phosphorus-radioisotopes and Synovitis

Many paediatric patients with haemophilia who might benefit from radiosynovectomy (RS) for the control of synovitis do not undergo the procedure as there is controversy in the literature regarding the safety of radiation exposure after two cases of acute lymphocytic leukaemia in children with haemophilia treated with (32) P RS were reported. The purpose of this review was to analyse the safety of RS in paediatric patients with haemophilia and provide a risk-benefit assessment, which practitioners could apply to their patients. Children undergoing knee RS receive a radiation dose of approximately 0.74 mSv (90 megabecquerels-MBq) and elbow and ankle RSs a dose of approximately 0.32 mSv (30-40 MBq). The radiation dose from natural sources is approximately 2 mSv and the recommended limit for patients (apart from natural sources) is 1 mSv per year. The lifetime cancer risk increases about 0.5% per 100 mSv per year. Considering the risks and benefits of RS, the authors recommend that clinicians consider this procedure in children with inhibitors or in patients without inhibitors when bleeding is recurrent and persistent despite aggressive factor replacement.

Topics: Hemophilia A; Humans; Knee Joint; Phosphorus Radioisotopes; Radiation Exposure; Radiography; Radiopharmaceuticals; Range of Motion, Articular; Synovitis

Haemophilic arthropathy occurs due to recurrent bleeding into joints leading to swelling, inflammation, destruction of cartilage and bone, and development of arthritis. Although prophylactic replacement therapy assists in preventing arthropathy, it is not always adequate or affordable. Radiosynovectomy is a minimally invasive intervention for treatment of synovitis in haemophilic joints. The procedure utilises locally injected radioisotopes (Y, P, Rh) to ablate abnormal synovium with the goal of decreasing bleeding, slowing progression of cartilage and bone damage and preventing arthropathy. The objective of this review is to summarize the radiosynovectomy literature and to present patient outcomes associated with radiosynovectomy over the past 17 years from two haemophilia treatment centers (HTCs), one in the United States and one in Spain. Articles from these two centers support the current literature. A retrospective medical records review was performed by the two reporting HTCs on patients who underwent radiosynovectomy prior to 2009. Data review included: site of procedure, isotope utilized, bleeding frequency, and procedure complications. Radiosynovectomy is a cost-effective, minimally invasive, well tolerated procedure. As the paradigm for care in haemophilia shifts towards prevention of joint disease, the number of target joints with synovitis will likely decrease, except in patients who develop inhibitors. We propose early consideration of radiosynovectomy for patients with haemophilic synovitis prior to appearance of articular cartilage damage.

Topics: Adolescent; Adult; Child; Contraindications; Hemophilia A; Humans; Indiana; Joint Diseases; Middle Aged; Neoplasms, Radiation-Induced; Phosphorus Radioisotopes; Radioisotopes; Radiosurgery; Rhenium; Spain; Synovitis; Treatment Outcome; Yttrium Radioisotopes

Joint bleeding is the hallmark of severe haemophilia and the major cause of disability in patients with this coagulopathy. Repeated bleeding into the same joint can lead to chronic synovitis and progressive arthropathy. Radiosynovectomy is one option for the treatment of chronic haemophilic synovitis, but concerns about the risks of exposure to ionizing radiation have divided clinicians as to the safety and appropriate use of the procedure. This article presents two differing viewpoints, one from a pair of orthopaedic surgeons who collectively have performed more than 300 radiosynovectomies in patients with haemophilia. They maintain that radiosynovectomy is a simple, effective, safe and low-cost technique children and adults with chronic haemophilic synovitis. The other perspective is from an experienced haemophilia treater who directs a major US haemophilia treatment centre. She believes that unresolved questions about the safety of radiation exposure in children argue against the use of radiosynovectomy in paediatric patients with haemophilia.

