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Glioblastoma (GBM) remains a deadly tumor. Treatment with chemo-radiotherapy and corticosteroids is known to impair the functionality of lymphocytes, potentially compromising the development of autologous CAR T cell therapies. We here generated pre-clinical investigations of autologous anti-GD2 CAR T cells tested against 2D and 3D models of GBM primary cells. We detected a robust antitumor effect, highlighting the feasibility of developing an autologous anti-GD2 CAR T cell-based therapy for GBM patients., (© 2024. The Author(s).)

Background: Chordomas are rare primary tumors of the bone that arise from embryonic notochord. They are locally aggressive tumors with a high tendency for postsurgical recurrence. On the other hand, distant metastases are rare. When they occur, they involve lungs, liver, lymph nodes, and bones. Skin and subcutaneous tissue involvement is even rarer and usually occurs by direct extension of the primary tumor or by local recurrence. Distant cutaneous metastasis from chordoma is an exceptional finding, with fewer than 20 cases reported in the literature. All the cutaneous metastases described derive from sacral chordomas, except for 2 cases in which the source of metastasis is skull-base chordomas., Case Description: We report the case of a 55-year-old man with skin metastasis from a cervical chordoma., Conclusions: Metastasis has to be taken into account in the differential diagnosis when a new skin lesion appears in a patient with a past medical history of chordoma. To the best of our knowledge, this is the first case of cutaneous metastasis from spinal cervical chordoma. A systematic literature review was performed., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Pituitary tumors are a heterogeneous group of lesions that are usually benign. Therefore, a proper understanding of the anatomy, physiology, and pathology is mandatory to achieve favorable outcomes. Accordingly, diagnostic tests and treatment guidelines should be determined and implemented. Thus, we decided to perform a multicenter study among Italian neurosurgical centers performing pituitary surgery to provide an actual depiction from the neurosurgical standpoint., Methods: On behalf of the SINch (Società Italiana di Neurochirurgia), a survey was undertaken with the participants to explore the activities in the field of pituitary surgery within 41 public institutions., Results: Of the 41 centers, 37 participated in the present study. The total number of neurosurgical procedures performed in 2016 was 1479. Most of the procedures were performed using the transsphenoidal approach (1320 transsphenoidal [1204 endoscopic, 53 microscopic, 53 endoscope-assisted microscopic] vs. 159 transcranial). A multidisciplinary tumor board is convened regularly in 32 of 37 centers, and a research laboratory is present in 18 centers., Conclusions: Diagnosing pituitary/hypothalamus disorders and treating them is the result of teamwork, composed of several diverse experts. Regarding neurosurgery, our findings have confirmed the central role of the transsphenoidal approach, with preference toward the endoscopic technique. Better outcomes can be expected at centers with a multidisciplinary team and a full, or part of a, residency program, with a greater surgical caseload., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: In the context of von Hippel-Lindau disease (VHL), the medulla oblongata is a relatively frequent site of growth of hemangioblastomas, posing related clinical and surgical difficulties. Their management requires a close correlation between clinical evolution and morphological surveillance. In order to describe their clinical and surgical features, we reviewed our experience in the treatment of these lesions., Methods: Between 2001 and 2009, 14 patients (9 female and 5 male, mean age 34 years) underwent removal of 15 lower brain stem hemangioblastomas. Based on the review of the clinical records and outpatient long-term follow-up visits, their clinical course was analyzed. Functional evaluation was measured with the Karnofsky Performance Scale (KPS) on admission, at discharge and at the last follow-up. The mean follow-up period was 30.8 months (range 4-99)., Results: All the operated hemangioblastomas were located in the dorsal medulla oblongata, in the context of multiple lesions, cerebellar and/or spinal. In ten patients hemangioblastomas were located in a median position at the obex area; in four cases a lateral location was observed. Cystic component was absent in two cases. Clinical onset preceded surgery by a mean of 8.5 months. Preoperatively three patients showed a KPS lower than 80, ten patients between 80 and 90, and one patient scored 100 (asymptomatic). There was no surgical mortality. Nine out of 14 patients showed a temporary surgical morbidity. One patient required a tracheostomy. At follow-up ten patients scored a KPS better than before the operation, while the other four patients remained stable. Permanent morbidity was observed in three patients., Conclusions: Lower brain stem hemangioblastomas in the context of VHL show an often gradual onset of signs and symptoms except for patients who develop an obstructive hydrocephalus. Although transient surgical complications are possible, surgery provides favorable long-term results.

