State of the Art—Treatment of Skull Base Diseases

Background: Postoperative imaging after nasopharyngeal endoscopic resection (NER) and skull base reconstruction is quite challenging due to the complexity of the post-surgical and regional anatomy. Methods: In this retrospective observational study, we included patients treated with NER from 2009 to 2019 and submitted to Magnetic Resonance Imaging (MRI) 6 and 12 months after surgery. A radiologist with 15 years of experience analyzed all MRI scans. Results: A total of 50 patients were considered in this study, 18 of whom were excluded due to imaging unavailability, and 16 of whom were not considered due to major complications and/or persistent disease. Sixteen patients were evaluated to identify the expected findings. Inflammatory changes were observed in 16/64 subsites, and regression of these changes was observed in 8/64 at 1 year. Fibrosis was observed in 5/64 subsites and was unmodified at 1 year. The nasoseptal flap showed homogeneous enhancement at 6 months (100%) and at 1 year. The temporo-parietal fascia flap (TPFF) showed a decrease in the T2- signal intensity of the mucosal layer in 57% of the patients at 1 year and a decrease in enhancement in 43%. Conclusions: Identifying the expected findings after NER and skull base reconstruction has a pivotal role in the identification of complications and recurrence. Full article

Background: The anterior transpetrosal approach (ATPA) is effective for reaching petroclival lesions, and it allows for complications such as impaired venous return and neuropathy to be resolved. However, there is still room for improvement regarding cerebrospinal fluid (CSF) leakage. Here, we aim to focus on describing specific preoperative, intraoperative, and postoperative countermeasures for preventing CSF leakage when using the ATPA. Methods: Eleven patients treated using the ATPA, who were treated at our hospital from June 2019 to February 2023, were included in this descriptive study. Preoperatively, we performed a 3D simulation of the opened air cells. Then, we classified patterns of dural closure into three types based on intradural manipulation and whether it involved opened air cells or not. Intraoperatively, we performed a dural closure that included the use of more-watertight sutures (DuraGen^®) and an endoscope. Furthermore, temporal bone air cell volume measurements were performed to confirm the correlation between the volume and factors related to CSF leakage. Results: No postoperative CSF leakage was observed in any patient. The temporal bone air cell volumes significantly corelated with the air cells of the petrous apex, the high-risk tract in the petrous apex, and postoperative fluid collection in mastoid air cells. Conclusions: We have described countermeasures for preventing CSF leakage when using the ATPA. Preoperative simulations and the use of multiple-layered dural reconstructions with endoscopes could be considered more reliable methods for preventing CSF leakage when using the ATPA. Full article

The significance of early postoperative magnetic resonance imaging (MRI) for meningioma resection has not yet been evaluated. We retrospectively reviewed patients with intracranial meningiomas resected at our institute between 2011 and 2021. Early postoperative MRI with contrast enhancement was routinely performed within 48 h after surgery while first follow-up MRI was performed approximately after 6 months. MRI findings were reviewed, and the risk factors for postoperative infarction and early recurrence were analyzed. Among the 245 resections performed, early postoperative MRI was performed in 200 cases. Postoperative radiological and symptomatic infarctions occurred in 54 (27%) and 17 patients (9%), respectively. Diameter > 5 cm (p = 0.015) and skull base location (p = 0.010) were independent risk factors for radiological infarctions. Follow-up postoperative MRI performed in 180 patients (90%) detected early recurrence in 24 patients (13%). Non-gross total resection was an independent risk factor for early recurrence (p < 0.0001). Additionally, early recurrence after gross total resection occurred significantly more frequently in meningiomas with dural sinus involvement than in those without (8.3% vs. 0%, p = 0.018). Thus, early postoperative MRI may enable the timely assessment of postoperative neurological deficits, especially after large skull base meningioma resections along with accurate detection of early recurrence, which is critical for meningiomas with dural sinus involvement. Full article

