Risk assessment of early therapeutic anticoagulation following cranial surgery: an institutional case series.

OBJECTIVE: Postoperative thrombotic complications represent a unique challenge in cranial neurosurgery as primary treatment involves therapeutic anticoagulation. The decision to initiate therapy and its timing is nuanced, as surgeons must balance the risk of catastrophic intracranial hemorrhage (ICH). With limited existing evidence to guide management, current practice patterns are subjective and inconsistent. The authors assessed their experience with early therapeutic anticoagulation (≤ 7 days postoperatively) initiation for thrombotic complications in neurosurgical patients undergoing cranial surgery to better understand the risks of catastrophic ICH. METHODS: Adult patients treated with early therapeutic anticoagulation following cranial surgery were considered. Anticoagulation indications were restricted to thrombotic or thromboembolic complications. Records were retrospectively reviewed for demographics, surgical details, and anticoagulation therapy start. The primary outcome was the incidence of catastrophic ICH, defined as ICH resulting in reoperation or death within 30 days of anticoagulation initiation. As a secondary outcome, post-anticoagulation cranial imaging was reviewed for new or worsening acute blood products. Fisher's exact and Wilcoxon rank-sum tests were used to compare cohorts. Cumulative outcome analyses were performed for primary and secondary outcomes according to anticoagulation start time. RESULTS: Seventy-one patients satisfied the inclusion criteria. Anticoagulation commenced on mean postoperative day (POD) 4.3 (SD 2.2). Catastrophic ICH was observed in 7 patients (9.9%) and was associated with earlier anticoagulation initiation (p = 0.02). Of patients with catastrophic ICH, 6 (85.7%) had intra-axial exploration during their index surgery. Patients with intra-axial exploration were more likely to experience a catastrophic ICH postoperatively compared to those with extra-axial exploration alone (OR 8.5, p = 0.04). Of the 58 patients with postoperative imaging, 15 (25.9%) experienced new or worsening blood products. Catastrophic ICH was 9 times more likely with anticoagulation initiation within 48 hours of surgery (OR 8.9, p = 0.01). The cumulative catastrophic ICH risk decreased with delay in initiation of anticoagulation, from 21.1% on POD 2 to 9.9% on POD 7. Concurrent antiplatelet medication was not associated with either outcome measure. CONCLUSIONS: The incidence of catastrophic ICH was significantly increased when anticoagulation was initiated within 48 hours of cranial surgery. Patients undergoing intra-axial exploration during their index surgery were at higher risk of a catastrophic ICH.

Metastatic Breast Cancer to the Spine: Incidence of Somatic Gene Alterations and Association of Targeted Therapies With Overall Survival.

BACKGROUND: The increase in use of targeted systemic therapies in cancer treatments has catalyzed the importance of identifying patient- and tumor-specific somatic mutations, especially regarding metastatic disease. Mutations found to be most prevalent in patients with metastatic breast cancer include TP53, PI3K, and CDH1. OBJECTIVE: To determine the incidence of somatic mutations in patients with metastatic breast cancer to the spine (MBCS). To determine if a difference exists in overall survival (OS), progression-free survival, and progression of motor symptoms between patients who do or do not undergo targeted systemic therapy after treatment for MBCS. METHODS: This is a retrospective study of patients with MBCS. Review of gene sequencing reports was conducted to calculate the prevalence of various somatic gene mutations within this population. Those patients who then underwent treatment (surgery/radiation) for their diagnosis of MBCS between 2010 and 2020 were subcategorized. The use of targeted systemic therapy in the post-treatment period was identified, and post-treatment OS, progression-free survival, and progression of motor deficits were calculated for this subpopulation. RESULTS: A total of 131 patients were included in the final analysis with 56% of patients found to have a PI3K mutation. Patients who received targeted systemic therapies were found to have a significantly longer OS compared with those who did not receive targeted systemic therapies. CONCLUSION: The results of this study demonstrate that there is an increased prevalence of PI3K mutations in patients with MBCS and there are a significant survival benefit and delay in progression of motor symptoms associated with using targeted systemic therapies for adjuvant treatment.

