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.

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.

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.

Medial femoral condyle free flap in combination with paramedian forehead flap for total/subtotal nasal reconstruction: Level of evidence: IV (therapeutic studies): Level of evidence: IV (therapeutic studies).

BACKGROUND: The nose is a functionally complex organ with also a critical role in aesthetics. For reconstruction of full thickness nasal defects, multiple stages are needed and there is risk for resorption resulting in residual deformity. The aim of this report was to develop and evaluate a new method for full thickness total/subtotal nose reconstruction using the medial femoral condyle free flap (MFCFF) in combination with a paramedian forehead flap. METHODS: Between November 2015 and January 2018, eight patients (four males, four females) mean age 52 years (range 40-73 years) undergoing a total/subtotal nasal excision and subsequential reconstruction with MFCFF plus paramedian forehead flap were enrolled. Six cases were squamous cell carcinomas while two were basal cell carcinomas. The MFCFF was stabilized, with the periosteum as inner layer, with plates and a paramedian forehead flap was used as external skin coverage. All patients were evaluated for with postoperative nasal endoscopy and CT scan. A postoperative questionnaire was given 6 months after surgery. RESULTS: The mean MFCFF size was 2-3.8 cm × 2.25-2.5 cm with a mean pedicle length of 6.3 cm (range 4.1-9.4 cm). The postoperative period was uneventful. The mean follow-up was 16 months, no bone displacement or resorption was observed at the CT scan, no evidence of nasal stenosis occurred. All patients had a satisfying aesthetic evaluation and a good subjective nasal function. CONCLUSIONS: In this series, the MFCFF in combination with the paramedian forehead flap appeared to provide a valid subtotal nose reconstruction, allowing for the recreation of all the three nasal layers and maintaining the nose projection and airway patency in the long term.

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.

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.

Thyroglossal Duct Cyst at the Base of Tongue: The Emerging Role of Transoral Endoscopic-Assisted Surgery.

Cystic lesions involving the tongue base are rare, generally presenting in pediatric patients, and they may encompass different pathologies such as ranula, lingual ectopic thyroid, thyroglossal duct cyst (TDC), dysontogenetic cysts, benign, and malignant tumors.This paper describes the case of a 19-year-old girl with phonation impairment and mild dysphagia due to limited tongue protrusion and movements. Radiologic examinations revealed a bulky cystic lesion at the base of tongue with displacement of extrinsic lingual muscles. A minimally invasive transoral removal of the mass was performed under the assistance of the endoscopic system. The histopathologic analysis confirmed the diagnosis of intralingual TDC. After 2 years of clinical and radiologic follow-up, no recurrence of disease was observed and the patient is completely asymptomatic.The present experience suggests that the endoscopic-assisted transoral removal of intralingual TDC can be proposed as a safe and effective procedure, alternative to traditional transcervical surgery as well as to transoral robotic surgery, leading to very appealing cosmetic results and encouraging functional outcomes in terms of phonation and swallowing. Preoperative radiologic examinations should be performed for an accurate diagnosis and appropriate selection of patients.

Endoscopic-assisted transoral-transpharyngeal approach to parapharyngeal space and infratemporal fossa: focus on feasibility and lessons learned.

The parapharyngeal space (PPS) is a challenging anatomical region, rich in vascular and nervous vital structures. Surgery is considered the treatment of choice for the majority of PPS lesions. Herein, we present a retrospective evaluation on ten patients with various types of lesions of the parapharyngeal and infratemporal fossa (ITF) regions operated on via an endoscopic-assisted transoral-transpharyngeal approach (EATTA), focusing on feasibility and safety. A retrospective evaluation of patients treated by means of EATTA to PPS and/or ITF lesions was carried out. The clinical records of patients who were operated on with EATTA for PPS and/or ITF lesions between March 2009 and October 2015 at two referral centres were reviewed and the intra-operative and post-operative complications were analysed. Ten patients who underwent EATTA on the PPS and ITF were included in this series. The procedure was performed in six patients for tumour removal, in three patients for diagnostic purposes and in one patient for pain control. No major complications occurred. No conversion to external approach was required. We observed only two minor complications which were promptly solved. No dysphagia or other problems during the food intake were observed in our series. One day after surgery all patients, except one, referred a value of VAS minor than 4. To date, no evidence of disease recurrence has been assessed in all six oncological cases. Although preliminary, our experience seems to demonstrate the feasibility and safety of EATTA when properly planned and performed.

