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Thick cement usage in percutaneous vertebroplasty for malignant vertebral fractures at high risk for cement leakage
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Diagnostic and Interventional Imaging (2017) xxx, xxx—xxx
ORIGINAL ARTICLE /Interventional imaging
Thick cement usage in percutaneous vertebroplasty for malignant vertebral fractures at high risk for cement leakage R.M. Reyad a, H.Z. Ghobrial a, S.M. Hakim b, R.H. Hashem c, A. Elsaman d, M.H. Shaaban c,∗ a
Department of Anesthesia and Pain Management, National Cancer Institute, Cairo University, Cairo, Egypt b Department of Anesthesiology, Intensive Care, and Pain Management, Faculty of Medicine, Ain Shams University, Cairo, Egypt c Departments of Diagnostic and Interventional Radiology, Faculty of Medicine, Cairo University, Cairo, Egypt d Departments of Neurosurgery, Faculty of Medicine, Cairo University, Cairo, Egypt
KEYWORDS Percutaneous vertebroplasty; Bone cement; Interventional radiology; Cement leakage; Pain relief
∗
Abstract Purpose: To assess the feasibility and safety of transpedicular percutaneous vertebroplasty (PVP) using thick bone cement in patients with intractable metastatic vertebral pain and at high risk for cement leakage. Methods: Unilateral transpedicular PVP using firm bone cement was performed in 77 patients with intractable pain due to vertebral metastases in the thoracolumbar spine, who had one or more relative contraindication to PVP. Primary outcome measures were the severity of pain as assessed on a 100-mm visual analogue scale and daily morphine consumption. Secondary outcome measures were the degree of disability and the incidence of procedure-related adverse outcomes. The outcome measures were assessed at the preoperative visit and at 1 day, 1 week, 4 weeks and 12 weeks after the procedure. Results: Sixty-three (81.8%) patients completed the 12-week follow-up period. There were 30 men and 33 women, with a mean age of 58 ± 11 (SD) [range: 34—81 years]. Compared with preprocedure value, all post-procedure pain scores were significantly lower (P < 0.0001). Likewise, there was a statistically significant reduction in daily morphine consumption at all follow-up times (P < 0.0001). The ambulation score, ADL, and ODI were all significantly lower at all assessment times compared with pre-procedure values (P < 0.0001). No serious adverse effects were observed.
Corresponding author. 5015 Mearage City, Maadi, Cairo, Egypt. E-mail address: [email protected] (M.H. Shaaban).
http://dx.doi.org/10.1016/j.diii.2017.02.010 2211-5684/© 2017 Editions franc ¸aises de radiologie. Published by Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Reyad RM, et al. Thick cement usage in percutaneous vertebroplasty for malignant vertebral fractures at high risk for cement leakage. Diagnostic and Interventional Imaging (2017), http://dx.doi.org/10.1016/j.diii.2017.02.010
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R.M. Reyad et al. Conclusion: PVP using thick bone cement could be administered with reasonable safety to patients suffering from intractable pain caused by vertebral metastases who were at high risk for cement leakage. The procedure was associated with significant improvement of pain and disability. © 2017 Editions franc ¸aises de radiologie. Published by Elsevier Masson SAS. All rights reserved.
Percutaneous vertebroplasty (PVP) is a minimally invasive, radiologically guided procedure that aims at relieving pain and partially stabilizing vertebral body fractures [1,2]. The technique is currently widely used for the management of painful vertebral fractures associated with trauma and malignancies [3]. The incidence of spinal metastases in cancer patients is 5% and these patients have limited life expectancy of 10 months [4]. Vertebral metastases are found in twothirds of patients who die of malignant diseases. Thoracic vertebrae are commonly affected (60—80%), followed by lumbar (20%) and lastly cervical vertebrae (10%) [5]. Osteolytic spinal lesions, together with the poor quality of new bone formed by osteoblastic metastases, may induce severe spinal pain, hypercalcemia, pathological fractures and spinal cord compression [6]. PVP has a role in pain relief and vertebral stabilization with little risk as compared with formal surgical procedures [7]. PVP is currently indicated after failure of conservative management of vertebral fractures and is considered a safer alternative to formal surgical fixation in this high risk surgical population [8]. Cement leakage is a serious complication of PVP because it may cause paralysis or radiculopathy [8]. Cement leakage has been reported in 20% [9] to 41% [10] of procedures. The risk of cement leakage increases in osteolytic spinal metastases, which involve the posterior portion of vertebrae in 10—20% of cases [11]. The risk of even small cement leakage is augmented by preexisting tumors invading spinal canal and is higher in the thoracic and cervical regions owing to the relatively smaller size of the vertebral bodies [12]. Polymethyl methacrylate (PMMA) is the type of cement most commonly used for augmentation vertebroplasty, including PVP. PMMA has a liquid phase and solid phase and is characterized by its bio-inertness and biocompatibility for long-term use [13]. We assumed that using firmer gum-like (thick cement) rather than the usual tooth paste-like bone cement for PVP with PMMA would reduce the risk for cement leakage, thus rendering the procedure a feasible treatment option in this high risk patient category. The purpose of this study was to assess the feasibility and safety of transpedicular PVP using thick bone cement in patients with painful malignant vertebral lesion involving the lower thoracic and lumbar regions, in whom PVP was relatively contraindicated because of a high risk for cement leakage.
Patients and methods Patients The present study was conducted at the National Cancer Institute, Cairo, Egypt during May 2011 to March 2015. After
approval of the institutional review board, 77 patients were selected from the pain clinic and were subjected to PVP. The patients suffered from intractable vertebral pain caused by vertebral metastases in the thoracolumbar spine and had one or more relative contraindication for PVP that rendered them at high risk for neurological sequels for the procedure. The risks of the procedure were discussed thoroughly with the patients who gave a written informed consent.
Inclusion criteria Patients were eligible if they were 18 years or older and had radiological evidence of vertebral involvement with axial pain that increased with activity or weight bearing (i.e., sitting up or standing) and did not respond satisfactorily (Pain Score > 40 on a 100 Visual Analogue Scale [VAS]) to conservative measures including rest, use of brace, and analgesics including paracetamol, ibuprofen, and oral morphine sulfate given in the highest tolerable dose for at least 4 weeks [14], if they were not indicated for radiotherapy as assessed by an oncologist consultant or their pain was not relieved after two weeks (VAS score is still > 40 mm) of palliative radiotherapy regimen. All patients had one or more of the following high risk criteria: • more than 70% loss of the vertebral height; • destruction of the posterior vertebral cortex; • severely destroyed vertebrae with a single intact pedicle (vertebral ghost); • epidural extension of tumor tissue; • cardiopulmonary comorbidities that would render patients at higher risk from pulmonary embolization of cement material [2,3,12,15].
Exclusion criteria Patients were not eligible if they had one or more of the following criteria: • systemic or local infection including osteomyelitis or discitis; • uncorrected coagulopathy; • hypersensitivity to bone cement; • impending spinal cord compression necessitating urgent surgical intervention.
