Introduction to special issue dedicated to the 35th anniversary of the joint section on tumors.

The American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) Joint Section on Tumors was formed in December of 1984 as the first professional organization devoted to the study and treatment of brain tumors. One year earlier, the Journal of Neuro-Oncology had been established and went on to be sponsored by the Joint Section on Tumors. To celebrate the 35th anniversary of the founding of the Section, we are thrilled to bring you this special issue of Journal of Neuro-Oncology in which current leaders of the Joint Section on Tumors highlight their work and the work of others that have led to significant recent advances in the management of tumors of the central nervous system.

Prediction of neuroblastoma cell response to treatment with natural or synthetic retinoids using selected protein biomarkers.

Although the administration of retinoids represents an important part of treatment for children suffering from high-risk neuroblastomas, approximately 50% of these patients do not respond to this therapy or develop resistance to retinoids during treatment. Our study focused on the comparative analysis of the expression of five genes and corresponding proteins (DDX39A, HMGA1, HMGA2, HOXC9 and PBX1) that have recently been discussed as possible predictive biomarkers of clinical response to retinoid differentiation therapy. Expression of these five candidate biomarkers was evaluated at both the mRNA and protein level in the same subset of 8 neuroblastoma cell lines after treatment with natural or synthetic retinoids. We found that the cell lines that were HMGA2-positive and/or HOXC9-negative have a reduced sensitivity to retinoids. Furthermore, the experiments revealed that the retinoid-sensitive cell lines showed a uniform pattern of change after treatment with both natural and sensitive retinoids: increased DDX39A and decreased PBX1 protein levels. Our results showed that in NBL cells, these putative protein biomarkers are associated with sensitivity or resistance to retinoids, and their endogenous or induced expression can distinguish between these two phenotypes.

Perfil dos pacientes pediátricos com tumores da glia internados para tratamento neurocirúrgico em hospital terciário no Rio de Janeiro / Clinical profile of patients with glial tumors hospitalized for neurosurgical treatment at a tertiary center in Rio de Janeiro

Os tumores do Sistema Nervoso Central representam uma patologia com grande impacto no sistema de saúde e sua incidência tem aumentado nos últimos anos. A maior parte destes tumores deriva das células da neuroglia e o tratamento neurocirúrgico é, muitas vezes, o primeiro passo na linha de tratamento oncológico multimodal. O presente estudo tem como objetivo descrever o perfil dos pacientes portadores de tumores da glia internados para tratamento neurocirúrgico em um centro terciário no Rio de Janeiro. Foram avaliados 74 registros de internação, com 70 pacientes entre 0 e 18 anos, através de revisão de prontuário, com resgate de informações referentes à história clínica, exame físico, exames de imagem, dados intra-operatórios e de internação em Unidade de Terapia Intensiva. No estudo, 57,1% dos pacientes pertenciam ao sexo masculino e a média de idade foi de 8,98 anos. A maioria dos tumores foi classificada como astrocitomas (50%) e a localização mais frequente foi a fossa posterior (54,28%), notadamente a região mediana do cerebelo. Não foi encontrada relação entre as características clínicas e o desfecho, mas a análise multivariada identificou quatro grupos que correspondem a perfis distintos, tanto no que se refere às características da lesão tumoral (histopatologia), tratamento neurocirúrgico (grau de ressecção, necessidade de reabordagens operatórias) e manejo peroperatório (duração da internação, complicações clínicas e cirúrgicas).

Central Nervous System tumors have a great impact on the health system and its incidence has increased in recent years. Most of these tumors are derived from the cells of the neuroglia and neurosurgical treatment is often the first step in the line of multimodal cancer treatment. The present study aims to describe the clinical profile of patients with glial tumors hospitalized for neurosurgical treatment at a tertiary center in Rio de Janeiro. A total of 74 hospitalization records were evaluated, with 70 patients between 0 and 18 years of age, through a review of medical records, retrieving informations on clinical history, physical examination, images, intraoperative and hospitalization in the Intensive Care Unit data. In the study, 57.1% of the patients were male and the average age was 8.98 years. Most tumors were classified as astrocytomas (50%) and the most frequent location was the posterior fossa (54.28%), notably the median region of the cerebellum. No relationship was found between clinical characteristics and outcome, but multivariate analysis identified four groups that correspond to distinct profiles, both regarding tumor lesion characteristics (histopathology), neurosurgical treatment (degree of resection, need for operative re-approaches) and perioperative management (length of stay, clinical and surgical complications).

[Influence of postoperative infection on hospitalization day and medical costs of patients with nervous system tumor].