Sinonasal cancers (SNCs) are rare and heterogeneous in histology and biological behavior. The prognosis is generally unfavorable, especially in inoperable cases. In recent years, for some histologies, such as undifferentiated sinonasal carcinoma (SNUC), multimodal treatment with a combination of induction chemotherapy, surgery, and chemo/radiotherapy (RT) has improved the prognosis. Nevertheless, still about half of the patients treated incur a recurrence, in most of the cases at the local site. Surgery with and without RT is usually the treatment choice in cases of recurrence after previous RT in combination with systemic therapy or RT in a histology-driven fashion. In the case of inoperable disease or contraindications to surgery, RT is still a valid treatment option. In this context, hadron therapy with protons (PT) or carbon ions (CIRT) is often preferred due to the physical and biological characteristics of charged particles, allowing the administration of high doses to the tumor target while sparing the surrounding healthy tissues and potentially limiting the side effects due to the high cumulative dose. In the absence of a standard of care for the recurrent setting, we aimed to investigate the role of re-RT with PT or CIRT. We retrospectively analysed 15 patients with recurrent, previously irradiated, SNCs treated at our institution between 2013 and 2020. Local control (LC) and overall survival (OS) were estimated by the Kaplan–Meier method. Acute and late toxicities were scored according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events CTCAE version 5.0. A total of 13 patients received CIRT and 2 patients received PT. The median re-RT dose was 54 GyRBE (range 45–64 GyRBE) delivered in 3 or 4 GyRBE/fr (fraction) for the CIRT, and 2 Gy RBE/fr for the PT schedule. LC was 44% at the 1-year follow-up and 35.2% at the 3-year follow-up. OS at 1 and 3 years were 92.9% and 38.2%, respectively. Fourteen patients developed G1–G2 acute toxicity (dermatitis and mucositis), and no patients developed G3–G5. Regarding late toxicity, 10 patients encountered at maximum G1–2 events, and 4 did not experience any toxicity. Only for one patient G3 late toxicity was reported (dysphagia requiring a percutaneous endoscopic gastrostomy). Full article

Craniopharyngioma (CP) is a histologically benign tumor with high mortality and morbidity. Although surgical treatment is essential in managing CP, the best surgical approach is debated. A retrospective cohort of 117 patients with adult-onset CP (AOCP) treated between 2018 and 2020 in Beijing Tiantan Hospital was identified and examined. The effects of traditional craniotomy (TC) and endoscopic endonasal transsphenoidal surgery (EETS) on the extent of surgical resection, hypothalamic involvement (HI), postoperative endocrine function, and postoperative weight were compared in the cohort. The cohort comprised 43 males and 74 females, divided into the TC (n = 59) and EETS (n = 58) groups. The EETS group possessed a higher rate of gross total resection (GTR) (adjusted odds ratio (aOR) = 4.08, p = 0.029) and improved HI (aOR = 2.58, p = 0.041) than the TC group. Worse postoperative HI was only observed in the TC group (5 patients). The EETS was associated with fewer adverse hormonal outcomes, including posterior pituitary dysfunction (aOR = 0.386, p = 0.040) and hypopituitarism (aOR = 0.384, p = 0.031). Additionally, multivariate logistic regression analysis confirmed that EETS was related to fewer cases of weight gain >5% (aOR = 0.376, p = 0.034), significant weight change (aOR = 0.379, p = 0.022), and postoperative obesity (aOR = 0.259, p = 0.032). Compared to TC, EETS shows advantages in accomplishing GTR, hypothalamus protection, postoperative endocrine function reservation, and postoperative weight control. These data suggest that the EETS deserves more application in managing patients with AOCP. Full article

Objective: Petrous apex cholesterol granuloma (PACG) is a lesion that can give rise to different symptoms, and correlations with etiopathology are ambiguous. The aim of this study is to analyze the association between PACG symptoms and radiological findings at presentation, in order to establish a reproduceable pre-operative radiological evaluation and guide the surgical indication. Methods: PACG patients were collected in two tertiary care hospitals. All cases underwent CT/MRI to evaluate the cyst localization and erosion of surrounding structures. Typical and atypical symptoms were then analyzed and compared to radiologic findings established in accordance with the literature. Results: Twenty-nine patients were recruited; the most common symptoms were headache (69%), diplopia (20.7%) and fainting (24.1%), an atypical clinical manifestation related to jugular tubercle involvement. Significant associations between symptoms and radiologic findings were noted in terms of headache and temporal lobe compression (p = 0.04), fainting and jugular tubercle erosion (p < 0.001), vestibular symptoms and internal auditory canal erosion (p = 0.02), facial paresthesia and Meckel’s cave compression (p = 0.03), diplopia and Dorello canal involvement (p = 0.001), and tinnitus and cochlear basal turn erosion (p < 0.001). All patients were treated via an endoscopic–endonasal approach, in which extension was tailored to each case. At a median follow-up of 46 months, 93.1% of patients experienced resolution of symptoms. Conclusions: This clinico-radiological series demonstrates associations between symptoms and anatomical subsites involved with PACG. Hence, it may guide the surgeon at the time of surgical decision, since it asserts that typical and atypical symptoms are actually related to PACG. Full article