Procedure details Before PVP with thick cement, all patients had formal neurosurgical assessment by a neurosurgeon before the procedure and underwent formal laboratory and radiological work-up including complete blood picture, coagulation profile, plain x-ray of targeted vertebral area (both in lying and standing positions), computed tomography (CT), and magnetic resonance imaging (MRI). All CT and MRI examinations were evaluated by a neuroradiologist.
Please cite this article in press as: Reyad RM, et al. Thick cement usage in percutaneous vertebroplasty for malignant vertebral fractures at high risk for cement leakage. Diagnostic and Interventional Imaging (2017), http://dx.doi.org/10.1016/j.diii.2017.02.010
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Thick cement usage for percutaneous vertebroplasty Ceftriaxone 1000 mg was administered intravenously 30 minutes before the procedure. The procedure was conducted in the prone position under fluoroscopic guidance. Standard monitoring included electrocardiography, pulse oximetry, and noninvasisve arterial blood pressure measurement. The procedure was conducted under conscious sedation using intravenous midazolam in a dose of 0.05 mg/kg midazolam plus intravenous fentanyl in a dose of 1 g/kg. Supplemental doses of intravenous propofol were allowed in increments of 20 to 30 mg as required during hammering and injection of cement. The skin was sterilized using povidone iodine and sterile drapes were applied. The target vertebral level was identified with C-arm fluoroscopy. The procedure was performed using a standard ® vertebroplasty kit (Mendec Spine-kit , Tecres, Verona, Italy) that included the liquid monomer and powder polymer components of the PMMA bone cement to be applied. A 10-cm long, 11- or 13-G bone biopsy needle was used to avoid the jet expulsion of cement under high pressure associated with smaller-sized needles. A beveled needle was used to allow accurate control of needle path and side deposition of bone cement. The unilateral transpedicular approach was utilized using a single-needle technique to minimize manipulation of the destroyed vertebrae; besides, the appropriateness of the unilateral approach has been proven recently [16]. Needle entrance stability was ensured by gentle hammering until the pediculo-vertebral angle is bypassed. At the terminal needle tip destination (usually in the lower half of the anterior third of the vertebral body), we performed swinging—screwing movement to ensure little cavitation that help in reducing intra vertebral pressure during cementation. First, cephalo-caudal orientation was assumed, then ipsilateral oblique (30◦ ) orientation was attempted to identify the standard ‘‘Scotty dog’’ appearance of the pedicle of the affected vertebra. The entry point was marked on the skin overlying the superolateral portion of the corresponding pedicle and local anesthesia was applied via a 22-G spinal needle using 10 mL of 1% lidocaine to anesthetize the soft
3 tissues and periosteum. The trajectory (end-on) technique was used for needle advancement under oblique view. Then, dead-lateral view was obtained to guide the needle parallel to the superior and inferior pedicular walls. Needle advancement was facilitated using gentle hammering until needle tip entered the vertebral body. The target end-point was the anterior one-third of the vertebral body, in the lower half of the body, if feasible. Venography was done using ® 2—3 mL of contrast medium (Omnipaque, Iohexol 300 mg I2 /mL, General-Electric Healthcare, Cork, Ireland) to verify the final position of the needle tip, in order to exclude vascular or epidural leakage and to predict the spread of the injected bone cement. Once the desired needle position was confirmed, the cement components were mixed according to the manufacture’s recommendation. To obtain cement of thick gum-like consistency or gelfoam texture, a few minutes were allowed beyond that recommended by the manufacture to get the standard tooth paste-like cement. Once the desired consistency was achieved, cement was injected under real-time lateral fluoroscopy using the delivery system included in the vertebroplasty kit (Fig. 1). If cement appeared at the epidural space or at the posterior one-third of the vertebral body, or if the patient complained of radicular pain, the injection was halted immediately. A cement control on the bench was checked continually until it solidified completely, before the needle was removed gently using a turning outward movement. After the procedure was completed, the patient was transferred to the recovery room where pain, hemodynamic variables, and neurologic status were checked for a minimum of 2 hours before discharge. Upon discharge, all patients were instructed to call urgently if they experienced undue back or leg pain that responded poorly to their regular analgesics, new motor or sensory deficit in the lower limbs, sphincteric dysfunction, difficulty of breathing, chest pain, or fever of 38 ◦ C or higher. Chest X-ray was repeated next day and patients were asked to attend the pain clinic in one week to have an X-ray and CT scan of the spine.
Figure 1. Percutaneous vertebroplasty in an 82-year-old man with prostatic carcinoma, who presented with a metastatic fracture of the 10th thoracic vertebra. A. Pre-procedure MR image in the sagittal plane shows a badly destroyed body of 10th thoracic vertebra (arrow). B. Dead-lateral fluoroscopic image shows the needle tip properly placed within the body of the fractured vertebra (arrow). C. CT scan one week after the procedure shows bone cement deposited within the body of the vertebra (thin arrows) and some cement leaking into the epidural space (thick arrow).
Please cite this article in press as: Reyad RM, et al. Thick cement usage in percutaneous vertebroplasty for malignant vertebral fractures at high risk for cement leakage. Diagnostic and Interventional Imaging (2017), http://dx.doi.org/10.1016/j.diii.2017.02.010
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Outcome measures The primary outcome measures were the severity of pain as assessed on a 100-mm visual analogue scale, the daily morphine consumption and the incidence of cement leakage whether during the procedure or shortly after (as detected with radiological follow-up after 1 week). Secondary outcome measures were: • the degree of disability as assessed using the ambulation score [17], the activities of daily living score (ADL) [17] and the Oswestry disability index (ODI) [18]; • the incidence of procedure-related adverse outcomes including back pain, local hematoma formation or infection, fracture of adjacent vertebrae, new neurological deficit, or cement embolization (as detected with chest x-ray on day 1 post-procedure). The outcome measures were assessed at the preoperative visit, and at 1 day, 1 week, 4 weeks and 12 weeks after the procedure.
Statistical analysis ®
®
Data were analyzed using MedCalc version 15.8 (MedCalc ® Software bvba, Ostend, Belgium) and XLSTAT version 2014.5.03 (Addinsoft, Inc., Brooklyn, NY, USA). Normality of numerical data distribution was examined using the d’Agostino—Pearson test. Normally distributed continuous variables were presented as mean and standard deviation and inter-group differences were compared using the independent-samples Student t-test. Discrete numerical variables were presented as median and interquartile range and between-group differences were compared using the Mann—Whitney U test. Categorical variables were presented as ratio or number and percentage, and differences between-groups were compared with Fisher exact test. For all tests, a two-sided P-value < 0.05 was considered statistically significant. Repeated-measures analysis of variance was used to compare normally distributed repeated-measures with application of the Bonferroni method for post-hoc pair-wise comparisons. For comparison of skewed repeated-measures, the Friedman test was used with application of the Nemenyi procedure for multiple post-hoc paired comparisons. Multivariate linear regression analysis was used to determine predictors of the pain score at 7 days after vertebroplasty. Variables associated with excellent (> 70%) improvement of pain with a permissive probability < 0.25 at univariate analysis were selected for multivariable analysis. Numerical variables not fulfilling the assumption of normality were subjected to logarithmic transformation. The enter method was used for calculation of the regression estimates.
