Fractionated Stereotactic Radiation Therapy for Pituitary Adenomas: An alternative escalating protocol of hypofractionated stereotactic radiotherapy delivering 35Gy in 5 fractions.

PURPOSE: Evaluate efficacy and toxicity of hypofractionated stereotactic radiotherapy (HSRT) for patients treated for pituitary adenoma (PA) with an alternative HSRT escalating protocol delivering 35Gy in 5 fractions. MATERIAL AND METHODS: From June 2007 to March 2017, 29 patients with pituitary adenoma were treated in Antoine Lacassagne Cancer Centre with an alternative HSRT protocol. Prescribed dose was 35Gy in 5 fractions of 7Gy. Radiographic responses were assessed by annual MRI. Hormone blood samples were evaluated each year after HSRT. RESULTS: A total of 29 patients aged between 23 and 86 years (median 54 years) were included. Twelve patients received HSRT for recurrent cases and 12 received postoperative adjuvant HSRT, 5 patients did not have surgery. After a median follow-up period of 47 months local control rate was 96%. One patient presented an out-field tumor regrowth 73 months after HSRT. The majority of PA were endocrine-active (18 patients, 62%). After HSRT, 8 patients (44%) presented complete response on initial secretion, 4 patients (23%) presented partial response on initial secretion. Four patients (14%) presented grade 2 or more acute radiation toxicities. One grade 4 visual disorder was observed for one patient. CONCLUSIONS: HSRT delivering 35Gy in 5 fractions represents a feasible treatment and shows promising results to reduce hormonal overproduction and to improve local control in PA.

[Oculoplastic complications of the excision of meningiomas with orbital extension]. / Complications oculoplastiques de l'exérèse des méningiomes à extension orbitaire.

INTRODUCTION: Meningiomas with orbital extension are the most frequent benign orbital tumors. The few studies available on the postoperative complications of their excision focus on the postoperative evolution of proptosis, visual acuity and visual field deficits. The goal of our study was to highlight the oculoplastic complications secondary to their excision. MATERIAL AND METHOD: We identified all cases of meningiomas with orbital extension undergoing excision either neurosurgically or via an orbital approach in the ophthalmology and neurosurgery departments of Pasteur university medical center in Nice between February 2011 and January 2017. The data collection included the postoperative presence of proptosis, oculomotor disturbance, lid disorders, dry eye and trigeminal nerve damage. RESULTS: Twenty-nine patients were included; 89.7 % were women. The mean age was 55 years. Postoperative complications included 25 % residual proptosis; 40.7 % oculomotor disturbance, 75 % of which regressed at least partially; 50 % ptosis, 21 % of which did not regress; 40 % dry eye; and in 21.4 % the trigeminal nerve was involved. CONCLUSION: The management of meningiomas with orbital extension is difficult due to their anatomical location and requires joint neurosurgical and oculoplastic management. Sufficient follow-up is required before recommending surgery for oculomotor disturbances. The frequency of occurrence of ptosis with potential recommendation for surgery requires caution given the occurrence of trigeminal nerve involvement and dry eye syndrome.

DOCK4 promotes loss of proliferation in glioblastoma progenitor cells through nuclear beta-catenin accumulation and subsequent miR-302-367 cluster expression.

Glioblastomas (GBM) are lethal primitive brain tumours characterized by a strong intra-tumour heterogeneity. We observed in GBM tissues the coexistence of functionally divergent micro-territories either enriched in more differentiated and non-mitotic cells or in mitotic undifferentiated OLIG2 positive cells while sharing similar genomic abnormalities. Understanding the formation of such functionally divergent micro-territories in glioblastomas (GBM) is essential to comprehend GBM biogenesis, plasticity and to develop therapies. Here we report an unexpected anti-proliferative role of beta-catenin in non-mitotic differentiated GBM cells. By cell type specific stimulation of miR-302, which directly represses cyclin D1 and stemness features, beta-catenin is capable to change its known proliferative function. Nuclear beta-catenin accumulation in non-mitotic cells is due to a feed forward mechanism between DOCK4 and beta-catenin, allowed by increased GSK3-beta activity. DOCK4 over expression suppresses selfrenewal and tumorigenicity of GBM stem-like cells. Accordingly in the frame of GBM median of survival, increased level of DOCK4 predicts improved patient survival.

