Impaired thymus-derived lymphocyte function in patients with malignant brain tumour

Cell-mediated immunity was evaluated in 28 patients with malignant glioma, using in vivo and in vitro tests of lymphocyte function. The results were compared to those found in patients with carcinomatosis (11 subjects), benign brain tumours (9), other neurological disorders (20) and normal, healthy controls (21). Significant impairments of delayed hypersensitivity responses to common antigens was found in patients with malignant glioma and in those with generalised malignancy. A less significant depression of lymphocyte responses was also detected in patients with meningioma. The impairment in cell-mediated immunity was shown not be due to a serum blocking factor. Our data indicate that there is defective T cell function in patients with glioma, similar to that reported in cases with malignancies outside the central nervous system. This impaired immunity may have clinical significance.     

Multifocal malignant glioma of the brain

Summary A case of multifocal malignant glioma of the brain in a 67-year-old male is presented. The main neoplastic focus occupied both the frontal lobes and the anterior portion of corpus callosum. Numerous small neoplastic foci, so-called satellite metastases surrounded the main neoplastic masses. There was a second neoplastic focus situated in the basal portion of the pons. This showed the histological features of the anaplastic glioma. No direct connection between two neoplastic foci was shown on serial section through the midbrain. There were blastomatoid glial cells seen in the unchanged nervous tissue of the pons and medulla, they were single or grouped in small clusters. The morphology of the pontine neoplasm and the presence of above mentioned blastomatoid astrocytes widespread throughout the brain stem suggested that we were dealing with primary multifocal growth of the glial tumour.

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Résumé On a presenté un cas de la tumeur neoplasmique, notamment un gliome maligne multiloculaire chez un malade âgé de 67 ans. Le foyer principal se trouve dans la région frontale bilateralement et infiltre la moitié anterieur du corps calleux. Ce foyer est entouré des petits foyers secondaires dits «métastases satellitaire». L'image microscopique de la tumeur correspond rélativement aux caractères d'un glioblastome multiforme.Dans la base du pont on a trouvé un autre foyer aux trais d'un gliome anaplastique, indepandant de la lésion principale.A part de cette seconde tumeur on a pu constater de nombreuses cellules blastomatiques parsemées parmi les fibres pontines, tantôt iselées, tantôt en petits groupe cellulaires.Les caractères morphologiques de la tumeur pontine et la présence des cellules blastomatiques isolées suggère qu'il s'agit dans ce cas d'un processus multifocalL'auteur discute la possibilité d'une gliopathie généralisée.

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With 3 Figures in the Text     

Quantitative analysis of brain edema in patients with malignant glioma treated with BCNU wafers

BCNU wafers are a form of interstitial chemotherapy that is expected to improve the survival of patients with malignant glioma. However, their adverse events, especially brain edema, sometimes cause significant clinical symptoms. In this study, we performed a volumetric analysis of brain edema after the implantation of BCNU wafers and reported on the clinical course, and exacerbation factors of brain edema. Twelve patients who underwent surgical resection of supratentorial malignant glioma and BCNU wafer implantation, were enrolled. Radiographic quantitative analysis was conducted and compared with a historical control. The volume change in brain edema was divided into three groups and correlation with clinical symptoms was then evaluated. Compared with the control group, the brain edema in the BCNU wafer implantation group was significantly prolonged after surgery. Radiographic volumetric analysis revealed an increase of more than 25% at any time after surgery in four patients (33%) and a reduction of less than 25%, 1 month after surgery in three patients (25%). Grade 3 clinical deterioration related to brain edema occurred in two patients and Grade 2 in one patient. Univariate analysis revealed that the radiographic deterioration of brain edema had no correlation with age, sex, diagnosis, tumor grade, preoperative volume of brain edema and tumor, residual tumor volume, or number of BCNU wafers. Radiographic quantitative analysis of brain edema indicated that BCNU wafer implantation may induce the prolongation and enlargement of brain edema with or without neurological deterioration. Brain edema may be controlled by intensive perioperative treatment with diuretics and corticosteroids.     

Primary malignant rhabdoid tumour of the brain in adults

Malignant rhabdoid tumour (MRT) was described for the first time in the kidney, and is rarely reported in the brain. Most rhabdoid tumours affect infants and young children and there have been only isolated adult patients reported. The optimal treatment for this very aggressive tumour has not yet been established. We describe the clinical and pathological features of a rare primary malignant rhabdoid tumour of the brain in a 27-year-old pregnant female. The literature is reviewed briefly and the role of the INI1 gene in adult MRTs and the also possible interactions between MRTs and pregnancy are discussed.     