Results During the study period, 77 patients underwent PVP. Fourteen out of 77 (18.2%) patients attended the pain clinic the day following the procedure and were lost to follow-up thereafter. None of these patients had serious complications as assessed upon their sole post-procedure visit. Sixty-three out of 77 (81.8%) patients completed the 12-week follow-up
period and were included in data analysis. There were 30 men and 33 women, with a mean age of 58 ± 11 (SD) [range: 34—81 years]. A total of 92 transpedicular PVP procedures were performed on the 63 patients. All procedures were performed on one side only (unilateral). Thirty-nine out of 63 (61.9%) patients underwent single-level PVP, whereas 24/63 (38.1%) had PVP performed on multiple levels. The reason for performing multi-level injections was multiple vertebral involvement by myeloma (3/24 patients; 12.5%), lymphoma (2/24 patients; 8.3%), metastatic breast carcinoma (10/24 patients; 41.7%), hepatocellular carcinoma (5/24 patients; 20.8%), or prostatic carcinoma (4/24 patients; 16.7%). The characteristics of the 63 patients who completed the followup are shown in Table 1.
Table 1 Variable
Characteristics of the study cohort. Metrics
Quantitative variables Age (years) 58 ± 11 [34—81] Procedure duration (min) 41 ± 10 [26—75] Cement volume (mL) 1.5 ± 0.5 [1—2.2] Solidification time (min) 7.0 ± 0.5 [6—8.3] Qualitative variables Gender Male 30/63 (47.6%) Female 33/63 (52.4%) Primary tumor Prostatic carcinoma 9/63 (14.3%) Lung carcinoma 11/63 (17.5%) Multiple myeloma 5/63 (7.9%) Breast carcinoma 15/63 (23.8%) Thyroid carcinoma 5/63 (7.9%) Rectal carcinoma 1/63 (1.6%) Lymphoma 3/63 (4.8%) Hepatocellular carcinoma 11/63 (17.5%) Colon carcinoma 3/63 (4.8%) Number of injected vertebrae per patient One 39/63 (61.9%) Two 21/63 (33.3%) Three 1/63 (1.6%) Four 2/63 (3.2%) Treated vertebrae T8 3/92 (3.3%) T9 4/92 (4.3%) T10 7/92 (7.6%) T11 8/92 (8.7%) T12 14/92 (15.2%) L1 9/92 (9.8%) L2 21/92 (22.9%) L3 6/92 (6.5%) L4 14/92(15.2%) L5 6/92 (6.5%) Quantitative variables are expressed as mean ± SD. Numbers in brackets are ranges. Qualitative variables are expressed as proportions and percentages. Numbers in parentheses are percentages.
Please cite this article in press as: Reyad RM, et al. Thick cement usage in percutaneous vertebroplasty for malignant vertebral fractures at high risk for cement leakage. Diagnostic and Interventional Imaging (2017), http://dx.doi.org/10.1016/j.diii.2017.02.010
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Thick cement usage for percutaneous vertebroplasty Table 2
Outcome measures.
Variable
Pain score Daily morphine consumption (mg) Ambulation score ADL ODI
5
Follow-up time Pre-procedure
Day 1
Day 7
Week 4
Week 12
P-value
74 ± 11 [50—95] 80 ± 5 (60—90) 4 [3—4] 4 [3—5] 71 [12]
23 ± 15 [0—62] NA
23 ± 15 [0—60] 20 ± 3 (20—30) 2 [1—2] 2 [1—3] 28 [12]
34 ± 13 [10—65] 0±5 (0—30) 2 [1—2] 2 [2—3] 35 [12]
39 ± 13 [10—68] 20 ± 5 (0—38) 2 [2—3] 3 [2—3] 40 [13]
< 0.001a
NA NA NA
< 0.00001b < 0.00001b < 0.00001b < 0.001a
Data are mean (SD) or median (interquartile range). ADL: activities of daily living score; NA: not assessed; ODI: Oswestry disability index. Numbers in brackets are ranges. Numbers in parentheses are interquartile ranges (Q1; Q3). a Repeated-measures analysis of variance (ANOVA). b Friedman test.
Table 2 shows the outcome measures. The mean ± SD of pre-procedure pain score was 74 ± 11 (SD). The pain score decreased to 23 ± 15 (SD), 23 ± 15 (SD), 34 ± (SD) and 39 ± (SD), 13 at day 1, day 7, week 4, and week 12 post-procedure, respectively (Fig. 2). Compared with pre-procedure value, all post-procedure pain scores were significantly lower (P < 0.0001). The median (interquartile range) daily morphine consumption decreased from a baseline value of 80 (60—90) mg, to 20 (20—30) mg 1 day after the procedure, 0 (0—30) mg at week 4, and 20 (0—38) mg at week 12 (Fig. 3). The reduction in morphine consumption was statistically significantly at all follow-up times (P < 0.0001). The ambulation score, ADL, and ODI were all significantly lower at all assessment times compared with the respective pre-procedure values (P < 0.0001). The main end-points for improvement of pain and disability are shown in Table 3. Thirty-three (52.4%) patients had excellent (> 70%) improvement of pain, 24 (38.1%)
Figure 3. Box plots show the daily morphine consumption in the study population. Markers represent individual observations. Box represents the interquartile range. Line inside the box represents the median. Error bars represent the minimum and maximum values excluding outliers and extreme observations (dark markers).
Table 3
Main end-points at day 7.
Variable Pain improvement at day 7 Excellent (> 70%) Satisfactory (50%—70%) Unsatisfactory (< 50%) ODI improvement at day 7 Excellent (> 70%) Satisfactory (50%—70%) Unsatisfactory (< 50%)
Figure 2. Mean pain score in the study population. Error bars represent the standard error of the mean. Markers represent individual observations.
Metric 33/63 (52.4%) 24/63 (38.1%) 6/63 (9.5%) 20/63 (31.7%) 28/63 (44.4%) 15/63 (23.8%)
Data are expressed as proportions and percentages (%). ODI: Oswestry Disability Index.
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had satisfactory (50%—70%) improvement, and 6 (9.5%) had unsatisfactory response (< 50% improvement). As regards the ODI, 20 (31.7%) patients had excellent (> 70%) improvement of disability, 28 (44.4%) had satisfactory (50%—70%) improvement, and 15 (23.8%) had unsatisfactory response (< 50% improvement). The incidence of adverse effects and complications are shown in Table 4. Thirty-nine (61.9%) patients reported an exacerbation of the back pain after the procedure. The exacerbation was transient, lasting for a maximum of 9 hours. Six (9.5%) patients developed a localized subcutaneous hematoma at the injection site. Cement leakage occurred in 5 (7.9%) patients and iatrogenic fracture of an adjacent vertebra in 2 (3.2%) patients. The leakage of cement was intradiscal in 1 (20%) patient, retroperitoneal in 1 (20%) patient, and extradural in 1 (20%) patient. In the remaining 2 (40%) patients, the leakage involved the perivertebral venous plexus and the cement material spread cephalad for a few levels above the injection site with no ensuing cardiorespiratory ill effects. The two patients suffering from vertebral fracture were 71 and 73 years of age, respectively and had extensive osteoporosis of the spine. In both patients, the fracture was diagnosed with CT examination done on week 1 follow-up visit and did not result in new neurological deficit. None of the patients developed discitis, osteomyelitis, or new neurological deficit.
