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Nancy Abu-Bonsrah, C. Rory Goodwin, Gezzer Ortega, Fizan Abdullah, Edward Cornwell, Rafael De la Garza-Ramos, Mari L. Groves, Michael Ain, Paul D. Sponseller, and Daniel M. Sciubba

OBJECTIVE

Spinal arthrodesis is routinely performed in the pediatric population. However, there is limited information on the short-term outcomes of pediatric patients who have undergone spine fusion. Thus, the authors conducted a retrospective review of the Pediatric National Surgical Quality Improvement Program (NSQIP) database to determine the short-term mortality, complication, reoperation, and readmission rates of pediatric patients who underwent spinal arthrodesis for all indications.

METHODS

The Pediatric NSQIP database was queried for all patients who underwent spinal arthrodesis between 2012 and 2014. Patient demographics, comorbidities, body mass index, American Society of Anesthesiologists classification, and operative time were abstracted. Short-term mortality, reoperation, and readmission rates and complications were also noted. Univariate and multivariate analyses were performed to delineate patient risk factors that influence short-term mortality, complications, reoperation, and readmission rates.

RESULTS

A total of 4420 pediatric patients who underwent spinal fusion were identified. Common indications for surgical intervention included acquired/idiopathic scoliosis or kyphoscoliosis (71.2%) and genetic/syndromic scoliosis (10.7%). The mean patient age was 13.7 ± 2.9 years, and 70% of patients were female. The overall 30-day mortality was 0.14%. Multivariate analysis showed that female sex and pulmonary comorbidities significantly increased the odds of reoperation, with odds ratios of 1.43 and 1.78, respectively.

CONCLUSIONS

In the NSQIP database for pediatric patients undergoing spinal arthrodesis for all causes, there was a 3.6% unplanned reoperation rate, a 3.96% unplanned readmission rate, and a 9.0% complication rate. This analysis provides data for risk stratification of pediatric patients undergoing spinal arthrodesis, allowing for optimized care.

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Rachel Sarabia-Estrada, Alejandro Ruiz-Valls, Sagar R. Shah, A. Karim Ahmed, Alvaro A. Ordonez, Fausto J. Rodriguez, Hugo Guerrero-Cazares, Ismael Jimenez-Estrada, Esteban Velarde, Betty Tyler, Yuxin Li, Neil A. Phillips, C. Rory Goodwin, Rory J. Petteys, Sanjay K. Jain, Gary L. Gallia, Ziya L. Gokaslan, Alfredo Quinones-Hinojosa, and Daniel M. Sciubba

OBJECTIVE

Chordoma is a slow-growing, locally aggressive cancer that is minimally responsive to conventional chemotherapy and radiotherapy and has high local recurrence rates after resection. Currently, there are no rodent models of spinal chordoma. In the present study, the authors sought to develop and characterize an orthotopic model of human chordoma in an immunocompromised rat.

METHODS

Thirty-four immunocompromised rats were randomly allocated to 4 study groups; 22 of the 34 rats were engrafted in the lumbar spine with human chordoma. The groups were as follows: UCH1 tumor–engrafted (n = 11), JHC7 tumor–engrafted (n = 11), sham surgery (n = 6), and intact control (n = 6) rats. Neurological impairment of rats due to tumor growth was evaluated using open field and locomotion gait analysis; pain response was evaluated using mechanical or thermal paw stimulation. Cone beam CT (CBCT), MRI, and nanoScan PET/CT were performed to evaluate bony changes due to tumor growth. On Day 550, rats were killed and spines were processed for H & E–based histological examination and immunohistochemistry for brachyury, S100β, and cytokeratin.

