Varun R. Kshettry

Descriptive epidemiology of pituitary tumors in the United States, 2004-2009.

OBJECT Pituitary tumors are abnormal growths that develop in the pituitary gland. The Central Brain Tumor Registry of the United States (CBTRUS) contains the largest aggregation of population-based data on the incidence of primary CNS tumors in the US. These data were used to determine the incidence of tumors of the pituitary and associated trends between 2004 and 2009. METHODS Using incidence data from 49 population-based state cancer registries, 2004-2009, age-adjusted incidence rates per 100,000 population for pituitary tumors with ICD-O-3 (International Classification of Diseases for Oncology, Third Edition) histology codes 8040, 8140, 8146, 8246, 8260, 8270, 8271, 8272, 8280, 8281, 8290, 8300, 8310, 8323, 9492 (site C75.1 only), and 9582 were calculated overall and by patient sex, race, Hispanic ethnicity, and age at diagnosis. Corresponding annual percent change (APC) scores and 95% confidence intervals were also calculated using Joinpoint to characterize trends in incidence rates over time. Diagnostic confirmation by subregion of the US was also examined. The overall annual incidence rate increased from 2.52 (95% CI 2.46-2.58) in 2004 to 3.13 (95% CI 3.07-3.20) in 2009. Associated time trend yielded an APC of 4.25% (95% CI 2.91%-5.61%). When stratifying by patient sex, the annual incidence rate increased from 2.42 (95% CI 2.33-2.50) to 2.94 (95% CI 2.85-3.03) in men and 2.70 (95% CI 2.62-2.79) to 3.40 (95% CI 3.31-3.49) in women, with APCs of 4.35% (95% CI 3.21%-5.51%) and 4.34% (95% CI 2.23%-6.49%), respectively. When stratifying by race, the annual incidence rate increased from 2.31 (95% CI 2.25-2.37) to 2.81 (95% CI 2.74-2.88) in whites, 3.99 (95% CI 3.77-4.23) to 5.31 (95% CI 5.06-5.56) in blacks, 1.77 (95% CI 1.26-2.42) to 2.52 (95% CI 1.96-3.19) in American Indians or Alaska Natives, and 1.86 (95% CI 1.62-2.13) to 2.03 (95% CI 1.80-2.28) in Asians or Pacific Islanders, with APCs of 3.91% (95% CI 2.88%-4.95%), 5.25% (95% CI 3.19%-7.36%), 5.31% (95% CI -0.11% to 11.03%), and 2.40% (95% CI -3.20% to 8.31%), respectively. When stratifying by Hispanic ethnicity, the annual incidence rate increased from 2.46 (95% CI 2.40-2.52) to 3.03 (95% CI 2.97-3.10) in non-Hispanics and 3.12 (95% CI 2.91-3.34) to 4.01 (95% CI 3.80-4.24) in Hispanics, with APCs of 4.15% (95% CI 2.67%-5.65%) and 5.01% (95% CI 4.42%-5.60%), respectively. When stratifying by age at diagnosis, the incidence of pituitary tumor was highest for those 65-74 years old and lowest for those 15-24 years old, with corresponding overall age-adjusted incidence rates of 6.39 (95% CI 6.24-6.54) and 1.56 (95% CI 1.51-1.61), respectively. CONCLUSIONS In this large patient cohort, the incidence of pituitary tumors reported between 2004 and 2009 was found to increase. Possible explanations for this increase include changes in documentation, changes in the diagnosis and registration of these tumors, improved diagnostics, improved data collection, increased awareness of pituitary diseases among physicians and the public, longer life expectancies, and/or an actual increase in the incidence of these tumors in the US population.