Background: Early surgical removal of cerebral AVMs is a relatively infrequent therapeutic option when dealing with a cerebral hemorrhage caused by AVM rupture: even in the case of low-grade AVMs, delayed treatment is, if possible, preferred because it is considered safer for patients and more comfortable for surgeons. To assess whether acute surgery may be a safe and effective management, we conducted a retrospective analysis of our early surgery strategy for ruptured low-grade AVMs., Methods: We reviewed 27 patients with SM grade I-II AVM treated during 2004 to 2008 in the acute stage of bleeding (within the first 6 days after bleed). All patients showed a cerebral AVM on DSA at admission, and surgical removal was controlled by postoperative angiography. Neurological outcomes were assessed with GOS. The average length of follow-up was 22 months (48-3 months)., Results: Before surgery, 16 (59%) patients showed a GCS of 8 or less, 2 of them presenting an acute rebleeding after first hemorrhage. All patients underwent radical AVM surgical removal and hematoma evacuation in a single-stage procedure. Most patients (78%) were operated within the first day of hemorrhage. A favorable functional outcome (GOS: good recovery or moderate disability) was observed in 23 patients (85%). Mortality was 7.4%. Outcome was not significantly correlated with GCS at presentation and with presence of preoperative anisocoria., Conclusions: Early surgery for grade I-II AVMs is a safe and definitive treatment, achieving both immediate cerebral decompression and patient protection against rebleeding, reducing time of hospital stay and allowing a more rapid rehabilitative course whenever necessary., (Copyright 2009 Elsevier Inc. All rights reserved.)

Aim: Von Hippel-Lindau (VHL) disease is a genetic syndrome predisposing to central nervous system (CNS) hemangioblastomas and several lesions in many organs. The cases of all VHL individuals operated on in the Neurosurgical Unit of Padua Hospital since year 2000 were reviewed in order to define which features lead to surgical treatment and to examine surgical outcome during postoperative follow-up., Methods: The authors evaluated 20 VHL subjects (7 males and 13 females, age at surgery 32+/-10 years) who underwent 28 operations in order to remove 48 CNS hemangioblastomas and 1 endolymphatic sac tumor. Among the 49 resected lesions, 21 (42%) were cerebellar, 9 (18%) at brainstem, 19 (38%) spinal (7 cervical, 6 dorsal, 6 at cone-cauda level), and 1 (2%) endolymphatic sac tumor in the petrous bone. Patients were graduated according to Karnofsky Performance Status (KPS) at admission, at discharge and during the last follow up visit. Genetic testing revealing the presence of a VHL disease-causing mutation was a prerequisite for inclusion in the study., Results: Nineteen individuals (95%) were symptomatic. Symptomatic hemangioblastomas were associated with a cyst or a syrinx in 22/27 circumstances (81%). Total removal, as confirmed by postoperative magnetic resonance imaging (MRI), was achieved in all but one lesion. Following surgery, at follow-up (38+/-20 months), patients improved their neurological status in 75% of cases, 20% remained stable and 5% worsened; 16 patients (80%) are able to carry on normal activity with or without minor symptoms, 3 patients require some grade of assistance, 1 patient died because of bronchopneumonia., Conclusion: VHL-associated hemangioblastomas generally affect a young adult population and can be successfully removed, either when symptomatic, or when they reach a critical volume. Microsurgery of hemangioblastomas has a favourable impact on survival and quality of life of VHL patients, although it is strongly influenced by preoperative conditions. Transient surgical complications are possible, particularly with brainstem and spinal cord hemangioblastomas.

Pituitary adenomas are slow-growing tumours arising within the pituitary gland. If secreting, they give rise to well-known syndromes such as Cushing's disease or acromegaly; when hormonally inactive, they come to clinical attention often with local mass effects or pituitary deficiency. Peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear hormone receptor with a key role in fat and glucose metabolism, but also involved in several neoplasia, has recently been detected in pituitary adenomas. In the present study, we evaluated the occurrence and splicing profile of PPARgamma in 43 cases of pituitary adenoma of different subtypes and compared it to 12 normal pituitary glands. By real-time polymerase chain reaction, PPARgamma was expressed as much in adrenocorticotrophic hormone (ACTH)-secreting and ACTH-silent adenomas as in controls, with a moderate underexpression in somatotrophinomas and prolactinomas and overexpression in 54% of nonfunctioning pituitary adenomas (NFPA). There was no apparent qualitative change in the splicing profile of pathological pituitary glands, nor was the presence of specific isoforms with dominant negative effects against PPARgamma detected. Western blotting revealed similar expression levels in the different subgroups of pituitary adenomas and normal glands. Immunohistochemistry confirmed PPARgamma expression in approximately one-half of analysed samples. The intra- and intergroup differences observed in pituitary adenomas may represent new elements in the process of understanding the different clinical responses of Cushing's and Nelson patients to PPARgamma-ligand treatment. Moreover, the higher level of PPARgamma expression detected in the NFPA subgroup may suggest its possible role as a molecular target in these pituitary adenomas, paving the way for investigations on the effectiveness of treatment with thiazolidinediones in such patients.