RESULTS

The spine tumors displayed typical chordoma morphology, that is, physaliferous cells filled with vacuolated cytoplasm of mucoid matrix. Brachyury immunoreactivity was confirmed by immunostaining, in which samples from tumor-engrafted rats showed a strong nuclear signal. Sclerotic lesions in the vertebral body of rats in the UCH1 and JHC7 groups were observed on CBCT. Tumor growth was confirmed using contrast-enhanced MRI. In UCH1 rats, large tumors were observed growing from the vertebral body. JHC7 chordoma–engrafted rats showed smaller tumors confined to the bone periphery compared with UCH1 chordoma–engrafted rats. Locomotion analysis showed a disruption in the normal gait pattern, with an increase in the step length and duration of the gait in tumor-engrafted rats. The distance traveled and the speed of rats in the open field test was significantly reduced in the UCH1 and JHC7 tumor–engrafted rats compared with controls. Nociceptive response to a mechanical stimulus showed a significant (p < 0.001) increase in the paw withdrawal threshold (mechanical hypalgesia). In contrast, the paw withdrawal response to a thermal stimulus decreased significantly (p < 0.05) in tumor-engrafted rats.

CONCLUSIONS

The authors developed an orthotopic human chordoma model in rats. Rats were followed for 550 days using imaging techniques, including MRI, CBCT, and nanoScan PET/CT, to evaluate lesion progression and bony integrity. Nociceptive evaluations and locomotion analysis were performed during follow-up. This model reproduces cardinal signs, such as locomotor and sensory deficits, similar to those observed clinically in human patients. To the authors’ knowledge, this is the first spine rodent model of human chordoma. Its use and further study will be essential for pathophysiology research and the development of new therapeutic strategies.

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Ganesh M. Shankar, Michelle J. Clarke, Tamir Ailon, Laurence D. Rhines, Shreyaskumar R. Patel, Arjun Sahgal, Ilya Laufer, Dean Chou, Mark H. Bilsky, Daniel M. Sciubba, Michael G. Fehlings, Charles G. Fisher, Ziya L. Gokaslan, and John H. Shin

OBJECTIVE

Primary osteosarcoma of the spine is a rare osseous neoplasm. While previously reported retrospective studies have demonstrated that overall patient survival is impacted mostly by en bloc resection and chemotherapy, the continued management of residual disease remains to be elucidated. This systematic review was designed to address the role of revision surgery and multimodal adjuvant therapy in cases in which en bloc excision is not initially achieved.

METHODS

A systematic literature search spanning the years 1966 to 2015 was performed on PubMed, Medline, EMBASE, and Web of Science to identify reports describing outcomes of patients who underwent biopsy alone, neurological decompression, or intralesional resection for osteosarcoma of the spine. Studies were reviewed qualitatively, and the clinical course of individual patients was aggregated for quantitative meta-analysis.

RESULTS

A total of 16 studies were identified for inclusion in the systematic review, of which 8 case reports were summarized qualitatively. These studies strongly support the role of chemotherapy for overall survival and moderately support adjuvant radiation therapy for local control. The meta-analysis revealed a statistically significant benefit in overall survival for performing revision tumor debulking (p = 0.01) and also for chemotherapy at relapse (p < 0.01). Adjuvant radiation therapy was associated with longer survival, although this did not reach statistical significance (p = 0.06).

CONCLUSIONS

While the initial therapeutic goal in the management of osteosarcoma of the spine is neoadjuvant chemotherapy followed by en bloc marginal resection, this objective is not always achievable given anatomical constraints and other limitations at the time of initial clinical presentation. This systematic review supports the continued aggressive use of revision surgery and multimodal adjuvant therapy when possible to improve outcomes in patients who initially undergo subtotal debulking of osteosarcoma. A limitation of this systematic review is that lesions amenable to subsequent resection or tumors inherently more sensitive to adjuvants would exaggerate a therapeutic effect of these interventions when studied in a retrospective fashion.

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Ming-Xiang Zou, Jing Li, Xiao-Bin Wang, and Guo-Hua Lv

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Rafael De la Garza Ramos, C. Rory Goodwin, Nancy Abu-Bonsrah, Ali Bydon, Timothy F. Witham, Jean-Paul Wolinsky, and Daniel M. Sciubba

OBJECTIVE

The aim of this study was to investigate the incidence of spinal tuberculosis (TB) in the US between 2002 and 2011.

