Faculty Bibliography

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.

The purpose of this study is to determine the role of computed tomography (CT) on the decision to administer blood transfusions in patients with abdominopelvic hemorrhage (trauma, surgery, invasive procedure, and spontaneous) and to determine the clinical parameters most likely to influence the decision to administer blood transfusions in patients with spontaneous abdominopelvic hemorrhage. In this IRB approved and HIPPA compliant study, retrospective analysis was performed on 298 patients undergoing abdominal and pelvic CT for suspected abdominopelvic hemorrhage and the CT reports and electronic medical records were reviewed. Odds ratios and 95% CI were calculated to compare the odds of abdominopelvic hemorrhage and transfusion for categorical and continuous predictors. The presence of abdominopelvic hemorrhage by CT was significantly associated with blood transfusions for trauma patients (p-value <0.0001) only. 106 patients with suspected spontaneous abdominopelvic hemorrhage had the lowest CT positivity rate (n = 23, 21.7%) but the highest blood transfusion rate (n = 62, 58.5%) compared to the patients with abdominopelvic hemorrhage from known preceding causes. In patients with spontaneous abdominopelvic hemorrhage, low hemoglobin and hematocrit levels immediately prior to obtaining the CT study were more predictive for receiving a blood transfusion (p-value <0.0001) than the presence of hemorrhage by CT. CT positivity is strongly correlated with the decision to administer blood transfusions for patients with abdominopelvic hemorrhage from trauma, indicating that CT studies play a significant role in determining the clinical management of trauma patients. For patients with spontaneous abdominopelvic hemorrhage, the decision to transfuse depends not on the CT study but on the patient's hemoglobin and hematocrit levels. CT studies should therefore not be performed for the sole purpose of determining the need for blood transfusion in patients with spontaneous abdominopelvic hemorrhage.

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.

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/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.