Surgical Synovectomy Research Articles

Clinical Responses to Gene Therapy in Joints of Two Subjects with Rheumatoid Arthritis

This paper provides the first evidence of a clinical response to gene therapy in human arthritis. Two subjects with rheumatoid arthritis received ex vivo, intraarticular delivery of human interleukin-1 receptor antagonist (IL-1Ra) cDNA. To achieve this, autologous synovial fibroblasts were transduced with a retrovirus, MFG-IRAP, carrying IL-1Ra as the transgene, or remained as untransduced controls. Symptomatic metacarpophalangeal (MCP) joints were injected with control or transduced cells. Joints were clinically evaluated on the basis of pain; the circumference of MCP joint 1 was also measured. After 4 weeks, joints underwent surgical synovectomy. There were no adverse events in either subject. The first subject responded dramatically to gene transfer, with a marked and rapid reduction in pain and swelling that lasted for the entire 4 weeks of the study. Remarkably, joints receiving IL-1Ra cDNA were protected from flares that occurred during the study period. Analysis of RNA recovered after synovectomy revealed enhanced expression of IL-1Ra and reduced expression of matrix metalloproteinase-3 and IL-1beta. The second subject also responded with reduced pain and swelling. Thus, gene transfer to human, rheumatoid joints can be accomplished safely to produce clinical benefit, at least in the short term. Using this ex vivo procedure, the transgene persisted within the joint for at least 1 month. Further clinical studies are warranted.

Successful treatment of relapsing Pigmented Villonodular Synovitis (PVNS) of the knee with radiosynoviorthesis

Poster presentation PVNS is a rare disorder characterised by benign proliferation of synovial tissue. The treatment is surgical but relapse rate is high (8% to 46%). We report a 13 years old girl with PVNS of the left knee diagnosed in February 2003. Three months after diagnosis she underwent surgical synovectomy. Two years later important swelling of left knee with pain and limitation of movement developed and MRI confirmed the relapse of PVNS. She was treated with 3 intraarticular injections of etanercept two months apart with mild reduction of fluid but not of synovial hypertrophy. In November 2006 radiosynoviorthesis with one intraarticular injection of 186Re was performed. No side effects were reported and patient presented an important reduction of pain and improvement of range of motion. Six months after the procedure MRI showed marked decrease of fluid accumulation, and a mild reduction of synovial hypertrophy. One further intraarticular injection of 186Re has been performed 18 months after the first in order to obtain a more complete effect on synovial thickening. In our case radiosynoviorthesis has been showed as a safe and effective treatment in relapsing PVNS, which can be considered both as alternative to surgical synovectomy and complementary to it in order to obtain a more persistent remission of the disease. The collaboration between paediatric rheumatologist, nuclear physician and orthopaedic surgeon is fundamental in establishing the timing of the procedure as well as type and dose of radioisotope to be used according to the age of the patient and the PVNS extension.

Treatment of skin necrosis after radiation synovectomy with yttrium-90: a case report

Chronic synovitis, unresponsive to systemic medical therapy including agents, anti-inflammatory drugs and remission-inducing agents, and intra-articular administration of corticosteroids can be treated with surgical, chemical and radiation synovectomy. We reported a case of a 23 years old male. Skin radiation necrosis (4 x 5 cm) developed after an injection of Yttrium-90 (Y-90). Full-thickness skin graft had been applied but we were not able to succeed. Skin radiation necrosis was treated with Limberg's flap. As a result we recommend flap surgery instead of skin graft in skin radiation necrosis.

Arthroscopic surgical synovectomy of the knee joint (indications, technic, follow-up results)

Between 1981 and 1986, synovectomy was performed arthroscopically at Düsseldorf University Orthopedic Clinic on 59 knee joints of 56 patients without opening the joint. Of these, 43 patients, i.e., 45 knee joints, were followed up on average 2.7 years postoperatively. In the author's experience arthroscopic-surgical synovectomy puts less strain on the patient. The risk of damaging cutaneous nerve branches is low, neuromuscular joint control is preserved, and no fibroarthrosis occurs. All the compartments of the knee joint - including, in particular, the posterior ones - are accessible from a few stab incisions. Since traumatization is minimal there is less postoperative pain than with the conventional method so that as a rule rehabilitation presents no problems, especially in the first six postoperative weeks. The indication threshold for arthroscopic synovectomy is lower than for conventional synovectomy, thus facilitating the decision to perform synovectomy early. In the event of recurrence the pathologic synovialis can once again be excised from the same approaches.

