Faculty Bibliography

OBJECT There is evidence that 5-aminolevulinic acid (ALA) facilitates greater extent of resection and improves 6-month progression-free survival in patients with high-grade gliomas. But there remains a paucity of studies that have examined whether the intensity of ALA fluorescence correlates with tumor cellularity. Therefore, a Phase II clinical trial was undertaken to examine the correlation of intensity of ALA fluorescence with the degree of tumor cellularity. METHODS A single-center, prospective, single-arm, open-label Phase II clinical trial of ALA fluorescence-guided resection of high-grade gliomas (Grade III and IV) was held over a 43-month period (August 2010 to February 2014). ALA was administered at a dose of 20 mg/kg body weight. Intraoperative biopsies from resection cavities were collected. The biopsies were graded on a 4-point scale (0 to 3) based on ALA fluorescence intensity by the surgeon and independently based on tumor cellularity by a neuropathologist. The primary outcome of interest was the correlation of ALA fluorescence intensity to tumor cellularity. The secondary outcome of interest was ALA adverse events. Sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), and Spearman correlation coefficients were calculated. RESULTS A total of 211 biopsies from 59 patients were included. Mean age was 53.3 years and 59.5% were male. The majority of biopsies were glioblastoma (GBM) (79.7%). Slightly more than half (52.5%) of all tumors were recurrent. ALA intensity of 3 correlated with presence of tumor 97.4% (PPV) of the time. However, absence of ALA fluorescence (intensity 0) correlated with the absence of tumor only 37.7% (NPV) of the time. For all tumor types, GBM, Grade III gliomas, and recurrent tumors, ALA intensity 3 correlated strongly with cellularity Grade 3; Spearman correlation coefficients (r) were 0.65, 0.66, 0.65, and 0.62, respectively. The specificity and PPV of ALA intensity 3 correlating with cellularity Grade 3 ranged from 95% to 100% and 86% to 100%, respectively. In biopsies without tumor (cellularity Grade 0), 35.4% still demonstrated ALA fluorescence. Of those biopsies, 90.9% contained abnormal brain tissue, characterized by reactive astrocytes, scattered atypical cells, or inflammation, and 8.1% had normal brain. In nonfluorescent (ALA intensity 0) biopsies, 62.3% had tumor cells present. The ALA-associated complication rate among the study cohort was 3.4%. CONCLUSIONS The PPV of utilizing the most robust ALA fluorescence intensity (lava-like orange) as a predictor of tumor presence is high. However, the NPV of utilizing the absence of fluorescence as an indicator of no tumor is poor. ALA intensity is a strong predictor for degree of tumor cellularity for the most fluorescent areas but less so for lower ALA intensities. Even in the absence of tumor cells, reactive changes may lead to ALA fluorescence.

OBJECTIVE Because the surgical strategies for primary and metastatic spinal tumors are different, the respective associated costs and morbidities associated with those treatments likely vary. This study compares the direct costs and 90-day readmission rates between the resection of extradural metastatic and primary spinal tumors. The factors associated with cost and readmission are identified. METHODS Adults (age 18 years or older) who underwent the resection of spinal tumors between 2008 and 2013 were included in the study. Patients with intradural tumors were excluded. The direct costs of index hospitalization and 90-day readmission hospitalization were evaluated. The direct costs were compared between patients who were treated surgically for primary and metastatic spinal tumors. The independent factors associated with costs and readmissions were identified using multivariate analysis. RESULTS A total of 181 patients with spinal tumors were included (63 primary and 118 metastatic tumors). Overall, the mean index hospital admission cost for the surgical management of spinal tumors was $52,083. There was no significant difference in the cost of hospitalization between primary ($55,801) and metastatic ($50,098) tumors (p = 0.426). The independent factors associated with higher cost were male sex (p = 0.032), preoperative inability to ambulate (p = 0.002), having more than 3 comorbidities (p = 0.037), undergoing corpectomy (p = 0.021), instrumentation greater than 7 levels (p < 0.001), combined anterior-posterior approach (p < 0.001), presence of a perioperative complication (p < 0.001), and longer hospital stay (p < 0.001). The perioperative complication rate was 21.0%. Of this cohort, 11.6% of patients were readmitted within 90 days, and the mean hospitalization cost of that readmission was $20,078. Readmission rates after surgical treatment for primary and metastatic tumors were similar (11.1% vs 11.9%, respectively) (p = 0.880). Prior hospital stay greater than 15 days (OR 6.62, p = 0.016) and diagnosis of lung metastasis (OR 52.99, p = 0.007) were independent predictors of readmission. CONCLUSIONS Primary and metastatic spinal tumors are comparable with regard to the direct costs of the index surgical hospitalization and readmission rate within 90 days. The factors independently associated with costs are related to preoperative health status, type and complexity of surgery, and postoperative course.

