J. Somville

The infrapatellar fat pad should be considered as an active osteoarthritic joint tissue: a narrative review

INTRODUCTION Osteoarthritis (OA) of the knee joint is caused by genetic and hormonal factors and by inflammation, in combination with biomechanical alterations. It is characterized by loss of articular cartilage, synovial inflammation and subchondral bone sclerosis. Considerable evidence indicates that the menisci, ligaments, periarticular muscles and the joint capsule are also involved in the OA process. This paper will outline the theoretical framework for investigating the infrapatellar fat pad (IPFP) as an additional joint tissue involved in the development and progression of knee-OA. METHODS A literature search was performed in Pubmed from 1948 until October 2009 with keywords InFrapatellar fat pad, Hoffa fat pad, intraarticular adipose tissue, knee, cartilage, bone, cytokine, adipokine, inflammation, growth factor, arthritis, and OA. RESULTS The IPFP is situated intracapsularly and extrasynovially in the knee joint. Besides adipocytes, the IPFP from patients with knee-OA contains macrophages, lymphocytes and granulocytes, which are able to contribute to the disease process of knee-OA. Furthermore, the IPFP contains nociceptive nerve fibers that could in part be responsible for anterior pain in knee-OA. These nerve fibers secrete substance P, which is able to induce inflammatory responses and cause vasodilation, which may lead to IPFP edema and extravasation of the immune cells. The IPFP secretes cytokines, interleukins, growth factors and adipokines that influence cartilage by upregulating the production of matrix metalloproteinases (MMPs), stimulating the expression of pro-inflammatory cytokines and inhibiting the production of cartilage matrix proteins. They may also stimulate the production of pro-inflammatory mediators, growth factors and MMPs in synovium. CONCLUSION These data are consistent with the hypothesis that the IPFP is an osteoarthritic joint tissue capable of modulating inflammatory and destructive responses in knee-OA.

Magnetic resonance imaging of soft tissue tumors.

Abstract. This article outlines the ability of MR imaging in staging, grading, tissue characterization, and posttherapeutic surveillance of soft tissue tumors. Well-known staging parameters, such as extent, relationship with adjacent structures, and detection of intralesional necrosis, are used in the MR protocol for locoregional staging. Bone scintigraphy and high-resolution CT scan of the lungs are best methods for ruling out metastatic spread. A variety of (solitary or combinations of) grading parameters are described in the radiological literature. The role of MR imaging is to afford recognition of these lesions that need further aggressive work-up, excluding all others. Despite controversial reports, the definite role of MR imaging in grading of soft tissue tumors seems to become established. As for grading, a lot of individual imaging characteristics used for tissue characterization have low sensitivity, but combinations of parameters (age, site, signal intensities) are more useful and often allow to predict a specific diagnosis or to narrow down the list of differential diagnoses. Local recurrences of soft tissue tumors are frequent and can be detected accurately by an easy-to-use MR algorithm.

MR imaging of clear cell sarcoma (malignant melanoma of the soft parts): A multicenter correlative MRI-pathology study of 21 cases and literature review

Abstract Objective. To evaluate MR imaging and pathology findings in order to define the characteristic features of clear cell sarcoma of the soft tissues (malignant melanoma of the soft parts). Design and patients. MR examinations of 21 patients with histologically proven clear cell sarcoma of the musculoskeletal system were retrospectively reviewed and assessed for shape, homogeneity, delineation, signal intensities on T1- and T2-weighted images, contrast enhancement, relationship with adjacent fascia or tendon, secondary bone involvement, and intratumoral necrosis. In 19 cases the pathology findings were available for review and for a comparative MR-pathology study. Results. On T1-weighted images, lesions were isointense (n=3), hypointense (n=7) or slightly hyperintense to muscle (n=11). Immunohistochemical examination was performed in 17 patients. All 17 specimens showed positivity for HMB-45 antibody. In nine of 11 lesions with slightly increased signal intensity on T1-weighted images, a correlative MR imaging-pathology study was possible. All nine were positive to HMB-45 antibody. Conclusions. Clear cell sarcoma of the musculoskeletal system often has a benign-looking appearance on MR images. In up to 52% of patients, this lesion with melanocytic differentiation has slightly increased signal intensity on T1-weighted images compared with muscle. As the presence of this relative higher signal intensity on T1-weighted images is rather specific for tumors displaying melanocytic differentiation, radiologists should familiarize themselves with this rare entity and include it in their differential diagnosis when confronted with a well-defined, homogeneous, strongly enhancing mass with slightly higher signal intensity compared with muscle on native T1-weighted images.

