Critical Steps and Common Mistakes during Temporal Bone Dissection: A Survey among Residents and a Step-by-Step Guide Analysis.

BACKGROUND: Given that the temporal bone is one of the most complex regions of the human body, cadaveric dissection of this anatomical area represents the first necessary step for the learning and training of the young oto-surgeon in order to perform middle ear surgery, which includes the management of inflammatory pathology, hearing rehabilitation, and also cognitive decline prevention surgery. The primary objective of this study was to identify common mistakes and critical passages during the initial steps of temporal bone dissection, specifically cortical mastoidectomy and posterior tympanotomy. METHODS: A survey among 100 ENT residents was conducted, gathering insights into the most prevalent errors encountered during their training to uncover the most challenging aspects faced by novice surgeons during these procedures. RESULTS: The most common mistakes included opening the dura of the middle cranial fossa (MCF), injury of the sigmoid sinus (SS), chorda tympani (CT), and facial nerve (FN) injury while performing the posterior tympanotomy. The most important critical steps to prevent mistakes are related to the absence of wide exposure during cortical mastoidectomy and the consequent impossibility of identifying the landmarks of the facial recess before performing posterior tympanotomy. Injury of these structures was more common in younger surgeons and in the ones who performed less than five temporal bone dissection courses. CONCLUSIONS: Numerous temporal bone dissections on cadavers are mandatory for ENT residents looking forward to performing middle ear surgery.

Transoral Approach to Parapharyngeal Space Tumours: Preliminary Reports from a Single-Centre Retrospective Analysis.

PURPOSE: The aim of this study is to identify certain parapharyngeal space tumours with specific characteristics that can be treated successfully through an endoscopically assisted transoral approach (EATA). METHODS: Nine patients with PPS tumours underwent surgery through an EATA between 2003 and 2021. All patients underwent clinical examination and fibrolaryngoscopy. Preoperative CT and/or MRI was performed on all patients. RESULTS: All the patients were successfully treated through an endoscopically assisted transoral approach. Histological examination revealed five pleomorphic adenomas, two schwannomas, one ectopic thyroid gland and one lipoma. The only long-term sequelae observed was Horner syndrome in the two schwannomas arising from the carotid space. The mean hospitalisation time was 2.6 days, while the mean follow-up time was of 9.7 years. CONCLUSIONS: An endoscopically assisted transoral approach (EATA) is a valid technique for treating benign capsulated tumours of the true PPS and some benign capsulated tumours of the superomedial aspect of the carotid space.

Long Process Incus necrosis in Revision Stapedotomy: Retrospective Clinical Study.

OBJECTIVES: We describe our experience with long process incus (LPI) necrosis in revision stapedotomy and discuss the different management methods proposed in the literature to identify surgical techniques that can lead to satisfactory results over time. METHODS: Twenty-two stapedotomy revisions, in 21 patients with the necrosis of the long process of the incus, are performed from 1997 to 2017. In cases of erosion or minimal necrosis of LPI, a new prosthesis of the same type or an angled prosthesis was applied higher on the residual incus stump. In cases of partial necrosis of LPI, a Donaldson type ventilation tube reshaped and placed on the residual incus stump to stabilize prosthesis, or glass ionomer bone cement was used. In cases of subtotal necrosis of LPI, a cup piston prosthesis in polycel was applied on incus residual stump. Pre- and postoperative (≥1 year) pure tone audiometry was performed for all cases. Air conduction threshold, bone conduction (BC) threshold, and air-bone gap (ABG) were documented according to the American Academy of Otolaryngology Head and Neck Surgery Committee of Hearing and Equilibrium guidelines. RESULTS: At 1-year follow-up, postoperative ABG was reduced to ≤10 dB in 13 (59%) cases and ≤20 dB in 19 (86.4%) cases. The mean postoperative ABG significantly decreased in each group. There was no significant change in postoperative BC thresholds, and there were no cases with postoperative SNHL. CONCLUSION: Excellent functional results can also be achieved in cases of long incus process necrosis. The choice of technique should be considered according to the degree of necrosis. Piston replacement with the same type or angled type prosthesis, in cases of erosion or minimal LPI necrosis, and modified Donaldson type ventilation tube, in cases of partial LPI necrosis, provided excellent hearing results.

Drug-induced inhibition of HMGA and EZH2 activity as a possible therapy for anaplastic thyroid carcinoma.

