Neurosurgery Blog

Neurosurgery 71:201–223, 2012

Significant work from many laboratories over the last decade in the study of cancer immunology has resulted in the development of the cancer immunoediting hypothesis. This contemporary framework of the naturally arising immune system–tumor interaction is thought to comprise 3 phases: elimination, wherein immunity subserves an extrinsic tumor suppressor function and destroys nascent tumor cells; equilibrium, wherein tumor cells are constrained in a period of latency under immune control; and escape, wherein tumor cells outpace immunity and progress clinically.

In this review, we address in detail the relevance of the cancer immunoediting concept to neurosurgeons and neuro-oncologists treating and studying malignant glioma by exploring the de novo immune response to these tumors, how these tumors may persist in vivo, the mechanisms by which these cells may escape/attenuate immunity, and ultimately how this concept may influence our immunotherapeutic approaches.

Neurosurgery 71:117–125, 2012 DOI: 10.1227/NEU.0b013e3182532e71

The management of spinal column tumors continues to be a challenge for clinicians. The mechanisms of tumor recurrence after surgical intervention as well as resistance to radiation and chemotherapy continue to be elucidated. Furthermore, the pathophysiology of metastatic spread remains an area of active investigation.

There is a growing body of evidence pointing to the existence of a subset of tumor cells with high tumorigenic potential in many spine cancers that exhibit characteristics similar to those of stem cells. The ability to self-renew and differentiate into multiple lineages is the hallmark of stem cells, and tumor cells that exhibit these characteristics have been described as cancer stem cells (CSCs).

The mechanisms that allow nonmalignant stem cells to promote normal developmental programming by way of enhanced proliferation, promotion of angiogenesis, and increased motility may be used by CSCs to fuel carcinogenesis.

The purpose of this review is to discuss what is known about the role of CSCs in tumors of the osseous spine. First, this article reviews the fundamental concepts critical to understanding the role of CSCs with respect to chemoresistance, radioresistance, and metastatic disease. This discussion is followed by a review of what is known about the role of CSCs in the most common primary tumors of the osseous spine.

Neurosurgery 69:980–994, 2011 DOI: 10.1227/NEU.0b013e318220a672

Despite advances in surgery, radiation, and chemotherapy, malignant gliomas are still highly lethal tumors. Traditional treatments that rely on nonspecific, cytotoxic approaches have a marginal impact on patient survival.

However, recent advances in the molecular cancer biology underlying glioma pathogenesis have revealed that abnormalities in common cell surface receptors, including receptor tyrosine kinase and other cytokines, mediate the abnormal cellular signal pathways and aggressive biological behavior among the majority of these tumors.

Some cell surface receptors have been targeted by novel agents in preclinical and clinical development. Such cancer-specific targeted agents might offer the promise of improved cancer control without substantial toxicity.

Here, we review these common cell surface receptors with clinical significance for malignant glioma and discuss the molecular characteristics, pathological significance, and potential therapeutic application of these cell surface receptors.

We also summarize the clinical trials of drugs targeting these cell surface receptors in malignant glioma patients.

J Neurosurg 112:233–246, 2010. (DOI: 10.3171/2009.12.JNS091600)

Object. The term “citation classic” has been used in reference to an article that has been cited more than 400 times. The purpose of this study is to identify such articles that pertain to clinical neurosurgery.

Methods. A list of search phrases relating to neurosurgery was compiled. A topic search was performed using the Institute for Scientific Information Web of Science for phrases. Articles with more than 400 citations were identified, and nonclinical articles were omitted. The journals, year of publication, topics, and study types were analyzed.

Results. There were 106 articles with more than 400 citations relating to clinical neurosurgery. These articles appeared in 28 different journals, with more than half appearing in the Journal of Neurosurgery or the New England Journal of Medicine. Fifty-three articles were published since 1990. There were 38 articles on cerebrovascular disease, 21 on stereotactic and functional neurosurgery, 21 on neurooncology, 19 on trauma, 4 on nontraumatic spine, 2 on CSF pathologies, and 1 on infection. There were 29 randomized trials, of which 86% appeared in the New England Journal of Medicine, Lancet, or the Journal of the American Medical Association, and half concerned the prevention or treatment of stroke. In addition, there were 16 prospective studies, 15 classification or grading systems, and 7 reviews. The remaining 39 articles were case series, case reports, or technical notes.

