Radiation Treatment for WHO Grade II and III Meningiomas

The treatment of meningiomas is tailored to their histological grade. While World Health Organization (WHO) grade I lesions can be treated with either surgery or external beam radiation, WHO Grade II and III lesions often require a combination of the two modalities. For these high-grade lesions, conventional external beam radiation is delivered to either the residual tumor or the surgical resection margin. The optimal timing of radiation, either immediately following surgical resection or at the time of recurrence, is yet to be determined. Additionally, another method of radiation delivery, brachytherapy, can be administered locally at the time of surgery for recurrent lesions. Altogether, the complex nature of WHO grade II and III meningiomas requires careful treatment planning and delivery by a multidisciplinary team

Malpractice Liability and Defensive Medicine: A National Survey of Neurosurgeons

BACKGROUND: Concern over rising healthcare expenditures has led to increased scrutiny of medical practices. As medical liability and malpractice risk rise to crisis levels, the medical-legal environment has contributed to the practice of defensive medicine as practitioners attempt to mitigate liability risk. High-risk specialties, such as neurosurgery, are particularly affected and neurosurgeons have altered their practices to lessen medical-legal risk. We present the first national survey of American neurosurgeons' perceptions of malpractice liability and defensive medicine practices. METHODS: A validated, 51-question online-survey was sent to 3344 practicing U.S. neurosurgeon members of the American Association of Neurological Surgeons, which represents 76% of neurosurgeons in academic and private practices. RESULTS: A total of 1028 surveys were completed (31% response rate) by neurosurgeons representing diverse sub-specialty practices. Respondents engaged in defensive medicine practices by ordering additional imaging studies (72%), laboratory tests (67%), referring patients to consultants (66%), or prescribing medications (40%). Malpractice premiums were considered a "major or extreme" burden by 64% of respondents which resulted in 45% of respondents eliminating high-risk procedures from their practice due to liability concerns. CONCLUSIONS: Concerns and perceptions about medical liability lead practitioners to practice defensive medicine. As a result, diagnostic testing, consultations and imaging studies are ordered to satisfy a perceived legal risk, resulting in higher healthcare expenditures. To minimize malpractice risk, some neurosurgeons have eliminated high-risk procedures. Left unchecked, concerns over medical liability will further defensive medicine practices, limit patient access to care, and increase the cost of healthcare delivery in the United States

Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of chemotherapeutic management and antiangiogenic treatment of newly diagnosed glioblastoma in adults

QUESTION: What is the role of temozolomide in the management of adult patients (aged 65 and under) with newly diagnosed glioblastoma? TARGET POPULATION: These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma. RECOMMENDATION: Level I: Concurrent and post-irradiation Temozolomide (TMZ) in combination with radiotherapy and post-radiotherapy as described by Stupp et al. is recommended to improve both PFS and OS in adult patients with newly diagnosed GBM. There is no evidence that alterations in the dosing regimen have additional beneficial effect. QUESTION: Is there benefit to adjuvant temozolomide treatment in elderly patients (\u3e 65 years old?). TARGET POPULATION: These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma. RECOMMENDATION: Level III: Adjuvant TMZ treatment is suggested as a treatment option to improve PFS and OS in adult patients (over 70 years of age) with newly diagnosed GBM. QUESTION: What is the role of local regional chemotherapy with BCNU biodegradable polymeric wafers in adult patients with newly diagnosed glioblastoma? TARGET POPULATION: These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma. RECOMMENDATION: Level III: There is insufficient evidence for the use of BCNU wafers following resection in patients with newly diagnosed glioblastoma who undergo the Stupp protocol after surgery. Further studies of higher quality are suggested to understand the role of BCNU wafer and other locoregional therapy in the setting of Stupp Protocol. QUESTION: What is the role of bevacizumab in the adult patient with newly diagnosed glioblastoma? TARGET POPULATION: These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma. RECOMMENDATION: Level I: Bevacizumab in general is not recommended in the initial treatment of adult patients with newly diagnosed GBM. It continues to be strongly recommended that patients with newly diagnosed GBM be enrolled in properly designed clinical trials to assess the benefit of novel chemotherapeutic agents compared to standard therapy

Interfacility Helicopter Ambulance Transport of Neurosurgical Patients: Observations, Utilization, and Outcomes from a Quaternary Level Care Hospital