The classical middle cranial fossa approach (MCFA) for vestibular schwannoma (VS) removal often requires a large incision and craniotomy, excessive temporal lobe manipulation, and a longer recovery. We describe a keyhole MCFA (KMCFA) with endoscopic assistance that allows for adequate access with minimal temporal lobe manipulation, resulting in a fast recovery and an invisible scar. Eight sides of four cadaveric heads were dissected through the endoscopic-assisted KMCFA to access the internal auditory canal (IAC). Furthermore, five patients with intracanalicular VS underwent tumor removal with the endoscopic-assisted KMCFA. During the endoscopic-assisted KMCFA with fine instruments, a 3-cm supra-auricular incision and a 2-cm diameter keyhole craniotomy achieved exposure of the entire length of the IAC in all cadaveric dissections without unintended violation of the cochlea, semicircular canal, and facial nerve. The gross tumor was totally removed in five patients with no major postoperative complications. The surgical time was reduced, the hearing outcomes were similar to those of the classical MCFA, and the scar was invisible 1 month after the surgery. The endoscopic-assisted KMCFA permits intracanalicular VS removal in a safe, efficient, and cosmetic way. For small intracanalicular VSs, this approach can replace the classical MCFA when indicated. Full article

Originally pioneered in adults, endoscopic endonasal approaches for skull base pathology are being increasingly applied as a minimally invasive alternative for young children. Intrinsic anatomic differences between these patient populations have sparked discussions on the feasibility, safety, and efficacy of these techniques in pediatric patients. This work aims to serve as a primer for clinicians engaged in the rapidly evolving field of pediatric endoscopic skull base surgery. A succinct overview of relevant embryology, sinonasal anatomy, and diagnostic workup is presented to emphasize key differences and unique technical considerations. Additional discussions regarding select skull base lesions, reconstructive paradigms, potential surgical complications, and postoperative care are also highlighted in the setting of multidisciplinary teams. Full article

Frontal sinus involvement by malignant tumors is a rare finding. Therefore, a systematic literature review along with a personal case series may contribute to defining more accurately the epidemiology, treatment options, and outcomes of these neoplasms. This is a retrospective review of patients affected by frontal sinus malignancies surgically treated in a tertiary-care referral center over a period of 20 years. Moreover, a systematic literature review of studies describing frontal sinus cancers from 2000 to date was performed according to PRISMA guidelines in order to analyze current evidence about the treatment and outcomes of such a rare disease. Our retrospective review was basedon 84 cases, treated with an exclusive endoscopic approach in 43 cases (51.2%), endoscopic approach with frontal osteoplastic flap in 6 cases (7.1%), and transfacial or transcranial approaches in 35 cases (41.7%). The five-year overall, disease-specific, disease-free, and recurrence-free survivals were 54.6%, 62.6%, 33.1%, and 59.1%, respectively. Age, dural involvement, type of surgical resection, and surgical margin status were significantly associated with the survival endpoints. In conclusion, the involvement of the frontal sinus is associated with a poor prognosis. Multidisciplinary management, including specific histology-driven treatments, represents the gold standard for improving outcomes and minimizing morbidity. Full article

Surgical navigation technology combines patient imaging studies with intraoperative real-time data to improve surgical precision and patient outcomes. The navigation workflow can also include preoperative planning, which can reliably simulate the intended resection and reconstruction. The advantage of this approach in skull-base surgery is that it guides access into a complex three-dimensional area and orients tumors intraoperatively with regard to critical structures, such as the orbit, carotid artery and brain. This enhances a surgeon’s capabilities to preserve normal anatomy while resecting tumors with adequate margins. The aim of this narrative review is to outline the state of the art and the future directions of surgical navigation in the skull base, focusing on the advantages and pitfalls of this technique. We will also present our group experience in this field, within the frame of the current research trends. Full article