STUDY DESIGN/METHODS:Retrospective cohort analysis. OBJECTIVE:To evaluate the economic impact of revision surgery for proximal junctional failures (PJF) after thoracolumbar fusions for adult spinal deformity (ASD). SUMMARY OF BACKGROUND DATA/BACKGROUND:PJF after fusions for ASD is a major cause of disability. Although clinical sequelae are described, PJF-revision operation costs are incompletely defined. METHODS:Consecutive adults who underwent thoracolumbar fusions for ASD (August, 2003 to January, 2013) were evaluated. Inclusion criteria include construct from pelvis to L2 or above and minimum 6 months follow-up after the index ASD operation. Direct costs (surgical supplies/implants, room/care, pharmacy, services) were identified from medical billing data and calculated for index ASD operations and subsequent surgeries for PJF. Not included in direct cost data were indirect costs, charges, surgeon fees, or revision operations for indications other than PJF (i.e., pseudarthrosis). Patients were compared based on the construct's upper-instrumented vertebra: upper thoracic (UT: T1-6) versus thoracolumbar junction (TLjxn: T9-L2). RESULTS:Of 501 patients, 382 met inclusion criteria. Fifty-one patients [UT:14; TLjxn: 40 at index; average follow-up 32.6 months (6-92 months)] had revisions for PJF, which summed to $3.2 million total direct cost. Average direct cost of index operations for the cohort ($68,294) was significantly greater than PJF-revisions ($55,547). Compared with TLjxn, UT had a significantly higher average cost for index operations ($79,860 vs. $65,868). However, PJF-revision cases were similar in average cost (UT:$60,103; TLjxn:$53,920; P = 0.09). Costs of PJF amounted to an additional 12.1% of the total index surgical cost in 382 patients. CONCLUSION/CONCLUSIONS:Revision operations for PJF after long thoracolumbar fusions for ASD are associated with an average direct cost of $55,547 per case. Revision costs for PJF are similar based on the index procedure's upper-instrumented vertebra level. At a major tertiary center over a 10-year period, PJF came at a very significant economic expense amounting to $3.2 million for 57 cases. LEVEL OF EVIDENCE/METHODS:3.

STUDY DESIGN: Retrospective analysis of prospective data. OBJECTIVE: Evaluate the utility of the Hart-International Spine Study Group proximal junctional kyphosis severity scale (Hart-ISSG PJKSS). SUMMARY OF BACKGROUND DATA: Proximal junctional kyphosis (PJK) and failure (PJF) are well-described complications after long-segment instrumentation. The Hart-ISSG PJKSS was recently developed and incorporates neurological deficit, pain, instrumentation issues, degree of kyphosis, presence of fracture, and level of upper-most instrumented vertebrae. METHODS: All adult spinal deformity patients with PJK or PJF were identified from two academic centers over a 7-year period. Health-related quality-of-life (HRQOL) outcomes were prospectively collected: Oswestry Disability Index (ODI), visual analogue scale (VAS) pain, SF-36 questionnaire, and SRS-30 questionnaire. Patients were retrospectively assigned Hart-ISSG PJKSS scores. Correlation between the Hart-ISSG PJKSS and outcomes was assessed with linear regression, Pearson correlation coefficients, and chi analysis. RESULTS: A total of 184 cases were included; 21.2% were men and mean age was 65.0 years. Weakness and/or myelopathy were present in 11.4% of patients and 88.6% had pain. Instrumentation issues occurred in 44.0% and 64.1% had PJK-associated fractures. PJK occurred in the upper thoracic spine in 21.7% of cases. Mean PJKSS score was 5.9. The Hart-ISSG PJKSS was significantly and strongly associated with ODI (P < 0.001, r = 0.611), VAS pain (P < 0.001, r = 0.676), SRS-30 function (P < 0.001, r = -0.401), SRS-30 mental health (P < 0.001, r = -0.592), SRS-30 self-image (P < 0.001, r = -0.511), SRS-30 satisfaction (P < 0.001, r = -0.531), and SRS-30 pain (P < 0.001, r = -0.445). Higher scores were associated with higher proportion of patients undergoing revision surgery (P < 0.001); scores of 9 to 11 and 12 to 15 underwent revision 96.0% and 100.0% of the time, respectively. CONCLUSION: The Hart-ISSG PJKSS was strongly correlated with validated functional outcomes and higher scores were associated with higher rates of revision surgery. The Hart-ISSG PJKSS may be a useful clinical tool in the treatment of patient with PJK. LEVEL OF EVIDENCE: 3.

