Filippo Gagliardi

Surgical strategies and modern therapeutic options in the treatment of craniopharyngiomas

The optimal treatment of patients with craniopharyngioma remains controversial. In particular, the role of aggressive treatment compared to less aggressive therapeutic options is poorly understood. Radical resection is the therapy of choice at any age, because it is associated with the best outcome in terms of survival. Nevertheless, aggressive behaviour, location, involvement of critical structures, tumour size, calcifications, and patient age may limit the extent of resection. Surgery can also carry significant morbidity in terms of visual, hypothalamic, and endocrinological disturbances. Long term sequelae reduce the quality of life in 50% of long-term survivors, notably obesity and neurobehavioral impairment due to hypthalamic involvement and iatrogenic induced lesions. The quality of life should be considered as a clinically important endpoint in patients, who currently experience good overall survival rates, regardless of the degree of surgical resection. Tendency to recur despite negative postoperative imaging led many authors to advocate a less aggressive surgical treatment followed by radiation therapy. We review the data reported in the literature, especially early outcome after surgical treatment and factors affecting the risk of tumour recurrence, to elucidate the role of attempted radical resection in the treatment of craniopharyngioma and to identify the clinical and morphological characteristics predictive for the best surgical prognosis.

Reconstruction techniques in skull base surgery.

One of the major challenges of cranial base surgery is reconstruction of basal dural defects. Ineffective reconstruction may result in potentially life-threatening complications such as cerebrospinal fluid leak, meningitis, and tension pneumocephalus. Goals of reconstructive procedures are to repair the dural defect and to separate intracranial contents from bacteria-laden secretion of the mouth, nose, and sinus. Different reconstructive techniques have been reported. Multiple factors may influence the surgical choice of reconstructive technique and its outcome. Regional pedicled flap and vascular free flaps represent the best reconstructive options because vascularized tissues promote fast and complete healing. A variety of endoscopic pedicled mucosal flaps within the nasal cavity have also been described. The different reconstruction techniques are described and discussed in terms of indications, advantages, and drawbacks.

Skull base chordomas: clinical outcome in a consecutive series of 45 patients with long-term follow-up and evaluation of clinical and biological prognostic factors

OBJECTIVE Skull base chordomas (SBCs) are rare dysembryogenetic invasive tumors with a variable tendency for recurrence. According to previous studies, the recurrence rate seems to be affected by both clinical variables and tumor biological features. The authors present the results of treatment of SBCs in a large series of patients and investigate the role of 1p36 chromosomal region loss of heterozygosity (LOH) as a prognostic factor. METHODS Between 1990 and 2011, 45 patients were treated for SBCs. The mean follow-up was 76 months (range 1-240 months). An LOH analysis was performed in 27 cases. Survival analysis was performed to determine clinical and biological parameters correlating with clinical outcome. RESULTS The 5- and 10-year overall survival rates were 67% and 57%, respectively. Five- and 10-year progression-free survival rates were 58% and 44%, respectively. Multivariate analysis showed that extent of resection, adjuvant radiation therapy, and absence of rhinopharynx invasion were positive independent predictors of overall survival. The latter 2 variables and a younger patient age were positive independent predictors of progression-free survival. Twenty-one patients showed 1p36 LOH. All events of recurrence and death clustered in the group of patients with 1p36 LOH; however, this biological marker was not statistically significant on multivariate analysis. CONCLUSIONS Resection is the treatment of choice in primary and recurrent SBC. Patient age, rhinopharynx invasion at diagnosis, extent of tumor removal, and postoperative radiation therapy influence SBC prognosis. Genetic analysis, even while showing interesting results, did not reveal 1p36 LOH as an independent predictor of clinical outcome.

The role of CXCR4 in highly malignant human gliomas biology: current knowledge and future directions.

