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.

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.

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.

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.

High-Definition 3D Exoscope in Pediatric Otorhinolaryngology: A Systematic Literature Review.

This PRISMA-compliant systematic review aimed to investigate the use of and the most common procedures performed with the novel 3D 4K exoscope in surgical pediatric head and neck settings. METHODS: Search criteria were applied to PubMed, EMBASE and the Cochrane Review databases and included all studies published up to January 2023 reporting 3D 4K exoscope-assisted surgeries in pediatric patients. After the removal of duplicates, selection of abstracts and full-text articles, and quality assessment, we reviewed eligible articles for number of patients treated, age, surgical procedures, and outcomes. RESULTS: Among 54 potentially relevant records, 5 studies were considered eligible and included in this systematic review, with reported treatment data for 182 patients. The surgical procedures belong to the otologic field (121 cases), head and neck surgery (25 cases) and transoral surgery (36 cases). Exoscopy allowed high quality visualization of anatomical structures during cochlear implantation and during reconstruction in head and neck surgery; moreover, it improved the surgical view of surgeons, spectators and ENT students. CONCLUSIONS: The use of 3D 4K exoscopy has shown promising potential as a valuable tool in pediatric ORL-head and neck surgery; nevertheless, further validation of these encouraging outcomes is necessary through larger-scale studies specifically focused on pediatric patients.

Diagnostic performance of inflammatory biomarkers and cytological analysis in salivary gland tumors.

BACKGROUND: This study aimed to evaluate the diagnostic performance of serum inflammatory biomarkers in salivary gland tumors with dubious results following cytological analysis. METHODS: A retrospective analysis of 239 cases following surgery between January 2011 and June 2022 was performed. Receiver Operating Characteristic curves were drawn and areas under the curves were computed to evaluate the diagnostic performance of the inflammatory biomarkers (SII, SIRI, PLR, and NLR). Optimal cut-offs for each marker were determined by maximizing the Youden index. RESULTS: Analysis showed that among the major biomarkers examined, SIRI performed an AUC of 0.77. The best SIRI cut-off was 0.94 with an accuracy of 79.9%. The accuracy, sensitivity, and specificity of cytological analysis were 77.8%, 59.6%, and 90.7% respectively. By combining SIRI with cytological analysis we demonstrated an increase in sensitivity to 82.8%. CONCLUSIONS: Inflammatory biomarkers could be evaluated to support the diagnosis and treatment of salivary gland tumors in difficult cases.

The role of the osteoplastic flap in the endoscopic era: a retrospective multicentre experience on revision surgery.

Objective: To retrospectively review the experience of five tertiary-care university hospitals on frontal sinus revision surgery with osteoplastic flap (OPF). Methods: Descriptive analysis of patients who underwent frontal sinus surgery with OPF after one or more endoscopic procedures for benign and inflammatory pathologies from 2000 to 2022. Clinical charts were reviewed for demographics, indications, clinical presentation, previous frontal procedures, OPF technique and outcomes. Results: Of the 124 patients who underwent an OPF procedure, 33 met inclusion criteria. With a mean of 2.1 previous endoscopic surgeries, Draf III was the most common former procedure. In 30 (91%) cases OPF was part of a combined procedure. The most common indications were inverted papilloma (61%), mucocele (9%) and chronic rhinosinusitis (6%). Frontal outflow stenosis (36%) and mucocele (9%) were the most frequent complications observed. Improvement of overall symptoms and patient satisfaction after the OPF procedure were recorded. Conclusions: Even in the endoscopic era, OPF still represents a paramount procedure that should be included in the rhino-surgeon's armamentarium, in particular in patients with challenging pathologies and anatomy when previous endoscopic endonasal attempts have failed.

International Multicenter Study of Clinical Outcomes of Sinonasal Melanoma Shows Survival Benefit for Patients Treated with Immune Checkpoint Inhibitors and Potential Improvements to the Current TNM Staging System.