La synovite villonodulaire de l’enfant : une revue de six cas

Pigmented villonodular synovitis is an exceptional condition in children. The clinical, biological and imaging presentation is not specific and a histology sample is required for certain diagnosis. Because of this lack of specificity, together with the rare occurrence of the disease, late diagnosis is not uncommon, making correct management an even greater challenge in the growing child. Between 1995 and 2001, six children were treated for pigmentary villonodular synovitis, four girls and two boys, mean age 11.5 years. The knee was involved in five cases (three diffuse forms and two localized forms). One diffuse form involved the ankle. The diagnosis was suggested by the MRI findings in all patients and confirmed at the histological examination of a biopsy sample. Surgery was used in five cases and medical treatment in one patient with a diffuse form affecting the knee. A synoviorthesis (Hexatrione) was used systematically in three diffuse forms affecting the knee joint. Mean follow-up was 58 months. Recurrence was noted in two diffuse forms, one involving the knee at 10 months from arthroscopic synovectomy and one involving the ankle 24 months after surgical synovectomy. Systematic use of the synoviorthesis did not prevent recurrence in one case. The synoviorthesis was also used in the two cases of recurrence as a complement to surgical treatment but with no effect. Growth was not affected in any of the children. The etiopathogenic mechanism underpinning pigmented villonodular synovitis remains unclear. Genetic factors are suspected in childhood cases. MRI is the complementary examination of choice for diagnosis and follow-up. In children, treatment of pigmented villonodular synovitis depends on marginal excision of the lesion for localized forms and total synovectomy for the diffuse forms. The efficacy of the triamcinolone hexacetonide synoviorthesis remains open to debate and would require a larger series with longer follow-up for evaluation.

Synovial Chondromatosis of the Metacarpophalangeal Joint - A Case Report -

Synovial chondromatosis is an uncommon lesion, which is characterized by cartilaginous and osseous metaplasia of the joint synovium. Synovial chondromatosis usually involves a large joint and rarely occurs in the hand. Intra-articular synovial chondromatosis during the hand should be considered in the differential diagnosis of swollen, stiff or painful joints. Other possible diagnoses include osteoarthritis, rheumatoid arthritis, gout, trauma and chronic infection. Moreover, if enchondral ossification of loose bodies is not seen a diagnosis of synovial chondromatosis can not be made preoperatively. Intra-articular synovial chondromatosis is a benign condition and surgical synovectomy remains the most effective treatment. The authors report a case of synovial chondromatosis of the fifth metacarpophalangeal joint.

Radioactive synoviorthesis for the treatment of haemophilic synovitis

Radioactive synoviorthesis, with (90)Y (knees) and (186)Rh (elbows and ankles) is a highly effective procedure that decreases both the frequency and the severity of recurrent intra-articular bleeds related to joint synovitis. The procedure should be performed as soon as possible to minimize the degree of articular cartilage damage, which based on many studies is irreversible. It can also be used in patients with inhibitors. On average, radioactive synoviorthesis has a 75-80% satisfactory outcome in the long-term. From the clinical standpoint, such efficacy can be measured by the decrease in the number of haemarthroses, with complete cessation for several years in some cases. One should bear in mind that in 20-25% of cases, radioactive synoviorthesis fails to control haemarthroses. In such cases, it can be repeated. Personal experience and the general recommendation among orthopaedic surgeons and haematologists is that when three early consecutive radioactive synoviortheses (repeated every three months) fail to halt synovitis, a surgical synovectomy (open or by arthroscopy) should be immediately considered.

