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The Bone & Joint Journal
Vol. 95-B, Issue 2 | Pages 192 - 198
1 Feb 2013
Ackman J Altiok H Flanagan A Peer M Graf A Krzak J Hassani S Eastwood D Harris GF

Van Nes rotationplasty may be used for patients with congenital proximal focal femoral deficiency (PFFD). The lower limb is rotated to use the ankle and foot as a functional knee joint within a prosthesis. A small series of cases was investigated to determine the long-term outcome. At a mean of 21.5 years (11 to 45) after their rotationplasty, a total of 12 prosthetic patients completed the Short-Form (SF)-36, Faces Pain Scale-Revised, Harris hip score, Oswestry back pain score and Prosthetic Evaluation Questionnaires, as did 12 age- and gender-matched normal control participants. A physical examination and gait analysis, computerised dynamic posturography (CDP), and timed ‘Up & Go’ testing was also completed. Wilcoxon Signed rank test was used to compare each PFFD patient with a matched control participant with false discovery rate of 5%.

There were no differences between the groups in overall health and well-being on the SF-36. Significant differences were seen in gait parameters in the PFFD group. Using CDP, the PFFD group had reduced symmetry in stance, and reduced end point and maximum excursions.

Patients who had undergone Van Nes rotationplasty had a high level of function and quality of life at long-term follow-up, but presented with significant differences in gait and posture compared with the control group.

Cite this article: Bone Joint J 2013;95-B:192–8.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVI | Pages 12 - 12
1 Aug 2012
Shekkeris A Perera J Bentley G Flanagan A Miles J Carrington R Skinner J Briggs T
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Articular cartilage implantation (ACI) and associated procedures (MACI = Matrix-assisted cartilage implantation) are now established treatments for osteochondral defects in the knee. The quality of repair in terms of histological appearance is frequently not known, whilst the correlation of histology results with functional outcomes remains undefined. Histological data of the quality of the repair tissue is sparse and a precise classification proved difficult.

This was a single-centre, prospective study. Over 12 years (1998-2010) 406 patients that underwent articular cartilage implantation procedures at our institution (ACI = 170, MACI = 205) had biopsies taken at the 1-2 year interval, in order to assess whether these contained ‘hyaline-like’ cartilage, ‘mixed hyaline-like with fibrocartilage’, fibrocartilage or fibrous tissue alone.

Histological sections of the biopsies were prepared and stained with haematoxylin, eosin and proteoglycan stains and viewed under polarised light. All biopsies were studied by a single histopathologist in a specialist, dedicated musculoskeletal laboratory.

All patients were assessed by the Cincinnati, Bentley and Visual Analogue scores both pre-operatively and at the time of the review.

The findings revealed that 56 patients healed with ‘hyaline-like’ cartilage (14.9%), 103 with ‘mixed’ (27.5%), 179 with fibrocartilage (47.7%) and 37 with fibrous tissue (9.9%).

These findings showed that 42.4% of defects were filled with ‘hyaline-like’ or ‘mixed’ cartilage, with 70% of these achieving a ‘fair’ to ‘excellent’ functional outcome. This was also observed in the fibrocartilage group, where 72% achieved similar results. Predictably 89% of the patients that healed by fibrous tissue had a poor functional outcome.

This study shows that 71% of patients whose osteochondral defects healed by either ‘hyaline-like’, ‘mixed’ or fibrocartilage experienced an improvement in the function. In contrast, only 11% of the patients whose defects filled with fibrous tissue, showed some functional improvement. Additionally, this data indicates the advantage of biopsies in assessing the overall results of cartilage implantation procedures.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XIV | Pages 23 - 23
1 Apr 2012
Bovée J Meijer D Szuhai K van den Akker B de Jong D Krenacs T Athanasou N Flanagan A Picci P Daugaard S Liegl-Atzwanger B Hogendoorn P Bovée J
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Besides conventional chondrosarcoma, several rare chondrosarcoma subtypes are described, comprising about 15% of all chondrosarcomas. Clear cell chondrosarcoma (CCS) is a low-grade malignant tumour, often recurring after curettage, and showing overall survival of about 85%. Mesenchymal chondrosarcoma (MCS) is a highly malignant tumour occurring in bone and soft tissue of relatively young patients. The tumour shows differentiated cartilage mixed with undifferentiated small round cells. It often metastasises and shows a 5-year overall survival of 55%. Dedifferentiated chondrosarcoma (DDCS) is a tumour containing a high-grade non-cartilaginous sarcoma (DD), and a usually low-grade malignant cartilage-forming tumour (WD).