Descriptive epidemiology of World Health Organization grades II and III intracranial meningiomas in the United States

BACKGROUND Because World Health Organization (WHO) grades II and III meningiomas are relatively uncommon, there is limited literature on the descriptive epidemiology of these tumors, and the existing literature predates the 2000 WHO classification revisions. Our purpose was to provide a modern, population-based study of the descriptive epidemiology of WHO II and III meningiomas in the United States. METHODS The Central Brain Tumor Registry of the United States (CBTRUS) was queried for intracranial meningiomas categorized by WHO grade for the 2004--2010 study period. Age-adjusted incidence (95% confidence interval in parentheses) per 100,000 population was calculated by age, sex, race, and ethnicity. Annual percent change (APC) was calculated using Joinpoint. RESULTS From 2004 to 2010, the incidence of WHO II intracranial meningiomas increased from 0.28 (95% CI, 0.27--0.29) to 0.30 (95% CI, 0.28-0.32), representing an APC of 3.6% (95%CI, 0.8%-6.5%). Conversely, from 2000-2010, the incidence of WHO III meningiomas decreased from 0.13 (95% CI, 0.11-0.14) to 0.06 (95%CI, 0.06-0.07), representing an APC of -5.4% (95% CI, -6.8% to -4.0%). From 2004 to 2010, the overall proportion of WHO I, II, and III intracranial meningiomas was 94.6%, 4.2%, and 1.2%, respectively. For WHO II/III meningiomas, females in the 35-64 year age group had a higher incidence than males in the same age group, whereas males in the ≥ 75 year age group ≥ had a higher incidence. Black and Asian Pacific Islander races were both associated with the highest incidence of WHO II/III meningiomas. Hispanic ethnicity was not associated with any difference in incidence. CONCLUSION This study presents the most comprehensive evaluation of the modern descriptive epidemiology of WHO II and III meningiomas. Temporal trends likely reflect the 2000 WHO histological criteria revisions.

Incidence and risk factors associated with in-hospital venous thromboembolism after aneurysmal subarachnoid hemorrhage

Our purpose was to determine the incidence and risk factors associated with in-hospital venous thromboembolism (VTE) in patients with aneurysmal subarachnoid hemorrhage (aSAH). The Nationwide Inpatient Sample database was queried from 2002 to 2010 for hospital admissions for subarachnoid hemorrhage or intracerebral hemorrhage and either aneurysm clipping or coiling. Exclusion criteria were age <18, arteriovenous malformation/fistula diagnosis or repair, or radiosurgery. Primary outcome was VTE (deep vein thrombosis [DVT] or pulmonary embolus [PE]). Multivariate logistic regression was used to assess association between risk factors and VTE. Secondary outcomes were in-hospital mortality, discharge disposition, length of stay and hospital charges. A total of 15,968 hospital admissions were included. Overall rates of VTE (DVT or PE), DVT, and PE were 4.4%, 3.5%, and 1.2%, respectively. On multivariate analysis, the following factors were associated with increased VTE risk: increasing age, black race, male sex, teaching hospital, congestive heart failure, coagulopathy, neurologic disorders, paralysis, fluid and electrolyte disorders, obesity, and weight loss. Patients that underwent clipping versus coiling had similar VTE rates. VTE was associated with pulmonary/cardiac complication (odds ratio [OR] 2.8), infectious complication (OR 2.8), ventriculostomy (OR 1.8), and vasospasm (OR 1.3). Patients with VTE experienced increased non-routine discharge (OR 3.3), and had nearly double the mean length of stay (p<0.001) and total inflation-adjusted hospital charges (p<0.001). To our knowledge, this is the largest study evaluating the incidence and risk factors associated with the development of VTE after aSAH. The presence of one or more of these factors may necessitate more aggressive VTE prophylaxis.

Peritumoral brain edema in intracranial meningiomas: the emergence of vascular endothelial growth factor-directed therapy.

