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Human Papillomavirus (HPV) related Multiphenotypic Sinonasal Carcinoma (HMSC) is a rare tumor with features of both atypical squamous cell and adenoid cystic carcinoma, making diagnosis challenging. Approximately 80% of HMSC cases carries HPV type 33 followed by type 35. We present a patient with HMSC. Pathological classification was aided by immunohistochemistry (IHC). The presence of HPV-DNA was tested using PCR and HPV E6/E7 expression by RNA in situ hybridization (RNA ISH). Whole exome sequencing (WES) was used to identify somatic gene mutations and copy number alterations. A 55-year-old male presented with an HMSC in the right nostril. Histological examination showed a solid basaloid subtype with mucinous spaces and ductal structures. IHC showed positive staining for SOX-10, SMA, p40, p63, PanCK, CK8 and MYB. Diffuse positive staining for p16 was observed and PCR and RNA ISH indicated the presence of HPV type 35. The patient was treated with endoscopic surgery and radiotherapy and is currently alive and recurrence-free after 16 months of follow-up. WES revealed 38 somatic sequence variants and several chromosomal regions with copy number alterations, including a copy number gain at 6q23 where MYB is located. EP300, ZNF22, ZNF609 and LRIG3 are some of the genes whose mutations were indicated as probably pathogenic. We did not find mutations predictive for drug response according to the ESMO Scale for Clinical Actionability of Molecular Targets database. This is the first report of WES analysis of an HMSC, in this case associated with HPV type 35. The detected mutation in EP300 and the overexpression of MYB may serve as molecular targets for personalized therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cubides-Córdoba, Sánchez-Fernández, Mendoza-Pacas, Cabal, García-Marín, Lorenzo-Guerra, García-Velasco, Hermsen and Llorente.)

Background: Recurrent intestinal-type sinonasal adenocarcinoma (ITAC) can occur several years after primary treatment and with different histology. We aimed to clarify if such recurrences could be second primary tumors and to identify actionable mutations as targets for personalized treatment of recurrent ITAC., Methods: Twelve pairs of primary and recurrent ITAC were histologically examined and analyzed by next-generation sequencing., Results: Histological differences between primary and recurrent tumor pairs were observed in five cases. Frequent mutations included TP53, APC, TSC2, ATM, EPHA2, BRCA2, LRP1B, KRAS, and KMT2B. There was 86% concordance of somatic mutations between the tumor pairs, while four cases carried additional mutations in the recurrence., Conclusions: We found all cases to be clonal recurrences and not second primary tumors. Moreover, tumor pairs showed a remarkable genomic stability, suggesting that personalized treatment of a recurrence may be based on actionable molecular genetic targets observed in the primary tumor., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Introduction: The development and research of new technologies for identifying microorganisms, has allowed the identification of hitherto unknown bacteria. Auritidibacter ignavus is a newly described Gram-positive rod possibly associated with otitis, although its role as an etiologic agent in otitis is currently controversial., Methods: We report two cases of recurrent otitis in paediatric patients in which A. ignavus was isolated and review the previous cases reported in the literature., Results: All the isolates were identified as A. ignavus by proteomic and genomic methods. Both patients recovered from their symptoms., Conclusion: A. ignavus was recovered from ear discharges of paedriatic patients with chronic ear problems. All the cases previously reported in the literature were adults. More evidence is needed for the association between A. ignavus and otitis, since data regarding this species are still scarce., (Copyright © 2023 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: Salvage surgery is mandatory when regional persistence/recurrence after chemoradiation. The aim of this study is to describe the outcomes of salvage surgery., Methods: A retrospective study was conducted in patients with locally advanced head and neck squamous cell carcinoma that were primarily treated with chemorradiation and underwent salvage neck dissection (ND) with suspected recurrent/persistent nodal disease. All patients had a response evaluation at 12 weeks through clinical examination and computed tomography-positron emission tomography. Decision for ND was taken in case of suspected persistence or if there was suspicion of recurrence, histologically confirmed., Results: There were 40 patients included. 32/40 (80%) ND were done because of confirmed/suspected persistence and 8/40 (20%) were done because of recurrences. Persistence was confirmed histologically in 14/32 (43.8%) cases and recurrence in 6/8 (75%) cases. Median survival from diagnosis was 39 months (95% CI 28.162-49.838). Significant differences were observed between patients who had viable tumour cells in the sample and those who did not, but the differences were only significant when only deaths due to tumour progression were considered (p = 0.014). 14/32 (43.8%) patients with suspected or confirmed persistence developed a recurrence after the ND and 3/8 (37.5%) patients with suspected or confirmed recurrence developed a new recurrence. New recurrences were more frequent in cases that had viable tumor in the specimen., Conclusions: Patients with nodal persistence/recurrence have a poor prognosis, even after salvage surgery. However, in a substantial number of patients the disease is controlled after ND, so it should be offer to these patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sinonasal teratocarcinosarcoma (TCS) is a rare tumor that displays a variable histology with admixtures of epithelial, mesenchymal, neuroendocrine and germ cell elements. Facing a very poor prognosis, patients with TCS are in need of new options for treatment. Recently identified recurrent mutations in SMARCA4 may serve as target for modern therapies with EZH1/2 and CDK4/6 inhibitors. Here, we present the first in vitro cell line TCS627, established from a previously untreated primary TCS originating in the ethmoid sinus with invasion into the brain. The cultured cells expressed immunohistochemical markers, indicating differentiation of epithelial, neuroepithelial, sarcomatous and teratomatous components. Whole-exome sequencing revealed 99 somatic mutations including SMARCA4 , ARID2 , TET2 , CDKN2A , WNT7A , NOTCH3 and STAG2 , all present both in the primary tumor and in the cell line. Focusing on mutated SMARCA4 as the therapeutic target, growth inhibition assays showed a strong response to the CDK4/6 inhibitor palbociclib, but much less to the EZH1/2 inhibitor valemetostat. In conclusion, cell line TCS627 carries both histologic and genetic features characteristic of TCS and is a valuable model for both basic research and preclinical testing of new therapeutic options for treatment of TCS patients.

Poorly differentiated sinonasal carcinomas (PDCs) are tumors that have a poor prognosis despite advances in classical treatment. Predictive and prognostic markers and new personalized treatments could improve the oncological outcomes of patients. In this study, we analyzed SOX2 and βIII-tubulin as biomarkers that could have prognostic and therapeutic impacts on these tumors. The cohort included 57 cases of PDCs: 36 sinonasal undifferentiated carcinoma (SNUC) cases, 13 olfactory neuroblastoma (ONB) cases, and 8 sinonasal neuroendocrine carcinoma (SNEC) cases. Clinical follow-up data were available for 26 of these cases. Sox2 expression was detected using immunohistochemistry in 6 (75%) SNEC cases, 19 (53%) SNUC cases, and 6 (46%) ONB cases. The absence of Sox2 staining correlated with a higher rate of recurrence ( p = 0.015), especially distant recurrence. The majority of cases showed βIII-tubulin expression, with strong positivity in 85%, 75%, and 64% of SNEC, ONB, and SNUC cases, respectively. Tumors with stronger βIII-tubulin expression demonstrated longer disease-free survival than those with no expression or low expression ( p = 0.049). Sox2 and βIII-tubulin expression is common in poorly differentiated sinonasal tumors and has prognostic and therapeutic utility.