Haemophilic synovitis: basic concepts

Chronic synovitis is a serious complication of haemophilia that should be understood to avoid or minimize its consequences (articular damage and joint degeneration). Haematological prophylaxis and treatment are paramount during the life of people with haemophilia. However, as about 80% of bleedings in haemophilia affect the musculo-skeletal system, the role of orthopaedic surgeons, rehabilitation physicians and physiotherapists is very important in the context of the multidisciplinary team. Synovitis can firstly be prevented and/or controlled with medical treatment and then be treated by synoviorthesis or surgical synovectomy. In this article, the author reviews some current basic principles on the prevention and treatment of haemophilic synovitis to avoid further development of joint destruction (haemophilic arthropathy).

Imaging of Synovial Chondromatosis with Radiologic-Pathologic Correlation

Primary synovial chondromatosis represents an uncommon benign neoplastic process with hyaline cartilage nodules in the subsynovial tissue of a joint, tendon sheath, or bursa. The nodules may enlarge and detach from the synovium. The knee, followed by the hip, in male adults are the most commonly involved sites and patient population. The pathologic appearance may simulate chondrosarcoma because of significant histologic atypia, and radiologic correlation to localize the process as synovially based is vital for correct diagnosis. Radiologic findings are frequently pathognomonic. Radiographs reveal multiple intraarticular calcifications (70%-95% of cases) of similar size and shape, distributed throughout the joint, with typical "ring-and-arc" chondroid mineralization. Extrinsic erosion of bone is seen in 20%-50% of cases. Computed tomography (CT) optimally depicts the calcified intraarticular fragments and extrinsic bone erosion. Magnetic resonance (MR) imaging findings are more variable, depending on the degree of mineralization, although the most common pattern (77% of cases) reveals low to intermediate signal intensity with T1-weighting and very high signal intensity with T2-weighting with hypointense calcifications. These signal intensity characteristics on MR images and low attenuation of the nonmineralized regions on CT scans reflect the high water content of the cartilaginous lesions. CT and MR imaging depict the extent of the synovial disease (particularly surrounding soft-tissue involvement) and lobular growth. Secondary synovial chondromatosis can be distinguished from primary disease both radiologically (underlying articular disease and fewer chondral bodies of variable size and shape) and pathologically (concentric rings of growth). Treatment of primary disease is surgical synovectomy with removal of chondral fragments; recurrence rates range from 3% to 23%. Malignant transformation to chondrosarcoma is unusual (5% of cases) and, although difficult to distinguish from benign disease, is suggested by multiple recurrences and marrow invasion. Recognizing the appearances of primary synovial chondromatosis, which reflect their underlying pathologic characteristics, improves radiologic assessment and is important to optimize patient management.

Les traitements non antibiotiques de la borréliose de Lyme

Non-antibiotic treatment of Lyme borreliosis is only indicated in a few specific clinical situations. In chronic Lyme arthritis, intra-articular steroids are useful to immediately relieve symptomatic joint effusion. Nevertheless, 4 studies with weak methodological evidence were convergent enough to recommend not proposing intra-articular injection before or even immediately after antibiotic treatment. The injection can only be recommended in the treatment of patients whose joint effusion persists despite 2 courses of oral antibiotherapy or one course of IV antibiotherapy. For some experts, the injection can only be made after negative PCR assessment of the joint fluid for spirochetes. This recommendation, although logical, has never been evaluated. Radiation synovectomy may be indicated in persistent synovitis after antibiotherapy and before surgical synovectomy. Further studies are mandatory to confirm the role of radiation synovectomy in the local therapy. Arthroscopic synovectomy can reduce the period of joint inflammation when persistent synovitis is associated with significant pain or limited function. Several experts recommend using the procedure only if synovitis persists after 2 months of antibiotherapy and a negative PCR joint fluid assessment. Non-steroidal anti-inflammatory drugs are often prescribed for their symptomatic effects. Experimental data is consensual on the deleterious consequences of systemic corticosteroid therapy. Corticosteroids are not indicated in Lyme's disease. In post Lyme's disease syndrome, patient complaints may lead to a multidisciplinary therapeutic management and the use of neuro-psychiatric drugs.