Objective: The etiological diagnosis of ACTH-dependent Cushing's syndrome is often a problem. In fact, no endocrine or radiological examination can conclusively distinguish the ectopic from the pituitary source of disease. The aim of our study was to evaluate the role of stimulation and suppression endocrine tests in the diagnostic and therapeutic approach of patients with Cushing's disease (CD) and negative pituitary magnetic resonance imaging (MRI), considering their post-surgical outcome in comparison with patients with CD and positive MRI., Patients and Methods: We retrospectively analyzed 31 patients (25 women and 6 men, median age 40 +/- 15 years) with a confirmed diagnosis of CD who underwent transsphenoidal pituitary surgery by the same neurosurgeon between 2001 and 2005. Preoperative endocrine assessment included corticotropin-releasing hormone (CRH), desmopressin (dDAVP), and overnight 8 mg dexamethasone suppression tests (8-DST) in all patients. Fifteen patients had a normal pituitary MRI and sixteen had a clearly evident pituitary microadenoma. Bilateral inferior petrosal sinus sampling (BIPSS) was performed in patients with discordant biochemical results or with signs and symptoms highly suggestive of an ectopic source of ACTH. Post-surgical median follow-up was 38.4 +/- 22.0 months., Results: Among patients with negative MRI, 60% had concordant positive endocrine tests and underwent neurosurgery without other examinations. BIPSS was performed in three other patients prompted by discordant endocrine tests (negative dDAVP) and in two patients with clinical suspicion of ectopic disease. Among patients with positive MRI, 87% underwent neurosurgery without BIPSS that was performed in two patients because of negative concomitant response to dDAVP and CRH tests. A pituitary adenoma, confirmed by pathological examination, was found in 40 and 81% of patients with negative and positive MRI respectively (P<0.05), corticotroph hyperplasia resulted more frequent in the group with negative MRI. Remission rate was not different between patients with negative and positive MRI (73 and 75% respectively; P=0.61) and between patients with negative MRI who did not undergo BIPSS and patients with positive MRI (P=0.56). The recurrence rate was also similar between groups (P=0.64), but higher, although not statistically different (P=0.07) in patients with corticotroph hyperplasia at histology., Conclusions: An accurate evaluation of presurgical endocrine tests results enabled us to reduce the number of BIPSS in patients with a negative MRI without any fallout on their post-surgical outcome. In the hands of an expert pituitary surgeon, the outcome after surgeryand the subsequent recurrence rate are much the same in patients with negative or positive MRI.

Between February 1993 and March 1994, 75 metastases, 16 gliomas and 2 AIDS-related malignant lymphomas were treated with Gamma Knife radiosurgery. Metastatic brain tumors (54% lung cancer, 14% breast cancer, 13.5% melanoma) were the most frequent and clinically rewarding cases. So-called local control was achieved in almost all patients, the vast majority showing neurological improvement associated with radiological disappearance or dramatic shrinkage of the tumor within 9-12 weeks from treatment. According to our modified 'Pittsburgh' protocol, we have treated up to four distinct intracranial lesions, up to a total maximum volume of 20 cm3, with an average surface dose of 25 Gy, with or without additional whole brain radiotherapy (WBR). Preliminary follow-up data seem to confirm increased quality of life and survival rates. The results were particularly striking whenever primary tumors were under control, and were poorly influenced by associated WBR. Gamma Knife treatment was also performed in a selected group of patients with small-to-medium-sized, well-defined, histologically proven, cerebral gliomas. The main indications for radiosurgery were high-risk surgery, multifocal disease, ventricular seeding and unresected or recurrent tumor. The prescription doses ranged from 18 to 30 Gy, with a mean of 27 Gy. Low-grade astrocytomas (9/16 cases) showed the better clinical and radiological response to treatment, with neurological recovery and significant reduction in tumor volume within 3-5 months in 5 of the 9 patients. In 4 of 7 high-grade gliomas, there was little or no response. However, an impressive radiological regression with full clinical recovery was observed in 2 high-grade cases with small tumor volumes: a recurrent, anaplastic 'mixed glioma' of the pineal region and a double ventricular seeding of a previously operated anaplastic astrocytoma.