Despite advances in surgery and radiotherapy, the overall prognosis of sinonasal intestinal-type adenocarcinoma (ITAC) is poor, and new treatment options are needed. Recent studies have indicated alterations in cellular signaling pathways that may serve as targets for modern inhibitors. Our aim was to evaluate the frequency of mTOR and ERK pathway upregulation in a retrospective series of 139 ITAC and to test the efficacy and mechanism of action of candidate targeted inhibitors in cell line ITAC-3. An immunohistochemical analysis on p-AKT, p-mTOR, p-S6, p-4E-BP1, and p-ERK indicated, respectively, a 68% and 57% mTOR and ERK pathway activation. In vitro studies using low doses of mTOR inhibitor everolimus and ERK inhibitor selumetinib showed significant growth inhibition as monotherapy and especially as combined therapy. This effect was accompanied by the downregulation of mTOR and ERK protein expression. Our data open a new and promising possibility for personalized treatment of ITAC patients.

Bovine tuberculosis (bTB) is a severe zoonotic disease that has major impacts on both health and the economy, and which has been subjected to specific eradication programmes in many countries for decades. This manuscript highlights the relevance of this disease in the context of the European Union (EU) and summarizes the epidemiological situation and the main tools (e.g. antemortem diagnostic tests, slaughterhouse surveillance, laboratories, comprehensive databases, etc.) used to control and eradicate bTB in the various EU countries with a focus on the situation in Spain. A comprehensive description of the specific bTB epidemiological situation in Spain is provided, together with an assessment of the evolution of different epidemiological indicators throughout the last decades. Moreover, the main features of the Spanish bTB eradication programme and its control tools are described, along with the studies carried out in Spain that have allowed the updating of and improvement to the programme over the years with the aim of eradication, which has been established for 2030., (© 2023. The Author(s).)

Objective: To characterize cell line CAE606 derived from a squamous cell carcinoma (SCC) of the external auditory canal (EAC) and to show its usefulness as a model for testing candidate therapeutic agents., Study Design: Preclinical translational research., Setting: Biomedical research institute., Methods: The cell line was initiated from a moderately differentiated T2N0M0 EAC SCC. We studied its histologic and genetic features as well as growth and invasion parameters. Sensitivity to cell CDK4/6 cell cycle inhibitor palbociclib was analyzed., Results: CAE606 cells expressed heavy molecular weight cytokeratin, p63, and vimentin. The population doubling time was 25.8 hours, and the cells showed fast collective cell migration in a wound-healing assay. Short tandem repeat analysis confirmed it to be derived from the primary tumor of the patient. Next-generation sequencing revealed alterations in cell cycle regulation genes, including inactivating mutations in CDKN2A and TP53 and high-level amplification of CCND1 and EGFR. CAE606 showed a strong decrease of phospo-Rb expression upon exposure to the CDK4/6 inhibitor palbociclib, causing significant growth inhibition with an IC 50 of 0.46 µM., Conclusion: This is the first report of a stable EAC SCC cell line. Its genetic features make it a useful tool for preclinical testing of new therapeutic agents for EAC SCC, particularly those targeting cell cycle regulation in combination with radio- and chemotherapy or other specific signaling pathway inhibitors., (© 2022 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Background: Surgical resection or radiotherapy (RT) are standard approaches for early-staged hypopharyngeal squamous cell carcinoma (HPSCC). Transoral laser microsurgery (TOLMS) seems to provide good oncological and functional results with few local complications. The aim of our study was to analyze the outcomes of TOLMS, with or without neck dissection or RT, in the treatment of HPSCC in a tertiary referral center., Methods: A retrospective study was conducted in patients with early T-category (T1-T2) HPSCC treated by TOLMS., Results: A total of 34 patients were included in the study. The series includes 17 (50%) T1 and 17 (50%) T2 classified tumors. The 5-year overall survival and disease-specific survival rates were 51% and 66%, respectively, with a 5-year local control rate of 92%. All patients reassumed oral diet and none of them had a tracheostomy at the end of the follow-up., Conclusions: TOLMS offers an effective treatment option in terms of oncologic control and function preservation in locally circumscribed HPSCC., (© 2022. The Author(s).)

Background: The purpose of this study was to evaluate p16, p53, EGFR, pEGFR protein expression and HPV infection as possible markers of tumor progression in a series of sinonasal inverted papilloma (SNIP) and sinonasal squamous cell carcinoma (SNSCC)., Methods: A series of 49 SNIP, 11 SNSCC associated with SNIP (SNIP-SNSCC) and 52 SNSCC not associated with SNIP were analyzed for p16, p53, EGFR, and phosphorylated EGFR (pEGFR) expression by immunohistochemistry. Human papillomavirus (HPV) infection status was evaluated by DNA-PCR. Results were correlated to clinical and follow-up data., Results: Reduced or loss of p16 expression was observed in 18% SNIP, 64% SNIP-SNSCC and 87% of SNSCC. Reduced or loss p16 staining in SNIP correlated with shorter recurrent SNIP-free follow-up. In contrast, p16 expression was not predictive of recurrent SNSCC in cases with SNIP-SNSCC and SNSCC. P53, EGFR, and pEGFR expression did not differ between the tumor groups, nor were they related to recurrent SNIP-free follow-up or recurrent SNSCC. Oncogenic HPV types 16 and 18 were detected in 5% of SNIP and 18% of SNIP-SNSCC, but not in SNSCC. There was no correlation between HPV infection and >70% p16 immunostaining., Conclusions: HPV infection appears to play a minor role in SNIP and SNSCC and p16 immunostaining does not appear a valid surrogate marker for HPV. However, reduced or loss p16 expression may have prognostic value as a risk marker for recurrent SNIP.

