Surgical treatment of metastases to the spinal cord and spine

This article is part of the research topic "Surgical treatment of metastases to the spinal cord and spine" View all 6 articles
Background: To investigate the clinical safety and efficacy of percutaneous vertebroplasty (PVP) in combination with bone-filled mesh container (BFC) in the treatment of spinal metastases with posterior wall defects.
Methods: Patients with spinal metastases and posterior wall defects treated with BFMC in combination with PVP treatment from January 2019 to December 2021 were included in the study. Visual analog scale (VAS) and Oswestry disability index (ODI) scores were performed preoperatively and 72 hours postoperatively. Postoperative radiographic and CT examinations were performed to monitor bone cement leakage and record complications. Follow-up CT and MRI were performed to evaluate the intraoperative status of the spine and the recurrence or progression of other bone metastases.
Results: A total of 43 patients and 44 surgical vertebrae were included. All patients underwent surgery successfully. The mean VAS score decreased from 7.35±0.78 before surgery to 1.63±0.93 before surgery (p < 0.05), and the ODI score decreased from 80.06±8.91 before surgery to 32.5±4.87 before surgery (p < 0.05). Bone cement leakage occurred in 18 operated vertebrae, all of them were asymptomatic, and there were no serious complications such as intraspinal leakage, postoperative spinal nerve compression, and pulmonary embolism. Twenty-one patients were followed up for more than a year, and no progression of spinal disease was observed. Thirteen target vertebrae showed obvious sclerosis and necrosis, and no adjacent Pathological Fractures were observed. Among them, 16 patients had metastases of varying degrees of severity in bones other than the operated vertebral body.
Conclusion: For spinal metastasis with posterior wall defects, the treatment with PVP combined with BFMC is highly safe and can effectively relieve pain in patients. One-year follow-up showed local tumor inhibition effect.
The spine is one of the main sites of metastasis in patients with advanced malignancies, and its incidence increases with the duration of the disease (1). The resulting skeletal-related events (SREs) seriously interfere with subsequent anticancer treatment of patients and even affect their survival (2). Effective surgical intervention is the key to saving the lives of such patients. Percutaneous vertebroplasty (PVP) has been used in clinical practice for several decades and has proven its efficacy and safety (3). However, bone cement leakage remains one of the major risks of PVP, which can lead to paralysis or even death of patients. Damage to the posterior vertebral wall increases the risk of cement leakage and is therefore considered a contraindication for PVP (4). In recent years, with the improvement of bone cement materials and the application of new technologies, some physicians have suggested that PVP may still be a treatment option even for patients with posterior vertebral wall defects. Bone-filled mesh container (BFMC) is one of the technologies that can control the diffusion of bone cement and reduce leakage, and it is used in the surgical treatment of osteoporosis and bone metastasis. In this study, a retrospective analysis of the use of PVP in combination with BFMC was performed in patients with osteolytic metastasis to the spine and posterior vertebral wall defects to evaluate the safety and efficacy of BFMC in combination with PVP. This study complies with the STROBE reporting checklist.
This is a retrospective cohort study including patients with spinal metastasis and posterior wall defects admitted to the Department of Spine Surgery, Shenzhen People's Hospital from January 1, 2019 to December 31, 2021, who underwent BFMC combined with PVP treatment. All patients underwent detailed preoperative evaluation to meet the exclusion criteria. Magnetic resonance imaging (MRI) or whole body scanning is used to confirm the location of vertebral metastasis, and then CT is performed to clarify the spinal segment with posterior wall defect and the extent of injury.
The main inclusion criteria were: 1) patients with metastases in the thoracic (T)9–lumbar (L)5 spine diagnosed by MRI or whole-body bone scan; 2) patients with chest and back pain caused by metastases and a visual analog scale (VAS) score of ≥5; 3) patients with posterior wall destruction diagnosed by MRI or CT; 4) patients with a survival time of ≥3 months. The main exclusion criteria were: 1) patients with terminal cancer and/or patients with impaired cardiac, pulmonary, hepatic, or renal function, severe anemia, or hypoproteinemia who cannot tolerate surgery; 2) patients with pathological vertebral fractures or metastatic lesions compressing the spinal cord or nerve roots who can only undergo open decompression surgery; 3) patients with severe bleeding disorders, severe systemic infections or skin infections at the surgical site.
