- Email: [email protected]
Supportive Care Aspects of Vertebroplasty in Patients with Cancer
Supportive Cancer Therapy
comprehensive review
Key words: Kyphoplasty, Metastases, Microfractures, Multiple myeloma, Polymethylmethacrylate, Spinal stability
Supportive Care Aspects of Vertebroplasty in Patients with Cancer Adam S. Wu, Daryl R. Fourney
Abstract Minimally invasive vertebroplasty involves the percutaneous injection of polymethylmethacrylate bone cement into a fractured vertebral body. Although most frequently performed for osteoporotic compression fractures, vertebroplasty has also been very effective in the palliation of back pain secondary to osteolytic metastases and myeloma bone disease. The mechanism of pain relief is unclear; however, stabilization of microfractures and restoration of vertebral body strength is the leading theory. The decision to perform vertebroplasty is made after multiple factors are considered, including clinical presentation, medical fitness, functional capacity, tumor type, location and extent of disease, anticipated radiation sensitivity, and quality of life. Cement extravasation beyond the vertebral body is the most frequent complication; however, it is asymptomatic in the vast majority of patients. In the cancer setting, vertebroplasty is used as an adjunct to other standard treatments, including medical therapy, radiation therapy, chemotherapy, and surgery. In well-selected patients, vertebroplasty offers rapid relief of axial back pain and the potential for improved function.
Introduction
metastases, and making issues of long-term pain control, functional support, and quality of life increasingly important in the management of these patients. Progressive bony involvement of the spinal column in multiple myeloma and malignancies that commonly metastasize to the spine, including lung, breast, and prostate cancer,2,3 gradually weaken the structural strength of the vertebral column and may ultimately lead to vertebral collapse. Pain is the initial complaint in the majority of cases.4
Destructive lesions affecting the spine are an increasingly common problem in the population of patients with cancer, affecting as many as 70% of patients with cancer at some point in the course of their disease, with approximately half being symptomatic and the cause of significant morbidity.1 Advances in oncologic treatment have dramatically increased the survival of patients with many types of cancer, allowing more time for the development of spinal
Address for correspondence: Daryl R. Fourney, MD, FRCSC, University of Saskatchewan, Division of Neurosurgery, Royal University Hospital, 103 Hospital Drive, Saskatoon, SK S7N 0W8, Canada Fax: 306-966-8140; e-mail: [email protected]
Division of Neurosurgery, Royal University Hospital, University of Saskatoon, Saskatchewan, Canada
Submitted: Nov 30, 2004; Revised: Dec 20, 2004; Accepted: Jan 3, 2005 Supportive Cancer Therapy, Vol 2, No 2, 98-104, 2005
Electronic forwarding or copying is a violation of US and International Copyright Laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Cancer Information Group, ISSN #1543-2912, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA 978-750-8400.
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Volume 2, Number 2 • January 2005
Figure 1
A small minority of patients will present with neurologic symptoms secondary to compression of the nerve roots or spinal cord. Multiple factors contribute to the cause of pain. Structural instability of the spinal column, alterations in biomechanics, mass effect from infiltrating and expanding tumor mass, compression of neural elements, and tumor inflammatory mediators all contribute in varying degrees.1,3 Pain and the resultant loss of mobility are associated with the development of pneumonia, deep venous thrombosis, pulmonary embolism, osteoporosis, atelectasis, and decubitus ulcer.1,3 The main goals of therapy are palliation of pain and restoration of function. A wide array of treatment options is available, but all have limitations. Traditional medical therapy includes analgesics, bed rest, and bracing.3 Certain tumor types may also respond to hormone therapy, cytotoxic drugs, and bisphosphonates.4 None of these treatments, however, can restore strength to the collapsed vertebral body or alter pathologic spinal biomechanics. Certain radiation-sensitive tumors respond well to radiation therapy, and external beam radiation will provide pain relief in more than half of these patients.1,2 However, pain relief is not immediate, and radiation therapy may not prevent progressive osteolytic collapse. Irradiation also impairs postoperative wound healing and bony fusion, should surgery ultimately be indicated. Surgical management consists of resection of tumor mass, spinal reconstruction, and stabilization. It usually involves vertebrectomy followed by reconstruction with a titanium cage or bone cement and stabilization with pedicle screws.4 However, perioperative and postoperative surgical risk in the cancer population is significant because of the frequent presence of multiple comorbid conditions and the general medical fragility of these patients. As a result, surgical options are usually limited to patients with single- or adjacent-level disease who are medically fit and have a fair anticipated life expectancy.2,3 Percutaneous vertebroplasty was first used in France in the mid-1980s for the treatment of painful vertebral hemangiomas.2 It involves the fluoroscopically guided injection of polymethylmethacrylate (PMMA) into the affected vertebral level(s). Vertebroplasty has been shown to be effective in relieving pain in osteoporotic compression fractures and osteolytic cancer, including multiple myeloma and metastases.4-16 In North America, the technique was not used frequently in the setting of malignant disease until recent years.3,4
Vertebral Body Metastasis A
B
C
D
A 66-year-old man presented with lung cancer treated with surgery and radiation therapy 6 months previously. He became bedridden secondary to progressive lower back pain over a 4-week period. He did not have radiculopathy. (A) Sagittal T2-weighted MR image shows L3 vertebral body metastasis associated with minimal central canal stenosis. Gadoliniumenhanced T1-weighted sagittal (B) and axial (C) MR images show the extent of vertebral disease limited to L3. (D) Axial CT shows osteolysis of L3 vertebral body with limited involvement of the posterior vertebral wall.