Caprine tuberculosis (TB) is a zoonosis caused by members of the Mycobacterium tuberculosis complex (MTBC). Caprine TB eradication programmes are based mainly on intradermal tuberculin tests and slaughterhouse surveillance. Different factors may affect the performance of the TB diagnostic tests used in caprine herds and, therefore, their ability to detect infected animals. The present study evaluates the effect of the fraudulent administration of two anti-inflammatory substances, dexamethasone and ketoprofen, on the performance of the TB diagnostic techniques used in goats, as well as the suitability of high performance liquid chromatography (HPLC) for their detection in hair samples. The animals ( n = 90) were distributed in three groups: (1) a group treated with dexamethasone ( n = 30); a second group treated with ketoprofen ( n = 30); and a third non-treated control group ( n = 30). Both dexamethasone and ketoprofen groups were subjected to intramuscular inoculation with the substances 48 h after the administration of bovine and avian purified protein derivatives (PPDs), that is, 24 h before the tests were interpreted. All the animals were subjected to the single and comparative intradermal tuberculin (SIT and CIT, respectively) tests, interferon-gamma release assay (IGRA) and P22 ELISA. The number of SIT test reactors was significantly lower in the dexamethasone ( p = 0.001) and ketoprofen ( p < 0.001) groups 72 h after the bovine PPD inoculation compared with the control group. A significantly higher number of positive reactors to IGRA was detected within the dexamethasone group ( p = 0.016) 72 h after PPD administration compared to the control group. Dexamethasone and ketoprofen detection in either hair or serum samples was challenging when using HPLC since these substances were not detected in animals whose skin fold thickness (SFT) was reduced, what could be an issue if they are used for fraudulent purposes. In conclusion, the parenteral administration of dexamethasone or ketoprofen 48 h after the PPDs administration can significantly reduce the increase in SFT (mm) and subsequently the number of positive reactors to SIT test., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ortega, de Juan, Sevilla, Garrido, Roy, Velasco, Romero, Domínguez, Pérez de Val, Nebot, Sáez-Llorente, Álvarez and Bezos.)

Purpose: To characterize the clinical features and outcomes of pediatric patients with retropharyngeal (RPA) or parapharyngeal abscesses (PPA) managed only with medical treatment and showing the importance of early symptoms and imaging studies in the diagnosis of deep neck space infections (DNIs) in children., Methods: A retrospective analysis of all patients diagnosed with RPA and PPA between 2007 and 2017 was performed in Hospital Universitario Central de Asturias., Results: 30 children were identified, with 11 RPA and 19 PPA. 23 children (76.7%) were under 5 years old, and all were treated with intravenous amoxicillin/clavulanic acid and corticosteroids. Torticollis and fever were present in all patients. The mean length of hospital stay was 7.5 days. There were no complications associated., Conclusion: DNIs can be treated in a conservative way, reserving the surgical drainage for cases with a complication associated (airway compromise, lack of response to antibiotic therapy, immunocompromised patients). Treatment with intravenous antibiotics and corticosteroids is a safe option, reducing the duration of symptoms and the length of hospital stay., (© 2022. The Author(s).)

The sinonasal cavities harbor a wide variety of rare cancer types. Histopathological classification can be challenging, especially for poorly differentiated tumors. Despite advances in surgery and radio-chemotherapy, the 5-year survival rate is still very low. Thus, there is an unmet clinical need for new therapeutic options. We retrospectively evaluated poorly differentiated tumors of 9 different histological subtypes from 69 patients who had received conventional treatments for the presence of CD8+ tumor-infiltrating lymphocytes (TILs), as well as the expression of PD-L1 and microsatellite instability (MSI) markers MLH1, MSH2, MSH6 and PMS2, as biomarkers for immunotherapy. CD8+ TILs were present in 23/69 (33%) cases, PD-L1 expression was observed in 23/69 (33%), and markers for MSI positivity in 5/69 (7%) cases. CD8+ TILs correlated with PD-L1 positivity, while both were mutually exclusive with MSI markers. None of the biomarkers were associated with clinical features as age, gender or tumor stage. Cases with CD8+ TILs and PD-L1 positivity showed a tendency toward worse disease-specific survival. Immune checkpoint inhibitors are emerging as new options for treatment of many tumor types. Our results indicate that also a substantial subset of patients with poorly differentiated sinonasal tumors may be a candidate to be treated with this promising new therapy.

Background: Laryngectomized patients have communicative limitations when they lose their phonatory function after surgery. The scale "Self-Evaluation of Communication Experiences after Laryngectomy" (SECEL) assesses the impact of total laryngectomy on quality of life related to communication. The aim of this study was to translate and adapt the SECEL from English to Spanish and to apply this first version to a group of patients to check its reliability and validity., Materials and Methods: One-hundred-and-one laryngectomized patients completed the SECEL scale adjusted to Spanish, the Voice Handicap Index (VHI-30), the Hospital Anxiety and Depression Scale (HADS) and the EORTC QLQ-H&N35 questionnaire., Results: The Spanish version of the SECEL questionnaire has the same format and conceptual, semantic and idiomatic meaning as the original. The resulting model is composed of 21 items dimensioned in two highly correlated factors that are clear, meaningful, and replicable leading to measures that are reliable enough to be used in clinical evaluation., Conclusion: The Spanish translation and validation of the SECEL questionnaire were performed. It can be considered an appropriate tool to assess communication skills from laryngectomized people.