Meningioma is the second most common type of adult intracranial neoplasm. A substantial subset of patients present with peritumoral brain edema (PTBE), which can cause significant morbidity via mass effect, complicate surgical management, and impact the safety of stereotactic radiosurgery. Recent studies suggest a close relationship between vascular endothelial growth factor-A (VEGF-A) expression and PTBE development in meningiomas. The authors performed a systematic review of the literature on the pathogenesis of PTBE in meningiomas, the effectiveness of steroid therapy, the role played by VEGF-A, and the current clinical evidence for antiangiogenic therapy to treat peritumoral brain edema. Mounting evidence suggests VEGF-A is secreted directly by meningioma cells to induce angiogenesis and edemagenesis of tumoral as well as peritumoral brain tissue. The VEGF-A cascade results in recruitment of cerebral-pial vessels and disruption of the tumor-brain barrier, which appear to be requisite for VEGF-A to have an edemagenic effect. Results of preliminary clinical studies suggest VEGF-directed therapy has modest activity against recurrent and progressive meningioma growth but can alleviate PTBE in some patients. A comprehensive understanding of the VEGF-A pathway and its modulators may hold the key to an effective therapeutic approach to treating PTBE associated with meningiomas. Further clinical trials with larger patient cohorts and longer follow-up periods are warranted to confirm the efficacy of VEGF-directed therapy.

Pseudoarthrosis rates in anterior cervical discectomy and fusion: a meta-analysis

BACKGROUND CONTEXT Anterior cervical discectomy and fusion (ACDF) is a commonly performed procedure for patients presenting with cervical radiculopathy, myelopathy, or deformity. A systematic literature review and meta-analysis of pseudoarthrosis rates associated with ACDF with plate fixation have not been previously performed. PURPOSE The purpose of this study was to identify all prospective studies reporting pseudoarthrosis rates for ACDF with plate fixation. STUDY DESIGN/SETTING This study is based on a systematic review and meta-analysis. PATIENT SAMPLE Studies reporting pseudoarthrosis rates in patients who received one-, two-, or three-level ACDF surgeries were included. OUTCOME MEASURES Outcomes of interest included reported pseudoarthrosis events after ACDF with plate fixation. METHODS We conducted a MEDLINE, SCOPUS, Web of Science, and EMBASE search for studies reporting complications for ACDF with plate fixation. We recorded pseudoarthrosis events from all included studies. A meta-analysis was performed to calculate effect summary mean values, 95% confidence intervals (CIs), Q statistics, and I(2) values. Forest plots were constructed for each analysis group. RESULTS Of the 7,130 retrieved articles, 17 met the inclusion criteria. The overall pseudoarthrosis rate was 2.6% (95% CI: 1.3-3.9). Use of autograft fusion (0.9%, 95% CI: -0.4 to 2.1) resulted in a reduced pseudoarthrosis rate compared with allograft fusion procedures (4.8%, 95% CI: 1.7-7.9). Studies were separated based on the length of follow-up: 12 to 24 and greater than 24 months. These groups reported rates of 3.1% (95% CI: 1.2-5.0) and 2.3% (95% CI: 0.1-4.4), respectively. Studies performing single-level ACDF yielded a rate of 3.7% (95% CI: 1.6-5.7). Additionally, there was a large difference in the rate of pseudoarthrosis in randomized controlled trials (4.8%, 95% CI: 2.6-7.0) versus prospective cohort studies (0.2%, 95% CI: -0.1 to 0.5), indicating that the extent of follow-up criteria affects the rate of pseudoarthrosis. CONCLUSIONS This review represents a comprehensive estimation of the actual incidence of pseudoarthrosis across a heterogeneous group of surgeons, patients, and ACDF techniques. The definition of pseudoarthrosis varied significantly within the literature. To ensure its diagnosis and prevent sequelae, standardized criteria need to be established. This investigation sets the framework for surgeons to understand the impact of surgical techniques on the rate of pseudoarthrosis.

