Faculty Bibliography

OBJECT/OBJECTIVE:Vascular endothelial growth factor (VEGF) is the major proangiogenic factor in many solid tumors. Vascular endothelial growth factor receptor (VEGFR) is expressed in abundance in pediatric patients with medulloblastoma and is associated with tumor metastasis, poor prognosis, and proliferation. Gadolinium enhancement on MRI has been suggested to have prognostic significance for some tumors. The association of VEGF/VEGFR and Gd enhancement in medulloblastoma has never been closely examined. The authors therefore sought to evaluate whether Gd-enhancing medulloblastomas have higher levels of VEGFR and CD31. Outcomes and survival in patients with enhancing and nonenhancing tumors were also compared. METHODS:A retrospective analysis of patients with enhancing, nonenhancing, and partially enhancing medulloblastomas was performed. Primary end points included risk stratification, extent of resection, and perioperative complications. A cohort of 3 enhancing and 3 nonenhancing tumors was selected for VEGFR and CD31 analysis as well as microvessel density measurements. RESULTS:Fifty-eight patients were analyzed, and 20.7% of the medulloblastomas in these patients were nonenhancing. Enhancing medulloblastomas exhibited strong VEGFR1/2 and CD31 expression relative to nonenhancing tumors. There was no significant difference in perioperative complications or patient survival between the 2 groups. CONCLUSIONS:These results suggest that in patients with medulloblastoma the presence of enhancement on MRI may correlate with increased vascularity and angiogenesis, but does not correlate with worse patient prognosis in the short or long term.

Study Design Systematic review. Clinical Questions Compared with no stimulation, does electrical stimulation promote bone fusion after lumbar spinal fusion procedures? Does the effect differ based on the type of electrical stimulation used? Methods Electronic databases and reference lists of key articles were searched up to October 15, 2013, to identify randomized controlled trials (RCTs) comparing the effect of electrical stimulation to no electrical stimulation on fusion rates after lumbar spinal fusion for the treatment of degenerative disease. Two independent reviewers assessed the strength of evidence using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) criteria. Results Six RCTs met the inclusion criteria. The following types of electrical stimulation were investigated: direct current (three studies), pulsed electromagnetic field (three studies), and capacitive coupling (one study). The control groups consisted of no stimulation (two studies) or placebo (four studies). Marked heterogeneity in study populations, characteristics, and design prevented a meta-analysis. Regardless of the type of electrical stimulation used, cumulative incidences of fusion varied widely across the RCTs, ranging from 35.4 to 90.6% in the intervention groups and from 33.3 to 81.9% in the control groups across 9 to 24 months of follow-up. Similarly, when stratified by the type of electrical stimulation used, fusion outcomes from individual studies varied, leading to inconsistent and conflicting results. Conclusion Given the inconsistency in study results, possibly due to heterogeneity in study populations/characteristics and quality, we are unable to conclude that electrical stimulation results in better fusion outcomes compared with no stimulation. The overall strength of evidence for the conclusions is low.

OBJECT/OBJECTIVE:The most common indications for circumferential cervical decompression and fusion are cervical spondylotic myelopathy (CSM) and cervical osteomyelitis (COM). Currently, the informed consent process prior to circumferential cervical fusion surgery is not different for these two groups of patients, as details of their diagnosis-specific risk profiles have not been quantified. The authors compared two patient cohorts with either CSM or COM treated using circumferential fusion. They sought to quantify perioperative morbidity and postoperative mortality in these two groups to assist with a diagnosis-specific informed consent process for future patients undergoing this type of surgery. METHODS:Perioperative and follow-up data from two cohorts of patients who had undergone circumferential cervical decompression and fusion were analyzed. Estimated blood loss (EBL), length of stay (LOS), perioperative complications, hospital readmission, 30-day reoperation rates, change in Nurick grade, and mortality were compared between the two groups. RESULTS:Twenty-two patients were in the COM cohort, and 24 were in the CSM cohort. Complications, hospital readmission, 30-day reoperation rates, EBL, and mortality were not statistically different, although patients with COM trended higher in each of these categories. There was a significantly greater LOS (p < 0.001) in the COM group and greater improvement in Nurick grade in the CSM group (p < 0.001). CONCLUSIONS:When advising patients undergoing circumferential fusion about perioperative risk factors, it is important for those with COM to know that they are likely to have a higher rate of complications and mortality than those with CSM who are undergoing similar surgery. Furthermore, COM patients have less neurological improvement than CSM patients after surgery. This information may be useful to surgeons and patients in providing appropriate informed consent during preoperative planning.