Objective: Patients with locally advanced laryngeal and hypopharyngeal cancer (LHC) are often treated with chemo-radiotherapy to avoid total laryngectomy, although voice problems may occur even if not markedly manifest. We sought to evaluate the impact of chemoradiation on voice and quality of life., Methods: We studied 21 patients with locally advanced LHC with tumour control at least two years after chemo-radiotherapy. None manifested clinical symptoms related to the treatment and maintained an activity considered as within normal limits. All patients had a voice handicap index (VHI) of less than 15. Voice function was evaluated by perceptual vocal analysis (CAPE-V) and aerodynamic and acoustic study. Quality of life was assessed with the EORTC-H&N35 (voice items 46, 53 and 54)., Results: Voice changes were frequent, with alterations in all CAPE-V attributes, and predominantly type II and III spectrograms in acoustic analysis (78%). The EORTC-H&N35 scale showed a reduction in scores in 10-40% of items related to voice., Conclusions: Subclinical voice disorders are common after chemo-radiotherapy. Although patients consider vocal impairment to be very minor and to not interfere with their daily life, it may contribute to a reduced quality of life., (Copyright © 2022 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Objectives: Acute bacterial rhinosinusitis (ABRS) is a common pediatric condition. Despite its tendency to heal without complications, orbital complications (OC) are seen in 6% of patients and can cause vision impairment and put life at risk. Current treatment of this complications involves systemic antibiotics with or without surgical drainage, remaining controversial the use of corticosteroids. The aim of this study is to describe our results in the management of this complication both through medical and surgical treatment, with the inclusion of corticosteroids on it., Methods: A retrospective cross-sectional study was conducted in a tertiary hospital over pediatric patients with this complication., Results: 23 patients were included with a mean age of 7.4 years. Ten of them (43.5%) presented ophthalmoplegia on admission and 2 of those also impaired visual acuity. A computerized tomography was performed in all patients and all of them received intravenous antibiotics and corticosteroids achieving that 60% did not require surgical treatment. The mean length of hospital stay was 6.2 days., Conclusions: The treatment of OC of ABRS with intravenous antibiotics and corticosteroids is safe, remaining surgical treatment available when necessary. When evolution is favorable, a reduced hospital stay must be sought., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy., Methods: We conducted a retrospective analysis of 404 primary, locally recurrent, and metastatic olfactory neuroblastoma (ONB) patients from 12 institutions in the United States of America, United Kingdom and Europe. Clinicopathological characteristics and treatment approach were evaluated. SSTR2 expression, SSTR2-targeted imaging and the efficacy of peptide receptor radionuclide therapy [PRRT]( 177 Lu-DOTATATE) were reported in a subset of our cohort (LUTHREE trial; NCT03454763)., Results: Dural infiltration at presentation was a significant predictor of overall survival (OS) and disease-free survival (DFS) in primary cases (n = 278). Kadish-Morita staging and Dulguerov T-stage both had limitations regarding their prognostic value. Multivariable survival analysis demonstrated improved outcomes with lower stage and receipt of adjuvant radiotherapy. Prophylactic neck irradiation significantly reduces the rate of nodal recurrence. 82.4% of the cohort were positive for SSTR2; treatment of three metastatic cases with SSTR2-targeted peptide-radionuclide receptor therapy (PRRT) in the LUTHREE trial was well-tolerated and resulted in stable disease (SD)., Conclusions: This study presents pertinent clinical data from the largest dataset, to date, on ONB. We identify key prognostic markers and integrate these into an updated staging system, highlight the importance of adjuvant radiotherapy across all disease stages, the utility of prophylactic neck irradiation and the potential efficacy of targeting SSTR2 to manage disease., Competing Interests: Conflict of interest statement NL receives research funding from Merck Inc., not related to this manuscript, and was a consultant for CoolTech Inc. and holds stock in Navigen Pharmaceuticals, both of which are unrelated to this manuscript. SW is on the advisory board of ALK, Genentech, OptiNose, SinopSys and a Consultant to NeurENT, Stryker, all of which are unrelated to this manuscript. All other authors declare no potential relevant conflicts of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Patients with advanced laryngeal and hypopharyngeal cancer are often treated with chemo-radiotherapy to avoid total laryngectomy. Subclinical swallowing disorders could be present in these patients even though patients do not complain of any symptoms. We sought to evaluate the impact of chemoradiation on swallowing and quality of life., Methods: We studied 21 patients undergoing chemo-radiotherapy for advanced laryngeal and hypopharyngeal cancer. All patients were tumor-free and none reported symptoms related to dysphagia during follow-up or showed altered routine screening tests (EAT-10) to detect it. Swallowing functions were assessed using volume-viscosity swallow test (V-VST) and fiberoptic endoscopic evaluation of swallowing (FEES). Quality of life was assessed with the EORT-H&N35, and SWAL-QOL scales., Results: Frequent alterations in swallowing efficacy (100%) and safety (85.5%) were detected with V-VST and FEES. Quality-of-life scales showed a reduction in their scores between 12 and 17%, mainly in the areas of symptoms., Conclusion: Swallowing disorders are common after chemo-radiotherapy, even in patients who do not clinically manifest these disorders, contributing to a decrease in patients' quality of life. FEES and V-VST are useful procedures to detect asymptomatic swallowing disorders., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Mucosal malignant melanoma (MMM) is a rare and aggressive tumor. Despite effective local therapies, tumor recurrence and metastasis remain frequent. The genetics of MMM remain incompletely understood. This study is aimed to identify actionable genetic alterations by next-generation sequencing. Fifteen MMM samples were analyzed by next-generation and Sanger sequencing. Gene copy number alterations were analyzed by MLPA. Mutation status was correlated with pERK, pAKT, and Ki-67 expression and follow-up data. Inactivating mutations and intragenic deletions in neurofibromatosis type-1 (NF1) were identified in 3 and 2 cases, respectively, (in total 5/15, 33%) and activating mutations in NRAS and KRAS (3/15, 20%) cases. Other mutated genes included CDKN2A, APC, ATM, MITF, FGFR1, and FGFR2. BRAF and KIT mutations were not observed. Cases with NF1 alterations tended to have worse overall survival. The mutational status was not associated with pERK, pAKT, or Ki-67 immunostaining. MMM carries frequent gene mutations activating the MAPK pathway, similar to cutaneous melanoma. In contrast, NF1 is the most frequently affected gene. Intragenic NF1 deletions have not been described before and may go undetected by sequencing studies. This finding is clinically relevant as NF1-mutated melanomas have worse survival and could benefit from therapy with immune checkpoint and MEK inhibitors., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The biallelic inheritance of an expanded intronic pentamer (AAGGG) exp in the gene encoding replication factor C subunit 1 ( RFC1 ) has been found to be a cause of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). This study describes clinical and genetic features of our patients with clinical suspicion of the syndrome., Study Design: A retrospective descriptive study from an ataxia database comprising 500 patients., Setting: The study was performed at the Otorhinolaryngology Department of a hospital in the north of Spain., Methods: Specific genetic testing for CANVAS was performed in 13 patients with clinical suspicion of complete or incomplete syndrome. The clinical diagnosis was supported by quantitative vestibular hypofunction, cerebellar atrophy, and abnormal sensory nerve conduction testing., Results: Nine of 13 (69%) patients met clinical diagnostic criteria for definite CANVAS disease. The first manifestation of the syndrome was lower limb dysesthesia in 8 of 13 patients and gait imbalance in 5 of 13. Eleven of 13 (85%) patients were carriers of the biallelic (AAGGG) exp in RFC1 ., Conclusion: A genetic cause of CANVAS has recently been discovered. We propose genetic screening for biallelic expansions of the AAGGG pentamer of RFC1 in all patients with clinical suspicion of CANVAS, since accurate early diagnosis could improve the quality of life of these patients.

Carotid blowout syndrome (CBS) is defined as a rupture of common carotid artery or its branches. Endovascular intervention has been advocated as first line of treatment for CBS. This Case Report describes 5 patients with prior history of head and neck cancer who presented with CBS. Two patients presented as acute, 2 as impending, and one as threatened CBS. The lesions found were pseudoaneurysm and focal vascular irregularities involving the common carotid artery, cervical internal carotid artery and lingual artery. Embolization and occlusion with detachable coils of the artery was used in all patients. Technical success and immediate hemostasis were achieved in all patients. One patient presented transient cranial nerve palsy. No recurrent CBS was reported during the follow-up. In our experience, coil embolization, if possible, is a safe and efficient technique in treatment of CBS secondary to head and neck cancers.

Due to limitations in local therapy approaches for sinonasal tumors, improvement in systemic therapies plays a pivotal role for prolongation of the patient's survival. The aim of this study was to examine potential biomarkers, including deficiency in mismatch repair proteins (dMMR)/microsatellite instability (MSI-H) in sinonasal cancers and their precancerous lesions. A comprehensive analysis of 10 sinonasal cancer cell lines by whole exome sequencing, screening 174 sinonasal tumors by immunohistochemistry (IHC) for mismatch repair deficiency and next generation sequencing (NGS) of 136 tumor samples revealed a dMMR/MSI-H sinonasal squamous cell carcinoma (SNSCC) cell line based on a somatic missense mutation in MLH1 and an overall frequency of dMMR/MSI-H SNSCC of 3.2% (4/125). Targetable EGFR mutations were found in 89.3% (25/28) of inverted sinonasal papilloma (ISP) and in 60% (6/10) of ISP-associated carcinomas. While PIK3CA and EGFR mutations were not mutually exclusive, KRAS mutated tumors were an EGFR -wildtype. The effect of potential driver mutations in FGFR2, FGFR3, BRAF, HRAS, MAP2K1, PTEN, NOTCH1 and CARD11 need further investigation. Our results suggest that biomarker testing, including MMR-IHC and NGS panel analysis, should be integrated into the diagnostics of clinically aggressive ISPs and SNSCC to assess prognosis and facilitate therapeutic decisions.