Diagnosis of plant-thorn synovitis by high-resolution ultrasonography: a case report and literature review

Plant-thorn synovitis is an uncommon cause of arthritis and has not been reported in Asian countries. Zanthoxylum ailanthoides, an aromatic plant distributed in East Asia, is used as a spice in Taiwan. We reported a case of acute monoarthritis over the third metacarpo-phalangeal joint of the right hand after an injury by the thorn of the Zanthoxylum ailanthoides. A thorn foreign body of 2.7 mm in length was detected in the joint by high-resolution ultrasonography and led to a surgical synovectomy. The patient recovered completely after synovectomy. Plant-thorn synovitis is easily negligible. Early diagnosis is difficult and frequently delayed. The removal of thorn by synovectomy is the only curative treatment for plant-thorn synovitis. Compared to CT and MRI, ultrasonography is inexpensive, nonradioactive, repeatable, and easily accessible. It could detect foreign bodies that are smaller than 0.5 mm. High-resolution ultrasonography is a useful tool for detecting plant thorn and could promote early diagnosis.

Cysteine and serine proteases of synovial tissue in rheumatoid arthritis and osteoarthritis

Objective: To compare the activities of cathepsin B (EC 3.4.22.1) and L (EC 3.4.22.15), calpain (EC 3.4.22.17), and dipeptidyl peptidase (EC 3.4.14.5 or DPP IV or CD26) in synovial membrane from patients with rheumatoid arthritis (RA), osteoarthritis (OA), and post‐traumatic joint injury (PT).Methods: Forty RA patients were divided into two groups on the basis of surgical procedure: the RAs group comprised 18 patients requiring surgical synovectomy; the RAr group comprised 22 patients requiring a total joint replacement or arthrodesis. A third group (the OA group) comprised 19 OA patients while six patients with post‐traumatic joint injury were included in the fourth group (the PT group). Cathepsin and calpain activity was assessed using a Cobas Fara II centrifugal analyser. DPP IV activity was determined kinetically using a fluorogenic substrate.Results: RAs patients were significantly younger than RAr patients, and the mean duration of RA was shorter in the RAs group than in the RAr group. Cathepsin and calpain activity in synovial membrane was higher in RA and OA patients than in the control group, but no statistical difference was observed between RA and OA. However, cathepsin, calpain, and DPP IV synovial activity was significantly higher in the RAs group than in either the OA or the PT group.Conclusion: Our results show that proteinase activity tends to be higher in joints with early synovitis in RA, and suggest that these enzymes are not all involved at the same stage of the disease.

Prise en charge de la synovite villonodulaire hémopigmentée du genou et de ses récidives: À partir d’une série rétrospective de 28 cas

Purpose of the study The objective of this retrospective study was to analyze clinical observations in pigmented villonodular synovitis (PVNS) of the knee as well as response to treatment in order to better define the diagnostic approach and surgical treatment and follow-up of this rare benign proliferative disease of the synovial observed primarily in the knee joint. Material and methods Twenty-eight patients (13 men and 15 women) were treated for PVNS in our unit between 1996 and 2004. Twenty patients had diffuse disease and eight localized disease. In the localized forms, symptoms mimicked those provoked by intra-articular foreign bodies or meniscal tears (n = 6) and had been present for 14 months on average at first consultation. Mean age at treatment onset was 40 years (range 20-62). Arthroscopic or open surgery was used for resection. In the diffuse forms, symptoms had begun 15 months on average before first consultation and were mainly spontaneous hemarthrosis or diffuse non-specific knee pain. Mean age at treatment onset was 38 years (range 15-59). Bone lesions were observed in four patients. Synoviorthesis or surgical synovectomy were performed. Mean follow-up was 97 months (range 12-309). Outcome was compared between the different aspects of localized and diffuse PVNS and treatment modalities. Results In the localized forms, there were no complications after surgical treatment and there were no cases of recurrence (one surgical revision at four months following incomplete resection). For the diffuse forms, the cumulative recurrence rate was 50%. Mean time to recurrence was 37 months. Three patients developed a stiff knee after open synovectomy. Surgical treatment was required in four patients seen late after development of bony lesions (total knee arthroplasty in three). Clinical outcome was good with a gain in knee flexion. Discussion MRI is essential for the topographic diagnosis and to guide surgical treatment. In severe or advanced primary diffuse di-sease or in the event of local recurrence, adjuvant synoviorthesis can be proposed four to eight weeks after initial surgery. The risk of recurrence for diffuse forms warrants an annual MRI for the first four years.