OBJECT/OBJECTIVE:Awake craniotomy is currently a useful surgical approach to help identify and preserve functional areas during cortical and subcortical tumor resections. Methodologies have evolved over time to maximize patient safety and minimize morbidity using this technique. The goal of this study is to analyze a single surgeon's experience and the evolving methodology of awake language and sensorimotor mapping for glioma surgery. METHODS:The authors retrospectively studied patients undergoing awake brain tumor surgery between 1986 and 2014. Operations for the initial 248 patients (1986-1997) were completed at the University of Washington, and the subsequent surgeries in 611 patients (1997-2014) were completed at the University of California, San Francisco. Perioperative risk factors and complications were assessed using the latter 611 cases. RESULTS:The median patient age was 42 years (range 13-84 years). Sixty percent of patients had Karnofsky Performance Status (KPS) scores of 90-100, and 40% had KPS scores less than 80. Fifty-five percent of patients underwent surgery for high-grade gliomas, 42% for low-grade gliomas, 1% for metastatic lesions, and 2% for other lesions (cortical dysplasia, encephalitis, necrosis, abscess, and hemangioma). The majority of patients were in American Society of Anesthesiologists (ASA) Class 1 or 2 (mild systemic disease); however, patients with severe systemic disease were not excluded from awake brain tumor surgery and represented 15% of study participants. Laryngeal mask airway was used in 8 patients (1%) and was most commonly used for large vascular tumors with more than 2 cm of mass effect. The most common sedation regimen was propofol plus remifentanil (54%); however, 42% of patients required an adjustment to the initial sedation regimen before skin incision due to patient intolerance. Mannitol was used in 54% of cases. Twelve percent of patients were active smokers at the time of surgery, which did not impact completion of the intraoperative mapping procedure. Stimulation-induced seizures occurred in 3% of patients and were rapidly terminated with ice-cold Ringer's solution. Preoperative seizure history and tumor location were associated with an increased incidence of stimulation-induced seizures. Mapping was aborted in 3 cases (0.5%) due to intraoperative seizures (2 cases) and patient emotional intolerance (1 case). The overall perioperative complication rate was 10%. CONCLUSIONS:Based on the current best practice described here and developed from multiple regimens used over a 27-year period, it is concluded that awake brain tumor surgery can be safely performed with extremely low complication and failure rates regardless of ASA classification; body mass index; smoking status; psychiatric or emotional history; seizure frequency and duration; and tumor site, size, and pathology.