Endoscopic Treatment of Ewing Sarcoma of the Sinonasal Tract.

The extra-skeletal form is an unusual type of Ewing sarcoma (ES) arising from soft tissue and in the literature there are reports of less than 50 patients describing the tumor in the paranasal sinuses and skull base. The histological diagnosis is crucial to plan the correct treatment and the molecular confirmation is mandatory in equivocal patients. A multimodality treatment with chemotherapy, surgery and radiotherapy improved the outcomes of these diseases during the last decades and a free-margin resection with the endoscopic transnasal technique is one of the most recent ways to manage these pathologies in selected patients, reducing the morbidities of the external approaches and preserving the quality of life of the patient.Here, the authors present the first patient of primary sinonasal ES free from disease after 5 years of follow-up and treated with an endoscopic endonasal approach and a second patient of sinonasal metastases of ES treated with and endoscopic transnasal approach.

Non-intestinal type sinonasal cancers and exposure to occupational carcinogens: a case-control study. / Tumori nasosinusali diversi da adenocarcinoma di tipo intestinale ed esposizione a cancerogeni professionali: uno studio caso-controllo.

BACKGROUND: Sinonasal cancers are rare, often fatal, tumors with a very high proportion of cases attributable to occupational exposures. The relevance of different carcinogens deeply varies among histological subtypes, with intestinal type adenocarcinomas (ITAC) characterized by a very large proportion of workers exposed to wood dust. The role of occupation in the etiology of other histotypes is less clear and more disputed, with authors questioning the possible occupational origin of non-ITAC cancers. METHODS: We conducted a hospital-based case-control study on 50 consecutives non-ITAC cancers and 50 controls, in Varese, Italy. Relative risks for previous exposure to carcinogens (any or single agent, i.e. wood/leather dust, solvents, metals) were calculated by multivariate logistic regression models adjusted for age, gender, smoking habits and residence (within or outside the Lombardy region). RESULTS: Having been exposed to any occupational carcinogen carried an OR of 3.04 (95%CI: 0.91-10.21). Considering single carcinogens, we observed no increased risk for wood dust exposure (OR=1.02, 95%CI: 0.21-4.94), while a large effect associated with previous exposure to other recognized carcinogens (leather dust, solvents or metals) appeared: OR=7.01 (95%CI: 1.51-32.8). DISCUSSION: Our results highlighted the importance of properly considering sinonasal cancers histological subtypes when investigating the role of occupational carcinogens. Grouping together all sinonasal cancers may end up in underestimating the role of wood in ITAC etiology as well as the relevance of other occupational exposures for non-ITAC tumors. All sinonasal cancers deserve a thorough investigation of the occupational history.

Treatment strategies for primary early-stage sinonasal adenocarcinoma: A retrospective bi-institutional case-control study.

OBJECTIVE: To investigate different treatment strategies for primary early-stage (pT1-T2) sinonasal adenocarcinomas. METHODS: Retrospective case-control study. From 2000 to 2011, 61 cases were radically resected using an endoscopic endonasal approach. Surgery as a single treatment modality was adopted for 33 patients (study group) while it was followed by postoperative radiotherapy (poRT) in 28 patients (control group). RESULTS: Median follow-up was 61 and 67 months for the study and control group respectively. Patients were stratified according to the pT classification and no statistically significant differences were found in terms of Overall (OS) and Recurrence-free (RFS) survival. When analyzing the high-grade tumors (47 cases), statistically significant differences were observed between the control and study groups both in terms of OS (90.5% ± 6.5% versus 57.6% ± 15.4%, P = 0.03) and RFS (92.3% ± 7.39% versus 80.2% ± 8.88%, P = 0.05). Using multivariate analysis, OS was independently determined by poRT (Hazard Ratio = 0.16; P = 0.03) thus confirming its protective role for high-grade adenocarcinomas. CONCLUSION: Our preliminary results suggest that endoscopic endonasal surgery could be used as a single treatment modality for primary early-stage low-grade sinonasal adenocarcinoma, resected with negative margins. Surgery followed by poRT offers the best treatment strategy not only for advanced-stage lesions but also for high-grade adenocarcinomas, regardless of the stage of disease at presentation.

Transorbital endoscopic assisted resection of a superior orbital fissure cavernous haemangioma: a technical case report.

