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.

360 Degrees Endoscopic Access to and Through the Orbit.

The treatment of pathologies located within and surrounding the orbit poses considerable surgical challenges, due to the intricate presence of critical neurovascular structures in such deep, confined spaces. Historically, transcranial and craniofacial approaches have been widely employed to deal with orbital pathologies. However, recent decades have witnessed the emergence of minimally invasive techniques aimed at reducing morbidity. Among these techniques are the endoscopic endonasal approach and the subsequently developed endoscopic transorbital approach (ETOA), encompassing both endonasal and transpalpebral approaches. These innovative methods not only facilitate the management of intraorbital lesions but also offer access to deep-seated lesions within the anterior, middle, and posterior cranial fossa via specific transorbital and endonasal corridors. Contemporary research indicates that ETOAs have demonstrated exceptional outcomes in terms of morbidity rates, cosmetic results, and complication rates. This study aims to provide a comprehensive description of endoscopic-assisted techniques that enable a 360° access to the orbit and its surrounding regions. The investigation will delve into indications, advantages, and limitations associated with different approaches, while also drawing comparisons between endoscopic approaches and traditional microsurgical transcranial approaches.

Marsupialization as an alternative to reconstruction in endoscopic skull base surgery. How I do it.

BACKGROUND: To treat extradural solid-cystic lesions of the ventral skull base, a pedicled nasoseptal flap (NSF) maintains patency of the marsupialized cavity and prevents restenosis and cyst recurrence. METHODS: The authors provide a step-by-step description of the surgical technique valid in different lesions of the skull base, all treated via the endoscopic endonasal approach (EEA). The application is demonstrated by an operative video. CONCLUSION: In selected lesions, endoscopic marsupialization using an NSF ensures drainage and ventilation of the surgical cavity. Re-epithelialization provided by a pedicled flap is a viable alternative to multilayer skull base reconstruction.

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.

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.

Molecular Biomarkers in Sinonasal Cancers: New Frontiers in Diagnosis and Treatment.

PURPOSE OF REVIEW: Sinonasal tumors are rare and heterogeneous diseases which pose challenges in diagnosis and treatment. Despite significant progress made in surgical, oncological, and radiotherapy fields, their prognosis still remains poor. Therefore, alternative strategies should be studied in order to refine diagnosis and improve patient care. RECENT FINDINGS: In recent years, in-depth molecular studies have identified new biological markers, such as genetic abnormalities and epigenetic variations, which have allowed to refine diagnosis and predict prognosis. As a consequence, new histological entities have been described and specific subgroup stratifications within the well-known histotypes have been made possible. These discoveries have expanded indications for immunotherapy and targeted therapies in order to reduce tumor spread, thus representing a valuable implementation of standard treatments. Recent findings in molecular biology have paved the way for better understanding and managing such rare and aggressive tumors. Although further efforts need to be made in this direction, expectations are promising.

Mild/Moderate Asthma Network in Italy (MANI): a long-term observational study.

OBJECTIVE: The prevalence of asthma in Italy is estimated to be around 4%; it affects approximately 2,000,000 citizens, and up to 80-90% of patients have mild-to-moderate asthma. Despite the clinical relevance of mild-to-moderate asthma, longitudinal observational data are very limited, including data on disease progression (worsening vs. improvement), the response to treatment, and prognosis. Studies are needed to develop long-term, observational, real-life research in large cohorts. The primary outcomes of this study will be based on prospective observation and the epidemiological evolution of mild and moderate asthma. Secondary outcomes will include patient-reported outcomes, treatments over time, disease-related functional and inflammatory patterns, and environmental and life-style influences. METHODS: This study, called the Mild/Moderate Asthma Network of Italy (MANI), is a research initiative launched by the Italian Respiratory Society and the Italian Society of Allergology, Asthma and Clinical Immunology. MANI is a cluster-based, real world, cross-sectional, prospective, observational cohort study that includes 20,000 patients with mild-to-moderate asthma. (ClinicalTrials.gov Identifier: NCT04796844). RESULTS AND CONCLUSION: Despite advances in asthma care, several research gaps remain to be addressed through clinical research. This study will add important new knowledge about long-term disease history, the transferability of clinical research results to daily practice, the efficacy of currently recommended strategies, and their impact on the burden and evolution of the disease. ABBREVIATIONS: MANI:Mild/Moderate Asthma Network of ItalySANI:Severe Asthma Network ItalyGINA:Global Initiative for AsthmaSABA:short acting ß2-agonistsICS:inhaled corticosteroidsCRF:Case Report Form.

