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Keywords:

  • embolization;
  • metastasis;
  • renal cell carcinoma;
  • spine;
  • surgery

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgments
  9. Conflict of interest
  10. References

We analyzed the results of direct decompressive surgery plus stabilization of the vertebrae involved (DDSS) in six non-ambulatory patients with metastatic extradural spinal cord compression (MESCC) due to renal cell carcinoma (RCC). Transcatheter arterial embolization (TAE) was performed prior to surgery to reduce intraoperative blood loss. Radiotherapy and systemic therapy, including cytokine or targeted therapy and zoledronic acid, were added to the surgery. The DDSS procedure was performed successfully in all patients, with an estimated mean blood loss of 1726 mL. After surgery, all patients regained ambulatory function within 2 months. Patients were ambulatory with the use of assisting apparatus for 4–29 months (median 10.5 months). Median overall survival time after surgery was 15 months (range 4–38 months). In conclusion, DDSS with preoperative TAE can be performed safely and significantly improves the ambulatory function of non-ambulatory RCC patients with MESCC.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgments
  9. Conflict of interest
  10. References

Renal cell carcinoma (RCC) often metastasizes to the spine, which may cause metastatic extradural spinal cord compression (MESCC).1 Progression of MESCC results in neurogenic pain, paraplegia, and bladder dysfunction, all of which have a major detrimental effect on a patient's activities of daily life (ADL) and quality of life (QOL).2 In addition, reduced motility is often associated with myelopathic complications, which may affect the patient survival.3,4 Direct decompressive surgery plus stabilization of the vertebrae involved (DDSS) followed by radiotherapy has been shown to improve ambulatory function compared with radiotherapy alone for patients with MESCC.5–7 However, there is a major concern about intraoperative bleeding because RCC is known as a highly vascular tumor.8

We have performed DDSS with preoperative TAE on non-ambulatory patients with MESCC due to RCC in collaboration with radiologists and orthopedists. In the present study, we evaluated the results of surgery and the effect of the procedure on the ambulatory function of these patients.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgments
  9. Conflict of interest
  10. References

Patients

From January 2006 until December 2010, six non-ambulatory RCC patients with MESCC underwent DDSS. Clinical and selected demographic data for these patients are given in Table 1.

Table 1.  Characteristics of the six patients with epidural spinal cord compression with metastatic renal cell carcinoma to the vertebra
Patient no.Age (years)/genderSite of spinal metastasesOther bone metastasesMetastases in other organsInterval between diagnoses of RCC and MESCC (months)MSKCC riskFrankel grade at admissionSteroid therapy for ambulatory dysfunctionInterval between admission and spinal surgery (days)Frankel grade at spinal surgeryTAE prior to spinal surgery
  1. Inter, intermediate; L, lumbar vertebra; LN, lymph nodes; MESCC, metastatic epidural spinal cord compression; MSKCC, Memorial Slone Kettering Cancer Center; Th, thoracic vertebra.

166/MTh4 & 56th Rib 0InterDYes7CYes
245/FTh7Lung0PoorDYes7CYes
362/FL3 & 4LN0PoorDYes18CYes
459/MTh1 & 2Ileum43InterDYes12CYes
564/ML17PoorDYes13CYes
652/MTh6Lung97InterDYes10CYes

Treatment strategy

The strategy of DDSS with preoperative TAE for RCC patients with MESCC who fit our criteria (see below) has been implemented in our hospital since 2006. The degree of clinical symptoms caused by MESCC was assessed in all patients using the classification system of Frankel et al.9 (Table 2). Indications for surgery were determined according to the Cochrane Database Systemic Review7as follows: (i) neurological symptoms due to MESCC with Frankel Grades B–D; (ii) the involved lesion limited to three or fewer consecutive vertebrae; (iii) progressive deterioration of neurological deficit despite treatment with corticosteroids and/or radiotherapy; (iv) paraplegic for no more than 48 h; and (v) estimated survival of 6 months or more.