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and lethal neoplasms in humans, and just limited progresses have been made to extend patient survival and decrease ATC-associated mortality. Thus, the identification of novel therapeutic strategies for treating ATC is needed. Recently, our group has identified two proteins with oncogenic activity, namely HMGA1 and EZH2, with pivotal roles in ATC cancer progression. Therefore, we tested the ability of trabectedin, a HMGA1-targeting drug, and GSK126, an inhibitor of EZH2 enzymatic activity, to impair cell viability of four ATC-derived cell lines. In the present study, we first confirmed the overexpression of HMGA1 and EZH2 in all ATC-derived cell lines and tissues compared to the normal primary thyroid cells and tissues. Then, treatment of the ATC cell lines with trabectedin and GSK126 resulted in a drastic induction of apoptotic cell death, which increased when the ATC cell lines were treated with a combination of both drugs. Conversely, normal primary human thyroid cells did not show any significant reduction in their viability when exposed to the same drugs. Noteworthy, both drugs induced the deregulation of EZH2- and HMGA1-controlled genes. Altogether, these findings propose the combination of trabectedin and GSK126 as possible novel strategy for ATC therapy.

Nasal Microbiome in COVID-19: A Potential Role of Corynebacterium in Anosmia.

The evolution and the development of the symptoms of Coronavirus disease 19 (COVID-19) are due to different factors, where the microbiome plays a relevant role. The possible relationships between the gut, lung, nasopharyngeal, and oral microbiome with COVID-19 have been investigated. We analyzed the nasal microbiome of both positive and negative SARS-CoV-2 individuals, showing differences in terms of bacterial composition in this niche of respiratory tract. The microbiota solution A (Arrow Diagnostics) was used to cover the hypervariable V1-V3 regions of the bacterial 16S rRNA gene. MicrobAT Suite and MicrobiomeAnalyst program were used to identify the operational taxonomic units (OTUs) and to perform the statistical analysis, respectively. The main taxa identified in nasal microbiome of COVID-19 patients and in Healthy Control subjects belonged to three distinct phyla: Proteobacteria (HC = 14%, Cov19 = 35.8%), Firmicutes (HC = 28.8%, Cov19 = 30.6%), and Actinobacteria (HC = 56.7%, Cov19 = 14.4%) with a relative abundance > 1% in all groups. A significant reduction of Actinobacteria in Cov19 group compared to controls (P < 0.001, FDR = 0.01) was found. The significant reduction of Actinobacteria was identified in all taxonomic levels down to the genus (P < 0.01) using the ANOVA test. Indeed, a significantly reduced relative abundance of Corynebacterium was found in the patients compared to healthy controls (P = 0.001). Reduced abundance of Corynebacterium has been widely associated with anosmia, a common symptom of COVID-19 as suffered from our patients. Contrastingly, the Corynebacterium genus was highly represented in the nasal mucosa of healthy subjects. Further investigations on larger cohorts are necessary to establish functional relationships between nasal microbiota content and clinical features of COVID-19.

Minimal Margin Surgery and Intraoperative Neuromonitoring in Benign Parotid Gland Tumors: Retrospective Clinical Study.

Extracapsular dissection (ECD) was introduced for the removal of superficial and small benign parotid tumors. According to a recent proposal, ECD is reserved for tumors that are 3 cm or less, mobile, and close to the parotid borders in cases of pleomorphic adenoma. The aim of the study is to evaluate the effectiveness of ECD for treatment of benign parotid tumors also in cases of tumors that were larger than 3 cm and deeper. All ECD for benign parotid neoplasms conducted between 2007 and 2017 were reviewed. The lesions included were limited to primary parotid tumors and categorized by Quer proposal. Facial nerve monitoring was used in all cases. Facial nerve palsy and local recurrences were assessed. The 88 ECD performed met inclusion criteria. The mean lesion size was 4.26 cm. Of the tumors, 68 were less than 3 cm in diameter and 20 were larger, 64 were superficial, and 24 were deep. The most common lesion types were pleomorphic adenoma (88.6%). There was no significant difference in complication rates between the size of tumor (p = 0.9) and location (p = 0.91). Our results suggest that extracapsular dissection could be considered an option for first-time diagnosed benign parotid tumors, even in cases of large dimensions and deep lobe involvement.