An Experimental Model for Kinematic Analysis of the Knee

The description of the relative motion between rigid bodies is called kinematics. The knee joint is the largest joint of the human body and has an intricate anatomy, and thus its kinematics have intrigued researchers for a long time1. Apart from direct visual observation, the most popular tool for studying the joint has been radiography. Historically, the knee has been treated as if it were a planar mechanism 2. In other words, the movement of the knee was reduced to a two-dimensional projection of a three-dimensional reality. In recent years, the limitations of this methodology have become clear, with the major flaw being the inability to ascertain the location of the axes of rotation before performing kinematic analyses3. In 1983, Grood and Suntay presented a joint coordinate system that provided a geometric description of the three-dimensional rotational and translational motion between two rigid bodies, and they applied this system to the knee joint4. With use of this model, the described joint displacements became independent of the order in which the component rotations and translations occur. The new mathematical insights led to the concept of the helical axis and opened the door for a correct scientific description of the kinematics of the knee, thus allowing for six degrees of freedom5. However, as the mathematical accuracy improved, the complexity increased and the model appeared to be impractical and difficult to apply to the clinical setting (i.e., the clinicians failed to understand the engineers). Hollister et al., and later Churchill et al., tried to bridge the gap, reducing the descriptive model to essentially two degrees of freedom6,7. In the model of Hollister et al., knee motion was described as pure rotations occurring around two axes: the so-called flexion-extension axis and …

Cytokine production by infrapatellar fat pad can be stimulated by interleukin 1β and inhibited by peroxisome proliferator activated receptor α agonist

Background Infrapatellar fat pad (IPFP) might be involved in osteoarthritis (OA) by production of cytokines. It was hypothesised that production of cytokines is sensitive to environmental conditions. Objectives To evaluate cytokine production by IPFP in response to interleukin (IL)1β and investigate the ability to modulate this response with an agonist for peroxisome proliferator activated receptor α (PPARα), which is also activated by lipid-lowering drugs such as fibrates. Methods Cytokine secretion of IPFP was analysed in the medium of explant cultures of 29 osteoarthritic patients. IPFP (five donors) and synovium (six donors) were cultured with IL-1β and PPARα agonist Wy14643. Gene expression of IL-1β, monocyte chemoattractant protein (MCP1), (IL-6, tumour necrosis factor (TNF)α, leptin, vascular endothelial growth factor (VEGF), IL-10, prostaglandin-endoperoxide synthase (PTGS)2 and release of TNFα, MCP1 and prostaglandin E2 were compared with unstimulated IPFP and synovium explants. Results IPFP released large amounts of inflammatory cytokines, adipokines and growth factors. IL-1β increased gene expression of PTGS2, TNFα, IL-1β, IL-6 and VEGF and increased TNFα release in IPFP. MCP1, leptin, IL-10 gene expression and MCP1, leptin and PGE2 release did not increase significantly. Synovium responded to IL-1β similarly to IPFP, except for VEGF gene expression. Wy14643 decreased gene expression of PTGS2, IL-1β, TNFα, MCP1, VEGF and leptin in IPFP explants and IL-1β, TNFα, IL-6, IL-10 and VEGF in synovium that responded to IL-1β. Conclusion IPFP is an active tissue within the joint. IPFP cytokine production is increased by IL-1β and decreased by a PPARα agonist. The effects were similar to effects seen in synovium. Fibrates may represent a potential disease-modifying drug for OA by modulating inflammatory properties of IPFP and synovium.

Peroxisome proliferator activated receptor alpha activation decreases inflammatory and destructive responses in osteoarthritic cartilage

OBJECTIVE Peroxisome proliferator activated receptor α (PPARα) agonists are used in clinical practice as lipid-lowering drugs and are also known to exert anti-inflammatory effects on various tissues. We hypothesized that PPARα activation leads to anti-inflammatory and anti-destructive effects in human OA cartilage. METHODS Cartilage explants obtained from six OA patients were cultured for 48 h with 10 ng/ml interleukin (IL)1β as a pro-inflammatory stimulus. 100 μM Wy-14643, a potent and selective PPARα agonist, was added to the cultures and gene expression of matrix metalloproteinase (MMP)1, MMP3, MMP13, collagen type II (COL2A1), aggrecan and PPARα in cartilage explants and the release of glycosaminoglycans (GAGs), nitric oxide (NO) and prostaglandin E(2) (PGE(2)) in the culture media were analyzed and compared to the control without Wy-14643. RESULTS Addition of Wy-14643 decreased mRNA expression of MMP1, MMP3 and MMP13 in cartilage explants that responded to IL1β, whereas Wy-14643 did not affect gene expression of COL2A1 and aggrecan. Wy-14643 also decreased secretion of inflammatory marker NO in the culture medium of cartilage explants responding to IL1β. Wy-14643 inhibited the release of GAGs by cartilage explants in culture media. CONCLUSION PPARα agonist Wy-14643 inhibited the inflammatory and destructive responses in human OA cartilage explants and did not have an effect on COL2A1 or aggrecan mRNA expression. These effects of PPARα agonists on osteoarthritic cartilage warrant further investigation of these drugs as a potential therapeutic strategy for osteoarthritis (OA).

