Gokaslan, Ziya L.

Introduction Although surgery is being increasingly used in patients with Metastatic Epidural Spinal Cord Compression (MESCC) as a complementary strategy to radiation and chemotherapy, the impact of surgery on quality of life (QoL) is not well established. This study aimed to prospectively evaluate survival, neurological, functional, and QoL outcomes in MESCC patients undergoing operative management. Material and Methods A total of 142 surgically treated patients with a single symptomatic MESCC lesion enrolled in a prospective North American multi-center study were followed for 12 months. Clinical data, such as Brief Pain Inventory (BPI), ASIA, SF-36, Oswestry Disability Index (ODI), and EQ-5D scores, were obtained both pre- and post-operatively. Results The median survival was 7.7 months. The 30-day and 12-month mortality rates were 9% and 62%, respectively. Six weeks post-operatively, ambulatory status ( p = 0.02) and bladder control ( p = 0.03) were significantly improved. Overall, 67.5% of ASIA B, C, or D patients gained at least 1 grade after surgery, 25% remained stable, and 7.5% deteriorated. ODI, EQ-5D, BPI scores were significantly improved at each follow-up (p ≤ 0.01). SF-36 scores were generally higher after surgery for mental and physical components, and for all domains except energy/fatigue. The incidence of wound complications was 10% and 2 patients required a second surgery (screw malposition and epidural hematoma). Conclusion Surgical intervention, as a complementary adjunct to radiation and chemotherapy, provides immediate and sustained improvement in pain, neurological, functional, and QoL outcomes with acceptable risks in patients with a focal symptomatic MESCC lesion.

OBJECTIVE The purpose of this study was to report the long-term clinical outcomes following 3- and 4-level anterior cervical discectomy and fusion (ACDF). METHODS A retrospective review of all adult neurosurgical patients undergoing elective ACDF for degenerative disease at a single institution between 1996 and 2013 was performed. Patients who underwent first-time 3- or 4-level ACDF were included; patients with previous cervical spine surgery, those undergoing anterior/posterior approaches, and those with corpectomy were excluded. Outcome measures included perioperative complication rates, fusion rates, need for revision surgery, Nurick Scores, Odom's criteria, symptom resolution, neck visual analog scale (VAS) pain score, and persistent narcotics usage. RESULTS Seventy-one patients who underwent 3-level ACDF and 26 patients who underwent 4-level ACDF were identified and followed for an average of 7.6 ± 4.2 years. There was 1 case (3.9%) of deep wound infection in the 4-level group and 1 case in the 3-level group (1.4%; p = 0.454). Postoperatively, 31% of patients in the 4-level group complained of dysphagia, compared with 12.7% in the 3-level group (p = 0.038). The fusion rate was 84.6% after 4-level ACDF and 94.4% after 3-level ACDF (p = 0.122). At last follow-up, a significantly higher proportion of patients in the 4-level group continued to have axial neck pain (53.8%) than in the 3-level group (31%; p = 0.039); the daily oral morphine equivalent dose was significantly higher in the 4-level group (143 ± 97 mg/day) than in the 3-level group (25 ± 10 mg/day; p = 0.030). Outcomes based on Odom's criteria were also different between cohorts (p = 0.044), with a significantly lower proportion of patients in the 4-level ACDF group experiencing an excellent/good outcome. CONCLUSIONS In this study, patients who underwent 4-level ACDF had significantly higher rates of dysphagia, postoperative neck pain, and postoperative narcotic usage when compared with patients who underwent 3-level ACDF. Pseudarthrosis and deep wound infection rates were also higher in the 4-level group, although this did not reach statistical significance. Additionally, a smaller proportion of patients achieved a good/excellent outcome in the 4-level group than in the 3-level group. These findings suggest a significant increase of perioperative morbidity and worsened outcomes for patients who undergo 4- versus 3-level ACDF.

