Fitostimoline® in fibro-endoscopic and trans-nasal trans-speculum septoplasty as a beneficial tool to improve post-surgical outcome: Preliminary results of a case-control study.

OBJECTIVES: Topic treatment can be useful to improve short and long-term nasal outcomes after nasal surgery, reducing discomfort and risk of synechia. This study aimed at evaluating the effect on clinical outcomes of nasal packaging using Fitostimoline® gauze in FESS and septoplasty. METHODS: A case-control study on hospitalized patients was performed in a tertiary referral center. The control group included 20 patients treated with the standard surgical protocol for septoplasty and standard nasal packaging; treatment group included 21 patients underwent same surgical procedure but in whom the nasal tampon was wrapped with a gauze containing Fitostimoline® before being placed into the nose. RESULTS: Patients in treatment group had better outcomes than control; nasal mucosa showed better healing - recovery of normal color- in those patients in whom we applied the Fitostimoline® gauze around tampons. Moreover, 100 % patients in the treatment group did not refer discomfort during at tampon removal versus 60 % subjects in the control group who referred pain, tension or tearing during the same action. CONCLUSION: Our results, although preliminary because of the small cohort of subjects included, suggest that the apposition of a gauze with Fitostimoline® after nasal surgery might improve the mucosal healing with consequent reduction of patients discomfort during the post-surgical period.

Endaural microscopic approach versus endoscopic transcanal approach in treatment of attic cholesteatomas.

PURPOSE: Compare the audiological results and postoperative outcomes of the endoscopic approach versus the endaural microscopic approach for treatment of attic cholesteatomas, using a randomized prospective model. MATERIALS AND METHODS: Eighty patients were consecutively enrolled in the study and randomized into two groups of treatment of 40 patients: Group A -tympanoplasty with a microscopic endaural approach; Group B -tympanoplasty with an exclusive trans-meatal endoscopic approach. Preoperative, intraoperative and postoperative outcomes were evaluated. Hearing was assessed preoperatively and at 1 month, 3 months and 6 months after surgery in both groups. RESULTS: There were no differences in the parameters analyzed (CT findings, patient age, disease duration, intraoperative cholesteatoma characteristics,) between the group A and B patients. No statistical difference between the two groups regarding hearing improvement, abnormal taste sensation, dizziness, post-operative pain and healing times emerged. Graft success rate was 94.5 % and 92.1 % for MES and ESS respectively. CONCLUSION: Both microscopic and exclusively endoscopic endaural approaches offer similar and excellent results in the surgical treatment of attic cholesteatomas.

Diabetes Mellitus and Hearing Loss: A Complex Relationship.

Background and Objectives: Discussion is open about the relationship between diabetes (DM) and hearing loss (HL). There is a lot of evidence in the literature suggesting a causal link between these conditions, beyond being considered simple comorbidities. The difficulty in identifying populations free from confounding factors makes it difficult to reach definitive conclusions on the pathophysiological mechanisms at play. Nonetheless, there is numerous evidence that demonstrates how the population affected by DM is more affected by sensorineural HL (SNHL) and exhibit a higher prevalence of idiopathic sudden sensorineural HL (ISSNHL). Materials and Methods: Articles reporting potentially relevant information were reviewed, and the most significant results are discussed in this article. Starting from the possible mechanisms relating to auditory impairment in the diabetic condition, this article summarizes the studies on auditory evaluation in subjects with DM1 and DM2 and addresses the relationship between DM and ISSNHL. Results: DM is considered a risk factor for SNHL, although some studies have reported no relationship when the associations were adjusted for age, gender, and hypertension. Macro and microvascular insults that cause decreased blood flow, oxygen exchange, and ion transport are major complications of hypertension and DM and can have a direct effect on the sensory and support cells of the cochlea. Conclusions: Given the difficulty of carrying out studies on populations without confounding factors, new laboratory studies are strongly required to clarify which specific physiopathological mechanisms underlie the diabetic damage caused to the hearing organs and how pharmacological management may contribute to counteracting the pathophysiological effects of the diabetic condition on the auditory system.

Symptoms and clinical features in patients affected by endolymphatic sac tumor: a systematic review and meta-analysis.