The BFMC system (Shandong Longguan Medical Instrument Co., Ltd., China) used in this study consists of a 4.0 mm diameter puncture needle, a fine drill, a metal retractor, a spiral pusher, and a mesh bag for bone filling (Figure 1A–C). The PVP system (Shandong Longguan Medical Instrument Co., Ltd., China) consists of a 4.0 mm diameter puncture needle and a pusher. The bone cement kit used in this study (Tecres SPA, Sommacampagna, Italy) mainly contains polymethyl methacrylate (PMMA), barium sulfate, and N,N-dimethyl-p-toluidine.
Fig. 1 BFMC system (AC) and operative flow (DI). (A) Compression mesh bag is connected to the working channel. (A) Metal expander. (C) Mesh bag filled with bone cement is in the stretched position. (D) Position of the affected vertebra under the C-arm of the device. (E) Metal expander is inserted to create space for the mesh bag. (F) Insert the compression mesh bag. (G) 1 mL of bone cement was injected into the mesh bag in the stretched position. (H) Continue injecting bone cement until it is evenly distributed and fills the anterior two-thirds of the vertebral body. Simultaneously, perform PVP on the other side. No obvious leakage was observed. (I) Postoperative images with BFMC applied to the left vertebra and PVP to the right vertebra. BFMC, mesh bag with bone filler; PVP - percutaneous vertebroplasty.
All patients underwent surgery in the prone position under local anesthesia, and spinal metastases were biopsied before further surgery. A bilateral approach was used in all cases. Preoperative CT scanning was used to localize the bone pedicle defect. During surgery, BFMC was implanted on the defective side of the posterior wall, and PVP was performed on the contralateral pedicle. Under C-arm fluoroscopy guidance, a puncture needle was inserted into the target vertebral body through the vertebral pedicle, the shaft of the puncture needle was removed, and a fine drill was inserted to form a bone tunnel. A metal expander was used to expand the bone bag space, and a mesh bag was inserted to fill it with bone tissue. At the same time, a working channel was created on the contralateral vertebral pedicle using a pusher. Under C-arm guidance, 1 ml of the prepared bone cement was slowly injected into the mesh bag. Ensure that the mesh bag is open and continue to inject bone cement from both sides. The injection is stopped when the bone cement is evenly distributed and fills the anterior two-thirds of the vertebral body without visible leakage (Figure 1D-I). The working canal is then removed and the procedure is completed.
VAS scores before and 72 hours after surgery were collected to evaluate the improvement in subjective pain symptoms in patients, and Oswestry Disability Index (ODI) scores were collected to evaluate the improvement in patients' motor function. Radiography and CT were performed 48 hours after surgery to evaluate the diffusion and leakage of bone cement. All postoperative complications were recorded in detail, including but not limited to systemic or local infection, spinal cord compression, and bone cement implantation syndrome. Follow-up was performed every 3 months, and imaging results were collected at 1 year after surgery to evaluate the spine, record necrosis and sclerosis of the operated vertebrae, and progression of surgical and non-surgical spinal tumors.
The data were analyzed using SPSS 20.0 software (IBM, Armonk, NY). Normally distributed data were expressed as mean ± standard deviation (x ± s). Paired sample t-test was used to compare preoperative and postoperative data. Count data were expressed as percentage (%). A p-value less than 0.05 indicates that the difference is statistically significant.
The study included 43 patients with posterior vertebral wall defects admitted to Shenzhen People's Hospital from January 1, 2019 to December 31, 2021. A total of 44 vertebrae were treated with PVP combined with BFMC. Among them, there were 20 patients with breast cancer, 13 with lung cancer, 5 with gastrointestinal tumors, and 5 with urinary tract malignancies (Table 1). The needle biopsy report showed that the primary cancer in all patients was the same malignancy. A total of 18 thoracic vertebrae and 26 lumbar vertebrae were affected. All patients underwent surgery successfully, and no serious adverse effects such as perioperative infection were observed. At 48 hours after surgery, the bilateral bone cement injection volume was (5.98±1.02) ml, and the leakage rate was 40.9% (18/44 vertebrae). However, all 18 patients were asymptomatic and no intraspinal leak was recorded (Figure 2), and no serious postoperative complications such as spinal nerve compression or pulmonary embolism were reported.
