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Acta Otorrinolaringol Esp. 2012;63(5):339---347
www.elsevier.es/otorrino
ORIGINAL ARTICLE
Endoscopic Endonasal Approach for the Treatment of Anterior Skull Base Tumours夽 Fernando López, Vanessa Suárez, María Costales, Juan P. Rodrigo, Carlos Suárez, José Luis Llorente∗ Servicio de Otorrinolaringología, Unidad de Base de Cráneo, Instituto Universitario de Oncología del Principado de Asturias, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain Received 11 February 2012; accepted 21 February 2012
KEYWORDS Endoscopic skull base surgery; Craniofacial resection; Adenocarcinoma; Angiofibroma; Skull base surgery; Sinonasal tumours
PALABRAS CLAVE Endoscopia de la base del cráneo; Resección craneofacial; Adenocarcinoma; Angiofibroma;
Abstract Introduction: The increasing expertise of transnasal endoscopic surgery has recently expanded its indications to include the management of tumours affecting the skull base. We report our experience with endoscopic management of these tumours, emphasising the indications and surgical technique used. Material and method: A retrospective analysis was performed of patients treated by an endoscopic endonasal approach (EEA) in our department from 2004 until 2011. Results: Sixty-three patients were analysed. We performed an endoscopic craniofacial resection in 32 patients (51%), an expanded EEA in 22 (35%), a transclival approach in 6 (9%) and a transpterygoid approach in 3 (5%). The most frequent benign tumour was nasopharyngeal angiofibroma (24%), while adenocarcinoma (30%) was the most common among malignancies. Mean follow-up was 26 months (range: 6---84 months). The complication rate was 5% and resection was complete in 56 cases (89%). The 5-year overall-survival was 71% in patients with malignant tumours and the effectiveness was 100% in benign tumours. Conclusion: Our results support that endoscopic surgery, when properly planned, represents a valid alternative to standard surgical approaches for the management of skull base tumours. © 2012 Elsevier España, S.L. All rights reserved.
Abordaje endoscópico endonasal para el tratamiento de tumores de la base del cráneo Resumen Introducción: La progresiva ampliación de las indicaciones de la cirugía endoscópica nasal ha permitido que sea utilizada como vía de abordaje en el tratamiento de tumores que afectan la base del cráneo. Presentamos nuestra experiencia en el tratamiento endoscópico de estos tumores.
夽
Please cite this article as: López F, et al. Abordaje endoscópico endonasal para el tratamiento de tumores de la base del cráneo. Acta Otorrinolaringol Esp. 2012;63:339---47. ∗ Corresponding author. E-mail address:
[email protected] (J.L. Llorente). 2173-5735/$ – see front matter © 2012 Elsevier España, S.L. All rights reserved.
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Cirugía de la base del cráneo; Tumores nasosinusales
F. López et al. Material y método: Se presenta una serie retrospectiva de los tumores tratados en nuestro servicio entre los a˜ nos 2004 y 2011 mediante un abordaje endoscópico endonasal (AEE). Resultados: Fueron analizados 63 pacientes. En 32 pacientes (51%) se realizó una resección craneofacial endoscópica, en 22 (35%) se realizó un AEE ampliado, en 6 (9%) un abordaje transclival y en 3 (5%) un abordaje transpterigoideo. El tumour benigno más frecuentemente fue el angiofibroma nasofaríngeo (24%) y el adenocarcinoma (30%) fue el más frecuente entre los malignos. El seguimiento medio fue de 26 meses (rango: 6 a 84 meses). La tasa de complicaciones fue del 5% y la resección fue completa en 56 casos (89%). La supervivencia en los pacientes con tumores malignos fue del 71% a los 5 a˜ nos y la efectividad fue del 100% en los tumores benignos. Conclusiones: Los resultados obtenidos permiten afirmar que, la cirugía endoscópica ampliada a la base del cráneo, con indicaciones precisas, es una alternativa válida a los tradicionales abordajes abiertos. © 2012 Elsevier España, S.L. Todos los derechos reservados.
