Faculty Bibliography

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/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.

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 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.

STUDY DESIGN/METHODS:An electronic survey administered to Scoliosis Research Society membership. OBJECTIVE:To characterize surgeon views regarding proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) management providing the framework in which a PJK/PJF classification system and treatment guidelines could be established. SUMMARY OF BACKGROUND DATA/BACKGROUND:PJK/PJF are common complications of adult spinal deformity surgery. To date, there is no consensus on PJK/PJF definitions, classification, and indications for revision surgery. There is a paucity of data on deformity surgeon practice pattern variations and consensus opinion on treatment and prevention. METHODS:An electronic 19-question survey regarding PJK/PJF was administered to members of the Scoliosis Research Society who treat adult spinal deformity. Determinants included the surgeons' type of practice, number of years in practice, agreement with given PJK/PJF definitions, importance of key factors influencing prevention and revision, prevention methods currently used, and the importance of developing a classification system. RESULTS:A total of 226 surgeons responded (38.8% response rate). Both 44.4% of surgeons selected "extremely important" and 40.8% selected "very important" that PJK in adult spinal deformity surgery is a very important issue and that a Scoliosis Research Society PJK/PJF classification system and guidelines for detection and prevention of PJK/PJF is a "must have" (18.1%) and "very likely helpful" (31.9%). Both 86.2% and 90.7% of surgeons agreed with the provided definitions of PJK and PJF, respectively. Top 5 revision indications included neurological deficit, severe focal pain, translation or subluxation fracture, a change in kyphosis angle of greater than 30°, chance fracture, spondylolisthesis greater than 6 mm, and instrumentation prominence. The majority of respondents use a PJK/PJF prevention strategy 60% of the time or more, the most common were terminal rod contour, preoperative bone mineral density testing, and frequent radiographical studies during first 3 months postoperative, preoperative bone mineral density medication for low bone mineral density. CONCLUSION/CONCLUSIONS:The results of this study provide insight from the practicing surgeons' perspective of the management of PJK and PJF that may aid in the validation of current definitions and consensus-based treatment decisions and prevention guidelines. LEVEL OF EVIDENCE/METHODS:5.

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.

OBJECT Resection is an appealing therapy for brain arteriovenous malformations (AVMs) because of its high cure rate, low complication rate, and immediacy, and has become the first-line therapy for many AVMs. To clarify safety, efficacy, and outcomes associated with AVM resection in the aftermath of A Randomized Trial of Unruptured Brain AVMs (ARUBA), the authors reviewed their experience with low-grade AVMs-the most favorable AVMs for surgery and the ones most likely to have been selected for treatment outside of ARUBA's randomization process. METHODS A prospective AVM registry was searched to identify patients with Spetzler-Martin Grade I and II AVMs treated using resection during a 16-year period. RESULTS Of the 232 surgical patients included, 120 (52%) presented with hemorrhage, 33% had Spetzler-Martin Grade I, and 67% had Grade II AVMs. Overall, 99 patients (43%) underwent preoperative embolization, with unruptured AVMs embolized more often than ruptured AVMs. AVM resection was accomplished in all patients and confirmed angiographically in 218 patients (94%). There were no deaths among patients with unruptured AVMs. Good outcomes (modified Rankin Scale [mRS] score 0-1) were found in 78% of patients, with 97% improved or unchanged from their preoperative mRS scores. Patients with unruptured AVMs had better functional outcomes (91% good outcome vs 65% in the ruptured group, p = 0.0008), while relative outcomes were equivalent (98% improved/unchanged in patients with ruptured AVMs vs 96% in patients with unruptured AVMs). CONCLUSIONS Surgery should be regarded as the "gold standard" therapy for the majority of low-grade AVMs, utilizing conservative embolization as a preoperative adjunct. High surgical cure rates and excellent functional outcomes in patients with both ruptured and unruptured AVMs support a dominant surgical posture for low-grade AVMS, with radiosurgery reserved for risky AVMs in deep, inaccessible, and highly eloquent locations. Despite the technological advances in endovascular and radiosurgical therapy, surgery still offers the best cure rate, lowest risk profile, and greatest protection against hemorrhage for low-grade AVMs. ARUBA results are influenced by a low randomization rate, bias toward nonsurgical therapies, a shortage of surgical expertise, a lower rate of complete AVM obliteration, a higher rate of delayed hemorrhage, and short study duration. Another randomized trial is needed to reestablish the role of surgery in unruptured AVM management.