Symptomatic ecchordosis physaliphora of the upper clivus: an exceedingly rare entity.

OBJECTIVE: This paper highlights the management of 5 patients affected by symptomatic ecchordosis physaliphora (EP), treated via endoscopic endonasal transsphenoidal-transclival approach and contextual multilayer skull base reconstruction. A detailed analysis of each case is provided, along with the review of the current body of literature. METHODS: A retrospective review of patients treated by means of endoscopic endonasal approach for EP from 2010 to 2020 in the Otolaryngology and Neurosurgery Departments of a tertiary-care referral center for endoscopic skull base surgery was analyzed. Only adult patients with a definitive histopathological and immunohistochemical diagnosis of EP were included in the study. A systematic literature review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed for EP. RESULTS: Five cases of EP were retrieved and included in the study. Four patients presented with CSF leakage: in two cases after minor head trauma, in one case with associated bacterial meningitis, and in one case as only referred symptom. One patient complained diplopia due to VI cranial nerve palsy. No complications or recurrences of the disease were observed after a median follow-up of 37.2 months (range, 18-72 months). A total of 27 studies were identified with the systematic literature review, encompassing 30 patients affected by symptomatic EP who were addressed to surgical treatment. Twenty-five patients underwent complete surgical removal of the EP, while in 5 cases, only subtotal resection was performed. CONCLUSIONS: EP might result in a "locus minoris resistentiae" of the skull base, predisposing, in rare cases, to CSF leakage and meningitis, spontaneously or after minor trauma. In cases of symptomatic EP, endoscopic endonasal transsphenoidal-transclival approach represents a safe and effective technique for both EP resection and contextual skull base reconstruction.

Emergency endovascular treatment of cavernous internal carotid artery acute bleeding with flow diverter stent: a single-center experience.

BACKGROUND AND OBJECTIVE: To describe our single-center experience in the treatment of cavernous internal carotid artery (ICA) acute bleeding with flow diverter stent (FDS), as a single endovascular procedure or combined with an endoscopic endonasal approach. METHODS: We analyze a case series of 5 patients with cavernous ICA acute bleeding, i.e., 3 iatrogenic, 1 post-traumatic, and 1 erosive neoplastic. After an immediate nasal packing to temporarily bleeding control, patients underwent digital subtraction angiography (DSA) to identify the site of the ICA injury. A concomitant balloon occlusion test (BOT) was performed, to exclude post-occlusive ischemic neurological damage. An FDS was placed with parallel intravenous infusion of abciximab in 3 cases and tirofiban in 2 cases. In two patients, an innovative "sandwich technique" combining the endovascular reconstruction with an extracranial intrasphenoidal cavernous ICA resurfacing with autologous flaps or grafts by endoscopic endonasal approach was performed. RESULTS: No patient had periprocedural ischemic-hemorrhagic complications. All patients had a regular clinical evolution, without general complications or new onset of focal neurological deficits. No further bleeding occurred in 3 patients, while 2 cases experienced a mild rebleeding in a period ranging from 5 to 15 days after the endovascular procedure. In these two cases, we proceeded with an endoscopic endonasal procedure to resurface the exposed ICA wall in the sphenoid sinus. CONCLUSIONS: Although the treatment of choice for cavernous ICA acute bleeding remains the occlusion of the injured vessel, in cases of poor hemodynamic compensation at the BTO, the endovascular FDS emergency placement can be effective. A combined endoscopic endonasal technique to support the extracranial side of the vessel using autologous flaps or grafts can be performed to prevent the risk of rebleeding.

Performing otolaryngological outpatient consultation during the Covid-19 pandemic.