Attitudes and trends in the use of radiolucent spinal implants: A survey of the North American Spine Society section of spinal oncology.

Background: In spinal oncology, titanium implants pose several challenges including artifact on advanced imaging and therapeutic radiation perturbation. To mitigate these effects, there has been increased interest in radiolucent carbon fiber (CF) and CF-reinforced polyetheretherketone (CFR-PEEK) implants as an alternative for spinal reconstruction. This study surveyed the members of the North American Spine Society (NASS) section of Spinal Oncology to query their perspectives regarding the clinical utility, current practice patterns, and recommended future directions of radiolucent spinal implants. Methods: In February 2021, an anonymous survey was administered to the physicians of the NASS section of Spinal Oncology. Participation in the survey was optional. The survey contained 38 items including demographic questions as well as multiple-choice, yes/no questions, Likert rating scales, and short free-text responses pertaining to the "clinical concept", "efficacy", "problems/complications", "practice pattern", and "future directions" of radiolucent spinal implants. Results: Fifteen responses were received (71.4% response rate). Six of the participants (40%) were neurosurgeons, eight (53.3%) were orthopedic surgeons, and one was a spinal radiation oncologist. Overall, there were mixed opinions among the specialists. While several believed that radiolucent spinal implants provide substantial benefits for the detection of disease recurrence and radiation therapy options, others remained less convinced. Ongoing concerns included high costs, low availability, limited cervical and percutaneous options, and suboptimal screw and rod designs. As such, participants estimated that they currently utilize these implants for 27.3% of anterior and 14.7% of all posterior reconstructions after tumor resection. Conclusion: A survey of the NASS section of Spinal Oncology found a lack of consensus with regards to the imaging and radiation benefits, and several ongoing concerns about currently available options. Therefore, routine utilization of these implants for anterior and posterior spinal reconstructions remains low. Future investigations are warranted to practically validate these devices' theoretical risks and benefits.

Primary Paraganglioma of the Spine: A Systematic Review of Clinical Features and Surgical Management in Cauda Equina versus Non-Cauda Equina Lesions.

BACKGROUND: Primary spine paragangliomas are rare tumors. Surgical resection plays a role, but aggressive lesions are challenging. We reviewed the literature on primary spine paragangliomas. METHODS: PubMed, Scopus, Web of Science, and Cochrane were searched following the PRISMA guidelines to include studies on primary spine paragangliomas. Clinical-radiologic features, treatments, and outcomes were analyzed and compared between cauda equina versus non-cauda equina tumors. RESULTS: We included 143 studies comprising 334 patients. Median age was 46 years (range, 6-85 years). The most frequent symptoms were lower back (64.1%) and radicular (53.9%) pain, and sympathetic in 18 patients (5.4%). Cauda equina paragangliomas (84.1%) had frequently lumbar (49.1%) or lumbosacral (29%) locations. Non-cauda equina tumors were mostly in the thoracic (11.4%), thoracolumbar (5.1%), and cervical (3.6%) spine. Median tumor diameter was 2.5 cm (range, 0.5-13.0 cm). Surgical resection (98.5%) was preferred over biopsy (1.5%). Decompressive laminectomy (53%) and spine fusion (6.9%) were also performed. Adjuvant radiotherapy was delivered in 39 patients (11.7%) with aggressive tumors. Posttreatment symptomatic improvement was described in 86.2% cases. Median follow-up was 19.5 months (range, 0.1-468.0 months), and 23 patients (3.9%) had tumor recurrences. No significant differences were found between cauda equina versus non-cauda equina tumors. CONCLUSIONS: Surgical resection is effective and safe in treating primary spine paragangliomas; however, adjuvant treatments may be needed for aggressive lesions.

Predictors of Nonelective Surgery for Spinal Metastases: Insights from a National Database.