Fig. 2. Typical images of bone cement leakage after BFMC surgery. (A) Paravertebral vascular cement leakage. (B) Paravertebral cement leakage. Both patients were asymptomatic. BFMC, mesh container filled with bones.
The VAS score decreased from 7.35±0.78 before surgery to 1.63±0.93 after surgery (p<0.05), indicating a significant relief of postoperative pain (Table 2). The ODI score decreased from 80.06±8.9 before surgery to 32.5±4.87 72 hours after surgery (p<0.05), indicating a significant improvement in the patient’s motor function.
The follow-up period for the included patients ranged from 7 to 30 months, during which 15 patients died and 21 patients (21 operated vertebrae) were followed for more than 1 year. Imaging studies of these 21 patients did not reveal progression of surgical lesions or pathological fractures of adjacent vertebrae, and 14 of the operated vertebrae had obvious signs of sclerosis (Figure 3). A total of 17 cases with varying degrees of progression of metastases in the bones of the vertebrae that were not subjected to surgical intervention were registered.
Fig. 3 Typical cases of BFMC and PVP. The patient was a 37-year-old woman diagnosed with stage IV breast cancer. (A–D) Preoperative MRI (A, B) and CT (C, D) of T12 vertebra revealed osteolytic bone destruction and pathological fracture, as well as a posterior wall defect of T12. (E, F) Immediately post-BFMC and PVP radiographs. The patient underwent BFMC on the right side and PVP on the left side. (G) Hematoxylin and eosin stain of the primary tumor at the time of patient diagnosis. (H) Hematoxylin and eosin stain of metastatic tumor of T12 vertebra. Pathology reports of both images (G, H) were consistent with breast cancer. (I–L) MRI (I, J) and CT (K, L) of T12 vertebra 12 months after surgery. (K) Cement leakage in the paraspinal vessels is observed, but there are no clinical manifestations. Compared with (A, B), tumor regression was observed in (I, J). Compared with (C, D), (K, L) demonstrates vertebral sclerosis. BFMC, bone-filled mesh container; PVP, percutaneous vertebroplasty.
Bone metastasis is a common complication of advanced malignancies, with the spine being the most common site of involvement. Numerous studies have shown that its incidence ranges from 30% to 70% (5). Uncontrolled spinal metastasis can cause spinal adverse events (SREs), including local pain, spinal cord and nerve compression, pathological fractures, spinal instability, etc., which ultimately leads to paralysis and disability, seriously affecting the patient's antitumor treatment. Surgery plays an important role in the comprehensive treatment of spinal metastasis. As a minimally invasive surgical method, PVP has shown significant efficacy in relieving pain, restoring spinal stability, and local tumor control.
PVP has been used to treat hemangiomas, osteoporotic fractures, and spinal metastases since 1984, and its effectiveness has long been recognized (6). Compared with nonsurgical treatment, the effectiveness of PVP in quickly relieving pain, preserving nerve function, and improving quality of life has been widely recognized. However, bone cement leakage remains a complication that cannot be ignored. Although bone cement leakage is mostly asymptomatic, it can occasionally lead to vascular embolism, pulmonary embolism, intracardiac bone cement embolism, and intraspinal leakage (7–10). According to literature, the incidence of bone cement leakage during PVP surgery is 31.6% for osteoporotic fractures and 50% to 72% for spinal metastases. Posterior vertebral wall defects significantly increase the risk of cement leakage and have long been considered a contraindication for PVP (4,11,12). The traditional treatment for such patients is open surgery, but it is more traumatic, requires a longer recovery period, and medical costs are also higher.
In recent years, with the improvement of bone cement materials and surgical techniques, minimally invasive surgical treatment of posterior vertebral wall defects has achieved greater safety and effectiveness (13). BFMC technology is one of the improved technologies. The principle of BFMC is to create a bone cavity with a metal expander and then inject a porous multilayer mesh structure into it, which can expand as the amount of bone cement injected increases. The bone filling mesh bag used in this study was made of polyethylene terephthalate (PET) woven into a mesh structure with a mesh size of 0.1 to 0.2 mm. Theoretically, BFMC can control the penetration rate and direction of bone cement, thereby reducing the leakage rate (14).
