the spine is the most common site of skeletal metastases , being involved up to 40% of cases , , . the tumors that most commonly metastasize to the spine are those of the lung , breast , prostate , and kidney . neoplastic invasion of the vertebral body can result in painful vertebral compression fractures , leading to disability and considerable morbidity . the first approach for pain relief is pharmacotherapy with nonsteroidal anti - inflammatory drugs ( nsaids ) and opioids . nonresponsive cases are treated with radiotherapy which , however , requires 24 weeks to take effect and moreover does not achieve complete pain relief in most cases . its analgesic and antitumoral effects are limited by the toxicity risk to adjacent structures , and it does not prevent the progression of a pathologic fracture , . open surgical procedures aimed at fracture stabilization or spinal cord decompression are rarely a realistic option in these patients because of an unfavorable risk / benefit ratio , . percutaneous vertebroplasty ( pvp ) is an effective method for reducing spinal pain in osteoporotic vertebral compression fractures and vertebral metastatic disease , , , , , , , , , , , . furthermore operative time , blood loss , postoperative pain , and overall cost are all lower with pvp than with open surgery . however , due to the problem of polymethyl methacrylate ( pmma ) leakage , long - term pain relief and vertebral stabilization is not possible with pvp . to overcome this problem , we have used pvp in combination with interventional tumor removal ( itr ) for better pain relief and improved stability in malignant vertebral compression fractures , . in this study , we compared the efficacies of pvp+itr and pvp alone in patients with spinal metastatic tumor without epidural involvement , focusing on pain relief , stability of vertebral fractures , and pmma leakage . this study was approved by the university committee on human investigation , and informed consent was obtained from each patient . from october 2009 to june 2015 , 69 patients with spinal metastatic tumor and malignant vertebral compression fractures without epidural involvement were recruited into the study . patients were eligible for recruitment into the study if they had : 1 ) malignant vertebral compression fractures and/or spinal metastatic tumor without epidural involvement ( i.e. , no break in the posterior cortex on mri imaging ) ; 2 ) intractable pain , unresponsive to nonoperative modalities such as radiation therapy , chemotherapy , and so on ; 3 ) confirmed histological diagnosis ; 4 ) height reduction in the vertebral body < 50% ; and 5 ) at least one clinical and mri follow - up 3 months after the initial treatment . patents without symptoms of neurologic compression , or with allergy to pmma , contraindication for mri , poor overall condition , or short life expectancy ( <3 months ) , were excluded . the enrolled patients ( or their family members ) were allowed to choose between the two approaches we provided : pvp+itr ( group a ) or pvp alone ( group b ) . fig . after administration of local anesthetic ( 2% lidocaine ) , a 14  g needle and guidewire were inserted and advanced until the tip was at the center of the vertebral body . the tract was then sequentially dilated with working cannulae until the last working cannula ( 5  mm in diameter ) reached the proximal pedicle of the vertebral arch . a trepan was inserted through the last working cannula and the pedicle of the vertebral arch was cut slowly until the cannula reached the distal pedicle of the vertebral arch . the guidewire and trepan were then removed and a monopolar or multiple polar radiofrequency ( rf ) needle electrode ( 18  g22  g ) was inserted through the working cannula under fluoroscopic monitoring until the uninsulated tip was properly positioned within the tumor . the electrode was then activated , resulting in transfer of electrical current from the non - insulated distal tip into the surrounding tissue . alternating current flowed toward grounding pads that had been placed previously , causing ionic agitation of the surrounding cells and ultimately leading to the production of frictional heat . the tumor was ablated at a temperature of 80  c for 510  min , with 1  cm of the tip of the rf probe exposed . after removal of the rf needle , itr was performed with marrow nucleus rongeurs inserted through the working cannula . pmma ( 510  