Intravascular Papillary Endothelial Hyperplasia (Masson's Tumor) of the Supraclavicular Region: Management of a Rare Case.

BACKGROUND Masson's tumor, also known as IPEH (intravascular papillary endothelial hyperplasia), is a rare benign vascular process, comprising approximately 2% of vascular tumors of the skin and subcutaneous tissue. IPEH presenting as a neck mass is rare, with only 5 reports of anterior neck mass and 7 cases of lateral neck lesions, of which 1 was in an external jugular vein aneurysm. To the best of our knowledge, the localization of intravascular papillary endothelial hyperplasia in the supraclavicular region is rarely reported. CASE REPORT We describe our management of a non-traumatic and non-painful mass on the right supraclavicular region in 24-year-old woman. Ultrasound revealed a heterogeneously hypoechoic mass with intense vascularization. Magnetic resonance imaging (MRI) showed a formation with lobulated contours and closely related to muscular layers of serratus anterior muscle. The findings of ultrasound-guided biopsy (FNA) were inconclusive. Complete removal of the mass was performed. Histopathological examination showed a well-circumscribed lesion with numerous small papillary structures. The papillae had hyalinized hypocellular cores covered by flattened endothelium. Immunohistochemical analysis showed endothelial positivity for CD34 and CD31. These features are typical of IPEH. No recurrence had occurred at 12 months after surgery. CONCLUSIONS The differential diagnosis of malignant tumors like angiosarcoma is important because the prognosis significantly differs. Surgical excision is the treatment of choice. In our experience, the size of the lesion and its critical landmarks have not influenced the outcomes of the surgical procedure in terms of potential functional damages.

Ultrasound for Assessment and Follow-up of Airway Stenosis.

BACKGROUND: Ultrasound is a reliable tool for airway assessment and management. We evaluated the accuracy of ultrasound in the preprocedure planning and follow-up evaluation of patients undergoing airway stenting for benign upper airway stenosis. METHODS: This was a retrospective single center study on patients with benign upper airway stenosis treated with airway stenting. Ultrasound evaluated the characteristics of the stenosis (distance from vocal folds, diameter, and length) before treatment and any complications after treatment; these results were then statistically compared with those obtained by computed tomography, taking the endoscopy as the reference method. RESULTS: Twenty-seven patients were evaluated. Ultrasound was significantly correlated with endoscopy and computed tomography scan measurements as distance of stenosis from vocal folds (r = 0.88; P < .001 and r = 0.87; P < .001, respectively), diameter of the stenosis (r = 0.97; P < .001 and r = 0.97; P < .001, respectively), and length of the stenosis (r = 0.97; P < .001 and r = 0.97; P < .001, respectively). Four out of 27 (15%) patients presented complications after treatment as stent migration (n = 2; 7%); stent obstruction (n = 1; 4%), and granulation of vocal fold (n = 1; 4%). All complications but granulation of vocal fold were correctly depicted by ultrasound and computed tomography without significant difference in comparison to endoscopy (P = .87) CONCLUSIONS: Ultrasound is a promising tool in assessment of airway stenosis and follow-up of patients after stenting; it may be routinely used in adjunction to computed tomography and/or endoscopy in this setting, if our results are corroborated by a future larger study.

Management of Low-Risk Thyroid Cancers: Is Active Surveillance a Valid Option? A Systematic Review of the Literature.

Thyroid cancer is the most common endocrine malignancy, representing 2.9% of all new cancers in the United States. It has an excellent prognosis, with a five-year relative survival rate of 98.3%.Differentiated Thyroid Carcinomas (DTCs) are the most diagnosed thyroid tumors and are characterized by a slow growth rate and indolent course. For years, the only approach to treatment was thyroidectomy. Active surveillance (AS) has recently emerged as an alternative approach; it involves regular observation aimed at recognizing the minority of patients who will clinically progress and would likely benefit from rescue surgery. To better clarify the indications for active surveillance for low-risk thyroid cancers, we reviewed the current management of low-risk DTCs with a systematic search performed according to a PRISMA flowchart in electronic databases (PubMed, Web of Science, Scopus, and EMBASE) for studies published before May 2021. Fourteen publications were included for final analysis, with a total number of 4830 patients under AS. A total of 451/4830 (9.4%) patients experienced an increase in maximum diameter by >3 mm; 609/4830 (12.6%) patients underwent delayed surgery after AS; metastatic spread to cervical lymph nodes was present in 88/4213 (2.1%) patients; 4/3589 (0.1%) patients had metastatic disease outside of cervical lymph nodes. Finally, no subject had a documented mortality due to thyroid cancer during AS. Currently, the American Thyroid Association guidelines do not support AS as the first-line treatment in patients with PMC; however, they consider AS to be an effective alternative, particularly in patients with high surgical risk or poor life expectancy due to comorbid conditions. Thus, AS could be an alternative to immediate surgery for patients with very-low-risk tumors showing no cytologic evidence of aggressive disease, for high-risk surgical candidates, for those with concurrent comorbidities requiring urgent intervention, and for patients with a relatively short life expectancy.