STUDY DESIGN: Secondary analysis of a national all-payer database. OBJECTIVE: Our objectives were to identify patient- and hospital-level factors independently associated with the receipt of nonelective surgery and determine whether nonelective surgery portends differences in perioperative outcomes compared to elective surgery for spinal metastases. SUMMARY OF BACKGROUND DATA: Spinal metastases may progress to symptomatic epidural spinal cord compression that warrants urgent surgical intervention. Although nonelective surgery for spinal metastases has been associated with poor postoperative outcomes, literature evaluating disparities in the receipt of nonelective versus elective surgery in this population is lacking. METHODS: The National Inpatient Sample (2012-2015) was queried for patients who underwent surgical intervention for spinal metastases. Multivariable logistic regression models were constructed to evaluate the association of patient- and hospital-level factors with the receipt of nonelective surgery, as well as to evaluate the influence of admission status on perioperative outcomes. RESULTS: After adjusting for disease-related factors and other baseline covariates, our multivariable logistic regression model revealed several sociodemographic differences in the receipt of nonelective surgery. Patients of black (odds ratio [OR] = 1.38, 95% confidence interval [CI]: 1.03-1.84, P = 0.032) and other race (OR = 1.50, 95% CI: 1.13-1.98, P = 0.005) had greater odds of undergoing nonelective surgery than their white counterparts. Patients of lower income (OR = 1.40, 95% CI: 1.06-1.84, P = 0.019) and public insurance status (OR = 1.56, 95% CI: 1.26-1.93, P < 0.001) were more likely to receive nonelective surgery than higher income and privately insured patients, respectively. Higher comorbidity burden was also associated with greater odds of non-elective admission (OR = 2.94, 95% CI: 2.07-4.16, P  < 0.001). With respect to perioperative outcomes, multivariable analysis revealed that patients receiving nonelective surgery were more likely to experience nonroutine discharge (OR = 2.50, 95% CI: 2.09-2.98, P  < 0.001) and extended length of stay [LOS] (OR = 2.45, 95% CI: 1.91-3.16, P < 0.001). CONCLUSION: The present study demonstrates substantial disparities in the receipt of nonelective surgery across sociodemographic groups and highlights its association with nonroutine discharge and extended LOS.Level of Evidence: 3.

Factors associated with adjacent-level tumor progression in patients receiving surgery followed by radiosurgery for metastatic epidural spinal cord compression.

OBJECTIVE: Separation surgery followed by spine stereotactic radiosurgery (SSRS) has been shown to achieve favorable rates of local tumor control and patient-reported outcomes in patients with metastatic epidural spinal cord compression (MESCC). However, rates and factors associated with adjacent-level tumor progression (ALTP) in this population have not yet been characterized. The present study aimed to identify factors associated with ALTP and examine its association with overall survival (OS) in patients receiving surgery followed by radiosurgery for MESCC. METHODS: Thirty-nine patients who underwent separation surgery followed by SSRS for MESCC were identified using a prospectively collected database and were retrospectively reviewed. Radiological measurements were collected from preoperative, postoperative, and post-SSRS MRI. Statistical analysis was conducted using the Kaplan-Meier product-limit method and Cox proportional hazards test. Subgroup analysis was conducted for patients who experienced ALTP into the epidural space (ALTP-E). RESULTS: The authors' cohort included 39 patients with a median OS of 14.7 months (range 2.07-96.3 months). ALTP was observed in 16 patients (41.0%) at a mean of 6.1 ± 5.4 months postradiosurgery, of whom 4 patients (10.3%) experienced ALTP-E. Patients with ALTP had shorter OS (13.0 vs 17.1 months, p = 0.047) compared with those without ALTP. Factors associated with an increased likelihood of ALTP included the amount of bone marrow infiltrated by tumor at the index level, amount of residual epidural disease following separation surgery, and prior receipt of radiotherapy at the index level (p < 0.05). Subgroup analysis revealed that primary tumor type, amount of preoperative epidural disease, time elapsed between surgery and radiosurgery, and prior receipt of radiotherapy at the index level were significantly associated with ALTP-E (p < 0.05). CONCLUSIONS: To the authors' knowledge, this study is the first to identify possible risk factors for ALTP, and they suggest that it may be associated with shorter OS in patients receiving surgery followed by radiosurgery for MESCC. Future studies with higher power should be conducted to further characterize factors associated with ALTP in this population.

