Microsurgery in carotid body paraganglioma.

Objectives: In carotid paraganglioma surgery, magnification is crucial to properly evaluate the anatomical relationships between mass, carotid wall, cranial nerves, tumour vascular supply and fascial envelope. The aims of this study are to describe the microsurgical technique, along with the underlying microsurgical anatomy, and to assess outcomes in terms of disease control, complications and functional results. Methods: Twenty-six patients, accounting for 29 carotid paragangliomas, treated with microsurgery by the same senior surgeon over a 35-year period, were included. Results: No carotid injury requiring repair, nor peri- or post-operative stroke occurred in this series. No surgical injury of the main trunk of VII to XII cranial nerves occurred. Complete excision was obtained in all cases and no recurrence was observed during follow-up. Conclusions: The small study size and its retrospective nature suggests caution; however, our results show that microsurgery can allow a safe and precise dissection of the carotids and nerves.

Contemporary Perspectives in Pathophysiology of Facial Nerve Damage in Oto-Neurological and Skull Base Surgical Procedures: A Narrative Review.

During the last decades, neuro-otological surgery has progressively reduced functional morbidity, including facial nerve damage. However, the occurrence of this sequela may significantly impact on patients' quality of life. The aim of this narrative review is to provide an update on the patho-physiological and clinical issues related to facial nerve damage in oto-neurological and skull base surgery, in the light of a comprehensive therapeutic and rehabilitative approach to iatrogenic disfunctions. The narrative review is based on a search in the PubMed, Scopus, and Web of Science databases. In this surgical setting, the onset of intraoperative facial nerve damage is related to various aspects, mainly concerning the anatomical relationship between tumor and nerve, the trajectory of the surgical corridor, and the boundaries of the resection margins. Mechanisms related to stretching, compression, devascularization, and heating may play a role in determining intraoperative facial nerve damage and provide the patho-physiological basis for possible nerve regeneration disorders. Most of the studies included in this review, dealing with the pathophysiology of surgical facial nerve injury, were preclinical. Future research should focus on the association between intraoperative trauma mechanisms and their clinical correlates in surgical practice. Further investigations should also be conducted to collect and record intraoperative data on nerve damage mechanisms, as well as the reports from neuro-monitoring systems.

Tumor Microenvironment in Sporadic Vestibular Schwannoma: A Systematic, Narrative Review.

Although diagnosis and treatment of vestibular schwannomas (VSs) improved in recent years, no factors have yet been identified as being capable of predicting tumor growth. Molecular rearrangements occur in neoplasms before any macroscopic morphological changes become visible, and the former are the underlying cause of disease behavior. Tumor microenvironment (TME) encompasses cellular and non-cellular elements interacting together, resulting in a complex and dynamic key of tumorigenesis, drug response, and treatment outcome. The aim of this systematic, narrative review was to assess the level of knowledge on TME implicated in the biology, behavior, and prognosis of sporadic VSs. A search (updated to November 2022) was run in Scopus, PubMed, and Web of Science electronic databases according to the PRISMA guidelines, retrieving 624 titles. After full-text evaluation and application of inclusion/exclusion criteria, 37 articles were included. VS microenvironment is determined by the interplay of a dynamic ecosystem of stromal and immune cells which produce and remodel extracellular matrix, vascular networks, and promote tumor growth. However, evidence is still conflicting. Further studies will enhance our understanding of VS biology by investigating TME-related biomarkers able to predict tumor growth and recognize immunological and molecular factors that could be potential therapeutic targets for medical treatment.

Survival Outcomes in Squamous Cell Carcinoma of the External Auditory Canal: A Systematic Review and Meta-Analysis.

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.

The contribution of oncological lateral skull base surgery to the management of advanced head-neck tumors.

BACKGROUND: Lateral skull base is a complex area between the brain and the neck that is characterized by a large anatomic variability in narrow spaces and wide heterogeneity of tissues. The complexity of the anatomy makes it more difficult to accurately identify tumor spread and surgical planning is here particularly demanding. AIMS: Oncological skull base surgery is conceived for malignant lesions originating in, secondarily infiltrating, or in close proximity to the lateral skull base. It is also conceived for selected aggressive or benign lesions of the parapharyngeal space and infratemporal fossa abutting the skull base, or crossing it from above downwards to the neck. This paper is focused on the role that oncological skull base surgery plays to resect tumors in this area. METHODS AND RESULTS: Three main types of head and neck lesions can be identified as paradigms of the philosophy of oncological lateral skull base surgery, and are herein presented: (i) primary malignant tumors of the ear; (ii) advanced malignant parotid tumors; (iii) primary malignant or locally aggressive tumors of the infratemporal fossa-parapharyngeal space. The en-bloc lateral and subtotal temporal bone resections, the en-bloc temporo-parotid resection and the combined subtemporal-transcervical-transparotid resection are described, respectively. CONCLUSIONS AND SIGNIFICANCE: Different histologies are found in the lateral skull base and adjacent areas, and each histology has its own pattern of growth and undetected spreading in a difficult-to-reach surgical area. The leading principle is to create a wide access through soft tissues and bone removal far enough from the tumor to obtain a complete resection, en-bloc radical resection in malignancies. The entity of dissection is obviously modulated on the tumor triad (histology, pattern of growth, extent) and is achieved through the en-bloc and combined approaches that are here described.

