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Disregarding the widely used division of skull base into anterior and lateral, since the skull base should be conceived as a single anatomic structure, it was to our convenience to group all those approaches that run from the antero-lateral, pure lateral and postero-lateral side of the skull base as “Surgery of the lateral skull base”. “50 years of endeavour” points to the great effort which has been made over the last decades, when more and more difficult surgeries were performed by reducing morbidity. The principle of lateral skull base surgery, “remove skull base bone to approach the base itself and the adjacent sites of the endo-esocranium”, was then combined with function preservation and with tailoring surgery to the pathology. The concept that histology dictates the extent of resection, balancing the intrinsic morbidity of each approach was the object of the first section of the present report. The main surgical approaches were described in the second section and were conceived not as a step-by-step description of technique, but as the highlighthening of the surgical principles. The third section was centered on open issues related to the tumor and its treatment. The topic of vestibular schwannoma was investigated with the current debate on observation, hearing preservation surgery, hearing rehabilitation, radiotherapy and the recent efforts to detect biological markers able to predict tumor growth. Jugular foramen paragangliomas were treated in the frame of radical or partial surgery, radiotherapy, partial “tailored” surgery and observation. Surgery on meningioma was debated from the point of view of the neurosurgeon and of the otologist. Endolymphatic sac tumors and malignant tumors of the external auditory canal were also treated, as well as chordomas, chondrosarcomas and petrous bone cholesteatomas. Finally, the fourth section focused on free-choice topics which were assigned to aknowledged experts. The aim of this work was attempting to report the state of the art of the lateral skull base surgery after 50 years of hard work and, above all, to raise questions on those issues which still need an answer, as to allow progress in knowledge through sharing of various experiences. At the end of the reading, if more doubts remain rather than certainties, the aim of this work will probably be achieved.

Chirurgia della base del cranio laterale: 50 anni di impegno.La base del cranio non è anatomicamente divisa in anteriore e laterale, ma è per semplicità che comunemente si intendono i corridoi chirurgici con direzione antero-laterale, laterale pura e postero laterale come “Approcci chirurgici della base del cranio laterale”. Una relazione con titolo “Cinquant’anni di impegno”, di sforzo o di dedizione, vuole essere il riconoscimento a questa chirurgia che nel corso degli anni ha sviluppato interventi sempre più complessi con una morbidità sempre minore. Il principio della chirurgia della base del cranio laterale si fonda sulla possibilità di “fare spazio”, esporre adeguatamente, rimuovere osso per salvaguardare il cervello, insieme alla possibilità di preservare la funzione e adattare l’approccio chirurgico all’istologia della lesione. Il concetto che l’istologia detta l’entità della resezione chirurgica, bilanciando la morbidità intrinseca di ciascun approccio, è oggetto di trattazione nella prima sezione di questa relazione. Nella seconda sezione sono descritti i principali approcci chirurgici, intesi non come descrizione tecnica di ciascun tempo chirurgico, ma dei principi che sono alla base di ciascun approccio. La terza sezione è dedicata alle questioni aperte, quelle ancora irrisolte, inerenti alcuni tumori ed il loro trattamento. L’argomento del neurinoma sporadico dell’ottavo nervo cranico è trattato riportando l'attuale dibattito sulla osservazione, la chirurgia di preservazione dell’udito, la riabilitazione con l’impianto cocleare, la radioterapia e le ricerche recenti su marcatori tumorali predittivi di crescita. Il paraganglioma del forame giugulare è trattato nel contesto della chirurgia radicale, chirurgia parziale, osservazione e radioterapia. La terapia dei meningiomi della base del cranio analizza il punto di vista specifico dell’otochirurgo e del neurochirurgo. Cordomi e condrosarcomi, tumori del sacco endolinfatico, carcinomi dell’orecchio e colesteatoma della rocca sono le altre lesioni affrontate. Infine, nella quarta sezione è proposto un contributo a libera scelta ad autori di riconosciuta esperienza. Lo scopo di questa relazione è stato quello di fornire un aggiornamento della chirurgia della base del cranio laterale dopo 50 anni di duro lavoro e, o forse soprattutto, di permettere alle tante questioni irrisolte, alle domande che ancora non hanno risposta, di trovare espressione, affinchè il dibattito ed il progresso possano continuare con la condivisione di esperienze. Se al termine della lettura vi saranno più domande che risposte, potremo dirci che l’obiettivo di questa relazione è stato raggiunto.Disregarding the widely used division of skull base into anterior and lateral, since the skull base should be conceived as a single anatomic structure, it was to our convenience to group all those approaches that run from the antero-lateral, pure lateral and postero-lateral side of the skull base as “Surgery of the lateral skull base”. “50 years of endeavour” points to the great effort which has been made over the last decades, when more and more difficult surgeries were performed by reducing morbidity. The principle of lateral skull base surgery, “remove skull base bone to approach the base itself and the adjacent sites of the endo-esocranium”, was then combined with function preservation and with tailoring surgery to the pathology. The concept that histology dictates the extent of resection, balancing the intrinsic morbidity of each approach was the object of the first section of the present report. The main surgical approaches were described in the second section and were conceived not as a step-by-step description of technique, but as the highlighthening of the surgical principles. The third section was centered on open issues related to the tumor and its treatment. The topic of vestibular schwannoma was investigated with the current debate on observation, hearing preservation surgery, hearing rehabilitation, radiotherapy and the recent efforts to detect biological markers able to predict tumor growth. Jugular foramen paragangliomas were treated in the frame of radical or partial surgery, radiotherapy, partial “tailored” surgery and observation. Surgery on meningioma was debated from the point of view of the neurosurgeon and of the otologist. Endolymphatic sac tumors and malignant tumors of the external auditory canal were also treated, as well as chordomas, chondrosarcomas and petrous bone cholesteatomas. Finally, the fourth section focused on free-choice topics which were assigned to aknowledged experts. The aim of this work was attempting to report the state of the art of the lateral skull base surgery after 50 years of hard work and, above all, to raise questions on those issues which still need an answer, as to allow progress in knowledge through sharing of various experiences. At the end of the reading, if more doubts remain rather than certainties, the aim of this work will probably be achieved.

