Feelings, preoperative anxiety, and need for information in patients undergoing intravitreal injections.

PURPOSE: To assess feelings, preoperative anxiety, and need for information in patients undergoing intravitreal injections (IVI). METHODS: An observational cross-sectional study was conducted in our tertiary university care center between December 2017 and December 2018. Consecutive patients undergoing IVI were included. A paper survey was completed before and after IVI to assess patient experience. Preoperative anxiety and need for information were assessed using the Amsterdam Preoperative Anxiety Information Scale (APAIS) score. RESULTS: Hundred patients with a median age of 76.5 years (42-95, SD = 10.1) were included. Median best-corrected visual acuity (BCVA) in both eyes was 0.4 logMAR. Main IVI indications were wet age-related macular degeneration (n = 58), diabetic macular edema (n = 19), and venous occlusion (n = 16). The IVI most unpleasant steps were as follows: using an eyelid retractor, needle entry, changing of physician from one IVI to another, the pre-IVI waiting time, and the high number of IVI required for disease control. Preoperative anxiety (APAIS score ≥ 11) was correlated in the multivariate analysis with the need for information (p = 0.004), changing of ophthalmologist between different IVI sessions (p = 0.006), and pain expected before the IVI (p = 0.010). The need for information (APAIS score ≥ 5) was only associated with the preoperative anxiety in the multivariate analysis (p = 0.001). CONCLUSION: Preoperative anxiety and need for information are common in patients undergoing IVI even after many IVI. Being injected by different practitioners was strongly correlated with preoperative anxiety and should be avoided as much as possible. Better educational and information programs are needed.

MET immunolabelling is a useful predictive tool for MET gene amplification in glioblastoma.

AIMS: MET gene amplification is rare in glioblastoma (GBM) and represents a potential target for MET inhibitors. An immunohistochemical screening may be useful to identify MET amplification. The aim of our study was to establish how MET immunolabelling correlates with MET amplification. METHODS: Three cohorts including 108 GBM (cohort 1, prospective), 104 GBM (cohort 2, retrospective) and 52 GBM (cohort 3, prospective) were investigated for MET expression by immunohistochemistry. MET amplification was assessed by comparative genomic hybridization on microarray (CGH-array) in all cohorts and by fluorescent in situ hybridization (FISH) in cohorts 2 and 3. Active form of MET was assessed using p-MET (Y1349) immunohistochemistry. RESULTS: Diffuse MET amplification detectable by CGH-array was associated with diffuse, strong MET immunolabelling (four cases in cohort 1 and one case in cohort 2). Focal MET amplification detectable only by FISH was observed in small foci of strongly immunopositive cells in two GBM (cohort 2). In both cohorts, MET amplification was never detected in GBM devoid of strongly immunopositive cells. MET overexpression, observed in 23% of unamplified GBM, was associated with a predominant weak-to-moderate staining intensity and with necrosis (P < 0.005). p-MET was detected in all MET-amplified GBM and in perinecrotic areas of nonamplified GBM. A strong MET immunostaining intensity, at least focal and distant from necrosis, showed 100% sensitivity and 84% specificity for predicting MET amplification in cohort 3. CONCLUSIONS: MET amplification is characterized by strongly immunopositive cells. Only GBM showing strong MET immunostaining is appropriate for the assessment of MET amplification.

Optic nerve sheath fenestration: Current status in France and comparison of 6 different surgical approaches.