Early surgery and definitive cure in small sporadic vestibular schwannoma.

Objective: To report surgical outcomes of a cohort of small sporadic vestibular schwannoma and discuss the role of early surgery. Methods: Retrospective descriptive analysis of 234 consecutive patients with small vestibular schwannoma operated on with translabyrinthine or hearing preservation surgical approaches. Outcome measures were control of disease, postoperative facial nerve function, complications and hearing outcome. Results: A translabyrinthine approach was performed in 59% of cases, hearing preservation surgery in 40% and transmeatal approach in 1%, respectively. Complete resection was achieved in 100% of cases. Overall, postoperative major and minor complications were 8.5% in the series, with complete recovery and no sequalae. Facial nerve function at one year postoperatively was House-Brackmann scale (HB) 1-2 in 95% of cases. The rate of hearing preservation was 70% A-B-C classes of Tokyo classification and 77% AB classes of AAOHNS classification. Conclusions: Early surgery in small vestibular schwannoma is a valid option, due to good functional outcomes, low morbidity and definitive cure. Early surgery is associated with better outcomes when considered in relation to non-surgical treatments reported in the literature.

Early Translabyrinthine Surgery for Small- and Medium-Sized Vestibular Schwannomas: Consecutive Cohort Analysis of Outcomes.

OBJECTIVE: Reappraisal of the role of translabyrinthine (TLAB) surgery in small- and medium-sized vestibular schwannomas (VSs). STUDY DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: A total of 330 consecutive patients diagnosed between 1973 and 2019 with small- and medium-sized VS up to 20 mm in the extrameatal portion submitted to surgical treatment. INTERVENTIONS: VS removal through microscopic TLAB approach. MAIN OUTCOME MEASURES: Facial nerve function according to the House-Brackmann scale at 12-month follow-up, postoperative complications and entity of tumor resection assessed with postoperative MRI. A comparative analysis of outcomes between two groups of patients was further conducted, according to tumor size: Group A, small-sized (intrameatal or ≤10 mm extrameatal tumors) and Group B, medium-sized VSs (extrameatal between 11 and 20 mm). RESULTS: Complete tumor removal was achieved in all cases. The overall complication rate was 5.5%, being cerebrospinal fluid leak the most frequent. Patients with small-sized VS (n = 121) presented a significantly better facial nerve function than patients with medium-sized tumors (n = 209), showing House-Brackmann Grades I to II in 92.6% versus 73.6% of cases, respectively ( p < 0.001). A nearly 4.5-fold higher risk of poor facial nerve function at 12 months affects patients with medium-sized tumors (odds ratio, 4.473; 95% confidence interval, 2.122-9.430; p < 0.001). CONCLUSION: In the current scenario of multioptional VS management, when hearing preservation is not feasible, early TLAB approach as first-line treatment for small-sized VSs showed favorable results. Factors supporting such proactive surgical treatment include long-term definitive cure, no major complications, good facial nerve outcomes, and the possibility of simultaneous hearing rehabilitation with a cochlear implant.

Treatment of advanced squamous cell carcinoma of the external auditory canal: Critical analysis of persistent failures in diagnosis and surgery with a competing-risk model.

BACKGROUND: A series of temporal bone squamous cell carcinomas (TBSCCs) was analyzed with the aim of (i) better understanding the causes for the persistent high failure rate in advanced SCCs and (ii) discussing a possible way out from this stalemate in treatment. METHODS: Forty-five TBSCCs consecutively treated surgically were reviewed. RESULTS: The 5-year cumulative incidence for postoperative local recurrence was 41.8%. At multivariable analysis, pT3-4 stages were associated with eightfold relative incidence of developing local recurrence during follow-up (sHR = 9.06, 95% confidence interval [CI] = 1.18-69.46, p = 0.034) and cause-specific death (sHR = 7.95, 95%CI = 1.01-62.27, p = 0.048). CONCLUSIONS: The poor outcome in advanced TBSCC occurred because of local recurrence due to defective resection. The fundamental pitfall of surgery on advanced TBSCC appeared to be the insufficient knowledge of microscopic tumor growth in the different sites and subsites of the temporal bone. The serial histopathological study of the en bloc surgical specimen and autopsy temporal bones seems to represent a way to enhance our understanding of these tumors.