The prognosis is poor. The lack of efficacious treatment of these rare tumours emphasises the need to learn more about their characteristics and to unravel potential targets for therapy.

We constructed tissue microarrays (TMAs) with 2mm cores of 45 DDCS (WD and DD), 24 CCS, and 25 MCS, in triplicate.

Using immunohistochemistry, we investigated protein expression of estrogen-signaling molecules, growth plate-signaling molecules, and other molecules which might be potential targets for therapy. In addition, we gathered genomic information using Agilent 44K oligo arrays.

30% of the WD components were positive for Cox-2. Almost all others were negative. For Bcl2, 88% of the small cells and 32% of the cartilage in MCS were positive. In CCS, WD, and DD 48%, 4%, and 12% were positive, respectively. We demonstrated the presence of ESR1 and aromatase protein in the majority of tumours in all subtypes. Using array CGH, we observed similar aberrations in the two components of DDCS, with additional aberrations in the DD.

Celecoxib treatment is not recommended, as most of the tumours are negative for Cox-2. However, the presence of ESR1 and aromatase support a possible effect of anti-estrogen treatment in all subtypes, and application of Bcl2 inhibitors might chemosensitise MCS.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_IV | Pages 131 - 131
1 Mar 2012
Jaiswal P Park D Carrington R Skinner J Briggs T Flanagan A Bentley G
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Introduction

We report the initial 2 and 3 year follow-up results of this randomised controlled trial of autologous chondrocyte implantation (ACI) using porcine-derived collagen membrane as a cover (ACI-C) versus matrix-carried autologous chondrocyte implantation (MACI) for the treatment of osteochondral defects of the knee.

Methods

217 patients were randomised to have either ACI (92 patients) or MACI (125 patients). The mean age in each group was 35.1 and 33 years respectively. There were equal proportion of males and females and there was no difference in the size of lesions in each of the treatment groups. One year following surgery, patients underwent check arthroscopy (with or without biopsy) to assess the graft. Functional assessment was performed yearly by using the Modified Cincinatti Knee score, the SF-36 score, the Bentley Functional Rating Score and the Visual Analogue Score.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_II | Pages 122 - 122
1 Feb 2012
Gooding C Bartlett W Bentley G Skinnner J Carrington R Flanagan A
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The results for autologous chondrocyte implantation (ACI) in the treatment of osteochondral defects in the knee are encouraging. At present, two techniques have been described to retain the chondrocyte suspension within the defect. The first involves using a periosteal flap harvested from the distal femur and the second involves using a type I/III collagen membrane. To the authors' knowledge there are no comparative studies of these two techniques in the current literature.

A total of 68 patients with a mean age of 30.52 years (range 15 to 52 years) with symptomatic articular cartilage defects were randomised to have either ACI with a periosteal cover (33 patients) or ACI with a type I/III collagen cover (35 patients). The mean defect size was 4.54 cm2 (range 1 to 12 cm2). All patients were followed up at 24 months.

A functional assessment using the Modified Cincinnati score showed that 74% of patients had a good or excellent result following the ACI with collagen cover compared with 67% after the ACI with periosteum cover at 2 years (p>0.05). Arthroscopy at 1 year also demonstrated similar results for both techniques. However, 36.4% of the periosteum covered grafts required shaving for hypertrophy compared with 1 patient for the collagen covered technique.

This prospective, randomised study has shown no statistical difference between the clinical outcome of ACI with a periosteal cover versus ACI with a collagen cover at 2 years. A significant number of patients who had the ACI with periosteum technique required shaving of a hypertrophied graft within the first year of surgery. We conclude that there is no advantage in using periosteum as a cover for retaining the chondrocytes within an osteochondral defect; as a result we advocate the use of an alternative cover such as a porcine-derived, type I/III collagen membrane.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_III | Pages 155 - 155
1 Feb 2012
Krishnan S Skinner J Jaggiello J Carrington R Flanagan A Briggs T Bentley G
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Aims

To investigate (1) The relationship between macroscopic grading and durability of cartilage repair following collagen-covered autologous chondrocyte implantation (ACI-C) in the knee; (2) The influence of histology on durability of cartilage repair; (3) The relationship between macroscopic appearance and histology of repair tissue.