METHODS

The Nationwide Inpatient Sample database from 2002 to 2011 was used to identify patients with a discharge diagnosis of TB and spinal TB. Demographic and hospital data were obtained for all admissions, and included age, sex, race, comorbid conditions, insurance status, hospital location, hospital teaching status, and hospital region. The incidence rate of spinal TB adjusted for population growth was calculated after application of discharge weights.

RESULTS

A total of 75,858 patients with a diagnosis of TB were identified, of whom 2789 had a diagnosis of spinal TB (3.7%); this represents an average of 278.9 cases per year between 2002 and 2011. The incidence of spinal TB decreased significantly—from 0.07 cases per 100,000 persons in 2002 to 0.05 cases per 100,000 in 2011 (p < 0.001), corresponding to 1 case per 2 million persons in the latter year. The median age for patients with spinal TB was 51 years, and 61% were male; 11.6% were patients with diabetes, 11.4% reported recent weight loss, and 8.1% presented with paralysis. There were 619 patients who underwent spinal surgery for TB, with the most common location being the thoracolumbar spine (61.9% of cases); 50% of patients had instrumentation of 3 or more spinal segments.

CONCLUSIONS

During the examined 10-year period, the incidence of spinal TB was found to significantly decrease over time in the US, reaching a rate of 1 case per 2 million persons in 2011. However, the absolute reduction was relatively small, suggesting that although it is uncommon, spinal TB remains a public health concern and most commonly affects male patients approximately 50 years of age. Approximately 20% of patients with spinal TB underwent surgery, most commonly in the thoracolumbar spine.

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Justin K. Scheer, Justin S. Smith, Frank Schwab, Virginie Lafage, Christopher I. Shaffrey, Shay Bess, Alan H. Daniels, Robert A. Hart, Themistocles S. Protopsaltis, Gregory M. Mundis Jr., Daniel M. Sciubba, Tamir Ailon, Douglas C. Burton, Eric Klineberg, Christopher P. Ames, and The International Spine Study Group

OBJECTIVE

The operative management of patients with adult spinal deformity (ASD) has a high complication rate and it remains unknown whether baseline patient characteristics and surgical variables can predict early complications (intraoperative and perioperative [within 6 weeks]). The development of an accurate preoperative predictive model can aid in patient counseling, shared decision making, and improved surgical planning. The purpose of this study was to develop a model based on baseline demographic, radiographic, and surgical factors that can predict if patients will sustain an intraoperative or perioperative major complication.

METHODS

This study was a retrospective analysis of a prospective, multicenter ASD database. The inclusion criteria were age ≥ 18 years and the presence of ASD. In total, 45 variables were used in the initial training of the model including demographic data, comorbidities, modifiable surgical variables, baseline health-related quality of life, and coronal and sagittal radiographic parameters. Patients were grouped as either having at least 1 major intraoperative or perioperative complication (COMP group) or not (NOCOMP group). An ensemble of decision trees was constructed utilizing the C5.0 algorithm with 5 different bootstrapped models. Internal validation was accomplished via a 70/30 data split for training and testing each model, respectively. Overall accuracy, the area under the receiver operating characteristic (AUROC) curve, and predictor importance were calculated.

RESULTS

Five hundred fifty-seven patients were included: 409 (73.4%) in the NOCOMP group, and 148 (26.6%) in the COMP group. The overall model accuracy was 87.6% correct with an AUROC curve of 0.89 indicating a very good model fit. Twenty variables were determined to be the top predictors (importance ≥ 0.90 as determined by the model) and included (in decreasing importance): age, leg pain, Oswestry Disability Index, number of decompression levels, number of interbody fusion levels, Physical Component Summary of the SF-36, Scoliosis Research Society (SRS)–Schwab coronal curve type, Charlson Comorbidity Index, SRS activity, T-1 pelvic angle, American Society of Anesthesiologists grade, presence of osteoporosis, pelvic tilt, sagittal vertical axis, primary versus revision surgery, SRS pain, SRS total, use of bone morphogenetic protein, use of iliac crest graft, and pelvic incidence–lumbar lordosis mismatch.