OBJECT Cushing's disease (CD) can lead to significant morbidity secondary to hormonal sequelae or mass effect from the pituitary tumor. A transsphenoidal approach to resection of the adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma is the first-line treatment. However, in the setting in which patients are unable to undergo surgery, have acute hypercortisolism, or have recurrent disease, medical therapy can play an important role. The authors performed a systematic review to highlight the efficacy of medical treatment of CD and discuss novel molecular insights that could guide the development of future medical treatments of CD. METHODS A search on current medical therapies for CD was performed. After individual medical therapeutic agents for CD were identified, each agent underwent a formal systematic search. The phrase "(name of agent) and Cushing's" was used as a search term in PubMed for all years up to 2014. The abstract of each article was reviewed for studies that evaluated the efficacy of medical treatment of CD. Only studies that enrolled at least 20 patients were included in the review. RESULTS A total of 11 articles on 6 individual agents were included in this review. Specific medical therapies were categorized based on the level of action: pituitary directed (cabergoline and pasireotide), adrenal/steroidogenesis directed (ketoconazole, metyrapone, and mitotane), and end-tissue directed/cortisol receptors (mifepristone). The studies identified consisted of a mix of retrospective reviews and small clinical trials. Only pasireotide and mifepristone have undergone Phase III clinical trials, from which they garnered FDA approval for the treatment of patients with CD. Overall, agents targeting ACTH secretion and steroidogenesis were found to be quite effective in reducing urine free cortisol (UFC) to levels near normal. A significant reduction in UFC was observed in 45%-100% of patients and a majority of patients gained clinical improvement. Similarly, inhibition at the end-tissue level led to clinical improvement in 87% of patients. However, side-effect rates associated with these drugs are high (up to 88%). Ketoconazole has been shown to enhance tumor appearance on MRI to facilitate pituitary resection. Promising molecular targets have been identified, including epidermal growth factor receptor, retinoic acid receptors, and cyclin dependent kinases. These pathways have been linked to the regulation of pro-opiomelanocortin expression, ACTH secretion, and tumor growth. CONCLUSIONS Despite encouraging Phase III clinical trials leading to FDA approval of 2 agents for treatment of patients with CD, no agent has yet produced results comparable to resection. As a result, the molecular insights gained into CD pathogenesis will need to continue to be expanded until they can lead to the development of medical therapies for CD with a favorable side-effect profile and efficacy comparable to resection. Ideally these agents should also reduce tumor size, which could potentially permit their eventual discontinuation.

OBJECT/OBJECTIVE:In the treatment of cervical spondylotic myelopathy (CSM), anterior cervical corpectomy and fusion (ACCF) and anterior cervical discectomy and fusion (ACDF) are effective decompressive techniques. It remains to be determined whether ACCF and ACDF offer equivalent outcomes for multilevel CSM. In this study, the authors compared perioperative, radiographic, and clinical outcomes between 2-level ACCF and 3-level ACDF. METHODS:Between 2006 and 2012, all patients at the authors' hospital who underwent 2-level ACCF or 3-level ACDF performed by 1 of 2 surgeons were identified. Primary outcomes of interest were sagittal Cobb angle, adjacent-segment disease (ASD) requiring surgery, neck pain measured by visual analog scale (VAS), and Nurick score. Secondary outcomes of interest included estimated blood loss (EBL), length of stay, perioperative complications, and radiographic pseudarthrosis rate. Chi-square tests and 2-tailed Student t-tests were used to compare the 2 groups. A subgroup analysis of patients without posterior spinal fusion (PSF) was also performed. RESULTS:Twenty patients underwent 2-level ACCF, and 35 patients underwent 3-level ACDF during a 6-year period. Preoperative Nurick scores were higher in the ACCF group (2.1 vs 1.1, p = 0.014), and more patients underwent PSF in the 2-level ACCF group compared with patients in the 3-level ACDF group (60.0% vs 17.1%, p = 0.001). Otherwise there were no significant differences in demographics, comorbidities, and baseline clinical parameters between the 2 groups. Two-level ACCF was associated with significantly higher EBL compared with 3-level ACDF for the anterior stage of surgery (382.2 ml vs 117.9 ml, p < 0.001). Two-level ACCF was also associated with a longer hospital stay compared with 3-level ACDF (7.2 days vs 4.9 days, p = 0.048), but a subgroup comparison of patients without PSF showed no significant difference in length of stay (3.1 days vs 4.4 days for 2-level ACCF vs 3-level ACDF, respectively; p = 0.267). Similarly, there was a trend toward more complications in the 2-level ACCF group (20.0%) than the 3-level ACDF group (5.7%; p = 0.102), but a subgroup analysis that excluded those who had second-stage PSF no longer showed the same trend (2-level ACCF, 0.0% vs 3-level ACDF, 3.4%; p = 0.594). There were no significant differences between the ACCF group and the ACDF group in terms of postoperative sagittal Cobb angle (7.2° vs 12.1°, p = 0.173), operative ASD (6.3% vs 3.6%, p = 0.682), and radiographic pseudarthrosis rate (6.3% vs 7.1%, p = 0.909). Both groups had similar improvement in mean VAS neck pain scores (3.4 vs 3.2 for ACCF vs ACDF, respectively; p = 0.860) and Nurick scores (0.8 vs 0.7, p = 0.925). CONCLUSIONS:Two-level ACCF was associated with greater EBL and longer hospital stays when patients underwent a second-stage PSF. However, the length of stay was similar when patients underwent anterior-only decompression with either 2-level ACCF or 3-level ACDF. Furthermore, perioperative complication rates were similar in the 2 groups when patients underwent anterior decompression without PSF. Both groups obtained similar postoperative cervical lordosis, operative ASD rates, radiographic pseudarthrosis rates, neurological improvement, and pain relief.