OBJECT Surgical procedures and/or adjuvant therapies are effective modalities for the treatment of symptomatic spinal metastases. However, clinical results specific to the skin cancer spinal metastasis cohort are generally lacking. The purpose of this study was to systematically review the literature for treatments, clinical outcomes, and survival following the diagnosis of a skin cancer spinal metastasis and evaluate prognostic factors in the context of spinal skin cancer metastases stratified by tumor subtype. METHODS The authors performed a literature review using PubMed, Embase, CINAHL, and Web of Science to identify articles since 1950 that reported survival, clinical outcomes, and/or prognostic factors for the skin cancer patient population with spinal metastases. The methodological quality of reviews was assessed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) tool. RESULTS Sixty-five studies met the preset criteria and were included in the analysis. Of these studies, a total of 25, 40, 25, and 12 studies included patients who underwent some form of surgery, radiotherapy, chemotherapy, or observation alone, respectively. Sixty-three of the 65 included studies were retrospective in nature (Class of Evidence [CoE] IV), and the 2 prospective studies were CoE II. Based on the studies analyzed, the median overall survival for a patient with a spinal metastasis from a primary skin malignancy is 4.0 months; survival by tumor subtype is 12.5 months for patients with basal cell carcinoma (BCC), 4.0 months for those with melanoma, 4.0 months for those with squamous cell carcinoma, 3.0 months for those with pilomatrix carcinoma, and 1.5 months for those with Merkel cell carcinoma (p < 0.0001). The overall percentage of known continued disease progression after spine metastasis diagnosis was 40.1% (n = 244/608, range 25.0%–88.9%), the rate of known recurrence of the primary skin cancer lesion was 3.5% (n = 21/608, range 0.2%–100.0%), and the rate of known spine metastasis recurrence despite treatment for all skin malignancies was 2.8% (n = 17/608, range 0.0%–33.3%). Age greater than 65 years, sacral spinal involvement, presence of a neurological deficit, and nonambulatory status were associated with decreased survival in patients diagnosed with a primary skin cancer spinal metastasis. All other clinical or prognostic parameters were of low or insufficient strength. CONCLUSIONS Patients diagnosed with a primary skin cancer metastasis to the spine have poor overall survival with the exception of those with BCC. The median duration of survival for patients who received surgical intervention alone, medical management (chemotherapy and/or radiation) alone, or the combination of therapies was similar across interventions. Age, spinal region, and neurological status may be associated with poor survival following surgery.

Study Design Review of the literature. Objective Surgery and cement augmentation procedures are effective palliative treatment of symptomatic spinal metastases. Our objective is to systematically review the literature to describe the survival, prognostic factors, and clinical outcomes of surgery and cement augmentation procedures for breast cancer metastases to the spine. Methods We performed a literature review using PubMed to identify articles that reported outcomes and/or prognostic factors of the breast cancer patient population with spinal metastases treated with any surgical technique since 1990. Results The median postoperative survival for metastatic breast cancer was 21.7 months (8.2 to 36 months), the mean rate of any pain improvement was 92.9% (76 to 100%), the mean rate of neurologic improvement was 63.8% (53 to 100%), the mean rate of neurologic decline was 4.1% (0 to 8%), and the local tumor control rate was 92.6% (89 to 100%). Kyphoplasty studies reported a high rate of pain control in selected patients. Negative prognostic variables included hormonal (estrogen and progesterone) and human epidermal growth factor receptor 2 (HER2) receptor refractory tumor status, high degree of axillary lymph node involvement, and short disease-free interval (DFI). All other clinical or prognostic parameters were of low or insufficient strength. Conclusion With respect to clinical outcomes, surgery consistently yielded neurologic improvements in patients presenting with a deficit with a minimal risk of worsening; however, negative prognostic factors associated with shorter survival following surgery include estrogen receptor/progesterone receptor negativity, HER2 negativity, and a short DFI.

