Electrochemotherapy in Spine Metastases: A Case Series Focused on Technical Aspects, Surgical Strategies and Results.

Metastases are complications of primary tumors due to prolonged cancer survival and have become an important issue for oncological patients and the most frequent cause of death and disability. Bone metastases occur at a later stage of cancer disease, and the spine is the most frequent site. To date, the aim of the treatment of metastases remains to be the control of disease and provide a satisfactory quality of life. The decision making of treatment is influenced by several factors such as the status of the primary disease, the number of metastases, site involvement, and the performance status of the patients. For this reason, the treatment of metastases is challenging and undergoes constant development. Therefore, alternative techniques with respect to surgery, which is the first option but not always practicable, and radiochemotherapy are attractive. Lately, electrochemotherapy has emerged as an innovative method for treating various primary and metastatic solid tumors, showing promising outcomes in terms of inducing tumor tissue necrosis and alleviating symptoms. This technique uses electric pulses to increase the uptake of chemotherapy by tumor cells. Despite the initial enthusiasm and good results in the treatment of bone tumors, relatively few papers have described its use in spine metastases. Therefore, we conducted a systemic review of this intriguing topic while also reporting our experience in the use of electrochemotherapy for the treatment of spine metastases.

HER2 expression and genOmic characterization of rESected brain metastases from colorectal cancer: the HEROES study.

BACKGROUND: Little is known about prognostic factors of brain metastases (BM) from colorectal cancer (CRC). HER2 amplification/overexpression (HER2+) was previously described; its impact on prognosis remains uncertain. METHODS: In the translational study HEROES, extensive molecular analysis was performed on primary CRC (prCRC) and their matched resected BM by means of NGS comprehensive genomic profiling and HER2 status as assessed by immunohistochemical/ in situ hybridization. Count of tumour-infiltrating lymphocytes (TILs) was also performed. PRIMARY OBJECTIVE: to describe the molecular landscape of paired BM/prCRC. SECONDARY OBJECTIVES: to search for new prognostic biomarkers of outcome after BM resection: intracranial-only Progression-Free Survival (BM-iPFS), Progression-Free Survival (BM-PFS), and Overall Survival (BM-OS). RESULTS: Out of 22 patients having paired samples of prCRC and BM, HER2+ was found on 4 (18%) BM, 3 (75%) of which also HER2+ in matched prCRC. Lower tumour mutation burden (HR 3.08; 95%CI 1.06-8.93; p = 0.0386) and HER2-negative BM (HER2neg) (HR 7.75;95%CI 1.97-30.40; p = 0.0033) were associated with longer BM-iPFS; HER2neg BM (HR 3.44; 95%CI 1.03-11.53; p = 0.0449) and KRASmut BM (HR 0.31; 95%CI 0.12-0.80; p = 0.0153) conferred longer BM-PFS. Longer BM-OS was found in pts with TILs-enriched (≥1.6/HPF) BM (HR 0.11; 95%CI0.01-0.91; p = 0.0403). CONCLUSIONS: This study shows HER2+ enrichment in both BM and their prCRC. TILs-enriched BM conferred better BM-OS.

Thalamopeduncular Tumors in Pediatric Age: Advanced Preoperative Imaging to Define Safe Surgical Planning: A Multicentric Experience.

Background: Thalamopeduncular tumors are challenging lesions arising at the junction between the thalamus and the cerebral peduncle. They represent 1-5% of pediatric brain tumors, are mainly pilocytic astrocytoma and occur within the first two decades of life. To date, the optimal treatment remains unclear. Methods: We retrospectively reviewed pediatric patients who underwent surgery for thalamopeduncular tumors in the Academic Pediatric Neurosurgery Unit of Padova and Verona from 2005 to 2022. We collected information on age, sex, symptoms, preoperative and postoperative neuroradiological studies, histological specimens, surgical approaches, and follow-up. Results: We identified eight patients with a mean age of 9 years. All lesions were pilocytic astrocytoma. The main symptoms were spastic hemiparesis, cranial nerve palsy, headache, and ataxia. The corticospinal tract was studied in all patients using diffusion-tensor imaging brain MRI and in two patients using navigated transcranial magnetic stimulation. The transsylvian approach was the most frequently used. A gross total resection was achieved in two patients, a subtotal resection in five and a partial resection in one. In three patients, a second treatment was performed due to the regrowth of the tumor, performing an additional surgery in two cases and a second-look surgery followed by adjuvant therapy in one. After the surgery, four patients maintained stability in their postoperative neurological exam, two patients improved, and two worsened but in one of them, an improvement during recovery occurred. At the last follow-up available, three patients were disease-free, four had a stable tumor residual, and only one patient died from the progression of the disease. Conclusions: Advanced preoperative tools allow one to define a safe surgical strategy. Due to the indolent behavior of thalamopeduncular tumors, surgery should be encouraged.

