SCIENTIFIC EXHIBIT. RadioGraphics 1999; 19:

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1 SCIENTIFIC EXHIBIT Therapeutic Percutaneous Injections in the Treatment of Malignant Acetabular Osteolyses 1 Anne Cotten, MD Xavier Demondion, MD Nathalie Boutry, MD Bernard Cortet, MD Patrick Chastanet, MD Bernard Duquesnoy, MD David Leblond, MD Percutaneous injection of methylmethacrylate or ethanol may provide marked pain relief or bone strengthening in patients with malignant acetabular osteolyses who are unable to tolerate surgery. Injection of methylmethacrylate is usually indicated when osteolysis involves the weight-bearing part of the acetabulum (ie, the acetabular roof); in all other cases, ethanol injection is preferred. Ethanol and methylmethacrylate injections may be performed together if both weight-bearing and non weight-bearing parts of the acetabulum are involved or extensive soft-tissue involvement is present. Moreover, these injections may be performed prior to radiation therapy, which complements their action due to similar but delayed effects on pain, or after radiation therapy that failed to relieve pain or in cases of local recurrence. Radiography and computed tomography must be performed prior to therapeutic percutaneous injection to assess the location and extent of the lytic process, the presence of cortical destruction or fracture, and the presence of soft-tissue involvement. Fever and transitory worsening in pain may occur secondary to inflammatory reaction in the hours following injection; however, these side effects usually resolve spontaneously within 1 3 days. The decision to perform therapeutic percutaneous injections should be made by a multidisciplinary team because the choice between this option and alternative methods of treatment depends on several factors including the location of the lesion, the local and general extent of the disease, the pain and functional disability experienced by the patient, and the patient s state of health and life expectancy. Index terms: Acetabulum Bone neoplasms, secondary, Bone neoplasms, therapy, Interventional procedures, Interventional procedures, complications, Methylmethacrylate, RadioGraphics 1999; 19: From the Departments of Skeletal Radiology (A.C., X.D., N.B., P.C.) and Rheumatology (B.C., B.D.), Hôpital Roger Salengro-CHRU de Lille, Blvd du Pr J Leclercq, Lille, France; and the Department of Radiology, Centre Oscar Lambret, Lille, France (D.L.). Presented as a scientific exhibit at the 1997 RSNA scientific assembly. Received February 19, 1998; revision requested April 27 and received June 10; accepted June 10. Address reprint requests to A.C. RSNA,