Meningiomas are one of the most common tumors affecting the central nervous system, exhibiting a great heterogeneity in grading, treatment and molecular background. This article provides an overview of the current literature regarding the molecular aspect of meningiomas. Analysis of potential biomarkers in serum, cerebrospinal fluid (CSF) and pathological tissues was reported. Applying bioinformatic methods and matching the common proteic profile, arising from different biological samples, we highlighted the role of nine proteins, particularly related to tumorigenesis and grading of meningiomas: serpin peptidase inhibitor alpha 1, ceruloplasmin, hemopexin, albumin, C3, apolipoprotein, haptoglobin, amyloid-P-component serum and alpha-1-beta-glycoprotein. These proteins and their associated pathways, including complement and coagulation cascades, plasma lipoprotein particle remodeling and lipid metabolism could be considered possible diagnostic, prognostic biomarkers, and eventually therapeutic targets. Further investigations are needed to better characterize the role of these proteins and pathways in meningiomas. The role of new therapeutic strategies are also discussed.

Background: The type of sellar barrier observed between a pituitary tumor and cerebrospinal fluid (CSF) on preoperative magnetic resonance imaging (MRI) may predict intraoperative CSF leak during endonasal pituitary surgery. This is the first multicentric prospective cohort trial to study the sellar barrier concept and CSF leak rate during endoscopic pituitary surgery. Methods: This multi-center, international study enrolled patients operated for pituitary adenomas via fully endoscopic endonasal surgery over a period of 4 months. The independent variable was the subtype of sellar barrier observed on preoperative MRI (strong, mixed or weak); the dependent variable was the presence of an intraoperative CSF leak. The primary goal was to determine the association between a particular type of sellar barrier and the risk of intraoperative CSF leak. Appropriate statistical methods were then applied for data analysis. Results: Over the study period, 310 patients underwent endoscopic endonasal surgery for pituitary tumor. Preoperative imaging revealed a weak sellar barrier in 73 (23.55%), a mixed sellar barrier in 75 (24.19%), and a strong sellar barrier in 162 (52.26%) patients. The overall rate of intraoperative CSF leak among all patients was 69 (22.26%). A strong sellar-type barrier was associated with significantly reduced rate of intraoperative CSF leak (RR = 0.08; 95% CI 0.03–0.19; p < 0.0001), while a weak sellar barrier associated with higher rates of CSF leak (RR = 8.54; 95% CI 5.4–13.5; p < 0.0001). Conclusions: The preoperative MRI of pituitary patients can suggest intraoperative CSF leak rates, utilizing the concept of the sellar barrier. Patients with a weak sellar barrier carry a higher risk for an intraoperative CSF leak, whereas a strong sellar barrier on MRI seems to mitigate intraoperative CSF leak. We propose that preoperatively assessment of the sellar barrier can prepare surgeons for intraoperative CSF leak repair.