Background: Minimally invasive video-assisted parathyroidectomy (MIVAP) has become a standard approach to primary hyperparathyroidism (pHPT) since described. Although intraoperative parathyroid hormone assay (IOPTH) has been generalized as a complementary technique to MIVAP, its actual impact on the surgical success of this technique is not without controversy. The aim of this study was to describe our results in the management of pHPT with successful preoperative localization, by MIVAP technique, without IOPTH determination, confirming in a larger series our preliminary results., Methods: A retrospective descriptive study was conducted in pHPT patients treated by MIVAP with no IOPTH determination in a tertiary hospital between 2007 and 2019., Results: A total of 167 patients were included in the study. Biochemical cure was achieved in 96.4%, and 94.1% did not present any surgical complication. The mean duration of surgery was 61 min, and the mean length of hospital stay was 1.8 days CONCLUSIONS: In case of positive preoperative localization studies, MIVAP is a safe and effective technique for the surgical treatment of pHPT due to a parathyroid adenoma, regardless of IOPTH determination, with a success rate > 95% and a low complication rate., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sinonasal intestinal-type adenocarcinoma (ITAC) is strongly related to occupational exposure to wood and leather dust, however, little is known on the genetic alterations involved in tumor development and progression. The aim of this study was to identify tumorigenic signaling pathways affected by gene mutations and their relation to clinical features. We applied whole exome sequencing of 120 cancer-related genes in 50 ITACs and analyzed the signaling activity of four specific pathways frequently affected by mutations. Genes involved in DNA damage response showed somatic mutations in 30% of cases, including four tumors that also harbored germline mutations. Genes in Wnt, MAPK and PI3K pathways harbored mutations in 20%, 20% and 24% of cases, respectively. Mutations and copy number gains in receptor tyrosine kinases possibly affecting MAPK and PI3K pathways occurred in 44% of cases. Expression of key pathway proteins showed no correlation to mutations in these pathways, except for nuclear β-catenin and APC/CTNNB1 mutation. No specific gene mutation, mutated pathway, nor pathway activity level showed correlation to clinical data or survival. In addition, a similar mutational profile was observed among histological subtypes. The wide spectrum of gene mutations suggests that ITAC is a genetically heterogeneous without specific characterizing gene mutations.

Introduction: This study aims to assess the most likely causes of Bovine tuberculosis (bTB) breakdowns in Spanish cattle herds and to identify the main risk factors at farm-level., Methods: Causes of bTB breakdowns were assessed through a qualitative risk-assessment based on decision-trees by analysing surveillance data from 3819 bTB breakdowns detected during 2014-2016. Results were compared to veterinary officers' (VO) opinions. Risk factors were identified through a case-control study with data from 196 bTB cases and 160 controls collected during 2014-2018., Results: The decision tree analysis identified residual infections and interactions with wildlife as the most frequent causes of breakdowns (36% each), followed by purchasing infected cattle (14%). These results were not supported by VOs' opinions. According to the regression models, the risk of bTB increased by sharing pastures (odds ratios [OR] = 2.7; 95% confidence interval [CI] = 1.6-4.4) and by increasing inwards cattle movements. The presence of wildlife reservoirs represented a significant risk for extensively-managed farms if other cattle farms are situated within a one-kilometre radius (OR = 2.3; 95% CI = 1.1-5.1)., Discussion: To prevent bTB breakdowns, efforts should be devoted to decrease the likelihood of residual infections and improve farm biosecurity. The adoption of biosecurity measures might be influenced by farmers' perceptions, which should be carefully evaluated to ensure the effectiveness of such strategies., (© 2021 British Veterinary Association.)

Purpose: The aim of this study was to determine the prevalence of dysphagia in patients with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), characterizing this condition, both in its objective dimension and in terms of quality of life (QoL)., Methods: A cross-sectional study was developed in 11 patients diagnosed of CANVAS. In all patients, clinical records were reviewed and the Eating assessment tool 10 (EAT-10) was performed as screening of oropharyngeal dysphagia. To evaluate the QoL impairment secondary to dysphagia, we applied the swallowing quality of life questionnaire (SWAL-QOL) and the MD Anderson Dysphagia Inventory (MDADI). To evaluate the deglutition mechanisms impaired, two objective-instrumental studies were performed: the volume-viscosity swallow test (V-VST) and the fiberoptic endoscopic evaluation of swallowing (FEES)., Results: 82% of the patients presented an abnormal EAT-10 score. A correlation was found between the EAT-10 and MDADI and between both QoL questionnaires. After the FEES and V-VST analysis, all 11 patients presented some degree of swallow effectiveness impairment, and most of them safety alterations as well., Conclusion: CANVAS remains an underestimated and underdiagnosed condition and the prevalence of swallowing disorders in those patients is higher than expected. Despite the possibility that EAT-10 works as a useful screening test to predict the results in the QoL questionnaires, the absence of correlation between QoL test and instrumental results suggests that to properly evaluate the patients swallowing status, objective instrumental procedures must be conducted.

Sinonasal squamous cell carcinoma (SNSCC) is an aggressive tumor predominantly arising in the maxillary sinus and nasal cavities. Advances in imaging, surgical and radiotherapeutic techniques have reduced complications and morbidity; however, the prognosis generally remains poor, with an overall 5-year survival rate of 30-50%. As immunotherapy may be a new therapeutic option, we analyzed CD8 + tumor-infiltrating lymphocytes (TILs) and the tumor microenvironment immune type (TMIT, combining CD8 + TILs and PD-L1) in a series of 57 SNSCCs. Using immunohistochemistry, tissue samples of 57 SNSCCs were analyzed for expression of CD8 on TILs and of PD-L1 on tumor cells. The results were correlated to the clinical and survival data. In total, 88% (50/57) of the tumors had intratumoral CD8 + TILs; 19% (11/57)-CD8 high (>10%); and 39/57 (68%)-CD8 low (1-10%). PD-L1 positivity (>5%) was observed in 46% (26/57) of the SNSCCs and significantly co-occurred with CD8 + TILs ( p = 0.000). Using univariate analysis, high intratumoral CD8 + TILs and TMIT I (CD8 high /PD-L1 pos ) correlated with a worse survival rate. These results indicate that SNSCCs are immunogenic tumors, similar to head and neck squamous cell carcinomas. Nineteen percent of the cases were both CD8 high and PD-L1 pos and this subgroup may benefit from therapy with immune checkpoint inhibitors.