2 INTRODUCTION Osteolytic metastases and myeloma of the acetabulum frequently cause severe pain and functional disability. Treatment of affected patients can be difficult. Surgery is the treatment of choice when there is no local contraindication but can be dangerous in patients with general medical impairment related to underlying disease or prior treatment. Moreover, the clinical benefits of surgical treatment must be weighed against its undesirable effects in patients with a short life expectancy (1). Radiation therapy, which may prevent tumor growth, usually results in partial or complete pain relief, with most patients experiencing some relief within days. Unfortunately, some patients may demonstrate insufficient pain relief or local tumor recurrence after initiation of therapy and are unable to tolerate additional therapy. Moreover, radiation therapy results in only minimal, delayed (2 4 months) bone strengthening that does not allow patients to stand who have extensive lytic lesions of the weight-bearing part of the acetabulum (2,3). Moreover, bone reconstruction is sometimes preceded by transitory osteoporosis, which increases the risk of pathologic fracture. Over the past few years, new techniques have been developed for radiologically-guided percutaneous treatment of osteolytic lesions, especially in the vertebral bodies. These new techniques allow greater pain reduction and bone strengthening (4 12). In this article, we discuss and illustrate the use of percutaneous injection of methylmethacrylate and ethanol in the treatment of malignant acetabular osteolyses. INDICATIONS Percutaneous injection of methylmethacrylate or ethanol for malignant acetabular osteolyses is a palliative procedure that should be offered only to patients who are unable to tolerate surgery. The choice of methylmethacrylate, ethanol, or a combination of the two depends on the therapeutic effect to be achieved and the location of the lesion. Either methylmethacrylate or ethanol may provide early and frequently striking pain relief. However, owing to the mechanical properties of bone cement, which hardens as polymerization occurs, methylmethacrylate may also provide bone strengthening with stabilization of microfractures and reduction of mechanical forces. Consequently, injection of methylmethacrylate is also indicated when the object is to improve mobility in patients with osteolysis involving the weight-bearing part of the acetabulum (ie, the acetabular roof) (13). We usually perform percutaneous injections of methylmethacrylate for osteolyses of the acetabular roof leading to pain or disability, but only when bone destruction is not too extensive and the cement may be expected to produce a mechanical effect. When osteolysis does not involve the weight-bearing part of the acetabulum or when extensive osteolysis or soft-tissue involvement is present, we prefer to perform ethanol injections because pain relief is the sole object of the procedure. Percutaneous injection may result in reduction in tumor volume, especially with repeat ethanol injections. Ethanol and methylmethacrylate injections may be performed together if both weight-bearing and non weight-bearing parts of the acetabulum are involved or extensive soft-tissue involvement is present. These injections may be performed prior to radiation therapy, which complements their action due to similar but delayed effects on pain; alternatively, they may be performed after radiation therapy that failed to relieve pain or in cases of local recurrence. We recommend injecting lesions of the acetabular roof with methylmethacrylate prior to radiation therapy to decrease the risk of pathologic fracture of the acetabulum and to improve walking. TECHNIQUE Radiography and computed tomography (CT) including contiguous thin-section acquisition must be performed in the days preceding therapeutic percutaneous injection to assess the location and extent of the lytic process, the pres- 648 Scientific Exhibit Volume 19 Number 3

3 Figure 1. (a d) Posteroanterior radiographs obtained with fluoroscopic guidance show a 10-gauge needle advanced to the cortical bone overlying the osteolytic metastasis of the acetabular roof (a), injection of the lesion with acrylic cement containing tungsten powder to increase its radiopacity (b), subsequent injection at a different site (c), and nearly complete filling in of the lesion (d). (e) CT scan of the acetabular roof helps confirm satisfactory distribution of the bone cement. A small cement leak into the adjacent soft tissue is seen (arrow). a. b. c. d. e. ence of cortical destruction or fracture (especially of the acetabular roof and acetabular fossa), and the presence of soft-tissue involvement. All procedures are performed with the patient under neuroleptanalgesia. Methylmethacrylate Injection We usually perform methylmethacrylate injection under anteroposterior and lateral fluoroscopic guidance, but CT may be used for needle positioning. A 10-gauge needle is inserted into the osteolytic lesion via a posterior or posterolateral access route with the bevel oriented to facilitate spread of the cement in the desired direction. Methylmethacrylate with the consistency of paste is then injected until resistance is met or until the cement reaches the borders of the osteolytic lesion (Fig 1). Additional injections May-June 1999 Cotten et al RadioGraphics 649

4 2. 3. Figures 2 4. (2) CT scan shows a 20-gauge needle inserted into an extensive osteolytic metastasis that does not involve the weight-bearing part of the acetabulum. (3) CT scan shows injection of contrast material through a 22-gauge needle into an osteolytic lesion of the left ischial bone. (4) CT scan shows injection of contrast material into an osteolytic lesion of the right posterior acetabulum. Note the small leak of contrast material near the needle (arrow), which may be hazardous to the adjacent sciatic nerve (arrowhead). may be performed depending on the distribution of the cement. A total of 7 25 ml (mean, 16 ml) of bone cement is usually injected. Injection is stopped if leakage of bone cement into the joint space or soft tissue is detected. It is highly recommended that CT, which allows assessment of lesion filling as well as detection of methylmethacrylate leakage, be performed in the hours following cement injection. Ethanol Injection In ethanol injection, we usually use CT for both needle positioning and the injection itself because this modality allows optimal assessment of the non weight-bearing part of the acetabulum and of extensive bone destruction or softtissue involvement. A thin (20 22-gauge) needle is inserted into the lesion, and a mixture of 4. lidocaine (1%) and contrast material is injected first to assess the expected distribution of ethanol and decrease the pain produced by the ethanol injection (Figs 2 4). If leakage of contrast material is detected, especially into the joint space, the needle is repositioned and a second test injection is performed. If no contrast material is visualized, the needle has been positioned intravascularly and needs to be repositioned (14). 650 Scientific Exhibit Volume 19 Number 3