Topics: Arthroscopy; Blood Coagulation Disorders, Inherited; Chronic Disease; Humans; Joints; Phosphorus Radioisotopes; Radiosurgery; Risk Factors; Synovitis; Yttrium Radioisotopes

Radionuclide synovectomy, so-called radioactive synoviorthesis, is easy to perform and a not very expensive procedure (for example, 150 US dollars for an adult knee). Moreover, it is very efficient in diminishing the frequency and intensity of recurrent hemarthrosis related to chronic hypertrophic hemophilic synovitis. It should be performed as soon as possible in order to try to halt the long-term damage that intra-articular blood will produce in the involved joint. Personal experience and the general recommendation among orthopedic surgeons and hematologists is that when three early consecutive synoviortheses (repeated every 3 months) fail to halt synovitis, a surgical synovectomy (open or by arthroscopy) should be immediately considered.

Topics: Child; Cost-Benefit Analysis; Gold Radioisotopes; Hemophilia A; Humans; Phosphorus Radioisotopes; Synovitis; Yttrium Radioisotopes

Topics: Chronic Disease; Colloids; Hemophilia A; Humans; Phosphorus Radioisotopes; Synovitis

Topics: Arthritis, Rheumatoid; Erbium; Gold Colloid, Radioactive; Gold Radioisotopes; Humans; Injections, Intra-Articular; Phosphorus Radioisotopes; Radioisotopes; Synovitis; Yttrium

The aim of this study was to assess the effects of treatment with our locally produced P-32 colloidal suspension on knee synovitic inflammations of hemophilic and rheumatoid arthritis (RA) patients, as well as to compare results with chemical synovectomy or corticoid intra-articular injections and evaluate the cost-benefit ratio.. Thirty-six hemophilic male patients, 4-28 years of age and sent by the Hemophilic Foundation (Buenos Aires, Argentina), were enrolled for knee radiosynovectomy (RS) with P-32 colloid (26 patients), or the antibiotic rifampicin with the cooperation of orthopaedists (10 patients). Parents' informed consent was obtained. The following procedures were performed: routine blood tests, X-ray, ultrasound, a 3-phase bone scan, plus monthly methylene diphosphonate (MDP) controls. Patients were included in this study only if several knee episodes had occurred. Exclusion criteria included bone destruction and big Baker's cyst. Twelve RA patients were included, with similar selection criteria: 6 RA patients received P-32 therapy, and the other 6 patients intra-articular corticoids. Clinical, blind evaluation (state of joint involvement, pain, motility, requirements of antihemophilic factors, corticoids, or analgesics) was registered in follow-up charts. If required, joint aspiration was carried out. Intra-articular instillation of saline plus flushing was done before the needle was withdrawn. P- 32 Bremsstrahlung emission was used in the gamma camera for early and late imaging to confirm the absence of leakage. For intra-articular chemical injections therapy, 4 MBq of Tc-99m MAA (macroaggregates) was used. Immobilization and relative rest for 72 hours followed the procedures.. There were neither local or systemic effects, nor leakage during P-32 treatment. Intra-articular rifampicin and corticoids procedures required frequent injections. Comparison of regions of interest (ROIs) in treated knees during soft-tissue scintigraphies in pre- and post-third MDP control showed knee improvement. The follow-up evaluation demonstrated an increase in joint motion, diminished volume, and less requirement and frequency of the use of antihemophilic factors (AHF) in 80% of the radiosynovectomies (21 of 26), thus lowering health costs. Five female RA patients (5 of 6) had decreased joint swelling and pains, resulting in increased joint motion.. Radiosynovectomy in RA showed a 3-month pain palliative effect. One intra-articular knee radiosynoviorthesis in haemophilic patients provides a more than 3- month relief of symptoms after treatment with locally produced P-32 (11 patients). This turned out to be a safe, economic alternative procedure in emerging nations where the availability of AHF is difficult and expensive.