Patients and methods

The modified Cincinnati scores (MCRS) of eighty-six patients were evaluated prospectively at one year and at the latest follow-up (mean follow-up = 4.7yrs. Range = 4 to 7 years). Needle biopsies of their cartilage repair site were stained with Haematoxylin and Eosin and some with Safranin O and the neo-cartilage was graded as hyaline-like (n=32, 37.2%), mixed fibro-hyaline (n=19, 22%) and fibro-cartilagenous tissue (n=35, 40.7%). Macroscopic grading of the repair tissue using the international cartilage repair society grading system (ICRS) was available for fifty-six patients in the study cohort. Statistical analyses were performed to investigate the significance of histology and ICRS grading on MCRS at 1 year and at the latest follow-up.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_III | Pages 153 - 153
1 Feb 2012
Park D Krishnan S Skinner J Carrington R Flanagan A Briggs T Bentley G
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Purpose

We report on minimum 2 year follow-up results of 71 patients randomised to autologous chondrocyte implantation (ACI) using porcine-derived collagen membrane as a cover (ACI-C) and matrix-induced autologous chondrocyte implantation (MACI) for the treatment of osteochondral defects of the knee.

Introduction

ACI is used widely as a treatment for symptomatic chondral and osteochondral defects of the knee. Variations of the original periosteum-cover technique include the use of porcine-derived type I/type III collagen as a cover (ACI-C) and matrix-induced autologous chondrocyte implantation (MACI) using a collagen bilayer seeded with chondrocytes.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_II | Pages 200 - 200
1 May 2011
Sri-Ram K Haddo O Dannawi Z Flanagan A Cannon S Briggs T Sinisi M Birch R
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Objective: This study was performed to review the current treatment and outcome of extra abdominal fibromatosis in our hospital, supplemented by a current review of the literature.

Method: A retrospective study of 72 patients with fibromatosis seen at the Royal National Orthopaedic Hospital (RNOH) between 1980 and 2009 was performed. Patients were identified using the databases at the peripheral nerves injury (PNI) unit and the histopathology department. Medical and radiological records were reviewed.

Results: There were 72 patients treated at the Sarcoma and PNI units. 40 patients were primary referrals, and 32 more had operations at the referring hospital. An operation was not carried out in 5 patients. 48 patients were treated by operation alone and this was supplemented by adjuvant therapy in 19 patients. Recurrence was seen in 24 (50.0%) of the operation alone group and 10 (52.6%) in the operation and adjuvant therapy group. The rate of recurrence was lower with complete excision. However, complete excision was impossible in some cases because of extension into the chest or spinal canal, or involvement with the axial vessels and lumbosacral or brachial plexus.

Conclusion: We suggest that operative excision should seek to preserve function and that supplementary adjuvant therapy may reduce the risk of recurrence, although excision margin appears to be the most important factor. The aggressive, infiltrative behaviour of deep fibromatoses and the associated genetic mutations identified, clearly distinguish them from the superficial fibromatoses and makes their treatment more difficult and dangerous, especially where vital structures are involved. We agree with the recent recommendation that these lesions should be treated in regional soft tissue sarcoma units.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_I | Pages 23 - 23
1 Jan 2011
Gikas P Aston W Saiffudin A Pollock R Skinner J Briggs T Cannon S Flanagan A
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Non-bacterial osteitis (NBO), a term referring to sterile bone lesions with non-specific histopathological features of inflammation, may be either uni- or multifocal, acute (6 months) or chronic, and recurrent. Only when the condition is chronic, recurrent and multifocal is it appropriate to use the term chronic recurrent multifocal osteomyelitis (CRMO).

We present our clinical experience as the largest reported series of children with NBO to date. Of 41 children (2–16 years) diagnosed with NBO in our institution over the last 6 years, 21 (51%) had recurrent disease and 18 of 41 (44%) had multifocal disease. The most common bones affected were the clavicle, femur and tibia (in order of decreasing prevalence) accounting for 44 (63%) of a total of 70 lesions. Only one individual had SAPHO syndrome and no other patients had evidence of bowel or skin disease. In the absence of evidence for an infective aetiology, we recommend non-steroidal anti-inflammatory agents as first line therapy, and bisphosphonates only in cases of resistant disease.