手术联合125I粒子植入治疗复发性脑胶质瘤及预后因素初步分析

目的探讨手术联合125I粒子植入治疗复发性脑胶质瘤的疗效及影响预后的主要因素。方法 60例手术加放化疗后复发的脑胶质瘤患者随机分为手术联合125I粒子植入组35例,单纯手术对照组25例进行治疗,术后每2个月复查MRI进行随访,收集临床资料和随访结果进行分析。用Kaplan-Meier法计算全组的累积生存率,Log-Rank检验做单因素分析,Cox比例风险回归模型进行多因素分析。结果全组随访32~128周,平均随访时间52.8周,125I粒子植入组中位生存期60.3周(95%CI,53.3~67.3周),1 a生存率为71.4%,单纯手术组中位生存期43.1周(95%CI,37.5~48.8周),1 a生存率为36%(P<0.05)1。25I粒子植入组中WHO病理分级Ⅱ、Ⅲ、Ⅳ期的患者1 a生存率分别为87.8%、65.3%、36.4%(P<0.01);肿瘤全切组和次全切的患者1 a生存率分别为79.2%和54.5%(P<0.05)。单因素分析显示,肿瘤组织学分级、肿瘤部位、肿瘤切除程度和放射性并发症是手术联合125I粒子植入治疗复发性胶质瘤的预后影响因素;多因素分析显示肿瘤组织学分级和肿瘤切除程度是影响预后的独立因素。结论手术联合125I粒子植入可有效地延缓脑胶质瘤的生存时间,提高患者的生存率,肿瘤组织学分级和肿瘤切除程度是影响其预后的最重要因素。     

Prophylactic anticonvulsants in patients with brain tumour

OBJECTIVE: We conducted a clinical trial to determine if prophylactic anticonvulsants in brain tumour patients (without prior seizures) reduced seizure frequency. We stopped accrual at 100 patients on the basis of the interim analysis. METHODS: One hundred newly diagnosed brain tumour patients received anticonvulsants (AC Group) or not (No AC Group) in this prospective randomized unblinded study. Sixty patients had metastatic, and 40 had primary brain tumours. Forty-six (46%) patients were randomized to the AC Group and 54 (54%) to the No AC Group. Median follow-up was 5.44 months (range 0.13-30.1 months). RESULTS: Seizures occurred in 26 (26%) patients, eleven in the AC Group and 15 in the No AC Group. Seizure-free survivals were not different; at three months 87% of the AC Group and 90% of the No AC Group were seizure-free (log rank test, p = 0.98). Seventy patients died (unrelated to seizures) and survival rates were equivalent in both groups (median survival = 6.8 months versus 5.6 months, respectively; log rank test, p = 0.50). We then terminated accrual at 100 patients because seizure and survival rates were much lower than expected; we would need > or = 900 patients to have a suitably powered study. CONCLUSIONS: These data should be used by individuals contemplating a clinical trial to determine if prophylactic anticonvulsants are effective in subsets of brain tumour patients (e.g. only anaplastic astrocytomas). When taken together with the results of a similar randomized trial, prophylactic anticonvulsants are unlikely to be effective or useful in brain tumour patients who have not had a seizure.     

Postoperative communicating hydrocephalus in patients with supratentorial malignant glioma

Postoperative communicating hydrocephalus in adult patients with supratentorial malignant glioma is a relatively uncommon condition that occurs months after the initial operation of tumor excision. It occurred in only five of 50 consecutive cases treated in our department during the past 10 years. The hydrocephalus appeared to be attributable to leptomeningeal dissemination of tumor cells and subsequent impairment in cerebrospinal fluid (CSF) absorption. The tumors were located adjacent to the lateral ventricles in all five patients, and the proximity of the tumor to the cerebral ventricles may have facilitated dissemination of the tumor cells into the CSF space, resulting in hydrocephalus. The hydrocephalus was treated by a shunt surgery in all five cases, and the symptoms temporarily improved. None of the five patients experienced shunt malfunction or abdominal symptoms attributable to metastasis to the peritoneal cavity, and all five patients died of regrowth of the intracranial tumor or of pneumonia.     

Steroid-induced CT changes in patients with recurrent malignant glioma

The magnitude and time course of steroid-induced CT changes were analyzed in 11 patients with recurrent malignant glioma. CTs were obtained before and at regular intervals after starting dexamethasone (16 mg/d). Midline shift, ventricular compression, edema, enhancement intensity, and the size of the enhancing mass often improved with steroid treatment. Improvement occurred within 2 weeks in most instances. Changes in the volume of the enhancing tumor were assessed quantitatively in eight patients. In six, the mass was smaller after 2 weeks of steroid therapy, and in two the reduction approached 50%. Steroid-induced CT changes can mimic treatment responses. If steroids are necessary for symptom control, patients should be taking these medications for 2 weeks before a baseline CT is obtained and investigational treatment started.     