Reducing Wrong-level Spinal Surgeries Through Root Cause Analyses: A 10-year Longitudinal Analysis of a Single Tertiary Institution's Iterative Policy Improvements.

MINI: This study is a comprehensive narrative of all wrong-level spine surgeries and prevention strategies employed at our institution between 2008 and 2019, and aims to provide a roadmap for developing a rigorous prevention protocol. We systematically track root cause analyses and policy changes to determine which prevention strategies are most effective.

Retrospective review. We aim to create a comprehensive narrative of all wrong-level spinal surgeries (WLSS) and subsequent prevention strategies employed at our institution and provide a roadmap for developing a rigorous prevention protocol. There is currently no published evidence-based protocol to prevent WLSS. Previous studies are limited to multi-institution surgeon surveys and opinion pieces; the impact of serial interventions to eliminate WLSS is lacking. No studies have longitudinally analyzed a single institution's serial root cause analyses (RCA) of individual WLSS cases and the stepwise impact of targeted interventions to reduce WLSS occurrence. We reviewed all wrong-site spine surgeries and prevention strategies employed at our institution between 2008 and 2019, and corresponding WLSS-related RCAs were collected from institutional records. We conducted a longitudinal analysis of these reports and tracked policy implementations that resulted along with the incidence of WLSS following each policy. Fifteen WLSS were identified with 13 corresponding RCAs of 21,179 spine surgeries between 2008 and 2019. Three policy categories emerged: imaging, operating room (OR) culture, and vertebral body marking. The salient changes from each category were: requiring two immovable vertebral markers (2013); requiring intraoperative radiographs with markers and retractors positioned (2014); open-ended questioning during spinal level verification by residents and fellows (2015); and requiring an impartial radiologist to have verbal contact with the operating surgeon intraoperatively to collaboratively discuss localization (2018). Each change resulted in WLSS incidence decline (five in 2014, three in 2015, 0 in 2019). Stepwise process improvement based on WLSS case review is necessary, as no one change in standard operating procedure effectively eliminated WLSS. Improvements in communication between OR staff, surgeon, and radiologist, as well as intraoperative imaging and marking optimization all contributed to improvements in WLSS rates. By focusing on lessons learned from RCAs using this methodology, institutions can iteratively improve rates of WLSS. Level of Evidence: 4.

Enhanced Recovery in Spine Surgery and Perioperative Pain Management.

Enhanced recovery after surgery is an interdisciplinary, multimodal approach to improve postoperative outcomes by applying multiple evidenced-based interventions. It has been adapted at multiple institutions for patients undergoing spine surgery to combat the rising rate of opioid consumption. Various preoperative, intraoperative, and postoperative pharmacologic and nonpharmacologic interventions have been introduced to augment patient care with the goal to decrease hospital length of stay and improve postoperative outcomes. Future studies will focus on health care-related quality of life outcomes to evaluate the effectiveness of enhanced recovery after surgery across various benchmarks.

Spine radiosurgery in adolescents and young adults: early outcomes and toxicity in patients with metastatic Ewing sarcoma and osteosarcoma.