On the basis of our findings we propose a patient questionnaire and protocol for investigating and managing patients who present to orthopaedic surgeons with NBO. We predict that this will benefit patients with this disorder by providing valuable information about the pathogenesis, clinical outcome and response to treatment. In the future, clarification of the pathogenesis of this disease will undoubtedly help rationalise the therapeutic approach improving both quality of life and outcome for these patients.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_I | Pages 76 - 76
1 Jan 2011
Rose B Tamvakopoulos G Dulay K Pollock R Flanagan A Skinner JA Briggs TWR Cannon SR
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Introduction: Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft tissue neoplasm most commonly presenting in young to middle-aged adults. LGFMS is an indolent tumour with a deceptively benign histological appearance. Local recurrences are not uncommon and tumours can metastasise. The FUS-CREB3L2 gene translocation has been shown to occur commonly in cases of LGFMS. The literature suggests that the FUS-CREB3L2 fusion-gene is a specific marker for LGFMS.

Methods: We report the cytogenetic analysis of 29 LGFMS cases, and clinical outcomes of 21 patients treated surgically between 1998 and 2008 at our regional bone and soft-tissue tumour centre.

Results: The mean age was 45.4 years and mean follow-up 30.1 months. The most common tumour location was the lower limb. There were no cases of local recurrence or metastasis. Fifteen patients (52.2%) were FUS-CREB3L2 translocation-positive, suggesting either that translocation incidence in our series is lower than other studies, or that reverse-transcriptase polymerase chain reaction (PCR) is less sensitive than the literature suggests. Patients testing positive presented at a younger age (38.2 years, compared to 45.6 years), and had larger tumours than their negative counterparts (mean diameter 97.6mm, compared to 65.2mm), although there was no difference in clinical outcome.

Discussion: We conclude that PCR testing for the FUS-CREB3L2 translocation is a useful tool for confirming the diagnosis of LGFMS, but has no role in predicting short-term clinical outcome. It is not necessary to perform wide excision, and marginal margins are adequate. Longer-term follow-up is required to elucidate differences in the long-term clinical outcome between translocation-positive and negative patients.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_I | Pages 77 - 77
1 Jan 2011
Tamvakopoulos GS Rose B De-Silva K Shankar S Flanagan A Saifuddin A Skinner J Briggs T Cannon S Pollock R
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Introduction: The Musculoskeletal Tumour Society recommends that patients with musculoskeletal tumours are treated in specialist centres. Core needle biopsy is an effective method of obtaining tissue diagnosis but a dilemma arises when the material is non-diagnostic. Our aim was to evaluate the management of non-diagnostic biopsies.

Method: We retrospectively reviewed all core needle biopsies performed between 2003 and 2009 in our regional centre. Non-diagnostic biopsies were identified and management reviewed.

Results: 4,520 core needle-biopsies were performed of which 120 (2.6%) were non-diagnostic. Of these 85 (70%) were treated definitively on the basis of existing imaging, 8 (7%) required further imaging before treatment and 27 (23%) had a repeat biopsy.

Of the 27 repeat biopsies a positive histological diagnosis was obtained in 22 patients. The remaining 5 were again non-diagnostic giving a total of 98 patients being treated definitively without a tissue diagnosis.

Of these 98 cases, 39 (40%) were treated non-operatively, 37 (38%) had curettage and 22 (22%) underwent wide excision.

In the curettage group 33 out of 37 patients had a benign tumour on final histology. Four patients turned out to have intermediate/high grade tumours and subsequently underwent wide excision.

In the wide excision group, 17 out of 22 patients had an intermediate/high grade tumour on final histology. Five patients underwent an unnecessarily wide excision of a benign lesion.

None of the patients treated non-operatively turned out to have a tumour.

Conclusion: After non-diagnostic core-needle biopsy, the patient can safely be managed without tissue diagnosis, with low error rate, provided they have been subjected to a multidisciplinary discussion.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 446 - 446
1 Jul 2010
Parratt M Delaney D Gokaraju K Spiegelberg B Flanagan A Cannon S Briggs T
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Primary solitary fibrous tumour (SFT) of bone is extremely rare with few cases reported in the literature. The incidence of the lesion is 0.08% of all primary bone tumours (0.1% of primary malignant bone neoplasms). Previously, such lesions may have been reported as haemangiopericytoma (HP).