BACKGROUND: The Covid-19 pandemic has had a profound impact on the Otolaryngology outpatient clinical practice, which is at high risk of respiratory viral transmission due to the close contact between the examiner and the patient's airway secretions [1]. Moreover, most otolaryngological procedures, including oropharyngoscopy, generate droplets or aerosols from high viral shedding areas [1]. Thus, only non-deferrable consultations were performed in the outbreak's acute phase. Along with the re-opening of elective clinical services and the impending second wave of the outbreak, a reorganization is necessary to minimize the risk of nosocomial transmission [1]. METHODS: This video (Video 1) shows how to safely conduct an outpatient Otorhinolaryngological consultation, focusing on complete ear, nose and throat examination, according to evidences from the published literature and Otolaryngological societies guidelines [2,3]. RESULTS: After telephonic screening, patients reporting Covid-19 symptoms or closecontact with a Covid-19 case within the last 14 days are referred to telehealth services [1-3]. To avoid crowding, the patient is admitted alone, after body temperature control, except for underage or disabled people [1]. The waiting room assessment must guarantee a social distance of 6 ft [1-3]. The consultation room is reorganized into two separate areas (Fig. 1): 1) a clean desk area, where an assistant wearing a surgical mask and gloves, handles the patient's documentation and writes the medical report, keeping proper distance from the patient, and 2) a separate consultation area, where the examiner, equipped with proper personal protective equipment (Fig. 2) [3,4], carries out the medical interview and physical examination. Endoscopic-assisted ear, nose and throat inspection using a dedicated monitor allows the examiner to maintain an adequate distance from the patient throughout the procedure while providing an optimal view (Figs. 3-6) [3]. Recent evidence shows that nasal endoscopy does not increase droplet production compared to traditional otolaryngological examination [5]. When necessary, nasal topic decongestion and anesthesia must be performed using cottonoids rather than sprays [3]. The patient keeps the nose and mouth covered throughout the consultation, lowering the surgical mask on the mouth for nasal endoscopy and removing it only for oropharyngoscopy. After the consultation, the doffing procedure must be carried out carefully to avoid contamination [4]. All the equipment and surfaces must undergo high-level disinfection with 70% alcohol or 0.1% bleach solutions [3]. Proper room ventilation must precede the next consultation [3]. CONCLUSIONS: The hints provided in this video are useful to ensure both patient and examiner safety during Otolaryngological outpatient consultations and to reduce SARS-CoV-2 transmission.

Real-life assessment of chronic rhinosinusitis patients using mobile technology: The mySinusitisCoach project by EUFOREA.

BACKGROUND: Chronic rhinosinusitis (CRS) is a chronic inflammatory disease associated with a substantial personal and socioeconomic burden. Monitoring of patient-reported outcomes by mobile technology offers the possibility to better understand real-life burden of CRS. METHODS: This study reports on the cross-sectional evaluation of data of 626 users of mySinusitisCoach (mSC), a mobile application for CRS patients. Patient characteristics of mSC users were analysed as well as the level of disease control based on VAS global rhinosinusitis symptom score and adapted EPOS criteria. RESULTS: The mSC cohort represents a heterogeneous group of CRS patients with a diverse pattern of major symptoms. Approximately half of patients reported nasal polyps. 47.3% of all CRS patients were uncontrolled based on evaluation of VAS global rhinosinusitis symptom score compared to 40.9% based on adapted EPOS criteria. The impact of CRS on sleep quality and daily life activities was significantly higher in uncontrolled versus well-controlled patients. Half of patients had a history of FESS (functional endoscopic sinus surgery) and reported lower symptom severity compared to patients without a history of FESS, except for patients with a history of more than 3 procedures. Patients with a history of FESS reported higher VAS levels for impaired smell. CONCLUSION: Real-life data confirm the high disease burden in uncontrolled CRS patients, clearly impacting quality of life. Sinus surgery improves patient-reported outcomes, but not in patients with a history of more than 3 procedures. Mobile technology opens a new era of real-life monitoring, supporting the evolution of care towards precision medicine.

Changes in the use of Otorhinolaryngology Emergency Department during the COVID-19 pandemic: report from Lombardy, Italy.

