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.
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.
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. 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.Introduction
Methods
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. 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.Aims
Patients and methods
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.
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. 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.Purpose
Introduction
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.
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.
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.
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.
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.
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).
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).
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.
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).
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).
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.
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.