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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 4  |  Issue : 2  |  Page : 26-31

Effect of embolization in the definitive and palliative management of bone and soft tissue tumors of the extremities


1 Department of Orthopaedics, IGMC, Shimla, Himachal Pradesh, India
2 Department of Community Medicine, SLBSGMC, Mandi, Himachal Pradesh, India
3 Department of Orthopaedics, PGIMER, Chandigarh, India
4 Department of Cardiology, IGMC, Shimla, Himachal Pradesh, India
5 Department of Orthopaedics, Civil Hospital, Nurpur, Himachal Pradesh, India
6 Department of Anaesthesia, IGMC, Shimla, Himachal Pradesh, India

Date of Submission15-Mar-2021
Date of Decision24-May-2021
Date of Acceptance02-Jun-2021
Date of Web Publication26-Aug-2021

Correspondence Address:
Dr. Amit Kumar Salaria
Department of Orthopaedics, PGIMER, Sector - 12, Chandigarh - 160 012
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jodp.jodp_2_21

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  Abstract 


Introduction: Surgery may be complex in some bone and soft tissue tumors. Preoperative intra-arterial embolization is a developing method for benign and malignant tumors. The present study was done to assess the outcome on the size of tumor and blood loss by preoperative tumor embolization and pain relief in patients with inoperable tumors. Materials and Methods: Twenty-five patients with biopsy-proven bony tumors of extremities were subjected to embolization. In 12 cases, embolization was done preoperatively to decrease the blood loss. In 13 patients, it was done as a palliative treatment to reduce pain, as patients were inoperable. The embolization was done with the right Judkins catheter. Some cases were done with a microcatheter. The material used for embolization was either polyvinyl alcohol (PVA) particles, microcoils, or gel foam used in various combinations, selectively into the feeding vessel. Results: Mean age of the patients was 44.5 years. Fifteen were male and 10 were female. A total of 60 vessels were embolized, 25 with gel foam, 24 with PVA particles, and 11 with microcoils. In 90% of operated patients, gel foam was used, whereas, in almost 100% of nonoperated patients, PVA particles were used. There was a significant decrease in blood loss in patients with preoperative embolization (865 ± 420 vs. 1633 ± 660 ml). In patients with palliative embolization, the mean pain score before embolization was 6.32–2.58, which was decreased to 3. 2–1.53. Conclusion: Preoperative and palliative transarterial embolization of soft tissue and bony tumors is a safe, effective, and minimally invasive modality for pain relief and de-vascularization of large bony tumors in anatomically difficult locations.

Keywords: Angioembolization, transarterial, tumor


How to cite this article:
Thakur R, Aggarwal V, Dogra E, Salaria AK, Bhardwaj R, Sharma S, Thakur P. Effect of embolization in the definitive and palliative management of bone and soft tissue tumors of the extremities. J Orthop Dis Traumatol 2021;4:26-31

How to cite this URL:
Thakur R, Aggarwal V, Dogra E, Salaria AK, Bhardwaj R, Sharma S, Thakur P. Effect of embolization in the definitive and palliative management of bone and soft tissue tumors of the extremities. J Orthop Dis Traumatol [serial online] 2021 [cited 2021 Oct 21];4:26-31. Available from: https://www.jodt.org/text.asp?2021/4/2/26/324596




  Introduction Top


The treatment modalities for bone tumors vary with the individual lesion, but in general, surgical excision is the treatment of choice with other adjunctive therapies. Tumor bulk, vascularity, vicinity to vital structures, and potentially inaccessible location of the lesion increase the complexity of the surgery. Preoperative, palliative, and curative selective/super-selective intra-arterial embolization is an effective and developing method. It is used for benign and malignant tumors, hypervascularized bone, and soft tissue tumors of the extremities, with proper embolizing agents.[1] The blockage is usually performed via an endovascular approach but may also be performed by direct percutaneous injection of embolic agents into the tumor.