PURPOSE: Most ELST data in the literature are case studies or limited to small cohorts (< 16 patients). We evaluated the main clinical signs observed at endolymphatic sac tumor (ELST) diagnosis in patients with or without Von Hippel-Lindau disease. METHODS: We conducted a comprehensive literature search in PubMed, Scopus, and Web of Science. We included studies with at least 1 patient, of any age, affected by sporadic or VHL-related ELSTs reporting levels of hearing loss and facial nerve function and a comprehensive description of presenting symptoms at ELST diagnosis. We combined data for proportional meta-analysis. p values of 0.05 were considered statistically significant. Methodological quality was evaluated. Analyses were performed with MedCalc 14.8.1 software. RESULTS: A total of 26 studies, including 113 patients and 118 cases of ELSTs were included. Pooled proportion rates (95% CI) of overall hearing loss was 88.7%, (82.4-93.4), severe hearing loss was 21.6% (12.8-32.1) profound hearing loss was 39.8% (28.7-51.5), vertigo/imbalance was 42.0% (33.8-50.5), tinnitus was 61.8% (53.4-69.8) and facial nerve palsy was 30.6% (23.2-38.9). Generally, symptoms were homogeneous or moderately heterogeneous among included studies. CONCLUSION: This is the first systematic review of clinical presentations at ELST diagnosis. The most serious clinical events include profound hearing loss and facial impairment. Fluctuating hearing loss, tinnitus and vertigo are frequently reported and may confound correct and prompt ELST diagnosis.

Orbital wall decompression in the management of Graves' orbitopathy: a systematic review with meta-analysis.

PURPOSE: To systematically review outcomes of orbital bony wall decompression for Grave's orbitopathy according to the surgical approach. METHODS: A systematic search for studies published in "Ovid MEDLINE", "Web of Science" and "Embase" of patients with surgical treatment of Grave's orbitopathy was performed. The overall postoperative change in Hertel exophthalmometry was calculated by random-effect meta-analysis model with 95% confidence interval (CI). RESULTS: A total of 33 studies, including 1686 patients and 2946 procedures, were included. The weighted mean Hertel value overall reduction was - 4.56 mm (95% CI - 5.05 to - 4.07 mm). According to surgical techniques the reduction was - 4.36 mm (95% CI - 5.22 to - 3.50) for infero-medial technique, - 4.88 mm (- 5.68 to - 4.08) for medial-lateral technique, - 4.32 mm (- 4.80to - 3.84) for lateral technique, - 5.45 mm (- 6.16 to - 4.74) for three-wall technique and - 3.47 mm (- 5.81 to - 1.12) for medial technique. The overall rate of new-onset of primary gaze diplopia was reported in 23 studies. The included procedures were 653 and results were heterogeneous (heterogeneity: Q = 78.8 df = 22, I2 = 72.09%, p < 0.01). The pooled proportion (95% CI) rate of new-onset of primary gaze diplopia was 12% (7-16). CONCLUSION: Our metanalysis highlights that orbital bony wall decompression represents an effective surgical procedure. The three wall approach was associated with the best results in terms of exophthalmos reduction. Data suggest that an exclusive lateral approach may help to avoid the new-onset of primary gaze diplopia during the postoperative period.

MiR-126 in intestinal-type sinonasal adenocarcinomas: exosomal transfer of MiR-126 promotes anti-tumour responses.

BACKGROUND: Intestinal-type sinonasal adenocarcinomas (ITACs) are aggressive malignancies related to wood dust and leather exposure. ITACs are generally associated with advanced stage at presentation due to the insidious growth pattern and non-specific symptoms. Therefore, biomarkers that can detect the switch from the benign disease to malignancy are needed. Essential for tumour growth, angiogenesis is an important step in tumour development and progression. This process is strictly regulated, and MiR-126 considered its master modulator. METHODS: We have investigated MiR-126 levels in ITACs and compared them to benign sinonasal lesions, such as sinonasal-inverted papillomas (SIPs) and inflammatory polyps (NIPs). The tumour-suppressive functions of MiR-126 were also evaluated. RESULTS: We found that MiR-126 can significantly distinguish malignancy from benign nasal forms. The low levels of MiR-126 in ITACs point to its role in tumour progression. In this context, restoration of MiR-126 induced metabolic changes, and inhibited cell growth and the tumorigenic potential of MNSC cells. CONCLUSIONS: We report that MiR-126 delivered via exosomes from endothelial cells promotes anti-tumour responses. This paracrine transfer of MiRs may represent a new approach towards MiR-based therapy.

Prognostic aspects in the treatment of juvenile nasopharyngeal carcinoma: a systematic review.