Discussion The present study showed that PVP could be performed with reasonable safety in patients with vertebral metastasisrelated pain who were considered to be at high risk for cement leakage and embolization in view of the extensive loss of vertebral substance, posterior location of metastases, epidural involvement by tumor, or presence of cardiopulmonary comorbidities. In the current trial, the procedure was associated with significant reduction in the severity of pain, daily opioid consumption, and disability scores. An interesting observation in the present trial was that the pain score on day 1 after the procedure was the only independent predictor for the severity of pain at 7 days. However, the external validity of this finding is difficult to assess in view of the paucity of evidence on the determinants of response in PVP in patients at high risk for the procedure. In our study, the improvement of pain at 7 days postprocedure was dramatic (VAS score, 0) in 14% of patients, excellent (> 70% reduction) in 36.5%, and satisfactory (50% to 70% reduction) in 39.7%, with an overall efficacy (≥ 50% Table 4
Incidence of adverse outcomes.
Adverse outcomes
Metric
Back pain Hematoma Cement leakage Fracture of an adjacent vertebra Discitis or osteomyelitis Neurological deficit
39/63 (61.9%) 6/63 (9.5%) 5/63 (7.9%) 2/63 (3.2%) 0/63 (0%) 0/63 (0%)
Data are expressed as proportions and percentages (%).
reduction) of approximately 90%, a figure that is higher than that reported for metastatic fractures or myeloma (70%) [19,20] and close to that reported for fractures associated with osteoporosis or hemangiomas (90%) [21]. In one trial on the efficacy of PVP for OVCF, 18.6% of subjects reported complete pain relief (VAS, 0) at 1 month and the mean VAS score was significantly lower compared with baseline [22]. In a randomized controlled trial (RCT) comparing PVP with medical treatment for painful OVCF, PVP was associated with immediate pain relief and improved mobility and function whereas 88% of subjects treated medically asked for PVP after 2 weeks of initiating medical treatment [23]. A large meta-analysis [8] comparing PVP and percutaneous kyphoplasty (PKP) for treating OVCF reported that both interventions were safe and effective. Similar results were reported by other systematic reviews [10,13,24]. In contradistinction to these results, two RCT [25,26] compared PVP with placebo for painful OVCF and reported that both treatments with comparable over a follow-up period of 6 months. The exact mechanism by which PVP exerts its favorable effect on the relief of pain is not clear. One mechanism may be the mechanical stabilization of microfractures [27]. Another proposed mechanism is that the exothermic reaction of PMMA polymerization may cause thermal destruction of sensory nerve terminals [28]. Additional mechanisms related to a neurotoxic effect of methyl methacrylate monomer of PMMA may also be implicated [29]. Moreover, biological mechanisms have been suggested that are linked to an inhibitory effect of PMMA on osteoclasts that are believed to be involved in the causation of neuropathic pain via vanilloid receptors and acid-sensing ion channel [30]. As per the manufacturer’s recommendation, polymerization of PMMA occurs within 20 to 50 seconds from mixing the component of cement, and injection should be in the creamy paste phase [31]. In the present study, the mean time for solidification of cement was 7 minutes with a standard deviation of 0.5 minutes, somewhat longer than previously described by other investigators [32], to allow for attainment of a firmer consistency of the injectate. The mean ± SD volume of cement injected in the present study was 2.2 ± 0.4 (SD) mL. Higher volumes may be accommodated by vertebral compression fractures (VCF) due to osteoporosis [21], and a reasonable rule of thumb may that the injected volume should be 16% to 20% of the vertebral volume [33]. This is of particular relevance in the present trial, where most of patients had marked loss of the effective vertebral volume by the metastases and the injected volume had to be reduced accordingly. Cement volumes similar to that employed in the current study were previously described by other investigators [34]. There has always been concern regarding the safety of PVP in patients with marked loss of vertebral substance or encroachment on the posterior vertebral cortex owing to the potential for cement leakage and subsequent neurological sequels [10,13]. In this regard, the most common procedurerelated adverse effect observed in the current study was temporary exacerbation of the back pain, which occurred in approximately 62% of the patients. The incidence of the more serious cement leak was in the order of 8%, a figure that was strikingly lower than that reported by previous investigators. In one such series, the incidence of cement
Please cite this article in press as: Reyad RM, et al. Thick cement usage in percutaneous vertebroplasty for malignant vertebral fractures at high risk for cement leakage. Diagnostic and Interventional Imaging (2017), http://dx.doi.org/10.1016/j.diii.2017.02.010
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Thick cement usage for percutaneous vertebroplasty leakage and/or embolization was approximately 15% in PVP performed for osteoporosis-related vertebral compression fractures, whereas much higher overall rates in the order of 20% [8,9] and 41% [10] were reported by two systematic reviews. The unexpectedly lower leakage rate observed in the present trial despite the increased risk for this untoward side effect may be attributed to two factors. Firstly, the relatively small volume of cement injected, and secondly, and perhaps the more importantly, the relatively firmer consistency of the cement. The use of firm bone cement has been described previously for treatment of osteoporosisrelated vertebral compression fractures [22]. However, to our knowledge, no previous study has used it for fixation of high risk metastatic vertebral fractures. One observation that warrants commenting is the rather different pattern of leakage observed in the present trial. In a systematic review the most common sites for leakage were, in decreasing order of frequency, the paraspinal space (32.5%), epidural space (32%), intradiscal (30.5%), foraminal (3.3%), and pulmonary (1.7%) [10]. In our study, 40% of incidents occurred into the paravertebral venous plexus, although the cement did not spread cephalad beyond the few adjacent levels and was associated with no ill effects. The remaining incidents of cement leakage were intradiscal (20%), retroperitoneal (20%), and extradural (20%). Again, these differences in the pattern of spread may be attributed to differences in the consistency and volume of cement injected in the current trial or to clinic-pathological differences related to the location of the metastases or the underlying indication for PVP. Our study has some limitations that include the relatively small number of patients involved in the study and the involvement of a specific patient subgroup that was considered to be at high risk for cement leakage and/or embolization, and hence, generalization of the current findings to other patient groups should be regarded with caution, and it is recommended to conduct further studies both to verify the current findings and to examine the generalizability of the findings to other patient populations. In conclusion, PVP using thick cement could be administered with reasonable safety to patients suffering from intractable pain caused by vertebral metastases who were considered to be at high risk for cement leakage. The procedure was associated with significant improvement of pain and disability and may serve as a feasible option in this high risk group in whom PVP may be relatively contraindicated.
Disclosure of interest The authors declare that they have no competing interest.