Angioembolization reduces the risk of bleeding during and after surgery. Tissue planes are better defined and the manipulation becomes easier. Aneurysmal bone cyst, giant cell tumor, osteoblastoma, osteosarcoma, vertebral, hemangioma, and osseous arteriovenous malformations are some of the common bone tumors amenable for angioembolization. Embolization also results in the palliation of pain, bleeding, fever, and hypercalcemia-like symptoms in inoperable tumors, thus preventing further dissemination of a tumor and increasing the response to chemotherapy and radiotherapy. Embolization may be a therapeutic alternative to surgery in cases in which surgery is inappropriate or associated with high risk.

Preoperative chemoembolization has also been shown to increase the sensitivity of some tumors to subsequent chemotherapy and radiotherapy. Angioembolization has also a role in the palliation of osseous metastatic lesions.[1]

The basic principle in transarterial embolization (TAE) is the occlusion of most of the capillary tumor beds. The occlusion of only the major tumor feeding arteries is ineffective because of numerous collaterals. Tumor embolization may be permanent or temporary. Embolization agents can be classified based on whether temporary or permanent and based on their physical state as liquid and particulate.[1],[2],[3],[4],[5],[6],[7],[8]

Thus, the study was planned to study the effect of embolization on curative and palliative care of bone and soft tissue tumors.


  Materials and Methods Top


A prospective study of 3 years was performed in the department of orthopedic surgery, in collaboration with the department of cardiology. In this period, 25 patients underwent selective embolization. Detailed history, general and local physical examination, radiological investigations, and biopsy of the tumor were done. Patients were enrolled in the study after obtaining due consent and applying the proper inclusion and exclusion criteria. Appropriate counseling and the various treatment options and complications were discussed in detail.

Inclusion criteria

  1. Patient of any age who has radiologically and histopathologically confirmed bone and soft tissue tumors in whom wide resection or safe surgical margins were deemed feasible on preoperative imaging
  2. The patient of any age who has radiologically and histopathologically confirmed bone and soft tissue tumors who qualify for cancer treatment with palliative intent.


Exclusion criteria

  1. The patient is in the stage of the end of life care
  2. Patient having coagulopathy (relative)
  3. Patient refusing treatment
  4. Renal dysfunction.


Tumor volume was calculated preoperatively with the help of magnetic resonance imaging (MRI). Selective angiography was done to ascertain feeding arteries of the tumor and collaterals, the tumor's relationship with adjacent vascular processes. Most of the catheterization was performed using a coaxial catheter system, which comprises a large 4–6 F catheter that is used to hook the artery and to provide stability to a microcatheter (2.7 F) when used.

Gel foam, polyvinyl alcohol (PVA) particles, and coils were used alone or in combination with such agents depending on case to case. Embolization was performed from either femoral or brachial artery or multiple sites according to individual case requirements. Percentage de-vascularization of the tumor was obtained immediately after the postembolization angiogram. Based on residual tumor staining, embolization was categorized as category 1 total (none) to nearly total (10%), category 2 subtotal (10% to 30%) to partial (30% to 70%), and category 3 incomplete/failed where no appreciable tumor de-vascularization was achieved.

Post embolization, all the patients were monitored for catheter site bleeding, hematoma, neurovascular deficits, etc. All the patients were assessed for pain relief postprocedure at 6 h, 1st day, 2nd day, and 7th day (when applicable). Pain assessment was done according to the visual analog scale both pre- and postembolization.

Thorough preanesthetic assessment, staging of the tumor, and preoperative planning were done.

In the case of sarcoma for wide resection, at least 2 cm of tumor-free intramedullary extent was taken. Templating was done to choose appropriate implants and anticipating needs during surgery.

Estimation of the expected blood loss was done by considering the tumor volume, tumor site, tumor vascularity/type, expected duration of surgery, and reconstruction method used. Intraoperative blood loss was calculated by the gravimetric method.

Utilitarian approaches for the surgical excision were used in all the patients by incorporating the previous biopsy site in the incision. Resection of the tumor with intralesion, marginal, wide margins was done in different cases followed by reconstruction of the defect with the transfer of tissues if necessary to allow an effective closure and eliminate potential dead space. Extensive postoperative monitoring was done regarding vitals, soakage, blood loss, and neurovascular status and pain.