To systematically review and discuss the published data about treatments and outcomes for children and adolescents affected by nasopharyngeal carcinoma. In April 2015, an appropriate string was run on PubMed to retrieve all relevant articles. A cross-check was performed by two of the authors on abstracts and full-text articles found using the selected inclusion and exclusion criteria. A meta-analysis concerning the rate of reported disease-free survival and overall survival was performed. Fifteen studies were identified comprising a total of 865 subjects affected by nasopharyngeal carcinoma. According to the American Joint Committee for Cancer Staging system, the majority of tumors were classified as Stage IV (57.3 %). All included patients underwent radiotherapy, while 687 (79.4 %) received also some regimen of chemotherapy. On the basis of our statistical analysis, the mean (95 % CI) rate of disease-free survival was 66 % (95 % CI 56-76). The mean (95 % CI) rate of the overall survival resulted 68 % (95 % CI 58-78). On the basis of our analysis, it may be affirmed that the prognosis of juvenile nasopharyngeal carcinoma is still unsatisfactory. New reports on homogeneous populations are needed to better define the most influencing prognostic factors and to evaluate the introduction of possible alternative therapeutic protocols.

Therapeutic modalities and oncologic outcomes in the treatment of T1b glottic squamous cell carcinoma: a systematic review.

T1a and T1b glottic squamous cell carcinoma (SCC) are often analyzed together by authors who investigate the oncologic outcomes achieved after different therapeutic options. Nevertheless, T1b definitely represents a more advanced tumor stage compared to T1a glottic SCC. The objective of this review was first to analyze the overall success rates in the treatment of patients affected by T1b glottic SCC. Moreover, a subgroup analysis was planned to specifically compare the outcomes obtained with radiotherapy (RT), transoral laser microsurgery (TLM) and open partial laryngectomies (OPL). An electronic library search of the relevant English literature was performed. Potentially eligible articles were reviewed. Qualified articles were selected and evaluated. Fifty-two studies comprising 2360 patients were included. The overall rate of disease-free survival (DFS) was 85% (95% CI 83-87). The overall rate of overall survival was 85% (95% CI 80-88) while the rate of disease-specific survival (DSS) was found to be 96% (95% CI 90-98). Statistical data concerning outcomes for each therapeutic modality showed an higher DFS rate for subjects treated with RT and OPL, respectively, 87% (95% CI 0.85-0.89) and 83% (95% CI 0.78-0.89), when compared to those who underwent TLM 77% (95% CI 0.69-0.83). In conclusion, our results showed a high level of overall DSS (96%) for patients affected by T1b glottic SCC. Regarding the specific therapeutic options, our subgroup analysis showed as patients treated with TLM present a higher rate of oncological recurrence in comparison to those who underwent RT or OPL. Nevertheless, on the basis of our data it was also noted that no significant differences subsist in terms of survival rates among the three different treatments. Moreover, the absence of a comparative analysis useful to confirm these conclusions must be considered.

Eustachian tube evaluation in aviators.

The aim of the study is to evaluate the Eustachian tube functionality in a group of aviators to underline a subclinical dysfunction and the related risk of ear fullness or barotitis. Hypobaric chamber allows to simulate the pressure variation of the flight. This prospective study enrolled 42 aviation pilots, members of the Italian Air Force, to whom were evaluated Eustachian tube functionality by Tubomanometry, patients subjective assessments concerning feasibility of Valsalva's and Toynbee's clinical symptoms, tympanometry, and objective Valsalva before and after exposure to hypobaric chamber. The new Eustachian tube score (ETS-7) was also calculated for each pilot before and after exposure to hypobaric chamber. Results of our examination showed that: before chamber exposition, in 92.8 % of pilots, an ETS-7 of eight or more was found bilaterally. In three (7.2 %) cases, a unilateral ETS-7 ≤ 7 was found and two of those had a positive history. After undergoing the hypobaric chamber session, the evaluation of ETS-7 showed only 19 % of pilots with an ETD score ≤7, in particular three bilateral and five unilateral cases. Three of those pilots were clinically positive: two airmen reported persistent fullness, while the other one had a barotitis. Therefore, the combined use of TMM and ETS-7 before and after hypobaric chamber exposure appears to be a reliable method for assessing the functional capacity of the Eustachian tube in aviators, the stressful effect of flight on it, to exclude subjects at increased risk of ear pain, fullness, or barotrauma.

Tympanomastoid cholesterol granuloma: radiological and intraoperative findings of blood source connection.

The hypothesis that the close contiguity between the cholesterol granulomas and some rich blood sources provided the trigger to the aggressive nature of tympanomastoid cholesterol granulomas has been recently reported. To corroborate this new etiopathogenetic theory we retrospectively reviewed a series of 14 patients with primary middle ear and mastoid cholesterol granulomas and investigated the temporal bone marrow invasion and its hematopoietic potentialities and a possible cholesterol granulomas contiguity with relevant vascular structures such as the carotid artery, sigmoid jugular system, mastoid or dural vein. Eight cases did not show radiological sign of bone marrow invasion or hematopoietic potentialities visible in MRI. Besides no intraoperative vascular connections that could explain an initial bleeding source were found. Cholesterol granulomas bone marrow invasion was present in six patients. A bone marrow hematopoietic potentiality was showed in four of these patients, whereas, an evident anatomical contiguity of the cholesterol granuloma with some important temporal bone vascular structures was visible in five cases. Analysis of cardiovascular risk factors showed that four patients presented one or more of the risk factors analysed.