ml ; osteo - firm ; cook medical , bloomington , in , usa ) was then carefully injected into the treated vertebral body until either substantial resistance was met or the cement reached the cortical edge of the broken vertebral body . immediately after the procedure , standard anteroposterior and lateral radiographs were obtained . after administration of local anesthesia , a 13  g bone puncture needle ( cook medical , bloomington , in , usa ) was placed transpedicularly in the fractured vertebral body . the inner needle was removed , and 38  ml pmma ( osteo - firm ) was carefully injected into the fractured vertebra . postprocedural fluoroscopic evaluation was performed to confirm optimal filling of the lesion , without extravasation of pmma . all patients were clinically examined by two of the authors at enrollment and at follow - up visits . first follow - up was at 1 week after the procedure , and then at 1 , 3 , and 6 months , and every 6 months thereafter . ct , with 2-mm slices of the treated vertebra , was performed 3 days after pvp to determine the distribution of cement in the lesion and to look for cement leakage outside the vertebral body or other local complications . ct and/or mri were repeated at 3 months and every 6 months after the procedure . pain was measured by a visual analog scale ( vas ) , with the score ranging from 0 ( no pain ) to 10 ( worst pain ever ) . pain relief was categorized as  excellent  ( 02 ) ,  good  ( 2.54.5 ) ,  fair  , and  poor  . the oswestry disability index ( odi ) questionnaire was used to quantify disabilities in walking , standing , sleeping . a 100-point karnofsky performance status ( kps ) extent of spinal cord injury was assessed using the american spinal injury association ( asia ) impairment scale  . . complications following pvp , such as wound infections , nerve injuries , cement leakage , and pulmonary embolism , were recorded . for each vertebra , the filling quality was evaluated as  good  ( more than 2/3 of the vertebral volume ) ,  mild  ( 1/3 to 2/3 ) , or  insufficient  ( less than 1/3 ) ; the filling volume in milliliters was also recorded . stability of the spine was measured by the spinal instability neoplastic score ( sins ) , which ranges from 0 ( stable ) to 18 ( unstable ) ; patients were categorized into three types : stable ( 06 ) , potentially unstable ( 712 ) , and unstable ( 1318 ) . whitney test , -test , or fisher 's exact test were used , as appropriate , for comparisons between the two groups . all statistical analyses were performed using spss version 13.0 ( spss inc . , chicago , il , usa ) . this study was approved by the university committee on human investigation , and informed consent was obtained from each patient . from october 2009 to june 2015 , 69 patients with spinal metastatic tumor and malignant vertebral compression fractures without epidural involvement were recruited into the study . patients were eligible for recruitment into the study if they had : 1 ) malignant vertebral compression fractures and/or spinal metastatic tumor without epidural involvement ( i.e. , no break in the posterior cortex on mri imaging ) ; 2 ) intractable pain , unresponsive to nonoperative modalities such as radiation therapy , chemotherapy , and so on ; 3 ) confirmed histological diagnosis ; 4 ) height reduction in the vertebral body < 50% ; and 5 ) at least one clinical and mri follow - up 3 months after the initial treatment . patents without symptoms of neurologic compression , or with allergy to pmma , contraindication for mri , poor overall condition , or short life expectancy ( <3 months ) , were excluded . the enrolled patients ( or their family members ) were allowed to choose between the two approaches we provided : pvp+itr ( group a ) or pvp alone ( group b ) . after administration of local anesthetic ( 2% lidocaine ) , a 14  g needle and guidewire were inserted and advanced until the tip was at the center of the vertebral body . the tract was then sequentially dilated with working cannulae until the last working cannula ( 5  mm in diameter ) reached the proximal pedicle of the vertebral arch . a trepan was inserted through the last working cannula and the pedicle of the vertebral arch was cut slowly until the cannula reached the distal pedicle of the vertebral arch . the guidewire and trepan were then removed and a monopolar or multiple polar radiofrequency ( rf ) needle electrode ( 18  g22  