Objectives Sinonasal mucosal melanoma (SNMM) is an extremely rare and challenging sinonasal malignancy with a poor prognosis. Standard treatment involves complete surgical resection, but the role of adjuvant therapy remains unclear. Crucially, our understanding of its clinical presentation, course, and optimal treatment remains limited, and few advancements in improving its management have been made in the recent past. Methods We conducted an international multicenter retrospective analysis of 505 SNMM cases from 11 institutions across the United States, United Kingdom, Ireland, and continental Europe. Data on clinical presentation, diagnosis, treatment, and clinical outcomes were assessed. Results One-, three-, and five-year recurrence-free and overall survival were 61.4, 30.6, and 22.0%, and 77.6, 49.2, and 38.3%, respectively. Compared with disease confined to the nasal cavity, sinus involvement confers significantly worse survival; based on this, further stratifying the T3 stage was highly prognostic ( p < 0.001) with implications for a potential modification to the current TNM staging system. There was a statistically significant survival benefit for patients who received adjuvant radiotherapy, compared with those who underwent surgery alone (hazard ratio [HR] = 0.74, 95% confidence interval [CI]: 0.57-0.96, p = 0.021). Immune checkpoint blockade for the management of recurrent or persistent disease, with or without distant metastasis, conferred longer survival (HR = 0.50, 95% CI: 0.25-1.00, p = 0.036). Conclusions We present findings from the largest cohort of SNMM reported to date. We demonstrate the potential utility of further stratifying the T3 stage by sinus involvement and present promising data on the benefit of immune checkpoint inhibitors for recurrent, persistent, or metastatic disease with implications for future clinical trials in this field.

Lateral Orbitotomy Cryo-Assisted Removal of Orbital Cavernous Hemangiomas: Case Report and Technical Hints.

Orbital cavernous hemangiomas are the most common adult benign vascular orbital neoformation, representing 5%-15% of all orbital masses, and may involve the extraconal or intraconal space.1 According to the International Society for the Study of Vascular Anomalies, orbital cavernous hemangiomas should be classified as low-flow nondistensible venous malformations and are characterized by slow growth, generally 0.2 cm3/year.2,3 For these characteristics, complete surgical resection is necessary for symptomatic patients or in case of significant volumetric increase in its size.4Video 1 demonstrates the cryo-assisted removal of an intraconal orbital hemangioma (22 × 26 mm) located in the superior-lateral aspect of the right orbit in a 55-year-old woman. The patient presented with right exophthalmos and diplopia on right lateral gaze. The lesion was completely removed using a right lateral orbitotomy combined with a superior eyelid endoscopic-assisted approach. Intraoperative neuronavigation was used to correctly identify the location of the orbital hemangioma. Exophthalmos resolved postoperatively, without any cosmetic sequelae or visual impairment. Magnetic resonance imaging performed 8 months after surgery demonstrated excellent surgical outcomes, with complete resolution of the exophthalmos and without evidence of persistence of disease. A multidisciplinary approach, involving different specialists familiar with orbital anatomy and physiology, is fundamental in the management of these rare orbital pathologies.

Impact of the COVID-19 pandemic on paediatric otolaryngology: a nationwide study.

Objective: The COVID-19 pandemic profoundly modified the work routine in healthcare; however, its impact on the field of paediatric otorhinolaryngology (ORL) has been rarely investigated. The aim of this study was to assess the impact of COVID-19 on paediatric ORL. Methods: A questionnaire was developed by the Young Otolaryngologists of the Italian Society of ORL-Head and Neck Surgery (GOS). The questionnaire consisted of 26 questions related to workplace and personal paediatric ORL activities. The link was advertised on the official social media platforms and sent by e-mail to 469 Italian otolaryngologists. Results: The questionnaire was completed by 118 responders. During the pandemic, the main reduction was observed for surgical activity (78.8%), followed by outpatient service (16.9%). The conditions that were mostly impacted by a delayed diagnosis were respiratory infections in 45.8% of cases and sensorineural hearing loss in 37.3% of cases. Conclusions: Paediatric ORL was highly impacted by the COVID-19 pandemic, with a significant reduction of surgical and outpatient activities and a delay in time-sensitive diagnosis. Therefore, the implementation of new strategies, such as telemedicine, is recommended.

