Through the orbit and beyond: Current state and future perspectives in endoscopic orbital surgery on behalf of the EANS frontiers committee in orbital tumors and the EANS skull base section.

Introduction: Orbital surgery has always been disputed among specialists, mainly neurosurgeons, otorhinolaryngologists, maxillofacial surgeons and ophthalmologists. The orbit is a borderland between intra- and extracranial compartments; Krönlein's lateral orbitotomy and the orbitozygomatic infratemporal approach are the historical milestones of modern orbital-cranial surgery. Research question: Since its first implementation, endoscopy has significantly impacted neurosurgery, changing perspectives and approaches to the skull base. Since its first application in 2009, transorbital endoscopic surgery opened the way for new surgical scenario, previously feasible only with extensive tissue dissection. Material and methods: A PRISMA based literature search was performed to select the most relevant papers on the topic. Results: Here, we provide a narrative review on the current state and future trends in endoscopic orbital surgery. Discussion and conclusion: This manuscript is a joint effort of the EANS frontiers committee in orbital tumors and the EANS skull base section.

Petroclival meningiomas: update of current treatment and consensus by the EANS skull base section.

BACKGROUND: The optimal management of petroclival meningiomas (PCMs) continues to be debated along with several controversies that persist. METHODS: A task force was created by the EANS skull base section along with its members and other renowned experts in the field to generate recommendations for the management of these tumors. To achieve this, the task force reviewed in detail the literature in this field and had formal discussions within the group. RESULTS: The constituted task force dealt with the existing definitions and classifications, pre-operative radiological investigations, management of small and asymptomatic PCMs, radiosurgery, optimal surgical strategies, multimodal treatment, decision-making, and patient's counselling. CONCLUSION: This article represents the consensually derived opinion of the task force with respect to the management of PCMs.

Endoscopic Third Ventriculostomy before Posterior Fossa Tumor Surgery in Adult Patients.

OBJECTIVE: Obstructive hydrocephalus in patients with posterior fossa tumors is frequently seen. Treatment options include immediate tumor removal or prior cerebrospinal fluid (CSF) diversion procedures. The necessity and feasibility of an ETV in these situations has not yet been proven in adult patients. METHODS: We retrospectively reviewed our prospectively maintained database for ETVs before surgery of posterior fossa tumors in adults. The primary focus of data analyses was the question of whether the ETV was suitable to treat the acute situation of hydrocephalus without an increased rate of complications due to the special anatomical situation with a posterior fossa tumor. We also analyzed whether any further CSF diverting procedures were necessary. RESULTS: A total of 40 adult patients who underwent an ETV before posterior fossa tumor surgery were analyzed. Overall, 33 patients (82.5%) had clinical signs of hydrocephalus, and all of them improved in their clinical course after ETV. Seven patients (17.5%) did not demonstrate clinical signs of hydrocephalus, but ETV was performed with prophylactic or palliative intent in six patients and one patient, respectively. No complications were observed due to ETV itself. No permanent shunting procedure was necessary in a mean follow-up of 76.5 months. Early additional CSF diverting procedures (redo ETV, external ventricular drain) were performed in five patients (12.5%). CONCLUSION: The present series confirms the feasibility and safety of ETV before posterior fossa tumor surgery in adult patients. If patients had symptomatic hydrocephalus before tumor surgery, an ETV can be performed, followed by early elective tumor surgery. A prophylactic ETV in asymptomatic patients is not advised. Early elective tumor surgery should be performed in these patients.

Endoscopic Biopsy for Intra- and Paraventricular Tumors: Rates of Complications, Mortality, and Tumor Cell Dissemination.

BACKGROUND AND STUDY AIM: Intra- and paraventricular tumors are frequently associated with cerebrospinal fluid (CSF) pathway obstruction. Thus the aim of an endoscopic approach is to restore patency of the CSF pathways and to obtain a tumor biopsy. Because endoscopic tumor biopsy may increase tumor cell dissemination, this study sought to evaluate this risk. PATIENTS, MATERIALS, AND METHODS: Forty-four patients who underwent endoscopic biopsies for ventricular or paraventricular tumors between 1993 and 2011 were included in the study. Charts and images were reviewed retrospectively to evaluate rates of adverse events, mortality, and tumor cell dissemination. Adverse events, mortality, and tumor cell dissemination were evaluated. RESULTS: Postoperative clinical condition improved in 63.0% of patients, remained stable in 30.4%, and worsened in 6.6%. One patient (2.2%) had a postoperative thalamic stroke leading to hemiparesis and hemineglect. No procedure-related deaths occurred. Postoperative tumor cell dissemination was observed in 14.3% of patients available for follow-up. CONCLUSIONS: For patients presenting with occlusive hydrocephalus due to tumors in or adjacent to the ventricular system, endoscopic CSF diversion is the procedure of first choice. Tumor biopsy in the current study did not affect safety or efficacy.