Cerebral vasospasm after transsphenoidal surgery for pituitary adenoma: Case report and review of the literature.

INTRODUCTION: Cerebral vasospasm (CVS) is a rare complication of transsphenoidal surgery for pituitary adenomas. CASE REPORT: The authors describe a symptomatic cerebral ischemia due to an internal carotid, left middle cerebral artery and anterior cerebral artery vasospasm in a patient undergoing transsphenoidal surgery for a pituitary macro adenoma. The patient was successfully treated by an endovascular balloon angioplasty. CONCLUSION: This issue should be taken into account, even when rare, in every patient who has surgery for a pituitary tumor, particularly when it concerns a large macro adenoma with suprasellar extension. Special precautions must be taken to avoid this rare complication.

Spinal cord compression due to a primary vertebral hydatid disease: A rare case report in metropolitan France and a literature review.

INTRODUCTION: Bone echinococcosis or bone hydatidosis is mainly caused by the larva of a dog taenia, Echinococcus granulosus. We described a rare imported case in metropolitan France of spinal cord compression from a primary vertebral hydatidosis. CASE: A 25-year-old woman, native of a rural area in the South of Romania, was admitted for backache and slight weakness of both legs. Radiological findings showed a paravertebral pluricystic lesion invading the spinal canal with spinal cord compression at the T9 level, without associated visceral localization. We performed an urgent surgical decompression using a posterior approach. The whole extradural cysts were carefully excised with irrigation of the cystic fluid with hypertonic saline. Treatment was completed with long-term anti-parasitic chemotherapy. DISCUSSION: Bone echinococcosis is rare and represents about 2% of hydatidosis. The spine localization is found in half of the cases. This pathology particularly occurs in the Eastern and Southern countries of Mediterranean sheep breeding areas, but still rare in metropolitan France. Spinal cord compression is a frequent presentation of spinal hydatidosis but neurological symptoms are various and non-specific. The reference treatment is removal surgery with particular precautions, followed by an anti-parasitic chemotherapy (albendazole) to limit recurrences. However, a long-term follow-up is mandatory due to later recurrences.

The miR 302-367 cluster drastically affects self-renewal and infiltration properties of glioma-initiating cells through CXCR4 repression and consequent disruption of the SHH-GLI-NANOG network.

Glioblastoma multiforme (GBM) is the most common form of primary brain tumor in adults, often characterized by poor survival. Glioma-initiating cells (GiCs) are defined by their extensive self-renewal, differentiation, and tumor initiation properties. GiCs are known to be involved in tumor growth and recurrence, and in resistance to conventional treatments. One strategy to efficiently target GiCs in GBM consists in suppressing their stemness and consequently their tumorigenic properties. In this study, we show that the miR-302-367 cluster is strongly induced during serum-mediated stemness suppression. Stable miR-302-367 cluster expression is sufficient to suppress the stemness signature, self-renewal, and cell infiltration within a host brain tissue, through inhibition of the CXCR4 pathway. Furthermore, inhibition of CXCR4 leads to the disruption of the sonic hedgehog (SHH)-GLI-NANOG network, which is involved in self-renewal and expression of the embryonic stem cell-like signature. In conclusion, we demonstrated that the miR-302-367 cluster is able to efficiently trigger a cascade of inhibitory events leading to the disruption of GiCs stem-like and tumorigenic properties.

Medicoeconomic evaluation of total disc replacement based on French National Health Care System data.

