Introduction: The rotator cuff is subject to constant pressure from the head of the humerus. This tends to ‘wring out’ the blood supply resulting in a functionally avascular critical zone, although microvessels can be identified. This zone is the site of degeneration and tears. Damage repair under these conditions would be difficult. Myofibroblasts are characteristic of the contractile phase of wound healing. We have examined their distribution in both healthy resected and torn, degenerating rotator cuff tissue and correlated their presence with vascularity and hypoxia in the surrounding tissue. Methods: Rotator cuff tissue was obtained from ten patients undergoing surgical repair. The size of tear was 1–4.5cm, Immunohistochemical staining with commercial monoclonal antibodies to HIF-1α (Hypoxia inducible factor), vimentin, smooth muscle actin (SMA), CD31 and VEGF was performed on formalin fixed paraffin embedded tissues. Visualisation used standard DAB chromagen technique. Results: Focal myofibroblast positivity (SMA+/VIM+) was detected, areas of positivity were found at the interface between torn and degenerating tissues adjacent to the tear. Myofibroblasts were absent in degenerating tissue. The areas of myofibroblast positivity were well vascularized, with strong VEGF positivity. Nuclear HIF-1α positivity was identified in the adjacent endothelial cell population and sporadically in fibroblast population, although not in the myofibroblasts. Conclusion: Evidence of an ongoing wound healing response was found in tissue from torn rotator cuffs. However, it was patchy and infrequent.

Aims: To assess the reliability of ultrasound guided (USG) tru-cut needle biopsy technique in the management of soft tissue tumours.

Methods: Pathology reports of patients who underwent USG needle biopsy and surgical resection of the tumour between 1994 and 2002 were reviewed. 141 biopsies (142 patients; 59 females and 82 males; mean age 52.5 years [range 16 to 96]) were included. Exclusions were those who did not undergo both procedures, had recurrent disease, had previous biopsy of same site, inadequate or damaged biopsy materials.

Results: Final histology showed 74 malignant and 68 benign tumours compared with 72 and 70, respectively, on biopsy reports, with 94.6% sensitivity, 97.1% specificity, 97.2% positive predictive value (PPV) and 94.3% negative predictive value (NPV). The histological grade was commented on in 48 cases. Final histology reported 18 high grades versus 30 low or medium grades compared to 17 and 31, respectively, on biopsy reports, giving 88.9% sensitivity, 96.7% specificity, 94.1% PPV and 93.5% NPV. Overall accuracy is 95.8% for malignant/benign reporting and 93.8% for grading. One patient developed superficial haematoma that underwent spontaneous uneventful resolution.

Conclusions: This technique is as reliable as open biopsy, yet avoids the need for general anaesthesia and inpatient admission. Tumour visualisation improves sampling while the larger needle gives greater volume than fine needle aspiration.

The role of matrix metalloproteinases (MMPs) in the aseptic loosening of hip prostheses is well established. Gelatinase MMPs have been identified in the interface membranes and the pseudosynovial tissues in the hips. Little data are available on gelatinase MMPs and their major regulators, including specific tissue inhibitors of matrix metalloproteinases (TIMPs) in the loosening of shoulder prostheses. The objectives of this study were to determine whether A) gelatinase MMPs and their regulators (MMP14, TIMP-1,-2) are produced by periprosthetic tissues in cases of aseptic loosening of shoulder prostheses, and, B) to identify which cell types, in both interface and synovial tissues, localize the enzymes.

Interface tissues and synovial tissues were obtained during revision surgery for loose shoulder implants. In 9 patients (6-Total Shoulder Replacement, 3-Hemiarthro-plasty (Bipolar), 9 samples of interface tissues and 8 samples of synovial tissues were obtained. Of the interface tissues 2 were from the interface of the bipolar and the unresurfaced glenoid. Formalin-fixed paraffin embedded sections were stained using primary antibodies for MMP2 (Neomarkers), MMP9 (Oncogene Ltd), TIMP1, TIMP2 & MMP14 (Chemicon Ltd). Antigen retrieval required pressure cooker treatment for MMP2 and MMP9 and trypsin for TIMP1. Visualisation used a standard DAB chromagen technique (Envision, Dako Ltd.). Appropriate control sections ensured reproducibility of the staining. The antibodies selected bind to both active and inactive forms of the MMPs.

Both HDPE and metal debris were seen in both the synovial and interface tissues. Transformation of macrophages to giant cells was associated with PE debris, and was not observed with metal debris alone.