[Comprehensive review on rhino-neurosurgery]. / Rhino-Neurochirurgie.

In the past 2 decades, an innovative and active field of surgical collaboration has been evolved and established combining the expertise of Neurosurgery and Rhinosurgery in treatment of different lesions affecting the anterior skull base together with the adjacent intranasal and intradural areas. Important prerequesites for this development were improvements of technical devices, definitions of transnasal surgical corridors and approvements in endonasal reconstruction e. g. by use of pedicled nasal mucosal flaps. Interdisciplinary surgical teams have been established constituting specialized centers of "rhino-neurosurgery". With growing experience of these groups, it could be shown that oncological results and perioperative complications were comparable to traditional surgery while at the same time, patient's morbidity could be reduced.The present review encompasses the recent literature focussing on the development, technical details, results and complications of "rhino-neurosurgery".

Regulation of interferon-inducible proteins by doxorubicin via interferon γ-Janus tyrosine kinase-signal transducer and activator of transcription signaling in tumor cells.

Activation of the immune system is a way for host tissue to defend itself against tumor growth. Hence, treatment strategies that are based on immunomodulation are on the rise. Conventional cytostatic drugs such as the anthracycline doxorubicin can also activate immune cell functions of macrophages and natural killer cells. In addition, cytotoxicity of doxorubicin can be enhanced by combining this drug with the cytokine interferon-γ (IFNγ). Although doxorubicin is one of the most applied cytostatics, the molecular mechanisms of its immunomodulation ability have not been investigated thoroughly. In microarray analyses of HeLa cells, a set of 19 genes related to interferon signaling was significantly over-represented among genes regulated by doxorubicin exposure, including signal transducer and activator of transcription (STAT) 1 and 2, interferon regulatory factor 9, N-myc and STAT interactor, and caspase 1. Regulation of these genes by doxorubicin was verified with real-time polymerase chain reaction and immunoblotting. An enhanced secretion of IFNγ was observed when HeLa cells were exposed to doxorubicin compared with untreated cells. IFNγ-neutralizing antibodies and inhibition of Janus tyrosine kinase (JAK)-STAT signaling [aurintricarboxylic acid (ATA), (E)-2-cyano-3-(3,4-dihydrophenyl)-N-(phenylmethyl)-2-propenamide (AG490), STAT1 small interfering RNA] significantly abolished doxorubicin-stimulated expression of interferon signaling-related genes. Furthermore, inhibition of JAK-STAT signaling significantly reduced doxorubicin-induced caspase 3 activation and desensitized HeLa cells to doxorubicin cytotoxicity. In conclusion, we demonstrate that doxorubicin induces interferon-responsive genes via IFNγ-JAK-STAT1 signaling and that this pathway is relevant for doxorubicin's cytotoxicity in HeLa cells. Immunomodulation is a promising strategy in anticancer treatment, so this novel mode of action of doxorubicin may help to further improve the use of this drug among different types of anticancer treatment strategies.

Long-term health-related quality of life after decompressive hemicraniectomy in stroke patients with life-threatening space-occupying brain edema.

BACKGROUND: Although randomized clinical trials have reported significant improvement in mortality and functional outcome as measured with modified Rankin Scale (mRS) or Barthel index (BI) in stroke patients with space-occupying anterior circulation infarctions treated with hemicraniectomy, many clinicians are still concerned about the long-term health-related quality of life (HRQoL). AIM: Assessment of HRQoL after hemicraniectomy to holistically reevaluate clinical outcome. METHODS: Eleven patients (6 men, 5 women; mean age 48 (SD 5.8) years) were examined at 9-51 months after hemicraniectomy. Test batteries comprised NIH stroke scale, BI, mRS, neuropsychological tests (Visual Object and Space Perception Battery and clock test), and HRQoL-scales (Short Form 36 Health Survey (SF-36), Nottingham Health Profile (NHP), Questions on Life Satisfaction, Hospital Anxiety and Depression Scale and EQ-5D). RESULTS: Median values for NIHSS, BI and mRS were 11.5, 55 and 3.5. In HRQoL-scales, subscales related to physical mobility and functioning were consistently severely impaired, while subscales related to psychological well-being were impaired to a lesser extent. Mean scores for physical functioning and physical role were 10.5 and 12.5 in the SF-36, and 61.3 and 43.3 for physical mobility and energy in the NHP; emotional role and mental health scored 63.3 and 66.4 (SF-36), scores for emotional reaction and social isolation were 18.9 and 16.0 (NHP), respectively. CONCLUSION: Although, physical components of HRQoL are highly impaired, these stroke patients achieved a satisfying level of psychological well-being which was endorsed by a nearly unanimous retrospective appraisal of life-saving hemicraniectomy.