Treatment of loco-regional recurrence of nasopharyngeal carcinoma in a non-endemic area: oncologic outcomes, morbidity, and proposal of a prognostic nomogram.

Introduction: The study assessed outcomes and toxicities of different treatment modalities for local and/or regional recurrent nasopharyngeal carcinoma (NPC) in a non-endemic area. Methods: Patients treated with curative intent for recurrent NPC with salvage surgery, photon-based radiotherapy, proton therapy (PT), with or without chemotherapy, at different Italian referral centers between 1998 and 2020 were included. Adverse events and complications were classified according to the Common Terminology Criteria for Adverse Events. Characteristics of the patients, tumors, treatments, and complications are presented along with uni- and multivariate analysis of prognostic factors. A survival predictive nomogram is also provided. Results: A total of 140 patients treated from 1998 to 2020 were retrospectively assessed. Cases with lower age, comorbidity rate, stage, and shorter disease-free interval (DFI) preferentially underwent endoscopic surgery. More advanced cases underwent re-irradiation, fairly distributed between photon-based radiotherapy and PT. Age and DFI were independent factors influencing overall survival. No independent prognostic effect of treatment modality was observed. No significant difference in the morbidity profile of treatments was observed, with 40% of patients experiencing at least one adverse event classified as G3 or higher. Conclusion: Recurrent NPC in a non-endemic area has dissimilar aspects compared to its endemic counterpart, suggesting the need for further studies that can guide the choice of the best treatment modality.

The SINTART 2 Study. A phase II non-randomised controlled trial of induction chemotherapy, photon-, proton- and carbon-ion-based radiotherapy integration in patients with locally advanced unresectable sinonasal tumours.

PURPOSE: Unresectable, locally advanced sinonasal epithelial tumours are rare diseases with poor prognosis. Multimodal approach is widely used, although no standard therapy has been established in prospective trials. This study assessed activity and safety of an innovative integration of multimodality treatment-induction chemotherapy (ICT), surgery and radiotherapy (RT)-modulated by histology and response to ICT. METHODS: Patients with untreated, unresectable sinonasal epithelial tumours with selected histotypes (squamous cell carcinoma, intestinal-type adenocarcinoma, sinonasal undifferentiated and neuroendocrine carcinoma, olfactory neuroblastoma) were enroled in a single-arm, open-label, phase II, multicentre clinical trial. Patients were treated with up to 5 ICT cycles, whose regimen was selected according to histotype. Photon and/or proton/carbon-ion-based RT was employed according to disease site, stage and ICT response. Primary end-point was 5-years progression-free survival (PFS), secondary end-points were overall survival (OS), ICT objective response rate per RECIST 1.1 and safety. RESULTS: Twenty-five patients were evaluable for primary end-point. Five-year PFS was 26.8% (95% confidence interval [CI]: 12.6-57.1), with a median PFS of 18 months. Five-year OS was 23.8% (95% CI: 9.5-59.3), with a median OS of 27 months. The overall response rate to ICT was 40%. Three-year PFS for patients achieving major volumetric partial response (mPRv) versus non-mPRv was 40% (95% CI: 13.7-100%) versus 23.1% (95% CI: 8.3-64.7%) (P = 0.318) and 3-year OS was 53.3% (95% CI: 21.4-100%) versus 37.7% (95% CI: 20.0-71.0%) (P = 0.114). CONCLUSION: Multimodal combination of ICT and innovative RT did not provide a significant improvement in survival rates with respect to previous experiences. This finding underscores the need for future research in this rare disease, still characterised by a heavy burden and poor prognosis. We observed longer survival in subjects achieving response to ICT. The overall treatment safety is acceptable.

The SINTART 1 study. A phase II non-randomised controlled trial of induction chemotherapy, surgery, photon-, proton- and carbon ion-based radiotherapy integration in patients with locally advanced resectable sinonasal tumours.