OBJECTIVE: There are limited data on spine stereotactic radiosurgery (SRS) in treating adolescent and young adult (AYA) patients. SRS has the advantages of highly conformal radiation dose delivery in the upfront and retreatment settings, means for dose intensification, and administration over a limited number of sessions leading to a decreased treatment burden. In this study, the authors report the oncological and toxicity outcomes for AYA patients with metastatic sarcoma treated with spine radiosurgery and provide clinicians a guide for considerations in dose, volume, and fractionation. METHODS: An institutional review board-approved database of patients treated with SRS in the period from October 2014 through December 2018 was queried. AYA patients, defined by ages 15-29 years, who had been treated with SRS for spine metastases from Ewing sarcoma or osteosarcoma were included in this analysis. Patients with follow-ups shorter than 6 months after SRS were excluded. Local control, overall survival, and toxicity were reported. RESULTS: Seven patients with a total of 11 treated lesions were included in this study. Median patient age was 20.3 years (range 15.1-26.1 years). Three patients had Ewing sarcoma (6 lesions) and 4 patients had osteosarcoma (5 lesions). The median dose delivered was 35 Gy in 5 fractions (range 16-40 Gy, 1-5 fractions). The median follow-up was 11.1 months (range 6.8-26.0 months). Three local failures were observed within the follow-up period. No acute grade 3 or greater toxicity was observed. One patient developed late grade 3 toxicity consisting of radiation enteritis. This patient had previously received radiation to an overlapping volume with conventional fractionation. SRS re-irradiation for this patient was also performed concurrently with chemotherapy administration. No late grade 4 or higher toxicities were observed. No pain flare or vertebral compression fracture was observed. Three patients died within the follow-up period. CONCLUSIONS: SRS for spine metastases from Ewing sarcoma and osteosarcoma can be considered as a treatment option in AYA patients and is associated with acceptable toxicity rates. Further studies must be conducted to determine long-term local control and toxicity for this treatment modality.

Development and implementation of a comprehensive spine surgery enhanced recovery after surgery protocol: the Cleveland Clinic experience.

Enhanced recovery after surgery (ERAS) protocols have been shown to be effective at reducing perioperative morbidity and costs while improving outcomes. To date, spine surgery protocols have been limited in scope, focusing only on specific types of procedures or specific parts of the surgical episode. The authors describe the creation and implementation of one of the first comprehensive ERAS protocols for spine surgery. The protocol is unique in that it has a comprehensive perioperative paradigm encompassing the entire surgical period that is tailored based on the complexity of each individual spine patient.

Novel Strategy of Ventral Dural Repair for Idiopathic Thoracic Spinal Cord Herniation: Report of Outcomes and Review of Techniques.

BACKGROUND: Idiopathic ventral thoracic spinal cord herniation is a rare condition that usually presents with progressive myelopathy or Brown-Séquard syndrome. More than 100 cases have been reported with significant variance in surgical treatment strategies and likewise, significant variance in patient outcomes. Although laminectomy has often been used, to date, there is no consensus regarding the optimal surgical approach or strategy for ventral dural repair. OBJECTIVE: To report and illustrate a novel approach to repair the ventral dural defect with more than 2 yr of clinical follow-up. The specific approach and graft used are both detailed. METHODS: A retrospective chart review of all known cases of idiopathic spinal cord herniation at the Cleveland Clinic over the last 15 yr was performed. Postoperative outcome scores (including the Japanese Orthopedic Association score, European Myelopathy score, and Nurick) were calculated preoperatively and postoperatively. RESULTS: A total of 5 patients were identified. Four of five patients improved clinically after surgery and 1 patient remained unchanged at last follow-up (average 23.2 mo, range 12-60 mo). There were no complications. All patients had postoperative magnetic resonance imaging demonstrating realignment of the spinal cord and no recurrence of tethering. CONCLUSION: A unilateral dorsolateral, transpedicular approach combined with laminectomy provides excellent exposure for ventral or ventrolateral dural defects associated with idiopathic spinal cord herniation and minimizes spinal cord manipulation. A collagen matrix graft used as an onlay between the spinal cord and ventral dural defect is a safe and effective option for ventral dural repair.

Rare Thymoma Metastases to the Spine: Case Reports and Review of the Literature.