The haemophilic ankle

Radiation synoviorthesis is a very effective procedure that decreases both the frequency and the intensity of recurrent ankle bleeds related to ankle synovitis. The procedure should be performed as soon as possible to minimize the degree of articular cartilage damage. It can also be used in patients with inhibitors with minimal risk of complications. On average, the efficacy of the procedure ranges from 76% to 80%, and can be performed at any age. The procedure slows the cartilaginous damage which intra-articular blood tends to produce in the long term. After 30 years of using radiation synovectomy worldwide, no damage has been reported in relation to the radioactive materials. Radiation synovectomy is currently the preferred procedure when radioactive materials are available; however, chemical synoviorthesis is an effective alternative method if radioactive materials are not available. Personal experience and the general recommendation among orthopaedic surgeons and haematologists is that when three early consecutive synoviorthesis (repeated every 3 months) fail to halt synovitis, a surgical synovectomy (open or by arthroscopy) should be immediately considered. For advanced haemophilic arthropathy of the ankle, the best solution is an ankle arthrodesis. Primary prophylaxis and radioactive synoviorthesis are the best ways that we have today of protecting against haemophilic synovitis and arthropathy of the ankle joint.

Prevention and treatment of musculoskeletal disease in the haemophilia population: role of prophylaxis and synovectomy

Prophylaxis is defined as primary (started before the onset of joint damage) or secondary (started after the onset of joint damage). The aim of primary prophylaxis is to prevent recurrent bleeding into joints and the development of chronic arthropathy in later life. When started early, and at most after two joint bleeds, the result is predictably excellent if there is compliance with the primary prophylaxis regimen. In order to decrease the need for central venous access devices to assure reliable venous access, a number of centres start primary prophylaxis with once weekly infusions with dose-escalation based on frequency of joint bleeding. A major unanswered question is whether primary prophylaxis can be safely discontinued in adolescents/young adults and if so, when. A promising predictor for the milder bleeding phenotype in persons with severe haemophilia is a later onset of joint bleeding. Once joint damage has occurred as a result of recurrent bleeding, secondary prophylaxis can only retard, but not prevent, ongoing joint damage. Other strategies to decrease recurrent bleeding from target joints include surgical synovectomy (ideally performed using an arthroscopic technique), radionuclide synovectomy and chemical synovectomy. These interventions have very good outcomes when performed by an experienced team. Given the very high cost of factor concentrates required for programmes of prophylaxis prospective studies that document benefits to the child and family, e.g. quality of life are to be encouraged.

Pigmentierte villös-noduläre Synovitis des distalen Radioulnargelenks

A 32-year-old female patient underwent surgical synovectomy in the right distal radioulnar joint because of local recurrence of pigmented villonodular synovitis (PVNS) after previous surgery. 7 weeks after her second surgery she received fractionated radiation therapy (RT) to a total dose of 36.0 Gy given in five weekly fractions of 2.0 Gy. Apart from a mild skin erythema the patient had no early morbidity related to the use of RT. After a follow-up of 36 months no local recurrence was detected. In accordance with literature data the hitherto course of the presented case corroborates that RT is a safe and effective treatment option for the prevention of PVNS recurrence.

Radiosynoviorthesis in the treatment of disabling arthritis

Chronic synovial inflammation leads to pannus formation and destruction of the articular cartilage. Synovitis results in proliferation of articular mucosa, destroys cartilage, penetrates bone, tears ligaments and tendons and results in joint destruction. Recurring hemarthrosis in hemophilia responds poorly to available therapy. Synovectomy is indicated in patients resistant to articular steroid injection. Chemical synovectomy using osmic acid or alkylating agents has limited acceptance. Surgical synovectomy is usually the treatment of choice and gives 2 to 3 years of relief. However, the long recovery period, expense, technical difficulty and post surgical complications, provide incentive to explore alternative forms of treatment like radionuclide synovectomy. Radiosynoviortheis means reconstruction/renewal of the articular mucosa (synovitis) with radioactive isotopes [1]. Radio nuclide synovectomy with radio colloidal gold (198Au-colloid) has been used to alleviate pain and swelling of rheumatoid arthritis and related joint diseases for more than 40 years. Initial results were not encouraging due to non-availability of ideal radio pharmaceuticals but availability of 90Y(Yttrium), 32P(Phosphorus), 186Re(Rhenium), 153Sm(Samarium), 165Dy(Dysprosium) and 168Ho(Holmium) has given a fresh impetus. The object of radio nuclide synovectomy is to destroy the diseased pannus and inflammed synovium by direct and selective irradiation with the expectation that the regenerated synovium will be free of disease. The histological changes include regression in size and hyperemia in the synovial villi, reduction of cellular infiltration and sclerosis of the synovium with minimal diffuse damage of articular cartilage.

