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.

The role of central neck dissection and adjuvant treatment in pT4aN0 laryngeal carcinoma treated with open partial horizontal laryngectomy.

PURPOSE: The study aimed to identify parameters that could predict oncological and functional outcomes in patients with pT4aN0 laryngeal squamous cell carcinoma (LSCC) who underwent open partial horizontal laryngectomy (OPHL). The role of paratracheal neck dissection (PTND) was analyzed as the primary outcome. Additionally, the study compared the outcomes of patients who underwent postoperative radio/chemotherapy (PORT/PORCT) with those who refused or did not adhere to adjuvant treatments. METHODS: Twenty-nine OPHL patients whose pathological exam was consistent with pT4aN0-x disease were enrolled and their clinical charts were retrospectively reviewed. The study analyzed oncological outcomes, such as local, regional, and distant recurrence rates (RR), overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS). Additionally, functional results were analyzed, including decannulation rate, hospitalization time, and postoperative complication rate. RESULTS: The study revealed and overall recurrence rate of 27%. The final rates for OS and DSS were 68% and 79%, respectively. Based on the univariate analysis the PTND was significantly associated with longer DFS. No significant differences inoncological outcomes were observed between pT4a patients who underwent adjuvant radio/radiochemotherapy and those who did not, in terms of RR, DFS, DSS or OS. However, adjuvant treatment was found to significantly increase decannulation time. CONCLUSIONS: In a properly super-selected subgroup of patients with pT4aN0 LSCC, OPHL may beconsidered as a conservative surgical option even without adjuvant treatment. However, for optimal oncological outcomes, it is strongly recommended to consider a central compartment dissection in cases of hypoglottic and anterior extra-laryngeal tumor extension.

Artificial intelligence for automatic detection and segmentation of nasal polyposis: a pilot study.

PURPOSE: Accurate diagnosis and quantification of polyps and symptoms are pivotal for planning the therapeutic strategy of Chronic rhinosinusitis with nasal polyposis (CRSwNP). This pilot study aimed to develop an artificial intelligence (AI)-based image analysis system capable of segmenting nasal polyps from nasal endoscopy videos. METHODS: Recorded nasal videoendoscopies from 52 patients diagnosed with CRSwNP between 2019 and 2022 were retrospectively analyzed. Images extracted were manually segmented on the web application Roboflow. A dataset of 342 images was generated and divided into training (80%), validation (10%), and testing (10%) sets. The Ultralytics YOLOv8.0.28 model was employed for automated segmentation. RESULTS: The YOLOv8s-seg model consisted of 195 layers and required 42.4 GFLOPs for operation. When tested against the validation set, the algorithm achieved a precision of 0.91, recall of 0.839, and mean average precision at 50% IoU (mAP50) of 0.949. For the segmentation task, similar metrics were observed, including a mAP ranging from 0.675 to 0.679 for IoUs between 50% and 95%. CONCLUSIONS: The study shows that a carefully trained AI algorithm can effectively identify and delineate nasal polyps in patients with CRSwNP. Despite certain limitations like the focus on CRSwNP-specific samples, the algorithm presents a promising complementary tool to existing diagnostic methods.

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.

Skull base surgery for malignant tumors: The 2nd international collaborative study (1995-2015).

BACKGROUND: The current study presents the effort of a global collaborative group to review the management and outcomes of malignant tumors of the skull base worldwide. PATIENTS AND METHODS: A total of 28 institutions contributed data on 3061 patients. Analysis evaluated clinical variables, survival outcomes, and multivariable factors associated with outcomes. RESULTS: The median age was 56 years (IQR 44-67). The open surgical approach was used in 55% (n = 1680) of cases, endoscopic resection was performed in 36% (n = 1087), and the combined approach in 9.6% (n = 294). With a median follow-up of 7.1 years, the 5-year OS DSS and RFS were 65%, 71.7% and 53%, respectively. On multivariable analysis, older age, comorbidities, histology, dural/intracranial involvement, positive margins, advanced stage, and primary site were independent prognostic factors for OS, DSS, and RFS. Adjuvant RT was a protective prognostic factor. CONCLUSION: The progress across various disciplines may have contributed to improved OS and DSS in this study compared to previous reports.