PURPOSE: Optic nerve sheath fenestration (ONSF) is a surgical procedure commonly performed in the Anglo-Saxon countries for the treatment of medically refractory idiopathic intracranial hypertension (IIH). We chose to compare 6 different trans-orbital surgical approaches to ONSF. We also desired to determine the number of optic nerve decompression procedures performed in France in 2019 and 2020. METHODS: Four fresh frozen orbits were dissected at the University of Nice anatomy laboratory. We performed the following surgical approaches: (i) eyelid crease, (ii) lid-split, (iii) medial transconjunctival with medial rectus disinsertion, (iv) medial transconjunctival without rectus disinsertion, (v) lateral transconjunctival and (vi) lateral orbitotomy. For each surgical approach, we measured the distance between the incision and the optic nerve dura mater. We also extracted data from the French National PMSI (Programme de Médicalisation des Systèmes d' Information) database from January 2019 through December 2020 to determine the annual number of optic nerve decompression procedures. RESULTS: The lid crease and medial transconjunctival approaches provided the shortest distance to the optic nerve (average 21mm and 24mm, respectively) and the lowest levels of difficulty compared to the other surgical routes. A total of 23 and 45 optic nerve decompressions were performed in France in 2019 and 2020, respectively. Among them, only 2 and 7 procedures, respectively, were performed through a trans-orbital approach. CONCLUSION: Upper lid crease incision and medial transconjunctival approaches are the most direct and easiest surgical routes when performing an ONSF. We found that ONSF was rarely performed in France. We strongly recommend close cooperation between ophthalmologists, neurologists, neurosurgeons and interventional radiologists.

Primitive cerebral melanoma: a diagnostic and management challenge. About 2 cases.

In this report of two cases of solitary cerebral meningeal melanoma, a rare tumor that presents both diagnostic and management challenges, the diagnosis of these lesions was based on a solitary leptomeningeal mass on MRI, a high mitotic rate on histology and the absence of extracerebral localizations. Although the radiological patterns can mimic those of other melanocytic tumors, MRI is a useful diagnostic tool for narrowing the differential diagnosis. Surgical removal remains the only effective treatment of these lesions, and can lead to prolonged survival in a few cases.

Post-traumatic cerebral venous sinus thrombosis associated with epidural hematoma: A challenging clinical situation.

Post-traumatic cerebral venous sinus thrombosis (ptCVST) is often associated with brain hemorrhage; consequently, the anticoagulation may be challenging. We report the case of a 42-year-old man who presented with post-traumatic epidural hematoma and rapidly developed transverse sinus thrombosis extending to the internal jugular vein. As the patient was asymptomatic, we decided not to use anticoagulants: close clinical and radiological monitoring was implemented. The hematoma resolved within 2 months, and the CVST diminished by the third month. Such a good outcome is not always the case in ptCVST. The present article also discusses pathophysiological mechanisms and treatment options when hematoma is associated with ptCVST.

Papilledema secondary to vestibular schwannoma: An atypical case without intracranial hypertension.

In most cases, vestibular schwannomas with papilledema are associated with intracranial hypertension secondary to hydrocephalus (obstructive or communicating). We describe the atypical case of a 39-years-old man who presented with bilateral papilledema revealing a vestibular schwannoma, but without hydrocephalus and with normal intracranial pressure. Ophtalmologic signs were completely resolved after tumor removal. The pathophysiological mechanism generally described to explain bilateral papilledema in such cases is tumor-induced hyperproteinorachia. However, in the absence of hydrocephalus or intracranial hypertension, this case raises the question of the mechanisms involved in the visual impairment related to vestibular schwannoma.

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.

Is implant placement performed at the same surgical time as orbital exenteration a viable procedure?

PURPOSE: To assess the efficacy and safety of bone-anchored dental implant placement at the same time as orbital exenteration compared with delayed implant placement. MATERIALS AND METHODS: A retrospective comparative study was conducted in a single tertiary care center between December 2003 and December 2017. Patients who underwent bone-anchored implant placement at the same time as orbital exenteration were included (group 1) and compared with patients who underwent delayed implant placement (group 2). The main outcome was the 1-year success rate of implant osseointegration. The secondary outcomes were the 5-year success rate of osseointegration, postoperative complications, and time between orbital exenteration and prosthesis placement. RESULTS: Ten and 11 patients (21 and 22 implants) with a mean follow-up of 50.2 and 48.5 months were included in groups 1 and 2, respectively. Patients in group 1 were significantly older (69.7 vs 61.2 years, P = .026). No significant differences were found between both groups regarding tumor type and location, prior treatments, smoking status, and postoperative radiation beam radiotherapy. The 1- and 5-year success rates of osseointegration were 95.5% and 93.3% in group 1, and 100% and 100% in group 2, respectively (P = .488 and P = .450 between both groups). One implant did not osseointegrate in group 1 due to osteitis. Ethmoidal fistula was the most common postoperative complication found in both groups (P = .670). The mean time between orbital exenteration and episthesis placement was 8 (3 to 14) vs 11 (3 to 15) months in groups 1 and 2, respectively (P = .467). CONCLUSION: Placing implants at the same time as orbital exenteration is a viable procedure. It reduces surgical morbidity and allows placement of implants in a nonirradiated area.

