Faculty Bibliography

OBJECT/OBJECTIVE:Leiomyosarcoma is a smooth-muscle sarcoma that rarely metastasizes to the spine. Its clinical course is variable, although patients with metastatic leiomyosarcoma can experience prolonged survival as compared with patients with more aggressive metastatic tumors. The authors report their single-institution experience in the surgical treatment of patients with leiomyosarcoma metastatic to the spine. METHODS:A retrospective review of the electronic medical records was performed to obtain details on clinical management and outcomes for patients who had undergone surgical intervention for metastatic leiomyosarcoma of the spine. The few articles available in the current literature on this topic were also analyzed. RESULTS:Eight patients with metastatic leiomyosarcoma of the spine underwent surgical management between 2005 and 2011. Six patients (75%) had improvement in their Nurick grade. Patients who had presented with pain as a primary symptom experienced significant relief. Five patients (63%) had lesion recurrence, and 4 underwent repeat surgery at a mean of 10.2 months after their initial surgery. The mean duration of survival was 11.7 months (range 3.3-23.0 months). CONCLUSIONS:Leiomyosarcoma rarely metastasizes to the spine. However, surgical intervention can relieve pain and improve neurological function. Given the potential for prolonged survival, aggressive management should be considered in well-selected patients.

INTRODUCTION/BACKGROUND:In patients who require additional surgery for velopharyngeal insufficiency (VPI), a higher incidence of obstructive sleep apnea (OSA) may be incurred. Although this phenomenon has been demonstrated with the posterior pharyngeal flap, the effect of dynamic sphincter pharyngoplasty (DSP) on OSA is less clear. The purposes of this case series were to (1) determine the incidence of OSA after DSP, (2) assess the changes in polysomnography after DSP, and (3) identify risk factors for the development of OSA after DSP. Our global hypothesis is that OSA and VPI exist on a continuum and that speech outcomes should not be considered in isolation. METHODS:For a 13-year period, 146 patients with idiopathic VPI, submucous cleft palate, cleft palate only, or cleft lip and palate underwent DSP for VPI. The diagnosis of OSA was defined as the prescription of continuous positive airway pressure therapy by a pediatric sleep medicine physician. The incidence of OSA preoperatively and postoperatively was compared using Fisher exact test. When available, preoperative and postoperative apnea-hypopnea indices (AHIs) were compared using the pairwise, 2-tailed, Student's t-test. Patient factors, such as obesity (body mass index ≥ 95th percentile), the presence of a craniofacial syndrome, surgical history, and a preexisting OSA diagnosis, were noted. A multiple logistic regression was performed to elucidate risk factors for the development of OSA. RESULTS:The average age at surgery was 9.2 years (range, 4-40 y), and the mean follow-up time was 4.5 years (range, 1 mo to 12 y). The incidence of OSA increased after DSP, from 2 to 33 patients (1.4%-22%, respectively; P = 0.05). In 23 patients (16%), both preoperative and postoperative AHIs were available. There was a significant increase in AHI after DSP, from 3.1 to 8.4 episodes per hour of sleep (P = 0.001). Previous tonsillectomy/adenoidectomy was predictive of OSA after DSP (relative risk = 2.4; P = 0.04). CONCLUSIONS:We report an increased incidence of OSA and higher-than-average AHIs postoperatively after DSP. Preoperative tonsillectomy/adenoidectomy predicted the development of OSA after DSP. A high index of suspicion for development of OSA must be maintained in patients who undergo secondary speech operations for VPI. Clinical screening for OSA should be used in this population, with a low threshold for polysomnographic evaluation. The surgeon must be wary that improvements in speech after DSP may change airway dynamics and increase the risk of OSA.