Given the extensive histomorphological heterogeneity of high‐grade gliomas, in terms of extent of invasiveness, angiogenesis, and necrosis and the poor prognosis for patients despite the advancements made in therapeutic management. The identification of genes associated with these phenotypes will permit a better definition of glioma heterogeneity, which may ultimately lead to better treatment strategies. CXCR4, a cell surface chemokine receptor, is implicated in the growth, invasion, angiogenesis and metastasis in a wide range of malignant tumors, including gliomas. It is overexpressed in glioma cells according to tumor grade and in glioma tumor initiating cells. There have been various reports suggesting that CXCR4 is required for tumor proliferation, invasion, angiogenesis, and modulation of the immune response. It may also serve as a prognostic factor in characterizing subsets of glioblastoma multiforme, as patients with CXCR4‐positive gliomas seem to have poorer prognosis after surgery. Aim of this review was to analyze the current literature on biological effects of CXCR4 activity and its role in glioma pathogenesis. A better understanding of CXCR4 pathway in glioma will lead to further investigation of CXCR4 as a novel putative therapeutic target. GLIA 2014;62:1015–1023

Current therapeutic options and novel molecular markers in skull base chordomas.

Chordomas are extremely rare tumours. They arise in the spheno-occipital region in 35% of cases. Chordomas usually present benign histopathological features but often exhibit a malignant clinical behaviour. Radical surgical removal and high-dose radiation therapy seem to be effective in tumour control and to improve survival rate. Despite the advancements in microsurgical techniques and the development of radiation therapies, clival chordomas still represent a challenge. Nevertheless it appears that chordomas that have been resected to the same extent and that received post-operative radiotherapy might exhibit different rates of regrowth. This result supports the hypothesis that the recurrence rate of chordomas might be dependent on biological variables other than the extent of resection and the post-operative radiotherapy. Genetic and molecular studies on oncogenesis of chordomas are still limited, but they represent the basis for the development of molecular targeted therapies. We present a review of the current knowledge about skull base chordomas biology, therapeutic options and related clinical outcome.

Surgical treatment of orbital cavernomas: clinical and functional outcome in a series of 20 patients

PurposeThe aim of this study is to assess the efficacy and safety of surgical treatment of orbital cavernomas in terms of clinical and functional results.MethodsTwenty consecutive patients underwent surgical removal of a unilateral orbital cavernoma between 1999 and 2009. Indications for surgical treatment were: visual impairment, diplopia due to ocular movement impairment, progressive and disfiguring unilateral proptosis, severe retroorbital pain clearly related to the orbital cavernoma. We used a topographic classification of the lesions within the orbit. The orbit has been divided into an anterior and a posterior compartment on the axial plane and into three sectors on the coronal plane. The proptosis was quantified on MRI scans.ResultsThe location of the cavernoma determined the choice of the surgical approach. We performed eight lateral orbitotomies and 12 fronto-orbito-zygomatic approaches. All the tumors were completely removed as assessed at follow-up MRI. We did not record any intraoperative or major postoperative complication requiring a reoperation. The postoperative visual acuity improved in four of five patients with visual impairment, it worsened in the other case. Proptosis improved in all the patients. Diplopia improved in four patients, and did not recover in another case.ConclusionSurgical treatment of symptomatic orbital cavernomas is safe and effective. Tumor location dictates the choice of surgical approach. Visual function and cosmetic result are the main parameters to evaluate the clinical outcome. Surgical approach and dissection technique are crucial in determining the visual outcome.

Management of spheno-orbital en plaque meningiomas: clinical outcome in a consecutive series of 40 patients

Abstract Objective. The clinical results of combined surgical–radiosurgical treatment of the spheno-orbital en plaque meningiomas in a consecutive series of 40 patients are presented. The clinical outcome is evaluated in terms of surgical morbidity, tumour control, visual function and cosmetic result. Methods. Forty patients harbouring spheno-orbital en plaque meningiomas were treated. Forty-two surgical procedures were performed through a fronto-temporal craniotomy. The reconstruction of the orbital walls was performed using a titanium mesh. In case of sub-total resection, the patients underwent Gamma-Knife radiosurgery on residual tumour. Visual function was evaluated considering visual acuity tested with a Snellen chart, funduscopy and Goldmann perimetry for visual field defects. Proptosis was quantified on CT scans. Results. Total or gross-total tumour resection was achieved in 56.1% of cases. Permanent morbidity was recorded in three patients after surgery. Visual acuity and visual field defect both improved in 66.7% of patients; improvement of proptosis was recorded in 92.7% of cases. Eighteen patients were treated with Gamma-Knife radiosurgery for residual tumour after surgery and four patients for tumour relapse at follow-up. The mean follow-up period was 72.6 months. Conclusions. Surgical treatment of spheno-orbital en plaque meningiomas is safe and effective: a low morbidity rate was recorded and visual function improved in about two-thirds of patients. Reconstruction of the orbital walls with titanium mesh provides for good functional and cosmetic results. In case of superior orbital fissure and cavernous sinus invasion, the combined surgical–radiosurgical treatment allows to minimise surgical morbidity and to achieve tumour control.