5 a. b. c. Figure 5. (a, b) Anteroposterior radiograph (a) and CT scan (b) depict osteolytic metastasis of the weightbearing part of the acetabulum and of the acetabular fossa (arrowheads in b). (c) Radiograph obtained 1 month after cement injection reveals that traumatic acetabular protrusion has occurred. Next, a solution of 95% ethanol is injected slowly. Injection volume depends on lesion size and diffusion of contrast material. A volume of 1 4 ml is usually sufficient for osteolytic lesions, but in patients with extensive soft-tissue involvement, the volume can reach ml. One or more injections may be performed at different sites on the same day, especially in bulky lesions. In such cases, repeat injections performed over the ensuing weeks may improve pain relief and decrease tumor size (14). CONTRAINDICATIONS Methylmethacrylate injection is contraindicated in coagulation disorders due to the large diameter of the needles used. The thin needles used for ethanol injection allow injections to be performed, albeit cautiously, in these patients. Fracture or destruction of the articular cortex of the acetabulum is not a contraindication for injection of cement or ethanol but should prompt the use of extreme caution during the procedure to prevent leakage into the joint space. In contrast, associated osteolysis of the acetabular fossa, which increases the risk of traumatic acetabular protrusion when the patient stands, may be a relative contraindication for the injection of bone cement because the mechanical effects and pain relief produced by methylmethacrylate allow patients to stand and to walk better (Fig 5). May-June 1999 Cotten et al RadioGraphics 651

6 Figures 6, 7. (6) Anteroposterior radiograph of the right hip demonstrates a leak of bone cement into the joint space (arrowhead) and soft tissue (arrow). (7) CT scan obtained in a different patient demonstrates an intraarticular leak of bone cement (arrowhead) SIDE EFFECTS AND COMPLICATIONS Regardless of which agent is injected, a fever and transitory worsening in pain may occur secondary to inflammatory reaction in the hours following injection (13,14). These side effects resolve spontaneously within days (mean, 1 3 days) following the procedure. To minimize these side effects, nonsteroidal anti-inflammatory drugs may be administered during this time. In one study, transitory renal insufficiency occurred after methylmethacrylate injection in a patient with myeloma and may have been related to the disease (13). Leakage of bone cement into the joint space represents the principal risk associated with methylmethacrylate injection, a risk that increases when there is destruction of the cortex of the acetabular roof and cement with a liquid consistency is injected (13). As soon as a leak is detected, the injection should be stopped and the hip mobilized to flatten the cement while it still has the consistency of paste. This complication was seen in two of our patients. The leaks were associated with a striking transitory increase in pain; ironically, however, they did not prevent either secondary pain relief or improved walking (Figs 6, 7). Small leaks of methylmethacrylate into the acetabular fossa were detected in three patients but were without clinical significance at follow-up. No intraarticular leaks of ethanol were observed. Small cement leaks into soft tissue due to cortical osteolysis or puncture holes were detected in half our patients but were also without clinical significance at follow-up. Other potential complications include vascular injury, nervous injury, and infection, none of which was observed. CLINICAL EFFECTS The principal effect of percutaneous injection of methylmethacrylate or ethanol is early and frequently striking pain relief, especially when initial pain is considerable. Pain relief has been reported within hours to 4 days (mean, 24 hours) after methylmethacrylate injection (13). This pain relief is probably attributable to tumor necrosis and destruction of sensitive nerve endings in surrounding tissue by vascular, chemical, thermal, or mechanical effects (5). Methylmethacrylate injection of the weightbearing parts of the acetabulum may also allow improved walking. Cotten et al (13) reported seeing this clinical effect in each of 11 patients within 1 5 days (mean, 3 days) of bone cement injection, especially in previously bedridden patients. This improvement in walking is not necessarily synchronous with pain relief and does not appear to be proportional to the quality 652 Scientific Exhibit Volume 19 Number 3