BACKGROUND:Neuroimmune activation in the spinal dorsal horn plays an important role in the pathogenesis of chronic pain after peripheral nerve injury. OBJECTIVE:The aim of this study was to examine the role of neuroimmune activation in below-level neuropathic pain after traumatic spinal cord injury (SCI). METHODS:Right hemilateral SCI was created in male Sprague-Dawley rats by controlled blunt impact through a T12 laminectomy. Pain-related behaviors were assessed using both evoked reflex responses and an operant conflict-avoidance test. Neuroimmune activation was blocked by the anti-inflammatory cytokine interleukin-10 (IL-10) delivered by a nonreplicating herpes simplex virus (HSV)-based gene transfer vector (vIL10). Markers of neuroimmune activation were assessed using immunohistochemistry and Western blot. RESULTS:One week after SCI, injured animals demonstrated mechanical allodynia, thermal hyperalgesia, and mechanical hyperalgesia in the hind limbs below the level of injury. Animals inoculated with vIL10 had a statistically significant reduction in all of these measures compared to injured rats or injured rats inoculated with control vector. Conflict-avoidance behavior of injured rats inoculated with vIL10 was consistent with significantly reduced pain compared with injured rats injected with control vector. These behavioral results correlated with a significant decrease in spinal tumor necrosis factor α (mTNFα) expression assessed by Western blot and astrocyte activation assessed by glial fibrillary acidic protein immunohistochemistry. CONCLUSION/CONCLUSIONS:Below-level pain after SCI is characterized by neuroimmune activation (increase mTNFα and astrocyte activation). Blunting of the neuroimmune response by HSV-mediated delivery of IL-10 reduced pain-related behaviors, and may represent a potential novel therapeutic agent.

OBJECT/OBJECTIVE:Identifying risk factors for surgical morbidity and mortality might improve the safety and efficacy of neurosurgical intervention. Cigarette smoking is a relatively common practice and is associated with several adverse health outcomes. The authors examined the relationship between smoking and intraoperative blood loss, postoperative outcomes, and survival following craniotomy for tumor resection. METHODS:A consecutive population of patients undergoing craniotomy for tumor resection between 2006 and 2009 was identified. Using multivariable models and Cox proportional hazard regression analysis, the authors assessed the relation between smoking and operative outcomes including blood loss, complication rates, hospital length of stay, 30-day mortality, and 1-year survival among patients who underwent craniotomy for tumor resection. RESULTS:A total of 453 patients were included in this study: 237 patients never smoked, 54 quit smoking for at least 1 year, and 162 were current smokers. Current smoking status was an independent risk factor for higher intraoperative blood loss, complication risk, and lower 1-year survival following intervention relative to patients who never smoked. Patients who quit smoking had significantly higher mean blood loss, but did not carry a higher risk for other outcomes such as postoperative complications and 1-year mortality compared with patients who never smoked. CONCLUSIONS:Current cigarette smoking is associated with poor surgical outcome and lower 1-year survival after undergoing craniotomy for tumor resection. However, quitting smoking and implementing strict smoking cessation programs may help mitigate these risks. Future research might investigate mechanisms underlying these associations.

OBJECT/OBJECTIVE:Advances in the management of trauma-induced intracranial hematomas and hemorrhage (epidural, subdural, and intraparenchymal hemorrhage) have improved survival in these conditions over the last several decades. However, there is a paucity of research investigating the relation between patient age and outcomes of surgical treatment for these conditions. In this study, the authors examined the relation between patient age over 80 years and postoperative outcomes following closed head injury and craniotomy for intracranial hemorrhage. METHODS:A consecutive population of patients undergoing emergent craniotomy for evacuation of intracranial hematoma following closed head trauma between 2006 and 2009 was identified. Using multivariable logistic regression models, the authors assessed the relation between age (> 80 vs ≤ 80 years) and postoperative complications, intensive care unit stay, hospital stay, morbidity, and mortality. RESULTS:Of 103 patients, 27 were older than 80 years and 76 patients were 80 years of age or younger. Older age was associated with longer length of hospital stay (p = 0.014), a higher rate of complications (OR 5.74, 95% CI 1.29-25.34), and a higher likelihood of requiring rehabilitation (OR 3.28, 95% CI 1.13-9.74). However, there were no statistically significant differences between the age groups in 30-day mortality or ability to recover to functional baseline status. CONCLUSIONS:The findings suggest that in comparison with younger patients, patients over 80 years of age may be similarly able to return to preinjury functional baselines but may require increased postoperative medical attention in the forms of rehabilitation and longer hospital stays. Prospective studies concerned with the relation between older age, perioperative parameters, and postoperative outcomes following craniotomy for intracranial hemorrhage are needed. Nonetheless, the findings of this study may allow for more informed decisions with respect to the care of elderly patients with intracranial hemorrhage.

