Growth factors play an important role in the development of the normal central nervous system as well as in the genesis of central nervous system tumors. Some of the more important growth factors and growth factor receptors, as they pertain to neurooncology, are reviewed in this article.
Barbara E. Lazio and Lawrence S. Chin
Lawrence S. Chin and David R. Hinton
✓ Tissue markers of cellular proliferation have been recently utilized as prognostic indicators in tumors of the central nervous system. Nucleolar organizer regions represent transcriptionally active sites of ribosomal deoxyribonucleic acid (DNA) and can be identified by a simple argyrophilic technique. The authors describe a standardized approach to the assessment of these argyrophilic nucleolar organizer regions in meningeal tumors. Twenty-five meningiomas were classified histologically into benign, atypical, or malignant groups. In addition, two hemangiopericytomas and one leptomeningeal melanoma were examined. Appropriate sections were silver stained and argyrophilic nucleolar organizer regions were counted in 200 nuclei. The mean argyrophilic nucleolar organizer region count was statistically different (p < 0.001) between benign tumors (245 ± 156, 1.23/cell), atypical tumors (497 ± 135, 2.49/cell), and malignant tumors (921 ± 59, 4.61/cell). The count for recurrent meningiomas (544 ± 76) was also statistically different (p < 0.02) from non-recurrent tumors (329 ± 183). The standardized assessment of argyrophilic nucleolar organizer regions can be easily performed by any surgical pathology laboratory without specialized equipment and, in meningeal tumors, may be useful as an independent indicator of biological behavior.
Haydn Hoffman, Taylor Furst, Muhammad S. Jalal and Lawrence S. Chin
There is increasing interest in the use of 30-day readmission (30dRA) as a quality metric to represent hospital and provider performance. Data regarding the incidence and risk factors for 30dRA after traumatic brain injury (TBI) are sparse. The authors sought to characterize these variables using a national database.
The Nationwide Readmissions Database was used to identify patients with a primary diagnosis of TBI who underwent craniotomy or craniectomy between 2010 and 2014. Our primary outcome of interest was 30dRA. Binary logistic regression was used to identify variables related to patient demographics, comorbidities, and index hospital admission that were associated with 30dRA.
A total of 25,354 patients met the inclusion criteria. The 30dRA rate during the entire study period was 15.5%. In 2010 the 30dRA rate was 16.8% and in 2014 it decreased to 15.1% (pooled OR 0.90, 95% CI 0.87–0.94). The mean cost associated with a 30dRA increased slightly but significantly, from $9999 in 2010 to $10,114 in 2014 (p = 0.021). Factors associated with increased odds of 30dRA in the binary logistic regression included increased age, greater comorbidity burden, more severe injury, tracheostomy, gastrostomy, sodium abnormality, and venous thromboembolism. In order of decreasing frequency, the most common causes for 30dRA were neurological, injury/iatrogenic, cardiovascular/cerebrovascular, infectious, and respiratory.
The incidence of 30dRA after craniotomy for TBI decreased slightly from 2010 to 2014. This study identified several variables associated with 30dRA that require confirmation in a prospective study, which could direct attempts to prevent readmissions.
Lawrence S. Chin, Keith L. Black and Julian T. Hoff
✓ A patient with herniated thoracic discs in tandem is reported. The previous literature is reviewed. Difficulties with the preoperative diagnosis and the surgical approach to these lesions are discussed.
Nader Sanai and Mitchel S. Berger
Lawrence S. Chin, Lijun Ma and Steven DiBiase
Object. Radiation necrosis is the only significant complication of gamma knife surgery (GKS). The authors studied treatment plan parameters in patients who had radiation necrosis to determine if risk factors for necrosis could be identified.
Methods. Between September 1994 and December 1998, 286 patients were treated with GKS by the senior author. Of the 243 patients who were suitable for analysis, 17 developed radiation necrosis and were prospectively followed. Concurrently, 17 patients without necrosis were randomly selected as case controls on the basis of histological findings in their lesions. Integral dose—volume histograms (DVHs) were calculated and dose—volume treatment parameters were determined. A comparison was made with both the established Kjellberg and Flickinger isonecrosis risk lines. Clinical outcome was assessed according to time to resolution of symptoms and return to normal radiographic appearance.
Conclusions. Treatment plan variables associated with the risk of necrosis were increased tumor volume (TV) integral dose, increased TV, and increased 10-Gy volume. Other risk factors included repeated radiosurgery to the same lesion and glioma histological findings. The Kjellberg 1% risk line predicted a 5% risk of radiation necrosis and the Flickinger 3% risk line predicted a 3% risk. The median time to development of necrosis was 4 months, and symptomatic and radiographic recovery times were 7.5 and 10.5 months, respectively. The median survival time in patients with necrosis was 30 months. The authors recommend prospective TV determination and DVH calculation for all radiosurgical treatments and the avoidance of repeated radiosurgical treatments to the same lesion when possible.
Lawrence S. Chin, Nicholas J. Szerlip and William F. Regine
Meningiomas are benign tumors attached to the dura that typically have a slow growth rate. After gliomas, they are the most common primary tumor of the brain. They are ideal radiobiological targets because single-fraction radiation has a high biologically effective dose. Furthermore, a highly conformal radiation plan can provide effective treatment to the tumor while sparing the surrounding brain. Meningioma control rates range from 90 to 95%, and the risk of morbidity is low. Radiosurgery is an excellent treatment for asymptomatic, small- to moderate-sized meningiomas. It is also ideal for patients with incompletely resected meningiomas, recurrent meningiomas, and risk factors precluding conventional surgery.
Lawrence S. Chin, Saytendra K. Singh and Howard M. Eisenberg
Zhigang Xie and Lawrence S. Chin
✓ The results of studies conducted in the past several years have suggested that malignant brain tumors may harbor a small fraction of tumor-initiating cells that are likely to cause tumor recurrence. These cells are known as brain tumor stem cells (BTSCs) because of their multilineage potential and their ability to self-renew in vitro and to recapitulate original tumors in vivo. The understanding of BTSCs has been greatly advanced by knowledge of neural progenitor/stem cells (NPSCs), which are multipotent and self-renewing precursor cells for neurons and glia. In this article, the authors summarize evidence that genetic mutations that deregulate asymmetric cell division by affecting cell polarity, spindle orientation, or cell fate determinants may result in the conversion of NPSCs to BTSCs. In addition, they review evidence that BTSCs and normal NPSCs may reside in similar vascularized microenvironments, where similar evolutionarily conserved signaling pathways control their proliferation. Finally, they discuss preliminary evidence that mechanisms of BTSC-associated infiltrativeness may be similar to those underlying the migration of NPSCs and neurons.
David H. Harter, Patrick F. Doherty and Lawrence S. Chin
Apoptosis is a carefully regulated process involved in developmental and immunological events. The alteration of apoptotic pathways is important in the establishment and progression of neoplasia. Apoptosis allows for the orderly removal of excess cells but, in contrast to necrosis, it is not an inflammatory process. Many of the molecular components and effectors of apoptosis have been described. In this review the authors briefly discuss the current understanding of apoptosis in the context of the two prevailing hypotheses, the “conflicting signal” and “dual signal” theories.