An early study (14) of 29 patients with osteoporosis, high-impact trauma, myeloma, or metastatic disease using mesh bags to treat symptomatic vertebral compression fractures showed that this new technique reduced the mean pain score from 8.72 ± 1.25 (SD) to 3.38 ± 2.35. Meanwhile, the mean activity score was 2.31 ± 1.94 before treatment and 0.59 ± 1.05 after treatment (p < 0.001). Thus, BFMC had a statistically significant advantage in reducing pain and mobility. He et al. compared the efficacy and safety of BFMC and simple percutaneous balloon angioplasty in the treatment of osteoporotic vertebral compression fractures (15). The study showed that both techniques could effectively relieve pain and correct the Cobb angle; However, the rate of bone cement leakage in any area of ​​the spinal cord, paravertebral veins, and adjacent vertebral soft tissues was significantly lower in the BFMC group than in the BFMC group. Another retrospective cohort study on the clinical efficacy of BFMC combined with posterior screw rod fixation in the treatment of thoracolumbar spine metastases (16) showed that the rate of bone cement leakage in this combined procedure was lower than in the control group of traditional vertebroplasty combined with posterior spinal fixation (14.29% vs. 31.43%). At the same time, both groups were comparable in terms of pain control, restoration of spinal height, and improvement in range of motion. Another retrospective study (17) evaluated the use of Mesh-Hold™ bone filling containers in the treatment of pathological vertebral fractures caused by osteolytic metastases and included 36 patients with 105 levels. The results showed that the VAS and ODI scores were significantly reduced after surgery, and the bone cement leakage rate was 16.2%.
In this study, bilateral PVP was combined with BFMC surgery to effectively relieve the patient's pain. The postoperative VAS score decreased from 7.35±0.78 before surgery to 1.63±0.93 after surgery (p<0.05). A total of 18 cases of bone cement leakage were detected in CT examination 48 hours after surgery, including 4 cases of intervertebral disc leakage, 5 cases of prevertebral/paravertebral leakage, and 9 cases of vascular leakage. No symptomatic cement leakage or intraspinal leakage was detected in this study. No bone cement leakage in the spinal canal was detected in this study, which may be associated with the use of the second-generation mesh bag to more effectively reduce the pressure of the outer layer of bone cement and the careful selection of the bone cavity site. During surgery, we usually decide to create a bone cavity in the anterior part of the vertebral body to avoid further damage to the posterior wall of the vertebral body by the expander and to maintain a larger distance between the mesh bag and the posterior wall of the vertebral body. The efficiency and leakage rate in other locations were comparable to those in previous studies.
In this study, a bilateral approach was used to implant BFMC on the side of the posterior vertebral wall defect confirmed by preoperative CT, while PVP was performed on the contralateral vertebral pedicle. The reason for choosing a bilateral approach instead of a unilateral one is to increase the filling rate of bone cement and reduce the risk of bone cement leakage. There is still controversy about which approach is more appropriate, unilateral or bilateral. Some studies have shown that for patients with osteoporotic fractures, the unilateral approach has advantages such as less morbidity, shorter operative time, lower risks associated with puncture, less radiation exposure, and lower medical costs. Other studies have shown that the bilateral approach provides a higher filling rate of bone cement and a lower leakage rate due to the smaller amount of bone cement injected on each side (18-20).
However, to our knowledge, no study has compared these two approaches in patients with spinal metastases, which usually depends on the experience of the physician. PMMA bone cement has a cytotoxic effect similar to that of alcohol before polymerization. During the polymerization process, the temperature can reach more than 75 °C, which leads to degeneration and necrosis of nerve fibers in the vertebral body, thereby reducing pain sensitivity. The thermal effect can also be cytotoxic to cells within a 3 mm radius of the surrounding area (21, 22). Based on the well-known “seed and soil” hypothesis, we speculate that the stroma surrounding metastases may underlie tumor progression or recurrence (23). Thus, the higher filling rate of bone cement may act as a space-filling and flow-interrupting agent, thereby better preventing the recurrence of metastatic tumors. Based on the above theory, a two-pronged approach was chosen for this study group.