Doxorubicin-induced cell death requires cathepsin B in HeLa cells.

The cysteine protease cathepsin B acts as a key player in apoptosis. Cathepsin B-mediated cell death is induced by various stimuli such as ischemia, bile acids or TNFα. Whether cathepsin B can be influenced by anticancer drugs, however, has not been studied in detail. Here, we describe the modulation of doxorubicin-induced cell death by silencing of cathepsin B expression. Previously, it was shown that doxorubicin, in contrast to other drugs, selectively regulates expression and activity of cathepsin B. Selective silencing of cathepsin B by siRNA or the cathepsin B specific inhibitor CA074Me modified doxorubicin-mediated cell death in Hela tumor cells. Both Caspase 3 activation and PARP cleavage were significantly reduced in cells lacking cathepsin B. Moreover, mitochondrial membrane permeabilization as well as the release of cytochrome C and AIF from mitochondria into cytosol induced by doxorubicin were significantly diminished in cathepsin B suppressed cells. In addition, doxorubicin associated down-regulation of XIAP was not observed in cathepsin B silenced cells. Lack of cathepsin B significantly modified cell cycle regulatory proteins such as cdk1, Wee1 and p21 without significant changes in G(1), S or G(2)M cell cycle phases maybe indicating further cell cycle independent actions of these proteins. Consequently, cell viability following doxorubicin was significantly elevated in cells with cathepsin B silencing. In summary, our data strongly suggest a role of cathepsin B in doxorubicin-induced cell death. Therefore, increased expression of cathepsin B in various types of cancer can modify susceptibility towards doxorubicin.

Malignant brain oedema after radiosurgery of a medium-sized vestibular schwannoma.

CASE REPORT: We present a patient with an unusual malignant brain oedema occurring after gamma knife radiosurgery of a medium-sized vestibular schwannoma. CLINICAL PRESENTATION: A 62-year-old female with a large vestibular schwannoma underwent partial microsurgical resection; 6 months later she underwent a second intervention with gamma knife radiosurgery for a medium-sized tumour remnant. With a latency period of 6 months after radiosurgery, she presented with progressive neurological deterioration. Serial magnetic resonance imaging revealed progression of the tumour and of the perifocal oedema which finally extended up to the ipsilateral internal capsule. The patient became comatose. INTERVENTION: The tumour was nearly completely removed via a standard retrosigmoid craniotomy. Histopathological examination demonstrated increased mitotic activity compared to the initial histology. The patient became conscious 10 days after surgery and recovered slowly. Surprisingly, the brain oedema resolved rapidly. The CT scan obtained 11 days after surgery showed almost complete disappearance of the oedema. CONCLUSION: Although rare, radiosurgery of medium-sized vestibular schwannomas causing brainstem compression may lead to life-threatening tumour progression and malignant brain oedema. Therefore, microsurgical gross total resection should be the preferred treatment option in vestibular schwannomas causing significant brainstem compression.

The value of intraoperative three dimensional fluoroscopy in anterior decompressive surgery of the cervical spine.

PURPOSE: Intraoperative use of the mobile Siremobil Iso-C3D C-arm (Siemens AG, Medical Solutions, Erlangen) considerably improves the information available during cervical spine surgery. We report our experiences with the Iso-C3D fluoroscopic unit during anterior decompressive surgery of the cervical spine. METHODS: We used the mobile Siremobil Iso-C3D C-arm during decompressive cervical spine surgery. The study included 25 patients (22 males, 3 females) with degenerative cervical stenosis. Mean age was 55.9 years (42-73 years). Eighteen patients were surgically treated for one-level, six for two-level and one for three-level disease. Intraoperative 3D imaging was performed to evaluate the extent of bony decompression and to assist correct positioning of the cages when the surgeon believed that sufficient decompression had been achieved. RESULTS: Visualization of the extent of bone removal was good in all patients. In 3 patients, insufficient bony decompression with persisting dorsal osteophytic spurs was noticed on sagittal and axial images. In these patients, surgery had to be continued. Successful decompression was proved thereafter by a second scan. The quality of the images of the cervical spine was sufficient, although slightly inferior to that of a CT scan. CONCLUSION: The Siremobil Iso-C3D provides intraoperative 3D images of bony structures of the cervical spine. Although the imagine quality is inferior to that of a CT, in our series surgical revisions could be avoided in 12.5% of the patients on the basis of these intraoperative images of incomplete bony decompression. This means a reduction of additional costs which would arise with surgical revision.