OBJECTIVE:Little is known about socioeconomic differences in postoperative outcomes after neurosurgery. We assessed the relation between insurance status and postoperative complication risk, neurosurgical intensive care unit stay, and hospital stay after neurosurgery. METHODS:We collected data on 918 consecutive craniotomy or spine-related neurosurgical cases in patients at least 18 years of age at the University of Michigan Hospitals after April 2006. Bivariate χ(2) tests and analysis of variance were used to assess bivariate relations, and multivariable logistic regression models and analysis of covariance were used to adjust for potential confounders. RESULTS:A total of 11.2% of privately insured patients, 23.6% of Medicare patients, 25.8% of Medicaid patients, and 27.3% of uninsured patients suffered complications within 30 days of surgery (P < 0.001). In adjusted models, odds of postoperative complications among Medicare (odds ratio [OR] = 2.1, 95% confidence interval [CI] 1.3-3.3), Medicaid (OR = 3.1, 95% CI 1.5-6.1), and uninsured patients (OR = 3.6. 95% CI 1.3-10.3) were higher than among privately insured patients. By analysis of covariance, only Medicaid patients had significantly longer intensive care unit (P = 0.040) and hospital stays (P = 0.028) than privately insured patients. CONCLUSIONS:Our findings suggest important socioeconomic disparities in outcomes after neurosurgical intervention. Access to postoperative outpatient care may mediate our findings.

STUDY DESIGN/METHODS: Comparative effectiveness review. STUDY RATIONALE/OBJECTIVE: Spinal fusion is believed to accelerate the degeneration of the vertebral segment above or below the fusion site, a condition called adjacent segment disease (ASD). The premise of dynamic stabilization is that motion preservation allows for less loading on the discs and facet joints at the adjacent, non-fused segments. In theory, this should decrease the rate of ASD. However, clinical evidence of this theoretical decrease in ASD is still lacking. We performed a systematic review to evaluate the evidence in the literature comparing dynamic stabilization with fusion. CLINICAL QUESTION/OBJECTIVE: In patients 18 years or older with degenerative disease of the cervical or lumbar spine, does dynamic stabilization lead to better outcomes and fewer complications, including ASD, than fusion in the short-term and the long-term? METHODS: A systematic search and review of the literature was undertaken to identify studies published through March 7, 2011. PubMed, Cochrane, and National Guideline Clearinghouse Databases as well as bibliographies of key articles were searched. Two individuals independently reviewed articles based on inclusion and exclusion criteria which were set a priori. Each article was evaluated using a predefined quality-rating scheme. RESULTS: No significant differences were identified between fusion and dynamic stabilization with regard to VAS, ODI, complications, and reoperations. There are no long-term data available to show whether dynamic stabilization decreases the rate of ASD. CONCLUSIONS: There are no clinical data from comparative studies supporting the use of dynamic stabilization devices over standard fusion techniques.