PURPOSE: This paper aims to report the impact of COVID-19 outbreak on Emergency Ear nose and Throat (ENT) activity, in Lombardy (Italy), during COVID-19 pandemic. METHODS: The number of accesses to Emergency Department requiring ENT consultations between February 21st and May 7th, 2020, was retrospectively collected, along with the conditions treated. Data were stratified in 1-week time spans, to evaluate the evolving trends during the on-going epidemic and a comparison with the two previous years was performed. RESULTS: A significant reduction in the number of consultations performed during the pandemic was observed, as high as - 91% compared to the same period of 2018. CONCLUSION: Multiple reasons can explain such a reduction of Emergency ENT consultations, not least the fear of potentially being infected by SARS-CoV-2 by while accessing the hospital. The analysis performed might be useful as a starting point for a future reorganization of first aid consultations once the epidemic will be resolved.

Strategies to overcome limitations in Otolaryngology residency training during the COVID-19 pandemic.

PURPOSE: The COVID-19 pandemic has produced an unequaled human crisis forcing a radical reorganization in the healthcare system. Otolaryngologists are at high risk of exposure, and changes in medical and surgical activities have reduced the learning opportunity for residents and fellows. We believe that even during COVID-19 crisis it is mandatory to guarantee an optimal training, and here, we propose some strategies, based on our experience, to further increase our trainees' learning curve. METHODS: We asked our trainees to fill out an electronic survey about several aspect of their training: a first section focused on the reduction of clinical activities and the perceived impact of the pandemic on residents' skills; the second part outlined the type of attended training activity and the perceived benefit. RESULTS: Surgical training has been reported by our residents as the activity perceived to be the most contracted during the pandemic. According to residents' opinion the most useful activities were dissection (n = 8, 53.4% residents) and online journal clubs/webinars (n = 7, 46.6% of residents). Residents' suggestions included actively participating to tracheostomy procedures on SARS-CoV-2 positive patients, attending lessons held by senior consultants on basic ENT topics and promoting collegial discussion of inpatient clinical cases. CONCLUSION: Building on this dramatic experience, we must be ready for a global restructuring of the residency program to provide an adequate trainee education for the future surgeons.

Radiological and endoscopic findings in patients undergoing revision endoscopic sinus surgery.

Over the last three decades, functional endoscopic sinus surgery (FESS) has become one of the most common surgical techniques, with significant data supporting its efficacy in treating chronic rhinosinusitis (CRS). However, despite this initial published success rate, approximately 10-15% of them will require a subsequent revision surgery. The severity of the disease, the comorbidities and the anatomical variation that are not addressed adequately in the primary surgery, are considered the main factors that cause the failure of the primary surgery. Our objective is to report anatomical findings that may contribute to recurrent disease to improve the success rate in the primary surgery. PATIENTS AND METHODS: A prospective cross sectional study was conducted for 24 patients presenting for revision functional endoscopic sinus surgery (FESS). Lund-kennedy and Lund-Mackay score systems, pre and intraoperative CT scan and endoscopic assessments utilized, respectively, to delineate the causes of the primary surgery's failure. The most common finding was persistent frontoethmoidal cell, anterior and posterior ethmoid cell: 81.2%, 72.9%, 70.8%, respectively. Bony osteitis and scarred frontal recess were visible in 66.7%. Recirculation phenomena, resected concha bullosa and persistent Onodi cell, were the least noticeable findings: 6.25%, 8.3%, 8.30% consecutively CONCLUSIONS: The recurrence of the CRS that needs revision FESS is multifactorial in etiology ranging from sever mucosal disease to anatomical variations that is not addressed precisely in primary surgery. Trials of studies with a larger number of patient series comparing the anatomical variations that impact on recurrence of CRS with and without polyp are required.

Comprehensive analysis of HPV infection, EGFR exon 20 mutations and LINE1 hypomethylation as risk factors for malignant transformation of sinonasal-inverted papilloma to squamous cell carcinoma.