Objective: To investigate the influence of postoperative infection on average hospitalization days and medical costs in patients with nervous system tumor. Methods: The tumor patients treated in neurosurgery ward from July 1, 2015 to June 30, 2017 were included in the study. The patients with and without postoperative infections were divided into a case group and a control group, respectively (1 ∶ 1 ratio), matched by admission time (±3 months), age (±5 years) and surgical site. Average hospitalization days and medical costs between the two groups were analyzed. Results: The incidence of postoperative infection was 5.66%, the surgical site infection and lower respiratory tract infection accounted for 54.72% and 31.32% of the total, respectively. The median of hospitalization days in the case group was 20.5, 8.5 days longer than that in the control group (Z=-10.618, P<0.001). The median of total medical costs in the case group was 91 573.42 yuan, higher than that of the control group by 30 518.17 yuan (Z=-9.988, P<0.001). The average costs of surgical and lower respiratory tract infection were 84 888.50 yuan and 110 442.64 yuan, respectively. Among them, surgical site infection or lower respiratory tract infection caused the extra cost of 23 627.49 yuan (Z=-6.627, P<0.001) and 43 631.36 yuan (Z=-4.954, P<0.001), respectively. Conclusions: Postoperative infection greatly increased the patient's financial burden, prolonged the hospitalization duration and resulted in unnecessary use of health resources. It is necessary to pay close attention to postoperative infection.

Survival and complications of stereotactic radiosurgery: A systematic review of stereotactic radiosurgery for newly diagnosed and recurrent high-grade gliomas.

BACKGROUND: Utilization of stereotactic radiosurgery (SRS) for treatment of high-grade gliomas (HGGs) has been slowly increasing with variable reported success rates. OBJECTIVE: Systematic review of the available data to evaluate the efficacy of SRS as a treatment for HGG with regards to median overall survival (OS) and progression-free survival (PFS), in addition to ascertaining the rate of radiation necrosis and other SRS-related major neurological complications. METHODS: Literature searches were performed for publications from 1992 to 2016. The pooled estimates of median PFS and median OS were calculated as a weighted estimate of population medians. Meta-analyses of published rates of radiation necrosis and other major neurological complications were also performed. RESULTS: Twenty-nine studies reported the use of SRS for recurrent HGG, and 16 studies reported the use of SRS for newly diagnosed HGG. For recurrent HGG, the pooled estimates of median PFS and median OS were 5.42 months (3-16 months) and 20.19 months (9-65 months), respectively; the pooled radiation necrosis rate was 5.9% (0-44%); and the pooled estimates of major neurological complications rate was 3.3% (0-23%). For newly diagnosed HGG, the pooled estimates of median PFS and median OS were 7.89 months (5.5-11 months) and 16.87 months (9.5-33 months) respectively; the pooled radiation necrosis rate was 6.5% (0-33%); and the pooled estimates of other major neurological complications rate was 1.5% (0-25%). CONCLUSION: Our results suggest that SRS holds promise as a relatively safe treatment option for HGG. In terms of efficacy at this time, there are inadequate data to support routine utilization of SRS as the standard of care for newly diagnosed or recurrent HGG. Further studies should be pursued to define more clearly the therapeutic role of SRS.

Emerging Indications for Fractionated Gamma Knife Radiosurgery.

BACKGROUND: Gamma Knife radiosurgery (GKRS) allows for the treatment of intracranial tumors with a high degree of dose conformality and precision. There are, however, certain situations wherein the dose conformality of GKRS is desired, but single session treatment is contraindicated. In these situations, a traditional pin-based GKRS head frame cannot be used, as it precludes fractionated treatment. OBJECTIVE: To report our experience in treating patients with fractionated GKRS using a relocatable, noninvasive immobilization system. METHODS: Patients were considered candidates for fractionated GKRS if they had one or more of the following indications: a benign tumor >10 cc in volume or abutting the optic pathway, a vestibular schwannoma with the intent of hearing preservation, or a tumor previously irradiated with single fraction GKRS. The immobilization device used for all patients was the Extend system (Leksell Gamma Knife Perfexion, Elekta, Kungstensgatan, Stockholm). RESULTS: We identified 34 patients treated with fractionated GKRS between August 2013 and February 2015. There were a total of 37 tumors treated including 15 meningiomas, 11 pituitary adenomas, 6 brain metastases, 4 vestibular schwannomas, and 1 hemangioma. At last follow-up, all 21 patients treated for perioptic tumors had stable or improved vision and all 4 patients treated for vestibular schwannoma maintained serviceable hearing. No severe adverse events were reported. CONCLUSION: Fractionated GKRS was well-tolerated in the treatment of large meningiomas, perioptic tumors, vestibular schwannomas with intent of hearing preservation, and in reirradiation of previously treated tumors.