A Pathophysiological Approach to Spontaneous Orbital Meningoceles: Case Report and Systematic Review.

BACKGROUND: Spontaneous orbital cephaloceles are a rare condition. The purpose of this study is to provide a description of a clinical case and to carry out a systematic literature review. METHODS: A systematic review of the English literature published on the Pubmed, Scopus, and Web of Science databases was conducted, according to the PRISMA recommendations. RESULTS: A 6-year-old patient was admitted for right otomastoiditis and thrombosis of the sigmoid and transverse sinuses, as well as the proximal portion of the internal jugular vein. Radiological examinations revealed a left orbital mass (22 × 14 mm) compatible with asymptomatic orbital meningocele (MC) herniated from the superior orbital fissure (SOF). The child underwent a right mastoidectomy. After the development of symptoms and signs of intracranial hypertension (ICH), endovascular thrombectomy and transverse sinus stenting were performed, with improvement of the clinical conditions and reduction of the orbital MC. The systematic literature review encompassed 29 publications on 43 patients with spontaneous orbital MC. In the majority of cases, surgery was the preferred treatment. CONCLUSIONS: The present case report and systematic review highlight the importance of ICH investigation and a pathophysiological-oriented treatment approach. The experiences described in the literature are limited, making the collection of additional data paramount.

The Impact of Dupilumab on Work Productivity and Emotional Health in CRSwNP: A Multicentric Study in Northeast Italy.

Chronic rhinosinusitis with nasal polyps (CRSwNP) in the severe forms is associated with a poor quality of life. Dupilumab has been suggested as an add-on treatment option for severe CRSwNP. Severe CRSwNP patients treated with Dupilumab in different rhinological units were considered for this study via their evaluation at the baseline at first and the consequential follow-up at 6-, 12-, and 24 months from the first administration. At baseline (T0) and at each follow-up, patients underwent NPS, Sinonasal Outcome Test (SNOT)-22, Visual Analogue Scale (VAS) for smell, and Sniffin' sticks identification test (SSIT). The SNOT-22 domains for function and emotion were also analysed separately. Two hundred and seventeen patients with at least 6 months of follow-up were included. All parameters have improved during treatment (p < 0.0001). Noticeably, both the function and emotion SNOT-22 domains have improved within 6 months of treatment and have continued to progress during every interval within 12 months from the baseline, positively influencing patients' emotivity and augmenting their social and economic performances. Dupilumab improves the QoL of CRSwNP patients with good effects on the reported productivity and emotional health. Clinicians should pay attention to these two aspects when dealing with patients affected by severe CRSwNP.

Isoprognostic functional CT map for open partial horizontal laryngectomy.

PURPOSE: To identify a radiological map of laryngeal subsites whose involvement by the tumor could predict patients' functional outcomes after open partial horizontal laryngectomy (OPHL). METHODS: The present retrospective analysis concerned 96 patients with glottic squamous cell carcinoma, who were radiologically staged with contrast-enhanced neck CT scans before undergoing supracricoid or supratracheal laryngectomy. A radiological map of patients' functional risk was developed by considering the distribution of functional outcomes in relation to the laryngeal subsites involved. The functional outcomes considered were: (i) decannulation at discharge; (ii) time to removal of the nasogastric feeding tube (NFT); (iii) postoperative complication rate; and (iv) length of hospital stay. RESULTS: Involvement of the anterior supraglottis was related to a longer need for NFT, and a longer hospital stay (p = 0.003, and p = 0.003, respectively). Involvement of the posterior glottis negatively affected the time to decannulation, and the likelihood of postoperative complications (p = 0.000, and p = 0.002, respectively). CONCLUSIONS: Anterior glottic small tumors (without significant subglottic and/or supraglottic extension) are related to the best functional outcomes after OPHL, since the suprahyoid epiglottis and both the arytenoids are likely to be spared.