Head and neck cancer: the role of anti-EGFR agents in the era of immunotherapy.

Head and neck cancers (HNC) represent the seventh most frequent cancer worldwide, with squamous cell carcinomas as the most frequent histologic subtype. Standard treatment for early stage diseases is represented by single modality surgery or radiotherapy, whereas in the locally advanced and recurrent or metastatic settings a more aggressive multi-modal approach is needed with locoregional intervention and/or systemic therapies. Epidermal Growth Factor Receptor (EGFR) plays an important role in HNC biology and has been studied extensively in preclinical and clinical settings. In this scenario, anti-EGFR targeted agent cetuximab, introduced in clinical practice a decade ago, represents the only approved targeted therapy to date, while the development of immune-checkpoint inhibitors has recently changed the available treatment options. In this review, we focus on the current role of anti-EGFR therapies in HNCs, underlying available clinical data and mechanisms of resistance, and highlight future perspectives regarding their role in the era of immunotherapy.

Expression of Matrix Metalloproteinases and Their Tissue Inhibitors in Chronic Rhinosinusitis With Nasal Polyps: Etiopathogenesis and Recurrence.

Chronic rhinosinusitis with nasal polyps is a multifactorial disease of the nasal and paranasal sinus mucosa and it includes, as comorbidities, anatomic and morphologic alterations, allergic rhinitis, and immunologic diseases. We investigated matrix metalloproteinases (MMP-2, MMP-7, and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2) concentration in different etiopathogenetical groups of patients with nasal polyposis (NP) in relation to recurrence after sinonasal surgery. The study group consisted of 45 patients with NP (those with allergic rhinitis, nonallergic rhinitis and asthma or nonallergic rhinitis, and obstruction of osteomeatal complex [OMC]) who underwent endonasal sinus surgery. We also collected 10 patients who underwent septoplasty as control. Immunohistochemistry of nasal mucosa fragments, Western blotting, and polymerase chain reaction analysis showed increased MMPs levels (MMP-9 more than MMP-2 and MMP-7) and decreased tissue inhibitors of MMPs levels (TIMP-1 less than TIMP-2), in patients with chronic rhinosinusitis with nasal polyps compared with control group, in particular in patients with nonallergic rhinitis and asthma compared to those with allergic rhinitis and nonallergic rhinitis and obstruction of OMC. We observed a higher risk of recurrence in patients with nonallergic rhinitis and asthma than in those with allergic rhinitis and nonallergic rhinitis and obstruction of OMC after 36 months from surgery. In this research, we evaluated pathogenesis of NP related to MMPs and their inhibitors concentrations in polypoid tissue.

Relationship between sleep quality and rhinitis in children: role of medical treatment with isotonic and hypertonic saline.

BACKGROUND: The nose represents the port of entry, the first part of the upper airway and accounts for 50% of its total resistance. Many authors identified rhinitis as relevant factor affecting quality of life, and sleep habits of sufferers and their caregiver's, particularly between 4-17 years old children. Both allergic rhinitis and non-allergic rhinitis may represent an important risk for obstructive sleep apnea syndrome in children. We evaluated the quality of sleep and the role of nasal irrigations with saline solutions in children with sign and symptoms of rhinitis. METHODS: An observational retrospective study was conducted on 58 children aged 3-6 years old receiving diagnosis of rhinitis according to clinical and amnestic evaluation. All recruited children were screened before medical topic treatment with the Pediatric Sleep Questionnaire test in order to evaluate the sleep habits and after isotonic and hypertonic saline nasal irrigation for six months. One-Way ANOVA was used for statistical analysis of the results. RESULTS: Forty-nine of 58 recruited children reached the follow-up control after six months of medical treatment. Mean score at Pediatric Sleep Questionnaire before and after medical treatments was respectively 0.39 and 0.28. One-Way ANOVA test showed a significant statistical difference (P<0.05). CONCLUSIONS: Nasal topic decongestant may be used only for short-term treatments, and they do not seem to have long-term results. Topic corticosteroids may be used for long term treatment and their correlations with OSA seem to have different results. This study aims to attracting the attention of pediatricians on the importance of nasal topic saline solutions irrigations in children with rhinitis in improving HRQoL decreasing snoring and apneas and so daytime symptoms.