Temporal Bone Squamous Cell Carcinoma: Molecular Markers Involved in Carcinogenesis, Behavior, and Prognosis: A Systematic Review.

Temporal bone squamous cell carcinoma (TBSCC) is an uncommon malignancy with a poor prognosis in advanced cases. The dismal outcome of advanced TBSSC cases is largely due to the cancer's local aggressiveness and the complex anatomy of this region, as well as to persistent pitfalls in diagnosis and treatment. Molecular changes occur in malignancies before any morphological changes become visible, and are responsible for the disease's clinical behavior. The main purpose of this critical systematic review is to assess the level of knowledge on the molecular markers involved in the biology, behavior, and prognosis of TBSCC. A search (updated to March 2022) was run in PubMed, Scopus, and Web of Science electronic databases without publication date limits for studies investigating molecular markers in cohorts of patients with primary TBSCC. The search terms used were: "temporal bone" OR "external auditory canal" OR "ear", AND "cancer" OR "carcinoma" OR "malignancy". We preliminarily decided not to consider series with less than five cases. Twenty-four case series of TBSCC were found in which different analytical techniques had been used to study the role of several biomarkers. In conclusion, only very limited information on the prognostic role of molecular markers in TBSCC are currently available; prospective, multi-institutional, international prognostic studies should be planned to identify the molecular markers involved in the clinical behavior and prognosis of TBSCC. A further, more ambitious goal would be to find targets for therapeutic agents able to improve disease-specific survival in patients with advanced TBSCC.

Primary temporal bone squamous cell carcinoma: Comparing the prognostic value of the American Joint Committee on Cancer TNM classification (8th edition) with the revised Pittsburgh staging system.

BACKGROUND: Retrospectively considering a temporal bone squamous cell carcinomas (TBSCCs) series, our aim was to compare the predictive power of the American Joint Committee on Cancer (AJCC) staging system (8th edition) with the revised Pittsburgh staging system (rPSS) in terms of disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). METHODS: Forty-three TBSCCs consecutively treated surgically were reviewed. The prognostic performance of AJCC and rPSS was compared. RESULTS: The areas under the curves for the prediction of DFS, DSS, and OS did not differ significantly between both staging systems (p = 0.518, p = 0.940, and p = 0.910, respectively). Harrel's C-indexes for respectively the AJCC and rPSS were 0.76 and 0.70 for DFS, 0.73 and 0.76 for DSS, 0.66 and 0.63 for OS. CONCLUSION: Comparable prognostic accuracy was observed between AJCC and rPSS. Levels of prognostic performance were only acceptable for both systems, according to Hosmer-Lemeshow scale. Further efforts are needed to define new TBSCC staging modalities with higher prognostic reliability.

Cochlear implant in vestibular schwannomas: long-term outcomes and critical analysis of indications.

PURPOSE: To describe our institutional experience in cochlear implantation after vestibular schwannoma (VS) resection, and compare the audiological outcomes between sporadic and neurofibromatosis type 2 (NF2) VS sub-cohorts of patients, and in relation to preoperative contralateral hearing. METHODS: Seventeen patients (8 sporadic and 9 NF2-associated VSs) who had undergone VS resection and cochlear implant (CI) were analyzed retrospectively. Audiological outcomes at 24 months were correlated with preoperative clinical variables. The results according to VS type (sporadic vs. NF2-associated) and contralateral hearing (impaired vs. normal) were compared. RESULTS: Fourteen CIs were actively used by the patients (77.8%). Twenty-four months after CI activation, the median postoperative PTA (pure tone average) was 45.6 dB nHL and a measurable WRS (Word Recognition Score) was achieved by 44.4% of patients (median WRS = 40%). The median postoperative PTA in the implanted ear resulted better in the group with an impaired contralateral hearing (36.3 dB nHL vs. 78.8 dB nHL, p = 0.019). Good preoperative contralateral hearing status (A-B classes of AAO-HNS) was a negative prognostic factor for CI performance on open-set discrimination (OR = 28.0, 95% CI 2.07-379.25, p = 0.012). CONCLUSIONS: CI is a viable rehabilitative option for patients with sporadic or NF2-associated VS. A good contralateral hearing adversely affects CI outcome and should be taken into consideration for patients' selection and rehabilitation programs.

Position of Retrosigmoid Craniotomy in Hearing Preservation Surgery for Vestibular Schwannoma.