Intracranial injectable tumor model: technical advancements.

Background and Objectives Few simulation models are available that provide neurosurgical trainees with the challenge of distorted skull base anatomy despite increasing importance in the acquisition of safe microsurgical and endoscopic techniques. We have previously reported a unique training model for skull base neurosurgery where a polymer is injected into a cadaveric head where it solidifies to mimic a skull base tumor for resection. This model, however, required injection of the polymer under direct surgical vision via a complicated alternative approach to that being studied, prohibiting its uptake in many neurosurgical laboratories. Conclusion We report our updated skull base tumor model that is contrast-enhanced and may be easily and reliably injected under fluoroscopic guidance. We have identified a map of burr holes and injection corridors available to place tumor at various intracranial sites. Additionally, the updated tumor model allows for the creation of mass effect, and we detail the variation of polymer preparation to mimic different tumor properties. These advancements will increase the practicality of the tumor model and ideally influence neurosurgical standards of training.

The combined interhemispheric subcommissural translaminaterminalis approach for large craniopharyngiomas.

OBJECTIVE We describe a variant of the interhemispheric translaminaterminalis approach for the resection of large suprasellar craniopharyngiomas. The approach is a translaminaterminalis route performed below and above the anterior communicating artery (ACoA). A cadaveric microanatomic study was conducted to describe the surgical technique. METHODS Four cadaveric specimens fixed with gluteraldehyde and injected with latex were dissected to illustrate the approach. RESULTS The surgical steps of the approach are reported. The ACoA anatomy was studied. In particular, the surgical route in-between and lateral to the first and second segments of the anterior cerebral artery and the ACoA complex were examined. The approach was adopted in a clinical setting; two illustrative cases regarding the removal of large craniopharyngiomas with suprasellar extension through this route are described. CONCLUSIONS The approach with preservation of the ACoA may represent a possible route to manage large suprasellar lesions. Combination of the unilateral interhemispheric corridor with the subfrontal and the trans-sylvian routes allows for a safe and radical resection of large suprasellar craniopharyngiomas.

The current role of Gamma Knife radiosurgery in the management of intracranial haemangiopericytoma

BackgroundHaemangiopericytomas (HPCs) are rare tumours characterised by aggressive behaviour with tendency to local recurrence and to metastasise. WHO grade II and grade III tumours show different progression-free survival and overall survival rates. Gross total tumour resection is still considered the treatment of choice. Adjuvant radiation therapies represent an option in the treatment strategy regardless the extent of resection. Based on this consideration, Gamma Knife radiosurgery has been introduced either as a primary treatment or as an adjuvant treatment for residual or recurrent tumours.MethodA systematic search was performed on PubMed, Web of Science and Google Scholar for clinical series reporting Gamma Knife radiosurgery, Cyberknife and Linear Accelerator (LINAC) for the management of intracranial HPCs.ResultsFourteen studies focusing on the effects of Gamma Knife radiosurgery for intracranial HPCs were included. Four studies reported data on Cyberknife radiosurgery and LINAC. A total of 208 patients harbouring 366 tumours have been reported. Patient’s features, radiosurgical treatment characteristics and follow-up data of the pertinent literature have been critically revised.ConclusionsGamma Knife radiosurgery and the other radiosurgical techniques represent a feasible and effective therapy in the management of HPCs. Tumour control and survival rate are comparable to those reported for radiotherapy. Further studies should be focused to define the exact role of Gamma Knife radiosurgery in the management of HPCs.