BACKGROUND: We report a series of 3 cases of metastatic thymoma to the spine with spinal cord compression. An extensive literature review of thymic metastases to the spine was completed to provide a comprehensive appraisal of current prognostic indicators and potential treatment algorithms to help guide clinicians in treatment management. CASE DESCRIPTIONS: Between 2000 and 2017, 3 patients received diagnoses of thymic metastases to the spine at our institution. Metastasis presentation occurred from 2 to 8 years after the initial diagnosis with thymic cancer. All 3 patients presented with signs and symptoms of spinal cord/cauda equina compression, and underwent surgical intervention. Postoperative treatments varied among all 3 patients, 1 receiving chemotherapy, another undergoing radiation, and the third having had no further treatment because of extensive systemic disease. CONCLUSIONS: Upon review of the literature, 16 case reports/series described 28 total patients with spine metastases secondary to thymoma/thymic carcinoma. The presentations varied widely, including age, neurologic deficits, time from initial diagnosis to metastasis, and histologic grading. The only widely accepted prognostic factor is completeness of tumor resection, whereas clinical staging, histologic type, or both may also have prognostic value. Thus, gross total resection and spinal decompression should be prioritized in cases of surgical intervention. Chemotherapy and radiotherapy are generally recommended. However, given the lack of standardized treatment algorithms, individualized regimens should be formulated on a case-specific basis.

Value in Single-level Lumbar Discectomy: Surgical Disposable Item Cost and Relationship to Patient-reported Outcomes.

STUDY DESIGN: This is a retrospective study. OBJECTIVE: Compare improvements in health status measures (HSMs) and surgical costs to determine whether use of more costly items has any relationship to clinical outcome and value in lumbar disc surgery. SUMMARY OF BACKGROUND DATA: Association between cost, outcomes, and value in spine surgery, including lumbar discectomy is poorly understood. Outcomes were calculated as difference in mean HSM scores between preoperative and postoperative timeframes. Prospective validated patient-reported HSMs studied were EuroQol quality of life index score (EQ-5D), Pain Disability Questionnaire (PDQ), and Patient Health Questionnaire (PHQ-9). Surgical costs consisted of disposable items and implants used in operating room. METHODS: We retrospectively identified all adult patients at Cleveland Clinic main campus between October 2009 and August 2013 who underwent lumbar discectomy (652) using administrative billing data, Current Procedural Terminology (CPT) code 63030. HSMs were obtained from Cleveland Clinic Knowledge Program Data Registry. RESULTS: In total, 67% of operations performed in the outpatient or ambulatory setting, 33% in the inpatient setting. Among 9 surgeons who performed >10 lumbar discectomies, there were 72.4 operations per surgeon, on average. Mean surgical costs of each surgeon differed (P<0.0001). In a multivariable regression, only the surgeon and surgery type (outpatient or inpatient) were statistically correlated with surgical costs (P<0.0001 and 0.046, respectively). Changes in EQ-5D, PDQ, and PHQ-9 were not correlated with surgical costs (P=0.76, 0.07, 0.76, respectively). In multivariable regression, only surgical cost was significantly correlated to mean difference in PDQ (P=0.030). More costly surgeries resulted in worse PDQ outcomes. CONCLUSIONS: Mean surgical costs varied statistically among 9 surgeons; costs were not shown to be positively correlated with patient outcomes. Performing an operation using more costly disposable supplies/implants does not seem to improve patient outcomes and should be considered when constructing preference cards and during an operation.

Quality of life outcomes following cervical decompression for coexisting Parkinson's disease and cervical spondylotic myelopathy.