of cement was injected.5 This may account for the observation in clinical studies that pain relief after vertebroplasty is not proportional to the degree of lesion filling.6 It has also been theorized that the heat generated during the polymerization of PMMA may destroy pain receptors and nerve endings in the affected vertebrae, as well as directly coagulate some of the tumor tissue. A direct cytotoxic effect of PMMA, which has been shown to cause necrosis at the PMMA–tumor interface, may also play a role.7
Mechanism of Action The mechanism of action of vertebroplasty is currently unclear and likely to be multifactorial. Biomechanical mechanisms seem to be the most important. Polymethylmethacrylate has been shown to stabilize microfractures and increase the stiffness of treated vertebrae.3,5 The compressive strength of vertebrae injected with PMMA easily surpasses that of noninjected controls. Biomechanical studies have shown that vertebral strength may be restored to regions where as little as 2 mL
Patient Selection, Indications, and Contraindications In the cancer setting, vertebroplasty is most clearly indicated in the patient with well-localized disabling spinal pain associated with thoracic or lumbar vertebral body fracture or
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Figure 2
offered only after a trial of conservative medical management had failed.4,8-12 The length of time conservative measures should be pursued before consideration of vertebroplasty remains poorly defined and is ultimately a matter of clinical judgment. Imaging studies are necessary to help determine candidacy for the procedure. Magnetic resonance imaging (MRI) is essential and must be carefully evaluated for evidence of spinal cord or nerve root compression by epidural disease.2-4 Computed tomography (CT) is also highly recommended because it best shows the extent of osseous destruction of the posterior vertebral cortex. Because vertebroplasty is most commonly performed using fluoroscopic guidance via a transpedicular approach, plain radiographs are necessary to ensure visualization of the pedicles. Poor definition of the pedicles may necessitate an extrapedicular approach or the use of CT guidance for vertebroplasty needle placement.4 For vertebral lysis secondary to metastatic disease or myeloma, vertebroplasty is an adjunctive measure and should be used in combination with other appropriate management strategies. In general, radiation therapy needs to be performed in conjunction with vertebroplasty for malignant spinal disease because cement injection alone does not prevent tumor growth. Radiation therapy does not interfere with the mechanical properties of PMMA and complements its action with additional although delayed effects on pain and bone strengthening.2 Vertebroplasty should be performed before radiation therapy whenever possible because the analgesic effects of the former are immediate and spinal stability is addressed. However, patients with significant epidural softtissue disease may become candidates for vertebroplasty only after shrinkage of tumor by radiation therapy has occurred.4 Absolute contraindications for vertebroplasty are uncorrected coagulopathy, infection at the site of planned injection, intolerance to prone positioning, and lack of surgical backup in the event of postprocedural complications.1,7 Disruption of the posterior vertebral body cortex is a relative contraindication3,7 because of the increased risk of cement leakage into the spinal canal. The presence of a neurologic deficit secondary to epidural compression is also a relative contraindication. Surgical decompression may be the most appropriate treatment for such patients; however, vertebroplasty may still be considered for the palliation of pain if surgery is not feasible. Technical factors somewhat limit the ability to perform vertebroplasty safely and effectively in patients with vertebra plana deformity.2,9 Shimony et al demonstrated that vertebroplasty could be performed safely and effectively in patients with malignant compression and epidural involvement.8 They reviewed 50 patients with metastatic disease or myeloma, dividing patients into 3 groups depending on the extent of epidural involvement. There were no significant differences in pain or mobility outcomes among groups.
Percutaneous Vertebroplasty A
B
C
D
E
The patient shown in Figure 1 underwent bipedicular L3 percutaneous vertebroplasty. Fluoroscopic images obtained during the procedure show transpedicular vertebral body needles in the anteroposterior (A) and lateral planes (B). Successful lesion filling with no evidence of cement extrusion is shown in the anteroposterior (C) and lateral (D) planes. (E) Postoperative axial CT confirms PMMA confinement to the vertebral body lesion. This patient experienced a significant reduction in pain after surgery and became ambulatory. He subsequently received palliative radiation therapy to the spine.
collapse, without evidence of significant epidural disease (Figures 1 and 2).4 However, any patient with intractable axial pain because of vertebral involvement of cancer is potentially a candidate. The care of such patients is multidisciplinary and involves input from the radiation oncologist, medical oncologist, neurosurgical or orthopedic spine surgeon, as well as the pain management and rehabilitation medicine specialists.2-4 Factors that need to be considered in the decision to perform vertebroplasty include clinical presentation, patient preferences, tumor type and location, expected survival, known or anticipated radiation sensitivity, medical stability, functional capacity, and quality of life. In the majority of studies done to date, vertebroplasty was
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Figure 3
In the cancer setting, in which there may be multiple spinal levels of disease, failure to localize the symptomatic level(s) is probably the most frequent contraindication for vertebroplasty. In our experience, a substantial proportion of patients with cancer who may benefit from treatment harbor ≥ 1 relative contraindications for the procedure. Careful clinical judgment must therefore be exercised in weighing the risks and benefits on a case-by-case basis.
Vertebroplasty for Painful Compression Fractures A
B
C
D
Vertebroplasty Procedure Vertebroplasty is most commonly performed under local anesthesia with fluoroscopic guidance. An 11- or 13-gauge needle (Osteo-Site bone biopsy needle) is introduced through a small skin incision and advanced to the rostral aspect of the target pedicle with the bevel directed laterally to avoid penetration of the spinal canal. The needle is then advanced into the anterior third of the vertebral body, proceeding anteriorly, medially, and caudally until the midline is reached in the sagittal plane. Within the vertebral body, the bevel of the needle is then directed medially—the optimal orientation for PMMA delivery. If the diagnosis is uncertain, a 16-gauge needle (Franseen biopsy needle) may be introduced coaxially at this stage to obtain biopsy specimens. The PMMA powder is mixed with barium sulfate powder for opacification and antibiotic powder for infection prophylaxis. Approximately 4-6 mL of PMMA per vertebral body is injected under constant fluoroscopic guidance. If PMMA fills < 50% of the vertebral body, contralateral cannulation of the pedicle and injection are performed (Figure 3). In our experience, unilateral injection provides sufficient filling in roughly two thirds of cases. If extravasation of cement is observed, the needle is adjusted and/or a contralateral injection is attempted. If neither of these adjustments is able to prevent further leakage, the procedure is terminated. A CT scan should be obtained in all cases of cement extravasation.4 Some authors recommend routine postprocedural CT scanning for malignant disease.3 The patient is kept in the supine position for 1 hour to allow the cement to more fully polymerize before being allowed to ambulate.4,11 In most cases, the patient can be discharged later the same day.
A 36-year-old man underwent T6 and T9 vertebroplasty for painful compression fractures secondary to multiple myeloma. Anteroposterior fluoroscopic images obtained during the procedure show (A) needle placement, (B) successful filling of T6 (unipedicular injection) with partial filling of T9, (C) needle placement for left-sided injection of T9 with successful filling of the remaining vertebral body, and (D) the final stabilization.