g ) was inserted through the working cannula under fluoroscopic monitoring until the uninsulated tip was properly positioned within the tumor . the electrode was then activated , resulting in transfer of electrical current from the non - insulated distal tip into the surrounding tissue . alternating current flowed toward grounding pads that had been placed previously , causing ionic agitation of the surrounding cells and ultimately leading to the production of frictional heat . the tumor was ablated at a temperature of 80  c for 510  min , with 1  cm of the tip of the rf probe exposed . after removal of the rf needle , itr was performed with marrow nucleus rongeurs inserted through the working cannula . pmma ( 510  ml ; osteo - firm ; cook medical , bloomington , in , usa ) was then carefully injected into the treated vertebral body until either substantial resistance was met or the cement reached the cortical edge of the broken vertebral body . after administration of local anesthesia , a 13  g bone puncture needle ( cook medical , bloomington , in , usa ) was placed transpedicularly in the fractured vertebral body . the inner needle was removed , and 38  ml pmma ( osteo - firm ) was carefully injected into the fractured vertebra . postprocedural fluoroscopic evaluation was performed to confirm optimal filling of the lesion , without extravasation of pmma . all patients were clinically examined by two of the authors at enrollment and at follow - up visits . first follow - up was at 1 week after the procedure , and then at 1 , 3 , and 6 months , and every 6 months thereafter . ct , with 2-mm slices of the treated vertebra , was performed 3 days after pvp to determine the distribution of cement in the lesion and to look for cement leakage outside the vertebral body or other local complications . ct and/or mri were repeated at 3 months and every 6 months after the procedure . pain was measured by a visual analog scale ( vas ) , with the score ranging from 0 ( no pain ) to 10 ( worst pain ever ) . pain relief was categorized as  excellent  ( 02 ) ,  good  ( 2.54.5 ) ,  fair  , and the oswestry disability index ( odi ) questionnaire was used to quantify disabilities in walking , standing , sleeping . a 100-point karnofsky performance status ( kps ) extent of spinal cord injury was assessed using the american spinal injury association ( asia ) impairment scale  . . complications following pvp , such as wound infections , nerve injuries , cement leakage , and pulmonary embolism , were recorded . for each vertebra , the filling quality was evaluated as  good  ( more than 2/3 of the vertebral volume ) ,  mild  ( 1/3 to 2/3 ) , or  insufficient  ( less than 1/3 ) ; the filling volume in milliliters was also recorded . stability of the spine was measured by the spinal instability neoplastic score ( sins ) , which ranges from 0 ( stable ) to 18 ( unstable ) ; patients were categorized into three types : stable ( 06 ) , potentially unstable ( 712 ) , and unstable ( 1318 ) . whitney test , -test , or fisher 's exact test were used , as appropriate , for comparisons between the two groups . all statistical analyses were performed using spss version 13.0 ( spss inc . , chicago , il , usa ) . a total of 69 patients with spinal metastatic tumor without epidural involvement were enrolled in this study . of these , 37 opted for pvp+itr ( group a ; fig . 11 were excluded from the study : 4 patients because they had follow - up for <3 months and 7 ( 3 in group a and 4 in group b ) because of loss to follow - up . thus , our final study sample comprised 58 patients : 31 in group a and 27 in group b. table 1 shows the baseline characteristics of the 58 patients . table 1 shows the technical and initial clinical outcomes in the two groups . in group a , the procedure was technically successful and well tolerated in all patients . each patient underwent single - level itr and pvp ; 10 of the 31 patients also underwent pvp alone at other levels . at discharge , pain relief was excellent in 11 ( 35% ) patients and good in 17 ( 55% ) patients ; 3 ( 10% ) patients had no improvement in pain . ct showed cement leakage in 11 ( 36% ) of the 31 vertebral bodies treated with pvp+itr , and in 8 ( 47% ) of the 17 vertebral bodies treated with pvp alone . leakages were into the intervertebral disk ( n=4 ) , puncture path ( n=3 ) , paravertebral space ( n=5 ) , or veins ( n=7 ) . in group b , pvp was technically