Management of nasal vestibule carcinomas: recommendations by the Oncological Committee of the Italian Society of Otorhinolaryngology - Head and Neck Surgery.

Objective: Squamous cell carcinoma of the nasal vestibule (NV SCC) is a head and neck malignancy for which there is no established consensus on most aspects of clinical management. The purpose of this document is to give updated recommendations that incorporate recent evidence on its clinical characteristics and the high efficacy of brachytherapy as primary treatment modality. Methods: A working group consisting of the members of the Scientific Committee for Oncology and Reconstructive Surgery of the Italian Society of Otorhinolaryngology Head and Neck Surgery and radiation oncologists expert in brachytherapy was formed to achieve a consensus. Results: Consensus was reached on a set of recommendations, proposing a refined anatomical definition of the nasal vestibule, a novel T staging system of the NV SCC, and brachytherapy as standard of care, with a new method for catheter implantation. Conclusions: The Committee emphasises the critical role of an accurate classification in clinical practice and encourages further research to validate the novel staging system and further improve treatment strategies. Where appropriate, it is recommended that patients be referred to centres with specific experience in brachytherapy for NV SCC.

Side-door temporoparietal fascia flap: First experience with a novel technique for anterior skull base reconstruction.

BACKGROUND: Modern achievements in transnasal endoscopic skull base (SB) surgery have led to complex resections that render reconstruction a challenge. Temporoparietal fascia flap (TPFF) is a suitable option for SB reconstruction. The side-door TPFF technique for anterior SB reconstruction is described here for the first time in a real-life surgical setting. METHODS: Patients affected by a SB malignancy who underwent cranioendoscopic resection were included. For reconstruction, a multilayer reconstruction technique including side-door TPFF transposition was employed. RESULTS: TPFF transposition was performed in five patients. The TPFF could be easily transposed via a side-door approach. It adequately covered the edges of the defect and supported optimal healing of the surgical site. During follow-up, vitality and integration of the TPFF were assessed endoscopically and radiologically. CONCLUSIONS: The TPFF side-door transposition technique is a valuable option in anterior SB reconstruction that can provide fast and effective healing, especially in patients needing adjuvant radiotherapy.

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.

Computer-aided designed 3D-printed polymeric scaffolds for personalized reconstruction of maxillary and mandibular defects: a proof-of-concept study.

PURPOSE: To investigate the potential reconstruction of complex maxillofacial defects using computer-aided design 3D-printed polymeric scaffolds by defining the production process, simulating the surgical procedure, and explore the feasibility and reproducibility of the whole algorithm. METHODS: This a preclinical study to investigate feasibility, reproducibility and efficacy of the reconstruction algorithm proposed. It encompassed 3 phases: (1) scaffold production (CAD and 3D-printing in polylactic acid); (2) surgical simulation on cadaver heads (navigation-guided osteotomies and scaffold fixation); (3) assessment of reconstruction (bone and occlusal morphological conformance, symmetry, and mechanical stress tests). RESULTS: Six cadaver heads were dissected. Six types of defects (3 mandibular and 3 maxillary) with different degree of complexity were tested. In all case the reconstruction algorithm could be successfully completed. Bone morphological conformance was optimal while the occlusal one was slightly higher. Mechanical stress tests were good (mean value, 318.6 and 286.4 N for maxillary and mandibular defects, respectively). CONCLUSIONS: Our reconstructive algorithm was feasible and reproducible in a preclinical setting. Functional and aesthetic outcomes were satisfactory independently of the complexity of the defect.

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.

Facial Surface Electromyography: A Novel Approach to Facial Nerve Functional Evaluation after Vestibular Schwannoma Surgery.