Despite being previously considered as separate entities, the two types of tumour (SFT and HP) are now generally accepted as related, sharing similar morphological and immunohistochemical features. Cytogenetic and molecular analysis has, so far, been unable to unite or divide the two. Although frequently having a histologically benign appearance or being labelled as intermediate grade, these tumours may exhibit an unpredictable clinical course and behave in an aggressive manner. We present two cases of osseous solitary fibrous tumour (cellular haemangiopericytoma).

Using the histopathology and bone tumour databases at our institution, we identified two patients (one female aged 21 and one male aged 40) with a histopathological diagnosis of osseous SFT. The site of primary tumour in both patients was the sacrum. In the female patient, the lesion was confined to the sacrum and she underwent curettage. In the male patient, the tumour extended beyond the sacrum to the sacro-iliac joint, ilium and gluteal mass, therefore, total sacrectomy was performed. At presentation neither patient had evidence of metastatic spread.

The female patient was disease free at four years with no evidence of recurrence of metastases. The male patient developed metastases in both lung fields and bone (ribs, vertebrae) three years post-operatively and died four years post-operatively.

Orthopaedic surgeons and histopathologists should remain aware of SFT due to its erratic behaviour and the recent move towards unifying it with HP in a continuous spectrum. We recommend early staging and treatment of these tumours, even for histologically benign/low grade lesions, due to their potentially aggressive behaviour.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 448 - 448
1 Jul 2010
Rose B Tamvakopoulos G Dulay K Pollock R Flanagan A Skinner J Briggs T Cannon S
Full Access

Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft tissue neoplasm most commonly presenting in young to middle-aged adults. LGFMS is an indolent tumour with a deceptively benign histological appearance. Local recurrences are not uncommon and the tumours can metastasise. A particular gene translocation, FUS-CREB3L2, has been shown to occur commonly in cases of LGFMS. The literature suggests that the FUS-CREB3L2 fusion-gene is a specific marker for LGFMS.

We report the cytogenetic analysis of 29 cases of LGFMS, and clinical outcomes of 21 patients treated surgically between 1998 and 2008 at our regional bone and soft-tissue tumour centre. The mean age was 45.4 years. The most common location of tumours in our series was the lower limb. The mean follow-up was 30.1 months (range 0 to 125 months). To date, there have been no cases of local recurrence or metastasis.

Fifteen of our patients (52.2%) were FUS-CREB3L2 translocation-positive. This suggests either that the translocation incidence in our LGFMS series is lower than other studies, or that reverse-transcriptase polymerase chain reaction (PCR) is substantially less sensitive than the literature suggests. The patients in this series testing positive presented at a younger age (38.2 years, compared to 45.6 years), and had larger tumours than their negative counterparts (mean diameter 97.6mm, compared to 65.2mm), although there was no difference in clinical outcome.

We conclude that PCR testing for the FUS-CREB3L2 translocation is a useful tool for confirming the diagnosis of LGFMS, but has no role in predicting short-term clinical outcome. In our experience it is not necessary to perform wide excision, and marginal margins are adequate. Longer-term follow-up is required to elucidate whether the previously reported recurrence and metastasis rates are a true reflection of the nature of this tumour, and may identify differences in the long-term clinical outcome between translocation-positive and negative patients.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 478 - 478
1 Jul 2010
Anazado A Flanagan A Tirabosco R Briggs T Cannon S Skinner J Pollock R Cassoni A Whelan J Michelagnoli M
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Medical records of children < /=5 years, treated by the London sarcoma service for malignant primary bone tumours (average new cases osteosarcoma (OS)/Ewings sarcoma (ES), all ages: 125/year) between 1999 and 2009, were reviewed.

Results: 5 OS and 6 ES. Mean age – 4.2 years (range 2.1–5.8), 8/11 males. OS primary sites: distal femur (2), proximal femur (1) and proximal humerus (2); localised tumours only. Primary sites in the ES cohort included 1 distal femur, 2 chest wall (1 – spinal extension), 1 buttock (spinal extension), 1 temporal bone and 1 ulna; 1 had bone/bone marrow involvement, 1 had chest metastases. 4/5 OS (Euramos, MRC B007) and 5/6 ES (Euro-Ewings 99) were entered into phase III clinical trials. Delayed surgery for OS occurred at mean 12.1 weeks (range 11–13) – 4 limb salvage prostheses with 2/4 non-invasive growers, 1 forequarter amputation. All had a good (> 90% necrosis) histologic response to neoadjuvant therapy. Delayed surgery for ES occurred at mean 21.7 weeks (range 12.8 – 35), 1 limb salvage with prosthesis (non-invasive grower), 1 biological reconstruction; remainder had tumour resections. Histologic response: 50% good. In the OS cohort, 1 child died a toxic death; 1 developed pulmonary metastases and died 2 years from diagnosis; 1 has a metastatic recurrence in the opposite humerus 2 years from diagnosis and starts 2nd line therapy; 1 had local recurrence 1 year from diagnosis but alive at 7.4 years;1 alive/disease free at 2.5 years. In the ES cohort 5/6 are alive disease free -1, 4.1, 5.2, 6.9 and 7 years from diagnosis; 2 needed 2nd line therapy for recurrent distant disease 4.5 and 5.8 years off therapy, 1 of whom has just recurred again (6.1 years from diagnosis).