Invasion and metastasis of aggressive breast cancer cells are the final and fatal steps during cancer progression. Clinically, there are still limited therapeutic interventions for aggressive and metastatic breast cancers available. Therefore, effective, targeted, and non-toxic therapies are urgently required. Id-1, an inhibitor of basic helix-loop-helix transcription factors, has recently been shown to be a key regulator of the metastatic potential of breast and additional cancers. We previously reported that cannabidiol (CBD), a cannabinoid with a low toxicity profile, down-regulated Id-1 gene expression in aggressive human breast cancer cells in culture. Using cell proliferation and invasion assays, cell flow cytometry to examine cell cycle and the formation of reactive oxygen species, and Western analysis, we determined pathways leading to the down-regulation of Id-1 expression by CBD and consequently to the inhibition of the proliferative and invasive phenotype of human breast cancer cells. Then, using the mouse 4T1 mammary tumor cell line and the ranksum test, two different syngeneic models of tumor metastasis to the lungs were chosen to determine whether treatment with CBD would reduce metastasis in vivo. We show that CBD inhibits human breast cancer cell proliferation and invasion through differential modulation of the extracellular signal-regulated kinase (ERK) and reactive oxygen species (ROS) pathways, and that both pathways lead to down-regulation of Id-1 expression. Moreover, we demonstrate that CBD up-regulates the pro-differentiation factor, Id-2. Using immune competent mice, we then show that treatment with CBD significantly reduces primary tumor mass as well as the size and number of lung metastatic foci in two models of metastasis. Our data demonstrate the efficacy of CBD in pre-clinical models of breast cancer. The results have the potential to lead to the development of novel non-toxic compounds for the treatment of breast cancer metastasis, and the information gained from these experiments broaden our knowledge of both Id-1 and cannabinoid biology as it pertains to cancer progression.

Before the advent of minimally invasive spine surgery (MIS), open transforaminal lumbar interbody fusion (TLIF) was performed to treat spondylosis, spondylolisthesis, and spondylolysis. Minimally invasive TLIF has recently become more popular based upon the premise that a smaller, less traumatic incision should afford better recovery and outcomes. However, the learning curve associated with this technique must be considered. To analyze the perioperative factors associated with the learning curve in patients who underwent MIS TLIF versus open TLIF, we identified 22 patients who underwent TLIF from 2005 to 2008 within levels L4-S1 by the senior author (D.C.). Patients were subdivided into two groups according to whether they underwent: (i) MIS TLIF (10 patients, the first MIS TLIF procedures performed by D.C.); or (ii) open TLIF (12 patients). Preoperative, perioperative and postoperative factors were evaluated. Patients who underwent MIS TLIF had a statistically significant lower intraoperative transfusion rate, and rate of required postoperative surgical drains; and shorter periods of required drainage, and time to ambulation. However, the MIS TLIF group tended to have a higher rate of complications, which might have been associated with the learning curve. Both groups had a minimum of 1-year follow-up.

BACKGROUND:Anterior approaches for thoracolumbar corpectomies can have significant morbidity. Spine surgeons have historically performed their own anterior approaches, but recently access surgeons are being used more frequently. OBJECTIVE:To evaluate the morbidity rates of approaches performed by an access surgeon and by an approach-trained spinal neurosurgeon. METHODS:From 2004 to 2008, 46 patients undergoing anterior thoracolumbar corpectomies (levels T2-L5) by the senior author (D.C.) were identified and subdivided into 2 groups based on whether an access surgeon was involved. Nine patients were excluded, leaving 37 patients in the final analysis. Blood loss, operative times, length of hospital stay, complications, and neurological outcomes were evaluated. RESULTS:Eighteen patients had anterior spinal access by an approach-trained spinal neurosurgeon, and 19 patients underwent the approach by an access surgeon. Surgeries performed by the spinal neurosurgeon alone were comparable to those performed by an access surgeon with respect to operative time, days spent in the hospital, blood loss, complication rates, and improvement in neurological function. CONCLUSION/CONCLUSIONS:There appears to be no increased morbidity of anterior approaches performed by an approach-trained spinal neurosurgeon compared with approaches performed by an access surgeon in terms of operative time, complication rate, and improvement in neurological function.