Table 2.  Frankel grades for the classification of the degree of clinical symptoms due to epidural spinal cord compression
Grade AComplete lesion (paraplegia)
Grade BOnly sensory function preserved
Grade CMotor function present, but no practical use (non-ambulatory)
Grade DMotor function present, sufficient to allow walking (ambulatory)
Grade ENo neurologic signs or symptoms

The following procedures were performed in patients who were considered suitable candidates for spinal surgery: (i) transcatheter arterial embolization (TAE) of the feeding arteries to metastatic lesions of the spine (within 24 h prior to surgery) to reduce intraoperative bleeding; (ii) DDSS, consisting of laminectomy, debulking of the tumor, and posterior stabilization for palliative purposes; (iii) rehabilitation, (iv) staged cytoreductive nephrectomy if needed; (v) postoperative radiation if not done before; and (vi) systemic therapy with targeted or cytokine therapy in addition to zoledronic acid if renal function was good enough.

Transcatheter arterial embolization of spinal tumors

All embolization procedures were performed under local anesthesia via a femoral sheath. The feeding arteries were identified with aortography and selective catheterization of the intercostal, subcostal, and lumber arteries was performed. The corresponding arteries, including one level above and below, were then embolized with Gelpart (Nippon Kayaku, Tokyo, Japan) and microcoils through the superselective catheterization. Pedicles with a spinal cord vascular supply were not embolized.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgments
  9. Conflict of interest
  10. References

Preoperative background of the patients and the results of the spinal surgery

Spinal metastases were found in a single vertebra in three patients and in multiple vertebrae but limited within three consecutive vertebrae in the remaining three patients (Table 1). Two patients (Patients 1 and 5) had already received radiation therapy to the vertebral metastases for the palliation of bone pain prior to surgery. All patients were ambulant at Frankel Grade D at the time of admission. However, DDSS with preoperative TAE (Fig. 1) was indicated because they had become non-ambulatory at Frankel Grade C despite conservative corticosteroid therapy.

image

Figure 1. Transcatheter arterial embolization (TAE) of spinal tumors in a representative case (Patient 2) before (a) and after (b) the procedure. Thoracic aortography shows tumor blush in the metastatic lesion of the 7th thoracic vertebral body (Th7), indicated by the white arrows. During the procedure, bilateral No. 6, 7, and 8 intercostal arteries were embolized with Gelpart (Nippon Kayaku, Tokyo, Japan) and microcoils (black arrows). Aortography after embolization shows no tumor blush on Th7.

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Postoperative course and prognosis

The DDSS procedure was performed successfully in all patients with mean intraoperative blood loss of 1726 mL (Table 3). No surgery-related complications were observed. Postoperative radiotherapy was performed after DDSS in three patients who had not received radiation treatment previously. One patient did not receive radiation therapy at their request. Cytoreductive nephrectomy was performed within 1 month of spinal surgery in three patients who showed symptoms of MESCC as the first presentation of RCC. All patients received systemic therapy after surgery. Interferon-α was used as first-line therapy in five patients, but sorafenib was used in one patient after 2008 when the molecular targeted agents became available in Japan.

Table 3.  Spinal surgery and postoperative course for the six patients in the present study
Patient no.Operation time (min)/intraoperative bleeding (mL)Timing of CN after spinal surgery (days)Timing of radiation relative to DDSS/doseFrankel grade after surgeryInterval between spinal surgery and becoming ambulatory (days)Systemic therapyZoledronic acidDuration of patients being ambulatory (months)Survival after spinal surgery/prognosis
  1. AWD, alive with disease; C, cervical vertebra; CN, cytoreductive nephrectomy; DDSS, direct decompressive surgery with stabilization of the vertebrae involved; DOD, died of disease; IFN, interferon-α; L, lumbar vertebra; LN, lymph nodes; Postop, postoperative; Th, thoracic vertebra.