BACKGROUND CONTEXT: Coexisting Parkinson's disease (PD) and cervical spondylotic myelopathy (CSM) presents a diagnostic and therapeutic challenge due to symptomatic similarities between the diseases. Whereas CSM patients are routinely treated with surgery, PD patients face poorer outcomes following spine surgery. No studies have investigated the quality of life (QOL) outcomes following decompression in coexisting PD and CSM. PURPOSE: The purpose of the present study was to characterize QOL outcomes for patients with coexisting PD and CSM following cervical decompression. STUDY DESIGN/SETTING: This is a matched cohort study at a single tertiary-care center. PATIENT SAMPLE: Patients with coexisting PD and CSM undergoing cervical decompression between June 2009 and December 2014 were included. These patients were matched to controls with CSM alone by age, gender, American Society of Anesthesiologists classification, Modified Japanese Orthopaedic Association scores, and operative parameters. OUTCOME MEASURES: The primary outcome measure was QOL outcomes assessed by change in the EuroQol 5-Dimensions (EQ-5D), Pain Disability Questionnaire (PDQ), and Patient Health Questionnaire-9 (PHQ-9) at last follow-up (LFU). Change in QOL exceeding the minimal clinically important difference (MCID) was secondary. METHODS: QOL data were collected using the institutional prospectively collected database of patient-reported health status measures. Simple and multivariable regressions were used to assess the impact of PD upon change in QOL. RESULTS: Eleven PD patients were matched to 44 controls. Control patients experienced QOL improvement across all three measures, whereas PD patients only improved with respect to PDQ(89.9-80.7, p=.03). Despite no significant differences in preoperative QOL, PD patients experienced poorer QOL at LFU in EQ-5D (0.526 vs. 0.707, p=.01) and PDQ (80.7 vs. 51.4, p=.03), and less frequently achieved an EQ-5D MCID (18% vs. 57%, p=.04). However, no differences in the achievement of an MCID in PDQ or PHQ-9 were observed between cohorts. Multivariable regression identified PD as a significant independent predictor of poorer improvement in EQ-5D (ß=-0.09, p<.01) and failure to achieve an EQ-5D MCID (odds ratio: 0.08, p<.01). CONCLUSIONS: This is the first study to characterize QOL outcomes following cervical decompression for patients with coexisting PD and CSM. Although myelopathy may have been less severe among PD patients, a significant reduction in pain-related disability was observed following decompression. However, PD predicted diminished improvement in overall QOL measured by the EQ-5D.

Molecular and clinical prognostic factors for favorable outcome following surgical resection of adult intramedullary spinal cord astrocytomas.

OBJECTIVE: Intramedullary spinal cord astrocytomas are uncommon but important entities. Aggressive surgical resection is believed to be critical to prevent subsequent neurological deterioration; however, the prognostic significance of numerous patient and molecular variables remains unclear. We sought to investigate the clinical and molecular factors associated with outcomes following surgical resection of adult spinal cord astrocytomas. METHODS: A consecutive retrospective chart review of all patients who underwent intramedullary spinal cord astrocytoma resection at a single tertiary-care institution between January 1996 and December 2011 was conducted. Molecular data collected included p53 mutation status, proliferative activity (Ki-67), 1p/19q chromosome loss, and EGFR amplification. Multivariable logistic and Cox proportional hazards regression were used to identify variable associated with postoperative outcomes. RESULTS: Among 13 patients undergoing surgical resection followed for a median of 54 months, 54% experienced improvement in neurological status, while 15% remained unchanged and 31% deteriorated. Following resection, the 5-year local control (LC), progression-free survival (PFS), and overall survival (OS) rates were 83%, 63%, and 83%. Median PFS time was found to be 5.6 years. Multivariable regression revealed limited characteristics associated with postoperative outcomes, though no molecular characteristics were found to be prognostic. Older age at surgery predicted decreased probability of PFS (HR 0.91, 95% CI 0.81-0.99, p=0.03) and trended towards predicting lack of neurological improvement (OR 0.94, 95% CI 0.83-1.02, p=0.21) and decreased OS (HR 0.93, 95% CI 0.81, 1.03, p=0.15). Preoperative motor symptoms (OR 0.12, 95% CI <0.01-1.91, p=0.14) and adjuvant chemotherapy (OR 0.07, 95% CI <0.01-1.82, p=0.12) also trended towards predicting lack of neurological improvement. CONCLUSION: Age was the only patient variable found to have a statistically significant association with profession-free survival and no other factors were significantly associated with postoperative outcomes. These findings were limited by a relatively small sample size; thus, future studies with increased power investigating the prognostic effects of molecular characteristics could provide further clarity in identifying patients most likely to benefit from surgical resection.

Morphological Transformation of Giant-Cell Tumor of Bone After Treatment with Denosumab: A Case Report.