Conclusion- improving early survival rates in the very young with OS remains a significant challenge. Quality of survival requires further age-appropriate study.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 83 - 83
1 Mar 2009
Krishnan S Jaggiello J Flanagan A Briggs T
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Aim: To report the clinical and histological outcome of autologous chondrocyte implantation (ACI) using two techniques -collagen covered ACI or ACI-C and matrix carried ACI or MACI- over eight year period.

Patients and methods: One hundred and seventy one patients (61 ACI-C and 110 MACI) who underwent ACI were followed-up prospectively using both objective and patient reported clinical outcome measures. Biopsy of the repair tissue was performed in 115 patients.

The mean clinical follow-up was 39.4 months (13mths to 8 years) and the mean timing of biopsy was 14.8 months. The mean age at the time of surgery was 32 years (15 to 55 years). The site of defect was as follows: medial femoral condyle-95, lateral femoral condyle-25, trochlea-7, patella 27 and multiple sites- 12. The mean proportion of viable cells available for implantation was 96.3 % (range: 86 to 100) and the mean number of multiplication of cells during culture was 90 (range: 9 to 667).

Results: 79 % of patients had an improvement in clinical outcome, 5 % of patients had no difference and 16 % had deterioration in clinical outcome. Short Form 36 (SF-36) health survey assessments demonstrated significant improvements in both mental and physical component scores (p< 0.001). The number of patients who demonstrated hyaline-like, mixture of hyaline-like and fibrocartilage, fibrocartilagenous and fibrous tissue histology were 32, 22, 59 and 2 respectively.

The most favourable sites were lateral femoral condyle and trochlea where as the least favourable site was patella. There was no correlation between the mental score of patients and the final clinical result. Improvement in functional score was significantly higher among those who had a higher pre-operative function (p< 0.001). There were 7 patients who had previously failed micro-fracture and all of them obtained significant improvements in pain and function. Those who had a higher proportion of viable cells after cell culture demonstrated a tendency towards better outcome, but failed to reach statistical significance (p=0.14). There was no correlation between the number of cell multiplications at the time of cell culture and final clinical outcome (p=0.65). There was no significant difference in clinical outcome between the ACI- C and MACI techniques of ACI (p> 0.05).

Conclusion: Autologous chondrocyte implantation is a useful procedure for patients with symptomatic chondral defects of the knee and produces significant improvement in both objective and patient reported clinical outcome scores in up to 79 % of patients.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 84 - 84
1 Mar 2009
Jaiswal P Park D Carrington R Skinner J Briggs T Flanagan A Bentley G
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Introduction: ACI is used widely as a treatment for symptomatic chondral and osteochondral defects of the knee. Variations of the original periosteum-cover technique include the use of porcine-derived type I/type III collagen as a cover (ACI-C) and matrix-induced autologous chondrocyte implantation (MACI) using a collagen bilayer seeded with chondrocytes. We report the minimum 2 year follow-up results of 192 patients randomised to autologous chondrocyte implantation (ACI) using porcine-derived collagen membrane as a cover (ACI-C) and matrix-induced autlogous chondrocyte implantation (MACI) for the treatment of osteochondral decfects of the knee.

Methods: 192 patients (mean age 34.2) were randomised to have either ACI (86 patients) or MACI (106 patients). 1 year following surgery patients underwent check arthroscopy (with or without biopsy) to assess the graft. Functional assessment was performed yearly by using the modified Cincinatti knee score, the Bentley functional rating score and the visual analogue score.

