T. W. R. Briggs

Autologous chondrocyte implantation versus matrix-induced autologous chondrocyte implantation for osteochondral defects of the knee: A PROSPECTIVE, RANDOMISED STUDY

Autologous chondrocyte implantation (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 have performed a prospective, randomised comparison of ACI-C and MACI for the treatment of symptomatic chondral defects of the knee in 91 patients, of whom 44 received ACI-C and 47 MACI grafts. Both treatments resulted in improvement of the clinical score after one year. The mean modified Cincinnati knee score increased by 17.6 in the ACI-C group and 19.6 in the MACI group (p = 0.32). Arthroscopic assessments performed after one year showed a good to excellent International Cartilage Repair Society score in 79.2% of ACI-C and 66.6% of MACI grafts. Hyaline-like cartilage or hyaline-like cartilage with fibrocartilage was found in the biopsies of 43.9% of the ACI-C and 36.4% of the MACI grafts after one year. The rate of hypertrophy of the graft was 9% (4 of 44) in the ACI-C group and 6% (3 of 47) in the MACI group. The frequency of re-operation was 9% in each group. We conclude that the clinical, arthroscopic and histological outcomes are comparable for both ACI-C and MACI. While MACI is technically attractive, further long-term studies are required before the technique is widely adopted.

The use of chondrogide membrane in autologous chondrocyte implantation

UNLABELLED Autologous chondrocyte implantation is a new technique for the treatment of chondral defects in the knee. The exact procedure involved is continuously being developed with the ultimate aim of achieving hyaline cartilage regeneration. We present the outcome of our series of 31 patients, focussing on the use of the chondrogide membrane in the implantation process. Assessment is presented both in the form of arthroscopic appearance at approximately 1 year, and in the form of clinical outcome measures at 1 year and at 2 years after the second stage of the procedure. CONCLUSION the use of chondrogide membrane in the fixation of cells during the implantation process is associated with satisfactory clinical outcome and does not appear to show evidence of hypertrophy at one-year arthroscopy, as compared to periosteum.

Autologous chondrocyte implantation at the knee using a bilayer collagen membrane with bone graft: A PRELIMINARY REPORT

Autologous chondrocyte implantation (ACI) is a technique used for the treatment of symptomatic osteochondral defects of the knee. A variation of the original periosteum membrane technique is the matrix-induced autologous chondrocyte implantation (MACI) technique. The MACI membrane consists of a porcine type-I/III collagen bilayer seeded with chondrocytes. Osteochondral defects deeper than 8 to 10 mm usually require bone grafting either before or at the time of transplantation of cartilage. We have used a variation of Petersons ACI-periosteum sandwich technique using two MACI membranes with bone graft which avoids periosteal harvesting. The procedure is suture-free and requires less operating time and surgical exposure. We performed this MACI-sandwich technique on eight patients, five of whom were assessed at six months and one year post-operatively using the modified Cincinnati knee, the Stanmore functional rating and the visual analogue pain scores. All patients improved within six months with further improvement at one year. The clinical outcome was good or excellent in four after six months and one year. No significant graft-associated complications were observed. Our early results of the MACI-sandwich technique are encouraging although larger medium-term studies are required before there is widespread adoption of the technique.

WHO IS THE IDEAL CANDIDATE FOR AUTOLOGOUS CHONDROCYTE IMPLANTATION

We investigated the prognostic indicators for collagen-covered autologous chondrocyte implantation (ACI-C) performed for symptomatic osteochondral defects of the knee. We analysed prospectively 199 patients for up to four years after surgery using the modified Cincinnati score. Arthroscopic assessment and biopsy of the neocartilage was also performed whenever possible. The favourable factors for ACI-C include younger patients with higher pre-operative modified Cincinnati scores, a less than two-year history of symptoms, a single defect, a defect on the trochlea or lateral femoral condyle and patients with fewer than two previous procedures on the index knee. Revision ACI-C in patients with previous ACI and mosaicplasties which had failed produced significantly inferior clinical results. Gender (p = 0.20) and the size of the defect (p = 0.97) did not significantly influence the outcome.

Histological evaluation of chondral defects after autologous chondrocyte implantation of the knee

We have performed a prospective, single-surgeon study analysing the histological results of autologous chondrocyte implantation. Fourteen patients underwent autologous chondrocyte implantation of the knee and were evaluated at one year by clinical assessment and arthroscopy. Standard staining was used to examine the sections. In addition, in situ hybridisation was used to establish type-IIa and type-IIb collagen mRNA expression and immunolocalisation techniques demonstrated the positions of type-II and type-X collagen. Eight patients regenerated hyaline cartilage and also contained type-X collagen in the deepest layers and type-II collagen in the deep layers. Three demonstrated fibrocartilage and had type-I collagen in the deep layers. In situ hybridisation revealed that all 14 samples had the potential to express both type-IIa and type-IIb collagen. We have shown that one year after the initial implantation chondrocytes are capable of producing type-II collagen and that they continue to proliferate and mature.

Collagen-covered autologous chondrocyte implantation for osteochondritis dissecans of the knee: two- to seven-year results.