OBJECT Spinal metastases most commonly affect the vertebral bodies of the spinal column, and spinal cord compression is an indication for surgery. Commonly, an open posterior approach is employed to perform a transpedicular costotransversectomy or lateral extracavitary corpectomy. Because of the short life expectancies in patients with metastatic spinal disease, decreasing the morbidity of surgical treatment and recovery time is critical. One potential approach to decreasing morbidity is utilizing minimally invasive surgery (MIS). Although significant advances have been made in MIS of the spine, data supporting the utility of MIS are still emerging. This study compared outcomes of patients who underwent mini-open versus traditional open transpedicular corpectomy for spinal metastases in the thoracic spine. METHODS A consecutive cohort from 2006 to 2013 of 49 adult patients who underwent thoracic transpedicular corpectomies for spinal metastases was retrospectively identified. Patients were categorized into one of 2 groups: open surgery and mini-open surgery. Mini-open transpedicular corpectomy was performed with a midline facial incision over only the corpectomy level of interest and percutaneous instrumentation above and below that level. The open procedure consisted of a traditional posterior transpedicular corpectomy. Chi-square test, 2-tailed t-test, and ANOVA models were employed to compare perioperative and follow-up outcomes between the 2 groups. RESULTS In the analysis, there were 21 patients who had mini-open surgery and 28 patients who had open surgery. The mean age was 57.9 years, and 59.2% were male. The tumor types encountered were lung (18.3%), renal/bladder (16.3%), breast (14.3%), hematological (14.3%), gastrointestinal tract (10.2%), prostate (8.2%), melanoma (4.1%), and other/unknown (14.3%). There were no significant intergroup differences in demographics, comorbidities, neurological status (American Spinal Injury Association [ASIA] grade), number of corpectomies performed, and number of levels instrumented. The open group had a mean operative time of 413.6 minutes, and the mini-open group had a mean operative time of 452.4 minutes (p = 0.329). Compared with the open group, the mini-open group had significantly less blood loss (917.7 ml vs. 1697.3 ml, p = 0.019) and a significantly shorter hospital stay (7.4 days vs. 11.4 days, p = 0.001). There was a trend toward a lower perioperative complication rate in the mini-open group (9.5%) compared with the open group (21.4%), but this was not statistically significant (p = 0.265). At follow-up, there were no significant differences in ASIA grade (p = 0.342), complication rate after the 30-day postoperative period (p = 0.999), or need for surgical revision (p = 0.803). The open approach had a higher overall infection rate of 17.9% compared with that in the mini-open approach of 9.5%, but this was not statistically significant (p = 0.409). CONCLUSIONS The mini-open transpedicular corpectomy is associated with less blood loss and shorter hospital stay compared with open transpedicular corpectomy. The mini-open corpectomy also trended toward lower infection and complication rates, but these did not reach statistical significance.