Aesthetic transaxillary subpectoral placement of vagus nerve stimulator in children and young adults: A technical note.

INTRODUCTION: Vagus nerve stimulation (VNS) is a neuromodulation therapy for drug-resistant epilepsy (DRE), refractory status epilepticus, and treatment-resistant depression. The lead is tunneled into the subcutaneous space and connected to the generator, which is usually implanted in a subcutaneous pocket below the clavicle. Surgical complications in the chest region include skin breakdown or infection. An alternative approach is to perform a subclavear subpectoral implantation. In our surgical series, we report a new aesthetic implantation method for VNS generators in children and young patients: the transaxillary subpectoral placement. MATERIALS AND METHODS: From May 2021 to May 2023, 10 vagus nerve stimulation generators were placed subpectorally with a transaxillary approach by the authors. We considered operative time, surgical complications such as blood loss, infections, device migration, pain, and adverse events at follow-up. RESULTS: In this surgical series, we reviewed all cases of subpectoral implantation of VNS generators in children and young adults at our institution in the last 2 years. All patients were treated with subpectoral Sentiva 1000 (Livanova PLC) insertion with axillary access by a neurosurgeon and a pediatric surgeon. The operative time was slightly longer compared to the traditional subcutaneous implant. All generators reported impedances within the optimal range. Blood loss was not significant and no other perioperative complications were reported. Patients and families were highly satisfied with the outcomes in terms of comfort and aesthetic results after surgery and at the last follow-up. No cases of infection occurred, and no malfunctions or displacements of the generator were registered at clinical follow-up. CONCLUSION: The transaxillary subpectoral placement of theVNS generator is an aesthetic and anatomic approach, which provides several benefits to children and young adults.

Navigated Transcranial Magnetic Stimulation Motor Mapping and Diffusion Tensor Imaging Tractography for Diencephalic Tumor in Pediatric Patients.

Background. In deep-seated brain tumors, adequate preoperative planning is mandatory to assess the best surgical corridor to obtain maximal safe resection. Functional diffusor tensor imaging (DTI) tractography based on navigated transcranial magnetic stimulation (nTMS) motor mapping has proven to be a valid preoperative examination method in adults. The aim of this paper is to present the application of nTMS and functional DTI tractography in a series of pediatric diencephalic tumors. Material and methods. Three patients affected by thalamic (one) and thalamopeduncular tumor (two) were successfully examined with nTMS motor mapping and DTI tractography between October 2020 and October 2021 (F:M 3:0, mean age 12 years ± 0.8). Cortical representation of leg, hand and mouth were determined in the affected hemisphere and the positive stimulation spots were set as seeds point for tractography. Results. Mapping of the motor cortex and tracts reconstruction for leg and hand were successful in all patients, while facial function was properly mapped in one patient only. In all cases, the procedure was well tolerated and no adverse events were recorded. Spatial relationships between tumor and functional tissue guided the surgical planning. Extent of the resection varied from 96.1% to 100% with a postoperative new motor deficit in one patient. Conclusions. nTMS and DTI fiber tracking is a feasible, effective and well-tolerated method to identify motor pathway in deep-seated lesion in pediatric population.

Acquired Chiari type I malformation: a late and misunderstood supratentorial over-drainage complication.