Depending on the estimated intraoperative blood loss and suction drain collection, the whole fresh blood was transfused. The drain was removed on the 2nd postoperative day or if the output was <50 ml. Depending on the general condition of the patients and fixation of implants, patients were allowed to stand and walk. All the patients were encouraged to do the physiotherapy. Postoperatively, neoadjuvant chemotherapy was given to patients with sarcoma and local radiotherapy was given where resection margins were not R0 (i.e., tumor tissue is encountered in the resection margin on histopathology).

Follow-up

At 6 months, all the patients with sarcoma and giant cell tumor were re-evaluated for recurrence and distal metastasis with X-ray of the chest, bone scan, positron-emission tomography scan, and computed tomography of the chest.

Every patient was advised to come for follow-up at 4–6 weeks' intervals. At every follow up the patients were monitored radiologically for calcification of tumor margins, increase in tumor size,recurrence or appearance of any new lesion. Musculoskeletal tumor society scoring was done at every follow up and compared to previous scoring done before embolization. At the same time, pain scoring was done.

Statistical analysis

Statistical analysis was performed using Friedman's ANOVA in SPSS version 17.0 to evaluate the difference between preembolization visual analog scale (VAS) score and postembolization VAS score. ANOVA was applied as we had more than two groups with qualitative data in the pain palliation group and Student's t-test was applied for comparing the qualitative data (blood loss) in two groups. The significance level was set at P < 0.05.


  Results Top


Of the 25 patients who were angioembolized, 12 were deemed operable and in the 13, it was used for palliation. Demographic and various tumor details, for example location, are shown in [Table 1]. The mean age in our study was 44.4 ± 21.4 years. Tumor location concerning to the upper limb, lower limb, and the axial skeleton was 36%, 40%, and 24%, respectively. Seventy-five percent of the patients required more than single-vessel embolization. Successful embolization was achieved in 92% of the patients. Various factors affecting blood loss are shown in [Table 2]. There was a statistically significant difference in the estimated blood loss without embolization and the actual blood loss after embolization (1633 ± 660 ml vs 865 ± 420 ml). The effect of embolization on tumor size at 6 weeks and 6 months of follow-up is shown in [Table 3]. The complication rate was 25% with fever, pain, bleeding, and thrombus formation at the catheter site occurring in six patients [Table 4]. The final patient outcome concerning to tumor is shown in [Table 5] with a tumor recurrence in four and mortality in six patients. There was significant pain relief post embolization. The VAS score decreased from a mean of 6.32 ± 2.58 (preembolization) to 3.2 ± 1.53 (postembolization) which was statistically significant. Gel foam, PVA particles, or a combination of gel foam and PVA particles were used in 40%, 36%, and 24% of the patients, respectively. Seventy-six percent of the patients required multiple feeder embolization, single large feeder embolization was sufficient in six patients.
Table 1: Demographic details and tumor characteristics

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Table 2: Factors affecting blood loss

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Table 3: Postembolization tumor size with the duration of follow-up

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Table 4: Complication associated with embolization

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Table 5: Patient outcome with the type of tumor

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In our study, we have calculated the expected blood loss as mentioned in the literature for nearly the same tumor volume, tumor site, tumor vascularity, expected duration of the surgery, and the reconstruction method used. There is a significant reduction in blood loss following angioembolization. Increased blood loss is seen in tumor volume more than 400 ml and the duration of surgery more than 270 min (P = 0.001). But in both the scenarios, there was a considerable difference in the expected and the actual blood loss following angioembolization which was statistically significant (P = 0.001). No statistically significant difference was found in the difference in the blood loss between the partial and complete embolization (P = 0.34). Furthermore, there was no difference found in the blood loss if the surgery was performed within 3 days post embolization or on day 4–7 post embolization (P = 0.94).


  Discussion Top


The patients in our series ranged from 8 to 75 years of age, with a mean of 44.5 ± 21.4 years. Which is concordant to the other studies.[9],[10]

In our series, majority of the patients were male (60%) with a male-to-female ratio of 3:2, as shown by the study by Boruban et al.[1]

In our series, the operated and palliative groups have an equal distribution of patients, with 12 in the operative group and 13 patients in the palliative group. We have performed palliative angioembolization in patients who either had extensive metastasis or the disease was advanced and in inaccessible locations so that curative intent was no longer feasible. Patients with advancing age had a tendency to be treated with palliative care. In the operative group, embolization was done with the intent to decrease the intraoperative blood loss, especially in situations where a tourniquet could not be used, where the expected duration of surgery was more than 2 h and tumors were highly vascular.