BACKGROUND: Vestibular schwannoma (VS) surgery may cause facial nerve damage. However, a comprehensive evaluation of post-operative facial outcomes may be difficult to achieve. Surface electromyography (sEMG) is a promising non-invasive evaluation tool. However, its use in the follow-up after VS surgery has not been reported yet. The main objective was to develop and validate a new sEMG application specifically for the post-VS surgery setting. Secondary goals were to provide a systematic description of facial muscle activity after VS surgery and assess the association between sEMG parameters and Sunnybrook scale scores. METHODS: Thirty-three patients with facial palsy following VS surgery were included. The clinical outcomes (Sunnybrook symmetry, movement, and synkinesis scores) and sEMG parameters (signal amplitude normalized by the maximal voluntary contraction (NEMG) and sEMG synkinesis score (ESS, number of synkinesis per movement sequence)) were evaluated at the end of the follow-up. RESULTS: In all tested muscles, NEMG variance was significantly higher on the affected side than the contralateral (variance ratio test, p < 0.00001 for each muscle). In total, 30 out of 33 patients (90.9%) showed an ESS ≥ 1 (median: 2.5, IQR: 1.5-3.0). On the affected side, NEMG values positively correlated with both dynamic and overall Sunnybrook scores (Spearman's model, p < 0.05 for each muscle, except orbicularis oculi). ESS significantly correlated with the Sunnybrook synkinesis score (Spearman's rho: 0.8268, p < 0.0001). CONCLUSIONS: We described and preliminarily validated a novel multiparametric sEMG approach based on both signal amplitude and synkinesis evaluation specifically for oto-neurosurgery. Large-scale studies are mandatory to further characterize the semiological and prognostic value of facial sEMG.

Prognostic Value of Anteroposterior Extension in Oral Tongue and Floor Squamous Cell Carcinoma.

Importance: The tongue and oral floor represent the most involved subsite by oral cancer, and there are no reported systems to classify anteroposterior tumor extension with prognostic effect. In other cancers, the anterior vs posterior tumor extension is a relevant prognostic factor. Objective: To establish whether anterior vs posterior tumor extension may represent a prognostic factor in oral tongue and floor squamous cell carcinoma (OTFSCC). Design, Setting, and Participants: This was a retrospective cohort study of patients who underwent surgery for OTFSCC from January 1, 2010, to December 31, 2021, at 2 tertiary-level academic institutions in Italy (University of Padua and University of Brescia). Patients eligible for the study had histologically proven primary OTFSCC; underwent surgery-based, curative treatment; and had available preoperative contrast-enhanced imaging. Exposures: Four anatomical lines were designed to assess tumor extension: (1) chin-palate line (CPL), (2) chin-basion line, (3) Stensen duct line, and (4) lingual septum line. Preoperative imaging was re-evaluated, and tumor extension was classified as either anterior or posterior according to the lines. Main Outcomes and Measures: Overall survival and time to recurrence (TTR) were evaluated according to tumor extension. These outcomes were reported as 5-year survival rates with 95% CIs. Results: Of the 133 patients included, 79 (59.4%) were male, and the mean (SD) age was 62.7 (15.4) years. The 5-year TTR difference was higher for posterior vs anterior OTFSCC classified according to CPL (21.0%; 95% CI, 8.3%-33.7%), Stensen duct line (15.5%; 95% CI, 1.0%-30.0%), and lingual septum line (17.2%; 95% CI, 2.2%-32.3%). Overall survival analysis showed similar results. At the multivariable analysis on TTR, N status (adjusted hazard ratio [HR], 3.0; 95% CI, 1.2-7.1) and anteroposterior classification according to CPL (adjusted HR, 7.1; 95% CI, 0.9-54.6) were the variables associated with the highest adjusted HRs. Conclusions and Relevance: In this cohort study, OTFSCC with a posterior extension to the CPL was associated with a higher risk of recurrence and death. This analysis suggests that the poor prognosis conveyed by the posterior tumor extension is independent of other relevant prognosticators except for the burden of nodal disease. This estimate is not precise and does not allow for definitive clinically important conclusions; therefore, further prospective studies are necessary to confirm these data.