PURPOSE: Acquired Chiari I malformation is an uncommon but possible late complication of supratentorial shunting in children. This condition can be caused by an abnormal thickening of the cranial vault and consequent reduction of the posterior cranial fossa (PCF) volume especially in children with already a small PCF volume. The management of Acquired Chiari I malformation is very challenging, and several options have been proposed for this condition. These are aimed to expand the PCF volume both through decompression and PCF remodeling in order to relieve symptoms of acquired Chiari I malformation. A cranial vault remodeling or a standard Chiari decompression is two proposed techniques aimed to expand the PCF volume thus relieving symptoms . METHODS: We describe the case of a 16-year-old girl undergone surgical removal of sellar-suprasellar glioneuronal tumor and ventriculo-peritoneal shunting, who developed an acquired symptomatic Chiari type I malformation some years after ventricular-peritoneal shunting. For this condition, she underwent successful standard Chiari decompression with C0-C1 craniectomy and duroplasty. RESULTS: We retrospectively analyzed MRI and CT scan performed during follow-up, in order to evaluate the volume of the posterior cranial fossa and to measure the variation of skull thickness at different periods. MRI and CT scan analysis showed a progressive thickening of the calvaria, in particular of the occipital bone, leading to a progressive reduction of PCF volume with the establishment of acquired Chiari type I malformation. In this case, standard C0-C1 Chiari decompression was effective in restoring PCF volume and relieving symptoms. CONCLUSION: Acquired Chiari I malformation due to chronic overhunting could be a severe and late complication in patient undergone supratentorial shunting. These patients require careful clinical and radiological follow-up to avoid over-drainage. According to our analysis, a careful selection of pediatric patients for supratentorial shunting should be made according to pre-operative PCF volume in order to foresee higher odds of possible late complications from over-drainage.

Intraoperative neurophysiology of the cerebellum: a tabula rasa.

PURPOSE: Cerebellar mutism (CM) is a condition that occurs predominantly in children, after posterior fossa surgery (PFS). It is characterized by motor, speech, and behavioral disorders. Despite widespread use of intraoperative neurophysiological monitoring (IONM), little is known about the neurophysiological aspects involved in the pathophysiology of CM. We reviewed the IONM literature to identify working hypotheses aimed to investigate intraoperatively the circuits involved in CM. METHODS: A systematic review of the literature was conducted using PubMed central database. Papers describing the use of IONM techniques in the cerebellum were selected, thoroughly reviewed, and discussed. RESULTS AND DISCUSSION: Only two studies reported the use of intraoperative neurophysiology of the cerebellum, suggesting a possible somatotopic motor organization of the cerebellar cortex. In addition, extra-operative studies using transcranial magnetic stimulation showed the possibility to modulate-possibly through the dentato-thalamic-cortical (DTC) pathway-primary motor cortex output using an appropriate cerebellar stimulus. In theory, the preservation of this either inhibitory or facilitatory modulation may predict the preservation of this pathway, while a loss of the effect may indicate an injury to the pathway, and predict a CM. Analogously, in the extra-operative setting, the comparison of pre-operative and post-operative transcranial magnetic stimulation of the cerebellum may predict the onset of CM whenever a pre-existing modulatory effect is lost as a result of surgery. CONCLUSION: Virtually, no data exist on the intraoperative neurophysiology of the cerebellum. This limited knowledge, nevertheless, offers a unique opportunity to pediatric neurosurgeons to develop and test working hypotheses on the pathophysiology of CM, through the use of IONM.

Long-term follow-up after surgical removal of meningioma of the inner third of the sphenoidal wing: outcome determinants and different strategies.

Meningioma arising in the inner third of the sphenoidal wing has been well recognized since the origin of neurosurgery, yet it still poses a formidable challenge for the surgeon. Treatment strategies can be optimized through a tailored approach to surgical timing and use of a non-surgical armamentarium. The aim of this study was to evaluate the long-term effect of different strategies on progression-free survival and overall survival. We examined the clinical records of brain tumor patients to assess determinants for surgery (extent of tumor removal, postoperative complications) and for progression-free survival and overall survival in relation to timing of surgery eventually followed by stereotactic radiosurgery (SRS). The records of 60 patients were retrospectively reviewed, from preoperative assessment to a median follow-up of 104 months. All were symptomatic with prevalently visual symptoms (42.2%), large tumors (median diameter 3.44 cm), extension into the cavernous sinus (38.3%), and severe vascular involvement of one or more encased or narrowed vessels (50%). Subtotal removal was achieved in 40% of cases, mainly determined by cavernous sinus and vascular involvement; neurological complications occurred in 18.3% (persistent in 6.7% due to oculomotor and vascular injury). The overall rate of symptom improvement was 32.3% at 3 months and 49.5% at 12 months. Radiological monitoring prevented clinical progression; tumor progression occurred in 11.7% of cases. There were significant differences in progression-free survival between patients with (median 46 months) and those without (median 104 months) recurrence (p = 0.002): 12.5% after total removal, 6.2% after subtotal removal and adjuvant SRS, and 28.5% after subtotal removal and observation. The related Kaplan-Meier survival curve showed no significant difference between the three strategies. Further, disease progression after recurrence was noted in 28.6% of cases, but overall survival was not influenced by either tumor recurrence or type of treatment. Treatment failure was recorded in four cases (6.7%): one perioperative death and three later on. Surgery is the mainstay for the treatment of symptomatic meningioma and to restore neurological function; however, resectability is limited by vascular and cavernous sinus involvement. Careful postoperative monitoring prevented clinical progression and adjuvant or adjunctive SRS proved effective in tumor control. A low surgical complication rate and excellent long-term outcomes were achieved with this strategy.

