Macrophages in Recurrent Glioblastoma as a Prognostic Factor in the Synergistic System of the Tumor Microenvironment.

Glioblastoma (GBM) is a common and highly malignant primary tumor of the central nervous system in adults. Ever more recent papers are focusing on understanding the role of the tumor microenvironment (TME) in affecting tumorigenesis and the subsequent prognosis. We assessed the impact of macrophages in the TME on the prognosis in patients with recurrent GBM. A PubMed, MEDLINE and Scopus review was conducted to identify all studies dealing with macrophages in the GBM microenvironment from January 2016 to December 2022. Glioma-associated macrophages (GAMs) act critically in enhancing tumor progression and can alter drug resistance, promoting resistance to radiotherapy and establishing an immunosuppressive environment. M1 macrophages are characterized by increased secretion of proinflammatory cytokines, such as IL-1ß, tumor necrosis factor (TNF), IL-27, matrix metalloproteinase (MMPs), CCL2, and VEGF (vascular endothelial growth factor), IGF1, that can lead to the destruction of the tissue. In contrast, M2 is supposed to participate in immunosuppression and tumor progression, which is formed after being exposed to the macrophage M-CSF, IL-10, IL-35 and the transforming growth factor-ß (TGF-ß). Because there is currently no standard of care in recurrent GBM, novel identified targeted therapies based on the complex signaling and interactions between the glioma stem cells (GSCs) and the TME, especially resident microglia and bone-marrow-derived macrophages, may be helpful in improving the overall survival of these patients in the near future.

Recurrent Atypical Meningiomas: Combining Surgery and Radiosurgery in One Effective Multimodal Treatment.

OBJECTIVE: Owing to their rarity and proteiform pathologic features, the clinical behavior of atypical meningiomas is not yet well characterized. Though the extent of resection is believed to be a key determinant of prognosis, limited data exist regarding optimal management of patients with recurrent disease. METHODS: In this 20-year retrospective case series, we reviewed the medical records of 46 patients with recurrent atypical meningiomas (185 lesions, 89 of which were local, 78 marginal, and 18 distant recurrences); treatment was radiosurgery (n = 60), surgery (n = 56), or both (n = 8). The median follow-up period was 53 months. Outcome measures were length of overall survival and disease-free intervals and prognostic factors for survival. RESULTS: Overall, the median progression-free survival was 26 months at the first recurrence and 100 months thereafter (the sum of the later intervals). Multivariate analysis showed that no treatment-related factors influenced prognosis, whereas recurrence at the skull base was a significant tumor-related factor limiting further treatment. Irrespective of treatment type, the recurrence-free interval was increasingly shorter during the clinical course, with a higher occurrence of marginal and distant lesions migrating to the midline and to the skull base. In sporadic cases, disease-free intervals were longer after wide craniotomy, tumor and dural resection with tumor-free margin. CONCLUSIONS: The disease-free interval was substantially similar after surgery and radiosurgery for treating recurrent disease in patients with atypical meningiomas. Surgery is the mainstay for prolonging survival, while radiosurgery can be an adjuvant strategy to gain time for clinical observation and planning aggressive surgical treatment.

Surgical management of ocular symptoms in spheno-orbital meningiomas. Is orbital reconstruction really necessary?

Spheno-orbital meningioma (SOM) is an intriguing tumor because of the many different factors that can influence clinical and oncological outcome after treatment. Reasoning that outcome indicator measurement is key to improving therapy, we retrospectively evaluated the management of proptosis and other ocular symptoms in 47 patients surgically treated for SOM at our department in the last 10 years. This patient series was characterized by a high rate of tumor infiltration of the extradural cranial base. Clinical outcome was assessed by comparing preoperative and postoperative ophthalmological and neurological signs. Acute postoperative complications were reported, and clinical and radiological outcome was assessed at 4-6 months, 12 months, and the last follow-up. Proptosis (measured by Hertel exophthalmometry), visual acuity, visual field defect (measured by Goldmann perimetry), diplopia (measured by the Hess-Lancaster test), and other disturbances were rated as normalized, improved, or unchanged/worsened. The most common presenting symptoms were proptosis (95.7%), visual impairment (51%), and cranial nerve deficit (38.2%). Surgery via the frontotemporal approach was performed in all 47 cases, with the primary aim to relieve symptoms/signs and maximize tumor resection. Bony orbital reconstruction was never performed. Complete resection was achieved in 51% of cases (Simpson grades I and II) with minimal morbidity. At a mean follow-up of 52 months (range, 12-112), proptosis normalized in 90.9% and improved in the remaining patients, visual acuity normalized in 20.8% and improved in 45.8% patients, cranial nerve deficit subsided in all but two cases. The recurrence rate was 29.7%. One of the gold standards of surgical treatment, normalization of proptosis, can be achieved by accurate resection of the superior and lateral orbital walls. In this setting, careful reconstruction of the frontobasal dura is far superior to bony reconstruction. Complete tumor resection should not be pursued at the expense of increased morbidity.

Dealing with the surgical and medical challenges of penetrating brain injuries.

Peacetime has reduced the overall incidence of penetrating brain injuries (PBI), and those related to missile penetration are not common anymore at least in western countries. Nevertheless, PBI still occur, and car crashes or work accidents are their main causes. The management of such cases is characterized by many challenges, not only from a surgical and medical point of view, but also for the different and sometimes bizarre dynamics by which they present. Herein we report an unusual deep penetrating brain injury, due to a high-energy crash against a metallic rod in a construction site, with a good surgical outcome despite dramatic clinical conditions on admission. A discussion of the surgical results and functional outcome related to PBI, as found in the English medical literature, is provided. Moreover the most common postoperative complications along with the diagnostic flow charts and therapeutic options useful to prevent inappropriate treatment are highlighted.

Thyroid neoplasm after central nervous system irradiation for medulloblastoma in childhood: report of two cases.

OBJECTIVE: Surgical excision combined with radio-chemotherapy represents the gold standard of therapy of medulloblastoma. The effectiveness of such a combined treatment has encouraged the use of radiotherapy even in young paediatric patients, in spite of the many adverse effects reported in literature, and, in particular, the increased risk of a second radioinduced malignancy. Irradiation is the well-known risk factor for development of benign and malignant thyroid tumours. Children are more exposed to this risk because of their thyroid gland is more sensitive to carcinogenic effect of ionising radiation. CASE REPORT: Two children underwent radiotherapy for the treatment of a medulloblastoma when they were 3 and 4 years old, respectively. At the age of 20 and 23, both of them underwent the surgical excision of a papillary thyroid carcinoma, 20 and 17 years after the radiotherapeutic treatment, respectively. CONCLUSIONS: Radioinduced thyroid tumours are a well-recognised nosographic entities due to the particular sensitivity of this gland to ionising radiations. However, only a few papers on radioinduced thyroid neoplasms after CNS irradiation have been published in the literature. We report on two additional cases of thyroid neoplasms following childhood CNS irradiation for the treatment of a posterior fossa medulloblastoma.