Introduction The treatment of tumours affecting the skull base remains a challenge for otolaryngologists due to their centrofacial location and the proximity of vital neurovascular structures, the central nervous system and orbit. There is a wide variety of benign and malignant neoplasms which may affect the cranial base. The treatment of most tumours affecting this location is based on surgical resection followed by postoperative radiation therapy, which yields an overall survival rate of 50%---60% at 10 years.1 However, for some histological types, the initial treatment consists of chemoradiation therapy, with surgery being reserved for salvage treatment after recurrence. Surgical resection of these tumours is complex and requires a high degree of specialisation. The open craniofacial approaches introduced by Ketcham et al.2 enable monoblock resection of a segment of the facial mass through a combined transcranial and transfacial approach. The philosophy of this approach was based on the observation that pure transfacial resection of tumours of the paranasal sinuses involving the ethmoid roof was insufficient to ensure radical treatment. The development of wide anterior and lateral approaches enabled surgical resection of tumours involving the ventral skull base. Although in experienced hands these approaches have acceptable rates of morbidity and mortality, Ganly et al.3 reported postoperative mortality and major complications in 4.7% and 36.3% of patients, respectively. Furthermore, in a study by Fukuda et al.,4 all patients reported a decrease in quality of life after surgery in relation to aesthetic and functional aspects. Since Jho and Carrau,5 among others, described the use of endoscopic surgery for resection of pituitary and sinonasal tumours in the late 1990s, and its indications have gradually increased and exceeded the limits established in the initial stages of the technique.6,7 Endonasal endoscopic approaches (EEA) provide surgical access to the ventral skull base, enabling treatment of a wide variety of intradural and extradural conditions, as well as reconstruction of the resulting defects.8---12 The evolution of these techniques has been influenced by an increase in surgical skills and a better understanding of the complex anatomy of the skull base.13 As established in numerous studies,10 EEA allows the
resection of lesions involving the skull base in a minimally invasive manner, with less morbidity compared with open approaches and without losing effectiveness and oncological radicality. The purpose of this study is to present our experience in the treatment of sinonasal and skull base tumours by EEA.
Material and Method We reviewed the surgical registry of the Otolaryngology Service from 2004 to June 2011, collecting data from medical records concerning 63 patients with tumours affecting the anterior section of the skull base and who were operated by EEA. Of these, 29 patients (46%) had been referred from hospitals in other Spanish regions. We included in the study those patients with a minimum follow-up period of 6 months. We excluded isolated cases which had taken place before the starting date of the study, as well as those patients who underwent EEA for the treatment of inverted papillomas14 and cerebrospinal fluid (CSF) leaks, because the philosophy and objectives of these surgeries were different from those of oncological surgery. We also excluded pituitary adenomas. Data collection was based on a review of clinical histories, from which we recorded data on age, gender, anatomopathological diagnosis, prior treatment, tumour size and staging, surgical approach, complications, length of hospital stay, complementary therapies, current status and follow-up. All patients underwent computed tomography (CT) with contrast and magnetic resonance imaging (MRI) before surgery, in order to study tumour extension. In addition, they also underwent angiography 24---48 h before surgery, so as to carry out preoperative tumour embolisation in patients presenting lesions with hypervascularisation (e.g. angiofibromas, meningiomas). In all cases, patients were advised of the possibility of having to conduct an open approach, based on surgical findings, in order to achieve an oncologically safe resection. The mean follow-up period was 26 months (range: 6---84 months). Unless they presented new symptoms, patients with malignant tumours were explored using nasal
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Endoscopic Endonasal Approach for the Treatment of Anterior Skull Base Tumours endoscopy and MRI every 6 months during the first 3 years, and every 12 months thereafter. In cases of benign tumours, we performed an endoscopic and MRI examination at 6 months after surgery and then once every 12 months. We used the statistical program SPSS 18.0 to analyse the data.
Surgical Approaches. Definition and Indications The indications for EEA in our department have undergone constant evolution. Initially, only patients with sinonasal tumours which did not infiltrate the outer limits of the ethmoid (e.g. lamina papyracea, cribriform plate and ethmoid roof), with minimal maxillary and/or frontal involvement and without lateral extension (e.g. pterygopalatine fossa), were considered eligible for EEA. Subsequently, and until the present time, the indications for this type of approach have been progressively extended, first with benign tumours (e.g. nasopharyngeal angiofibromas and inverted papillomas) and later with malignant tumours. At present, in our service, EEA is considered as the route of choice in most sinonasal tumours, including those lesions in contact with the dura mater or with small intradural invasion, and clival region tumours with lateral extension to the pterygopalatine and/or infratemporal fossae. We used 4 types of EEA, selected according to the location of the tumour, in order to obtain good exposure and control of key anatomical structures: • Endoscopic craniofacial resection (ECFR)15 : this was used in tumours with extensive sinonasal involvement of the cribriform plate/ethmoid roof and/or lamina papyracea and/or lateral extension to the pterygopalatine and/or infratemporal fossae. This approach enables the resection of a segment of the facial mass and anterior skull base. • Extended EEA16 : this was used in large sinonasal tumours (without involvement of the cribriform plate/ethmoid roof) and in those with involvement of the pterygopalatine and/or infratemporal fossae, the cavum or upper clivus. • Transpterygoid approach17 : this was used in tumours with exclusive involvement of the pterygopalatine and/or infratemporal fossae. • Transclival approach18 : this was used to approach medium and low clivus tumours.