CASE: Denosumab, an inhibitor of RANKL (receptor activator of nuclear factor κ-B ligand), was recently introduced for the treatment of giant-cell tumor of bone (GCTB). We describe the clinical, radiographic, and histological features of a GCTB of the spine in a 24-year-old woman that progressed after neoadjuvant treatment with denosumab. Disappearance of the multinuclear osteoclastic giant cells was accompanied by newly formed woven bone, which was deposited in interconnected strands with a prominent fibrovascular stroma that was histologically and radiographically similar to that of an osteoblastoma. CONCLUSION: Pathologists, radiologists, and surgeons should be aware of this post-treatment transformation to avoid misdiagnosis.

Prediction of quality of life improvements in patients with lumbar stenosis following use of membrane stabilizing agents.

OBJECTIVE: Membrane stabilizing agents (MSAs) improves function and reduces neuropathic pain in a subset of patients with LSS. No study has investigated the pre-treatment demographic and psychosocial factors associated with quality of life (QOL) outcomes following the use of MSAs. In this study we sought to create prediction models for post-treatment outcome. METHODS: All patients who were diagnosed with LSS and treated with MSAs at a single institution between September 2010 and March 2013 were retrospectively reviewed. QOL outcomes were collected prospectively. Prediction tools were created using multivariable logistic regression and Cox proportional hazard models. Outcome measures were: 1 - need for surgery within 1 year after initiating MSA treatment, 2 - time until surgery after initiating MSA treatment, 3 - any improvement in EuroQol (EQ)-5D QOL index, 4 - improvement in EQ-5D index exceeding the minimum clinically important difference (MCID). RESULTS: 1346 patients were included. For goal 1 (need for surgery), the prediction model was less robust. For goal 2 (time to surgery), only age was a significant predictor, with each 10-year increase in age causing the hazard of eventually having surgery to increase by 20%. 382 patients were available for analysis for goals 3 and 4 (predicting improvement in EQ-5D). Prediction models for these goals were good with C-statistics 0.73 and 0.85, respectively. Predictive factors for superior outcomes included lower baseline EQ-5D index (worse QOL), less baseline depression, greater median income, and being married. CONCLUSION: MSA treatment provides improvements in quality of life for those individuals with LSS. Treatment effects of MSAs will be greatest in those with worse quality of life, less depression, married patients, and those of higher socio-economic status.

Spinal sealant system provides better intraoperative watertight closure than standard of care during spinal surgery: a prospective, multicenter, randomized controlled study.

STUDY DESIGN: Prospective, 3:1 randomized, single-blind, multicenter investigational study. OBJECTIVE: To assess the safety and efficacy of a low-swell spinal sealant when used as an adjunct to sutured dural repair compared with standard of care methods to obtain watertight dural closure in subjects undergoing spinal surgery. SUMMARY OF BACKGROUND DATA: Watertight dural closure is paramount in spinal surgery to avoid complications of cerebrospinal fluid leak. Prior reports have proven the efficacy of a synthetic, absorbable polyethylene glycol (PEG) hydrogel sealant in spinal surgery compared with standard of care. Given the potential concerns of swelling in spinal applications, the hydrogel was modified to a low-swell formulation. METHODS: The primary endpoint was success rate in obtaining intraoperative watertight dural closure in subjects receiving PEG hydrogel sealant versus a control group of subjects receiving any standard method designed to provide intraoperative watertight closure. Subjects were evaluated at discharge and at 30 and 90 days postprocedure for cerebrospinal fluid leaks, surgical site infections, and adverse events. RESULTS: Between May 2007 and May 2009, 98 subjects (74 PEG hydrogel spinal sealant, 24 control) were randomized at 14 clinical sites in the United States. Patients treated with the PEG hydrogel spinal sealant had a significantly higher rate of watertight closure than the control (98.6% vs. 79.2%, P = 0.003). No statistical differences were seen in postoperative cerebrospinal fluid, infection, and wound healing. No neurological deficits were seen attributable to the sealant. CONCLUSION: The low-swell PEG hydrogel spinal sealant evaluated in this study has been proven safe and effective for providing watertight closure when used as an adjunct to sutured closure of intentional durotomies during spinal surgery. PEG hydrogel sealants have again proved superior to other standard of care technologies for safe, efficacious dural closure. LEVEL OF EVIDENCE: 2.