Role of α-Tocopherol Acetate on Nasal Respiratory Functions: Mucociliary Clearance and Rhinomanometric Evaluations in Primary Atrophic Rhinitis.

Primary atrophic rhinitis is a disease of the nose and of paranasalsinuses characterized by a progressive loss of function of nasal and paranasal mucosa caused by a gradual destruction of ciliary mucosalepithelium with atrophy of serous-mucous glands and loss of bonestructures.The aim of this study was to evaluate the therapeutic effects of topic α-tochopherol acetate (vitamin E) in patients with primary atrophicrhinitis based on subjective and objective data.We analyzed 44 patients with dry nose sensation and endoscopic evidence of atrophic nasal mucosa. We analyzed endoscopic mucosascore, anterior rhinomanometry, and nasal mucociliary clearance before and after 6 months of topic treatment with α-tochopherol acetate. For statistical analysis, we used paired samples t test (95% confidence interval [CI], P < .05) for rhinomanometric and muciliary transit time evaluations and analysis of variance 1-way test (95% CI, P < .05) for endoscopic evaluation. All patients showed an improvement in "dry nose" sensation and inperception of nasal airflow. Rhinomanometric examination showed increase of nasal airflow at follow-up (P < .05); nasal mucociliaryclearance showed a reduction in mean transit time (P < .05); and endoscopic evaluation showed significative improvement of hydration of nasalmucosa and significative decreasing nasal crusts and mucusaccumulation (P < .05). Medical treatment for primary atrophic rhinitis is not clearly documented in the literature; in this research, it was demonstrated that α-ochopherol acetate could be a possible treatment for atrophic rhinitis.

The CO2-laser in the treatment of laryngeal and tracheal stenosis Our personal experiences.

AIM: In the last twenty years, the statement of the CO2 laser in laryngeal microsurgery has proved particularly useful in the surgical treatment of laryngotracheal stenosis. The Authors report their surgical experiences and discuss them considering the location, size and pathologic features of the disease. The aim of this study was to evaluate the results that may be obtained in the treatment of laryngotracheal stenosis by endoscopy using the CO2 laser, and analyze the advantages and limitations of surgical methods implemented. MATERIAL OF STUDY: It includes 128 patients treated from 1981 to 2016 by endoscopy using the CO2 laser. RESULTS: The healing occurred in 121 of the 128 patients (94.5%); in the remaining 7 cases (5.5%) - 4 subjects (3.1%) with supraglottic cicatricial stenosis and 3 patients (2.3%) with widespread laryngotracheal stenosis - it had to integrate the technique of endoscopic surgery with a traditional surgery of recovery. In particular, it has observed as follows: In supraglottic stenosis: - oedematous forms healed without difficulty, a limited number of controls (1-2) was necessary to practice and any type of stent has not been used; - cicatricial forms required a greater number of controls (3-6) and the execution in 2 cases (1.6%) of an arytenoidectomy, we had 4 failures (3.1%) for which it had to implement a recovery surgery of traditional type; In glottic/ipoglottic stenosis: - all oedematous forms healed with a number of checks less than 3, without use of stents; - scarring forms resolved after a higher number of controls (3-6), in 4 of them (3.1%) it was necessary to practice an arytenoidectomy (associated to exeresis of 1/3 posterior ipsilateral true vocal cord) and in 4 (3.1%) had to applied an endolaryngeal guardian (in one case a Traissac stent and in 3 ones a Montgomery T-tube); In tracheal stenosis has occurred healing in all cases, more specifically: - in limited forms to the third anterior of the trachea were enough 1-2 checks and it was not necessary using stent; - in extended forms (involvement of the 2/3 anterior and/or of the whole tracheal circumference) a higher number of controls (3-6) was necessary; - in concentric forms, with total obstruction of the lumen, the application of endoluminal stent (3 Montgomery T-tubes and 2 tracheal cannulas of Silastic) was always necessary in addition to a number of controls superior to 7. - In laryngotracheal spread forms, 3 failures (2.3%) recorded, in all cases, however, many controls (greater than 7) was necessary and a Montgomery T-tube was placed. CONCLUSIONS: The introduction of the CO2 laser in the surgical treatment of laryngotracheal stenosis has undoubtedly improved the chances of endoscopic surgery; it is currently able to offer significant advantages compared to traditional techniques (cures faster, less traumatic interventions, post-operative elapsed better tolerated by patients, etc.) but it is also indisputable that to ensure the success of these operations is essential a correct understanding of the size and pathologic features of the same stenosis: the data, in fact, affect the choice of surgical addresses to adopt in individual cases and the prognostic judgment. KEY WORDS: Airway management, Airway problems, CO2 laser, Direct laryngoscopy, Endoscopy, External surgical approach, Laryngotracheal stenosis, Minimally invasive surgery, Montgomery Safe T-tube, Tracheal stenosis, Tracheostomy.