OBJECT While extent of resection has been shown to correlate with outcomes after myxopapillary ependymoma (MPE) resection, the effect of capsular violation has not been well studied. The role of adjuvant radiation also remains controversial. In this paper the authors' goals were to evaluate outcomes following resection of MPE based on intraoperative capsular violation and to explore the role of adjuvant radiotherapy in cases of capsular violation. METHODS A retrospective review of patients undergoing resection of MPE at 2 academic institutions between 1990 and 2013 was performed. Cases with dissemination at presentation, less than 12 months of follow-up, or incomplete records were excluded. Extent of resection was defined as en bloc if all visible tumor was removed without capsular violation, gross-total resection (GTR) if all visible tumor was removed, but with capsular violation, and subtotal resection (STR) if a known residual was left at the time of surgery. Postoperative MR images were reviewed to confirm the extent of resection. Primary outcomes were progression-free survival (PFS) and overall recurrence rates. The effects of extent of resection, capsular violation, and adjuvant radiotherapy on recurrence rates and PFS were analyzed using Kaplan-Meier statistics. Associations between recurrence and preoperative variables were evaluated using Fisher exact methods and t-tests where appropriate. RESULTS Of the 107 patients reviewed, 58 patients (53% were male) met inclusion criteria. The mean age at surgery was 40.8 years (range 7–68 years). The median follow-up was 51.5 months (range 12–243 months). Extent of resection was defined as en bloc in 46.5% (n = 27), GTR in 34.5% (n = 20), and STR in 18.9% (n = 11). No recurrences were noted in the en bloc group, compared with 15% (n = 3) and 45% (n = 5) in the GTR and STR groups. En bloc resection was achieved most frequently in tumors involving the conus. Twelve patients (20%) underwent adjuvant radiotherapy following either STR or GTR. The overall recurrence rate was 13.8% (n = 8), and the 5-year PFS was 81%. Capsular violation was associated with a higher recurrence rate (p = 0.005). Adjuvant radiotherapy showed a nonsignificant trend of lower recurrence rates (16.7% vs 31.6%, p = 0.43) and longer PFS at 5 years (83.3% vs 49.9%, p = 0.16) in cases of capsular violation. CONCLUSIONS A strong correlation between capsular violation and recurrence was found following removal of MPE and should be assessed when defining extent of resection in future studies. Although the use of adjuvant radiotherapy in cases of capsular violation showed a trend toward improved PFS, further investigation is needed to establish its role as salvage therapy also appears to be effective at halting disease progression.

Study Design Literature review. Objective Functional secretory tumors metastatic to the spine can secrete hormones, growth factors, peptides, and/or molecules into the systemic circulation that cause distinct syndromes, clinically symptomatic effects, and/or additional morbidity and mortality. En bloc resection has a limited role in metastatic spine disease due to the current paradigm that systemic burden usually determines morbidity and mortality. Our objective is to review the literature for studies focused on en bloc resection of functionally active spinal metastasis as the primary indication. Methods A review of the PubMed literature was performed to identify studies focused on functional secreting metastatic tumors to the spinal column. We identified five cases of patients undergoing en bloc resection of spinal metastases from functional secreting tumors. Results The primary histologies of these spinal metastases were pheochromocytoma, carcinoid tumor, choriocarcinoma, and a fibroblast growth factor 23–secreting phosphaturic mesenchymal tumor. Although studies of en bloc resection for these rare tumor subtypes are confined to case reports, this surgical treatment option resulted in metabolic cures and decreased clinical symptoms postoperatively for patients diagnosed with solitary functional secretory spinal metastasis. Conclusion Although the ability to formulate comprehensive conclusions is limited, case reports demonstrate that en bloc resection may be considered as a potential surgical option for the treatment of patients diagnosed with solitary functional secretory spinal metastatic tumors. Future prospective investigations into clinical outcomes should be conducted comparing intralesional resection and en bloc resection for patients diagnosed with solitary functional secretory spinal metastasis.