Surgical Treatment of Neuromas Improves Patient-Reported Pain, Depression, and Quality of Life.

BACKGROUND: Surgical management of neuromas is difficult, with no consensus on the most effective surgical procedure to improve pain and quality of life. This study evaluated the surgical treatment of neuromas by neurectomy, crush, and proximal transposition on improvement in pain, depression, and quality of life. METHODS: Patients who underwent neuroma excision and proximal transposition were evaluated. Preoperative and postoperative visual analogue scale scores for pain (worst and average), depression, and quality of life were assessed using linear regression, and means were compared using paired t tests. The Disabilities of the Arm, Shoulder, and Hand questionnaire score was calculated preoperatively and postoperatively for upper extremity neuroma patients. Patients with long-term follow-up were analyzed using repeated measures analysis of variance comparing preoperative, postoperative, and long-term visual analogue scale scores. RESULTS: Seventy patients (37 with upper extremity neuromas and 33 with lower extremity neuromas) met inclusion criteria. Statistically significant improvements in visual analogue scale scores were demonstrated for all four patient-rated qualities (p < 0.01) independent of duration of initial clinical follow-up. The change in preoperative to postoperative visual analogue scale scores was related inversely to the severity of preoperative scores for pain and depression. Neuroma excision and proximal transposition were equally effective in treating lower and upper extremity neuromas. Upper extremity neuroma patients had a statistically significant improvement in Disabilities of the Arm, Shoulder, and Hand questionnaire scores after surgical treatment (p < 0.02). CONCLUSIONS: Surgical neurectomy, crush, and proximal nerve transposition significantly improved self-reported pain, depression, and quality-of-life scores. Surgical intervention is a viable treatment of neuroma pain and should be considered in patients with symptomatic neuromas refractory to nonoperative management. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Laser Interstitial Thermal Therapy: Lighting the Way to a New Treatment Option in Neurosurgery.

ABBREVIATIONS: LITT, laser interstitial therapyNd:YAG, neodymium-doped yttrium aluminum.

The role of high-dose myeloablative chemotherapy with haematopoietic stem cell transplantation (HSCT) in children with central nervous system (CNS) tumours: protocol for a systematic review and meta-analysis.

OBJECTIVES: The objective of the study is to conduct a systematic review to compare the effects of high-dose chemotherapy (HDCT) with autologous haematopoietic stem cell transplantation (HSCT) versus standard-dose chemotherapy (SDCT) in children with malignant central nervous system (CNS) tumours. METHODS: Standard systematic review methods aimed at minimising bias will be employed for study identification, selection and data extraction. Ten electronic databases will be searched, along with citation searching and reference checking. Studies assessing the effects of HDCT with HSCT in children with CNS tumours will be included. The outcomes are survival (overall, progression-free, event-free, disease-free), response rates, short- and long-term adverse events and health-related quality of life (HRQoL). Two reviewers will independently screen and select randomised and non-randomised controlled trials and controlled and uncontrolled observational studies for inclusion. Quality assessment will be tailored to the different study designs. Where possible data will be summarised using combined estimates of effect for the hazard ratio for survival outcomes and the risk ratio for response rates. A fixed effect model will be used; sub-group analyses and meta-regression will be used to explore potential sources of heterogeneity between studies. DISCUSSION: Given the poor prognosis of malignant brain tumours in children in terms of survival and quality of life, this review will help guide clinical practice by summarising the current evidence on the use of high-dose myeloblative chemotherapy with stem cell support in children with CNS tumours.

Vagus nerve schwannoma in the parapharyngeal space: surgical, histological and immunohistochemical aspects. A case report.

Tumors of the parapharyngeal space are rare accounting approximately for 0.5% of all head and neck tumors. In the retrostyloid space, schwannomas are a more common finding, in contrast to other tumors. Usually, they present with a variety of slight symptoms until they grow in size and compress surrounding organs. Surgical treatment of parapharyngeal space tumors is difficult; due to the anatomical complex area, they develop in, and include several approaches, according to its size and relations. In this paper, we present a case of a 63-year-old female with a vagus nerve schwannoma in the parapharyngeal space. Beside the surgical difficulties, the resected tumor had a peculiar histopathological aspect (large areas of degeneration and atypia and little typical palisading) that compelled a thorough histological and immunohistochemical evaluation for positive and differential diagnosis.