Background: We performed a comparative analysis between an organ-preservation protocol and surgery followed by radiotherapy in patients with locally advanced squamous cell carcinoma of the larynx and hypopharynx; Methods: 60 previously untreated patients who were treated with induction chemotherapy followed by chemoradiotherapy in responders were compared with a control group of 60 patients treated with up-front surgery. Both groups were statistically comparable, according to the subsite, TNM (tumor-node-metastasis) stage, age, and sex; Results: Mean age was 58 years and 92% were male. No significant statistical difference was observed for overall survival (OS) (HR 0.75; 95% CI 0.48-1.18; P = 0.22) and disease-specific survival (DSS) (HR 0.98; 95% CI 0.52-1.83, P = 0.96). Also, there was no significant difference for recurrence-free survival (HR 0.931; 95% CI 0.57-1.71; P = 0.81), metastases-free survival (HR 2.23; 95% CI 0.67-7.41; P = 0.19), and the appearance of second primary tumors (HR 1.22; 95% CI 0.51-2.88; P = 0.64); Conclusions: The results of the organ-preservation approach did not appear inferior to those of surgery plus (chemo)radiotherapy for patients with T3/T4a larynx and T2-T4a hypopharynx cancer with respect to OS and DSS, locoregional control and metastases-free survival.

Colistin use has mostly been stopped in human medicine, due to its toxicity. However, nowadays, it still is used as a last-resort antibiotic to treat hospital infections caused by multi-drug resistant Enterobacteriaceae. On the contrary, colistin has been used in veterinary medicine until recently. In this study, 210 fecal samples from pigs ( n = 57), calves ( n = 152), and the farmer ( n = 1) were collected from a farm where E. coli harboring mcr -1- mcr -3 was previously detected. Samples were plated, and mcr -genes presence was confirmed by multiplex-PCR. Hybrid sequencing which determined the presence and location of mcr-1 , other antibiotic resistance genes, and virulence factors. Eighteen colistin resistant isolates (13 from calves, four from pigs, and one from the farmer) contained mcr -1 associated with plasmids (IncX4, IncI2, and IncHI2), except for two that yielded mcr -1 in the chromosome. Similar plasmids were distributed in different E. coli lineages. Transmission of mcr -1 to the farmer most likely occurred by horizontal gene transfer from E. coli of calf origin, since plasmids were highly similar (99% coverage, 99.97% identity). Moreover, 33 virulence factors, including stx2 for Shiga toxin E. coli (STEC) were detected, highlighting the role of livestock as a reservoir of pathotypes with zoonotic potential.

Intestinal-type sinonasal adenocarcinoma (ITAC) is a rare tumor carrying poor prognosis and needing new treatment options. The aim of this study was to identify actionable gene mutations that can guide new personalized target-specific therapies in ITAC patients. A series of 48 tumor and 27 corresponding germline DNA samples were analyzed by next generation sequencing using a panel of 120 genes. In total, 223 sequence variants were found in 70 genes. Matched tumor/germline comparison in 27 cases revealed that 57% were in fact germline variants. In 20 of these 27 cases, 58 somatic variants in 33 different genes were identified, the most frequent being PIK3CA (5 cases), APC and ATM (4 cases), and KRAS, NF1, LRP1B and BRCA1 (3 cases). Many of the somatic gene variants affected PI3K, MAPK/ERK, WNT and DNA repair signaling pathways, although not in a mutually exclusive manner. None of the alterations were related to histological ITAC subtype, tumor stage or survival. Our data showed that thorough interpretation of somatic mutations requires sequencing analysis of the corresponding germline DNA. Potentially actionable somatic mutations were found in 20 of 27 cases, 8 of which being biomarkers of FDA-approved targeted therapies. Our data implicate new possibilities for personalized treatment of ITAC patients.

Purpose: Large pharyngocutaneous fistulas or pharyngostomes are difficult complications to solve, which generate high morbidity and mortality, a poor quality of life and an increase in health costs. Its management must be comprehensive according to general, local and regional factors. We review our experience in treating these pharyngostomes with free flaps., Methods: Retrospective study analyzing the results of the reconstruction of 50 patients using free flaps during the period 1991-2019. We exclude patients who required free-flap reconstruction due to primary tumor or those who resolved in other ways. The different types of reconstruction were classified into three types., Results: The 86% (43) were men, and the mean age was 57 years (25-76). In 48% (24/50) the flaps performed were anterolateral thigh (ALT), in 24% (12/50) forearm, in 22% (11/50) parascapular, in 4% (2/50) jejunum and in 2% (1/50) ulnar. A salivary by-pass was placed in 74% (37/50) of the cases. Four cases (8%) presented flap necrosis and two patients died due to treatment. In 86% (43/50) there was some type of complication and 34% (17/50) required surgical revision. 94% (45/48) were able to reintroduce oral feeding., Conclusion: According to our experience, we proposed a regardless size classification: type 1 when only a mucous closure (pharynx) are required (6%), type 2 exclusively skin for cutaneous coverage (10%) and mixed type 3 (mucous and skin) (84%). The treatment of large pharyngostomes with free flaps, despite its complexity, is in our experience the best option for its management.

Background: To evaluate the involvement of EGFR signalling and HPV infection in a cohort of inverted sinonasal papilloma (ISP) and sinonasal squamous cell carcinoma (SNSCC) and their value for prognosis and clinical treatment., Methods: We analysed 55 ISP, 14 SNSCC associated with ISP (SNSCC-isp) and and 60 SNSCC not associated with ISP (SNSCC-novo) for EGFR gene mutation and copy number gain, protein expression of EGFR and phosporylated EGFR (pEGFR), and HPV-infection and KRAS mutation. Findings were correlated to clinico-pathological and follow-up data., Results: We found EGFR exon 20 mutations in 38% (7/18) ISP, in 50% (6/12) SNSCC-isp and in 5% (1/19) SNSCC-novo. EGFR was expressed in 92% of ISP, while pEGFR was observed in 54% (21/39). SNSCC-isp and SNSCC-novo demonstrated comparable expression of EGFR (57% and 33%) and of pEGFR (44% and 38%). We observed an inverse relation between EGFR exon 20 mutation and pEGFR expression. Four of 39 (10%) ISP carried HPV-16. Oncogenic HPV was detected in 3/12 (25%) SNSSC-isp and in 1/8 (13%) SNSCC-novo. KRAS mutations were not detected in any of the samples. HPV infection was inversely correlated with pEGFR expression but not with EGFR mutation. ISP with EGFR activation by mutation or by phosphorylation had longer ISP-free survival, however, neither EGFR exon 20 mutation, pEGFR expression nor HPV infection demonstrated prognostic value in SNSCC., Conclusions: EGFR exon 20 mutation is frequent in ISP and SNSCC-isp, while activation of EGFR through phosphorylation also plays an important role. Our data indicate that a large proportion of SNSCC patients could benefit from therapy with modern EGFR inhibitors.