Topics: Adolescent; Adult; Arthritis, Rheumatoid; Child; Child, Preschool; Colloids; Follow-Up Studies; Hemophilia A; Humans; Knee; Male; Middle Aged; Phosphorus Radioisotopes; Synovitis

This study was performed to prospectively evaluate the safety, efficacy, and cost of injecting P-colloid into joints of children with hemophilia and synovitis to decrease the rate of joint bleeding.. Eligibility included a diagnosis of hemophilia, history of more than six hemorrhages into a joint within a 6-month period, and evidence of synovitis by objective imaging. With written, informed consent, 0.25 to 1.0 mCi of P-colloid was injected into the problem joints. Safety was monitored by external beta-scanning and physical assessment. Efficacy was determined by analysis of the change in joint hemorrhage frequency from 6 months before and up to 96 months after the injection using a signed-rank test. Physical assessment and pain assessment were analyzed similarly using values obtained within 1 week before and 6 months after the radiosynoviorthesis. Cost was modeled using charges from the authors' institution in relation to existing alternative therapies.. One hundred injections were given into 91 joints in 59 children. Seven children had high-titer neutralizing antibodies to factor VIII or IX. Nine children were infected with HIV. Joints injected included 44 ankles, 19 knees, 27 elbows, and 1 shoulder. Nine joints required reinjection. All children showed a significant decrease in bleeding rate (P < 0.0001) and pain (P = 0.03), with improved physical function (P = 0.02). In one child acute lymphocytic leukemia developed, but it was judged unrelated to the two P injections that he had received 3 and 10 months before the leukemia diagnosis. There were no cases of bleeding, infection, or inflammation caused by the injection. Cost was substantially less than medical and surgical alternatives.. Radiosynoviorthesis is effective in limiting the frequency of joint hemorrhage, decreasing pain and improving function in children with hemophilia. However, long-term safety studies are needed.

Topics: Adolescent; Adult; Ankle; Child; Child, Preschool; Cost-Benefit Analysis; Elbow; Female; Hemophilia A; Hemorrhage; Humans; Injections; Knee; Magnetic Resonance Imaging; Male; Phosphorus Radioisotopes; Radionuclide Imaging; Synovitis; Time Factors; Treatment Outcome

Various modes of therapy have been directed at breaking the vicious cycle at early stage of synovitis in haemophilia patients. This study was planned to assess the short-term clinico-radiological outcome of chronic knee synovitis among haemophilia A patients post phosphorus-32 (P-32) radiosynoviorthesis.. P-32 samarium radiocolloid was injected into the knee and patients were followed up at 1 and 3 months, respectively. Clinical outcomes was assessed using Tegner Lysholm scores (TLSs), Modified Knee Society Clinical Rating System (MKSS) score and circumference of the knee joint. The radiological outcomes were assessed using X-ray, ultrasonography and bone scan.. Among the fifteen haemophilia A patients studied, there was statistically significant difference in TLS ( χ. P-32 radiosynoviorthesis done for chronic synovitis among haemophilia A patients showed significant improvement in both clinical and radiological parameters. Ultrasonography can be utilized as non-invasive radiological modality for follow-up of P32 response for knee joint.

Topics: Adolescent; Adult; Child; Chronic Disease; Female; Follow-Up Studies; Hemophilia A; Humans; Injections, Intra-Articular; Knee Joint; Male; Phosphorus Radioisotopes; Synovitis; Time Factors; Treatment Outcome; Young Adult

A new therapeutic radio colloid for radiosynoviorthesis (RS) applications is reported. The method of preparation involves the reaction of SmCl3 carrier with carrier added [32P]H3PO4 in the presence of gelatin. The pure colloid was recovered by dialysis purification leading to radiochemical yield of around 90%. The radiochemical purity of the pure colloid formulated in isotonic saline was over 98%, for the usage period of 14 days, as assessed by paper chromatography. Ninety percent of colloid particles were in the size of 1-10 microm as evident from the laser diffraction particle size analysis, ideally suitable for the intended end use. Animal studies revealed complete retention of the radio colloid in the rabbit knee joint. The results of clinical trials in humans are satisfactory and encouraging, satisfactory retention of the colloid in the knee joint and negligible leakage into the systemic circulation.