Complications The most frequent complication of vertebroplasty is PMMA extravasation beyond the confines of the vertebral body. Theoretically, risk of cement leakage is greater in patients with cancer because the posterior wall of the vertebral body may be disrupted by malignant disease.12 The vast majority of leakages are asymptomatic; however, seepage of cement into the neural foramen may result in radiculopathy, and extavasation into the spinal canal may cause compressive myelopathy. Symptomatic compression of the neural elements may require urgent surgery,6 although radicular compression
has been managed effectively with corticosteroids and selective nerve blocks.11 There are rare reports of cement leakage into the paravertebral venous plexus resulting in pulmonary embolism.1,7 Extravasation of cement into the paravertebral soft tissues is generally considered benign. However, there has been one reported case of femoral neuropathy secondary to cement leakage into the psoas muscle.3 An increasingly reported complication is the risk of adjacent fractures after vertebroplasty.13-15 Uppin et al reported that of 177 patients with osteoporosis treated with vertebro-
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patients who underwent vertebroplasty.10 Shimony et al found that 52% of patients had improved mobility after vertebroplasty.8 Similarly, Chow et al reported that 53% of patients had functional improvement after the procedure.9 Finally, Alvarez et al reported that 77% of patients who had ambulatory difficulties before vertebroplasty were improved after the procedure.12 Symptomatic complications were rare in all studies. Rates of cement leakage ranged from 0 to 73%.4,6,12 This wide range of events appeared to largely reflect the criteria used by the authors to define a leak. The vast majority of cement leaks were entirely asymptomatic.
plasty, 22 (12.4%) developed a total of 36 new vertebral body fractures after treatment.13 Twenty-four (67%) of these new fractures involved vertebrae immediately adjacent to the previously treated level. The majority of new vertebral fractures occurred within 30 days after injection of the initial fracture. These authors hypothesized that the increased stiffness of the treated vertebral body may alter the distribution of forces to nearby vertebrae and thus increase the risk of fracture. Baroud et al suggested that the risk of adjacent vertebral body fracture could be lowered by decreasing the amount of PMMA injected or by using a biomaterial softer than PMMA.14 The importance of this risk for patients with cancer is unclear, because nonosteoporotic adjacent vertebrae may be able to tolerate these altered biomechanics within the limited remaining life span of the patient. Other reported complications include infection, allergic reaction of contrast agents, rib fractures from prone positioning in very frail patients, pneumothorax during injection of thoracic levels, and transient increase in pain (usually proportional to the volume of cement injected).7 Thermal injury to the spinal cord or nerve roots from the curing reaction of PMMA had been proposed as a theoretical risk but, to our knowledge, has never been reported.
How Does Vertebroplasty Compare with Kyphoplasty? Kyphoplasty is a recent modification of vertebroplasty in which a balloon is inflated within the collapsed vertebral body before the injection of PMMA.1,4 The advantage of kyphoplasty over vertebroplasty is that use of the balloon allows for some restoration of the vertebral body height and correction of kyphotic deformity. In addition, the bony cavity created by balloon inflation allows for a lower-pressure injection of higher viscosity PMMA, which theoretically reduces the risk of cement leakage. This purported advantage of kyphoplasty has been questioned because the majority of the pressure required for cement delivery during vertebroplasty is derived from the force needed to move PMMA along the long, thin cannula, and not from the highly porous cancellous bone.15 At this time, experience with kyphoplasty is limited in comparison with vertebroplasty. We are not aware of any controlled trials comparing the safety and efficacy of these procedures. In the study reported by Fourney et al, 9.2% of vertebroplasties (6 of 65 procedures) were complicated by a cement leak, whereas there were no reports of cement leakage with kyphoplasty (32 procedures).4 However, cement leakage was asymptomatic in all patients, and the clinical outcome in terms of pain relief, analgesic consumption, and function was similar after either procedure. Kyphoplasty has a number of disadvantages compared with vertebroplasty.4 Because it requires specialized equipment, kyphoplasty is more expensive to perform. Although vertebroplasty is accomplished with a unilateral injection in roughly two thirds of cases, kyphoplasty is almost always performed bilaterally. Owing to its increased complexity, procedural times for kyphoplasty are generally longer by comparison. Finally, whereas vertebroplasty is almost always performed under local anesthesia, kyphoplasty usually requires general anesthesia. Precise indications for kyphoplasty and vertebroplasty are still evolving.4 Controlled trials to evaluate the safety and efficacy of these procedures are needed.
Results Table 1 summarizes most of the clinical series where vertebroplasty has been used in the setting of malignant disease. In patients with back pain secondary to osteolytic metastases and myeloma, the majority report a significant decrease in pain after vertebroplasty.4,6,8-12,16-18 An evaluation of self-reported pain relief with use of a visual analogue scale (VAS) was provided in several reports.4,9,10,16 Diamond et al reported that 86% of patients experienced a drop in VAS scores of > 50% after vertebroplasty.10 Chow et al reported a drop in VAS scores from 10 to 1 with movement, and from 7 to 0 at rest.9 Martin et al reported a mean reduction of VAS scores by 4.3 points after vertebroplasty.16 In patients treated with vertebroplasty and/or kyphoplasty, Fourney et al reported a median decrease in VAS scores from 7 to 2; this effect was durable throughout the first year.4 Improvements in pain control after vertebroplasty led to a reduction in analgesic requirements in a number of studies.4,9,11,12 Fourney et al reported a significant postprocedural decrease in analgesic use in patients who underwent vertebroplasty and/or kyphoplasty.4 Chow et al found a nonsignificant trend toward decreased analgesic consumption after vertebroplasty.9 Cohen et al reported that 76% of patients were able to reduce analgesic dosages after the vertebroplasty,11 but Alvarez et al noted the same in only 50% of patients.12 Functional improvement has also been reported in several studies.4,8-10,12 Diamond et al noted a 50%-60% improvement in standardized scores of activities of daily living in