INTRODUCTION: Total disc replacement (TDR) has existed since 1984 but is not covered by the French national healthcare system (Sécurité Sociale). The present study assessed clinical outcomes, and also pre-, peri- and postoperative treatment costs. HYPOTHESIS: Surgical management of low back pain (LBP) provides medical and economic benefit. MATERIALS AND METHODS: A prospective study recruited 19 patients in the Nice University Hospital Center (France); mean age, 41 years; 15 female. Inclusion criteria were: age less than 60 years; chronic low back pain (LBP) with single-segment discopathy; work related injuries and patients not covered under the General provision of the Sécurité Sociale were excluded. VAS, Oswestry and SF36 scores and return to work capability were analyzed. The local national health insurance branch office (Caisse Primaire d'Assurance Maladie [CPAM]) provided detailed coverage data for a 39-month period around the operation. RESULTS: Revision surgery was required for one instance of vertebral fracture. Preoperative follow-up was 14 months, postoperative FU 21 months and the perioperative period 4 months. LBP and quality of life showed improvement. Seventy-nine percent of patients reported satisfaction, 59% returned to work, and 84% had leisure activity. Total CPAM payout (reimbursement) was €399,082. Daily sickness benefit and disability compensation were the main cost items. Mean TDR cost per patient was €6833. Mean reimbursements were 19% lower post- than preoperatively. Pre- and postoperative clinical results did not correlate, while pre- and postoperative reimbursement costs did, as did cost and postoperative clinical status (r=-0.72). Preoperative cost was a predictive factor for postoperative clinical result. DISCUSSION: TDR achieves favorable medicoeconomic results. LEVEL OF EVIDENCE: III: case-control study.

Lethal acute demyelinization with encephalo-myelitis as a complication of cured Cushing's disease.

Cushing's disease is usually associated with higher mortality rate, especially from cardiovascular causes. Development or exacerbation of autoimmune or inflammatory diseases is known to occur in patients with hypercortisolism after cure. We report for the first time a 34-year old woman with a psychiatric background, who developed four months after the surgical cure of Cushing's disease an acute disseminated encephalomyelitis (ADEM) presenting initially as a psychiatric illness. We hypothesize that the recent correction of hypercortisolism triggered ADEM and that the atypical presentation, responsible for diagnosis delay, led to the death of this patient.

[Genetic diseases and glioblastomas]. / Maladies génétiques et glioblastomes.

Some cancers are involved in inherited genetic syndromes. These genetic diseases are suspected of being involved in approximately 1% of gliomas. Few data are available on glioblastomas and their characteristics among these diseases. Familial syndromes known to predispose individuals to glioblastoma are neurofibromatosis type 1, Li-Fraumeni's syndrome, tuberous sclerosis, and Turcot's syndrome. This review discusses glioblastomas related to these diseases and the current knowledge on the statistical, clinical, and molecular biology data. Non-syndromic glioma families are discussed: a better understanding of molecular abnormalities in these groups should help understand the mechanisms of gliomagenesis. A case of malignant glioma requires the physician to actively search for the possibility of inherited factors and eventually suggest genetic counseling.

[Glioblastoma incident studies from May 2006 to May 2007 in Angers and Nice, France]. / Études des glioblastomes incidents de mai 2006 à mai 2007, Angers-Nice.

The present work is a retrospective study on glioblastomas treated in the Angers and Nice Hospital Departments of Neurosurgery between 2006 and 2007. This study was conducted 2 years after the audit on incident glioblastoma in France in 2004. New events that may modify the care or survival of glioblastoma have occurred since 2004, justifying the present study. The results show that the Karnowsky Index is more often included in the clinical files and that the rate of complete resection has increased, indicating that neurosurgeons are becoming aware of neuro-oncology. Patients with total resection still have the longest survival (14 months). Surprisingly, less than half the patients having surgery received concomitant radiochemotherapy according to the Stupp protocol. Median overall survival remains at 9 months with intention to treat. For patients treated with concomitant chemoradiotherapy with temozolomide, the median survival is 12 months. For patients having a total resection, the median survival is 14 months, whatever adjuvant treatment is used. Median survival for patients having total resection and chemoradiotherapy with temozolomide is 18 months, with a 23.3% 2-year survival rate, less than the ORTC trial rate.