This study included 21 patients who underwent follow-up imaging examinations for more than 1 year. Of these, 13 operated vertebrae had spondylosclerosis, 16 unoperated vertebrae had tumor progression, and no fractures of adjacent vertebrae were detected. This confirmed our hypothesis that the higher the filling rate of bone cement, the better the local tumor control. Sun et al. (24) evaluated the effect of bone cement augmentation in the treatment of osteolytic lesions of spinal metastases. A total of 268 vertebrae with metastatic tumors were treated with PVP and followed up. The lesion extent was recorded at 3, 6, 12, and 18 months after surgery. The results showed that the tumor control rate in the group where the affected vertebral body was completely filled with bone cement was significantly higher than in the group where residual tumor destruction was still observed around the bone cement. Liu et al (25) treated 268 spinal metastases with PVP and conducted a follow-up by recording the extent of the lesion at 3, 6, 12, and 18 months after surgery. Redel et al studied 54 patients with spinal metastases and found that the amount of bone cement, the completeness of bone cement filling, and the filling rate were negatively correlated factors for the progression of local bone destruction over 6 months (25). Patients with a slow filling rate were more likely to have early progression of bone destruction than those with a fast filling rate. Redel et al studied 55 patients with breast cancer spinal metastases (137 treated vertebrae) to evaluate the effect of PVP treatment in preventing progression or local recurrence (26). The results showed that the rate of local tumor progression or recurrence in the PVP-treated vertebrae was 14% (19/137), and 47 of 55 patients (86%) developed new distant bone metastases, partially demonstrating the antitumor effect of bone cement. However, no statistical correlation was observed between the rate of cement filling of lesions and progression or local recurrence after PVP treatment.
This study also has certain limitations. It was a relatively small retrospective study with a single cohort of patients and the surgery was performed at a single center. Analyses based on cohort stratification were also limited by the small sample size. Therefore, our findings need to be verified and confirmed by further studies with larger cohorts and more centers.
In summary, this study conducted a retrospective cohort study on the efficacy and safety of PVP combined with BFMC in the treatment of patients with spinal metastases and posterior vertebral wall defects. The results showed that this treatment method is highly safe, can effectively relieve pain, and local antitumor effect was observed during the follow-up of 1 year. Therefore, PVP combined with BFMC is a recommended treatment method for patients with spinal metastases and posterior vertebral wall defects.
The original materials presented in this study are included in the main text/supplementary materials. If you have any further questions, please contact the corresponding author.
The studies involving human participants were approved by the Ethics Committee of Shenzhen People's Hospital. The study was conducted in accordance with local laws, regulations, and institutional requirements. In accordance with national laws, regulations, and institutional requirements, written informed consent was not required from the participants or their legal guardians/next of kin. Written informed consent was obtained from the individuals for publication of any potentially identifiable images or data included in this article.
KZ: conceptualization, investigation, methodology, writing – original draft. KC: data collection, investigation, writing – review & editing. GG: conceptualization, supervision, writing – review & editing. YX: conceptualization, formal analysis, methodology, software, writing – review & editing.
The author(s) declare that they received financial support for the research, authorship, and/or publication of this article. This article was funded by the Natural Science Foundation of Guangdong Province (2016A030310070), the Young and Middle-Aged Technical Professionals Research and Training Project of Shenzhen People's Hospital (Peak Program) (SYKYPY201920), and the Science and Technology Plan Project of Heyuan City Social Development (230530081609952). The funders had no role in study design, data collection, analysis, writing, or the decision to submit this article for publication.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
All opinions expressed in this article are solely those of the authors and do not necessarily reflect the views of their institutions, publishers, editors, or reviewers. Any products evaluated in this article, or any claims made by their manufacturers, are not guaranteed or endorsed by the publisher.