Topics: Animals; Arthritis; Brachytherapy; Colloids; Hemophilia A; Humans; Knee Joint; Particle Size; Phosphorus Radioisotopes; Rabbits; Radiopharmaceuticals; Samarium; Synovitis

Radionuclide synovectomy has been identified as the procedure of choice in treating chronic haemophilic synovitis among Caucasian populations. Its effectiveness among East Asians has not been studied. A retrospective study was carried out on 12 Asian haemophiliacs who underwent 12 radionuclide synovectomies. The average follow-up was 30.7 months (range 6-55) for primary procedures. 32P chromic phosphate and 188Re-tin colloid were injected into target joints according to protocol. There was a significant 80% decrease in the median frequency of haemarthrosis from 1.4 per month (range 0.2-7.0) to 0.25 per month (range 0.0-1.8) (P<0.05). Half of the patients had excellent results by 1 year of synovectomy. The median factor usage for target joint haemarthrosis postsynovectomy was 792 units per month (range 0-3209) reduced significantly from a presynovectomy level of 1452 units per month (range 306-7125) (P<0.05). Patients also reported a reduction in joint pain scores, and an improvement in joint mobility and quality of life. The majority of patients were satisfied with the overall outcome of radionuclide synovectomy. Radionuclide synovectomy appears to be effective in reducing the incidence of target joint haemarthrosis and quantity of factor usage for such bleeds among Asians with haemophilic synovitis.

Topics: Adolescent; Adult; Chronic Disease; Follow-Up Studies; Hemarthrosis; Hemophilia A; Hemophilia B; Humans; Male; Middle Aged; Pain Measurement; Patient Satisfaction; Phosphorus Radioisotopes; Quality of Life; Radioisotopes; Retrospective Studies; Rhenium; Severity of Illness Index; Singapore; Synovial Membrane; Synovitis; Treatment Outcome

The principal medical consequence of haemophilia is the development of arthropathy, initiated by a haemarthrosis giving rise to chronic synovitis. Traditional methods of synovectomy include open excision and arthroscopy each of which require substantial amounts of clotting factor concentrate for several weeks, and in the case of open synovectomy, is often associated with loss of range of motion and arthrofibrosis. Radiosynovectomy, the intra-articular injection of low penetration radiocolloids, has been utilized outside the United States for over 20 years. Since 1988, our centre has performed 170 radiosynovectomies utilizing 32P chromic phosphate (32P). This study reports results of 130 32P radiosyovectomies with an average follow-up of 36.5 months (6-140 months). For primary procedures, excellent and good results (haemarthrosis reduction from 75 to 100%) were obtained in 79.2% of cases at 6 months to 8 years. For repeat procedures a combination of excellent and good results were obtained in 62.4% of cases at 6 months to 3 years. Regression analysis showed no correlation between results and age or degree of arthropathy. Radiation was well contained within the joint. There were no observed or identified complications. The procedure is highly cost effective in comparison to open surgical or arthroscopic synovectomy.

Topics: Adolescent; Adult; Age Factors; Child; Child, Preschool; Chromium Compounds; Chronic Disease; Combined Modality Therapy; Follow-Up Studies; Hemarthrosis; Hemophilia A; Hemorrhage; Humans; Injections, Intra-Articular; Middle Aged; Phosphates; Phosphorus Radioisotopes; Retrospective Studies; Risk Assessment; Synovectomy; Synovitis; Treatment Outcome