Conclusions. More than half of the citation classics identified in this study have been published in the past 20 years. Case series, classifications, and reviews appeared more frequently in neurosurgical journals, while randomized controlled trials tended to be published in general medical journals.

J Neurosurg 112:223–232, 2010.(DOI: 10.3171/2009.12.JNS091599)

Object. The number of citations a published article receives is a measure of its impact in the scientific community. This study identifies and characterizes the current 100 top-cited articles in journals specifically dedicated to neurosurgery.

Methods. Neurosurgical journals were identified using the Institute for Scientific Information Journal Citation Reports. A search was performed using Institute for Scientific Information Web of Science for articles appearing in each of these journals. The 100 top-cited articles were selected and analyzed.

Results. The 100 most cited manuscripts in neurosurgical journals appeared in 3 of 13 journals dedicated to neurosurgery. These included 79 in the Journal of Neurosurgery, 11 in the Journal of Neurology, Neurosurgery and Psychiatry, and 10 in Neurosurgery. The individual citation counts for these articles ranged from 287 to 1515. Seventy- seven percent of articles were published between 1976 and 1995. Representation varied widely across neurosurgical disciplines, with cerebrovascular diseases leading (43 articles), followed by trauma (27 articles), stereotactic and functional neurosurgery (13 articles), and neurooncology (12 articles). The study types included 5 randomized trials, 5 cooperative studies, 1 observational cohort study, 69 case series, 8 review articles, and 12 animal studies. Thirty articles dealt with surgical management and 12 with nonsurgical management. There were 15 studies of natural history of disease or outcomes after trauma, 11 classification or grading scales, and 10 studies of human pathophysiology.

Conclusions. The most cited articles in neurosurgical journals are trials evaluating surgical or medical therapies, descriptions of novel techniques, or systems for classifying or grading disease. The time of publication, field of study, nature of the work, and the journal in which the work appears are possible determinants of the likelihood of citation and impact.

Journal of Neurosurgery, Aug 2009, Vol. 111, No. 2, Pages 387-392

Object
Assessing academic productivity through simple quantification may overlook key information, and the use of statistical enumeration of academic output is growing. The h index, which incorporates both the total number of publications and the citations of those publications, has been recently proposed as an objective measure of academic productivity. The authors used several tools to calculate the h index for academic neurosurgeons to provide a basis for evaluating publishing by physicians.

Methods
The h index of randomly selected academic neurosurgeons from a sample of one-third of the academic programs in the US was calculated using data from Google Scholar and from the Scopus database. The mean h index for each academic rank was determined. The h indices were also correlated with various other factors (such as time spent practicing neurosurgery, authorship position) to identify how these factors influenced the h index. The h indices were then compared with other citation statistics to evaluate the robustness of this metric. Finally, h indices were also calculated for a sampling of physicians in other medical specialties for comparison.

Results
As expected, the h index increased with academic rank and there was a statistically significant difference between each rank. A weighting based on position of authorship did not affect h indices. The h index was positively correlated with time since American Board of Neurological Surgery certification, and it was also correlated with other citation metrics. A comparison among medical specialties supports the assertion that h index values may not be comparable between fields, even closely related specialties.

Conclusions
The h index appears to be a robust statistic for comparing academic output of neurosurgeons. Within the field of academic neurosurgery, clear differences of h indices between academic ranks exist. On average, an increase of the h index by 5 appears to correspond to the next highest academic rank, with the exception of chairperson. The h index can be used as a tool, along with other evaluations, to evaluate an individual’s productivity in the academic advancement process within the field of neurosurgery but should not be used for comparisons across medical specialties.