1. Coleman RE, Croucher PI, Padhani AR, Clezarden P, Chow E, Fallon M, et al. Bone metastases. Nat Rev Dis Primers (2020) 6(1):83. DOI: 10.1038/s41572-020-00216-3
2. Coleman RE, Hadji P, Bodie JJ, Santini D, Chow E, Terpos E, et al. Bone health in cancer: an ESMO clinical practice guideline. Annals of Oncology (2020) 31(12):1650–63. doi: 10.1016/j.annonc.2020.07.019
3. Yao A, Sarkiss CA, Ladner TR, Jendins AL. Current treatment paradigms for spine tumors and outcomes for spine metastases: a systematic review of metastases to the breast, prostate, kidney, and lung. Journal of Clinical Neuroscience (2017) 41:11–23. doi: 10.1016/j.jocn.2017.04.004
4. Duran S, Sirvanci M, Aydogan M, Ozturk E, Ozturk S, Akman S. Pulmonary cement embolism: a complication of percutaneous vertebroplasty. Acta Radiologica Sinica (2007) 48(8):854–9. DOI: 10.1080/02841850701422153
5. Barzilai O., Laufer I., Yamada Y., Higginson D.S., Schmitt A.M., Lis E., et al. A decision framework for applying evidence-based medicine to the treatment of spinal metastases: neurologic, oncologic, mechanical stability, and systemic diseases. J Clinical Oncology (2017) 35(21):2419–2427. doi: 10.1200/JCO.2017.72.7362
6. Galibert P, Deramond H, Rosat P, Gars DL. Percutaneous acrylic vertebroplasty for vertebral hemangiomas: a preliminary description. Neurosurgery (1987) 33(2):166–8.
7. Zheng Yongsheng, Zhang Yan, Lin Jiangdong, Shi Jianhua, Wang Qingkai. Analysis of risk factors for bone cement leakage after vertebroplasty and kyphoplasty. Chinese Journal of Traumatology (2015) 31(4):312–6. doi: 10.3760/cma.j.issn.1001-8050.2015.04.006
8. Trumm KG, Pahl A, Helmberger TK, Jacobs TF, Zech SJ, Stahl R, et al. CT-fluoroscopy-guided percutaneous vertebroplasty for spinal malignancies: technical results, PMMA leakage, and complications in 202 patients. Skeletal Radiol (2012) 41(11):1391–400. doi: 10.1007/s00256-012-1365-x
9. Mansour A, Abdel-Razek N, Abuali H, Makose M, Sheikh-Salem N, Abushalha K, et al. Cement-induced pulmonary embolism is a complication of percutaneous vertebroplasty in patients with cancer. Cancer Imaging (2018) 18(1):5. doi: 10.1186/s40644-018-0138-8
10. Kim HT, Kim YN, Shin HW, Kim IC, Kim H, Park NH, et al. Late complications of percutaneous vertebroplasty: bone cement leakage leading to foreign body entry into the heart. Korean Journal of Internal Medicine (2013) 28(2):247–50. doi: 10.3904/kjim.2013.28.2.247
11. Zhan Y, Jiang J, Liao H, Tang H, Yang Q. Risk factors for bone cement leakage after vertebroplasty or kyphoplasty: a meta-analysis of published data. World Neurosurgery (2017) 101: 633–42. doi: 10.1016/j.wneu.2017.01.124
12. Shi XY, Cui Y, Pan Y, Wang B, Lei M. Epidemiology and detection of bone cement leakage in patients with spinal metastasis treated with percutaneous vertebroplasty: a 10-year observational study. Journal of Bone Cancer (2021) 28:100365. doi: 10.1016/j.jbo.2021.100365
13. Amoretti N, Diego P, Amelie P, Andreani O, Foti P, Schmid-Antomarchi H, et al. Percutaneous vertebroplasty for tumor-associated vertebral fractures involving the posterior vertebral wall: feasibility and safety. European Journal of Radiology (2018) 104:38–42. doi: 10.1016/j.ejrad.2018.04.010
14. Flors L, Lojedo E, Leyva-Salinas S, Martí-Bonmatí L, Martínez-Rodrigo JJ, López-Pérez E, et al. Angioplasty: a new technical approach for the treatment of symptomatic vertebral compression fractures. AJR Am J Roentgenol (2009) 193(1):218–26. doi: 10.2214/AJR.08.1503
15. He Changjian, Liu Guanda. Comparison of the efficacy and safety of bone-filled mesh container and simple percutaneous balloon kyphoplasty in the treatment of osteoporotic vertebral compression fractures. Pain Doctor (2018) 21(3): 259–68.
16. Zhu Q, Qiao YQ, Yang JQ, Chen JQ, Lin JZ, Xie TU, et al. Clinical efficacy of bone mesh vertebroplasty combined with posterior screw rod fixation in the treatment of thoracolumbar spine metastasis: a retrospective cohort study. Ann Palliate Med (2022) 11(4):1401–9. doi: 10.21037/apm-22-25