Endoneurosonography: technique and equipment, anatomy and imaging, and clinical application.

OBJECTIVE: To evaluate the usefulness of transendoscopic ultrasound in neurosurgery, we studied two new sonoprobes measuring 6 and 8 French in diameter in 20 fresh specimens. The application and indication are discussed in the first clinical series of 75 patients. METHODS: Sonocatheters (ALOKA, Meerbusch, Germany) 1.9 mm (6 French) and 2.4 mm (8 French) in diameter were introduced into the working channel of an endoscope. The preparations were done in nonfixed skulls in a surgical simulation-setting laboratory. Based on these experiences with imaging possibilities, intraoperative transendoscopic ultrasound was applied in 75 patients and a variety of lesions. It was used for imaging (41 patients), targeting (18 patients), and neuronavigation (16 patients) in neuroendoscopy. RESULTS: The sonoprobe adds a transverse scan at the tip of the probe to the anterior endoscopic view. This axial scan to the longitudinal axis of the endoscope is geometrically comparable with radar scanning. Three probes working with 10, 15, and 20 MHz were used, resulting in a short penetration with a radius of 3 cm. The orthogonal scanning plane had limitations, which were documented. We observed precise imaging of well known anatomic structures and, moreover, achieved an additional dimension in endoscopy. The axial scan presents the anatomic landmarks like a map at the tip of the endoscope where the endoscope is represented as a spot. The real-time imaging and representation of the tip of the endoscope showed a capacity for navigation. This preclinical study rectified clinical application. The real-time imaging of this technique showed the ability of the navigation of endoscopes to detect more overall movements, such as blood flow or change of ventricle size during endoscopy. The primary benefit in this first clinical series was witnessed in difficult endoscopy cases and complex lesions, but benefit was also observed in cases in which vision through the endoscope alone was obscured. The main limitation was the result of little penetration depth and lack of anterior scanning. CONCLUSION: Application of transendoscopic ultrasound is appropriate in neurosurgery. Training is necessary to understand the imaging and the geometry of scans because this technique does not scan along the axis of the endoscope. Further development to overcome the current limits of this technique and more clinical experience are needed.

Long-term results after microsurgical repair of traumatic nerve lesions of the upper extremities.

OBJECTIVE: Peripheral nerve injuries are still underestimated. This study examines the outcomes after surgical treatment of traumatic nerve lesions of the upper extremities. The different surgical techniques are analyzed with regard to the long-term outcome. METHODS: This retrospective study presents the data of 93 patients (female: 24; male: 69) who were operated on for peripheral nerve injuries of the upper extremities in our department between 1991 and 2003. Mean age was 31 years (range, 5-67 years). Altogether 100 traumatic nerve lesions (ulnar nerve: 20; radial nerve: 22; median nerve: 25; axillary nerve: 6; accessory nerve: 7; musculocutaneous nerve: 2; long thoracic nerve: 1; digital nerve: 3; combined nerves: 7) were surgically treated. Surgical management included primary nerve suture in 16, neurolysis in 25, and nerve grafting in 59 patients. RESULTS: 74 patients (80%) were available for follow-up examination. The mean follow-up period was 35 months (range, 18-132 months). All patients up to the age of 20 years demonstrated good or excellent sensorimotor recovery. A good functional outcome was observed in 79% of the patients older than 20 years. Overall, good to excellent improvements of motor function were achieved for lesions of the musculocutaneous, radial, accessory and axillary nerves (100%, 89%, 100%, 100% functional useful muscle innervation, muscle recovery grade 3 and more). The length of grafts, in cases of secondary nerve reconstruction, did not influence functional outcome. CONCLUSION: Generally, early surgical repair of a nerve lesion predicted a better outcome. A good functional motor recovery was dependent on the age of the patient. Traumatic nerve lesions, without signs of reinnervation, should be treated surgically within a period of three months after injury.

[Interdisciplinary management of severe midfacial trauma]. / Interdisziplinäres Management von Mittelgesichtsverletzungen.