影响恶性胶质瘤生存预后的临床因素分析

目的 探讨与大脑半球恶性胶质瘤生存预后相关的临床因素. 方法 选择中山大学附属第一医院神经外科自2004年1月至2009年12月收治的194例恶性胶质瘤患者,其中间变性星形细胞瘤120例,胶质母细胞瘤74例,随访其生存状况,Kaplan-Meier生存分析与Cox多元同归分析患者无进展生存时间与总生存时间的影响因素. 结果 间变性星形细胞瘤和胶质母细胞瘤患者的无进展生存时间分别为18、10个月,总生存时间分别为21、12个月;Kaplan-Meier生存分析法显示年轻、KPS评分高、肿瘤无强化、术前有抽搐症状及间变性星形细胞瘤患者无进展生存时间及总生存时间均较长,差异有统计学意义(P＜0.05); Cox多元回归分析显示患者年龄、KPS评分、有无抽搐、病理分级是无进展生存时间、总生存时间的影响因素,年轻、KPS评分较高、有抽搐症状、间变性星形细胞瘤患者无进展生存时间与总生存时间较长. 结论 年龄较小、高KPS评分、间变性星形细胞瘤及术前有抽搐症状被提示是恶性胶质瘤患者获得较长生存期的保护因素,而性别、肿瘤部位、大小和手术切除程度对预后无影响,肿瘤强化与预后的关系有待进一步研究证实.     

Bevacizumab does not increase the risk of remote relapse in malignant glioma

Preclinical evidence and uncontrolled clinical studies suggest an increased risk for distant spread and development of a gliomatosislike phenotype at recurrence or progression of malignant glioma patients treated with bevacizumab (BEV), an antibody to vascular endothelial growth factor (VEGF). Here we asked whether BEV treatment of recurrent malignant glioma increases the risk of distant or diffuse tumor spread at further recurrence. BEV-treated patients were compared with matched pairs of patients treated without anti-VEGF regimens. T1 contrast-enhanced (T1+c) and fluid-attenuated inversion recovery (FLAIR) images were analyzed using a novel automated tool of image analysis. At the start of the study, 20.5% of BEV-treated and 22.7% of non-BEV-treated patients had displayed distant or diffuse recurrence. Distant or diffuse recurrences were observed in 22% (BEV) and 18% (non-BEV) on T1+c and in 25% and 18% on FLAIR (p > 0.05). The correlation between changes on T1+c and FLAIR at progression was high. The risk of distant or diffuse recurrence at the time of failure of BEV-containing treatments was not higher than with anti-VEGF-free regimens, arguing against a specific property of BEV that promotes distant tumor growth or a gliomatosislike phenotype at recurrence.     

博莱霉素缓释化疗在恶性脑胶质瘤中的应用

目的探讨应用纤维蛋白粘合剂和博莱霉素的混合剂行脑胶质瘤术中肿瘤残腔局部缓释化疗的可行性和疗效。方法选择大脑半球胶质瘤患者16例，随机分为A组8例，B组8例。两组均行开颅手术，切除肿瘤后，A组取5mg博莱霉素，B组取10mg博莱霉素，与生物胶中催化剂溶液混合后喷洒在肿瘤残腔壁上。术后12～14d、1个月、2个月复查CT，以了解局部脑组织的反应。观察记录病人术后的临床表现。结果16例术后2～14d均有明显的颅内压增高症状，复查CT证实为肿瘤残腔周围脑水肿所致，且B组水肿范围较A组重。经脱水、激素治疗后缓解。6例术后随访已达10个月，未见肿瘤复发。结论脑胶质瘤手术中肿瘤残腔喷洒生物胶博莱霉素混合刺既可对残余肿瘤进行缓释化疗，又可起到残腔止血作用，可安全应用于临床。     

Quality of life in patients with malignant glioma and their relatives

Maintaining Quality of Life (QoL) plays an important role in oncology as despite an increasing number of therapeutic opportunities numerous tumours can not be cured yet. Among those tumours are malignant gliomas. Their prognosis is usually very poor. For patients and their relatives the diagnosis of this life threatening disease is a crucial moment in their lives which may be followed by significant decrease of QoL due to both the poor prognosis and the existing or increasing neurological deficits. The central question of this study was to determine whether the disease has an impact on the QoL of patients and their relatives and what kind of impact that may be. Therefore, QoL was investigated in patients currently being treated as well as in long-term survivors. The results indicate that the diagnosis of a malignant glioma confronts both the patients and the relatives with a disease process that predisposes to restrictions in QoL but does not lead necessarily to a poor QoL. For this reason, only the evaluation of individual circumstances and strains allows to assess QoL and hence specific interventions to maintain or re-establish QoL.     