To evaluate the clinical usefulness of phosphorus-32 chromic phosphate synoviorthesis in patients with hemophilia, recurrent hemarthrosis, and synovitis.. Forty-four P-32 colloid synoviorthesis procedures were performed in 38 patients with these abnormalities. P-32 colloid was injected intramuscularly in a dose of 1.0 mCi (37.0 MBq) in adult knees and 0.5 mCi (18.5 MBq) in adult elbows. A thin-window Geiger-Müller counter was used to survey treated joints, lymph nodes, and liver in order to detect leakage from the joint. Follow-up extended to a maximum of 4 years after treatment.. No evidence of clinically significant leakage was seen. Twenty-two of 28 treatments (78%) with longer than 6 months follow-up were associated with improvement in range of motion and frequency of hemorrhage. Of 15 treatments with longer than 2 years follow-up, 10 (67%) were associated with improvement in range of motion; 12 (80%), with improvement in frequency of hemorrhage; and 12 (80%) with improvement in quality-of-life activities.. P-32 colloid synoviorthesis is a clinically useful out-patient procedure in patients with hemophilia, recurrent hemarthrosis, and synovitis in whom hemostatic therapy has failed.

Topics: Adolescent; Adult; Child; Chromium Compounds; Colloids; Follow-Up Studies; Hemarthrosis; Hemophilia A; Humans; Injections, Intra-Articular; Middle Aged; Phosphates; Phosphorus Radioisotopes; Recurrence; Synovial Membrane; Synovitis

Thirty-one synoviortheses were performed in 22 joints of 14 hemophilic patients (aged 12 to 28 years) with chronic synovitis and for whom "conventional treatments" were considered ineffective. Except for patients with inhibitors, conventional treatments included three to six months of adequate prophylactic therapy with the missing coagulation factors, intensive physiotherapy and, when indicated, antiinflammatory agents and orthosis. Colloidal 32P chromic phosphate was injected intraarticularly in doses of 1.0 mCi for knees and of 0.5 mCi for the other joints. Time of follow-up ranged from two to five years. Frequency and importance of bleeding decreased in all patients. Effect on range of motion was best in knees; six of the seven treated improved and one was unchanged. In elbows, flexion-extension was improved in four cases, unchanged in five and decreased in one; pronation-supination was decreased in four cases. Range of motion was not affected in shoulders and ankles except for internal-external rotation which was improved in two of three shoulders treated. The results of 13 synoviortheses in four hemophilic patients with high titer factor VIII inhibitors were comparable to those in hemophiliacs with no inhibitors. However, in three of the four patients synoviorthesis had to be repeated after two to four years for recurrence of synovitis. Extraarticular escape of radioactivity was monitored 62 times for 17 synoviortheses in 12 patients; extraarticular counts never exceeded 4% of the intraarticular counts. Chromosome aberrations were found not to be increased after treatment in the seven patients in whom adequate analysis could be done.

Topics: Adolescent; Adult; Child; Chromium; Chromium Compounds; Colloids; Elbow Joint; Follow-Up Studies; Hemarthrosis; Hemophilia A; Humans; Injections, Intra-Articular; Knee Joint; Phosphates; Phosphorus Radioisotopes; Radiation Monitoring; Synovitis

Topics: Adolescent; Factor VIII; Hemophilia A; Humans; Injections, Intra-Articular; Middle Aged; Phosphorus Radioisotopes; Synovial Membrane; Synovitis

Topics: Adult; Aged; Chronic Disease; Female; Follow-Up Studies; Humans; Knee Joint; Male; Middle Aged; Phosphorus Radioisotopes; Synovitis; Time Factors

32P-CrPO4 in colloid form has been used for radiosynoviorthesis. There were no acute or subacute side reactions observed. The therapy results were equal to those following 90Y colloid application: 60% very good to good results after 6 months. The substance can be kept on stock since it has a relatively long shelf-life. The cost reduction and the simplification of treatment planning have proved to be the most important advantages of 32P-CrPO4.

Topics: Chromium; Chromium Compounds; Colloids; Humans; Middle Aged; Phosphates; Phosphorus Radioisotopes; Synovitis

Topics: Humans; Phosphorus Radioisotopes; Synovial Membrane; Synovitis