The Journal of Bone & Joint Surgery

The Journal of Bone & Joint Surgery, Volume 90, Issue 2

Scientific Articles | February 01, 2008

Unacceptable Complications Following Intra-Articular Injection of Yttrium 90 in the Ankle Joint for Diffuse Pigmented Villonodular Synovitis

Jacob Bickels, MD¹; Josephine Isaakov, MD¹; Yehuda Kollender, MD¹; Isaac Meller, MD¹

¹ National Unit of Orthopedic Oncology (J.B., I.M., and Y.K.) and Department of Pathology (J.I.), Tel-Aviv Sourasky Medical Center, 6 Weizmann Street, Tel-Aviv 64239, Israel. E-mail address for J. Bickels: jbickels@012.net.il

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Disclosure: The authors did not receive any outside funding or grants in support of their research for or preparation of this work. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

Investigation performed at the National Unit of Orthopedic Oncology and the Department of Pathology, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

The Journal of Bone and Joint Surgery, Inc.

J Bone Joint Surg Am, 2008 Feb 01;90(2):326-328. doi: 10.2106/JBJS.G.00441

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Abstract

Background: Simple resection of diffuse pigmented villonodular synovitis of the ankle joint is associated with local recurrence rates as high as 50%. Thus, adjuvant treatment modalities, such as radiation or intra-articular isotope injection, are sometimes used after tumor resection. Our initial and highly satisfactory experience with the injection of radioactive yttrium 90 to treat pigmented villonodular synovitis of the ankle joint eroded with time so much so that we discontinued its use in the ankle and believe that it is important to alert our colleagues to the complications that we observed.

Methods: Between 1989 and 2006, we treated seven patients who had diffuse pigmented villonodular synovitis of the ankle joint with subtotal synovectomy followed by intra-articular injection of 15 mCi of yttrium 90.

Results: Two of the study patients had full-thickness skin necrosis develop around the injection site, necessitating free muscle flap transfer within three months of treatment, and a third patient had development of a draining sinus that was associated with chronic severe pain. The other four patients reported pain after the injection that was reasonably controlled by the use of nonsteroidal anti-inflammatory drugs. At the most recent follow-up evaluation, no study patient had recurrent disease.

Conclusions: Because of the unacceptably high rate of serious complications associated with the injection of yttrium 90 into the ankle joint following subtotal synovectomy, we discontinued its use as a local adjuvant in the management of diffuse pigmented villonodular synovitis of the ankle.

Level of Evidence: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.

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Introduction

Introduction | Materials and Methods | Results | Discussion | References

Pigmented villonodular synovitis is a benign, proliferative histiocytic disorder of the synovium, which may cause destruction of the articular cartilage, bone erosion, and subsequent extensive degeneration of the affected joint. Simple resection of the lesion is associated with local recurrence rates as high as 50%, and thus adjuvant treatment modalities, such as radiation or intra-articular isotope injection, may be employed after tumor resection^1-3. We routinely used intra-articular injection of yttrium 90 following subtotal synovectomy of the affected joints, as have others^1-3.

Yttrium 90 is a beta-emitting radiocolloid with a physical half-life of sixty-four hours and a beta radiation of 2.27 MeV, the maximal penetration of which in the synovium and cartilage is 11 and 8.5 mm, respectively⁴. Intra-articular injection of yttrium 90 has been reported to relieve pain and inflammation, and has been considered to be an acceptable alternative to surgical synovectomy in patients with rheumatoid arthritis and other inflammatory arthropathies^4,5. Intra-articular injection of a beta-emitting radiocolloid such as yttrium 90 (termed synoviorthesis) leads to phagocytosis of the isotope by the synovial lining cells. The released beta-energy then causes necrosis and subsequent fibrosis of the synovial membrane, cessation of inflammation, and alleviation of the pain and effusion⁵.

In 2002, we reported our experience with the management of diffuse pigmented villonodular synovitis with subtotal synovectomy followed by intra-articular injection of yttrium 90 in ten patients³. The lesion was located in the knee in six patients, in the ankle in three patients, and in the hip in one patient³. No study patient had wound-healing problems or skin necrosis following treatment³. Nine patients had no clinical or radiographic evidence of local recurrence, while one patient had a stable course with no further joint damage³. Encouraged by these findings, we continued to use yttrium-90 injections in the management of diffuse pigmented villonodular synovitis in an additional thirty-nine patients (the lesion was in the knee in thirty-three patients, in the ankle in four patients, and in the hip and shoulder in one patient each). With time, however, the patients with pigmented villonodular synovitis of the ankle joint had an unacceptable number of severe complications that were not observed in other anatomic sites. In the present study, we report our experience with the management of diffuse pigmented villonodular synovitis of the ankle and make recommendations accordingly.