Results The sample consisted of 63 patients, 50 males (79%) and 13 females (21%), whose mean age at diagnosis was 49 years (range: 12---88 years). Of these, 45 patients (71%) had not been treated previously, whilst 18 (29%) had been treated previously and presented tumour persistence or recurrence (Table 1). The anatomopathological study of the tumours revealed a wide variety of histological subtypes, with 23 cases (37%) corresponding to benign tumours and 40 (63%) to malignant tumours. Nasopharyngeal angiofibromas (NA) were the most common benign tumours (Fig. 1) (15 cases, 24% of the total) and adenocarcinomas were the most common malignant tumours (Fig. 2) (19 cases, 30% of total). Table 2 lists the various histological subtypes and the surgical approaches used in each case.
Table 1 EEA.
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Previous Treatments of Patients Intervened by
Previous Treatments
Number of Patients, %
Surgery Surgery and radiotherapy Surgery, radiotherapy and chemotherapy Chemoradiotherapy Radiotherapy Chemotherapy Total
10 (16) 3 (5) 1 (2) 2 (3) 1 (2) 1 (2) 18/63 (29)
According to the TNM classification system of UICC (7th edition),19 the distribution of adenocarcinomas within the tumour (T) category was as follows: 2 (11%) T3, 13 (68%) T4a and 4 (21%) T4b. The classification of NA was based on the Andrews scale,20 whereby 3 NA (20%) belonged to group I, 9 (60%) to group II and 3 (20%) to group IIIa. The only case of esthesioneuroblastoma in our series was Kadish21 stage B, and 3 chordomas belonged to group II and 1 to group III according to the classification of Al-Mefty and Borba.22 Table 3 summarises skull base involvement, stratified by the type of surgical approach employed. As we can see, the most common type of approach was ECFR (51%) (Fig. 3) followed by extended EEA (35%). One patient with a chordoma required an associated cervicotomy and 2 cases (1 adenocarcinoma and 1 craniopharyngioma) also underwent craniectomy for total tumour excision. One patient with recurrent cavum carcinoma required association of functional lymph node dissection. The mean hospital stay was 8 days (range: 3---28 days). One patient intervened for an ethmoid adenocarcinoma died in the immediate postoperative period due to a case of cerebritis which caused intracranial hypertension. Noteworthy complications only occurred in 2 cases (3%). One case of meningitis in a patient intervened for adenocarcinoma was resolved with medical treatment, as was also the case with 1 periorbital haematoma developed by a patient with a localised inflammatory tumour in the pterygopalatine fossa. There were no cases of CSF leak requiring placement of lumbar drainage or surgical treatment. Tumour resection was complete in 56 cases (89%). Of the remaining 7 cases where tumour persistence was observed, 1 patient (chordoma) died due to intercurrent causes before receiving adjuvant therapy and 1 patient (atypical meningioma) died due to intracranial tumour progression. A total of 5 patients received adjuvant treatment. In all cases, given the tumour type, surgery had been indicated as a first step in treatment. After adjuvant treatment, all patients remained alive and with stable tumoural residue in the vicinity of the cavernous sinus (Table 4). Adjuvant therapy was administered to 29 patients (46%). Of these, 27 patients received only radiotherapy, 1 patient received radiosurgery and 1 patient received concomitant chemoradiotherapy. The criteria for administration of adjuvant treatment were the presence of residual disease, aggressive histology and tumour proximity to vital structures (e.g. eye, brain, cavernous sinus, internal carotid artery).