The clinical benefit of helicopter transport over ground transportation for interfacility transport is unproven. We sought to determine actual practice patterns, utilization, and outcomes of patients undergoing interfacility transport for neurosurgical conditions.We retrospectively examined all interfacility helicopter transfers to a single trauma center during 2008. We restricted our analysis to those transfers leading either to admission to the neurosurgical service or to formal consultation upon arrival. Major exclusion criteria included transport from the scene, death during transport, and transport to any area of the hospital other than the emergency department. The primary outcome was time interval to invasive intervention. Secondary outcomes were estimated ground transportation times from the referring hospital, admitting disposition, and discharge disposition. Of 526 candidate interfacility helicopter transfers to our emergency department in 2008, we identified 167 meeting study criteria. Seventy-five (45%) of these patients underwent neurosurgical intervention. The median time to neurosurgical intervention ranged from 1.0 to 117.8 hours, varying depending on the diagnosis. For 101 (60%) of the patients, estimated driving time from the referring institution was less than one hour. Four patients (2%) expired in the emergency department, and 34 patients (20%) were admitted to a non-ICU setting. Six patients were discharged home within 24 hours. For those admitted, in-hospital mortality was 28%.Many patients undergoing interfacility transfer for neurosurgical evaluation are inappropriately triaged to helicopter transport, as evidenced by actual times to intervention at the accepting institution and estimated ground transportation times from the referring institution. In a time when there is growing interest in health care cost containment, practitioners must exercise discretion in the selection of patients for air ambulance transport--particularly when it may not bear influence on clinical outcome. Neurosurgical evaluation via telemedicine may be one strategy for improving air transport triage

Craniectomy for Malignant Cerebral Infarction: Prevalence and Outcomes in US Hospitals

Randomized trials have demonstrated the efficacy of craniectomy for the treatment of malignant cerebral edema following ischemic stroke. We sought to determine the prevalence and outcomes related to this by using a national database.Patient discharges with ischemic stroke as the primary diagnosis undergoing craniectomy were queried from the US Nationwide Inpatient Sample from 1999 to 2008. A subpopulation of patients was identified that underwent thrombolysis. Two primary end points were examined: in-hospital mortality and discharge to home/routine care. To facilitate interpretations, adjusted prevalence was calculated from the overall prevalence and two age-specific logistic regression models. The predictive margin was then generated using a multivariate logistic regression model to estimate the probability of in-hospital mortality after adjustment for admission type, admission source, length of stay, total hospital charges, chronic comorbidities, and medical complications.After excluding 71,996 patients with the diagnosis of intracranial hemorrhage and posterior intracranial circulation occlusion, we identified 4,248,955 adult hospitalizations with ischemic stroke as a primary diagnosis. The estimated rates of hospitalizations in craniectomy per 10,000 hospitalizations with ischemic stroke increased from 3.9 in 1999-2000 to 14.46 in 2007-2008 (p for linear trend<0.001). Patients 60+ years of age had in-hospital mortality of 44% while the 18-59 year old group was found to be 24% (p = 0.14). Outcomes were comparable if recombinant tissue plasminogen activator had been administered.Craniectomy is being increasingly performed for malignant cerebral edema following large territory cerebral ischemia. We suspect that the increase in the annual incidence of DC for malignant cerebral edema is directly related to the expanding collection of evidence in randomized trials that the operation is efficacious when performed in the correct patient population. In hospital mortality is high for all patients undergoing this procedure

Sporadic hemangioblastomas are characterized by cryptic VHL inactivation

Abstract Hemangioblastomas consist of 10-20% neoplastic “stromal” cells within a vascular tumor cell mass of reactive pericytes, endothelium and lymphocytes. Familial cases of central nervous system hemangioblastoma uniformly result from mutations in the Von Hippel-Lindau (VHL) gene. In contrast, inactivation of VHL has been previously observed in only a minority of sporadic hemangioblastomas, suggesting an alternative genetic etiology. We performed deep-coverage DNA sequencing on 32 sporadic hemangioblastomas (whole exome discovery cohort n = 10, validation n = 22), followed by analysis of clonality, copy number alteration, and somatic mutation. We identified somatic mutation, loss of heterozygosity and/or deletion of VHL in 8 of 10 discovery cohort tumors. VHL inactivating events were ultimately detected in 78% (25/32) of cases. No other gene was significantly mutated. Overall, deep-coverage sequence analysis techniques uncovered VHL alterations within the neoplastic fraction of these tumors at higher frequencies than previously reported. Our findings support the central role of VHL inactivation in the molecular pathogenesis of both familial and sporadic hemangioblastomas.http://deepblue.lib.umich.edu/bitstream/2027.42/110224/1/40478_2014_Article_167.pd

Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma

Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny. Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures. We infer that most cancer cells are differentiated along two specialized glial programs, whereas a rare subpopulation of cells is undifferentiated and associated with a neural stem cell expression program. Cells with expression signatures for proliferation are highly enriched in this rare subpopulation, consistent with a model in which CSCs are primarily responsible for fuelling the growth of oligodendroglioma in humans. Analysis of copy number variation (CNV) shows that distinct CNV sub-clones within tumours display similar cellular hierarchies, suggesting that the architecture of oligodendroglioma is primarily dictated by developmental programs. Subclonal point mutation analysis supports a similar model, although a full phylogenetic tree would be required to definitively determine the effect of genetic evolution on the inferred hierarchies. Our single-cell analyses provide insight into the cellular architecture of oligodendrogliomas at single-cell resolution and support the cancer stem cell model, with substantial implications for disease management

Investigating the scope of resident patient care handoffs within neurosurgery.