Intrinsic Laryngeal Lipoma Treated with Transoral CO2 Laser Microsurgery: An Unusual Case Report.

BACKGROUND Lipomas, the most common soft tissue tumors, represent almost half of all benign mesenchymal neoplasms and are characterized by the absence of symptoms. However, if they grow in a laryngeal site, they can cause dyspnea and dysphonia which represents one of the major symptoms of benign laryngeal diseases (such as polyps or nodules); these symptoms are often the first symptom of neoplastic diseases. CASE REPORT We present a case of a 28-year-old female patient with a rounded pseudocyst neoformation located in the left aryepiglottic fold that partially hid the homolateral vocal cord and limited its mobility. Due to the site of the lesion and MRI images showing a well-capsulated neoformation without contrast enhancement, we decided to surgically remove it with a micro-laryngoscopic approach after an evaluation of the patient's upper airway by an anesthetist. This case demonstrates that a micro-endoscopic approach using transoral laser microsurgery for surgical excision was useful for removing the entire mass and avoiding relapses. CONCLUSIONS Laryngeal lipomas are benign and rare lesions, in particular intrinsic lipomas are uncommon, but, if they grow, they can cause life-threatening symptoms. In our case, a lipoma reached a size of around 2 centimeters and was not pedunculated, only a histopathological examination of the surgical specimens could provide a differential diagnosis against a lipoma-like liposarcoma. The use of Transoral Laser CO2 Micro-laryngoscopy (TLM) provided good management of a small intrinsic lipomas of the larynx, minimizing the potential for relapses.

Anthropometric Parameters for Nose Evaluation and Nasal Surgery Planning.

BACKGROUND: The esthetic characteristics of face and nose are commonly evaluated before rhinoplasty using a completely subjective method, due to the lack of validated and reliable methods for quantifying facial esthetics and for accurate nose treatment planning. The aim of the study was to review the literature to determine and evaluate the points, distances, and angles commonly used in the treatment planning for rhinoplasty. METHODS: Research based on anthropometric studies of the face and nose, published from 1987 to 2018 was included. Finally, 138 papers were selected after a statistical analysis through a simple random and non-random sample selection, and all papers were evaluated in their entirety. RESULTS: According to the frequency of citation, 198 points, 336 distances, and 199 angles were listed. The first quartile of each distribution was eliminated, and frequency of more than 25% was selected. A group of 49 points, 77 distances, and 11 angles, were classified according to their anatomical region, that is, bone and soft tissues, was obtained. CONCLUSIONS: An enormous inhomogeneity and lack of standardized anthropometric measurement system, specifically of the nose, was evident, as the studies were conducted by authors of different origins. According to universally accepted parameters, the importance of a reliable method for nose surgery planning is highlighted.

Definition of miRNA Signatures of Nodal Metastasis in LCa: miR-449a Targets Notch Genes and Suppresses Cell Migration and Invasion.