TruFit plug for repair of osteochondral defects: where is the evidence? : systematic review of literature

Objective: Treatment of osteochondral defects remains a challenge in orthopedic surgery. The TruFit plug has been investigated as a potential treatment method for osteochondral defects. This is a biphasic scaffold designed to stimulate cartilage and subchondral bone formation. The aim of this study is to investigate clinical, radiological, and histological efficacy of the TruFit plug in restoring osteochondral defects in the joint. Design: We performed a systematic search in five databases for clinical trials in which patients were treated with a TruFit plug for osteochondral defects. Studies had to report clinical, radiological, or histological outcome data. Quality of the included studies was assessed. Results: Five studies describe clinical results, all indicating improvement at follow-up of 12 months compared to preoperative status. However, two studies reporting longer follow-up show deterioration of early improvement. Radiological evaluation indicates favorable MRI findings regarding filling of the defect and incorporation with adjacent cartilage at 24 months follow-up, but conflicting evidence exists on the properties of the newly formed overlying cartilage surface. None of the included studies showed evidence for bone ingrowth. The few histological data available confirmed these results. Conclusion: There are no data available that support superiority or equality of TruFit compared to conservative treatment or mosaicplasty/microfracture. Further investigation is needed to improve synthetic biphasic implants as therapy for osteochondral lesions. Randomized controlled clinical trials comparing TruFit plugs with an established treatment method are needed before further clinical use can be supported.

Late peritoneal metastasis in a patient with osteosarcoma

A 19-year-old man with a high-grade osteosarcoma of the femur, treated with neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy suffered from lung metastases 15 months after diagnosis. They were resected. Thirteen months later, he had vague abdominal complaints which, after analysis, proved to be caused by peritoneal metastasis. A review of the literature, possible physiopathological mechanisms of increased occurrence of unusual metastases and the role of bone scintigraphy in the follow-up of patients with osteosarcoma are discussed.

Relationship of the Scarf Valgus-Inducing Osteotomy of the Calcaneus to the Medial Neurovascular Structures

Background: The Scarf valgus inducing osteotomy of the calcaneus is an operative technique to correct varus deformity of the hindfoot. It is versatile with significant corrective power; however, the neurovascular structures are in close proximity on the medial side and thus may be harmed during the osteotomy. Moreover, because this type of osteotomy can cause a great lateral translation, traction of the medial neurovascular structures is possible. We performed an anatomic study to evaluate the medial soft tissues after a lateralizing Scarf-type calcaneal osteotomy. Materials and Methods: The osteotomies were carried out on ten fresh-frozen cadaver specimens. We performed the osteotomy and induced valgus. Then we performed a medial dissection to identify the important medial structures: the medial and lateral plantar nerve (MPN, LPN) and the posterior tibial artery (PTA). We noted their relation to the osteotomy and their integrity. Results: In several cases, one or more of the structures were sectioned. In five cases, all the structures crossed the osteotomy, four of which even a transection of one or both of the plantar nerves occurred. Although the PTA crossed the osteotomy in eight specimens, there was no transection of this structure. Conclusion: Scarf osteotomy of the calcaneus is a highly corrective osteotomy. However, caution must be exercised when performing as the medial neurovascular structures cross the osteotomy lines and transection can occur. Clinical Relevance: When performing the osteotomy one should keep in mind that vigorous sawing and large displacement can cause damage to the medial neurovascular structures.

Soft tissue sarcoma of the extremities: Pending questions on surgery and radiotherapy

Soft tissue sarcomas are uncommon tumours of mesenchymal origin, most commonly arising in the extremities. Treatment includes surgical resection in combination with radiotherapy. Resection margins are of paramount importance in surgical treatment of soft tissue sarcomas but unambiguous guidelines for ideal margins of resection are still missing as is an uniform guideline on the use of radiotherapy.The present paper reviews the literature on soft tissue sarcomas of the extremities regarding the required resection margins, the impact of new radiotherapy techniques and the timing of radiotherapy, more particularly if it should be administered before or after surgical resection.This review was started by searching guidelines in different databases (National Guideline Clearinghouse, EBMPracticeNet, TRIP database, NCCN guidelines,…). After refinement of the query, more specific articles were found using MEDLINE, PubMed, Web of Science and Google Scholar. Used keywords include “soft tissue sarcoma”; “extremities OR limbs”; “radiotherapy”, “surgery”, “margins”, “local recurrence” and “overall survival”. Finally, the articles were selected based on the accessibility of the full text, use of the English language and relevance based on title and abstract.Literature demonstrates positive resection margins to be an important adverse prognostic factor for local recurrence of soft tissue sarcomas of the extremities. Still, no consensus is reached on the definition of what a good margin might be. The evolution of new radiation techniques, especially Intensity Modulated Radiotherapy, resulted in a s healthy surrounding tissues. However, the timing of radiotherapy treatment remains controversial as both preoperative and postoperative radiotherapy are characterised by several advantages and disadvantages.