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[27] McKiernan F, Faciszewski T, Jensen R. Does vertebral height restoration achieved at vertebroplasty matter? J Vasc Interv Radiol 2005;16:973—9. [28] Heini PF, Wälchli B, Berlemann U. Percutaneous transpedicular vertebroplasty with PMMA: operative technique and early results. A prospective study for the treatment of osteoporotic compression fractures. Eur Spine J 2000;9:445—50. [29] Bostrom MP, Lane JM. Future directions. Augmentation of osteoporotic vertebral bodies. Spine 1997;22:38S—42S. [30] Scholz J, Woolf CJ. Can we conquer pain? Nat Neurosci 2002;5:1062—7. [31] Centenera LV, Choi S, Hirsch JA. Percutaneous vertebroplasty treats compression fractures. Diagn Imaging 2000;22:147—8. [32] Heini PF. The current treatment — a survey of osteoporotic fracture treatment. Osteoporotic spine fractures: the spine surgeon’s perspective. Osteoporos Int 2005;162:S85—92. [33] Boszczyk B. Volume matters: a review of procedural details of two randomised controlled vertebroplasty trials of 2009. Eur Spine J 2010;19:1837—40. [34] Cotten A, Dewatre F, Cortet B, Assaker R, Leblond D, Duquesnoy 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;200:525—30.
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ORIGINAL ARTICLE /Interventional imaging
Thick cement usage in percutaneous vertebroplasty for malignant vertebral fractures at high risk for cement leakage R.M. Reyad a, H.Z. Ghobrial a, S.M. Hakim b, R.H. Hashem c, A. Elsaman d, M.H. Shaaban c,∗ a
Department of Anesthesia and Pain Management, National Cancer Institute, Cairo University, Cairo, Egypt b Department of Anesthesiology, Intensive Care, and Pain Management, Faculty of Medicine, Ain Shams University, Cairo, Egypt c Departments of Diagnostic and Interventional Radiology, Faculty of Medicine, Cairo University, Cairo, Egypt d Departments of Neurosurgery, Faculty of Medicine, Cairo University, Cairo, Egypt
KEYWORDS Percutaneous vertebroplasty; Bone cement; Interventional radiology; Cement leakage; Pain relief
∗
Abstract Purpose: To assess the feasibility and safety of transpedicular percutaneous vertebroplasty (PVP) using thick bone cement in patients with intractable metastatic vertebral pain and at high risk for cement leakage. Methods: Unilateral transpedicular PVP using firm bone cement was performed in 77 patients with intractable pain due to vertebral metastases in the thoracolumbar spine, who had one or more relative contraindication to PVP. Primary outcome measures were the severity of pain as assessed on a 100-mm visual analogue scale and daily morphine consumption. Secondary outcome measures were the degree of disability and the incidence of procedure-related adverse outcomes. The outcome measures were assessed at the preoperative visit and at 1 day, 1 week, 4 weeks and 12 weeks after the procedure. Results: Sixty-three (81.8%) patients completed the 12-week follow-up period. There were 30 men and 33 women, with a mean age of 58 ± 11 (SD) [range: 34—81 years]. Compared with preprocedure value, all post-procedure pain scores were significantly lower (P < 0.0001). Likewise, there was a statistically significant reduction in daily morphine consumption at all follow-up times (P < 0.0001). The ambulation score, ADL, and ODI were all significantly lower at all assessment times compared with pre-procedure values (P < 0.0001). No serious adverse effects were observed.
Corresponding author. 5015 Mearage City, Maadi, Cairo, Egypt. E-mail address: [email protected] (M.H. Shaaban).
http://dx.doi.org/10.1016/j.diii.2017.02.010 2211-5684/© 2017 Editions franc ¸aises de radiologie. Published by Elsevier Masson SAS. All rights reserved.
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R.M. Reyad et al. Conclusion: PVP using thick bone cement could be administered with reasonable safety to patients suffering from intractable pain caused by vertebral metastases who were at high risk for cement leakage. The procedure was associated with significant improvement of pain and disability. © 2017 Editions franc ¸aises de radiologie. Published by Elsevier Masson SAS. All rights reserved.
Percutaneous vertebroplasty (PVP) is a minimally invasive, radiologically guided procedure that aims at relieving pain and partially stabilizing vertebral body fractures [1,2]. The technique is currently widely used for the management of painful vertebral fractures associated with trauma and malignancies [3]. The incidence of spinal metastases in cancer patients is 5% and these patients have limited life expectancy of 10 months [4]. Vertebral metastases are found in twothirds of patients who die of malignant diseases. Thoracic vertebrae are commonly affected (60—80%), followed by lumbar (20%) and lastly cervical vertebrae (10%) [5]. Osteolytic spinal lesions, together with the poor quality of new bone formed by osteoblastic metastases, may induce severe spinal pain, hypercalcemia, pathological fractures and spinal cord compression [6]. PVP has a role in pain relief and vertebral stabilization with little risk as compared with formal surgical procedures [7]. PVP is currently indicated after failure of conservative management of vertebral fractures and is considered a safer alternative to formal surgical fixation in this high risk surgical population [8]. Cement leakage is a serious complication of PVP because it may cause paralysis or radiculopathy [8]. Cement leakage has been reported in 20% [9] to 41% [10] of procedures. The risk of cement leakage increases in osteolytic spinal metastases, which involve the posterior portion of vertebrae in 10—20% of cases [11]. The risk of even small cement leakage is augmented by preexisting tumors invading spinal canal and is higher in the thoracic and cervical regions owing to the relatively smaller size of the vertebral bodies [12]. Polymethyl methacrylate (PMMA) is the type of cement most commonly used for augmentation vertebroplasty, including PVP. PMMA has a liquid phase and solid phase and is characterized by its bio-inertness and biocompatibility for long-term use [13]. We assumed that using firmer gum-like (thick cement) rather than the usual tooth paste-like bone cement for PVP with PMMA would reduce the risk for cement leakage, thus rendering the procedure a feasible treatment option in this high risk patient category. The purpose of this study was to assess the feasibility and safety of transpedicular PVP using thick bone cement in patients with painful malignant vertebral lesion involving the lower thoracic and lumbar regions, in whom PVP was relatively contraindicated because of a high risk for cement leakage.
Patients and methods Patients The present study was conducted at the National Cancer Institute, Cairo, Egypt during May 2011 to March 2015. After
approval of the institutional review board, 77 patients were selected from the pain clinic and were subjected to PVP. The patients suffered from intractable vertebral pain caused by vertebral metastases in the thoracolumbar spine and had one or more relative contraindication for PVP that rendered them at high risk for neurological sequels for the procedure. The risks of the procedure were discussed thoroughly with the patients who gave a written informed consent.
Inclusion criteria Patients were eligible if they were 18 years or older and had radiological evidence of vertebral involvement with axial pain that increased with activity or weight bearing (i.e., sitting up or standing) and did not respond satisfactorily (Pain Score > 40 on a 100 Visual Analogue Scale [VAS]) to conservative measures including rest, use of brace, and analgesics including paracetamol, ibuprofen, and oral morphine sulfate given in the highest tolerable dose for at least 4 weeks [14], if they were not indicated for radiotherapy as assessed by an oncologist consultant or their pain was not relieved after two weeks (VAS score is still > 40 mm) of palliative radiotherapy regimen. All patients had one or more of the following high risk criteria: • more than 70% loss of the vertebral height; • destruction of the posterior vertebral cortex; • severely destroyed vertebrae with a single intact pedicle (vertebral ghost); • epidural extension of tumor tissue; • cardiopulmonary comorbidities that would render patients at higher risk from pulmonary embolization of cement material [2,3,12,15].