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Table 1
Summary of Results of Vertebroplasty in Patients with Cancer (Vertebral Metastases and Myeloma Bone Disease)4,6,8-12,16-18* Number of Patients (Levels Treated)
Results
Complications
Follow-up
Shimony et al (2004)8
50 (129)
82% Improved pain; 52% Improved mobility
None; 14% Had increased pain/new areas of pain during follow-up caused by progression of disease
Median, 3 months
Chow et al (2004)9
15 (20)
VAS reduced with movement (10 to 1) and at rest (7 to 0); 53% improved function; Trend to reduced analgesic use
1 Case of cement leakage into spinal canal (motor intact but loss of proprioception); 1 case of reversible tachycardia
12-Week study (3 patients died during follow-up)
Diamond et al (2004)10
7 (14)
86% Had ³ 50% improvement in pain scores; 86% reduced analgesic use
None reported
6 Weeks
Cohen et al (2004)11
31 (43)
76% Reduced analgesic use
Complications specific to tumor subgroup not reported; 5 of 192 (2.6%) procedure-related radiculopathies in entire series
30 Days
Fourney et al (2003)4
34 (65)
86% Improved pain; Median VAS reduced from 7 to 2; Trend to improved ambulation
6 of 65 (9.2%) cement leak, none symptomatic
Median, 4.5 months (range, 1-19.7 months)
Martin et al (2003)16
32 (51)
75% Improved pain; Mean 4.3 decrease in VAS
4 of 51 (8%) cement leak, none symptomatic
2-5 Days
Alvarez et al (2003)12
21 (27)
81% Improved pain (average VAS reduced from 9.1 to 3.2); 50% reduced analgesic use; 10 of 13 patients with gait disorder had improved ambulation (77%)
12 of 27 (44%) cement leak, all asymptomatic except 1 patient with transient radiculitis
Mean, 5.6 months (range, 1-18 months)
Barr et al (2000)17
8 (13)
50% Improved pain
1 Patient with "significant" cement extravasation (asymptomatic)
Mean, 12 months among survivors (4 patients died at mean of 10 months); range, 3 weeks to 35 months
Cotton et al (1997)6
37 (40)
97% Had partial or complete relief of pain; Pain relief not proportional to percentage of lesion filling
29 of 40 (73%) cement leak detected by CT (all asymptomatic except 2 with foraminal extravasation requiring surgery and 1 with transient femoral neuropathy)
Mean, 4.2 months (range, 6 days to 6 months)
73% Had improvement in pain, stable at 6 months; Trend to improved ambulation
3 Patients had transient radiculopathy caused by cement leakage (1 patient required surgical removal of cement from the neural foramen); 2 patients with brief (< 72 hours) increase in local pain, resolved with corticosteroids; 2 patients with cervical vertebroplasty had transient difficulty swallowing
Mean, 7.1 months
Author
Wiell et al (1996)18
37 (52)
*Some results are subgroups of larger series that included patients with non-neoplastic indications, and/or procedures other than vertebroplasty. Only those studies that reported results for the subgroup of patients treated with vertebroplasty for malignant spinal disease are listed.
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Conclusion
6. Cotton A, Dewatr F, Cortet B, et al. Percutaneous vertebroplasty for osteolytic metastases and myeloma: effects of percentage of lesion filling and the leakage of methyl methacrylate at clinical follow-up. Radiology 1996; 200:525-530. 7. Gangi A, Guth S, Imbert JP, et al. Percutaneous vertebroplasty: indications, technique, and results. Radiographics 2003; 23:e10-e10 (Online). 8. Shimony JS, Gilula LA, Zeller AJ, et al. Percutaneous vertebroplasty for malignant compression fractures with epidural involvement. Radiology 2004; 232:846-853. 9. Chow E, Holden L, Danjoux C, et al. Successful salvage using percutaneous vertebroplasty in cancer patients with spinal metastases or osteoporotic compression fractures. Radiother Oncol 2004; 70:265-267. 10. Diamond TH, Hartwell T, Clarke W, et al. Percutaneous vertebroplasty for acute vertebral body fracture and deformity in multiple myeloma: a short report. Br J Haematol 2004; 124:485-487. 11. Cohen JE, Lylyk P, Ceratto R, et al. Percutaneous vertebroplasty: technique and results in 192 procedures. Neurol Res 2004; 26:41-49. 12. Alvarez L, Perez-Higueras A, Quinones D, et al. Vertebroplasty in the treatment of vertebral tumours: postprocedural outcome and quality of life. Eur Spine J 2003; 12:356-360. 13. Uppin AA, Hirsch JA, Centenera LV, et al. Occurrence of new vertebral body fracture after percutaneous vertebroplasty in patients with osteoporosis. Radiology 2003; 226:119-124. 14. Baroud G, Heini P, Nemes J, et al. Biomechanical explanation of adjacent fractures following vertebroplasty [letter]. Radiology 2003; 229:606-607. 15. Baroud G, Bohner M, Heini P, et al. Injection biomechanics of bone cements used in vertebroplasty. Biomed Mater Eng 2004; 14:487-504. 16. Martin JB, Wetzel SG, Seium Y, et al. Percutaneous vertebroplasty in metastatic disease: transpedicular access and treatment of lysed pedicles—initial experience. Radiology 2003; 229:593-597 17. Barr JD, Barr MS, Lemlet TJ, et al. Percutaneous vertebroplasty for pain relief and spinal stabilization. Spine 2000; 25:923-928. 18. Wiell A, Chiras J, Simon JM, et al. Spinal metastases: indications for and results of percutaneous injection of acrylic surgical cement. Radiology 1996; 199:241-247.
Percutaneous vertebroplasty is a minimally invasive technique that has shown considerable promise in the management of pain secondary to lytic spinal metastases and myeloma bone disease. Studies to date have shown that in appropriately selected patients, vertebroplasty offers rapid, durable pain relief in the majority of patients with minimal risk of complications. Effective pain control often translates into improved functional capacity for the patient. For malignant spinal disease, vertebroplasty is an adjunct to other standard medical therapies and radiation therapy. A multidisciplinary approach to patient selection and management is essential. Although kyphoplasty may be differentiated from vertebroplasty on the basis of height restoration and, perhaps, risk of cement extravasation, whether the additional complexity and costs of kyphoplasty are offset by these potential benefits is not known at this time.
References 1. Lieberman I, Reinhardt MK. Vertebroplasty and kyphoplasty for osteolytic vertebral collapse. Clin Orthop 2003; 415(suppl):S176-S186. 2. Lemke DM, Hacein-Bey L. Metastatic compression fractures–vertebroplasty for pain control. J Neurosci Nurs 2003; 35:50-55. 3. Jensen ME, Kallmes DE. Percutaneous vertebroplasty in the treatment of malignant spinal disease. Cancer J 2002; 8:194-206. 4. Fourney DR, Schomer DF, Nader R, et al. Percutaneous vertebroplasty and kyphoplasty for painful vertebral body fractures in cancer patients. J Neurosurg Spine 2003; 98:21-30. 5. Belkoff SM, Mathis JM, Jasper LE, et al. The biomechanics of vertebroplasty. The effect of cement volume on mechanical behavior. Spine 2001; 26:1537-1541.