Squamous cell carcinomas (SCC) of the external auditory canal (EAC) are rare tumors representing a surgical challenge. Current knowledge is based largely on case series; thus, the level of evidence is weak. This study sought to systematically review the available SCC of the EAC literature and to identify risk factors for overall survival (OS) and disease-specific survival (DSS). A systematic review and meta-analysis of papers searched up to December 2022 through PubMed, Scopus, Web of Science, and Cochrane Library databases was conducted. Quality assessment of the eligible studies was done according to the Newcastle-Ottawa Scale. Pooled univariate and multivariable analyses and meta-analysis using a random-effects or fixed-effects Mantel-Haenszel model were performed. Fifteen articles (282 patients) met the inclusion criteria and were included in the quantitative analysis. The pooled multivariable analysis revealed cT3 and cT4 as independent prognostic factors for OS (p = 0.005, and p < 0.001, respectively) and DSS (p = 0.002, and p < 0.001, respectively). Local recurrence rate was 32.3%. The meta-analysis estimated significantly higher odds ratios for advanced T categories, than cT1-T2 tumors for OS and DSS (OR = 3.55; 95% CI, 1.93–6.52, and OR = 3.73; 95% CI, 2.00–6.97, respectively). In conclusion, locally advanced tumors were associated with poor prognosis. Poor outcomes mostly occurred due to local recurrence. Full article

Despite the progress of surgery, radiotherapy, and neoadjuvant chemotherapy, the prognosis for advanced sinonasal cancers (SNCs) remains poor. In the era of precision medicine, more research has been conducted on the molecular pathways and recurrent mutations of SNCs, with the aim of understanding carcinogenesis, helping with diagnosis, identifying prognostic factors, and finding potentially targetable mutations. In the treatment of SNC, immunotherapy is rarely used, and no targeted therapies have been approved, partly because these tumors are usually excluded from major clinical trials. Data on the efficacy of targeted agents and immune checkpoint inhibitors are scarce. Despite those issues, a tumor-agnostic treatment approach based on targeted drugs against a detected genetic mutation is growing in several settings and cancer subtypes, and could also be proposed for SNCs. Our work aims to provide an overview of the main molecular pathways altered in the different epithelial subtypes of sinonasal and skull base tumors, focusing on the possible actionable mutations for which potential target therapies are already approved in other cancer types. Full article

