Intraoperative surgical navigation as a precision medicine tool in sinonasal and craniofacial oncologic surgery.

INTRODUCTION: Recent evidence supports the efficacy of surgical navigation (SN) in improving outcomes of sinonasal and craniofacial oncologic surgery. This study aims to demonstrate the utility of SN as a tool for integrating surgical, radiologic, and pathologic information. Additionally, a system for recording and mapping biopsy samples has been devised to facilitate sharing of spatial information. MATERIALS AND METHODS: SN was utilized for biopsy mapping in 10 sinonasal/craniofacial oncologic procedures. Twenty-five raters with experience in anterior skull base oncology were interviewed to identify 15 anatomical structures in preoperative imaging, relying on topographical descriptions and surgical video clips. The difference in the localization of anatomical structures by raters was analyzed, using the SN-mapped coordinates as a reference (this difference was defined as spatial error). RESULTS: The analysis revealed an average spatial error of 9.0 mm (95 % confidence interval: 8.3-9.6 mm), with significant differences between surgeons and radiation oncologists (7.9 mm vs 12.5 mm, respectively, p < 0.0001). The proposed model for transferring SN-mapped coordinates can serve as a tool for consultation in multidisciplinary discussions and radiotherapy planning. CONCLUSIONS: The current standard method to evaluate disease extension and margin status is associated with a spatial error approaching 1 cm, which could affect treatment precision and outcomes. The study emphasizes the potential of SN in increasing spatial precision and information sharing. Further research is needed to incorporate this method into a multidisciplinary workflow and measure its impact on outcomes.

Morbidity of multimodal treatments including endoscopic surgery for sinonasal malignancies: Results of an international collaborative study on 940 patients (MUSES).

INTRODUCTION: In the management of sinonasal malignancies treatment-induced morbidity and mortality is gaining relevance both for surgical approaches (endoscopic and open resection) and non-surgical therapies. The aim of this multicenter study is to assess complications associated with endoscopic surgery and non-surgical treatments (neoadjuvant and/or adjuvant) for malignant sinonasal tumors. METHODS: All patients with nasoethmoidal malignancies treated with curative intent with endoscopic or endoscopic-assisted surgery at three referral centers with uniform management policies were included. Neo- and/or adjuvant (chemo)radiotherapy was administered according to histology and pathological report. Demographics, treatment characteristics, and complications related both to the surgical and non-surgical approaches were retrieved. The data were analyzed with univariate and multivariate statistics to assess independent predictors of complications. RESULTS: Nine hundred and forty patients were included, 643 males (68%) and 297 females (32%). A total of 225 complications were identified in 187 patients (19.9%): cerebrospinal fluid (CSF) leak (3.5%), mucocele (2.3%), surgical site bleeding (2.0%), epiphora (2.0%), and radionecrosis (2.0%) were the most common. Treatment-related mortality was 0.4%. Variables independently associated with complications at multivariate analysis were principally dural resection (OR 1.92), cranioendoscopic or multiportal resection (OR 2.93), dural repair with multilayer technique with less than three layers (OR 2.17), and graft different from iliotibial tract (OR 3.29). CONCLUSION: Our study shows that modern endoscopic treatments and radiotherapy for sinonasal malignancies are associated with limited morbidity and treatment-related mortality. CSF leak and radionecrosis, although rare, remain the most frequent complications and should be further addressed by future research efforts.

Follow-up strategies in pediatric cholesteatoma: a systematic review.

PURPOSE: The aim of this article was to systematically review the literature on the pediatric population surgically treated for cholesteatoma and describe the applied post-operative follow-up strategies. METHODS: A systematic review was conducted following the Primary Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement recommendations. After running the selected search string in PubMed, Scopus and Google Scholar, studies in English, reporting on surgically treated pediatric cholesteatoma patients (age younger or equal to 18 year-old) were retrieved. Both primary and revision cholesteatoma surgeries were included. Articles lacking specific data on post-surgical follow-up and case series with less than 10 patients were excluded. RESULTS: Nineteen papers, published between 2000 and 2023, were included for final analysis. Fourteen studies were retrospective and five prospective, for a total of 1319 patients and 1349 operated ears. Male to female ratio was 1.8:1, with a mean age at surgery of 10.4 years (range 1-18). The mean length of the follow-up after surgery was 4.4 ± 1.7 years (range 1-6.9). Clinical follow-up was detailed in 9 studies (47%) with otomicroscopy being the most common evaluation. In most articles (n = 8, 50%), MRI alone was utilized for radiological follow-up, while in 3 studies (19%), CT scans were employed exclusively. In 5 studies (31%), MRI was combined with CT scans. The timing of radiological investigations varied widely (ranging from 6 months to 3 years). A second-look strategy was reported in 14 studies (74%). CONCLUSION: This systematic review highlights the heterogeneity of the follow-up strategies applied to pediatric patients after cholesteatoma surgery, both in terms of timing and types of investigations.