Introduction Treatment of symptomatic spinal metastases through surgical decompression and reconstruction is known to improve quality of life in patients with cancer. However, most studies have been performed on patients with mixed tumor histopathology. We systematically review the literature for prognostic factors specific to the surgical treatment of prostate metastases to the spine to determine the indications and outcomes of the surgical treatment. Material and Methods A systemic review of the literature was conducted to answer the following questions: Q1. Describe the survival and functional outcomes of surgery or vertebral augmentation for prostate metastases to the spine; Q2. Determine whether overall tumor burden, Gleason score, preoperative functional markers, and favorable hormonal naivety for operative intervention; Q3. Establish whether clinical outcomes vary with the evolution of operative techniques. Expert consensus was obtained using a modified Delphi process. Results A total of 16 studies met the preset inclusion criteria. These studies were all retrospective series with a level of evidence of IV. Included studies consistently showed a large effect of hormone naivety on overall survival. In addition, studies consistently demonstrated an improvement in motor function and the ability to maintain/regain ambulation following surgery resulting in moderate strength of recommendation. All other parameters were of insufficient or low strength. Conclusion There is scant literature on the surgical treatment of prostate metastases to the spine, which represents an opportunity for future research. On the basis of the existing evidence, it appears that the surgical treatment of prostate metastases to the spine has consistently favorable results. While no consistent preoperative indicators favor nonoperative treatment, hormone naivety and high Karnofsky Performance Scores have positive effects on survival and clinical outcomes.

Introduction Symptomatic metastatic epidural spinal cord compression (MESCC) afflicts up to 10% of all cancer patients. MESCC is associated with shortened survival and worsened quality of life; thus, early diagnosis and management is crucial. In a multidisciplinary setting, life expectancy must be considered along with other factors, such as patient's symptoms and overall medical condition, to select the optimal patient-specific treatment plan. This study aims to identify and compare key survival prognostic factors in surgically treated symptomatic MESCC patients with a 12-month postoperative follow-up. Materials and Methods Over a 5-year period, 145 patients surgically treated for a single symptomatic MESCC lesion were enrolled in a prospective North American multicenter study. Univariate analyses, Kaplan–Meier methods, and log-rank tests were used to evaluate the prognostic value of various clinical predictors. Preoperative prognostic factors evaluated: age, gender, comorbidities, history of smoking, metastases outside the spine, site of primary tumor, previous systemic treatment for the primary tumor, MESCC location, number of vertebral body involved, previous MESCC treatment, ASIA score, motor deficits, bladder dysfunction, Oswestry Disability Index (ODI), EQ-5D, SF-36v2 mental and physical components, and ability to walk four steps. Predictors with p < 0.2 in univariate analyses were included into the final Cox proportional hazards model. Results The overall median survival was 7.7 months (235 days). Lung and breast cancer had the shortest and longest median survival, respectively (4.5 vs. 12.1 months). Nine patients (6%), whose primary cancer were lung (3), kidney (3), melanoma (1), prostate (1), and breast (1), died within 30 days after surgery; 46 (32%), 61 (42%), 74 (51%), and 86 (59%) patients died at 3, 6, 9, and 12 months, respectively. The site of primary tumor, number of vertebrae involved, ODI, EQ-5D, ASIA score, metastases outside the spine, bladder dysfunction, and ability to walk four steps were significant predictors on the univariate analyses. However, the multivariate Cox-regression analysis demonstrated that only spinal metastasis involving four or more vertebral bodies had a negative impact on survival ( p = 0.002, HR: 25). Conclusion The extent of spinal metastasis, which is regarded as an indicator of the severity of patient's metastasis burden, and the site of the primary tumor, although not statistically significant in our regression model but well recognized in the literature as an important clinical predictor, are considered as independent predictors of poor prognosis in patients with a single-level symptomatic MESCC lesion. MESCC patients are a challenging and vulnerable heterogenous population. It is essential to identify factors predicting survival, functional and clinical outcomes in this population to guide patient-centered management to optimize quality of life.