Exclusion criteria Patients were not eligible if they had one or more of the following criteria: • systemic or local infection including osteomyelitis or discitis; • uncorrected coagulopathy; • hypersensitivity to bone cement; • impending spinal cord compression necessitating urgent surgical intervention.
Procedure details Before PVP with thick cement, all patients had formal neurosurgical assessment by a neurosurgeon before the procedure and underwent formal laboratory and radiological work-up including complete blood picture, coagulation profile, plain x-ray of targeted vertebral area (both in lying and standing positions), computed tomography (CT), and magnetic resonance imaging (MRI). All CT and MRI examinations were evaluated by a neuroradiologist.
Please cite this article in press as: Reyad RM, et al. Thick cement usage in percutaneous vertebroplasty for malignant vertebral fractures at high risk for cement leakage. Diagnostic and Interventional Imaging (2017), http://dx.doi.org/10.1016/j.diii.2017.02.010
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Thick cement usage for percutaneous vertebroplasty Ceftriaxone 1000 mg was administered intravenously 30 minutes before the procedure. The procedure was conducted in the prone position under fluoroscopic guidance. Standard monitoring included electrocardiography, pulse oximetry, and noninvasisve arterial blood pressure measurement. The procedure was conducted under conscious sedation using intravenous midazolam in a dose of 0.05 mg/kg midazolam plus intravenous fentanyl in a dose of 1 g/kg. Supplemental doses of intravenous propofol were allowed in increments of 20 to 30 mg as required during hammering and injection of cement. The skin was sterilized using povidone iodine and sterile drapes were applied. The target vertebral level was identified with C-arm fluoroscopy. The procedure was performed using a standard ® vertebroplasty kit (Mendec Spine-kit , Tecres, Verona, Italy) that included the liquid monomer and powder polymer components of the PMMA bone cement to be applied. A 10-cm long, 11- or 13-G bone biopsy needle was used to avoid the jet expulsion of cement under high pressure associated with smaller-sized needles. A beveled needle was used to allow accurate control of needle path and side deposition of bone cement. The unilateral transpedicular approach was utilized using a single-needle technique to minimize manipulation of the destroyed vertebrae; besides, the appropriateness of the unilateral approach has been proven recently [16]. Needle entrance stability was ensured by gentle hammering until the pediculo-vertebral angle is bypassed. At the terminal needle tip destination (usually in the lower half of the anterior third of the vertebral body), we performed swinging—screwing movement to ensure little cavitation that help in reducing intra vertebral pressure during cementation. First, cephalo-caudal orientation was assumed, then ipsilateral oblique (30◦ ) orientation was attempted to identify the standard ‘‘Scotty dog’’ appearance of the pedicle of the affected vertebra. The entry point was marked on the skin overlying the superolateral portion of the corresponding pedicle and local anesthesia was applied via a 22-G spinal needle using 10 mL of 1% lidocaine to anesthetize the soft
3 tissues and periosteum. The trajectory (end-on) technique was used for needle advancement under oblique view. Then, dead-lateral view was obtained to guide the needle parallel to the superior and inferior pedicular walls. Needle advancement was facilitated using gentle hammering until needle tip entered the vertebral body. The target end-point was the anterior one-third of the vertebral body, in the lower half of the body, if feasible. Venography was done using ® 2—3 mL of contrast medium (Omnipaque, Iohexol 300 mg I2 /mL, General-Electric Healthcare, Cork, Ireland) to verify the final position of the needle tip, in order to exclude vascular or epidural leakage and to predict the spread of the injected bone cement. Once the desired needle position was confirmed, the cement components were mixed according to the manufacture’s recommendation. To obtain cement of thick gum-like consistency or gelfoam texture, a few minutes were allowed beyond that recommended by the manufacture to get the standard tooth paste-like cement. Once the desired consistency was achieved, cement was injected under real-time lateral fluoroscopy using the delivery system included in the vertebroplasty kit (Fig. 1). If cement appeared at the epidural space or at the posterior one-third of the vertebral body, or if the patient complained of radicular pain, the injection was halted immediately. A cement control on the bench was checked continually until it solidified completely, before the needle was removed gently using a turning outward movement. After the procedure was completed, the patient was transferred to the recovery room where pain, hemodynamic variables, and neurologic status were checked for a minimum of 2 hours before discharge. Upon discharge, all patients were instructed to call urgently if they experienced undue back or leg pain that responded poorly to their regular analgesics, new motor or sensory deficit in the lower limbs, sphincteric dysfunction, difficulty of breathing, chest pain, or fever of 38 ◦ C or higher. Chest X-ray was repeated next day and patients were asked to attend the pain clinic in one week to have an X-ray and CT scan of the spine.
Figure 1. Percutaneous vertebroplasty in an 82-year-old man with prostatic carcinoma, who presented with a metastatic fracture of the 10th thoracic vertebra. A. Pre-procedure MR image in the sagittal plane shows a badly destroyed body of 10th thoracic vertebra (arrow). B. Dead-lateral fluoroscopic image shows the needle tip properly placed within the body of the fractured vertebra (arrow). C. CT scan one week after the procedure shows bone cement deposited within the body of the vertebra (thin arrows) and some cement leaking into the epidural space (thick arrow).
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Outcome measures The primary outcome measures were the severity of pain as assessed on a 100-mm visual analogue scale, the daily morphine consumption and the incidence of cement leakage whether during the procedure or shortly after (as detected with radiological follow-up after 1 week). Secondary outcome measures were: • the degree of disability as assessed using the ambulation score [17], the activities of daily living score (ADL) [17] and the Oswestry disability index (ODI) [18]; • the incidence of procedure-related adverse outcomes including back pain, local hematoma formation or infection, fracture of adjacent vertebrae, new neurological deficit, or cement embolization (as detected with chest x-ray on day 1 post-procedure). The outcome measures were assessed at the preoperative visit, and at 1 day, 1 week, 4 weeks and 12 weeks after the procedure.
Statistical analysis ®
®
Data were analyzed using MedCalc version 15.8 (MedCalc ® Software bvba, Ostend, Belgium) and XLSTAT version 2014.5.03 (Addinsoft, Inc., Brooklyn, NY, USA). Normality of numerical data distribution was examined using the d’Agostino—Pearson test. Normally distributed continuous variables were presented as mean and standard deviation and inter-group differences were compared using the independent-samples Student t-test. Discrete numerical variables were presented as median and interquartile range and between-group differences were compared using the Mann—Whitney U test. Categorical variables were presented as ratio or number and percentage, and differences between-groups were compared with Fisher exact test. For all tests, a two-sided P-value < 0.05 was considered statistically significant. Repeated-measures analysis of variance was used to compare normally distributed repeated-measures with application of the Bonferroni method for post-hoc pair-wise comparisons. For comparison of skewed repeated-measures, the Friedman test was used with application of the Nemenyi procedure for multiple post-hoc paired comparisons. Multivariate linear regression analysis was used to determine predictors of the pain score at 7 days after vertebroplasty. Variables associated with excellent (> 70%) improvement of pain with a permissive probability < 0.25 at univariate analysis were selected for multivariable analysis. Numerical variables not fulfilling the assumption of normality were subjected to logarithmic transformation. The enter method was used for calculation of the regression estimates.