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comprehensive review
Key words: Kyphoplasty, Metastases, Microfractures, Multiple myeloma, Polymethylmethacrylate, Spinal stability
Supportive Care Aspects of Vertebroplasty in Patients with Cancer Adam S. Wu, Daryl R. Fourney
Abstract Minimally invasive vertebroplasty involves the percutaneous injection of polymethylmethacrylate bone cement into a fractured vertebral body. Although most frequently performed for osteoporotic compression fractures, vertebroplasty has also been very effective in the palliation of back pain secondary to osteolytic metastases and myeloma bone disease. The mechanism of pain relief is unclear; however, stabilization of microfractures and restoration of vertebral body strength is the leading theory. The decision to perform vertebroplasty is made after multiple factors are considered, including clinical presentation, medical fitness, functional capacity, tumor type, location and extent of disease, anticipated radiation sensitivity, and quality of life. Cement extravasation beyond the vertebral body is the most frequent complication; however, it is asymptomatic in the vast majority of patients. In the cancer setting, vertebroplasty is used as an adjunct to other standard treatments, including medical therapy, radiation therapy, chemotherapy, and surgery. In well-selected patients, vertebroplasty offers rapid relief of axial back pain and the potential for improved function.
Introduction
metastases, and making issues of long-term pain control, functional support, and quality of life increasingly important in the management of these patients. Progressive bony involvement of the spinal column in multiple myeloma and malignancies that commonly metastasize to the spine, including lung, breast, and prostate cancer,2,3 gradually weaken the structural strength of the vertebral column and may ultimately lead to vertebral collapse. Pain is the initial complaint in the majority of cases.4
Destructive lesions affecting the spine are an increasingly common problem in the population of patients with cancer, affecting as many as 70% of patients with cancer at some point in the course of their disease, with approximately half being symptomatic and the cause of significant morbidity.1 Advances in oncologic treatment have dramatically increased the survival of patients with many types of cancer, allowing more time for the development of spinal
Address for correspondence: Daryl R. Fourney, MD, FRCSC, University of Saskatchewan, Division of Neurosurgery, Royal University Hospital, 103 Hospital Drive, Saskatoon, SK S7N 0W8, Canada Fax: 306-966-8140; e-mail: [email protected]
Division of Neurosurgery, Royal University Hospital, University of Saskatoon, Saskatchewan, Canada
Submitted: Nov 30, 2004; Revised: Dec 20, 2004; Accepted: Jan 3, 2005 Supportive Cancer Therapy, Vol 2, No 2, 98-104, 2005
Electronic forwarding or copying is a violation of US and International Copyright Laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Cancer Information Group, ISSN #1543-2912, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA 978-750-8400.
98
Volume 2, Number 2 • January 2005
Figure 1
A small minority of patients will present with neurologic symptoms secondary to compression of the nerve roots or spinal cord. Multiple factors contribute to the cause of pain. Structural instability of the spinal column, alterations in biomechanics, mass effect from infiltrating and expanding tumor mass, compression of neural elements, and tumor inflammatory mediators all contribute in varying degrees.1,3 Pain and the resultant loss of mobility are associated with the development of pneumonia, deep venous thrombosis, pulmonary embolism, osteoporosis, atelectasis, and decubitus ulcer.1,3 The main goals of therapy are palliation of pain and restoration of function. A wide array of treatment options is available, but all have limitations. Traditional medical therapy includes analgesics, bed rest, and bracing.3 Certain tumor types may also respond to hormone therapy, cytotoxic drugs, and bisphosphonates.4 None of these treatments, however, can restore strength to the collapsed vertebral body or alter pathologic spinal biomechanics. Certain radiation-sensitive tumors respond well to radiation therapy, and external beam radiation will provide pain relief in more than half of these patients.1,2 However, pain relief is not immediate, and radiation therapy may not prevent progressive osteolytic collapse. Irradiation also impairs postoperative wound healing and bony fusion, should surgery ultimately be indicated. Surgical management consists of resection of tumor mass, spinal reconstruction, and stabilization. It usually involves vertebrectomy followed by reconstruction with a titanium cage or bone cement and stabilization with pedicle screws.4 However, perioperative and postoperative surgical risk in the cancer population is significant because of the frequent presence of multiple comorbid conditions and the general medical fragility of these patients. As a result, surgical options are usually limited to patients with single- or adjacent-level disease who are medically fit and have a fair anticipated life expectancy.2,3 Percutaneous vertebroplasty was first used in France in the mid-1980s for the treatment of painful vertebral hemangiomas.2 It involves the fluoroscopically guided injection of polymethylmethacrylate (PMMA) into the affected vertebral level(s). Vertebroplasty has been shown to be effective in relieving pain in osteoporotic compression fractures and osteolytic cancer, including multiple myeloma and metastases.4-16 In North America, the technique was not used frequently in the setting of malignant disease until recent years.3,4
Vertebral Body Metastasis A
B
C
D
A 66-year-old man presented with lung cancer treated with surgery and radiation therapy 6 months previously. He became bedridden secondary to progressive lower back pain over a 4-week period. He did not have radiculopathy. (A) Sagittal T2-weighted MR image shows L3 vertebral body metastasis associated with minimal central canal stenosis. Gadoliniumenhanced T1-weighted sagittal (B) and axial (C) MR images show the extent of vertebral disease limited to L3. (D) Axial CT shows osteolysis of L3 vertebral body with limited involvement of the posterior vertebral wall.