Fibrous Pituitary Macroadenomas: Predictive Role of Preoperative Radiologic Investigations for Proper Surgical Planning in a Cohort of 66 Patients.

OBJECTIVE: The endoscopic technique is in many cases the technique of choice for the removal of pituitary adenomas. Extended endoscopic approaches make it possible to remove lesions with suprasellar and parasellar extension and fibrous consistency. We identify some characteristics that might point to the adoption of an expanded approach in the preoperative phase. METHODS: We considered 66 consecutive cases treated for pituitary macroadenomas. All patients underwent preoperative magnetic resonance imaging and computed tomography, as well as postoperative magnetic resonance imaging. From the analysis of surgical reports and preoperative radiologic investigations, we extracted data related to size, extension, morphologic characteristics, consistency, and type of approach used (sellar or expanded). The degree of removal was judged to be total, near total, subtotal, or partial. RESULTS: The data showed that in some cases it is possible to assume in advance that there is a need for an expanded endoscopic approach. The features that led to an extended approach for extracapsular dissection of the lesion were the size of the tumor; an hourglass/dumbbell shape; lateral extension to the suprasellar carotid artery; Knosp degree 3 or 4; contrast enhancement heterogeneity; intratumoral hemorrhage, erosion, or discontinuity of the sellar floor; and increased sellar depth, which predicts increased thickness. CONCLUSIONS: The ability to predict the consistency of pituitary adenomas allows the surgeon to design a surgical procedure tailored to the patient. This approach has advantages concerning the extent of resection and allows a radical strategy with a single surgical procedure to be pursued.

Neurosurgical applications of the 2-µm thulium laser: histological evaluation of meningiomas in comparison to bipolar forceps and an ultrasonic aspirator.

OBJECTIVE: The authors evaluated the histological effects of the 2-µm thulium laser on meningioma tissue, comparing them to the results obtained using bipolar forceps and an ultrasonic aspirator. METHODS: The authors analyzed nine samples of intracranial meningiomas. Four slices were obtained for every sample, and one incision was performed on each slice. Two incisions were made with a 2-µm thulium laser (one set to a 6 W and another set to a 12 W power level). One incision was made using a bipolar forceps and the other using an ultrasonic aspirator. Tissue was addressed and analyzed. Upon microscope analysis, three zones of laser action were identified: (A) a central crater; (B) a vaporized zone; and (C) a shrunken layer. These three layers were measured and compared. RESULTS: When addressed with the laser, all nine meningiomas presented a crater having an average depth of 1 mm. Three layers were clearly distinguished and measured: A (average depth: 0.8 mm at 6 W and 1.24 mm at 12 W); B (average depth: 0.32 mm at 6 W and 0.72 mm at 12 W); and C (average depth: 0.39 mm at 6 W and 0.44 mm at 12 W). On slices treated with bipolar forceps incisions, only zones B and C were identified. Ultrasonic aspirator incisions showed a deeper A zone (average depth: 2.93 mm), no B zone, and a tiny C zone (average depth: 0.16 mm). CONCLUSIONS: Thulium laser can be safely used for the surgical removal of intracranial meningiomas; beyond 2 mm under the surface of action, no tissue alterations were found. The lesions produced on meningiomas were characterized by vaporization and shrinking. When compared with bipolar forceps, the thulium laser offers cutting precision and vaporization of the tissue. When compared to the cavitron ultrasonic surgical aspirator (CUSA), the laser offers shrinking and coagulation of small vessels.