The prognostic value of cognitive functioning in the survival of patients with high-grade glioma

The authors studied cognitive functioning as a potential predictor of survival in 68 newly diagnosed patients with high-grade glioma. In a combined Cox proportional hazards model, the influence of tumor, treatment, and patient characteristics, including cognitive functioning, was studied. Older age and higher tumor grade were associated with poorer survival. Although cognitive impairment was not found to be an independent prognostic factor for the entire sample, it was associated with significantly poorer survival among older patients with World Health Organization grade IV gliomas. Assessment of cognitive functioning in these patients may improve clinical decision making and thus quality of treatment.     

Immunotherapy for patients with malignant glioma: from theoretical principles to clinical applications

Malignant gliomas are the most common type of primary brain tumor and are in great need of novel therapeutic approaches. Advances in treatment have been very modest, significant improvement in survival has been lacking for many decades and prognosis remains dismal. Despite 'gross total' surgical resections and currently available radio-chemotherapy, malignant gliomas inevitably recur due to reservoirs of notoriously invasive tumor cells that infiltrate adjacent and nonadjacent areas of normal brain parenchyma. In principle, the immune system is uniquely qualified to recognize and target these infiltrative pockets of tumor cells, which have generally eluded conventional treatment approaches. In the span of the last 10 years, our understanding of the cancer-immune system relationship has increased exponentially, and yet, we are only beginning to tease apart the intricacies of the CNS and immune cell interactions. This article reviews the complex associations of the immune system with brain tumors. We provide an overview of currently available treatment options for malignant gliomas, existing gaps in our knowledge of brain tumor immunology, and molecular techniques and targets that might be exploited for improved patient stratification and design of 'custom immunotherapeutics'. We will also examine major new immunotherapy approaches that are being actively investigated to treat patients with malignant glioma, and identify some current and future research priorities in this area.     

A randomised control trial of walking to ameliorate brain injury fatigue: a NIDRR TBI model system centre-based study

ABSTRACT

Fatigue is one of the most commonly reported sequelae after traumatic brain injury (TBI). This study evaluated the impact of a graduated physical activity programme on fatigue after TBI. Using a prospective randomised single-blind crossover design, 123 individuals with TBI, over the age of 18, were enrolled. Interventions included a home-based walking programme utilising a pedometer to track daily number of steps at increasing increments accompanied by tapered coaching calls over a 12-week period. Nutritional counselling with the same schedule of coaching calls served as the control condition. Main outcome measures included: the Global Fatigue Index (GFI), the Barrow Neurological Institute (BNI) Fatigue Scale Overall Severity Index Score, and the Multidimensional Fatigue Inventory (MFI). Step counts improved over time regardless of group assignment. The walking intervention led to a decrease in GFI, BNI Total, and MFI General scores. Participants reported less fatigue at the end of the active part of the intervention (24 weeks) and after a wash out period (36 weeks) as measured by the BNI Overall. The study suggests that walking can be used as an efficient and cost-effective tool to improve fatigue in persons who have sustained a TBI.     

手术切除联合放射性粒子永久性植入治疗复发性胶质瘤

目的探讨外科手术切除联合放射性粒子永久性植入治疗复发性胶质瘤的疗效。方法117例复发性胶质瘤完全随机分组,65例为间质放疗组,52例为普通放疗对照组,均行电磁导航辅助下显微神经外科手术全切除或次全切除。间质放疗组术中根据术前计算机三维治疗计划系统（TPS）在瘤床永久性植入125^I放射性粒子进行组织间近距离连续照射,总量为50～60Gy。对照组术后行常规外照射,50～60Gy/25～30次。随访3～36个月,观察肿瘤再次复发率、中位生存期。结果间质化疗组第2次手术后12个月复发31例（47.7%）;24个月复发46例（70.8%）,较对照组（71.2%、86.5%）有显著差异;中位生存时间18.2月,较对照组13.5月显著延长;对照组并发症发生率53.8%,间质化疗组无显著的放疗并发症。结论力争手术全切除联合放射性粒子永久性植入对复发性恶性胶质瘤细胞近距离持续照射,疗效明显提高,安全且并发症少。