Feasibility of the EORTC/NCIC Trial Protocol in a Neurosurgical Outpatient Unit: The Case for Neurosurgical Neuro-Oncology.

OBJECTIVE: With the publication of the European Organization for Research and Treatment of Cancer/National Cancer Information Center (EORTC/NCIC) trial, concomitant radiochemotherapy followed by intermittent chemotherapy became the new treatment standard for patients with primary glioblastoma. Eight years after widespread introduction of this protocol, it is of interest to investigate whether this new standard has been established in daily neuro-oncologic practice. We were particularly interested in its practicality within a neurosurgical neuro-oncologic setting. PATIENTS AND METHODS: We analyzed primary glioblastoma patients diagnosed between 2005 and 2013 treated at our center according to the EORTC/NCIC trial. Parameters associated with treatment performance (interruption of radiotherapy, concomitant chemotherapy and intermittent chemotherapy, total number of cycles, and side effects) were retrospectively analyzed and compared with the available data from the EORTC/NCIC trial. RESULTS: In this single-center retrospective study, we identified 189 patients (116 men, 73 women; median age: 62 years) who were treated according to the EORTC/NCIC trial protocol. A total of 176 patients received cytoreductive surgery; 13 patients had stereotactic biopsy only (EORTC/NCIC trial: 239 patients and 48 patients, respectively). Radiotherapy had to be interrupted in 9 patients (5%) (EORTC/NCIC trial: 15 patients [5%]) and concomitant chemotherapy in 26 patients (14%) (EORTC/NCIC trial: 37 patients [13%]). In 156 patients (83%), adjuvant TMZ chemotherapy was initiated (6 median temozolomide [TMZ] cycles; range: 1-30). In the EORTC/NCIC trial, 223 patients (47%) received the intermittent chemotherapy protocol (median: 3 cycles; range: 1-7). Overall, 97 patients (62%) completed 6 TMZ cycles (EORTC/NCIC-trial: 105 patients [47%]); dose escalation to 200 mg/qm at the second cycle was performed in 91 patients (58%) (versus 149 patients [67%]). Intermittent TMZ therapy was discontinued in 59 patients (38%) (versus 118 patients [53%]). Median overall survival in our patient cohort was 19 months (versus 14.6 months); median time to progression was 9 months (versus 6.9 months). CONCLUSION: Comparison between the feasibility of the treatment protocol established by the EORTC/NCIC trial (performed within the setting of a prospective randomized trial) and the daily routine in a dedicated neurosurgical neuro-oncologic department demonstrates that the protocol is suitable for daily practice within a neurosurgical unit.

Neuroma-in-continuity of the median nerve managed by nerve expansion and direct suture with vein conduit.

Autologous nerve grafting is the current standard for bridging large gaps in major sensory and motor nerves. It allows both function and pain improvement with predictable results. Clinical observations of nerve elongation caused by tumours have prompted experimental animal studies of induced gradual elongation of the nerve stump proximal to the gap. This technique allows direct suturing of the two nerve ends to bridge the gap. Here, we describe a case of neuroma-in-continuity of the median nerve managed by resection and direct suture after nerve elongation with a tissue expander. We are not aware of similar reported cases. Secondary repair 3 years after the initial injury improved the pain and hypersensitivity and restored a modest degree of protective sensory function (grade S1).

Patterns of mediastinal tumors operated at the Tikur Anbessa Hospital, Addis Ababa, Ethiopia over a six years period.