Endoscopic-assisted transorbital extended orbital exenteration: A multi-institutional preclinical study.

BACKGROUND: Sinonasal malignancies with orbital invasion have dismal prognosis even when treated with orbital exenteration (OE). Sugawara et al. developed a surgical strategy called "extended-OE (EOE)," showing encouraging outcomes. We hypothesized that a similar resection is achievable under endoscopic guidance through the exenterated orbit (endoscopic-EOE). METHODS: The study was conducted in three institutions: University of Vienna; Mayo Clinic; University of Insubria; 48 orbital dissections were performed. A questionnaire was developed to evaluate feasibility and safety of each step, scoring from 1 to 10, ("impossible" to "easy," and "high risk" to "low risk," respectively), most likely complication(s) were hypothesized. RESULTS: The step-by-step technique is thoroughly described. The questionnaire was answered by 25 anterior skull base surgeons from six countries. Mean, median, range, and interquartile range of both feasibility and safety scores are reported. CONCLUSIONS: Endoscopic-EOE is a challenging but feasible procedure. Clinical validation is required to assess real-life outcomes.

Endovascular coils extrusion after internal carotid artery occlusion: From management to follow-up.

KEY POINTS: ICA coil extrusion (ICA-CE) occurs most frequently in the nasopharyngeal/sinonasal site. Evaluating the ICA coils stability, through an angiography, is of primary importance. ICA-CE management needs to be decided based on the patient's symptoms and general status.

Surgical management of advanced sinonasal cancer: a 10-year mono-institutional experience.

Objective: Endoscopic endonasal surgery is effective in the treatment of sinonasal cancers. However, in cases of well-differentiated locally advanced neoplasms as well as recurrences, the most appropriate treatment is debated. The purpose of this study is to report a mono-institutional experience on craniofacial surgery performed in a tertiary-care referral centre. Methods: This was a retrospective analysis of 90 patients treated with transcranial and/or transfacial resection for sinonasal cancer between 2010 and 2020. Outcome measures included overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS) and recurrence-free survival (RFS). Results: The 5-year OS, DSS and DFS were 48.2%, 60.6% and 28.7%, respectively. Factors correlated with prognosis were pT-classification (p = 0.002), histotype (p = 0.012) and dural involvement (p = 0.004). Independent prognostic factors were orbital apex infiltration (p = 0.03), age (p = 0.002) and adjuvant therapy (p = 0.03). Conclusions: When endoscopic endonasal surgery is contraindicated and chemoradiotherapy is not appropriate, craniofacial and transfacial approaches still represent an option to consider, despite the non-negligible morbidity.

Salvage endoscopic nasopharyngectomy for recurrent nasopharyngeal carcinoma in a non-endemic area.

PURPOSE: To analyze oncological outcomes of endoscopic surgical treatment of locally recurrent EBV-related undifferentiated non-keratinizing nasopharyngeal carcinoma (uNK-NPC) in a non-endemic area. METHODS: Retrospective review of patients affected by recurrent uNK-NPC treated with nasopharyngeal endoscopic resection (NER) in a tertiary-care referral center from 2003 to 2022, by evaluating survival rates, prognostic factors, and follow-up strategies. RESULTS: The oncological outcomes of 41 patients were analyzed, over a mean follow-up period of 57 months. The 5-year overall, disease-specific, and disease-free survival of the cohort were 60.7% ± 8.9%, 69% ± 9%, and 39.7% ± 9.2%, respectively. The local (rT) and regional (rN) extension of recurrent disease, stage of disease, and status of resection margins appeared to significantly influence survivals. After a mean follow-up period of 21 months, a further recurrence after NER was observed in 36.6% of cases. Skull base osteonecrosis induced by previous irradiation and post-surgical bone remodeling represent the major challenges for early detection of further local relapses during postoperative follow-up. CONCLUSION: NER appeared as a safe and effective treatment for recurrent uNK-NPC. The adequate selection of patients eligible for NER is essential, to maximize the chances to cure and minimize the risk of local complications.