OBJECT/OBJECTIVE:Cervical kyphosis can lead to spinal instability, spinal cord injury, and disability. The correction of cervical kyphosis is technically challenging, especially in severe cases. The authors describe the anterior sequential interbody dilation technique for the treatment of cervical kyphosis and evaluate perioperative outcomes, degree of correction, and long-term follow-up outcomes associated with the technique. METHODS:In the period from 2006 to 2011, a consecutive cohort of adults with cervical kyphosis (Cobb angles ≥ 0°) underwent sequential interbody dilation, a technique entailing incrementally increased interbody distraction with the sequential placement of larger spacers (at least 1 mm) in the discectomy and/or corpectomy spaces. The authors retrospectively reviewed these patients, and primary outcomes of interest included kyphosis correction, blood loss, hospital stay, complications, Nurick grade, pain, reoperation, and pseudarthrosis. A subgroup analysis among patients with preoperative kyphosis of 0°-9° (mild), 10°-19° (moderate), and ≥ 20° (severe) was performed. RESULTS:One hundred patients were included in the study: 74 with mild preoperative cervical kyphosis, 19 with moderate, and 7 with severe. The mean patient age was 53.1 years, and 54.0% of the patients were male. Mean estimated blood loss was 305.6 ml, and the mean length of hospital stay was 5.2 days. The overall complication rate was 9.0%, and there were no deaths. Sixteen percent of patients underwent supplemental posterior fusion. There was significant correction in cervical alignment (p < 0.001), and the mean overall kyphosis correction was 12.4°. Patients with severe preoperative kyphosis gained a correction of 24.7°, those with moderate kyphosis gained 17.8°, and those with mild kyphosis gained 10.1°. A mean correction of 32.0° was obtained if 5 levels were addressed. The mean follow-up was 26.8 months. The reoperation rate was 4.7%. At follow-up, there was significant improvement in visual analog scale neck pain (p = 0.020) and Nurick grade (p = 0.037). The pseudarthrosis rate was 6.3%. CONCLUSIONS:Sequential interbody dilation is a feasible and effective method of correcting cervical kyphosis. Complications and reoperation rates are low. Similar benefits are seen among all severities of kyphosis, and greater correction can be achieved in more severe cases.

INTRODUCTION/BACKGROUND:Cranial defects following the removal of tumor involved bone require repair and reconstruction for brain protection and cosmesis. A variety of autologous bone substrates and synthetic materials can be employed, alone or in combination. In this article, we describe the use of dual thin and thick titanium mesh, connected together using plate hardware, to repair a right frontotemporal sphenoidal bone defect following resection of a hyperostosing sphenoid wing meningioma. METHODS:Reconstruction of the pterion was done with a dual mesh cranioplasty. After replacement of the native orbitozygomatic and frontotemporal bone pieces, a piece of thinner mesh was molded to the pterional defect connecting the two bone pieces and re-creating the concave shape of the pterion below the superior temporal line. The circular area of the bony defect overlying the frontal and temporal lobes was supplemented by cutting and molding an additional piece of thicker mesh which was secured to the thinner mesh with burr hole cover sectors using rescue screws. RESULTS:A 30-year-old woman presented with painless proptosis and was found to have a hyperostosing right sphenoid wing meningioma. The patient underwent a frontotemporal orbitozygomatic craniotomy for tumor resection and extensive bony osteotomy. Repair and reconstruction of the cranial defect in the region were accomplished at the time of open operation using two thicknesses of mesh connected one to another with titanium plate pieces and rescue screws. The patient underwent gross total resection of the meningioma and near total resection of the soft tissue and bony components (Simpson Grade II). The external cosmetic results following the orbital-cranial reconstruction with the dual mesh technique was deemed "very good" by the surgeon and patient. Postoperative CT imaging demonstrated symmetric re-approximation of the shape of the pterion as compared to the opposite side. CONCLUSIONS:We present a method for connecting two titanium mesh sheets with available hardware to improve the strength in compression while maintaining the ability to mold thinner sheets as necessary for the best cosmetic results. This method is an option for coverage of bony defects in the region of the pterion for young, physically active patients providing them with additional mesh cranioplasty strength.