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.

STUDY DESIGN/METHODS:Systematic review of literature. OBJECTIVE:To perform a comprehensive English language systematic literature review of proximal junctional kyphosis (PJK) and proximal junctional failure (PJF), concentrating on incidence, risk factors, health related quality of life impact, prevention strategy, and classification systems. SUMMARY OF BACKGROUND DATA/BACKGROUND:PJK and PJF are well described clinical pathologies and are a frequent cause of revision surgery. The development of a PJK classification that correlates with clinical outcomes and guides treatment decisions and possible prevention strategies would be of significant benefit to patients and surgeons. METHODS:The phrases "proximal junctional," "proximal junctional kyphosis," and "proximal junctional failure" were used as search terms in PubMed for all years up to 2014 to identify all articles that included at least one of these terms. RESULTS:Fifty-three articles were identified overall. Eighteen articles assessed for risk factors. Eight studies specifically reviewed prevention strategies. There were no randomized prospective studies. There were 3 published studies that have attempted to classify PJK. The reported incidence of PJK ranged widely, from 5% to 46% in patients undergoing spinal instrumentation and fusion for adult spinal deformity. It is reported that 66% of PJK occurs within 3 months and 80% within 18 months after surgery. The reported revision rates due to PJK range from 13% to 55%. Modifiable and nonmodifiable risk factors for PJK have been characterized. CONCLUSION/CONCLUSIONS:PJK and PJF affect many patients after long segment instrumentation after the correction of adult spinal deformity. The epidemiology and risk factors for the disease are well defined. A PJK and PJF scoring system may help describe the severity of disease and guide the need for revision surgery. The development and prospective validation of a PJK classification system is important considering the prevalence of the problem and its clinical and economic impact. LEVEL OF EVIDENCE/METHODS:N/A.

OBJECT/OBJECTIVE:Glioblastoma is the most aggressive and diffusely infiltrative primary brain tumor. Recurrence is expected and is extremely difficult to treat. Over the past decade, the accumulation of knowledge regarding the molecular and genetic profile of glioblastoma has led to numerous molecularly targeted therapies. This article aims to review the literature and highlight the mechanisms and efficacies of molecularly targeted therapies for recurrent glioblastoma. METHODS:A systematic search was performed with the phrase "(name of particular agent) and glioblastoma" as a search term in PubMed to identify all articles published up until 2014 that included this phrase in the title and/or abstract. The references of systematic reviews were also reviewed for additional sources. The review included clinical studies that comprised at least 20 patients and reported results for the treatment of recurrent glioblastoma with molecular targeted therapies. RESULTS:A total of 42 articles were included in this review. In the treatment of recurrent glioblastoma, various targeted therapies have been tested over the past 10-15 years. The targets of interest include epidermal growth factor receptor, vascular endothelial growth factor receptor, platelet-derived growth factor receptor, Ras pathway, protein kinase C, mammalian target of rapamycin, histone acetylation, and integrins. Unfortunately, the clinical responses to most available targeted therapies are modest at best. Radiographic responses generally range in the realm of 5%-20%. Progression-free survival at 6 months and overall survival were also modest with the majority of studies reporting a 10%-20% 6-month progression-free survival and 5- to 8-month overall survival. There have been several clinical trials evaluating the use of combination therapy for molecularly targeted treatments. In general, the outcomes for combination therapy tend to be superior to single-agent therapy, regardless of the specific agent studied. CONCLUSIONS:Recurrent glioblastoma remains very difficult to treat, even with molecular targeted therapies and anticancer agents. The currently available targeted therapy regimens have poor to modest activity against recurrent glioblastoma. As newer agents are actively being developed, combination regimens have provided the most promising results for improving outcomes. Targeted therapies matched to molecular profiles of individual tumors are predicted to be a critical component necessary for improving efficacy in future trials.