of cement was injected.5 This may account for the observation in clinical studies that pain relief after vertebroplasty is not proportional to the degree of lesion filling.6 It has also been theorized that the heat generated during the polymerization of PMMA may destroy pain receptors and nerve endings in the affected vertebrae, as well as directly coagulate some of the tumor tissue. A direct cytotoxic effect of PMMA, which has been shown to cause necrosis at the PMMA–tumor interface, may also play a role.7
Mechanism of Action The mechanism of action of vertebroplasty is currently unclear and likely to be multifactorial. Biomechanical mechanisms seem to be the most important. Polymethylmethacrylate has been shown to stabilize microfractures and increase the stiffness of treated vertebrae.3,5 The compressive strength of vertebrae injected with PMMA easily surpasses that of noninjected controls. Biomechanical studies have shown that vertebral strength may be restored to regions where as little as 2 mL
Patient Selection, Indications, and Contraindications In the cancer setting, vertebroplasty is most clearly indicated in the patient with well-localized disabling spinal pain associated with thoracic or lumbar vertebral body fracture or
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Supportive Care Aspects of Vertebroplasty in Cancer
Figure 2
offered only after a trial of conservative medical management had failed.4,8-12 The length of time conservative measures should be pursued before consideration of vertebroplasty remains poorly defined and is ultimately a matter of clinical judgment. Imaging studies are necessary to help determine candidacy for the procedure. Magnetic resonance imaging (MRI) is essential and must be carefully evaluated for evidence of spinal cord or nerve root compression by epidural disease.2-4 Computed tomography (CT) is also highly recommended because it best shows the extent of osseous destruction of the posterior vertebral cortex. Because vertebroplasty is most commonly performed using fluoroscopic guidance via a transpedicular approach, plain radiographs are necessary to ensure visualization of the pedicles. Poor definition of the pedicles may necessitate an extrapedicular approach or the use of CT guidance for vertebroplasty needle placement.4 For vertebral lysis secondary to metastatic disease or myeloma, vertebroplasty is an adjunctive measure and should be used in combination with other appropriate management strategies. In general, radiation therapy needs to be performed in conjunction with vertebroplasty for malignant spinal disease because cement injection alone does not prevent tumor growth. Radiation therapy does not interfere with the mechanical properties of PMMA and complements its action with additional although delayed effects on pain and bone strengthening.2 Vertebroplasty should be performed before radiation therapy whenever possible because the analgesic effects of the former are immediate and spinal stability is addressed. However, patients with significant epidural softtissue disease may become candidates for vertebroplasty only after shrinkage of tumor by radiation therapy has occurred.4 Absolute contraindications for vertebroplasty are uncorrected coagulopathy, infection at the site of planned injection, intolerance to prone positioning, and lack of surgical backup in the event of postprocedural complications.1,7 Disruption of the posterior vertebral body cortex is a relative contraindication3,7 because of the increased risk of cement leakage into the spinal canal. The presence of a neurologic deficit secondary to epidural compression is also a relative contraindication. Surgical decompression may be the most appropriate treatment for such patients; however, vertebroplasty may still be considered for the palliation of pain if surgery is not feasible. Technical factors somewhat limit the ability to perform vertebroplasty safely and effectively in patients with vertebra plana deformity.2,9 Shimony et al demonstrated that vertebroplasty could be performed safely and effectively in patients with malignant compression and epidural involvement.8 They reviewed 50 patients with metastatic disease or myeloma, dividing patients into 3 groups depending on the extent of epidural involvement. There were no significant differences in pain or mobility outcomes among groups.
Percutaneous Vertebroplasty A
B
C
D
E
The patient shown in Figure 1 underwent bipedicular L3 percutaneous vertebroplasty. Fluoroscopic images obtained during the procedure show transpedicular vertebral body needles in the anteroposterior (A) and lateral planes (B). Successful lesion filling with no evidence of cement extrusion is shown in the anteroposterior (C) and lateral (D) planes. (E) Postoperative axial CT confirms PMMA confinement to the vertebral body lesion. This patient experienced a significant reduction in pain after surgery and became ambulatory. He subsequently received palliative radiation therapy to the spine.
collapse, without evidence of significant epidural disease (Figures 1 and 2).4 However, any patient with intractable axial pain because of vertebral involvement of cancer is potentially a candidate. The care of such patients is multidisciplinary and involves input from the radiation oncologist, medical oncologist, neurosurgical or orthopedic spine surgeon, as well as the pain management and rehabilitation medicine specialists.2-4 Factors that need to be considered in the decision to perform vertebroplasty include clinical presentation, patient preferences, tumor type and location, expected survival, known or anticipated radiation sensitivity, medical stability, functional capacity, and quality of life. In the majority of studies done to date, vertebroplasty was
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Figure 3
In the cancer setting, in which there may be multiple spinal levels of disease, failure to localize the symptomatic level(s) is probably the most frequent contraindication for vertebroplasty. In our experience, a substantial proportion of patients with cancer who may benefit from treatment harbor ≥ 1 relative contraindications for the procedure. Careful clinical judgment must therefore be exercised in weighing the risks and benefits on a case-by-case basis.
Vertebroplasty for Painful Compression Fractures A
B
C
D
Vertebroplasty Procedure Vertebroplasty is most commonly performed under local anesthesia with fluoroscopic guidance. An 11- or 13-gauge needle (Osteo-Site bone biopsy needle) is introduced through a small skin incision and advanced to the rostral aspect of the target pedicle with the bevel directed laterally to avoid penetration of the spinal canal. The needle is then advanced into the anterior third of the vertebral body, proceeding anteriorly, medially, and caudally until the midline is reached in the sagittal plane. Within the vertebral body, the bevel of the needle is then directed medially—the optimal orientation for PMMA delivery. If the diagnosis is uncertain, a 16-gauge needle (Franseen biopsy needle) may be introduced coaxially at this stage to obtain biopsy specimens. The PMMA powder is mixed with barium sulfate powder for opacification and antibiotic powder for infection prophylaxis. Approximately 4-6 mL of PMMA per vertebral body is injected under constant fluoroscopic guidance. If PMMA fills < 50% of the vertebral body, contralateral cannulation of the pedicle and injection are performed (Figure 3). In our experience, unilateral injection provides sufficient filling in roughly two thirds of cases. If extravasation of cement is observed, the needle is adjusted and/or a contralateral injection is attempted. If neither of these adjustments is able to prevent further leakage, the procedure is terminated. A CT scan should be obtained in all cases of cement extravasation.4 Some authors recommend routine postprocedural CT scanning for malignant disease.3 The patient is kept in the supine position for 1 hour to allow the cement to more fully polymerize before being allowed to ambulate.4,11 In most cases, the patient can be discharged later the same day.
A 36-year-old man underwent T6 and T9 vertebroplasty for painful compression fractures secondary to multiple myeloma. Anteroposterior fluoroscopic images obtained during the procedure show (A) needle placement, (B) successful filling of T6 (unipedicular injection) with partial filling of T9, (C) needle placement for left-sided injection of T9 with successful filling of the remaining vertebral body, and (D) the final stabilization.