Immediate Titanium Cranioplasty After Debridement and Craniectomy for Postcraniotomy Surgical Site Infection

BACKGROUND: For postcraniotomy surgical site infection (SSI) involving the bone, typical management involves craniectomy, debridement, and delayed cranioplasty. Disadvantages to delayed cranioplasty include cosmetic deformity, vulnerability of unprotected brain, and risks and costs associated with an additional operation. Many authors have attempted bone flap salvage by using various techniques. OBJECTIVE: We evaluate our experience with immediate titanium mesh cranioplasty at the time of craniectomy and debridement. METHODS: We retrospectively reviewed SSIs in patients that underwent craniotomy for treatment of a brain tumor. These patients were treated with craniectomy, debridement, and immediate titanium mesh cranioplasty followed by antibiotics. The primary outcome was recurrent infection. RESULTS: Twelve patients met the inclusion criteria. Risk factors for infection included preoperative radiation therapy (33%), prior craniotomy (33%), and postoperative CSF leak (25%). Median follow-up was 14 months. Ten (83%) patients had long-term resolution without recurrent infection. One patient required additional surgical debridement for persistent infection with successful placement of new titanium mesh. Another patient developed recurrent infection but opted for hospice care because of tumor progression. CONCLUSION: This series demonstrates the safety and feasibility of performing immediate titanium cranioplasty at the time of craniectomy and debridement in patients with postcraniotomy infections. This has been shown in patients with risk factors for poor wound healing. Immediate cranioplasty avoids the drawbacks, risks, and costs of delayed cranioplasty.

Lumbar microdiscectomy complication rates: a systematic review and meta-analysis

OBJECT Lumbar microdiscectomy and its various minimally invasive surgical techniques are seeing increasing popularity, but a systematic review of their associated complications has yet to be performed. The authors sought to identify all prospective clinical studies reporting complications associated with lumbar open microdiscectomy, microendoscopic discectomy (MED), and percutaneous microdiscectomy. METHODS The authors conducted MEDLINE, Scopus, Web of Science, and Embase database searches for randomized controlled trials and prospective cohort studies reporting complications associated with open, microendoscopic, or percutaneous lumbar microdiscectomy. Studies with fewer than 10 patients and published before 1990 were excluded. Overall and interstudy median complication rates were calculated for each surgical technique. The authors also performed a meta-analysis of the reported complications to assess statistical significance across the various surgical techniques. RESULTS Of 9504 articles retrieved from the databases, 42 met inclusion criteria. Most studies screened were retrospective case series, limiting the number of studies that could be included. A total of 9 complication types were identified in the included studies, and these were analyzed across each of the surgical techniques. The rates of any complication across the included studies were 12.5%, 13.3%, and 10.8% for open, MED, and percutaneous microdiscectomy, respectively. New or worsening neurological deficit arose in 1.3%, 3.0%, and 1.6% of patients, while direct nerve root injury occurred at rates of 2.6%, 0.9%, and 1.1%, respectively. Hematoma was reported at rates of 0.5%, 1.2%, and 0.6%, respectively. Wound complications (infection, dehiscence, orseroma) occurred at rates of 2.1%, 1.2%, and 0.5%, respectively. The rates of recurrent disc complications were 4.4%, 3.1%, and 3.9%, while reoperation was indicated in 7.1%, 3.7%, and 10.2% of operations, respectively. Meta-analysis calculations revealed a statistically significant higher rate of intraoperative nerve root injury following percutaneous procedures relative to MED. No other significant differences were found. CONCLUSIONS This review highlights complication rates among various microdiscectomy techniques, which likely reflect real-world practice and conceptualization of complications among physicians. This investigation sets the framework for further discussions regarding microdiscectomy options and their associated complications during the informed consent process.

Transoral and transnasal odontoidectomy complications: A systematic review and meta-analysis

