Journal Club

November 2010

Autologous Chondrocyte Implantation in Cartilage Lesions of the Knee. Long-term evaluation with Gandolinium-Enhanced MRI

Author: Vasialadis, Danielson, Ljungberg, Mckeon, Lindahl, Peterson

Institution: University of Gothenburg Sweden and Sahlgrenska University Hospital Gothenberg, MRI mapping Beth Israel Deaconess Medical Centre, Boston Massachusetts

Journal:

MRI funded by grant from Genzyme

Reviewed by

Dr Owen Mattern
MBBS | Unaccredited Orthopaedic Registrar

Introduction

  • ACI implant quality considered most likely predictor of long term clinical outcome
  • Second-look arthroscopy and biopsy considered most effective way of evaluation
    • Associated risks with second operation and potential graft damage through biopsy
  • MRI proven effective diagnostic tool for examining structures of the knee
  • Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) assesses hyaline cartilage
  • Gadolinium spreads inversely in relation to gylcoaminoglycans (GAG)
    • GAG concentration is related to cartilage degeneration
    • Measured on T1 weighted films
      • 487.3 in control patients
      • 458.0 in mild arthritis

Hypothesis

  • dGEMRIC MRI can give valuable information regarding quality and quantity of ACI repair
    • May provide potential substitute for invasive methods

Methodology

  • 31 volunteers with 36 treated knees selected from 219 patients who had ACI performed by senior author atleast 9 years previously (do not mention how patients were selected)

    • 27 femoral condyle, 8 patella, 1 trochlear
    • Used a technique previously described in 1994 NEJM paper
  • Retrospective patient file review
    • Lesions size and location
    • History of previous cartilage treatment surgery
    • Concomitant lesions
  • Clinically evaluated using KOOS (5 subgroups looking at pain, symptoms, functions of daily living, sports and recreation, knee-related quality of life

    Methods - MRI

    • 30mL gadolinium IV 90min before MRI
    • Patients walked for 15 minutes IV infusion
    • MRI assessed for
      • Filling of defect
      • Smoothness of surface
      • Integration to surrounding tissue and subchondral bone
      • Subchondral oedema

Methods - MRI

    • Two regions of interest (ROI1 and ROI2) examined
      • ROI1 repair tissue zone
      • ROI2 same slice MRI as ROI1
        • Middle of healthy cartilage away from treated area

Methods - Statistics

    • T-test to compare independent means and paired T-test to compare ROI values (commonly applied when a test would follow a standard distribution)
    • Wilcoxon test nonnormal data (non-parametric data. Used when t-test distribution cannot be assumed)
    • Chi-square compare percentage of patients
    • Pearson correlation coefficient to compare correlation between ROI1 and ROI2 (frequency of distribution is equal to what is expected)

Results

  • Results - Patient Demographics

    • Mean age 29.40 (17.5-50.5)
    • Lesion size 5.14cm2
    • 12.9 years after ACI (9-18years)
    • 16 women, 15 men
    • 23 right, 13 left
    • MFC 20, LFC 7, Trochlea 1, Patella 8

    Results - MRI Measurements

    • T1 value
      • ROI1: 467.5, ROI2: 495.3 - not SS (T1 values from baseline study: 487.3 in control patients,458.0 in mild arthritis)
      • “no significant differences were detected between ROI1 and ROI2, suggesting a comparable proteoglycan content in repair tissue and the surrounding cartilage”
    • ROI1
      • 39% subchondral cysts (14pts)
      • 64% intralesional osteophyte (23pts)
      • Lesion size had no predictor for MRI findings
      • 75% covered >50%, 7 covered <50%, 2 exposed subchondral bone

    Results - KOOS

    • Pain 80.0
    • ADL 85.6
    • Symptoms 70.7
    • Sports and recreation 48.3
    • QOL 57.8
    • Irregular surface lesions had better KOOS outcome than smooth surface in all facets (p<0.05)

Discussion

  • Discussion

    • Mention that clinical scores can be unreliable and that evaluation of the quality of the repair can predict long-term function
    • Biopsy provides best current option
      • Morbidity associated with biopsy
      • May miss intralesional osteophytes
      • Often done on patients with complications
        • Patient selection bias

    Discussion

    • Osteophytes had no association with poor clinical outcomes
      • “probably constitute a negative prognostic factor”
    • T1 relaxation times similar to other studies
      • Different dose of gadolinium compared to other published studies
      • Different measurement between ROI1 and ROI2 not discussed
        • Actually state that ROI1=ROI2
    • Majority of discussion is regarding quality of ACI graft
      • Not the aim of the paper
      • “9-18 years after ACI, the cartilage defect area s restored, and the quality of the repair tissue is identical to the surrounding cartilage”

Pros of Study

  • Very few
  • Long follow up time of patients
  • Reading of MRI cross-referenced to outside specialist institution

Cons of Study

  • Sponsored by Genzyme
  • No discussion on how volunteers were selected
    • Large potential from selection bias
  • Hypothesis was based on dGEMERIC MRI giving valuable information
    • No cross-reference to arthroscope finding
    • No correlation to KOOS outcome
    • Used standard dose of gadolinium when other papers have used weight adjusted dosing
  • KOOS only calculated pre-operatively
  • No power calculation with paper appearing under powered
  • Conclusions do not match with data

Take home message

  • dGEMRIC MRI may be useful, but this study does not help in this determination

 

 

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