Novel cellular systems unveil mucosal melanoma initiating cells and a role for PI3K/Akt/mTOR pathway in mucosal melanoma fitness.

BACKGROUND: Mucosal Melanomas (MM) are highly aggressive neoplasms arising from mucosal melanocytes. Current treatments offer a limited survival benefit for patients with advanced MM; moreover, the lack of pre-clinical cellular systems has significantly limited the understanding of their immunobiology. METHODS: Five novel cell lines were obtained from patient-derived biopsies of MM arising in the sino-nasal mucosa and designated as SN-MM1-5. The morphology, ultrastructure and melanocytic identity of SN-MM cell lines were validated by transmission electron microscopy and immunohistochemistry. Moreover, in vivo tumorigenicity of SN-MM1-5 was tested by subcutaneous injection in NOD/SCID mice. Molecular characterization of SN-MM cell lines was performed by a mass-spectrometry proteomic approach, and their sensitivity to PI3K chemical inhibitor LY294002 was validated by Akt activation, measured by pAkt(Ser473) and pAkt(Thr308) in immunoblots, and MTS assay. RESULTS: This study reports the validation and functional characterization of five newly generated SN-MM cell lines. Compared to the normal counterpart, the proteomic profile of SN-MM is consistent with transformed melanocytes showing a heterogeneous degree of melanocytic differentiation and activation of cancer-related pathways. All SN-MM cell lines resulted tumorigenic in vivo and display recurrent structural variants according to aCGH analysis. Of relevance, the microscopic analysis of the corresponding xenotransplants allowed the identification of clusters of MITF-/CDH1-/CDH2 + /ZEB1 + /CD271 + cells, supporting the existence of melanoma-initiating cells also in MM, as confirmed in clinical samples. In vitro, SN-MM cell lines were sensitive to cisplatin, but not to temozolomide. Moreover, the proteomic analysis of SN-MM cell lines revealed that RICTOR, a subunit of mTORC2 complex, is the most significantly activated upstream regulator, suggesting a relevant role for the PI3K-Akt-mTOR pathway in these neoplasms. Consistently, phosphorylation of NDRG1 and Akt activation was observed in SN-MM, the latter being constitutive and sustained by PTEN loss in SN-MM2 and SN-MM3. The cell viability impairment induced by LY294002 confirmed a functional role for the PI3K-Akt-mTOR pathway in SN-MM cell lines. CONCLUSIONS: Overall, these novel and unique cellular systems represent relevant experimental tools for a better understanding of the biology of these neoplasms and, as an extension, to MM from other sites.

Nasoseptal flap with extended pedicle dissection based on the maxillary artery: Clinical series of 55 cases.

KEY POINTS: Nasoseptal flap with extended pedicle dissection is a low morbidity and high success rate flap. It is a flap that can be applied to reconstruct a wide range of ipsilateral skull base defects.

Squamous Cell Carcinoma of the Nasal Vestibule: A Multi-Centric Observational Cohort Study.

OBJECTIVES: Squamous cell carcinoma of the nasal vestibule (NV-SCC) is a rare but challenging entity, due to the complex anatomy of the region. Consensus on the best treatment strategy is still lacking, as well as a dedicated staging system. Our aim was to analyze oncological outcomes of surgically treated patients and to investigate possible prognostic factors. METHODS: We performed a retrospective multi-centric observational study including six Academic Hospitals over a 10-year period, including only patients who underwent upfront surgery for primary NV-SCC. Patients were staged according to all currently available staging systems. The Kaplan-Meier method was used to compute overall, disease-free, and disease-specific survival. Logistic regression models were used to correlate between survival outcomes and clinical and pathological variables. RESULTS: Seventy-one patients with a median follow-up of 38 months were included in the study. Partial and total rhinectomy were the most commonly performed procedures, respectively, in 49.3% and 25.4% of cases. Neck dissection was performed on 31% of patients, and 45.1% of them underwent adjuvant radiotherapy. Three years overall, disease-specific and disease-free survival were, respectively, 86.5%, 90.3%, and 74.2%. None of the currently available staging systems were able to effectively stratify survival outcomes. Factors predicting lower overall survival on multivariate analysis were age (p = 0.021) and perineural invasion (p = 0.059), whereas disease-free survival was negatively affected by age (p = 0.033) and lymphovascular invasion (p = 0.019). CONCLUSION: Currently available staging systems cannot stratify prognosis for patients who underwent surgery for NV-SCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2634-2645, 2024.