Orbital exenteration and conjunctival melanoma: a 14-year study at the Jules Gonin Eye Hospital.

PURPOSE: To report our 14-year experience with orbital exenteration and assess risk factors for poor prognosis by focusing on conjunctival melanoma. PATIENTS AND METHOD: A retrospective study was conducted in our tertiary care centre (Jules Gonin Eye Hospital, Lausanne, Switzerland) between 2003 and 2017. Inclusion criteria were patients aged ≥18 years with a follow-up >12 months, without metastatic spread at the time of surgery. Data recorded were age, gender, tumour histology, surgical technique, postoperative complications, surgical margin status, local recurrence, postoperative radiation beam therapy and metastatic status. RESULTS: Twenty-five patients with a mean age of 63.2 years (38-92) were included. Conjunctival melanoma was the most frequently identified tumour (n = 14, 56%) followed by conjunctival squamous cell carcinoma (n = 4, 16%), sebaceous carcinoma (n = 3, 12%), choroidal melanoma (n = 2, 8%) and basal cell carcinoma (n = 2, 8%). Eighteen tumours (72%) originated from the conjunctival tissue. Clear surgical margins were achieved in 21 (84%) patients. Fourteen (56%) patients experienced distant metastases and died from metastatic spread after a mean follow-up of 52.3 months (6-120). The 1-, 3- and 5-year overall survival (OS) was 96%, 72% and 60%, respectively. In the univariate analysis, positive surgical margins, local recurrence and metachronous metastases were associated with a decreased OS (p = 0.002, p = 0.005 and p = 0.007, respectively). In the multivariate analysis, positive surgical margins and metachronous metastases were also associated with a decreased OS (p = 0.02 and p = 0.042, respectively). Conjunctival melanoma was not associated with a poorer prognosis (p = 0.280). CONCLUSION: Free surgical margins are needed to increase OS. To achieve clearer surgical margins, neoadjuvant targeted therapies/immunotherapies may be considered.

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.

Pain during awake craniotomy for brain tumor resection. Incidence, causes, consequences and management.

INTRODUCTION: Awake craniotomy for brain tumor resection is usually well-tolerated and most of the patients are satisfied. However, in studies reporting the patients' postoperative perception of the awake craniotomy procedure, about half of them have experienced some degree of intraoperative pain. Pain was mild (intensity between 1 and 2 on the visual analogical score) short lasting in most cases, and did not challenge the procedure. Pain was reported as moderate in about 25% and exceptionally severe. METHODS: We conducted a preliminary survey among French centers (n=9) routinely performing awake craniotomy. RESULTS: Neurosurgeons' opinions were concordant with patient's reports. Intraoperative pain exceptionally challenged the awake craniotomy procedure or led to changes in the resection strategy. For neurosurgeons, the most challenging causes of intraoperative pain were the patient's inadequate installation, the contact of surgical tools with pain-sensitive intracranial structures, especially the dura mater of the skull base, falx cerebri, and the leptomeninges of the lateral fissure and neighboring sulci. CONCLUSION: Strategies to deal with these causes included focusing the patient on the intraoperative functional tests to distract their attention away from the pain, and avoiding contacts with the pain-sensitive intracranial structures during the awake phase. Adequate preoperative patient information and preparation, trained anesthesiologists and application of recommendations for awake craniotomy procedures as well as adaptation of surgical technique to avoid contact with pain-sensitive intracranial structures are key factors to prevent intraoperative pain and ensure patient's postoperative satisfaction.

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.

[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.