STUDY DESIGN/METHODS:Retrospective study. PURPOSE/OBJECTIVE:The aim of this study was to evaluate the clinical management and outcomes of patients who underwent surgical intervention for metastatic colorectal adenocarcinoma of the spine. OVERVIEW OF LITERATURE/BACKGROUND:Gastrointestinal (GI) cancer metastasis to the spine are relatively rare and represent later manifestations of the disease. Studies and reports on the outcomes of patients who undergo surgery for spinal metastasis of GI origin are scarce. METHODS:A retrospective chart review of all patients who underwent surgery for spinal metastasis of colorectal origin was performed. Four patients were identified. Patient characteristics, outcomes, and survival were analyzed. RESULTS:Two patients experienced improvement in pain or myelopathic symptoms. Although the mean survival was 15.3 months, this average included a patient still living at 57.1 months. The mean survival was just 1.3 months for the 3 patients who expired. CONCLUSIONS:In certain cases, symptomatic improvement with prolonged survival is possible after surgery for metastatic spinal lesions of colorectal origin; however, survival is poor in the majority of cases.

OBJECT/OBJECTIVE:Smoking is one of the leading causes of preventable morbidity and death in the U.S. and has been associated with perioperative complications. In this study, the authors examined the effects of smoking on perioperative outcomes and pseudarthrosis rates following anterior cervical corpectomy. METHODS:All adult patients from 2006 to 2011 who underwent anterior cervical corpectomy were identified. Patients were categorized into 3 groups: patients who never smoked (nonsmokers), patients who quit for at least 1 year (quitters), and patients who continue to smoke (current smokers). Demographic, medical, and surgical covariates were collected. Multivariate analysis was used to define the relationship between smoking and blood loss, 30-day complications, length of hospital stay, and pseudarthrosis. RESULTS:A total of 160 patients were included in the study. Of the 160 patients, 49.4% were nonsmokers, 25.6% were quitters, and 25.0% were current smokers. The overall 30-day complication rate was 20.0%, and pseudarthrosis occurred in 7.6% of patients. Mean blood loss was 368.3 ml and mean length of stay was 6.5 days. Current smoking status was significantly associated with higher complication rates (p < 0.001) and longer lengths of stay (p < 0.001); current smoking status remained an independent risk factor for both outcomes after multivariate logistic regression analysis. The complications that were experienced in current smokers were mostly infections (76.5%), and this proportion was significantly greater than in nonsmokers and quitters (p = 0.013). Current smoking status was also an independent risk factor for pseudarthrosis at 1-year follow-up (p = 0.012). CONCLUSIONS:Smoking is independently associated with higher perioperative complications (especially infectious complications), longer lengths of stay, and higher rates of pseudarthrosis in patients undergoing anterior cervical corpectomy.

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.