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Figure 1 Sagittal (A) and coronal (B) preoperative MRI scans of a stage II angiofibroma. Coronal (C) and axial (D) postoperative CT scans of the same patient, after being resected by endoscopic surgery.
A total of 3 (5%) patients suffered relapse during follow-up. All of them had been intervened for adenocarcinomas. One of them (T3) had undergone salvage surgery at 18 months using an open craniofacial approach. This patient later died due to intercurrent causes (pneumonia). Another patient (T4a) presented massive intra- and extracranial recurrence at 6 months and subsequently died. Finally, the third patient (T4a) suffered a severe centrofacial recurrence which was treated with radiotherapy and he remains alive with tumoural presence. At the end of the follow-up period, 49 patients (78%) were alive and without tumour, 4 patients (6%) died due
to their tumours (1 patient with undifferentiated carcinoma due to spread into the spinal canal, 1 with an adenocarcinoma due to distant metastases, 1 due to massive local recurrence of adenocarcinoma and 1 due to intracranial progression of an atypical meningioma), 3 (5%) patients died from intercurrent causes (1 patient with a chordoma and 2 with adenocarcinomas) and 6 patients (9%) remain alive with tumours (2 patients with undifferentiated carcinoma, 2 with cystic adenoid carcinomas, 1 with meningioma and 1 with adenocarcinoma). The overall survival rate for all patients with malignant tumours was 71% at 5 years, and disease-free survival was
Figure 2 Preoperative CT scan of an ethmoid adenocarcinoma (T4a) (A) and postoperative MRI scan of the same patient after endoscopic craniofacial resection (B).
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Endoscopic Endonasal Approach for the Treatment of Anterior Skull Base Tumours Table 2
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Final Histology of Intervened Patients.
Histology
Approach, %
Number of Patients, %
Ethmoid adenocarcinoma Nasopharyngeal angiofibroma Undifferentiated carcinoma
• • • • • • • • • • • • • • • • • • • • • •
19 (30) 15 (24)
Chordoma Cystic adenoid carcinoma Meningioma Cavum carcinoma Hemangiopericytoma Unspecific/inflammatory tumour Esthesioneuroblastoma Epidermoid carcinoma Oncocytoma Fibrous dysplasia Ameloblastoma Craniopharyngioma Lymphoma Chondrosarcoma Vidian nerve neuroma
Craniofacial resection: 19 (100) Extended EEA: 15 (100) Craniofacial resection: 4 (80) Transclival: 1 (20) Transclival: 4 (100) Craniofacial resection: 2 (77) Transpterygoid: 1 (33) Extended EEA: 2 (100) Extended EEA: 2 (100) Extended EEA: 1(50) Transpterygoid: 1(50) Extended EEA: 1 (50) Transclival: 1 (50) Craniofacial resection: 1 (100) Craniofacial resection: 1 (100) Craniofacial resection: 1 (100) Craniofacial resection: 1 (100) Extended EEA: 1 (100) Craniofacial resection: 1 (100) Craniofacial resection: 1 (100) Extended EEA: 1 (100) Transpterygoid: 1 (100)
5 (8) 4 (6) 3 (5) 2 (3) 2 (3) 2 (3) 2 1 1 1 1 1 1 1 1 1
(3) (2) (2) (2) (2) (2) (2) (2) (2) (2)
EEA: endonasal endoscopic approach.
Table 3
Approaches Employed According to the Affected Region of the Skull Base.
Skull Base Region
Craniofacial
Extended
Transclival
Transpterygoid
Number of Cases, %
Patients, % Sphenoid sinus (except anterior wall) Ethmoid roof/cribriform plate Pterygopalatine fossa Dura mater Infratemporal fossa Lamina papyracea Clivus Cavernous sinus Frontal sinus Orbital apex Intradural
32 (51) 27 30 11 13 0 8 3 5 5 4 3
22 (35) 5 0 14 0 5 2 1 0 0 0 0
6 (9) 5 0 3 4 1 0 5 1 0 0 0
3 (5) 0 0 3 0 3 0 0 0 0 0 0
63 (100) 39 (62) 30 (48) 31 (49) 19 (30) 9 (14) 10 (16) 9 (14) 6 (9) 5 (8) 4 (6) 3 (5)
Table 4
Patients With Persistent Disease After Surgery.