[Glioblastoma: clinical, radiological and biological prognostic factors]. / Glioblastomes : facteurs pronostiques cliniques, radiologiques et biologiques.

The main prognostic factors of glioblastomas (GBM) are age, neurological and cognitive status, frontal tumor location, extent of surgical resection, adjuvant therapies received, presence of IDH1 mutations, and MGMT expression. Other molecular prognostic factors have been proposed, such as mutations of TP53 and PTEN, amplification of EGFR, and deletion of 10q, but their prognostic values remain controversial. MGMT promotor gene methylation is correlated with higher chemosensitivity and consequently is a good prognostic factor only in patients treated with chemotherapy. In the future, the gene expression profile will probably be a stronger prognostic factor than histological grade, but the most relevant gene clusters, whose expression may be correlated with survival, remain to be identified. Long survivors are characterized by younger age, better neurological status, and a more aggressive therapeutic strategy. In daily clinical practice, recursive partitioning analysis (RPA) classifications can estimate the median survival of a given patient according to several basic factors. RPA class is also important so as to adapt individual therapeutic strategies, considering that the benefit of adjuvant treatments tends to decrease in the highest RPA class patients.

[Radiotherapy in adult glioblastomas]. / Radiothérapie des glioblastomes de l'adulte.

Radiation therapy is a treatment of malignant gliomas in adults. It improves survival rates, whether used alone, in addition to surgery, or in combination with chemotherapy. Three-dimensional imaging techniques, image fusion, and conformational radiotherapy are optimizing treatment plans for the treatment of these tumors and are sparing healthy tissue. After a review of the physical and biological bases of ionizing radiation, we present the techniques, results, side effects, and results of irradiation of glioblastomas.

[Second surgery for glioblastoma. A 4-year retrospective study conducted in both the Montpellier and Nice Departments of Neurosurgery. A literature review]. / Intérêt d'une seconde chirurgie d'exérèse dans les glioblastomes. Etude rétrospective sur quatre ans aux centres hospitalo-universitaires de Montpellier et de Nice et revue de la littérature.

BACKGROUND AND PURPOSE: Glioblastoma, the most common malignant primary brain tumor in adults, is usually rapidly fatal. The current care standards for newly diagnosed glioblastoma consist, when feasible, in surgical resection, radiotherapy, and chemotherapy, as described in the Stupp protocol. Despite optimal treatment, nearly all malignant gliomas recur. If the tumor is symptomatic for mass effect, repeated surgery may be proposed. METHODS: We retrospectively analyzed the survival of patients with histologically confirmed primary glioblastoma (WHO grade 4) who were operated in two centers between January 2004 and December 2007. All patients who underwent a second resection for recurrent glioblastoma were included. RESULTS: During this period, 320 patients were operated in the two centers, with 240 surgical resections and 80 surgical biopsies. In the surgical resection group, 8.3% (20 patients) underwent a second surgical resection for glioblastoma. The mean age was 52 years. At the end of the study, seven patients were alive. The median survival was 24 months and progression-free survival was 7.5 months. CONCLUSIONS: The effect of resection of recurrent glioblastoma on survival has not been extensively studied. No randomized trials have been conducted. Our data were globally identical to other retrospective studies. Selected patients with recurrent glioblastoma may be candidates for repeated surgery when the situation appears favorable based on assessment of the individual patient's factors. Factors such medical history, neurological status, location of the tumor, and progression-free survival have been proven in retrospective studies to give better results.

[Spinals and paraspinals tumors treated by CyberKnife: feasibility and efficacy]. / Tumeurs spinales et paraspinales traitées par irradiation stéréotaxique par CyberKnife((R)) au centre Antoine-Lacassagne de Nice.