Results During the study period, 77 patients underwent PVP. Fourteen out of 77 (18.2%) patients attended the pain clinic the day following the procedure and were lost to follow-up thereafter. None of these patients had serious complications as assessed upon their sole post-procedure visit. Sixty-three out of 77 (81.8%) patients completed the 12-week follow-up
period and were included in data analysis. There were 30 men and 33 women, with a mean age of 58 ± 11 (SD) [range: 34—81 years]. A total of 92 transpedicular PVP procedures were performed on the 63 patients. All procedures were performed on one side only (unilateral). Thirty-nine out of 63 (61.9%) patients underwent single-level PVP, whereas 24/63 (38.1%) had PVP performed on multiple levels. The reason for performing multi-level injections was multiple vertebral involvement by myeloma (3/24 patients; 12.5%), lymphoma (2/24 patients; 8.3%), metastatic breast carcinoma (10/24 patients; 41.7%), hepatocellular carcinoma (5/24 patients; 20.8%), or prostatic carcinoma (4/24 patients; 16.7%). The characteristics of the 63 patients who completed the followup are shown in Table 1.
Table 1 Variable
Characteristics of the study cohort. Metrics
Quantitative variables Age (years) 58 ± 11 [34—81] Procedure duration (min) 41 ± 10 [26—75] Cement volume (mL) 1.5 ± 0.5 [1—2.2] Solidification time (min) 7.0 ± 0.5 [6—8.3] Qualitative variables Gender Male 30/63 (47.6%) Female 33/63 (52.4%) Primary tumor Prostatic carcinoma 9/63 (14.3%) Lung carcinoma 11/63 (17.5%) Multiple myeloma 5/63 (7.9%) Breast carcinoma 15/63 (23.8%) Thyroid carcinoma 5/63 (7.9%) Rectal carcinoma 1/63 (1.6%) Lymphoma 3/63 (4.8%) Hepatocellular carcinoma 11/63 (17.5%) Colon carcinoma 3/63 (4.8%) Number of injected vertebrae per patient One 39/63 (61.9%) Two 21/63 (33.3%) Three 1/63 (1.6%) Four 2/63 (3.2%) Treated vertebrae T8 3/92 (3.3%) T9 4/92 (4.3%) T10 7/92 (7.6%) T11 8/92 (8.7%) T12 14/92 (15.2%) L1 9/92 (9.8%) L2 21/92 (22.9%) L3 6/92 (6.5%) L4 14/92(15.2%) L5 6/92 (6.5%) Quantitative variables are expressed as mean ± SD. Numbers in brackets are ranges. Qualitative variables are expressed as proportions and percentages. Numbers in parentheses are percentages.
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Thick cement usage for percutaneous vertebroplasty Table 2
Outcome measures.
Variable
Pain score Daily morphine consumption (mg) Ambulation score ADL ODI
5
Follow-up time Pre-procedure
Day 1
Day 7
Week 4
Week 12
P-value
74 ± 11 [50—95] 80 ± 5 (60—90) 4 [3—4] 4 [3—5] 71 [12]
23 ± 15 [0—62] NA
23 ± 15 [0—60] 20 ± 3 (20—30) 2 [1—2] 2 [1—3] 28 [12]
34 ± 13 [10—65] 0±5 (0—30) 2 [1—2] 2 [2—3] 35 [12]
39 ± 13 [10—68] 20 ± 5 (0—38) 2 [2—3] 3 [2—3] 40 [13]
< 0.001a
NA NA NA
< 0.00001b < 0.00001b < 0.00001b < 0.001a
Data are mean (SD) or median (interquartile range). ADL: activities of daily living score; NA: not assessed; ODI: Oswestry disability index. Numbers in brackets are ranges. Numbers in parentheses are interquartile ranges (Q1; Q3). a Repeated-measures analysis of variance (ANOVA). b Friedman test.
Table 2 shows the outcome measures. The mean ± SD of pre-procedure pain score was 74 ± 11 (SD). The pain score decreased to 23 ± 15 (SD), 23 ± 15 (SD), 34 ± (SD) and 39 ± (SD), 13 at day 1, day 7, week 4, and week 12 post-procedure, respectively (Fig. 2). Compared with pre-procedure value, all post-procedure pain scores were significantly lower (P < 0.0001). The median (interquartile range) daily morphine consumption decreased from a baseline value of 80 (60—90) mg, to 20 (20—30) mg 1 day after the procedure, 0 (0—30) mg at week 4, and 20 (0—38) mg at week 12 (Fig. 3). The reduction in morphine consumption was statistically significantly at all follow-up times (P < 0.0001). The ambulation score, ADL, and ODI were all significantly lower at all assessment times compared with the respective pre-procedure values (P < 0.0001). The main end-points for improvement of pain and disability are shown in Table 3. Thirty-three (52.4%) patients had excellent (> 70%) improvement of pain, 24 (38.1%)
Figure 3. Box plots show the daily morphine consumption in the study population. Markers represent individual observations. Box represents the interquartile range. Line inside the box represents the median. Error bars represent the minimum and maximum values excluding outliers and extreme observations (dark markers).
Table 3
Main end-points at day 7.
Variable Pain improvement at day 7 Excellent (> 70%) Satisfactory (50%—70%) Unsatisfactory (< 50%) ODI improvement at day 7 Excellent (> 70%) Satisfactory (50%—70%) Unsatisfactory (< 50%)
Figure 2. Mean pain score in the study population. Error bars represent the standard error of the mean. Markers represent individual observations.
Metric 33/63 (52.4%) 24/63 (38.1%) 6/63 (9.5%) 20/63 (31.7%) 28/63 (44.4%) 15/63 (23.8%)
Data are expressed as proportions and percentages (%). ODI: Oswestry Disability Index.
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had satisfactory (50%—70%) improvement, and 6 (9.5%) had unsatisfactory response (< 50% improvement). As regards the ODI, 20 (31.7%) patients had excellent (> 70%) improvement of disability, 28 (44.4%) had satisfactory (50%—70%) improvement, and 15 (23.8%) had unsatisfactory response (< 50% improvement). The incidence of adverse effects and complications are shown in Table 4. Thirty-nine (61.9%) patients reported an exacerbation of the back pain after the procedure. The exacerbation was transient, lasting for a maximum of 9 hours. Six (9.5%) patients developed a localized subcutaneous hematoma at the injection site. Cement leakage occurred in 5 (7.9%) patients and iatrogenic fracture of an adjacent vertebra in 2 (3.2%) patients. The leakage of cement was intradiscal in 1 (20%) patient, retroperitoneal in 1 (20%) patient, and extradural in 1 (20%) patient. In the remaining 2 (40%) patients, the leakage involved the perivertebral venous plexus and the cement material spread cephalad for a few levels above the injection site with no ensuing cardiorespiratory ill effects. The two patients suffering from vertebral fracture were 71 and 73 years of age, respectively and had extensive osteoporosis of the spine. In both patients, the fracture was diagnosed with CT examination done on week 1 follow-up visit and did not result in new neurological deficit. None of the patients developed discitis, osteomyelitis, or new neurological deficit.