OBJECT The craniovertebral junction (CVJ) is a complex region of the spine with unique anatomical and functional relationships. To alleviate symptoms associated with pathological processes involving the odontoid process, decompression is often required, including odontoidectomy. Accurate knowledge of the complication rates following the transoral and transnasal techniques is essential for both patients and surgeons. METHODS We conducted MEDLINE, Scopus and Web of Science database searches for studies reporting complications associated with the transoral and transnasal techniques for odontoidectomy. Case series presenting data for less than three patients were excluded. Rates of complication and clinical outcomes were calculated and subsequently analyzed using a fixed-effects model to assess statistical significance. RESULTS Of 1288 articles retrieved from MEDLINE, Scopus, and Web of Science, twenty-six met inclusion criteria. Transoral and transnasal procedures resulted in the following respective complication rates: arterial injury 1.9% and 0.0%, intraoperative CSF leak 0.3% and 30.0%, postoperative CSF leak 0.8% and 5.2%, 30-day mortality 2.9% and 4.4%, medical complications 13.9% and 28.6%, meningitis 1.0% and 4.0%, pharyngeal wound dehiscence 1.7% (transnasal not reported), pneumonia 10.3% (transnasal not reported), prolonged or re-intubation 5.6% and 6.0%, reoperation 2.5% and 5.1%, sepsis 1.9% and 7.7%, tracheostomy 10.8% and 3.4%, velopharyngeal insufficiency 3.3% and 6.4% and wound infection 3.3% and 1.9%. None of these differences were statistically significant, except for postoperative tracheostomy, which was significantly higher after transoral odontoidectomy 8.4% (95% CI 4.9% -11.9%) compared to transnasal odontoidectomy 0.8% (95% CI -1.0% -2.9%). Neurologic outcome was improved in 90.0% and worse in 0.9% of patients after transoral compared to 94.0% and 0.0% after transnasal odontoidectomy (p=0.30). CONCLUSIONS This work presents a systematic review of complications reported for transoral or transnasal odontoidectomy across a heterogeneous group of surgeons and patients. Due to inconsistent reporting, statistical significance was only achieved for postoperative tracheostomy, which was significantly higher in the transoral group. This investigation sets the framework for further discussions regarding odontoidectomy approach options and their associated complications during the informed consent process.

The Dorello canal: historical development, controversies in microsurgical anatomy, and clinical implications

Interest in studying the anatomy of the abducent nerve arose from early clinical experience with abducent palsy seen in middle ear infection. Primo Dorello, an Italian anatomist working in Rome in the early 1900s, studied the anatomy of the petroclival region to formulate his own explanation of this pathological entity. His work led to his being credited with the discovery of the canal that bears his name, although this structure had been described 50 years previously by Wenzel Leopold Gruber. Renewed interest in the anatomy of this region arose due to advances in surgical approaches to tumors of the petroclival region and the need to explain the abducent palsies seen in trauma, intracranial hypotension, and aneurysms. The advent of the surgical microscope has allowed more detailed anatomical studies, and numerous articles have been published in the last 2 decades. The current article highlights the historical development of the study of the Dorello canal. A review of the anatomical studies of this structure is provided, followed by a brief overview of clinical considerations.

Seizure-free and neuropsychological outcomes after temporal lobectomy with amygdalohippocampectomy in pediatric patients with hippocampal sclerosis

OBJECT Temporal lobe epilepsy is an uncommon clinical syndrome in the pediatric population. The most common underlying pathologies include low-grade gliomas, cortical dysplasia, and, less commonly, hippocampal sclerosis (HS). There is a paucity of data on neuropsychological and seizure-free outcomes in these patients after temporal lobectomy. In this study, the authors reviewed their seizure-free and neuropsychological outcomes after temporal lobectomy for pediatric HS. METHODS The authors retrospectively reviewed the medical records of pediatric patients with HS who underwent anterior temporal lobectomy and amygdalohippocampectomy between 1998 and 2011 at the Cleveland Clinic. Results of neuropsychological assessment before and after surgery and seizure-free outcome at last follow-up were obtained. RESULTS Forty-five patients met the inclusion criteria. Thirty-four (76%) patients had pathology of HS alone and 10 (22%) had HS and cortical dysplasia. The mean duration of follow-up was 60.2 months. Eighty-four percent of patients had postoperative Engel Class I or II outcomes. Neuropsychological outcomes remained unchanged or minimally improved postoperatively. CONCLUSIONS Seizure-free outcomes in pediatric HS are similar to historical rates in adult HS. Neuropsychological assessments remain stable after temporal lobectomy. Standard temporal lobectomy should be considered in pediatric patients with medically intractable epilepsy secondary to HS.