Different risk factors are suspected to be involved in malignant transformation of sinonasal papillomas and include HPV infection, tobacco smoking, occupational exposure, EGFR/KRAS mutations and DNA methylation alterations. In our study, 25 inverted sinonasal papillomas (ISPs), 5 oncocytic sinonasal papillomas (OSP) and 35 squamous cell carcinomas (SCCs) from 54 patients were genotyped for 10 genes involved in EGFR signalling. HPV-DNA detection was performed by in-situ hybridisation and LINE-1 methylation was quantitatively determined by bisulphite-pyrosequencing. High-risk HPV was observed only in 13% of ISP-associated SCC and in 8% of de novo-SCC patients. EGFR mutations occurred in 72% of ISPs, 30% of ISP-associated SCCs and 17% of de novo-SCCs. At 5-year follow-up, SCC arose in only 30% (6/20) of patients with EGFR-mutated ISPs compared to 76% (13/17) of patients with EGFR-wild-type ISP (p = 0.0044). LINE-1 hypomethylation significantly increased from papilloma/early stage SCC to advanced stage SCC (p = 0.03) and was associated with occupational exposure (p = 0.01) and worse prognosis (p = 0.09). In conclusion, our results suggest that a small subset of these tumours could be related to HPV infection; EGFR mutations characterise those ISPs with a lower risk of developing into SCC; LINE-1 hypomethylation is associated with occupational exposure and could identify more aggressive nasal SCC.

Transsphenoidal surgery for pituitary adenomas in pediatric patients: a multicentric retrospective study.

INTRODUCTION: Pediatric pituitary adenomas are rare lesions. Incidence is reported between 1 and 10% of all childhood brain tumors and between 3 and 6% of all surgically treated adenomas. Although pituitary adenomas present with symptoms of hormone hypersecretion or neurological disruptions secondary to mass effect, they are almost constantly benign. Characteristics of patients may vary in different studies according to age, gender, size of adenoma, hormonal activity, and recurrence rates. METHODS: Data on consecutive pediatric patients who were operated for pituitary adenoma with endoscopic endonasal transsphenoidal surgery (EETS) and transsphenoidal microsurgery (TMS) in the Department of Neurosurgery, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey, in the Neurosurgical Unit of the San Matteo Hospital, Pavia, Italy, and in the Division of Neurological Surgery Department of Biotechnology and Life Sciences, University of Insubria-Varese, ASST Sette Laghi, Ospedale di Circolo e Fondazione Macchi, Varese, Italy, between July 1997 and May 2018, were analyzed. Twenty-seven patients (11 males and 16 females), who were 18 years old or younger at the time of surgery, were included in the study. Medical records, images, and operative notes of patients were retrospectively reviewed. RESULTS: There were 16 females (59.3%) and 11 males (40.7%). Mean age was 15.3 ± 3.3 (4-18). Thirty-two surgical procedures were performed for 27 patients (6 children required second operation). Thirteen patients (48.14%) had Cushing's disease (CD), 5 patients (18.5%) had growth hormone (GH)-secreting adenoma, 5 patients (18.5%) had prolactinoma, and 4 patients (14.8%) had non-functional adenoma. Twenty-two patients (81.4%) met remission criteria, and 5 patients (18.5%) did not meet remission criteria. Four patients met remission criteria after the second operation. CONCLUSION: Transsphenoidal approach affords effective release of mass effect and not only restoration but also perpetuation of normal endocrine functions in the majority of pediatric pituitary adenoma patients. Satisfactory results are reported with both EETS and TMS in the literature. Despite the technical difficulties in pediatric age, transsphenoidal resection of adenoma is still the mainstay treatment that provides cure in pediatric patients.

Endoscopic Endonasal Approaches for Treatment of Craniovertebral Junction Tumours.