Management of the foot in rheumatoid arthritis

Rheumatoid arthritis is an autoimmune-mediated, systemic, inflammatory disease which is chronic and progressive in nature. It is the most common form of inflammatory arthritis and affects 1% of men and 3% of women. Diagnostic criteria, as defined by the American Rheumatism Association, are morning

Distribution of Radiation in Synovectomy of the Knee with 166Ho-FHMA Using Image Fusion

Radiation synovectomy is an effective technique for the treatment of chronic synovitis in patients with rheumatoid arthritis (RA), and is an alternative for surgical synovectomy. Holmium ferric hydroxide macroaggregates (166Ho-FHMA) is suitable for radiation synovectomy, especially because it emits high-energy beta particles and a smaller proportion of low-energy photons that are suitable for gamma-camera imaging. The aim of this study was to develop a method to fuse 166Ho-FHMA single photon emission computed tomography (SPECT) and magnetic resonance (MRI) images, to show the distribution of 166Ho-FHMA inside the joint with images that localize synovitis. The knees of 6 patients with RA were treated with 166Ho-FHMA. (99m)Tc-human immunoglobulin ((99m)Tc-HIG) SPECT images and MRI images were taken before 166Ho-FHMA injections. 166Ho-FHMA SPECT images were taken 4, 28, and 40 hours after injections. SPECT and MRI images were merged using a specific image fusion method, called mutual information algorithm, to study associations between anatomical and metabolic information from these images. Fusion of SPECT and MRI images indicated that intensity of radioactivity was associated with the amount of synovitis. Activity distribution of 166Ho-FHMA could be registered using anatometabolic images. A new method to fuse the distribution of radiation in the synovectomy of the knee was developed using SPECT/MRI image registration. Image registration of SPECT and MRI can be used to determine the activity distribution of radioisotopes in relation to synovitis.

Elimination of rheumatoid synovium in situ using a Fas ligand 'gene scalpel'

Surgical synovectomy to remove the inflammatory synovium can temporarily ameliorate rheumatoid inflammation and delay the progress of joint destruction. An efficient medically induced programmed cell death (apoptosis) in the rheumatoid synovium might play a role similar to synovectomy but without surgical tissue damage. Gene transfer of Fas ligand (FasL) has increased the frequency of apoptotic cells in mouse and rabbit arthritic synovium. In this study, we investigated whether repeated FasL gene transfer could remove human inflammatory synovial tissue in situ and function as a molecular synovectomy. Briefly, specimens of human synovium from joint replacement surgeries and synovectomies of rheumatoid arthritis (RA) patients were grafted subcutaneously into male C.B-17 severe combined immunodeficiency (SCID) mice. Injections of a recombinant FasL adenovirus (Ad-FasL) into the grafted synovial tissue at the dosage of 1011 particles per mouse were performed every two weeks. Three days after the fifth virus injection, the mice were euthanized by CO2 inhalation and the human synovial tissues were collected, weighed and further examined. Compared to the control adenovirus-LacZ (Ad-LacZ) and phosphate buffered saline (PBS) injected RA synovium, the Ad-FasL injected RA synovium was dramatically reduced in size and weight (P < 0.005). The number of both synoviocytes & mononuclear cells was significantly reduced. Interestingly, an approximate 15-fold increased frequency of apoptotic cells was observed in RA synovium three days after Ad-FasL injection, compared with control tissues. In summary, our in vivo investigation of gene transfer to human synovium in SCID mice suggests that repeated intra-articular gene transfer of an apoptosis inducer, such as FasL, may function as a 'gene scalpel' for molecular synovectomy to arrest inflammatory synovium at an early stage of RA.