Patient
Diagnosis
Approach Employed
Complementary Treatment
Current Status
1 2 3 4 5 6 7
Undifferentiated carcinoma Undifferentiated carcinoma Cystic adenoid carcinoma Cystic adenoid carcinoma Meningioma Meningioma Chordoma
Craniofacial resection Transclival Craniofacial resection Transpterygoid Extended EEA Extended EEA Transclival
CT and RT CT and RT RT RT RT RT No
AWT AWT AWT AWT AWT D DOC
AWT: alive with tumour; CT: chemotherapy; D: death caused by tumour; DOC: death by other causes; EEA: endonasal endoscopic approach; RT: radiotherapy.
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Figure 3 Intraoperative endoscopic view of a craniofacial resection. (A) The dura mater of the anterior skull base is opened and resected along with the olfactory bulbs. (B) Fracture and removal of the crista galli (arrow) separately from the rest of the cribriform plate. (C) Intradural placement of a fragment of fascia lata. A narrow band of dura mater (star) enabling placement can be observed in the midline.
85% at 5 years (Fig. 4). Due to the heterogeneity of the studied sample, disease-specific survival was calculated only for the largest group of patients, which were those suffering from ethmoid adenocarcinomas, and yielded rates of 88% at 4 years follow-up and a disease-free survival of 78% at 4 years. Among benign tumours, the effectiveness of treatment was 100% in all cases, with no patient presenting tumoural persistence or recurrence.
Discussion The management of tumours affecting the skull base has evolved significantly in the past decades.11,12 Their endoscopic management has gradually become the preferred approach, achieving safety and efficacy figures similar to those of external approaches when the indication is correct.23 This technique can be used alone or combined with traditional open approaches, which still have some indications.24 In this evolutionary context of change in the treatment of tumours affecting the skull base, we present our experience with EEA for the treatment of tumours
involving the anterior skull base. Although the number of cases in our series is not very high, to our knowledge it is the largest series from a single institution published by a Spanish otolaryngology group. Thus, we do not attempt to analyse the results of different histological subtypes thoroughly. While surgery of the skull base is the ideal scenario for cooperation between otolaryngologists and neurosurgeons, this cooperation is sometimes complicated and otolaryngologists must gain experience in the management of intracranial pathologies. In our case, previous experience in conducting open approaches25---30 and the progressive acquisition of surgical experience in endoscopic surgery, according to the sequential model proposed by the Pittsburgh group,13 has led EEA to be established as the approach of choice in the treatment of most tumours affecting the anterior skull base. From the standpoint of otolaryngology, the anterior skull base is the region most frequently affected by extracranial neoplasms. Most cases consist of neoplasms originating in the nasal cavity or paranasal sinuses. However, as shown in our series, a wide variety of benign and malignant otolaryngological neoplasms can also affect the anterior skull base.
1.0
1.0
A
B 0.8
Disease-free survival
Survival
0.8
0.6
0.4
0.2
0.0
0.4
0.2
0.0 0
12
24
36
Months
Figure 4
0.6
48
60
0
12
24
36
48
60
Months
Kaplan---Meier graph illustrating mean survival of the 40 patients with malignant tumours (A) and disease-free survival (B).