Background/Objectives: Tuberculum sellae meningiomas (TSMs) constitute 5–10% of intracranial meningiomas, often causing visual impairment. Traditional microsurgical transcranial approaches (MTAs) have been effective, but the emergence of innovative surgical trajectories, such as endoscopic endonasal approaches (EEAs), has sparked debate. While EEAs offer advantages like reduced brain retraction, they are linked to higher cerebrospinal fluid leak (CSF leak) risk. This meta-analysis aims to comprehensively compare the efficacy and safety of EEAs and MTAs for the resection of TSMs, offering insights into their respective outcomes and complications. Methods: A comprehensive literature review of the databases PubMed, Ovid MEDLINE, and Ovid EMBASE was conducted for articles published on TSMs treated with either EEA or MTA until 2024. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Meta-analysis was performed to estimate pooled event rates and assess heterogeneity. Fixed- and random-effects were used to assess 95% confidential intervals (CIs) of presenting symptoms, outcomes, and complications. Results: A total of 291 papers were initially identified, of which 18 studies spanning from 2000 to 2024 met the inclusion criteria. The exclusion of 180 articles was due to reasons such as irrelevance, non-reporting of selected results, systematic literature review or meta-analysis, and a lack of details on method/results. The 18 studies comprised a total sample of 1093 patients: 444 patients who underwent EEAs and 649 patients who underwent MTAs for TSMs. Gross total resection (GTR) rates ranged from 80.9% for EEAs to 79.8% for MTAs. The rate of visual improvement was 86.6% in the EEA group and 65.4% in the MTA group. The recurrence rate in the EEA group was 6.9%, while it was 5.1% in MTA group. The postoperative complications analyzed were CSF leak, infections, dysosmia, intracranial hemorrhage (ICH), and endocrine disorders. The rate of CSF leak was 9.8% in the EEA group and 2.1% in MTA group. The rate of infections in the EEA group was 5.7%, while it was 3.7% in the MTA group. The rate of dysosmia ranged from 10.3% for MTAs to 12.9% for EEAs. The rate of ICH in the EEA group was 0.9%, while that in the MTA group was 3.8%. The rate of endocrine disorders in the EEA group was 10.8%, while that in the MTA group was 10.2%. No significant difference was detected in the rate of GTR between the EEA and MTA groups (OR 1.15, 95% CI 0.7–0.95; p = 0.53), while a significant benefit in visual outcomes was shown in EEAs (OR 3.54, 95% CI 2.2–5.72; p < 0.01). There was no significant variation in the recurrence rate between EEA and MTA groups (OR 0.92, 95% CI 0.19–4.46; p = 0.89). While a considerably increased chance of CSF leak from EEAs was shown (OR 4.47, 95% CI 2.52–7.92; p < 0.01), no significant difference between EEA and MTA groups was detected in the rate of infections (OR 1.92, 95% CI 0.73–5.06; p = 0.15), the rate of dysosmia (OR 1.25, 95% CI 0.31–4.99; p = 0.71), the rate of ICH (OR 0.61, 95% CI 0.20–1.87; p = 0.33), and the rate of endocrine disorders (OR 1.16, 95% CI 0.69–1.95; p = 0.53). Conclusions: This meta-analysis suggests that both EEAs and MTAs are viable options for TSM resection, with distinct advantages and drawbacks. The EEAs demonstrate superior visual outcomes in selected cases while GTR and recurrence rates support the overall effectiveness of MTAs and EEAs. Endoscopic endonasal approaches had a higher chance of CSF leaks, but there are no appreciable variations in other complications. These results provide additional insights regarding patient outcomes in the intricate clinical setting of TSMs. Full article

Background: The anatomical characteristics of the anterior ethmoidal artery (AEA) exhibit a high degree of variability, especially regarding its topography. Methods: PubMed, Scopus, Embase, Web of Science, Cochrane Library, and Google Scholar were searched to identify all studies that included information regarding the morphometric and topographical characteristics of the AEA. Results: Ultimately, a compilation of 38 studies meeting the predetermined criteria, and possessing comprehensive and pertinent data, were incorporated into the current meta-analysis. In the overall analysis, reports of the AEA being embedded within the skull base or at the level of the skull base producing a bony protrusion were found in 56.91% of cases (95% CI: 43.55–69.80%). The mean diameters of the AEA in the intraorbital and intracranial areas were 0.94 mm and 0.76 mm, respectively. Moreover, the artery coursed most commonly between the second and third lamellae, with a prevalence of 65.82% (95% CI: 55.39–75.56%). Conclusions: The AEA may be at a high risk of iatrogenic injury during various sinus and skull base surgeries, especially if the surgeon performing these procedures is unfamiliar with the vast number of variations this vessel may exhibit. The spatial relationship between this vessel and the skull base is especially variable, and understanding this variability goes hand in hand with intraoperative safety. Full article

Undifferentiated carcinoma of the nasopharynx (NPC) is a rare disease, which usually occurs in the Asian population. Due to its anatomic location, it is characterised by rich lymph node drainage and has a high incidence of cervical node metastasis. However, cervical nodal metastasis commonly involves retropharyngeal nodes and level II nodes, followed by level III nodes. In recent years, innovations in terms of systemic treatments and radiotherapy techniques have improved oncological outcome and treatment-related toxicities. Therefore, there is a growing interest in de-intensification strategies of reducing volumes and treatment-related side effects, especially in patients with NPC with N0–N1-stage disease. Proton therapy could represent a valid alternative to Intensity Modulated Radiotherapy (IMRT) in the management of NPC in this setting. With this Commentary, we aim to explore the feasibility of Intensity Modulated Proton Therapy (IMPT) in upper-neck irradiation of NPC N1-stage disease. We selected an NPC patient with N1 disease and compared the original IMRT plan with the IMPT plan in terms of dosimetric parameters. IMPT offers a minimal dosimetric advantage over IMRT in the bilateral lower-neck sparing. Clinical trials are needed to evaluate the significance of these proposed suggestions and their applicability in non-endemic areas. Full article