Discussion The present study showed that PVP could be performed with reasonable safety in patients with vertebral metastasisrelated pain who were considered to be at high risk for cement leakage and embolization in view of the extensive loss of vertebral substance, posterior location of metastases, epidural involvement by tumor, or presence of cardiopulmonary comorbidities. In the current trial, the procedure was associated with significant reduction in the severity of pain, daily opioid consumption, and disability scores. An interesting observation in the present trial was that the pain score on day 1 after the procedure was the only independent predictor for the severity of pain at 7 days. However, the external validity of this finding is difficult to assess in view of the paucity of evidence on the determinants of response in PVP in patients at high risk for the procedure. In our study, the improvement of pain at 7 days postprocedure was dramatic (VAS score, 0) in 14% of patients, excellent (> 70% reduction) in 36.5%, and satisfactory (50% to 70% reduction) in 39.7%, with an overall efficacy (≥ 50% Table 4
Incidence of adverse outcomes.
Adverse outcomes
Metric
Back pain Hematoma Cement leakage Fracture of an adjacent vertebra Discitis or osteomyelitis Neurological deficit
39/63 (61.9%) 6/63 (9.5%) 5/63 (7.9%) 2/63 (3.2%) 0/63 (0%) 0/63 (0%)
Data are expressed as proportions and percentages (%).
reduction) of approximately 90%, a figure that is higher than that reported for metastatic fractures or myeloma (70%) [19,20] and close to that reported for fractures associated with osteoporosis or hemangiomas (90%) [21]. In one trial on the efficacy of PVP for OVCF, 18.6% of subjects reported complete pain relief (VAS, 0) at 1 month and the mean VAS score was significantly lower compared with baseline [22]. In a randomized controlled trial (RCT) comparing PVP with medical treatment for painful OVCF, PVP was associated with immediate pain relief and improved mobility and function whereas 88% of subjects treated medically asked for PVP after 2 weeks of initiating medical treatment [23]. A large meta-analysis [8] comparing PVP and percutaneous kyphoplasty (PKP) for treating OVCF reported that both interventions were safe and effective. Similar results were reported by other systematic reviews [10,13,24]. In contradistinction to these results, two RCT [25,26] compared PVP with placebo for painful OVCF and reported that both treatments with comparable over a follow-up period of 6 months. The exact mechanism by which PVP exerts its favorable effect on the relief of pain is not clear. One mechanism may be the mechanical stabilization of microfractures [27]. Another proposed mechanism is that the exothermic reaction of PMMA polymerization may cause thermal destruction of sensory nerve terminals [28]. Additional mechanisms related to a neurotoxic effect of methyl methacrylate monomer of PMMA may also be implicated [29]. Moreover, biological mechanisms have been suggested that are linked to an inhibitory effect of PMMA on osteoclasts that are believed to be involved in the causation of neuropathic pain via vanilloid receptors and acid-sensing ion channel [30]. As per the manufacturer’s recommendation, polymerization of PMMA occurs within 20 to 50 seconds from mixing the component of cement, and injection should be in the creamy paste phase [31]. In the present study, the mean time for solidification of cement was 7 minutes with a standard deviation of 0.5 minutes, somewhat longer than previously described by other investigators [32], to allow for attainment of a firmer consistency of the injectate. The mean ± SD volume of cement injected in the present study was 2.2 ± 0.4 (SD) mL. Higher volumes may be accommodated by vertebral compression fractures (VCF) due to osteoporosis [21], and a reasonable rule of thumb may that the injected volume should be 16% to 20% of the vertebral volume [33]. This is of particular relevance in the present trial, where most of patients had marked loss of the effective vertebral volume by the metastases and the injected volume had to be reduced accordingly. Cement volumes similar to that employed in the current study were previously described by other investigators [34]. There has always been concern regarding the safety of PVP in patients with marked loss of vertebral substance or encroachment on the posterior vertebral cortex owing to the potential for cement leakage and subsequent neurological sequels [10,13]. In this regard, the most common procedurerelated adverse effect observed in the current study was temporary exacerbation of the back pain, which occurred in approximately 62% of the patients. The incidence of the more serious cement leak was in the order of 8%, a figure that was strikingly lower than that reported by previous investigators. In one such series, the incidence of cement
Please cite this article in press as: Reyad RM, et al. Thick cement usage in percutaneous vertebroplasty for malignant vertebral fractures at high risk for cement leakage. Diagnostic and Interventional Imaging (2017), http://dx.doi.org/10.1016/j.diii.2017.02.010
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Thick cement usage for percutaneous vertebroplasty leakage and/or embolization was approximately 15% in PVP performed for osteoporosis-related vertebral compression fractures, whereas much higher overall rates in the order of 20% [8,9] and 41% [10] were reported by two systematic reviews. The unexpectedly lower leakage rate observed in the present trial despite the increased risk for this untoward side effect may be attributed to two factors. Firstly, the relatively small volume of cement injected, and secondly, and perhaps the more importantly, the relatively firmer consistency of the cement. The use of firm bone cement has been described previously for treatment of osteoporosisrelated vertebral compression fractures [22]. However, to our knowledge, no previous study has used it for fixation of high risk metastatic vertebral fractures. One observation that warrants commenting is the rather different pattern of leakage observed in the present trial. In a systematic review the most common sites for leakage were, in decreasing order of frequency, the paraspinal space (32.5%), epidural space (32%), intradiscal (30.5%), foraminal (3.3%), and pulmonary (1.7%) [10]. In our study, 40% of incidents occurred into the paravertebral venous plexus, although the cement did not spread cephalad beyond the few adjacent levels and was associated with no ill effects. The remaining incidents of cement leakage were intradiscal (20%), retroperitoneal (20%), and extradural (20%). Again, these differences in the pattern of spread may be attributed to differences in the consistency and volume of cement injected in the current trial or to clinic-pathological differences related to the location of the metastases or the underlying indication for PVP. Our study has some limitations that include the relatively small number of patients involved in the study and the involvement of a specific patient subgroup that was considered to be at high risk for cement leakage and/or embolization, and hence, generalization of the current findings to other patient groups should be regarded with caution, and it is recommended to conduct further studies both to verify the current findings and to examine the generalizability of the findings to other patient populations. In conclusion, PVP using thick cement could be administered with reasonable safety to patients suffering from intractable pain caused by vertebral metastases who were considered to be at high risk for cement leakage. The procedure was associated with significant improvement of pain and disability and may serve as a feasible option in this high risk group in whom PVP may be relatively contraindicated.
Disclosure of interest The authors declare that they have no competing interest.
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Please cite this article in press as: Reyad RM, et al. Thick cement usage in percutaneous vertebroplasty for malignant vertebral fractures at high risk for cement leakage. Diagnostic and Interventional Imaging (2017), http://dx.doi.org/10.1016/j.diii.2017.02.010