successful and well tolerated in all patients . of the 27 patients , 12 underwent single - level pvp , and 15 underwent multiple - level pvp . at discharge , 6 ( 35% ) patients had excellent pain relief and 19 ( 55% ) had good pain relief ; 2 ( 10% ) patients had no improvement in pain . ct showed cement leakage in 27 ( 54% ) of the 50 vertebral bodies treated with pvp . leakages were into the intervertebral disk ( n=6 ) , puncture path ( n=3 ) , paravertebral space ( n=7 ) , or veins ( n=11 ) . the mean cement filling volume in the 48 pvp - treated vertebrae in group a was 5.121.60  ml ( range , 48  ml ) vs. 4.381.37  ml ( range , 27  ml ) in the 50 pvp - treated vertebrae in group b ; the difference was statistically significant ( p<0.05 ) . follow - up data were available for 31 patients in group a. mean follow - up was for 126 months ( range , 325 months ) . in the 28 patients with excellent or good pain relief at the time of discharge , 2 patients complained of worsening of pain at follow - up at 4 months and 5 months ; mri revealed new metastatic vertebral lesions adjacent to the treated site . thus , overall , 29 patients exhibited satisfactory pain relief over the follow - up period , a pain relief rate of 94% ( 95% ci : 84% , 103% ) . mean follow - up in group b was for 169 months ( range , 743 months ) . in the 25 patients with excellent or good pain relief at the time of discharge , 3 patients experienced worsening of pain at 3- , 5- , and 9-month follow - ups due to new lesions in vertebrae adjacent to the treated site . worsening of pain was experienced by 8 patients with pain relief at discharge due to progression of the vertebral metastases and compression fractures . in addition , symptoms of neurological compression were observed in 8 patients in group b during follow - up . thus , overall , 16 patients exhibited satisfactory pain relief during follow - up in group b , giving a pain relief rate of 56% ( 95% ci : 35% , 77% ) . the overall pain relief rate was significantly higher in group a than in group b ( 94% vs. 56% ; p=0.002 ) . there were no significant differences between the two groups in average vas , odi and kps scores at baseline and 1 week and 1 month postoperatively , but the average scores at 3 months , 6 months , 1 year , and > 1 year were significantly lower in group a than in group b ( table 2 ; p<0.05 ) . there was no significant difference in patient survival between the two groups ( log rank test p=0.828 ) . at the time of submission of this manuscript , no patient had experienced malignant vertebral compression fracture in group a , whereas 6 patients in group b had suffered such fractures ; the difference in recurrence rate of the treated vertebrae was statistically significant ( fisher 's exact test p=0.007 ) . the stability of the treated vertebrae was significantly higher in group a than in group b ( 3.032.73 vs. 6.784.80 ; mann  whitney test p=0.007 ) . at the time of this report , 17 patients in group a are continuing with follow - up care ; the other 14 patients have died : 9 of multiple organ failure and 5 of diffuse metastasis . mean survival has been for 15.571.55 months ( kaplan - meier analysis ) . in group b , 13 patients are continuing with follow - up care ; the other 14 patients have died : 10 of multiple organ failure and 4 of diffuse metastasis . a total of 69 patients with spinal metastatic tumor without epidural involvement were enrolled in this study . of these , 37 opted for pvp+itr ( group a ; fig . 11 were excluded from the study : 4 patients because they had follow - up for <3 months and 7 ( 3 in group a and 4 in group b ) because of loss to follow - up . thus , our final study sample comprised 58 patients : 31 in group a and 27 in group b. table 1 shows the baseline characteristics of the 58 patients . table 1 shows the technical and initial clinical outcomes in the two groups . in group a , the procedure was technically successful and well tolerated in all patients . each patient underwent single - level itr and pvp ; 10 of the 31 patients also underwent pvp alone at other levels . at discharge , pain relief was excellent in 11 ( 35% ) patients and good in 17 ( 55% ) patients ; 3 ( 10% ) patients had no improvement in pain . ct showed cement leakage in 11 ( 36% ) of the 31 vertebral bodies treated with pvp+itr , and in 8 ( 47% ) of the 17 vertebral bodies treated with pvp alone . leakages were into the