INTRODUCTION: Handoffs are defined as verbal and written communications during patient care transitions. With the passage of recent ACMGE work hour rules further limiting the hours interns can spend in the hospital, many fear that more handoffs will occur, putting patient safety at risk. The issue of handoffs has not been studied in the neurosurgical literature. METHODS: A validated, 20-question online-survey was sent to neurosurgical residents in all 98 accredited U.S. neurosurgery programs. Survey results were analyzed using tabulations. RESULTS: 449 surveys were completed yielding a 56% response rate. 63% of neurosurgical residents surveyed had not received formal instruction in what constitutes an effective handoff; 24% believe there is high to moderate variability among their co-residents in terms of the quality of the handoff provided; 55% experience three or more interruptions during handoffs on average. 90% of neurosurgical residents surveyed say that handoff most often occurs in a quiet, private area and 56% report a high level of comfort for knowing the potential acute, critical issues affecting a patient when receiving a handoff. CONCLUSIONS: There needs to be more focused education devoted to learning effective patient-care handoffs in neurosurgical training programs. Increasingly, handing off a patient adequately and safely is becoming a required skill of residency

Conflict of interest in spine research reporting.

BACKGROUND: Medical studies are more likely to report favorable findings when a conflict of interest is declared. We aim to quantify and determine the effect of author disclosure of conflict of interest on scientific reporting. METHODS: Abstracts from an international spine research meeting (North American Spine Society 2010) were selected that specifically evaluated a device, biologic, or proprietary procedure. They were then made anonymous to reviewers. An item of interest was established in each of the abstracts in order to standardize evaluation. Next, three blinded reviewers independently rated the abstracts as favorable, neutral, or unfavorable with regard to the item of interest. Additionally, the blinded reviewers attempted to predict whether a related disclosure was made. The meeting disclosure index was used to tabulate the minimum US dollar value attributable to disclosures. RESULTS: Of the 344 total abstracts, 76 met inclusion criteria. In 79%, a related conflict of interest was reported. The amount of the disclosure was incompletely reported in 30% of cases. Where available, it averaged a cumulative minimum of $219,634 USD per abstract. The results of the abstracts were judged to be favorable, neutral, and unfavorable in 63%, 32% and 5% of abstracts, respectively. There was no correlation between the presence of a related disclosure and the findings of the studies (p = 0.81), although interpretation of this is limited by a small sample size and an overall apparent bias to report favorable studies. Additionally, the blinded reviewers were unable to predict whether a related disclosure was made (p = 0.40). CONCLUSION: No association existed between the presence of a related disclosure and the results of the studies. While the actual compliance with reporting a potential conflict of interest is unable to be determined, the value amount related to the disclosures made was inadequately reported according to meeting guidelines

Trends in Peptic Ulcer Disease and the Identification of Helicobacter Pylori as a Causative Organism: Population-based Estimates from the US Nationwide Inpatient Sample

Background: Peptic ulcer disease can lead to serious complications including massive hemorrhage or bowel perforation. The modern treatment of peptic ulcer disease has transitioned from the control of gastric acid secretion to include antibiotic therapy in light of the identification of Helicobacter pylori as a causative infectious organism. We sought to determine trends related to this discovery by using a national database. Materials and Methods: Patient discharges with peptic ulcer disease and associated sequelae were queried from the Nationwide Inpatient Sample, 1993 to 2007, under the auspices of a data user agreement. To account for the Nationwide Inpatient Sample weighting schema, design-adjusted analyses were used. Standard error was calculated using SUDAAN software (Research Triangle International, NC, USA). Results: Decreases in the incidences of gastrointestinal perforation, gastrointestinal hemorrhage, and surgical procedures most specific to peptic ulcer disease were statistically significant over the study period [range of P value (two tailed) = 0.000 - 0.00353; significant at P < 0.001 to < 0.01]. The incidence of H. pylori rose dramatically, peaking at an estimated 97,823 cases in 1998 [SE = 3155; 95% CI = 6,184]. Since that time it has decreased and then stabilized. Conclusions: The identification of H. pylori as the causative agent in the majority of peptic ulcer disease has revolutionized the understanding and management of the disease. Medical conditions and surgical procedures associated with end-stage peptic ulcer disease have significantly decreased according to analysis of selected index categories. Resident physician education objectives may need to be modified in light of these trends. Review Criteria: We reviewed patients with peptic ulcer disease. The database used was the Nationwide Inpatient Sample, 1993 to 2007. Message for the Clinic: Medical therapy has resulted in decreased morbidity from H. pylori infection as it is the causative agent in the majority of peptic ulcer disease. Aggressive screening and treatment of this infection will lead to further reduction in morbidity