Objectives Hyperglycaemia is a common metabolic disorder in very-low-birth-weight (VLBW) infants and is associated with increased morbidity and mortality. The objective is to describe the incidence, duration, episodes and distribution of hyperglycaemia during the first 7 days of life of VLBW infants. Methods This is a prospective cohort study of 60 newborns weighing <1,500 g. Blood glucose levels were monitored with a continuous glucose monitoring system (CGMS) during the first 7 days of life. Hyperglycaemia was defined as glucose ≥180 mg/dL (≥10 mmol/L). Results Incidence of hyperglycaemia recorded with the CGMS was 36.6% (95%CI: 24.6-50.1). In almost 74.6±5.48% of these cases the duration of the episode exceeded 30 min and in 45.25% (95%CI: 2.26-57.82) it exceeded 2 h. The condition occurred most frequently during the first 72 h of life. One-fifth of cases were not detected with scheduled capillary tests and 84.6% of these had hyperglycaemic episode durations of 30 min or more. Agreement between the two techniques was very good (r=0.90, p<0.001) and the CGMS proved to be reliable, accurate and safe. Hyperglycaemia detected by a CGMS is associated with lower gestational age (OR: 0.66, p=0.002), lower birth weight (OR: 0.99, p=0.003), the use of ionotropic drugs (OR: 11.07, p=0.005) and death (OR: 10.59, p=0.03), and is more frequent in preterm infants with sepsis (OR: 2.73, p=0.1). No other association was observed. Conclusions A CGMS could be useful during the first week of life in VLBW infants due to the high incidence and significant duration of hyperglycaemia and the high proportion of cases that remain undetected. The advantage of the CGMS is that it is able to detect hyperglycaemic episodes that the capillary test does not.

Introduction: Sensorineural hearing loss (SNL) is the most prevalent sensory deficit in our environment. Next generation genomic sequencing (NGS) enables an aetiological diagnosis in a high percentage of patients. Our pilot study shows the results of the systematic application of NGS in a Childhood Hearing Loss Unit, as well as its implications for the clinical management of patients and their families., Material and Method: We included 27 patients diagnosed with SNL between 2014 and 2017, in which an environmental cause was ruled out. The genetic test consisted of a panel of genes analyzed by NGS (OTOgenicsTM panel). This panel has been designed to include genes associated with sensorineural or mixed hearing loss, early onset or late, syndromic and non-syndromic, regardless of their inheritance pattern., Results: A genetic diagnosis was obtained in 56% (15/27) of the patients (62% in the case of bilateral SNL). Of the patients, 5/27 (19%) presented pathogenic variants in the GJB2 gene and the rest pathogenic and / or probably pathogenic variants in other genes associated with isolated SNL (PR2X2, TECTA and STRC), with syndromic SNL (CHD7, GATA3, COL4A5, MITF and SOX10) or with syndromic and non-syndromic SNL (BSND, ACTG1 and CDH23)., Discussion: The aetiological diagnosis of SNL is a challenge in clinical practice. Our series demonstrates that it is possible to implement genetic diagnosis in the care routine and that this information has prognostic and therapeutic implications., (Copyright © 2019 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Intestinal-type adenocarcinoma (ITAC) is a rare tumour occurring in the ethmoid sinus. Recent years have brought advances in endoscopic surgery and precision radiotherapy; however, five-year overall survival has not improved and remains at 35-80%, depending on tumour stage and histology. Therefore, there is a need for new therapeutic options., Methods: We evaluated CD8 + tumour-infiltrating lymphocytes (TILs) and tumour microenvironment immune type (TMIT, combining CD8 + TILs and PD-L1) as predictive biomarkers for immunotherapy in a series of 133 ITAC. All results were correlated to clinical and follow-up data., Results: The presence of intratumoural CD8 + TILs was low in 57% of cases and high in 8% of cases. Tumoural PD-L1 positivity was observed in 26% of cases. CD8 + TILs and TMIT correlated with the histological subtype of ITAC and with better overall survival. The presence of stromal PD-L1-positive macrophages was related to intratumoural CD8 + TILs. PD-L1 expression on tumour cells or macrophages did not show prognostic value., Conclusions: TMIT classification did not have additional prognostic value over CD8 + TILs alone. The modest percentage of CD8 high /PD-L1 pos cases indicates that ITAC is a lowly immunogenic tumour type. Nevertheless, a proportion of ITAC, especially the papillary and colonic subtypes, could benefit from therapy with immune checkpoint inhibitors.

The sinonasal cavities harbor a wide variety of histologically distinct cancers, the majority very aggressive with 5-year survival rates between 30-60% and local recurrence as the main cause of death. This is a complex anatomic area, close to structures such the eyes and the brain, which is of special relevance for surgery and postoperative radiotherapy. The low incidence of these rare tumors hampers accumulation of experience with diagnosis and clinical managment as well as knowledge on recurrent genetic aberrations or testing of new treatment strategies. However, recent years have seen a growing number of publications on genetic aberrations providing data that can aid or fine-tune classification and provide molecular targets for treatment with specific inhibitors. In addition, new sinonasal cancer models are created that enable preclinical testing of candidate inhibitor drugs. With more and more novel targeted therapies being developed, options for personalized treatment of sinonasal cancer patients are now opening up., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A large number of tumor types arise from the mucosa of the sinonasal cavities. Although presenting clinically distinct behavior, due to poorly differentiated histologic features, they can be difficult to classify correctly. Our aim was to investigate whether IDH2 and IDH1 mutations may be specific to a subset of undifferentiated and poorly differentiated sinonasal carcinomas. A total of 125 tumor samples of 7 different histologic subtypes were analyzed for IDH mutations by sequencing and mutant-specific immunohistochemistry, and the results were correlated to clinical and follow-up data. The highest incidence of IDH2 mutations occurred in sinonasal undifferentiated carcinoma, with 11/36 (31%) cases affected. However, also, 1/9 neuroendocrine carcinomas, 2/4 high-grade non-intestinal-type adenocarcinomas, and 1/8 poorly differentiated squamous cell carcinomas carried the IDH2 mutation, whereas 1/48 intestinal-type adenocarcinomas harbored an IDH1 mutation. Immunohistochemical analysis of mutant IDH1/2 produced a number of false-negative results, but also 1 false-positive tumor was found. Disease-specific survival was more favorable in IDH2-mutant versus wild-type cases. Our data suggest that IDH-mutant sinonasal cancers, independent of their histologic subtype, may represent a distinct tumor entity with less aggressive clinical behavior. Clinically, patients with these mutations may benefit from specific IDH-guided therapies.