Materials and Methods

Introduction | Materials and Methods | Results | Discussion | References

Between 1989 and 2006, seven patients who had diffuse pigmented villonodular synovitis of the ankle joint underwent subtotal synovectomy and injection of yttrium 90 in our department. Patients who had the localized, nodular form of pigmented villonodular synovitis were treated by surgery alone and were not included in the study. There were five men and two women who ranged in age from twenty-one to fifty-six years (median, thirty-six years; average, thirty-nine years). They were first treated by an open subtotal synovectomy, carried out through medial and lateral incisions. Postoperatively, all study patients received an intra-articular injection of 15 mCi (555 MBq) of yttrium-90 citrate colloidal suspension (Amersham, Buckinghamshire, United Kingdom). That yttrium-90 injection was done at least six weeks (range, six to sixteen weeks; median, 8.5 weeks) after surgery in order to allow complete healing of the surgical wounds, restoration of muscle strength and range-of-motion around the ankle, and healing of the joint capsule that would prevent the leakage of the yttrium 90 into the surrounding soft tissues. The intra-articular position of the needle was verified by an injection of contrast medium under fluoroscopy prior to the yttrium-90 injection.

Following the injection, passive motion of the ankle joint was performed on the operating table to ensure spreading of the yttrium 90 throughout the joint space. A Geiger counter was used to confirm that there had been no extra-articular or systemic leakage of yttrium 90. A bulky dressing was then applied over the ankle for forty-eight to seventy-two hours, after which gradual movement of the joint and weight-bearing were allowed.

Follow-up evaluations took place every two weeks for the first two months after surgery, every three months for two years, and annually thereafter. The evaluation included inspection of the ankle for radiation-induced soft-tissue damage, joint effusion, and soft-tissue masses, and a determination of pain, tenderness, and range-of-motion. Magnetic resonance images were acquired every six months for the first two years and once yearly thereafter. These patients were followed for twelve to 114 months (median, twenty-eight months; average, forty-seven months).

Results

Introduction | Materials and Methods | Results | Discussion | References

Immediately following yttrium-90 injection, all seven study patients reported pain associated with redness and swelling of the involved ankle. Those findings were attributed to the inflammatory response induced by the presence of yttrium 90 within the joint and are frequently observed following such injections at other anatomic sites. The pain was located around the injection site and was constant and unrelated to position or physical activity. That pain was reasonably controlled in four patients by the use of nonsteroidal anti-inflammatory drugs and subsided after three to four days. In the other three patients, however, the pain, redness, and swelling progressed and became exceptionally severe in magnitude, requiring constant daily administration of narcotics. Full-thickness ulcers, 4 and 5 cm in diameter, were evident after three to four weeks in two patients (Fig. 1). These ulcers were treated with surgical débridement and application of a vacuum dressing for three weeks, but they failed to form viable granulation tissue. These two patients were then managed with definitive reconstructive surgery that included extensive débridement and wound coverage with a free gracilis muscle flap and an overlying skin graft. In one patient, the flap and skin graft were satisfactorily incorporated. In the second patient, the flap was not viable despite repeated attempts at vascularization. It was removed twenty-four hours after surgery, and the wound was covered with a full-thickness skin graft. Only part of that graft remained viable, and the remaining area of the open wound was allowed to heal secondarily over ten weeks. A third patient had a small draining sinus on the lateral aspect of the ankle around the injection site. It was 2 mm in diameter and was associated with constant pain and local tenderness. It healed spontaneously after three months, but the overlying skin had residual discoloration and the tenderness persisted. At the time of the most recent follow-up, no study patient had clinical or radiographic evidence of recurrent disease.

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Fig. 1: Full-thickness ulceration of the medial aspect of the ankle joint four weeks after intra-articular injection of 15 mCi of yttrium 90.

Discussion

Introduction | Materials and Methods | Results | Discussion | References

Patients in the current study who had yttrium 90 injected into the ankle joint following subtotal synovectomy to treat pigmented villonodular synovitis demonstrated unacceptably high rates of complications, which we contend are most probably the results of tissue necrosis induced by the isotope. Stucki et al.⁶ reported no side effects in twenty-three patients with various forms of synovitis around the ankle joint who were treated with an intra-articular injection of 2 mCi of yttrium 90. Kampen et al.⁵ recommended the initial use of 5 to 6 mCi of yttrium 90 in the management of rheumatoid arthritis and other forms of inflammatory synovitis. We had used a relatively larger dose of yttrium 90 (15 mCi) because of the local aggressiveness of the pigmented villonodular synovitis. We hypothesize that the large dose of yttrium 90 could have had a role in the development of the reported complications. We also speculate that local anatomic considerations may have played a part in the evolution of those complications: unlike the hip or the knee joints, the ankle joint is not surrounded by a layer of muscle that could act as a biological barrier to dermal injury but rather has only a thin layer of skin and subcutaneous tissue.