Complications The most frequent complication of vertebroplasty is PMMA extravasation beyond the confines of the vertebral body. Theoretically, risk of cement leakage is greater in patients with cancer because the posterior wall of the vertebral body may be disrupted by malignant disease.12 The vast majority of leakages are asymptomatic; however, seepage of cement into the neural foramen may result in radiculopathy, and extavasation into the spinal canal may cause compressive myelopathy. Symptomatic compression of the neural elements may require urgent surgery,6 although radicular compression
has been managed effectively with corticosteroids and selective nerve blocks.11 There are rare reports of cement leakage into the paravertebral venous plexus resulting in pulmonary embolism.1,7 Extravasation of cement into the paravertebral soft tissues is generally considered benign. However, there has been one reported case of femoral neuropathy secondary to cement leakage into the psoas muscle.3 An increasingly reported complication is the risk of adjacent fractures after vertebroplasty.13-15 Uppin et al reported that of 177 patients with osteoporosis treated with vertebro-
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patients who underwent vertebroplasty.10 Shimony et al found that 52% of patients had improved mobility after vertebroplasty.8 Similarly, Chow et al reported that 53% of patients had functional improvement after the procedure.9 Finally, Alvarez et al reported that 77% of patients who had ambulatory difficulties before vertebroplasty were improved after the procedure.12 Symptomatic complications were rare in all studies. Rates of cement leakage ranged from 0 to 73%.4,6,12 This wide range of events appeared to largely reflect the criteria used by the authors to define a leak. The vast majority of cement leaks were entirely asymptomatic.
plasty, 22 (12.4%) developed a total of 36 new vertebral body fractures after treatment.13 Twenty-four (67%) of these new fractures involved vertebrae immediately adjacent to the previously treated level. The majority of new vertebral fractures occurred within 30 days after injection of the initial fracture. These authors hypothesized that the increased stiffness of the treated vertebral body may alter the distribution of forces to nearby vertebrae and thus increase the risk of fracture. Baroud et al suggested that the risk of adjacent vertebral body fracture could be lowered by decreasing the amount of PMMA injected or by using a biomaterial softer than PMMA.14 The importance of this risk for patients with cancer is unclear, because nonosteoporotic adjacent vertebrae may be able to tolerate these altered biomechanics within the limited remaining life span of the patient. Other reported complications include infection, allergic reaction of contrast agents, rib fractures from prone positioning in very frail patients, pneumothorax during injection of thoracic levels, and transient increase in pain (usually proportional to the volume of cement injected).7 Thermal injury to the spinal cord or nerve roots from the curing reaction of PMMA had been proposed as a theoretical risk but, to our knowledge, has never been reported.
How Does Vertebroplasty Compare with Kyphoplasty? Kyphoplasty is a recent modification of vertebroplasty in which a balloon is inflated within the collapsed vertebral body before the injection of PMMA.1,4 The advantage of kyphoplasty over vertebroplasty is that use of the balloon allows for some restoration of the vertebral body height and correction of kyphotic deformity. In addition, the bony cavity created by balloon inflation allows for a lower-pressure injection of higher viscosity PMMA, which theoretically reduces the risk of cement leakage. This purported advantage of kyphoplasty has been questioned because the majority of the pressure required for cement delivery during vertebroplasty is derived from the force needed to move PMMA along the long, thin cannula, and not from the highly porous cancellous bone.15 At this time, experience with kyphoplasty is limited in comparison with vertebroplasty. We are not aware of any controlled trials comparing the safety and efficacy of these procedures. In the study reported by Fourney et al, 9.2% of vertebroplasties (6 of 65 procedures) were complicated by a cement leak, whereas there were no reports of cement leakage with kyphoplasty (32 procedures).4 However, cement leakage was asymptomatic in all patients, and the clinical outcome in terms of pain relief, analgesic consumption, and function was similar after either procedure. Kyphoplasty has a number of disadvantages compared with vertebroplasty.4 Because it requires specialized equipment, kyphoplasty is more expensive to perform. Although vertebroplasty is accomplished with a unilateral injection in roughly two thirds of cases, kyphoplasty is almost always performed bilaterally. Owing to its increased complexity, procedural times for kyphoplasty are generally longer by comparison. Finally, whereas vertebroplasty is almost always performed under local anesthesia, kyphoplasty usually requires general anesthesia. Precise indications for kyphoplasty and vertebroplasty are still evolving.4 Controlled trials to evaluate the safety and efficacy of these procedures are needed.
Results Table 1 summarizes most of the clinical series where vertebroplasty has been used in the setting of malignant disease. In patients with back pain secondary to osteolytic metastases and myeloma, the majority report a significant decrease in pain after vertebroplasty.4,6,8-12,16-18 An evaluation of self-reported pain relief with use of a visual analogue scale (VAS) was provided in several reports.4,9,10,16 Diamond et al reported that 86% of patients experienced a drop in VAS scores of > 50% after vertebroplasty.10 Chow et al reported a drop in VAS scores from 10 to 1 with movement, and from 7 to 0 at rest.9 Martin et al reported a mean reduction of VAS scores by 4.3 points after vertebroplasty.16 In patients treated with vertebroplasty and/or kyphoplasty, Fourney et al reported a median decrease in VAS scores from 7 to 2; this effect was durable throughout the first year.4 Improvements in pain control after vertebroplasty led to a reduction in analgesic requirements in a number of studies.4,9,11,12 Fourney et al reported a significant postprocedural decrease in analgesic use in patients who underwent vertebroplasty and/or kyphoplasty.4 Chow et al found a nonsignificant trend toward decreased analgesic consumption after vertebroplasty.9 Cohen et al reported that 76% of patients were able to reduce analgesic dosages after the vertebroplasty,11 but Alvarez et al noted the same in only 50% of patients.12 Functional improvement has also been reported in several studies.4,8-10,12 Diamond et al noted a 50%-60% improvement in standardized scores of activities of daily living in