Objective: To determine the effectiveness and outcomes of SND in the treatment of patients with squamous cell carcinoma of the head and neck (SCCHN) with clinically positive neck (cN+) at diagnosis., Material and Methods: We retrospectively reviewed 159 patients with SCCHN with cN+ at diagnosis, who underwent a SND with curative intent at a tertiary care academic teaching hospital in Spain. We registered patient and tumor characteristics, date and site of recurrences, together with the outcomes. Survival rates were calculated by the Kaplan-Meier method. The minimum follow-up was 18 months or till death., Results: A total of 28 neck recurrences were found in the whole series but only 10 neck recurrences occurred in absence of local recurrence. The regional control in the neck in absence of local recurrence was observed in 94% of patients. The neck recurrence rates did not correlated with the pN classification (P = 0.49), the administration of postoperative radiotherapy (P = 0.49) or extranodal extension (P = 0.43). The 5-year regional recurrence-free survival rate was 80% and 92% if only isolated neck recurrences are considered., Conclusions: SND offers an effective and oncologically safe surgical procedure in selected patients with clinically positive metastatic nodes in the neck. Our findings suggest that in cN1 and cN2 tumors, SND could replace the modified radical neck dissection without compromising oncologic efficacy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction and Objectives: Radioiodine is the principal treatment for differentiated thyroid carcinomas. The aim of this study is to present our experience in the management of these tumours., Material and Method: We present a retrospective study of 55 patients operated for differentiated thyroid carcinoma in our hospital between 2007 and 2011., Results: The mean age at time of diagnosis was 49 years, and females predominated (78% of cases). Seventy eight percent of the patients were in the initial stages (stages i and ii). The definitive histopathological diagnosis was papillary carcinoma in 84% and follicular carcinoma in the remaining 16%. All of the patients, with the exception of 2 (4%), underwent total thyroidectomy, with lymphadenectomy in 58% of cases. Nine percent of the patients had permanent hypoparathyroidism and although 18% suffered transitory unilateral paralysis, 40% of these female patients had completely recovered after 6 months. Eighty-nine percent of the patients were given radioiodine postoperatively. There was a recurrence rate of 40% most of which was at cervical level (29% of the patients). Survival at 5 years was 87%, 95% of the papillary subtype, falling to 56% of the follicular subtype (P=.001)., Discussion/conclusions: The prognosis for differentiated thyroid carcinomas is excellent after appropriate surgical treatment, thorough preoperative assessment,and strict postoperative follow-up due to the significant recurrence rates., (Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: The objective was to determine the results of the treatment of severe and/or refractory epistaxis requiring hospital admission. In addition, the results of arterial ligation versus embolization were compared., Material and Method: Sixty-three patients with severe and/or refractory epistaxis requiring hospital admission between August 2014 and December 2016 were included prospectively., Results: Eleven patients (17%) underwent embolization, 5 (8%) endoscopy ligation and the remaining 47 (75%) underwent conservative treatment with tamponade. The mean age of the patients in which conservative measures were sufficient was 72 years, while the age of those treated with embolization was 71 years and of those who underwent surgery was 53 years. For the patients who underwent conservative treatment or surgery, the average stay was 6 days, compared to 9 days for those who underwent embolization. One patient suffered a hemispheric stroke after embolization. No post-surgical complications were observed., Conclusions: Most cases of severe and/or refractory epistaxis are resolved by conventional tamponade. Endoscopy ligation is associated with a decrease in hospital stay, without serious complications. It is advisable to have all the possible therapeutic options available, for which the presence of interventional radiologists and experienced surgeons is essential to avoid complications and decide the treatment to be performed individually for each patient., (Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.)

The quality of anti-virus software relies on simple patterns extracted from binary files. Although these patterns have proven to work on detecting the specifics of software, they are extremely sensitive to concealment strategies, such as polymorphism or metamorphism. These limitations also make anti-virus software predictable, creating a security breach. Any black hat with enough information about the anti-virus behaviour can make its own copy of the software, without any access to the original implementation or database. In this work, we show how this is indeed possible by combining entropy patterns with classification algorithms. Our results, applied to 57 different anti-virus engines, show that we can mimic their behaviour with an accuracy close to 98% in the best case and 75% in the worst, applied on Windows' disk resident malware.

Background and Objectives: Juvenile angiofibroma (JA) is a benign tumour, for which the treatment of choice is surgery. It may be associated with significant morbidity because of its anatomical location and its locally destructive growth pattern. Severe haemorrhage constitutes a high risk in JA and its surgical management can be complex. The management of JA remains a challenge. The objective of this study was to review a series of patients with JA treated via the endonasal/endoscopic approach., Material and Methods: Medical records of patients operated for JA were reviewed., Main Outcome Measures: tumour stage, intraoperative blood loss, complications and persistence/recurrence rates., Results: A total of 30 male patients and one female were included. The mean age was 17 years. Using the Radkowski classification, one JA was classified as stage I, 5 stage IIA, 9 stage IIB, 4 stage IIC, 10 stage IIIA and 2 stage IIIB. Thirty-nine percent of the JA was classified as advanced stage JA (IIIA and IIIB). The mean blood loss was 1.156mL Except in one case, no significant complications were observed. Tumour persistence/recurrence was observed in 2 JA (6%), at the end of the follow-up. Mean postoperative follow-up time was 86 months., Conclusions: This retrospective study supports the notion that endonasal endoscopic approaches for a JA are a feasible option associated with good long-term results., (Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Contralateral sensorineural hearing loss (CSNHL) after vestibular schwannoma (VS) is a severe complication, especially in those cases in which hearing preservation in the operated side was not possible. There are several theories that attempt to explain this issue, but there is no established guideline of treatment., Material and Methods: We report 4 patients treated in our institution who developed a severe CSNHL after surgery., Results: Of the 185 cases of VS treated with surgery, 4 patients (2.2%) developed a CSNHL after VS surgery. After medical treatment, partial recovery of hearing occurred in one patient the other 3 patients presented a well-established severe SNHL., Conclusions: Established treatment guidelines do not exist, but the use of high doses of corticosteroids has been recommended and cochlear implant in cases with no recovery and complete hearing loss may be useful., (Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background and Objectives: We have previously indicated that EGFR has a role in carcinogenesis in a subgroup of sinonasal squamous cell carcinomas (SNSCC). In addition, EGFR activates 2 of the most important intracellular signalling pathways: PI3K/pAKT/mTOR/pS6 and MAP pathway kinases. The objective of this study was to evaluate the involvement of the EGFR/PI3K/pAKT/mTOR/pS6 pathway and its relationship with clinical-pathological parameters and follow-up of sinonasal squamous cell carcinoma., Material and Methods: The immunohistochemical expression of different components of the PI3K/AKT/mTOR/pS6 pathway and its relationship with various clinical-pathological parameters was studied in a series of 54 patients with SNSCC., Results: Loss of PTEN expression was observed in 33/54 cases (61%) and pAKT, mTOR and pS6 pre-expression was observed in 19/54 cases (35%), 8/54 cases (15%), and 47/54 cases (87%), respectively. Loss of PTEN expression was related to intracranial invasion and development of regional metastases (p=0.005). Overexpression of pS6 was associated with a decrease in survival (p=0.008), presence of local recurrences (p=0.055), and worsening of overall prognosis (p=0.007). No significant relationships were observed between pAKT and mTOR expression and the clinicopathological parameters studied., Conclusions: Alterations in the expression of EGFR/PI3K/pAKT/mTOR/pS6 pathway components are common in a subgroup of SNSCC. This study reveals that the absence of pS6 overexpression is associated with better clinical outcomes. Therefore, pS6 expression could be considered as an unfavourable prognostic marker., (Copyright © 2018. Publicado por Elsevier España, S.L.U.)