BACKGROUND: The mediastinum is the space that lies between the two pleural cavities containing many vital structures in it. When tumors or cysts arise in the mediastinum they can be either asymptomatic or present as space occupying lesions causing symptoms and signs by their effect on the neighboring organs. Though mediastinal tumors are routinely treated at the study center, there are no studies in Ethiopia concerning the patterns, and modes of treatments of Mediastinal space occupying lesions. OBJECTIVE: To review all the primary mediastinal tumors and cysts operated upon at the Tikur Anbessa Teaching Hospital, Addis Ababa University over a six year period, from August 2005-2011. METHODOLOGY: Clinical retrospective review. RESULTS: In the six years, 73 patients were operated, 49 (67.1%) were males, the and male to female ratio being 2.04:1. The mean age of patients was 35.9 +/- 10.5 years (range 14 to 74). Forty-five (61.6%) had lesions of the anterior mediastinum, 23 (31.5%) in the posterior mediastinum and 5 (6.8%) in the middle. The commonest anterior mediastinal tumors were thymic origin (24/45), and thymic lesions were found more common in females (17:7 ratio). From the 23 patients with posterior mediastinal tumors, 18 had benign neurogenic tumors (4 of which were dumbbell tumors). Chest pain and shortness of breath (dyspnea) were the two most common symptoms in 31 (42.4%) of the patients. Twenty three patients (31.5%) were asymptomatic, and all had benign lesions. None of the malignant lesions were asymptomatic. Eleven (15%) patients; eight with anterior and three with posterior mediastinal masses, had undergone pre-operative tissue diagnosis procedure by image guided FNAC. Fifty-nine (80.8%) patients were operated with intent of therapeutic surgical procedures. There were 28 (38.5%) midline sternotomies, 40 (54.7%) thoracotomies, four underwent a left sided mediastinotomies and one mediastinoscopy performed. The rate of malignancy in this study was 24 (32.8%), of which 19 (79.1%) were in the anterior compartment. A total of 13 (17.8%) patients had complications in the hospital and four (5.4%) of the patients died CONCLUSION: Primary mediastinal tumors are not so rare in the setting. We would also like to recommend further large scale prospective studies which also included long-term outcome so that we can further understand the situation in the country.

The evolution of neurosurgery: how has our practice changed?

INTRODUCTION: Neurosurgery is a rapdily evolving speciality and has often taken a lead in adopting new technologies. Advancing technology however is not the only force driving change in this discipline. Other factors include an escalation in patient expectations, an increasing (and ageing) population and the prevailing economic conditions. The aim of our study was to analyse the trends in neurosurgical practice over a 10-year period. MATERIALS AND METHODS: The details of every neurosurgical procedure performed at Wellington Regional Hospital from 2001 to 2011 were prospectively recorded in a relational database. This was then retrospectively interrogated to provide data for this study. RESULTS: Neurosurgical practice has clearly evolved over the last decade. Predictable changes include a trend towards coiling rather than clipping of cerebral aneurysms, an increasing number of tumour resections (particularly for malignant glioma) coupled with the increased use of image guidance and endoscopy. The number of operations on the cervical spine has also increased although overall the number of procedures for spinal degenerative conditions has declined, perhaps reflecting local practice. The rates of craniotomy for trauma and burr holes for chronic subdural haematoma have remained essentially unchanged. We have demonstrated a significant increase in annual case-load that is disproportionate to any change in population size. Collaboration between specialties is increasingly evident. CONCLUSION: The most important changes have occured in the fields of neuro-oncology, vascular neurosurgery and spinal surgery. Inter-specialty collaboration is establishing itself as a model of care. These data may guide resource allocation for a population increasing both in number and in age.

Laparoscopic management of sacral nerve root schwannoma with intractable vulvococcygodynia: report of three cases and review of literature.

Herein we report the feasibility of laparoscopic resection of schwannomas of the sacral nerves roots in 3 women with intractable vulvodynia and coccygodynia. Laparoscopic en bloc resection of the sacral schwannomas was performed, with primary control of the tumor blood supply and with exposure and sparing of the sacral nerve roots. In all 3 patients, laparoscopy was successful, with minimal blood loss and without complications. Histologic examination confirmed the diagnosis of schwannoma without malignant transformation in all 3 women. At mean follow-up of 27.66 months, no patient reported recurrence or worsening of symptoms. All patients are able to walk normally without gait aids. Primary control of the tumor blood supply during laparoscopic surgery to resect deep sacral masses reduces considerably the risk of operative hemorrhage. Compared with classic neurosurgical approaches, laparoscopic exposure of the rectum, ureters, and sacral nerve roots renders the procedure safer and easier, with less risk of postoperative functional morbidity.

Cervical sympathetic chain schwannoma: a case report.

Nerve sheath tumours arising from the sympathetic chain are extremely rare and are a diagnostic challenge. We report the case of a 31- year-old man who presented with an asymptomatic right cervical swelling. He was evaluated with sonography, CT, MR and angiography. Surgical excision of the lesion was performed, and histological examination revealed a schwannoma. The differential diagnosis of such tumours and their management are discussed.

CT appearance of intercostal nerve neurotisation.

A nerve transfer or neurotisation procedure is performed to repair damaged nerves, in particular those of the brachial plexus following an avulsion injury. An intercostal to phrenic nerve transfer to re-innervate the diaphragm in patients with high cervical spine injury has also been reported in the literature. We present the imaging finding in a 65-year-old female who had an intercostal nerve transfer for a damaged phrenic nerve following a resection for a non-small cell lung carcinoma.