Tumours involving the craniovertebral junction (CVJ) are challenging because of their local invasiveness and high recurrence rates, as well as their proximity to critical neurovascular structures and the difficulty of reconstructing the resulting skull base defect at this site. Several surgical techniques are currently available to access these lesions, including the far lateral, extreme lateral, direct lateral, transcervical, transoral and transnasal approaches. In this paper, application of the endoscopic endonasal approach (EEA) in the treatment of CVJ tumours is analysed. The indications, contraindications, preoperative workup, step-by-step surgical technique, skull base reconstruction options and postoperative management are described. The advantages and limitations of the EEA are also discussed. Finally, a systematic review of the literature is provided to elucidate the levels of evidence supporting the use of the EEA in this field. Employment of this approach to the CVJ has contributed to high success rates in achieving gross total resection of tumours and improvement in neurological symptoms. Intraoperative and postoperative complication rates are acceptable, with cerebrospinal fluid leakage being the major concern (with a 17-25% incidence). Moreover, in comparison with traditional approaches to the CVJ, the EEA provides lower rates of postoperative dysphagia and respiratory complications. Use of the EEA for treatment of CVJ tumours appears to be a rational alternative to the conventional transoral, transcranial and transcervical approaches in selected cases. Multidisciplinary teamwork including different specialists-such as medical and radiation oncologists, radiologists, otorhinolaryngologists and neurosurgeons-is strongly recommended for the purpose of offering the best treatment strategy for the patient.

Frontal Sinus Preservation During Cerebrospinal Fluid Leak Repair.

BACKGROUND: To validate the repair of frontal sinus cerebrospinal fluid (CSF) leaks with preservation of frontal sinus drainage pathway (FSDP), independently of the approach used, and to establish the indications and limits of the endoscopic approach. METHODS: A retrospective evaluation of patients undergoing surgery for frontal sinus CSF leaks was performed. Demographics, indications for both endoscopic/combined endoscopic and open approaches, complications, methods for maintaining FSDP, and perioperative outcomes were examined. RESULTS: Fifty-three patients (average age 45 years) with frontal sinus CSF leaks were treated surgically from 2000 to 2018. All CSF leak repairs were successful at the 1st attempt with a mean follow-up of 76.8 months (range 4-227 months). Etiology was spontaneous (14), traumatic (26), and iatrogenic (13). In 17 patients, a purely endoscopic approach was performed, while an endoscopic endonasal orbital transposition procedure was added in 4 out of this group. In 23 patients, a combined endoscopic and osteoplastic procedure was employed, while in 13 patients a combined craniotomy and endoscopic procedure was performed. All frontal sinuses remained patent except for 2 cranialization patients. CONCLUSION: With contemporary endoscopic instrumentation and techniques, endoscopic closure of frontal sinus CSF leaks even in the far superolateral wall is feasible in selected patients. However, the surgeon should consider the option of combining an external approach when required. Preserving the FSDP should be the main aim regardless of the approach.

Septal branches of the anterior ethmoidal artery: anatomical considerations and clinical implications in the management of refractory epistaxis.

PURPOSE: Epistaxis is a commonly presenting complaint. In severe cases, nosebleeds may occur despite antero-posterior nasal packing and often in the absence of identifiable sources of bleeding. In such cases, epistaxis may occur from septal branches of the anterior ethmoidal artery (sbAEA). The purposes of this study are to highlight the clinical role of the sbAEA in different fields of endoscopic endonasal surgery and to evaluate the efficacy and safety of their selective endoscopic endonasal ligation in the management of refractory epistaxis. METHODS: A retrospective review was performed of all patients presenting with epistaxis who underwent endoscopic endonasal coagulation of sbAEA in three Italian tertiary-care referral centers between October 2010 and October 2017. RESULTS: A total of 30 patients met the inclusion criteria. Sixteen patients had never experienced nosebleeds before, while 14 patients recalled previous epistaxes. Seventeen patients were treated under local anesthetic, while 13 required general anesthesia. No intra- or post-operative complications were observed and none of the patients received nasal packing after the procedure. In all cases the coagulation was effective in controlling the bleeding, with only two relapses in the series (2/30, 6.7%). CONCLUSIONS: The sbAEA are of great interest in endoscopic endonasal surgery, both as surgical landmarks and as feeding vessels for a variety of pedicled nasal flaps. What is more, they can be crucial for the management of refractory epistaxis. Their selective endoscopic coagulation represents an effective and safe procedure in cases of difficult-to-control epistaxis from the upper nasal fossa, with several advantages over nasal packing.