Introduction Surgical treatment and cement augmentation procedures are effective palliative techniques for the treatment of symptomatic spinal metastases. However, clinical results specific to a breast cancer cohort are generally lacking. We aim to systematically review the literature for clinical outcomes following operative interventions and prognostic factors for the treatment of breast metastases to the spine. Specifically, we describe the survival and clinical outcomes of surgery and cement augmentation procedures for breast metastases to the spine and to determine prognostic variables that may help recognize which patients will perform better or worse following surgery. Methods We performed a literature review using PubMed to identify articles that reported outcomes and/or prognostic factors of the breast cancer patient population with spinal metastases treated with any surgical technique since 1990. Results A total of 19 surgical studies, 4 cement augmentation studies, and 6 nonsurgical prognostic variable studies met the preset inclusion criteria. All but three studies (two surgical and one cement augmentation) were retrospective in nature, and all studies were of level of evidence IV. Median postoperative survival for metastatic breast cancer was 21.7 months (8.2–36 months), mean rate of pain improvement was 92.9% (76–100%), mean rate of neurological improvement was 63.8% (53–100%), mean rate neurological decline was 4.1% (0–8%), and mean rate LTC was 92.6% (89–100%). Kyphoplasty studies reported a high rate of pain control in selected patients. Negative prognostic variables included: hormonal (estrogen and progesterone) and HER2 receptor refractory tumor status, high degree of axillary lymph node involvement, and short disease-free interval (DFI). All other clinical or prognostic parameters were of low or insufficient strength. Conclusion With respect to clinical outcomes, studies consistently found that surgery resulted in neurological improvement for a majority of patients, with a minimal risk of worsening, and kyphoplasty studies reported a high rate of pain control. Increased postoperative survival 2002 onwards was likely due to FDA approval of new chemotherapies. However, specific factors associated with shorter survival following surgery involve hormone and HER2 receptor status and disease-free interval.

Introduction Primary spinal osteosarcomas are rare and aggressive neoplasms with poor outcomes. Enneking appropriate, en bloc resection is recommended for appendicular osteosarcomas. Obtaining even marginal margins is technically demanding in the spine, resulting in significant morbidity and possible functional sacrifice. The aim of this study was to identify prognostic variables on local recurrence and mortality, in surgically treated patients diagnosed with a primary osteosarcoma of the spine. Methods A multicenter ambispective database of surgically treated patients with primary spine osteosarcomas was developed by the AOSpine knowledge forum tumor. Patient demographic, diagnosis, treatment, perioperative morbidity, local recurrence, and cross-sectional survival data were collected. Tumors were classified according to Enneking principles and analyzed in the following two cohorts: Enneking appropriate (EA) and Enneking inappropriate (EI). EA was defined by the final pathology margin matching the Enneking recommended surgical margin and EI by not matching. Prognostic variables including age, previous spine tumor operation, biopsy type, spine level, tumor size, and chemotherapy timing were analyzed in reference to local recurrence and survival. Results Between 1987 and 2012, 57 patients (31 females and 26 males) underwent surgical treatment for a primary spinal osteosarcoma at a mean age of 36 ± 16 years. Patients were followed for a mean period of 3.4 ± 3.5 years (range, 0.5 days–14.3 years). Median survival for the entire cohort was 6.7 years postoperative. Overall, 24 (42%) patients died and 17 (30%) patients suffered a local recurrence, 10 (59%) of which died. Overall, 28 (52%) patients underwent EA resection while 26 (48%) patients were treated by EI resection. Median survival for patients with EA was 6.8 years postoperative, whereas median survival for EI patients was 3.7 years postoperatively ( p = 0.062). EI patients were at a higher risk of local recurrence than EA patients ( p = 0.002). Patient age, previous spine tumor operation, tumor size, spine level, and chemotherapy timing did not significantly influence recurrence and survival. Conclusion Osteosarcoma of the spine presents a significant challenge and most patients die from their disease in spite of aggressive surgery. There is a significant decrease in recurrence with en bloc resection when compared with intralesional resection.