Results: 24 patients were excluded from the study as they underwent additional procedures (e.g. high tibial osteotomy). In the ACI group the modified Cincinatti score increased from 42.5 pre-operatively to 56.7, 54.1, and 60.4 at 1 year, 2 years and 3 years respectively. In the MACI group the Cincinatti scores increased from 46.0 pre-operatively to 59.9, 58.9, and 58.4. Arthroscopic assessment showed a good to excellent International Cartilage Repair Society score in 90.7% of ACI-C grafts and 68.4% of MACI grafts. Hyaline-like cartilage or hyaline-like with fibrocartilage was found in biopsies of 51.9% of ACI-C grafts and 25.9% of MACI grafts.

Conclusions: ACI grafts are more likely to produce hyaline-like or mixed hyaline-like cartilage and fibro-cartilage with better ICRS grades than MACI grafts. However, this does not translate to better a clinical functional outcome. More importantly, ACI and MACI had similar results that were maintained at 3 years.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 391 - 391
1 Jul 2008
Krishnan S Skinner J Jagiello J Carrington R Flanagan A Briggs T Bentley G
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Aims: To investigate

the influence of histology on durability of cartilage repair following collagen-covered autologous chon-drocyte implantation (ACI-C) in the knee.

the relationship between macroscopic grading and durability of cartilage repair; and

the relationship between macroscopic appearance and histology of repair tissue.

Patients and methods: The modified Cincinnati scores (MCRS) of eighty-six patients were evaluated prospectively at one year and at the latest follow-up (mean follow-up = 4.7yrs. Range = 4 to 7 years). Biopsies of their cartilage repair site were stained with Haema-toxylin and Eosin and some with Safranin O and the neo-cartilage was graded as hyaline-like (n=32), mixed fibro-hyaline (n=19) and fibro-cartilagenous tissue (n=35). Macroscopic grading of the repair tissue using the international cartilage repair society grading system (ICRS) was available for fifty-six patients in this study cohort. Statistical analyses were performed to investigate the significance of histology and ICRS grading on MCRS at 1 year and at the latest follow-up.

Results: The MCRS of all three histology groups were comparable at one year evaluation (p=0.34). However, their clinical scores at the latest follow-up showed a significantly superior result for those with hyaline-like repair tissue when compared to those with mixed fibro-hyaline and fibro-cartilagenous repair (p=0.05).

There was no correlation between the ICRS grading and MCRS either at one year (p=0.12) or at the latest follow-up (p=0.16). Also, the ICRS grading of the repair tissue did not correlate with its histological type (p=0.12).

Conclusion: We conclude that any form of cartilage repair gives good clinical outcome at one year. At four years and beyond, hyaline-like repair tissue produces a more favourable clinical outcome. Macroscopic evaluation using the ICRS grading system does not reflect the clinical outcome or its durability or the histological type of repair tissue.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 393 - 393
1 Jul 2008
Park D Krishnan S Skinner J Carrington R Flanagan A Briggs T Bentley G
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Purpose: We report on minimum 2 year follow-up results of 71 patients randomised to autologous chon-drocyte implantation (ACI) using porcine-derived collagen membrane as a cover (ACI-C) and matrix-induced autologous chondrocyte implantation (MACI) for the treatment of osteochondral defects of the knee.

Introduction: ACI is used widely as a treatment for symptomatic chondral and osteochondral defects of the knee. Variations of the original periosteum-cover technique include the use of porcine-derived type I/type III collagen as a cover (ACI-C) and matrix-induced autolo-gous chondrocyte implantation (MACI) using a collagen bilayer seeded with chondrocytes.

Results: 71 patients with a mean age of 33 years (15–48) were randomised to undergo either an ACI-C or a MACI. 37 had ACI-C and 34 MACI. The mean size of the defect was 5.0cm2. Mean duration of symptoms was 104.4 months (9–456). Mean follow-up was 33.5 months (24–45). Functional assessment using the modified Cincinnati knee score, the Bentley functional rating score and the visual analogue score was carried out. Assessment using the modified Cincinnati knee score showed a good to excellent result in 57.1% of patients followed up at 2 years, and 65.2% at 3 years in the ACI-C group; and 63.6% of patients at 2 years, and 64% at 3 years in the MACI group. Arthroscopic assessments showed a good to excellent International Cartilage Repair Society score in 81.8% of ACI-C grafts (22 patients) and 50% of MACI grafts (6 patients). Fisher’s exact test showed a p value of p=0.35 (not statistically significant). Hyaline-like cartilage or hyaline-like cartilage with fibrocartilage was found in biopsies of 56.3% of the ACI-C grafts (9 out of 16 patients) and 30% of the MACI grafts (3 out of 10 patients) after 2 years. Fisher’s exact test showed a p value of p=0.25 (not statistically significant).

