESSION 32% by 1 grade 12% by 2 grades 4% by 3 grades OVERALL Fairbanks, 36% NO PROGRESSION 32% by 1 grade 32% by 2 grades 0% by 3 grades Radiological outcome

  30. MRI outcome preop FU > 10y Signal intensity of graft: Grade III stable articular cartilage: no progression MMTX

  31. MRI outcome MMTX Signal intensity of graft: Grade 0 stable articular cartilage (F+T): progression by 1 grade

  32. MRI outcome Signal intensity of graft: Grade 0  III articular cartilage: progression by 1 (F) and 1.5 (T) grade LMTX

  33. MRI outcome Signal intensity of graft: Grade 0 stable articular cartilage: no progression MMTX

  34. OVERALL Femoral 47% NO PROGRESSION 6% by .5 grade 29% by 1 grades 12% by 1.5 grades 6% by 2 grades OVERALL Tibial 41% NO PROGRESSION 18% by .5 grade 23% by 1 grades 12% by 1.5 grades 6% by 2 grades MRI outcome: Cartilage OVERALL: 35% no progression on BOTH femoral and tibial cartilage

  35. Viable Meniscal Allograft TransplantationSOME BIOLOGICAL CONSIDERATIONSpreliminary data BY PETER C.M. VERDONK, MD, KARL FREDRIK ALMQVIST, MD, PHD, GUST VERBRUGGEN, MD, PHD, AND RENÉ VERDONK, MD, PHD Investigation performed at the Departments of Orthopaedic Surgery and Rheumatology, Ghent University Hospital, Ghent, Belgium P. VERDONK M.D.

  36. Histological analysis Viable allograft, 1Y postop, Recipient DNA

  37. Histological analysis Viable allograft, 1Y postop, recipient DNA

  38. Histological analysis Core= No cells Deepfrozen allograft, 1Y postop, recipient DNA

  39. Histological analysis • VIABLE GRAFT: Suggesting complete repopulation of the graft with fibrochondrocyte-like cells • DEEPFROZEN GRAFT: suggesting only superficial and low repopulation. • Phenotype of repopulating cell??? (Rodeo SA et al. Histological analysis of human meniscal allografts. A preliminary report. J Bone Joint Surg Am. 2000;82:1071-82.)

  40. Discussion Preservation technique • Lyophilisation abandoned (Wirth et al.) • No clear clinical benefit deepfrozen/cryopreservation/viable • Biological difference??? • start of a propspective study deepfrozen vs. viable Surgical fixation • No clear clinical difference soft tissue vs. Bone bloc • We still prefer open sugery

  41. Discussion Associated procedures • ACL needs to be reconstructed! (Van Arkel and de Boer) • Influence of HTO on survival of MMTx in varus knee • MTx in combination with cartilage surgery? Scoring system • Clinical • Objective AND subjective • Radiology • MRI NEED FOR CONSENSUS

  42. Discussion Does it prevent further cartilage degeneration???? • inconclusive evidence • Wirth et al.: progression observed (lyophil+deepfrozen) • Verdonk et al.: some do not progress… • CHONDROPROTECTIVE POTENTIAL… • NEED FOR CORRECT CONTROL GROUPS!!! UTOPIA?

  43. Conclusion • Reduces PAIN • Improves FUNCTION • In approx. 70% at 10 years • …Chondroprotective potential?

  44. Thank you for your attention Department of Orthopaedic Surgery and Physical Medicine, Ghent University Hospital, Ghent, Belgium

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