PURPOSE: Sinonasal tumours are rare diseases with poor prognosis. Multimodal approach including surgery is widely used, although no standard therapy has been established in prospective trials. This study assessed activity and safety of an innovative integration of multimodality treatment-induction chemotherapy (ICT), surgery and radiotherapy (RT)-modulated by histology and response to ICT. METHODS: Patients with untreated, operable sinonasal tumours with selected histotypes (squamous cell carcinoma, intestinal-type adenocarcinoma, sinonasal undifferentiated and neuroendocrine carcinoma, olfactory neuroblastoma) were enrolled in a single-arm, phase II, multicenter clinical trial. Patients were treated with up to 5 ICT cycles, whose regimen was selected according to histotype, followed either by curative chemo-RT for pts with ≥80% reduction of initial tumour diameter or surgery and adjuvant (chemo)RT. Photon and/or proton/carbon ion-based RT was employed according to the disease site and stage. Primary end-point was 5-year progression-free survival (PFS), secondary end-points were overall survival (OS), ICT objective response rate (ORR) per RECIST 1.1 and safety. RESULTS: Thirty-five patients were evaluable for primary end-point. Fourteen patients (40%) were treated with definitive (CT)RT and 20 (57%) underwent surgery. Five-year PFS was 38% (95% confidence interval [CI], 21-69), with a median PFS of 26 months. Five-year OS was 46% (95% CI, 28-75), with a median OS of 36 months. Three-year PFS-OS for pts achieving PR/CR versus stable disease (SD)/PD to ICT were 49.8-57% versus 43.2-53%, respectively. Three-year PFS for patients achieving major volumetric partial response (≥80% reduction of initial tumour volume, major partial volumetric response [mPRv]) versus non-mPRv were 82% versus 28% and 3-year OS were 92% versus 36% (p value 0.010 and 0.029, respectively). The ORR to ICT was 54% and 60% across all histotypes and in the sinonasal undifferentiated carcinoma (SNUC) subpopulation, respectively, with 6/15 SNUCs (40%) achieving mPRv. CONCLUSION: Treatment of advanced sinonasal cancer with histology-driven ICT followed by (CT)RT in responsive patients was feasible. Overall, these findings suggest a possible role of ICT as the primary approach in newly diagnosed, resectable sinonasal tumours-especially SNUC-to select patients with favourable prognosis. Histology heterogeneity limits generalisation of trial results.

Sinonasal Malignancies Involving the Frontal Sinus: A Mono-Institutional Experience of 84 Cases and Systematic Literature Review.

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.

Surgical Approaches for Possible Positions of an Olfactory Implant to Stimulate the Olfactory Bulb.

INTRODUCTION: Current scientific developments seem to allow for an "olfactory implant" in analogy to cochlear implants. However, the position and surgical approaches for electrical stimulation of the olfactory system are unclear. METHODS: In a human anatomic cadaver study, we investigated different endoscopic approaches to electrically stimulate the olfactory bulb (OB) based on the following considerations: (1) the stimulating electrode should be close to the OB. (2) The surgical procedure should be as non-invasive and safe as possible and (3) as easy as possible for an experienced ENT surgeon. RESULTS: In summary, the endoscopic intracranial positioning of the electrode via a widened ostium of the fila olfactoria or a frontal sinus surgery like a Draf IIb procedure is a good option in terms of patients' risk, degree of difficulty for ENT surgeons, and position to the OB. Endoscopic intranasal positioning appeared to be the best option in terms of patient risk and the degree of difficulty for ENT surgeons. Although a bigger approach to the OB using a drill and the combined intranasal endoscopic and external approach enabled a close placement of the electrode to the OB, they do not seem relevant in practice due to their higher invasiveness. CONCLUSION: The study suggested that an intranasal positioning of a stimulating electrode is possible, with placements beneath the cribriform plate, extra- or intracranially, applying elegant surgical techniques with low or medium risk to the patient and a close placement to OB.