CONCLUSIONS

A successful model (87% accuracy, 0.89 AUROC curve) was built predicting major intraoperative or perioperative complications following ASD surgery. This model can provide the foundation toward improved education and point-of-care decision making for patients undergoing ASD surgery.

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Niketh Bhashyam, Rafael De la Garza Ramos, Jonathan Nakhla, Rani Nasser, Ajit Jada, Taylor E. Purvis, Daniel M. Sciubba, Merritt D. Kinon, and Reza Yassari

OBJECTIVE

The goal of this study was to compare 30-day readmission and reoperation rates after single-level anterior cervical discectomy and fusion (ACDF) versus those after cervical disc replacement (CDR).

METHODS

The authors used the 2013–2014 American College of Surgeons National Surgical Quality Improvement Program database. Included were adult patients who underwent first-time single-level ACDF or CDR for cervical spondylosis or disc herniation. Primary outcome measures were readmission and/or reoperation within 30 days of the original surgery. Logistic regression analysis was used to assess the independent effect of the procedure (ACDF or CDR) on outcome, and results are presented as odds ratios with 95% confidence intervals.

RESULTS

A total of 6077 patients met the inclusion criteria; 5590 (92.0%) patients underwent single-level ACDF, and 487 (8.0%) patients underwent CDR. The readmission rates were 2.6% for ACDF and 0.4% for CDR (p = 0.003). When stratified according to age groups, only patients between the ages of 41 and 60 years who underwent ACDF had a significantly higher readmission rate than those who underwent CDR (2.5% vs 0.7%, respectively; p = 0.028). After controlling for patient age, sex, body mass index, smoking status, history of chronic obstructive pulmonary disease (COPD), diabetes, hypertension, steroid use, and American Society of Anesthesiologists (ASA) class, patients who underwent CDR were significantly less likely to undergo readmission within 30 days than patients who underwent ACDF (OR 0.23 [95% CI 0.06–0.95]; p = 0.041). Patients with a history of COPD (OR 1.97 [95% CI 1.08–3.57]; p = 0.026) or hypertension (OR 1.62 [95% CI 1.10–2.38]; p = 0.013) and those at ASA Class IV (OR 14.6 [95% CI 1.69–125.75]; p = 0.015) were significantly more likely to require readmission within 30 days. The reoperation rates were 1.2% for ACDF and 0.4% for CDR (p = 0.086), and multivariate analysis revealed that CDR was not associated with lower odds of reoperation (OR 0.60 [95% CI 0.14–2.55]; p = 0.492). However, increasing age was associated with a higher risk (OR 1.02 [95% CI 1.00–1.05]; p = 0.031) of reoperation; a 2% increase in risk per year of age was found.

CONCLUSIONS

Patients who underwent single-level ACDF had a higher readmission rate than those who underwent single-level CDR in this study. When stratified according to age, this effect was seen only in the 41- to 60-year age group. No significant difference in the 30-day single-level ACDF and single-level CDR reoperation rates was found. Although patients in the ACDF group were older and sicker, other unmeasured covariates might have accounted for the increased rate of readmission in this group, and further investigation is encouraged.

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Benjamin D. Elder, Wataru Ishida, C. Rory Goodwin, Ali Bydon, Ziya L. Gokaslan, Daniel M. Sciubba, Jean-Paul Wolinsky, and Timothy F. Witham

OBJECTIVE

With the advent of new adjunctive therapy, the overall survival of patients harboring spinal column tumors has improved. However, there is limited knowledge regarding the optimal bone graft options following resection of spinal column tumors, due to their relative rarity and because fusion outcomes in this cohort are affected by various factors, such as radiation therapy (RT) and chemotherapy. Furthermore, bone graft options are often limited following tumor resection because the use of local bone grafts and bone morphogenetic proteins (BMPs) are usually avoided in light of microscopic infiltration of tumors into local bone and potential carcinogenicity of BMP. The objective of this study was to review and meta-analyze the relevant clinical literature to provide further clinical insight regarding bone graft options.