The anatomy of the craniofacial skeleton is complex, the bones being closely associated with important neurological structures and sensory organs. The face itself is intimately associated with hereditary features and emotional feelings, and, as a consequence, midfacial trauma may lead to important aesthetic, functional and personal problems. Patients suffering from severe midfacial injuries reveal significant concomitant lesions of other body regions in a high percentage of cases. Thus, midfacial trauma patients require an elaborate interdisciplinary regimen of diagnostics and therapy. This paper provides on overview of the interdisciplinary management of midfacial trauma patients. The overlapping multispecialty fields are analyzed with emphasis on the viewpoint of the practicing ENT-surgeon. Assuming that basic principles of trauma care are known, interdisciplinary strategies and specific responsibilities for problem solving are provided. The ENT-surgeon is guided and called upon to play an active and cooperative part in the midfacial traumatology team.

Limitations of dorsal transpedicular stabilization in unstable fractures of the lower thoracic and lumbar spine: an analysis of 133 patients.

The optimal treatment of thoracic and lumbar fractures remains controversial. While many authors recommend dorsal instrumentation with an internal fixator, others favour an anterior approach. To evaluate the posterior approach and to identify conditions under which an anterior approach should be preferred, 133 patients with unstable thoracic and lumbar fractures of the spine who underwent dorsal instrumentation with an internal fixator were analyzed. Clinical data were recorded prospectively with respect to fracture type, neurological findings, operative complications, spinal deformation correction, and long-term outcome. All fractures were located between the 7th thoracic and the 5th lumbar vertebrae and were considered to be unstable with respect to the three column model. Seventy-six patients (57%) received surgery within the first seven days after the trauma. Postoperatively, 98% of patients with a radicular lesion or an incomplete transverse syndrome (47 patients, 35%) improved. Stable fracture consolidation after fixator removal was obtained in 98% (130 of 133 patients). The preoperative kyphosis angle decreased from an average of 10.1 degrees to 7.4 degrees at the three year follow up. Major operative complications consisted of two isolated nerve root lesions (1.5%), two deep wound infections with need of fixator removal (1.5%), and mallocation of two pedicle screws with need for another procedure in two patients (1.5%). Three patients (2%) suffered from insufficient bony fusion with increase of kyphotic deformation and required subsequent anterior stabilization. These three patients presented with an initial kyphosis or wedge angle of 20 degrees or higher. In conclusion, dorsal stabilization with the internal fixator is a safe and reliable treatment for unstable fractures of the lower thoracic and lumbar spine. The authors recommend this procedure because of its low-invasiveness in conjunction with satisfactory reconstruction and stabilization. However, an anterior approach should be considered in fractures with initial kyphotic deformation or wedge angle of 20 or more degrees.

Towards waterjet dissection in neurosurgery: experimental in-vivo results with two different nozzle types.

Waterjet dissection is under close investigation as a new neurosurgical tool. Experimentally, a precise tissue dissection with vessel preservation has been demonstrated in the porcine cadaver brain. The safety of the device has been shown in first clinical applications. However, a detailed in-vivo analysis of the waterjet device is still awaited. In the present study, two often applied nozzle types (100 microm diameter emitting a coherent straight jet; 120 microm diameter emitting a helically rotating jet) were experimentally studied in vivo. Forty-one rabbits received a frontal waterjet corticotomy on either side with one nozzle type after microsurgical removal of the arachnoid membranes. Animals were sacrificed at 1, 3, 7 days and 6 weeks after surgery. Dissection morphology and vessel preservation were evaluated. Tissue trauma was analyzed by the extent of intra-operative haemorrhage, postsurgical oedema formation and astrocytic as well as microglial reactions. In all animals, reliable brain dissection was observed. Macroscopically, only minor bleeding occurred. Microscopically, also very precise brain dissection with both nozzle types was found. Vessels were preserved with both pressures applied (5 and 10 bar). Dissections with the 100 microm straight nozzle were more precise with respect to dissection margins. However, no significant difference in vessel preservation and extent of haemorrhage, oedema formation, astrocytic and microglial reactivity was shown. Malfunction defined as clotting of the instrument occurred only with the 100 microm nozzle. In four 100 microm straight nozzle hemispheres, even no brain dissection was seen. The results indicate that the waterjet enables very precise and reliable brain parenchyma dissection with minimal trauma and vessel preservation in vivo. If this can be proven to be of clinical relevance, the instrument will become a valuable neurosurgical tool. Based on these results, the authors selected the 120 microm Helix nozzle for further research with this device in the CNS.