7 of lesion filling (13). Indeed, excellent clinical and functional results can be obtained in some patients despite what appears to be insufficient lesion filling. Owing to the rapid onset of clinical improvement, hospitalization time is short (24 hours for ethanol injection and an average of 4 days for methylmethacrylate injection), which is important in patients with a short life expectancy. The results of clinical follow-up in patients who undergo percutaneous injection are more difficult to assess. Methylmethacrylate injection is usually followed by radiation therapy, which has similar effects on pain and walking. Clinical improvement seems to be maintained unless the lytic lesion is not stabilized with radiation therapy or pathologic fracture of the acetabulum occurs. Repeat ethanol injections may be performed, increasing pain relief and in some cases reducing tumor volume, especially in extensive lesions (14). CONCLUSIONS Percutaneous injection of methylmethacrylate or ethanol is a palliative procedure that may be helpful in the treatment of malignant acetabular osteolyses by providing rapid and frequently striking pain relief and improved walking. The decision to use this procedure should be made by a multidisciplinary team because the choice between this option and surgery, radiation therapy, medical treatment, or a combination of these alternative methods depends on several factors. These factors include the location of the lesion, the local and general extent of the disease, the pain and functional disability experienced by the patient, and the patient s state of health and life expectancy. REFERENCES 1. Harrington KD. The management of acetabular insufficiency secondary to metastatic malignant disease. J Bone Joint Surg [Am] 1981; 63: Shepherd S. Radiotherapy and the management of metastatic bone pain. Clin Radiol 1988; 39: Gilbert HA, Kagam AR, Nussbaum H, et al. Evaluation of radiation therapy for bone metastases: pain relief and quality of life. AJR 1977; 129: Galibert P, Deramond H, Rosat P, Legars D. Note préliminaire sur le traitement des angiomes vertébraux par vertébroplastie percutanée. Neurochirurgie 1987; 33: Deramond H, Darrasson R, Galibert P. Percutaneous vertebroplasty with acrylic cement in the treatment of aggressive spinal angiomas. Rachis 1989; 1: Cotten A, Deramond H, Cortet B, et al. Preoperative percutaneous injection of methyl methacrylate and N-butyl cyanoacrylate in vertebral hemangiomas. AJNR 1996; 17: Weill A, Chiras J, Simon JM, Rose M, Sola- Martinez T, Enkaoua E. Spinal metastases: indications for and results of percutaneous injection of acrylic surgical cement. Radiology 1996; 199: Heiss JD, Doppman JL, Olfield EH. Brief report: relief of spinal cord compression from vertebral hemangioma by intralesional injection of absolute ethanol. N Engl J Med 1994; 331: Heiss JD, Doppman JL, Olfield EH. Treatment of vertebral hemangioma by intralesional injection of absolute ethanol. N Engl J Med 1996; 16: Chiras J, Cognard C, Rose M, et al. Percutaneous injection of an alcoholic embolizing emulsion as an alternative preoperative embolization for spine tumor. AJNR 1993; 14: Cotten A, Dewatre F, Cortet B, et al. Percutaneous vertebroplasty for osteolytic metastases and myeloma: effects of the percentage of lesion filling and the leakage of methyl methacrylate at clinical follow-up. Radiology 1996; 200: Gangi A, Kastler BA, Dietemann JL. Percutaneous vertebroplasty guided by a combination of CT and fluoroscopy. AJNR 1994; 15: Cotten A, Deprez X, Migaud H, Chabanne B, Duquesnoy B, Chastanet P. Malignant acetabular osteolyses: percutaneous injection of acrylic bone cement. Radiology 1995; 197: Gangi A, Dietemann J-L, Schultz A, Mortazavi R, Jeung MY, Roy C. Interventional radiologic procedures with CT guidance in pain management. RadioGraphics 1996; 16: May-June 1999 Cotten et al RadioGraphics 653