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Endoscopic Endonasal Approach for the Treatment of Anterior Skull Base Tumours Table 5 Infiltration of Structures Contraindicating the Exclusive Performance of an Endonasal Approach. A. Absolute B. Relative
• Skin and facial soft tissues • Hard palate • Lateral section of the frontal sinus • Extensive cerebral infiltration • Cavernous sinus • Orbit • Nasal bones • Maxillary anterior wall and superior wall lateral to V2 • Lachrymal duct
The indications and limitations of this surgical technique have been defined progressively during its evolution.31 Several factors may represent limitations to achieve a safe resection. Some of these factors include anatomical restrictions, tumour histopathology, difficulties in surgical technique, the experience of the surgical team and technical resources available. It is important to remember that, although EEA is considered a minimally invasive surgery, only the approach itself can be considered as such because, from the oncological standpoint, it needs to be a radical approach and resection cavities must be equivalent to those of open approaches. Therefore, the surgical principles when performing indication of an EEA should be equal to those considered for an open approach and with equal morbidity. Moreover, it has been shown that monoblock excision of the tumour is not necessary and its prior fragmentation does not violate oncological principles, since the ultimate goal is to obtain negative margins.11 It is only desirable to resect in a single piece the area of tumour implantation and invasion of the skull base.7 Often, when endoscopy cannot achieve safety margins, it is difficult for these to be obtained without morbidity by conversion into open surgery.31 Although it is advisable to obtain complete tumour resection, whether benign or malignant, when they affect vital structures, if this generates considerable morbidity, it is sometimes preferable to leave the tumour in these areas and administer adjuvant chemotherapy/radiotherapy, since the oncological results are similar.32 Although, as mentioned, the indications and contraindications of EEA vary according to the authors, we do not believe that conducting an endoscopic approach is sensible when it includes skin and soft tissue in cases of externalised tumours (Table 5A). The relative contraindications (Table 5B) do not prevent an EEA. However, an open approach, a combined one or leaving a tumoural remainder for adjuvant treatment could also be an alternative. We do not believe that the need for orbital exenteration contraindicates an EEA, since this may be done by a small transconjunctival incision. The surgical technique used by our group is similar to that described previously by other groups.7,8,11,15,31 At present, EEA can be used to treat tumours involving the region from the posterior wall of the frontal sinus to the posterior side of the sphenoid sinus and between both orbits. Tumours involving the clivus, the cavum or the pterygopalatine and infratemporal fossae can also be approached using this technique. ECFR is performed in both adenocarcinomas and
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esthesioneuroblastomas, making it necessary to excise the ethmoid roof and olfactory cilia. This must be taken into account in order to prepare the reconstruction method and prevent a CSF leak. Within benign tumours, NA represent a surgical challenge due to their hypervascularity and invasion of the skull base. However, until they reach stage IIIA, these tumours can be resected by endoscopy.33 According to our philosophy of treatment, the results obtained in our series are similar to those obtained by other authors, taking into account that in most series there is great histological diversity. Although the number of patients was limited and histology was heterogeneous, survival and recurrence rates were not different from those in the published literature. Our disease-free survival of 85% at 5 years was comparable with those of 73% reported by Lund et al.34 and 81% reported by Nicolai et al.11 In addition, excision was complete in 89% of cases and in the remaining 11% the tumour remainders were in the cavernous sinus. These figures were slightly inferior to those reported in other series, both with endoscopic surgery and with open approaches.3,9 Adjuvant therapy is essential in patients with tumoural residue or risk. Within sinonasal tumours in our series, adenocarcinomas constituted the largest group followed by undifferentiated carcinomas. In their series of 44 adenocarcinomas, Bogaerts et al.35 obtained a 5-year survival of 83%, similar to the 88% in our series. In agreement with this author, we believe that bilateral removal of the entire ethmoid is important in this type of tumour, in order to prevent recurrences. Undifferentiated carcinomas are highly aggressive tumours and their complete resection is complex because they may affect vital structures at the time of diagnosis. However, the use of external approaches does not improve the results of EEA.10 Therefore, adjuvant treatment is crucial. The results of endoscopic treatment of NA are comparable to the most favourable results reported in other patient series.8,10 Some authors advocate the use of EEA for the treatment of clivus chordomas, as it would enable complete macroscopic resection with less morbidity than generated with open approaches.36 In our series, the rates of CSF leak and other complications observed were low and comparable to those in other published series (8%---11%).11,12,37 In our experience, multilayer closure with heterologous fascia lata is a safe method for the reconstruction of the skull base. However, our mean stay was higher than in other series (8 days vs 3.7 days).11 This could be because a large number of patients came from other geographical regions and, therefore, hospital discharge was usually delayed for a few days. The purpose of this study was not to recommend EEA versus open techniques, which are still useful and, in most cases, do not cause significant aesthetic or functional sequelae. However, this series, along with the rest of those published, provides evidence of the usefulness of EEA for the management of tumours affecting the skull base, being the technique of choice in selected cases. Since this pathology is rare, we recommended that it be treated in reference centres for skull base surgery, in order to gain experience and gradually expand its indications, improve its results and reduce its complications. Moreover, it is also essential to have experience in open approaches before conducting EEA.
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Conclusions This study presents the experience at single institution with the use of EEA for the treatment of tumours affecting the skull base. The results in relation to efficacy and safety are similar to those obtained in other published series. Therefore, we believe that, in selected cases and in the hands of surgeons with experience in skull base surgery, EEA is a valid alternative to traditional open approaches.
15.
16.
17.
Conflict of Interests 18.
The authors have no conflict of interests to declare.
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