The geographical distribution of the tumor in our series includes 9 cases (36%) in the upper extremity, 10 cases (40%) in the lower extremity, and 6 (24%) in the axial skeleton. In the upper extremity, the proximal humerus was involved in four cases, distal radius involved in two cases, and scapula in three cases. In the lower extremity, four tumors were involving proximal femur, five involving the iliac wing, acetabulum, and/or superior–inferior pubic rami, and one involving the calf. In the axial skeleton, sacrum and iliac wing were the affected sites.

In our series, 28% of the tumors were benign and 36% were metastatic and malignant each. Out of all benign tumors, 85.7% were below 40 years of age in which one was cavernous hemangioma and three were giant cell tumors and aneurysmal bone cyst each. In the malignant group, two were chondrosarcoma, four were Ewing's sarcoma, two were multiple myeloma, and 1 was spindle cell sarcoma with age distribution ranging from 13 years to 76 years with a tendency of bimodal distribution, with a first peak occurring in the second to the third decade and a second peak occurring in patients of fifth to sixth decade. In metastatic tumors, four were adenocarcinoma from lungs and GIT, two were renal cell carcinoma, and one each from breast, cervix, and osteosarcoma. The combined mean tumor volume of 722.68 ± 1428.75 ml (range 19–7280 ml) inoperative and the palliative group also correlated with the studies conducted by Al-Hadithy et al.[11]

All metastatic tumors were above 40 years of age. In the epidemiological study done by Franchi A, the age-specific incidence rates of bone sarcomas typically showed a bimodal distribution, with a first peak occurring in the second decade and a second peak occurring in patients older than 60 years of age. On the other hand, the majority of benign bone tumors and tumor-like lesions occurred in the first two decades of life, which correlates with our study.[9],[12],[13],[14],[15],[16] Tumor de-vascularization was checked immediately after embolization in all cases. Complete to near-total de-vascularization following embolization in the desired targets was achieved in 15 (60%) cases and subtotal to partial de-vascularization achieved in 8 (32%) cases. Subtotal to partial de-vascularization was achieved mostly in cases where there were numerous tumor feeders and where doubt existed concerning nontarget embolization. Hence, it was considered prudent to angioembolize the main tumor feeders and avoids the suspicious ones. In one case, embolization was incomplete due to marked tortuosity and numerous tumor feeder vessels and in one case, embolization could not be achieved due to numerous direct feeders from the subclavian artery.

Shi et al. in their study achieved a total to nearly total de-vascularization rate in 83% of cases,[9] Boruban et al.[1] in 53%, Manke et al.[17] in 50% of cases, and Kato et al.[18] in 30% of cases.

On comparing with the above studies where complete embolization was achieved in 30% to 83% of total tumors , in our study, complete to near-total embolization was achieved in 60% of total tumors which was falling in the range of the above studies. The broad range may be explained due to differences in criteria of complete embolization due to observer biases.

In our series, the mean expected blood loss was 1633 ± 660 ml (range 700–2500 ml) and actual blood loss was 865 ± 420 ml (range 400–1579 ml), which is found to be statistically significant (P = 0.001). There was not much difference in the blood loss when complete or near-total embolization was compared to the blood loss in the subtotal or partial group. Tumors having a volume of more than 400 cm3 have significantly more blood loss as compared to smaller tumor volumes. Reconstructive surgeries with tumor mega-prosthesis had a duration of surgery of more than 270 min and the mean intraoperative blood loss was 1174 ± 359 ml. Whereas in tumors with a duration of surgery <270 min, mean intraoperative blood loss was 556 ± 171 ml (P = 0.003) which was found to be statistically significant. There was no significant difference in blood loss as long as the patients were operated on within a week postembolization.