Chin et al.¹ reported on thirty patients with diffuse pigmented villonodular synovitis who were treated with surgery followed by intra-articular injection of dysprosium-165-ferric hydroxide aggregates that was associated with a minimal rate of wound complications. All tumors in that study, however, were located in the knee. Similarly, Ward et al.⁷ reported on ten patients with diffuse pigmented villonodular synovitis who had been treated with surgery and intra-articular injection of colloidal chromic P32. Of those ten patients, one who had pigmented villonodular synovitis in the ankle had swelling of the foot and ankle develop without clinical or radiographic evidence of tumor recurrence⁷. Although reports of treatment of diffuse pigmented villonodular synovitis with surgery and radiation therapy have shown good local tumor control with minimal morbidity, ankle lesions are rare and thus the safety of adjuvant radiation therapy at that site is yet to be proved^8,9.

To the best of our knowledge, this is the first report of such extensive complications following intra-articular injection of yttrium 90 in any anatomic site. The small number of patients in our study precludes the calculation of a true frequency of complications, but, because of the complications we have described, we no longer use intra-articular injections of yttrium 90 in the ankle. Yttrium-90 injection, however, is still applied with use of the same doses previously described by us in the management of diffuse pigmented villonodular synovitis in other anatomic locations. Image Not Available

References

Introduction | Materials and Methods | Results | Discussion | References

Chin KR, Barr SJ, Winalski C, Zurakowski D, Brick GW. Treatment of advanced primary and recurrent diffused pigmented villonodular synovitis of the knee. J Bone Joint Surg Am.2002;84:2192-202.842192 2002 [PubMed]

Mendenhall WM, Mendenhall CM, Reith JD, Scarborough MT, Gibbs CP, Mendenhall NP. Pigmented villonodular synovitis. Am J Clin Oncol.2006;29:548-50.29548 2006 [CrossRef]

Shabat S, Kollender Y, Merimsky O, Isakov J, Flusser G, Nyska M, Meller I. The use of surgery and yttrium 90 in the management of extensive and diffused pigmented villonodular synovitis of large joints. Rheumatology (Oxford).2002;41:1113-8.411113 2002 [CrossRef]

Boerbooms AM, Buijs WC, Danen M, van de Putte LB, Vandenbroucke JP. Radio-synovectomy in chronic synovitis of the knee joint in patients with rheumatoid arthritis. Eur J Nucl Med.1985;10:446-9.10446 1985

Kampen WU, Voth M, Pinkert J, Krause A. Therapeutic status of radiosynoviorthesis of the knee with yttrium [90Y] colloid in rheumatoid arthritis and related indications. Rheumatology (Oxford).2007;46: 16-24.4616 2007 [CrossRef]

Stucki G, Bozzone P, Treuer E, Wassmer P, Felder M. Efficacy and safety of radiation synovectomy with Yttrium-90: a retrospective long-term analysis of 164 applications in 82 patients. Br J Rhematol.1993;32:383-6.32383 1993 [CrossRef]

Ward WG Sr, Boles CA, Ball JD, Cline MT. Diffused pigmented villonodular synovitis: preliminary results with intralesional resection and p32 synoviorthesis. Clin Orthop Relat Res.2007;454:186-91.454186 2007 [CrossRef]

Berger B, Ganswindt U, Bamberg M, Hehr T. External beam radiotherapy as postoperative treatment of diffuse pigmented villonodular synovitis. Int J Radiat Oncol Biol Phys.2007;67:1130-4.671130 2007 [CrossRef]

Wu CC, Pritsch T, Bickels J, Wienberg T, Malawer MM. Two incision synovectomy and radiation treatment for diffuse pigmented villonodular synovitis of the knee with extra-articular component. Knee.2007;14:99-106.1499 2007 [CrossRef]

Topics

ankle ; ankle joint ; intra-articular injections ; pigmented villonodular synovitis ; yttrium

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Jacob Bickels, Josephine Isaakov, Yehuda Kollender, Isaac Meller; Unacceptable Complications Following Intra-Articular Injection of Yttrium 90 in the Ankle Joint for Diffuse Pigmented Villonodular Synovitis. The Journal of Bone & Joint Surgery. 2008 Feb;90(2):326-328.

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