intervertebral disk ( n=4 ) , puncture path ( n=3 ) , paravertebral space ( n=5 ) , or veins ( n=7 ) . in group b , pvp was technically successful and well tolerated in all patients . of the 27 patients , 12 underwent single - level pvp , and 15 underwent multiple - level pvp . at discharge , 6 ( 35% ) patients had excellent pain relief and 19 ( 55% ) had good pain relief ; 2 ( 10% ) patients had no improvement in pain . ct showed cement leakage in 27 ( 54% ) of the 50 vertebral bodies treated with pvp . leakages were into the intervertebral disk ( n=6 ) , puncture path ( n=3 ) , paravertebral space ( n=7 ) , or veins ( n=11 ) . the mean cement filling volume in the 48 pvp - treated vertebrae in group a was 5.121.60  ml ( range , 48  ml ) vs. 4.381.37  ml ( range , 27  ml ) in the 50 pvp - treated vertebrae in group b ; the difference was statistically significant ( p<0.05 ) . follow - up data were available for 31 patients in group a. mean follow - up was for 126 months ( range , 325 months ) . in the 28 patients with excellent or good pain relief at the time of discharge , 2 patients complained of worsening of pain at follow - up at 4 months and 5 months ; mri revealed new metastatic vertebral lesions adjacent to the treated site . thus , overall , 29 patients exhibited satisfactory pain relief over the follow - up period , a pain relief rate of 94% ( 95% ci : 84% , 103% ) . in group mean follow - up in group b was for 169 months ( range , 743 months ) . in the 25 patients with excellent or good pain relief at the time of discharge , 3 patients experienced worsening of pain at 3- , 5- , and 9-month follow - ups due to new lesions in vertebrae adjacent to the treated site . worsening of pain was experienced by 8 patients with pain relief at discharge due to progression of the vertebral metastases and compression fractures . in addition , symptoms of neurological compression were observed in 8 patients in group b during follow - up . thus , overall , 16 patients exhibited satisfactory pain relief during follow - up in group b , giving a pain relief rate of 56% ( 95% ci : 35% , 77% ) . the overall pain relief rate was significantly higher in group a than in group b ( 94% vs. 56% ; p=0.002 ) . there were no significant differences between the two groups in average vas , odi and kps scores at baseline and 1 week and 1 month postoperatively , but the average scores at 3 months , 6 months , 1 year , and > 1 year were significantly lower in group a than in group b ( table 2 ; p<0.05 ) . there was no significant difference in patient survival between the two groups ( log rank test p=0.828 ) . at the time of submission of this manuscript , no patient had experienced malignant vertebral compression fracture in group a , whereas 6 patients in group b had suffered such fractures ; the difference in recurrence rate of the treated vertebrae was statistically significant ( fisher 's exact test p=0.007 ) . the stability of the treated vertebrae was significantly higher in group a than in group b ( 3.032.73 vs. 6.784.80 ; mann  whitney test p=0.007 ) . at the time of this report , 17 patients in group a are continuing with follow - up care ; the other 14 patients have died : 9 of multiple organ failure and 5 of diffuse metastasis . mean survival has been for 15.571.55 months ( kaplan - meier analysis ) . in group b , 13 patients are continuing with follow - up care ; the other 14 patients have died : 10 of multiple organ failure and 4 of diffuse metastasis . we compared the efficacy of pvp+itr with that of pvp alone in the treatment of patients with spinal metastases . there are four main findings : 1 ) pvp+itr provided overall better pain relief than pvp alone ( 94% vs .56% ; p=0.002 ) ; 2 ) average vas score , odi score and kps at 3 months , 6 months , 1 year , and > 1 year was significantly lower in patients treated with pvp+itr than in those treated with pvp alone ( p<0.05 ) ; 3 ) the mean cement filling volume in the treated vertebrae was significantly higher in group a than in group b ; and 4 ) the stability of the treated vertebrae was significantly higher in group a than in group b. these results indicate that pvp+itr is a safe and effective procedure in patients with spinal malignant compression fractures . metastases to the spine can cause vertebral destruction , with consequent impairment of the supporting function of the spine , or invade and compress the spinal cord . traditionally , surgery has been used to eliminate pain , achieve decompression , prevent further crushing , and avoid the complications resulting from prolonged immobilization . however , patients with spinal metastases are poor candidates for surgery because they are likely to be immunocompromised , with poor nutritional status and comorbid medical conditions . furthermore , surgery is not advisable for patients with short life expectancy or multi - vertebral metastases . in recent years , different minimally invasive interventions , such as pvp , have emerged as reasonable alternatives to treat spinal metastatic disease . these new procedures cause less soft tissue trauma and blood loss , require shorter hospitalization time , and rarely interfere with the adjuvant treatments . compared with pvp alone , the novel perspectives of pvp+itr were to remove some spinal metastatic tumor and create a cavity with the marrow nucleus rongeurs in the affected vertebral body and subsequent injection of pmma cement into the newly perfossate cavity . the advantages of the combination of pvp+itr are that 1 ) cement can be correctly directed into target areas ; 2 ) clinical efficacy can be improved and risk of recurrence reduced by removal of most of the tumor via itr ; 3 ) larger amount of pmma can be injected into the cavities , thus increasing the stability of the involved vertebra and reducing risk of compression fracture ( fig . our preliminary results suggest that this technique is a promising treatment option in patients with spinal metastases , with results comparable to that achieved with approaches such as surgery , , vertebral augmentation , , kyphoplasty , and radiofrequency ablation and vertebroplasty . we achieved significant pain relief in 94% of our patients after treatment with pvp+itr , which is at the higher end of the range of 73100% reported with other treatment modalities , , , , , , , . itr removes the malignant tumor , and the pvp eliminate the metastatic vertebral tumor as much as possible , which resulted in shrinkage or obliteration of the vertebral tumor tissue . in addition , with removal of the malignant tumor by itr , more pmma could be injected into the vertebral body with lower injection pressure , which increase the stability of the involved vertebra and prevent compression fracture , as shown in fig . this was a single - center experience , and the number of patients treated was relatively small . some of these patients had short life expectancy and died early due to rapid disease progression ; this might have masked both the benefits and risks of the procedure . our study results demonstrate that the combination of pvp and itr is a safe and effective procedure that can provide greater pain relief and vertebral stability than pvp alone in patients with spinal metastatic tumor without epidural involvement .
aimto evaluate the efficacy of percutaneous vertebroplasty ( pvp ) combined with interventional tumor removal ( itr ) in providing pain relief , reducing disability , and improving functional performance in patients with malignant vertebral compression fractures without epidural involvement.methodspatients with malignant vertebral compression fractures ( n=58 ) were treated with either pvp+itr ( n=31 , group a ) or pvp alone ( n=27 , group b ) . a 14  g needle was inserted into the vertebral body , and the tract was sequentially dilated with working cannulae . when the last working cannula had reached the distal pedicle of vertebral arch , 
 itr was performed with a marrow nucleus rongeurs inserted through the working cannula . 
 finally , cement was injected into the excavated vertebral body . 
 patients were followed up at 1 , 3 , and 6 months after the procedure , and every 6 months thereafter.resultsthe overall excellent and good pain relief rate during follow - ups was significantly better in group a than in group b ( 94% vs.56% ; p=0.002 ) . 
 the average vas , odi , and kps scores at 3 months , 6 months , 1-year , and > 1 year were all significantly lower in group a than in group b ( p<0.05 ) . 
 the mean cement filling volume and the stability of the treated vertebrae were significantly higher in group a than in group b ( p<0.05).conclusionsthe combination of pvp+itr is a safe and effective procedure , capable of providing significantly greater pain relief and vertebral stability than pvp alone in patients with malignant vertebral compression fractures .