OBJECT/OBJECTIVE:Long-segment spinal instrumentation ending at the sacrum places substantial biomechanical stress on sacral screws. Iliac (pelvic) screws relieve some of this stress by supplementing the caudal fixation. It remains an open question whether there is any clinically significant difference in sacropelvic fixation with bilateral versus unilateral iliac screws. The primary purpose of this study was to compare clinical and radiographic complications in the use of bilateral versus unilateral iliac screw fixation. METHODS:The authors retrospectively reviewed 102 consecutive spinal fixation cases that extended to the pelvis at a single institution (University of California, San Francisco) in the period from 2005 to 2012 performed by the senior authors. Charts were reviewed for the following complications: reoperation, L5-S1 pseudarthrosis, sacral insufficiency fracture, hardware prominence, iliac screw loosening, and infection. The t-test, Pearson chi-square test, and Fisher exact test were used to determine statistical significance. RESULTS:The mean follow-up was 31 months. Thirty cases were excluded: 12 for inadequate follow-up, 15 for lack of L5-S1 interbody fusion, and 3 for preoperative osteomyelitis. The mean age among the 72 remaining cases was 62 years (range 39-79 years). Forty-six patients underwent unilateral and 26 bilateral iliac screw fixation. Forty-one percent (n = 19) of the unilateral cases and 50% (n = 13) of the bilateral cases were treated with reoperation (p = 0.48). In addition, 13% (n = 6) of the unilateral and 19% (n = 5) of the bilateral cases developed L5-S1 pseudarthrosis (p = 0.51). There were no sacral insufficiency fractures. Thirteen percent (n = 6) of the unilateral and 7.7% (n = 2) of the bilateral cases developed postoperative infection (p = 0.70). CONCLUSIONS:In a retrospective single-institution study, single versus dual pelvic screws led to comparable rates of reoperation, iliac screw removal, postoperative infection, pseudarthrosis, and sacral insufficiency fractures. For spinopelvic fixation, placing bilateral (vs unilateral) pelvic screws produced no added clinical benefit in most cases.

Holospinal epidural abscess (HEA) is an extremely rare condition in which spinal epidural abscesses extend from the cervical to the sacral spine. We report two patients who presented with myelopathy secondary to HEA. Both patients underwent urgent surgical decompression and abscess drainage, and had significant improvement in neurological function. We discuss the surgical management strategies and briefly review the literature regarding HEA.

BACKGROUND:Local recurrence of spinal metastasis after surgical resection is relatively common. We sought to determine risk factors and independent predictors for local recurrence after primary surgical resection of spinal metastasis. METHODS:Demographic and clinical variables were collected for patients who underwent surgery for spinal metastasis June 2005 to June 2011. Primary outcome of interest was local recurrence. Significant associations between covariates of interest and recurrence were identified using the chi-square test. Multivariable logistic regression models for recurrence risk were fit and adjusted for potential confounders. RESULTS:A total of 99 patients were analyzed. Mean time to metastatic recurrence was 9.8 months. Thirty-two patients (32.3 %) had local recurrence of metastatic disease following initial surgery. Patients who underwent radiotherapy had significantly higher recurrence rates than patients who did not (39.2 % vs. 12.0 %, respectively; P = 0.012). Patients with metastatic disease affecting more levels had significantly lower recurrence rates. On multivariate analysis, older age was an independent predictor of decreased likelihood of local recurrence. Melanoma was the only cancer type independently associated with higher risk for recurrence. Patients with recurrence had significantly higher 1- and 2-year survival rates than patients without recurrence. Median length of survival was longer in the recurrent group as well. CONCLUSIONS:Other than melanoma, covariates significantly associated with recurrence were factors likely associated with increased survival, including less-extensive spinal disease and radiotherapy. Thus, longer survival time following surgery likely results in a greater chance for local recurrence. As advancements in treatment provide prolonged survival, local recurrence rates will likely increase.

Severe thoracic kyphosis caused by pathologic fractures often needs to be corrected by resection of the collapsed vertebral body, reconstruction of the anterior spinal column, and correction of the kyphosis with long-segment fixation. The resection of this pathologic bone functions essentially as a vertebral column resection. With the advent of minimally invasive technology, the powerful corrective forces afforded in open cases can be applied using a less invasive approach. In this article, we describe a mini-open posterior technique for thoracic kyphosis via a vertebrectomy and cantilever technique. Two patients underwent kyphosis correction via mini-open vertebrectomy. One patient was corrected from 92 degrees to 65 degrees, and the second patient was corrected from 70 degrees to 53 degrees. Both patients underwent a mini-open approach. Cantilever correction was accomplished over an expandable cage with a minimally invasive pedicle screw system. We describe our technique of mini-open vertebral column resection and kyphosis correction in the thoracic spine.