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Table 1
Summary of Results of Vertebroplasty in Patients with Cancer (Vertebral Metastases and Myeloma Bone Disease)4,6,8-12,16-18* Number of Patients (Levels Treated)
Results
Complications
Follow-up
Shimony et al (2004)8
50 (129)
82% Improved pain; 52% Improved mobility
None; 14% Had increased pain/new areas of pain during follow-up caused by progression of disease
Median, 3 months
Chow et al (2004)9
15 (20)
VAS reduced with movement (10 to 1) and at rest (7 to 0); 53% improved function; Trend to reduced analgesic use
1 Case of cement leakage into spinal canal (motor intact but loss of proprioception); 1 case of reversible tachycardia
12-Week study (3 patients died during follow-up)
Diamond et al (2004)10
7 (14)
86% Had ³ 50% improvement in pain scores; 86% reduced analgesic use
None reported
6 Weeks
Cohen et al (2004)11
31 (43)
76% Reduced analgesic use
Complications specific to tumor subgroup not reported; 5 of 192 (2.6%) procedure-related radiculopathies in entire series
30 Days
Fourney et al (2003)4
34 (65)
86% Improved pain; Median VAS reduced from 7 to 2; Trend to improved ambulation
6 of 65 (9.2%) cement leak, none symptomatic
Median, 4.5 months (range, 1-19.7 months)
Martin et al (2003)16
32 (51)
75% Improved pain; Mean 4.3 decrease in VAS
4 of 51 (8%) cement leak, none symptomatic
2-5 Days
Alvarez et al (2003)12
21 (27)
81% Improved pain (average VAS reduced from 9.1 to 3.2); 50% reduced analgesic use; 10 of 13 patients with gait disorder had improved ambulation (77%)
12 of 27 (44%) cement leak, all asymptomatic except 1 patient with transient radiculitis
Mean, 5.6 months (range, 1-18 months)
Barr et al (2000)17
8 (13)
50% Improved pain
1 Patient with "significant" cement extravasation (asymptomatic)
Mean, 12 months among survivors (4 patients died at mean of 10 months); range, 3 weeks to 35 months
Cotton et al (1997)6
37 (40)
97% Had partial or complete relief of pain; Pain relief not proportional to percentage of lesion filling
29 of 40 (73%) cement leak detected by CT (all asymptomatic except 2 with foraminal extravasation requiring surgery and 1 with transient femoral neuropathy)
Mean, 4.2 months (range, 6 days to 6 months)
73% Had improvement in pain, stable at 6 months; Trend to improved ambulation
3 Patients had transient radiculopathy caused by cement leakage (1 patient required surgical removal of cement from the neural foramen); 2 patients with brief (< 72 hours) increase in local pain, resolved with corticosteroids; 2 patients with cervical vertebroplasty had transient difficulty swallowing
Mean, 7.1 months
Author
Wiell et al (1996)18
37 (52)
*Some results are subgroups of larger series that included patients with non-neoplastic indications, and/or procedures other than vertebroplasty. Only those studies that reported results for the subgroup of patients treated with vertebroplasty for malignant spinal disease are listed.
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Conclusion
6. Cotton A, Dewatr F, Cortet B, et al. Percutaneous vertebroplasty for osteolytic metastases and myeloma: effects of percentage of lesion filling and the leakage of methyl methacrylate at clinical follow-up. Radiology 1996; 200:525-530. 7. Gangi A, Guth S, Imbert JP, et al. Percutaneous vertebroplasty: indications, technique, and results. Radiographics 2003; 23:e10-e10 (Online). 8. Shimony JS, Gilula LA, Zeller AJ, et al. Percutaneous vertebroplasty for malignant compression fractures with epidural involvement. Radiology 2004; 232:846-853. 9. Chow E, Holden L, Danjoux C, et al. Successful salvage using percutaneous vertebroplasty in cancer patients with spinal metastases or osteoporotic compression fractures. Radiother Oncol 2004; 70:265-267. 10. Diamond TH, Hartwell T, Clarke W, et al. Percutaneous vertebroplasty for acute vertebral body fracture and deformity in multiple myeloma: a short report. Br J Haematol 2004; 124:485-487. 11. Cohen JE, Lylyk P, Ceratto R, et al. Percutaneous vertebroplasty: technique and results in 192 procedures. Neurol Res 2004; 26:41-49. 12. Alvarez L, Perez-Higueras A, Quinones D, et al. Vertebroplasty in the treatment of vertebral tumours: postprocedural outcome and quality of life. Eur Spine J 2003; 12:356-360. 13. Uppin AA, Hirsch JA, Centenera LV, et al. Occurrence of new vertebral body fracture after percutaneous vertebroplasty in patients with osteoporosis. Radiology 2003; 226:119-124. 14. Baroud G, Heini P, Nemes J, et al. Biomechanical explanation of adjacent fractures following vertebroplasty [letter]. Radiology 2003; 229:606-607. 15. Baroud G, Bohner M, Heini P, et al. Injection biomechanics of bone cements used in vertebroplasty. Biomed Mater Eng 2004; 14:487-504. 16. Martin JB, Wetzel SG, Seium Y, et al. Percutaneous vertebroplasty in metastatic disease: transpedicular access and treatment of lysed pedicles—initial experience. Radiology 2003; 229:593-597 17. Barr JD, Barr MS, Lemlet TJ, et al. Percutaneous vertebroplasty for pain relief and spinal stabilization. Spine 2000; 25:923-928. 18. Wiell A, Chiras J, Simon JM, et al. Spinal metastases: indications for and results of percutaneous injection of acrylic surgical cement. Radiology 1996; 199:241-247.
Percutaneous vertebroplasty is a minimally invasive technique that has shown considerable promise in the management of pain secondary to lytic spinal metastases and myeloma bone disease. Studies to date have shown that in appropriately selected patients, vertebroplasty offers rapid, durable pain relief in the majority of patients with minimal risk of complications. Effective pain control often translates into improved functional capacity for the patient. For malignant spinal disease, vertebroplasty is an adjunct to other standard medical therapies and radiation therapy. A multidisciplinary approach to patient selection and management is essential. Although kyphoplasty may be differentiated from vertebroplasty on the basis of height restoration and, perhaps, risk of cement extravasation, whether the additional complexity and costs of kyphoplasty are offset by these potential benefits is not known at this time.
References 1. Lieberman I, Reinhardt MK. Vertebroplasty and kyphoplasty for osteolytic vertebral collapse. Clin Orthop 2003; 415(suppl):S176-S186. 2. Lemke DM, Hacein-Bey L. Metastatic compression fractures–vertebroplasty for pain control. J Neurosci Nurs 2003; 35:50-55. 3. Jensen ME, Kallmes DE. Percutaneous vertebroplasty in the treatment of malignant spinal disease. Cancer J 2002; 8:194-206. 4. Fourney DR, Schomer DF, Nader R, et al. Percutaneous vertebroplasty and kyphoplasty for painful vertebral body fractures in cancer patients. J Neurosurg Spine 2003; 98:21-30. 5. Belkoff SM, Mathis JM, Jasper LE, et al. The biomechanics of vertebroplasty. The effect of cement volume on mechanical behavior. Spine 2001; 26:1537-1541.
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