All of these findings are similar to the studies conducted by Al-Hadithy et al.,[11] Manke et al.,[17] Kato et al.,[18] Gellad et al.,[19] and Wilson et al.[20] Only one study by Barton et al. concluded that surgery must be performed within 3 days of embolization to avoid revascularization.[10] This can be explained by the difference in the embolism agents used. By this, we can infer that if complete embolization was done including most of the tumor beds and their major tumor feeders, the resection could be performed within 7 days without significant blood loss. This is especially significant in the situation where a full-time experienced team for tumor embolization is not available all the days or there is a delay in surgery due to some medical condition or operation theatre time.

In our series, we assessed pain pre embolization and post embolization in visual analog score depicted in the form of numeric pain scale immediately at 6 h post embolization, on 1st postembolization day, on 2nd postembolization day, and in follow-up at 6 weeks and at 6 month post embolization. The mean pain score pre embolization was 6.32 ± 2.58 which was decreased to 3.92 ± 1.93 within 6 h with further improvement of pain in the next 2 days with a mean score of 3.2 ± 1.53 which is statistically significant (P ≤ 0.001). All the other studies showed a similar reduction of pain after embolization.[19],[20],[21],[22],[23],[24]

In our series, we encountered minor complications in 4 (16%) patients and the overall complication rate was 24%. In one patient, we encountered mild fever with increased postembolization pain at the tumor site and in another patient, thrombus formation at the catheterization site with increased postembolization pain at the tumor site. We also encountered mild bleeding post embolization in one patient and one patient had postembolization burning sensation over right forearm and hand along the distribution of C5 and C6 nerve root which was resolved spontaneously within 2 days.

Barton et al.[10] reported postembolization syndrome in 72% of patients and Mavrogenis et al.[25] in their study reported minor complication rates ranging from 18% to 86%. In our series, all the patients were admitted before embolization, thoroughly investigated, all embolization was performed by an experienced interventional cardiologist, and all the patients were kept under observation for at least 2 days for monitoring the complications. Our complication rate falls on the lower side of the range as compared with the literature.[26]

In our series, the mean number of vessels embolized was 2.4 ± 1.3 (range 1–5). In 9 (36%) cases, three or more vessels embolized out of which 8 (32%) cases were malignant and metastatic. This could be explained due to more aggressive neovascularization in metastatic and malignant tumors.

In our study 9 (75%) of operated cases, only gel foam was used and in the rest 3 (25%) cases, combination of PVA with gel foam or coil with gel foam was used. In the palliative group, in 6 (46%) cases, only PVA particles were used, in one case, only gel foam was used, and in another 6 (46%) cases, a combination of embolizing agents was used. In the operated group, in 9 (75%) cases, only gel foam was used as it is cost-effective and most of them have been operated within 3 days of embolization. In 3 (25%) cases, a combination of gel foam with PVA or gel foam with the coil was used. In the palliative group, permanent embolization was done with PVA particle and/or coil and one patient was embolized with gel foam with an aimed resection, but the patient refused surgical intervention. Similar embolizing agents were used in the other published studies.[27] In our study, the mean follow-up duration was 8.35 ± 7.2 months which is similar to the studies done by Boruban et al., Forauer et al., and Puri and Agarwal.[1],[28],[29] Several recent studies published in the literature have also advocated preoperative embolization as an adjunct to surgery in the management of musculoskeletal tumors, particularly in the reduction of intraoperative blood loss, decreasing transfusion requirement, and decrease in operative time.[12],[30] Although the sample size is small and there are no control groups, multiple conclusions cannot be drawn from our study, but it definitely supports the role of embolization. There is also some conflicting evidence regarding the efficacy of embolization.[31] Further randomized control trials taking into account the primary tumor, metastatic location, and the type of surgery performed are desired to obtain a higher level of evidence and to draw definitive conclusions.


  Conclusion Top


  • Preoperative and palliative selective TAE is a safe, effective, and minimally invasive interventional modality for pain relief and de-vascularization of large, highly vascular bone tumors in anatomically difficult locations
  • This method helps in downstaging tumor vascularity and reducing intraoperative blood loss
  • Preoperative arterial embolization can be combined with other treatment modalities such as radiation therapy and chemotherapy
  • For optimal results, feeding arteries must be catheterized super-selectively and the procedure must be undertaken with the most appropriate embolic agent to protect the normal tissues.


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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[PUBMED]  [Full text]  
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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