Laryngeal cancer (LCa), a neoplasm of the head and neck region, is a leading cause of death worldwide. Surgical intervention remains the mainstay of LCa treatment, but a crucial point is represented by the possible nodal involvement. Therefore, it is urgently needed to develop biomarkers and therapeutic tools able to drive treatment approaches for LCa. In this study, we investigated deregulated microRNAs (miRNAs) in tissues from LCa patients with either lymph node metastases (N+) or not (N-). miRNA expression profiling was performed by a comprehensive PCR array and subsequent validation by RT-qPCR. Results showed a significant decrease of miR-449a expression in N+ compared to N- patients, and miR-133b down-modulation in LCa tissues compared to paired normal ones. Receiver operating characteristic (ROC) curve analysis revealed the potential diagnostic power of miR-133b for LCa detection. According to the validation results, we selected miR-449a for further in vitro studies. Ectopic miR-449a expression in the LCa cell line Hep-2 inhibited invasion and motility in vitro, slowed cell proliferation, and induced the downregulation of Notch1 and Notch2 as direct targets of miR-449a. Collectively, this study provides new promising biomarkers for LCa diagnosis and a new opportunity to use miR-449a for the treatment of nodal metastases in LCa patients.

Choanal Polyp with Osseous Metaplasia: Radiological and Therapeutic Management of a Rare Case and a Review of Bone Metaplastic Lesions of Sinonasal Tract.

BACKGROUND Osseous metaplasia is a heterotopic normal bone in soft tissues. It is occasionally found in mucosal polyps of the external auditory canal, tongue, gut, stomach, nasal cavity, and uterus. Choanal polyp with osseous metaplasia originating from the lateral wall of the nasopharynx has not been previously reported. In fact, osseous metaplasia in nasal polyps represents a very uncommon histological finding with only 12 cases described in the literature. CASE REPORT We reported here, the clinical, radiological, and therapeutic management of a nasopharynx choanal polyp in a patient with severe nasal obstruction and rhinolalia history. Endoscopic examination of nasal cavities revealed a polypoid-like mass in the left nasal fossa, extending to the choanal area and nasopharynx. Computed tomography scan and contrast-enhanced magnetic resonance imaging confirmed the presence of a solitary and lobulated mass in the choanal area and nasopharynx. We performed the removal of the mass through careful hemostasis of left sphenopalatine artery using both transnasal and transoral paths, with no complications for the patient. Histopathological examination of the biopsy revealed a benign inflammatory polyp with osseous metaplasia. No recurrence was noted 24 months after surgery. CONCLUSIONS The incidence of ossifying areas in nasal polyps is very low, with only 12 cases reported in the literature. Ossifying polyps originating from the lateral wall of nasopharynx has never been reported before. The use of a combined endoscopic and transoral surgical approach was shown to be reliable in terms of adequate exposure and visualization of the lesion, control of bleeding, and complete removal of the mass.

The Long Non-Coding RNA Prader Willi/Angelman Region RNA5 (PAR5) Is Downregulated in Anaplastic Thyroid Carcinomas Where It Acts as a Tumor Suppressor by Reducing EZH2 Activity.

Anaplastic thyroid carcinoma (ATC) represents one the most aggressive neoplasias in humans, and, nowadays, limited advances have been made to extend the survival and reduce the mortality of ATC. Thus, the identification of molecular mechanism underlying its progression is needed. Here, we evaluated the long non-coding RNA (lncRNA) expression profile of nine ATC in comparison with five normal thyroid tissues by a lncRNA microarray. By this analysis, we identified 19 upregulated and 28 downregulated lncRNAs with a fold change >1.1 or <-1.1 and p-value < 0.05, in ATC samples. Some of them were subsequently validated by qRT-PCR. Then, we investigated the role of the lncRNA Prader Willi/Angelman region RNA5 (PAR5), drastically and specifically downregulated in ATC. The restoration of PAR5 reduces proliferation and migration rates of ATC-derived cell lines indicating that its downregulation contributes to thyroid cancer progression. Our results suggest that PAR5 exerts its anti-oncogenic role by impairing Enhancer of Zeste Homolog 2 (EZH2) oncogenic activity since we demonstrated that PAR5 interacts with it in thyroid cancer cell lines, reducing EZH2 protein levels and its binding on the E-cadherin promoter, relieving E-cadherin from the negative regulation by EZH2. Consistently, EZH2 is overexpressed in ATC, but not in differentiated thyroid carcinomas. The results reported here define a tumor suppressor role for PAR5 in undifferentiated thyroid neoplasias, further highlighting the pivotal role of lncRNAs in thyroid carcinogenesis.