METHODS

A web-based MEDLINE search was conducted in accordance with preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines, which yielded 27 articles with 383 patients. Information on baseline characteristics, tumor histology, adjunctive treatments, reconstruction methods, bone graft options, fusion rates, and time to fusion were collected. Pooled fusion rates (PFRs) and I2 values were calculated in meta-analysis. Meta-regression analyses were also performed if each variable appeared to affect fusion outcomes. Furthermore, data on 272 individual patients were available, which were additionally reviewed and statistically analyzed.

RESULTS

Overall, fusion rates varied widely from 36.0% to 100.0% due to both inter- and intrastudy heterogeneity, with a PFR of 85.7% (I2 = 36.4). The studies in which cages were filled with morselized iliac crest autogenic bone graft (ICABG) and/or other bone graft options were used for anterior fusion showed a significantly higher PFR of 92.8, compared with the other studies (83.3%, p = 0.04). In per-patient analysis, anterior plus posterior fusion resulted in a higher fusion rate than anterior fusion only (98.8% vs 86.4%, p < 0.001). Although unmodifiable, RT (90.3% vs 98.6%, p = 0.03) and lumbosacral tumors (74.6% vs 97.9%, p < 0.001) were associated with lower fusion rates in univariate analysis. The mean time to fusion was 5.4 ± 1.4 months (range 3–9 months), whereas 16 of 272 patients died before the confirmation of solid fusion with a mean survival of 3.1 ± 2.1 months (range 0.5–6 months). The average time to fusion of patients who received RT and chemotherapy were significantly longer than those who did not receive these adjunctive treatments (RT: 6.1 months vs 4.3 months, p < 0.001; chemotherapy: 6.0 months vs 4.3 months, p = 0.02).

CONCLUSIONS

Due to inter- and intrastudy heterogeneity in patient, disease, fusion criteria, and treatment characteristics, the optimal surgical techniques and factors predictive of fusion remain unclear. Clearly, future prospective, randomized studies will be necessary to better understand the issues surrounding bone graft selection following resection of spinal column tumors.

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Michael S. Virk, James E. Han, Anne S. Reiner, Lily A. McLaughlin, Daniel M. Sciubba, Eric Lis, Yoshiya Yamada, Mark Bilsky, and Ilya Laufer

OBJECTIVE

The purpose of this study was to determine the rate of symptomatic vertebral body compression fractures (VCFs) requiring kyphoplasty or surgery in patients treated with 24-Gy single-fraction stereotactic radiosurgery (SRS).

METHODS

This retrospective analysis included all patients who had been treated with 24-Gy, single-fraction, image-guided intensity-modulated radiation therapy for histologically confirmed solid tumor metastases over an 8-year period (2005–2013) at Memorial Sloan Kettering Cancer Center. Charts and imaging studies were reviewed for post-SRS kyphoplasty or surgery for mechanical instability. A Spinal Instability Neoplastic Score (SINS) was calculated for each patient both at the time of SRS and at the time of intervention for VCF.

RESULTS

Three hundred twenty-three patients who had undergone single-fraction SRS between C-1 and L-5 were included in this analysis. The cumulative incidence of VCF 5 years after SRS was 7.2% (95% CI 4.1–10.2), whereas that of death following SRS at the same time point was 82.5% (95% CI 77.5–87.4). Twenty-six patients with 36 SRS-treated levels progressed to symptomatic VCF requiring treatment with kyphoplasty (6 patients), surgery (10 patients), or both (10 patients). The median time to symptomatic VCF was 13 months. Seven patients developed VCF at 11 levels adjacent to the SRS-treated level. Fractured levels had no evidence of tumor progression. The median SINS changed from 6.5 at SRS (interquartile range [IQR] 4.3–8.8) to 11.5 at stabilization (IQR 9–13). In patients without prior stabilization at the level of SRS, there was an association between the SINS and the time to fracture.

CONCLUSIONS

Five years after ablative single-fraction SRS to spinal lesions, the cumulative incidence of symptomatic VCF at the treated level without tumor recurrence was 7.2%. Higher SINSs at the time of SRS correlated with earlier fractures.