Conclusion: At this stage of the trial we conclude that the clinical, arthroscopic and histological outcomes are comparable for both ACI-C and MACI.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 323 - 324
1 Jul 2008
Krishnan S Skinner J Jagiello J Carrington R Flanagan A Briggs T Bentley G
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Aim: The aim of this study was to correlate the histology of cartilage repair site with long term clinical function.

Materials and methods: We have analyzed the clinical results of a cohort of patients who had collagen-covered autologous chondrocyte implantations performed since 1998. Our hypothesis was that the hyaline cartilage repair does influence the clinical outcome.

The modified Cincinnati scores (MCRS) of eighty-six patients were evaluated prospectively at one year and at the latest follow-up following ACI-C (mean follow-up= 4.7 years. Range= 4 to 7 years). All these patients underwent biopsies of their cartilage repair site performed at variable periods between six months and five years following ACI-C (mean=22.2 months). The neo-cartilage was graded as hyaline (n=32), mixed fibrohyaline (n=19), fibrocartilagenous (n=35) and fibrous (n=0).

Results: The clinical results showed that at one year, the percentage of patients with excellent and good results was 84.4, 89.5 and 74.3 respectively for those with hyaline, mixed fibro-hyaline and fibro-cartilagenous histology respectively. Their mean MCRS were 70.8, 72.4 and 66.2 respectively. This difference was not statistically significant (p=0.34).

However, their clinical scores at the latest follow-up demonstrated a significantly superior result for those with hyaline repair tissue when compared to those with mixed fibro-hyaline and fibro-cartilagenous repair tissue (p=0.05). The percentage of patients with excellent and good results for those with hyaline, mixed fibro-hyaline and fibro-cartilagenous repair was 75, 42 and 68.6 respectively. Their mean MCRS were 70.6, 56.8 and 63.9 respectively.

Conclusion: This study demonstrates that any form of cartilage repair would give good clinical outcome at one year. At four years and beyond, it appears that patients with hyaline repair tissue tend to show a more favourable clinical outcome whereas those who demonstrated mixed fibrohyaline and fibrocartilagenous repair would show less favourable clinical results.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 114 - 114
1 Mar 2006
Bartlett W Gooding C Amin A Skinner J Carrington R Flanagan A Briggs T Bentley G
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Background: Autologous chondrocyte implantation (ACI) was introduced over 15 years ago as a treatment for full-thickness chondral defects in the knee. Current understanding of ACI graft morphology and maturation in humans is limited. The aims of this study were determine the incidence of hyaline-like repair following ACI, and to clarify the relationship between repair morphology and clinical outcome.

Methods: A retrospective review of 194 ACI graft biopsies from 180 patients, and their clinical outcome was conducted. 154 Biopsies were performed 1 year after implantation and 40 biopsies were performed at 2 years. Three techniques of ACI implantation were used; Collagen covered ACI (ACI-C), periosteum covered ACI (ACI-P) and Matrix-Induced ACI (MACI).

Results: At 1 year, hyaline repair tissue was found in 48 (53%) ACI-C grafts, 7 (44%) ACI-P grafts, and 12 (36%) MACI grafts. The frequency of hyaline tissue found in biopsies performed at 2 years (84%) was significantly higher than those performed at 1 year (48.6%), p=0.0001, suggesting that grafts continue to remodel after the first year post implantation.

Clinical outcomes during the first two postoperative years did not vary according to repair morphology type, though hyaline repair was associated with better clinical outcomes beyond 2 years; At 1 year, good to excellent clinical scores were observed in 29 (78.4%) patients with hyaline-like repair, 23 (76.7%) patients with fibrohyaline repair, and 54 (74.0%) patients with fibrocartilage repair. By years 3 and 4 post-implantation, clinical scores further improved in patients with hyaline-like repair yet declined in those with fibrocartilage and fibrohyaline. The difference was significant at 3 years though not at 4 due to the small number of cases.

Conclusions: Achieving hyaline-like repair is critical to the longevity of cartilage repair. The finding of hyaline-like cartilage or fibrohyaline cartilage in 31 of 37 biopsies (84%) performed after 2 years is therefore encouraging and supports further use of the ACI technique.