BACKGROUND: Surgical access to the internal auditory canal (IAC) fundus is a crucial aspect of the retrosigmoid approach for hearing preservation surgery in vestibular schwannoma. An appropriate positioning of the retrosigmoid craniotomy is necessary to obtain an adequate surgical corridor for full fundus exposure and labyrinth preservation. OBJECTIVE: To describe how the position of the posterior edge of the access related to the probability of exposing the fundus and to propose novel criteria for positioning the retrosigmoid craniotomy. METHODS: Data on fundus exposure were retrospectively collected in 33 consecutive cases of sporadic vestibular schwannoma, submitted to the retrosigmoid craniotomy in a park-bench position. Patients' computed tomography images were analyzed to calculate the position of the posterior edge of the craniotomy with reference to the fundus-labyrinth line (FLL), which starts at the fundus and, running just posterior to the labyrinth, reaches the occipital squama. A logistic regression model was used to correlate the craniotomy position with the probability of exposing the fundus. RESULTS: The fundus exposure rate was significantly higher (P = .005) for craniotomies located posteromedially to the FLL. In a logistic regression model, the probability of exposing the fundus reached 95% for craniotomies located 11.3 mm posteromedially to the FLL. CONCLUSION: This study showed a strong association between craniotomy position and fundus exposure rate. Our findings suggest that the posteromedial edge of the retrosigmoid craniotomy should lie approximately 11 mm posteromedially to FLL to maximize the chances of exposing the fundus.

Facial nerve sacrifice in lateral approaches to the skull base: Simultaneous reconstruction by graft interposition.

PURPOSE: To evaluate the outcome of facial nerve (FN) cable graft interposition in lateral skull base surgery. MATERIALS AND METHODS: A group of 16 patients who underwent FN graft interposition procedure was retrospectively considered. Postoperative FN function was evaluated using the House-Brackmann (HB) grading system, the Sunnybrook Facial Grading System (SFGS), the Facial Disability Index (FDI) and the Oral Functioning Scale (OFS) questionnaires. RESULTS: 56.2% of patients had a good postoperative FN outcome (HB grade II-III). Postoperative electromyography (EMG) showed re-innervation potentials in 60% of patients; median age of these patients was significantly lower compared to who did not manifest re-innervation (p = 0.039). CONCLUSION: FN primary reconstruction remains the advisable rehabilitative option when the nerve is interrupted during lateral skull base surgeries, allowing to satisfactory postoperative results in more than half of patients. EMG confirmed the restoring of nerve conduction and it was more frequent in younger patients. The SFGS, the FDI and the OFS are important tools especially in the setting of a rehabilitation program.

Tumor budding to investigate local invasion, metastasis and prognosis in temporal bone squamous cell carcinoma.

BACKGROUND: Few studies have tried to go beyond the conventional clinic-pathological prognostic factors investigating the molecular markers involved in the biology of temporal bone squamous cell carcinoma (TBSSC). Tumor budding represents a very aggressive subpopulation of cancer cells and demonstrates the heterogeneity of cancer cells residing in different locations within tumors. The main aim of this exploratory study was to investigate the role of tumor budding in primary TBSCC prognosis. We also analyzed the association between TBSCC tumor budding and: (i) loco-regional aggressiveness evaluated according to the revised Pittsburgh staging system, (ii) tumor infiltrating lymphocytes, lymphovascular invasion (LVSI), perineural invasion, pattern of invasion, and type of stroma. METHODS: Thirty-two TBSCCs treated surgically were considered. The three-tier grading system recommended by the International Tumor Budding Consensus Conference was used first on TBSCC. RESULTS: Advanced (T3-4) TBSCC was related with high risk intra-tumoral budding (ITB) at two-tier risk grading (p = 0.0361). N + status was associated with intermediate/high budding (Bd2-3) at three-tier risk grading for peri-tumoral budding (PTB) (p = 0.0382). Disease-free survival (DFS) was related with T-stage (p = 0.0406), N-status (p < 0.0001), PTB two-tier risk grading (p = 0.0463), LVSI (p < 0.0001). Overall survival (OS) was associated with N-status (p = 0.0167), PTB absolute count (p = 0.0341), PTB three-tier risk grading (p = 0.0359), PTB two-tier risk grading (p = 0.0132), and LVSI (p = 0.0004). At the multivariate analysis, DFS was related with N-status (p = 0.0147) and LVSI (p < 0.0001), while OS resulted associated only with LVSI (p = 0.0144). CONCLUSIONS: Our preliminary findings suggest that tumor budding in TBSCC, regardless of its localization (the main tumor body [ITB] or invasive front [PTB]) may be a reliable predictor of neck lymph node metastasis and poor prognosis. Tumor budding and LVI could be predictive markers for precise treatment in TBSCC. Further investigations on larger prospective series should be designed to confirm this evidence both in post-operative specimens and in preoperative biopsies.