1274/1454151.5 months before/46 GyD30IFN1516 months/DOD
2276/1200260.3 months after/46 GyD47IFN [RIGHTWARDS ARROW]Yes1415 months/DOD
Sorafenib [RIGHTWARDS ARROW] Sunitinib
3258/2260191 months after/30.6 GyD54IFNYes67 months/DOD
4322/26870.7 months after/40 GyD51IFN411 months/DOD
5247/16259.5 months before/46 GyD37IFNYes2938 months/AWD
6213/1130 No radiationD38SorafenibYes44 months/suicide

All patients regained their ambulatory function at Frankel Grade D within 30–54 days after DDSS, and were ambulatory with the use of assisting apparatus for 4–29 months, depending on outcome. Most patients were ambulatory just before they reached the terminal stage due to the progression of the disease. In one patient (Patient 4), MESCC due to the other vertebra occurred and required additional radiotherapy 4 months after DDSS. This patient lost the ability to walk from that time. Excluding one patient who committed suicide, median survival after DDSS was 15 months.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgments
  9. Conflict of interest
  10. References

In the present study, we have summarized the outcomes of DDSS with preoperative TAE to the spinal tumors for non-ambulatory patients with MESCC due to RCC. The procedure (i.e. DDSS with preoperative TAE) was performed successfully in all patients, without any complications, and the patients regained ambulatory function for 4–29 months.

Early surgical treatment for MESCC consisted of laminectomy alone, but this failed to show additional therapeutic effects in terms of patients' ambulatory function compared with radiotherapy alone.10 Recent advances in surgical instruments have enabled us to perform DDSS.11 Patchell et al. reported that 63% of non-ambulatory patients regained the ability to walk with DDSS followed by radiotherapy compared with only 19% of those receiving radiotherapy alone.6 Similar results have been reported by others.5,12,13 Total en bloc spondylectomy is the only curative surgery for spinal metastasis but, because of the high complication rate, is reserved for patients with solitary spinal metastasis and an otherwise good prognosis rate.14

The possible role of preoperative TAE is to reduce intraoperative blood loss; this may be important in RCC tumors because of the hypervascularity of these tumors.15,16 Recent evidence supports the significant role of preoperative TAE with a very low complication rate by avoiding overembolization.17,18 In the present series of patients, intraoperative blood loss was approximately 2000 mL, which is lower than the reported blood loss of non-embolized patients (median blood loss 5000 mL),19 and we had no TAE-related complications resulting from the careful procedures performed by the radiologist.

Whether DDSS improves patient survival remains contentious.7,20 However, there have been several reports regarding the survival benefits afforded by DDSS. Rades et al. reported 1-year survival rates of 45% after DDSS, compared with 29% after radiotherapy alone, in patients with MESCC from relatively radio-resistant tumors, including RCC.21 Patchell et al. have reported similar results.6 Improved ambulatory function is likely associated with improvement inpatient survival in part because of the elimination of deaths from myelopathic complications, including pneumonia, infected pressure sores, and urosepsis.3 In addition, increased depression in non-ambulatory patients has been reported,3 which can affect the survival of cancer patients by impairing the endocrine or immune systems.22–24 Thus, improvements in ambulant function by DDSS may have the potential to prolong the survival of patients with MESCC. The mean survival time of patients with MESCC due to RCC who underwent decompressive surgery has been reported to be 10–12 months.25,26 This is similar to the survival of RCC patients with bone metastases.27 Because we have no survival data for patients for whom DDSS was not performed, it is difficult to conclude at present what effect the procedure has had on overall survival. The role of targeted therapy or zoledronic acid also needs to be clarified in improving the QOL or survival of RCC patients with MESCC.28–30

Conclusions

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgments
  9. Conflict of interest
  10. References

We should consider DDSS with preoperative TAE for selected non-ambulatory patients with MESCC to improve ambulatory function, although it remains undetermined whether this surgical intervention improves overall survival.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgments
  9. Conflict of interest
  10. References

The authors thank Ms Clare Dover and Barbara Levene for English language editing of this manuscript.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgments
  9. Conflict of interest
  10. References
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