PURPOSE: Stereotactic radiotherapy using the CyberKnife has become a key treatment in the multidisciplinary management of secondary tumours, as well as primary benign or malignant tumours located within or adjacent to vertebral bodies and the spinal cord. The aim of this treatment is to improve local control and clinical response, including previously irradiated cases. PATIENTS AND METHODS: In this study, we present the first patients treated with CyberKnife between December 2006 and December 2007 for spinal or paraspinal tumours. The primary aim was to assess the feasibility and tolerance of stereotactic radiotherapy using the CyberKnife. Secondary aims were to establish the short-term local control, to calculate the local progression-free survival and overall survival. Clinical examination and imaging procedures were performed every three months. Response was assessed according to RECIST criteria. RESULTS: During that period, 16 patients were treated with CyberKnife. Thirteen patients had been pre-treated, three of whom had received spinal cord doses considered to be maximal. Three patients did not receive previous irradiation. The median age was 59 (36-74). The most frequent symptoms were pain (n = 8) and motor weakness (n = 4). The median dose was 30 Gy (16-50). The median number of fractions was 3 (1-5). No patient developed acute myelitis. Three patients developed acute reaction. Overall survival at 18 months was 72.4%, with a mean survival of 18.2 months (95% CI: 15.4-20.9). Local progression-free survival at 18 months was 58.4%, with a mean value of 16.9 months (95% CI: 13.6-20.2). CONCLUSION: The use of stereotactic radiotherapy with CyberKnife represents a major progress in the management of paraspinal tumours. The main advantages are better sparing of the spinal cord and the possibility of increasing the dose to the tumour target volume.

[Coordination of health vigilances: for a global management of hospital risks]. / La coordination des vigilances sanitaires : pour une gestion plus globale des risques hospitaliers.

The sanitary vigilances represent a permanent sanitary surveillance. They signal, enregister, treat and investigate the adverse events occurring through the use of health products. They assure the traceability of these health products and the management of the sanitary alerts. The sanitary vigilances are part of the sanitary security. They are optimized when coordinated and integrated to the global risk management process of the health care establishments.

[Subthalamic nucleus stimulation using a Fisher ZD stereotactic frame, MR-CT fusion guidance and peroperative orthogonal radiographs, in Parkinson disease]. / Evaluation de la stimulation du noyau sous-thalamique utilisant un cadre de Fischer adapté, un guidage par fusion IRM-scanner et un contrôle radiographique stéréotaxique peropératoire, dans la maladie de Parkinson.

BACKGROUND: We present the method and results of an original technique to implant electrodes in the subthalamic nucleus (STN) to treat Parkinson's disease, based on adaptations of the Fisher ZD stereotactic frame. METHODS: Targets coordinates were calculated after fusion of stereotactic CT-scan and MRI images. STN was localized by its theoretical coordinates according to AC-PC and by its direct visualization on T2 images. Electrodes were implanted after local anesthesia, using peroperative multicanal microrecordings and test stimulation. Electrodes location was checked by peroperative perpendicular radiographs. To avoid projection of the frame arm on the area of interest on anteroposterior and lateral radiographs, the arm was fixed at 45 degrees from the usual 90 degrees position. This original fixation needed a trigonometric transformation of the X and Y stereotactic coordinates. Radiopaque markers, fixed on the frame, were identified on the radiographs, allowing the calculation of the stereotactic coordinates of the electrode tip, which were then entered in the stereotactic MRI, to check its location from the defined target. RESULTS: No problem due to adaptations of the frame occurred in the 60 patients. In all cases, peroperative radiographs allowed to confirm the correct location of electrodes. Six months after surgery, UPDRS III score without medication was decreased by 52% with stimulation "on". UPDRS IV items 32, 33 and 39 scores were decreased by 75,7, 79,5 and 72%. Daily dopa-equivalent dose was decreased by 71%. One asymptomatic thalamic hematoma and two wound infections occurred. CONCLUSION: This method was efficient and safe to implant deep electrodes.