OBJECTIVES: Superior orbital fissure and orbital apex lesions are challenging to manage, regardless of the approach chosen, due to the potential morbidity. The objectives of this study are to describe an innovative, minimally invasive surgical approach addressing this critical area and to discuss its indications and outcomes. SUBJECT: A young patient presented with visual disturbances (reduction of color discrimination, central scotoma) and mild exophthalmos owing to the presence of a right orbital apex cavernous haemangioma with superior orbital fissure invasion. METHODS: The lesion was removed via a minimally invasive, neuronavigated, transorbital superior eyelid endoscopic-assisted approach. MAIN OUTCOME MEASURES: Technical feasibility and safety, early and late complications, length of hospitalization time and follow-up data were collected and analyzed. RESULTS: The lesion was radically resected minimizing the surgical morbidity and hospitalization time for the patient and with encouraging functional and cosmetic outcomes. No recurrences were observed 1 year after surgery. CONCLUSIONS: The endoscopic-assisted transorbital approach should be considered a safe and effective option that can be applied in the treatment of lesions affecting such complex anatomical regions, as it offers excellent visualization of the surgical field, acceptable sequelae and reduced morbidity in relation to the traditional transcranial/transfacial approaches. Further studies and larger case series are needed in order to validate the reproducibility and range of applications of this surgical technique.

Palatovaginal (pharyngeal) artery: clinical implication and surgical experience.

The palatovaginal or pharyngeal artery is a small branch of the internal maxillary artery supplying the nasopharynx. Bleeding from this artery is exceptional and only one case of traumatic epistaxis from this artery has been reported previously. We report a case of a 66-year-old male presenting with right recurrent posterior epistaxis. Endoscopic dissection of the pterygopalatine fossa and direct visualization of the palatosphenoidal canal permitted to identify the origin of bleeding, and coagulation of the pharyngeal artery solved the epistaxis. Although rare, intractable posterior epistaxis may arise from the pharyngeal artery. The anatomical knowledge of this artery and of the palatosphenoidal canal is of outmost importance in endoscopic transpterygoid and nasopharyngeal procedures, to identify the vidian canal, evaluate nasopharyngeal cancer spread in the pterygopalatine fossa, reduce bleeding during surgery of the nasopharynx, and harvest adequately the pedicle of the nasoseptal flap.

The "great imitator": IgG4-related disease of the oral cavity. Two case reports and scoping review.

This study aimed to review the lesser-known intraoral manifestations of immunoglobulin G4-related disease (IgG4-RD). In this paper we report an unprecedented case of oral IgG4-RD mimicking angiolymphoid hyperplasia with eosinophilia (ALHE), and another case presenting as plasma cell gingivitis. We then performed a scoping review of published cases of IgG4-RD involving the oral cavity. The following data were collected for each case: age, sex, intraoral site(s) involved, clinical appearance, imaging features, serum IgG4 values, histopathology, treatment, and follow-up duration. Fifty-one cases of oral IgG4-RD were published in literature. The hard palate and jaw bones were the two main locations reported, while the histological identification of a IgG4/IgG plasma cells ratio ≥40% was fundamental for diagnosis. Conversely, the pathological features of storiform fibrosis and obliterative phlebitis were not common. Future reports regarding oral IgG4-RD should report clear adherence to the recognized international diagnostic criteria of the disease.

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.

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 vaccination strategies based on optimal stimulation of CD4+ T helper cells for the treatment of oral squamous cell carcinoma.

Oral Squamous Cell Carcinoma (OSCC) is the most common malignant tumor of the oral cavity. Despite recent advances in the field of oral cancer therapy, including the introduction of immunotherapeutic approaches, the 5-year survival rate remains steadily assessed around 50%. Thus, there is an urgent need for new therapeutic strategies. After the characterization of the immune phenotype of three human OSCC cell lines (CAL-27, SCC-25, and SCC-4) and one mouse OSCC cell line (MOC2) showing their similarities to resected patient tumors, we explored for the first time an experimental preclinical model of therapeutic vaccination with mouse OSCC MOC2 cell line stably expressing MHC class II antigens after CIITA gene transfection (MOC2-CIITA). Mice injected with MOC2-CIITA reject or strongly retard tumor growth; more importantly, vaccinated animals that fully reject MOC2-CIITA tumors display anti-tumor immunological memory protective against challenge with parental MOC2 tumor cells. Further experiments of adoptive cell transfer or in vivo cell depletion show that both CD4+ and CD8+ T lymphocytes prove fundamental in tumor rejection. This unprecedented approach for oral cancer opens the way for possible future translation of novel immunotherapeutic strategies to the human setting for the treatment of this tumor.

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.