The presence of gelatinase MMPs in both interface and synovial tissues in aseptic loosening of shoulder prostheses was demonstrated. Differences between the MMP content of macrophages and giant cells between the tissues was detected, positivity was associated with the presence of metallic and/or HDPE debris. Activation of endothelial MMP2 by both MMP14 and low levels of TIMP2 would support the development of a vascular network.

The overall incidence of cuff tears increases with age, individuals over 80years having a 51% incidence of a tear. Currently, the aetiology of rotator cuff tears remains unclear and successful repair is achieved in only 30% patients. Matrix metalloproteinases (MMPs) have roles in a wide range of physiological processes including placentation and embryogenesis, tissue remodelling and wound healing. However, the ability of MMPs to dissolve extracellular matrix has been linked to a variety of pathological processes including rheumatoid arthritis, osteoarthritis, periodontitis and multiple sclerosis, which involve excessive matrix destruction. Production of gelatinase MMPs by torn rotator cuff has been demonstrated. The objectives of this study were to examine the expression of MMPs and their association with histological changes in full thickness tears of the rotator cuff.

Rotator cuff tissue was obtained from ten patients (age 40–80years) undergoing surgical repair. The size of tear was 1–4.5cm; time from presentation to surgery was 1 month (acute) to between 0.5–4years (chronic). Immunohistochemical staining with commercial monoclonal antibodies to a range of MMPs, endothelial, macrophage and fibroblast markers was performed. Production of gelatinase MMPs was measured by gelatin zymography on tissue culture supernatant. Visualisation used a standard DAB chromagen technique.

In the acute specimens there was an infiltrate of macrophages with little collagen degeneration; the fibro-blasts were MMP1 positive and endothelial cells MMP2 positive. At 12 months post-tear mature collagen, plump fibroblasts and proliferating endothelial cells were identified adjacent to the resection edge. Towards the torn edge areas of lower cellularity, sparse vascularity and collagen degeneration were observed. Vimentin positive, CD68 negative cells within this matrix were rounded with foamy cytoplasm, and intensely positive for MMP1 and MMP2, and positive for MMP-3, -10, -11, -13 and -14. Tissue culture supernatant demonstrated active and latent MMP2 production in all cases.

The prolonged interval between trauma and surgical repair, with potential pharmacological intervention, remedial physiotherapy and disuse immobility, make assessment of the factors contributing to tendon degeneration difficult to determine. Fatty infiltration, dystrophic calcification and patchy collagen degeneration were common. However, clear evidence of cellular activities typical of wound repair were also identified, including fibroblast and endothelial cell proliferation. The most striking finding was the association between areas of poor collagen structure with fibroblasts staining intensely for both MMP1 and MMP2 and positive for other matrix metalloproteinases. The production of MMP1 and MMP2 may contribute to active remodelling of the tendon matrix. Success of repair could be influenced by both the quality of the matrix and the cell types and activities in the tissue at the resection edge.

Purpose: To investigate the relationships between vascular endothelial growth factor (VEGF), a proliferation marker (Ki-67) and the cell cycle inhibitor p27 (cyclin-dependent kinase inhibitor p27), in endothelial cells in chronic degeneration of the rotator cuff.

Background: The rotator cuff is subject to constant pressure from the head of the humerus. This tends to ‘wring out’ the blood supply resulting in a functionally avascular critical zone, although microvessels can be identified. This zone is the site of degeneration and tears. Attempts at repair under these circumstances could be compromised by inadequate local function of the vascular system particularly sprouting of the capillaries to support the repair process.

Methods: Rotator cuff tissue was obtained from ten patients (age 40–80y) undergoing surgical repair. The size of tear was 1–4.5cm, time from presentation to surgery was 1 month (acute) to between 0.5–4y (chronic). Immunohistochemical staining with commercial mono-clonal antibodies to VEGF, p27, Ki-67 was performed on formalin fixed paraffin embedded tissues. Endothelial cells were identified by CD31 and smooth muscle actin (SMA) positivity. Visualisation used a standard DAB chromagen technique.

Results: Microvessel distribution varied according to tissue location, being pronounced towards the muscle insertion and torn edges of tissue, but much reduced in areas of healthy tendon and absent from areas with clear signs of advanced matrix degeneration without tears. Widespread VEGF positivity was observed in fibroblast and endothelial cell populations and diffusely within the matrix. Strong P27 positivity was observed in many endothelial cells which consequently demonstrated little Ki-67 staining.

Conclusion: Thus the endothelial cells appear to be simultaneously under both a mitogenic, VEGF drive, and subject to an inhibition of proliferation i.e. p27 positivity.