We prospectively studied the clinical, arthroscopic and histological results of collagen-covered autologous chondrocyte implantation (ACI-C) in patients with symptomatic osteochondritis dissecans of the knee. The study included 37 patients who were evaluated at a mean follow-up of 4.08 years. Clinical results showed a mean improvement in the modified Cincinnati score from 46.1 to 68.4. Excellent and good clinical results were seen in 82.1% of those with juvenile-onset osteochondritis dissecans but in only 44.4% of those with adult-onset disease. Arthroscopy at one year revealed International Cartilage Repair Society grades of 1 or 2 in 21 of 24 patients (87.5%). Of 23 biopsies, 11 (47.8%) showed either a hyaline-like or a mixture of hyaline-like and fibrocartilage, 12 (52.2%) showed fibrocartilage. The age at the time of ACI-C determined the clinical outcome for juvenile-onset disease (p = 0.05), whereas the size of the defect was the major determinant of outcome in adult-onset disease (p = 0.01).

Non-invasive distal femoral expandable endoprosthesis for limb-salvage surgery in paediatric tumours

We report our early experience with the use of a non-invasive distal femoral expandable endoprosthesis in seven skeletally immature patients with osteosarcoma of the distal femur. The patients had a mean age of 12.1 years (9 to 15) at the time of surgery. The prosthesis was lengthened at appropriate intervals in outpatient clinics, without anaesthesia, using the principle of electromagnetic induction. The patients were functionally evaluated using the Musculoskeletal Tumour Society scoring system. The mean follow-up was 20.2 months (14 to 30). The prostheses were lengthened by a mean of 25 mm (4.25 to 55) and maintained a mean knee flexion of 110 degrees (100 degrees to 120 degrees ). The mean Musculoskeletal Tumour Society score was 68% (11 to 29). Complications developed in two patients; one developed a flexion deformity of 25 degrees at the knee joint, which was subsequently overcome and one died of disseminated disease. The early results from patients treated with this device have been encouraging. The implant avoids multiple surgical procedures, general anaesthesia and assists in maintaining leg-length equality.

Metal ion levels after metal-on-metal proximal femoral replacements: A 30-YEAR FOLLOW-UP

Metal-on-metal hip bearings are being implanted into younger patients. The consequence of elevated levels of potentially carcinogenic metal ions is therefore a cause for concern. We have determined the levels of cobalt (Co), chromium (Cr), titanium (Ti) and vanadium (Va) in the urine and whole blood of patients who had had metal-on-metal and metal-on-polyethylene articulations in situ for more than 30 years. We compared these with each other and with the levels for a control group of subjects. We found significantly elevated levels of whole blood Ti, Va and urinary Cr in all arthroplasty groups. The whole blood and urine levels of Co were grossly elevated, by a factor of 50 and 300 times respectively in patients with loose metal-on-metal articulations when compared with the control group. Stable metal-on-metal articulations showed much lower levels. Elevated levels of whole blood or urinary Co may be useful in identifying metal-on-metal articulations which are loose.

Peri-acetabular resection and endoprosthetic reconstruction for tumours of the acetabulum

We treated 98 patients with peri-acetabular tumours by resection and reconstruction with a custom-made pelvic endoprosthesis. The overall survival of the patients was 67% at five years, 54% at ten years and 51% at 30 years. One or more complications occurred in 58.1% of patients (54), of which infection was the most common, affecting 30% (28 patients). The rate of local recurrence was 31% (29 patients) after a mean follow-up of 71 months (11 to 147). Dislocation occurred in 20% of patients (19). Before 1996 the rate was 40.5% (17 patients) but this was reduced to 3.9% (two patients) with the introduction of a larger femoral head. There were six cases of palsy of the femoral nerve with recovery in only two. Revision or excision arthroplasty was performed in 23.7% of patients (22), principally for uncontrolled infection or aseptic loosening. Higher rates of death, infection and revision occurred in men. This method of treatment is still associated with high morbidity. Patients should be carefully selected and informed of this pre-operatively.

Chromosomal Aberrations in the Peripheral Blood of Patients with Metal-on-Metal Hip Bearings

BACKGROUND Approximately one-third of patients undergoing joint replacement are under sixty years of age. Many of these patients may be exposed to wear debris from the orthopaedic implant for several decades. Clinical follow-up of this group of patients has been short compared with the lifetimes of the patients, and the long-term effects of this chronic exposure are unknown. METHODS By using cytogenetic biomarkers (twenty-four-color fluorescent in situ hybridization [FISH]), we analyzed the peripheral blood leukocytes for chromosomal aberrations in three groups of subjects: (1) six age and sex-matched control subjects who had no implant and did not smoke (control group), (2) five subjects in whom an implant with a metal-on-metal articulation had been in situ for an average of thirty-five years (metal-on-metal group), and (3) four subjects in whom a metal-on-metal implant had been revised to a metal-on-polyethylene articulation at an average of twenty-two years (revised group). RESULTS The number of chromosomal aberrations in the metal-on-metal group was greater than that in the control group. Specifically, the percentage of aneuploidy gain was three times greater (p = 0.01) in the metal-on-metal group. Structural aberrations were not seen in the control group, and this difference was highly significant (p = 0.003). Also, the number of chromosomal aberrations in the metal-on-metal group was greater than that in the revised group. Specifically, the percentage of structural aberrations was thirty-one-fold higher (p = 0.013). The percentage of aneuploidy gain in the metal-on-metal group was about twice that in the revised group, although this difference was not significant (p = 0.37). The percentage of aneuploidy gain in the revised group was about double that in the control group, although this difference was also not significant (p = 0.41). Translocations were seen only in subjects with a metal-on-metal articulation. CONCLUSIONS The clinical consequences of the chromosomal changes seen in this study are unknown, and it is unknown if the changes are present in other cells in the body. The results emphasize the need for additional investigations into the effect of chronic exposure to elevated levels of metal ions produced by orthopaedic implants.