The prognostic value of cyclin D1 expression in head and neck squamous cell carcinoma.

The correlation between cyclin D1 overexpression and the clinical outcome of head and neck cancer is not defined. The aim of this meta-analysis was to evaluate the prognostic value of cyclin D1 in patients with head and neck cancer. A search thorough Ovid MEDLINE was performed to enroll all eligible articles. Twenty-two studies comprising a total of 1,929 patients with different head and neck cancers were included. Cyclin D1 overexpression was significantly associated with lymph node metastasis [OR 2.25; 95 % confidence interval (CI) 1.76-2.87] and worse disease-free survival (OR 3.06; 95 % CI 2.42-3.87]. Subgroup analysis revealed that cyclin D1 overexpression correlated significantly with nodal metastasis for laryngeal cancer (OR 2.26; 95 % CI 1.61-3.16) and was a significant poor predictor for nasopharyngeal cancer (OR 4.44; 95 % CI 1.89-10.42). Our meta-analysis suggests that cyclin D1 overexpression could represent an important prognostic indicator for patients with head and neck cancer.

Wood dust exposure induces cell transformation through EGFR-mediated OGG1 inhibition.

A high risk of neoplastic transformation of nasal and paranasal sinuses mucosa is related to the occupational exposure to wood dust. However, the role of occupational exposures in the aetiology of the airway cancers remains largely unknown. Here, an in vitro model was performed to investigate the carcinogenic effect of wood dusts. Human bronchial epithelial cells were incubated with hard and soft wood dusts and the DNA damage and response to DNA damage evaluated. Wood dust exposure induced accumulation of oxidised DNA bases, which was associated with a delay in DNA repair activity. By exposing cells to wood dust at a prolonged time, wood dust-initiated cells were obtained. Initiated-cells were able to form colonies in soft agar, and to induce blood vessel formation. These cells showed extensive autophagy, reduced DNA repair, which was associated with reduced OGG1 expression and oxidised DNA base accumulation. These events were found related to the activation of EGFR/AKT/mTOR pathway, through phosphorylation and subsequent inactivation of tuberin. The persistence in the tissue of wood dusts, their repetitious binding with EGFR may continually trigger the activation switch, leading to chronic down-regulation of genes involved in DNA repair, leading to cell transformation and proliferation.

Taste and olfaction in middle ear surgery.

OBJECTIVE: The aim of this study was to assess pre- and postoperative taste ability in patients undergoing middle ear surgery for otosclerosis or chronic otitis media. Olfactory function was also evaluated to rule out taste deficits due to concomitant nasal pathology. METHODS: All patients underwent ear, nose, and throat examination, otomicroscopy, nasal endoscopy, anterior rhinomanometry, taste testing, and olfactory testing. Patients were evaluated at 1 to 5 days preoperatively (T0), and at 1 (T1), 6 (T6), and 12 (T12) months postoperatively. RESULTS: Both groups of patients experienced worsening of the mean taste threshold postoperatively. This phenomenon was more serious in poststapedotomy patients. Follow-up showed progressive improvement in both groups. All values of olfactory testing were within the normal range for otosclerosis patients. Patients with chronic otitis media showed variable postoperative findings. CONCLUSION: Chorda tympani function can be negatively affected by middle ear surgery. Deficits may be more marked in stapedotomy patients than in those undergoing tympanoplasty. Postoperative recovery of taste is satisfactory, although with different timelines for the 2 types of pathology.

A 1-year follow-up study with C-VEMPs, O-VEMPs and video head impulse testing in vestibular neuritis.

The aim of this paper was to evaluate prospectively, in a group of patients affected by VN, a diagnostic protocol employing C-VEMPs, O-VEMPs and vHIT together. The diagnosis of vestibular neurolabyrinthitis was based on the clinical history, absence of associated auditory or neurological symptoms, and a neuro-otological examination with an evaluation of lateral semicircular canal function using the Fitzgerald-Hallpike caloric vestibular test and ice test. Our series revealed an incidence of 55% of superior and inferior vestibular neurolabyrinthitis, 40% of superior vestibular neurolabyrinthitis and 5% of inferior vestibular neurolabyrinthitis. These data, however, comprised different degrees of vestibular involvement considering the evaluation of each single vestibular end-organ with potential different prognosis. Four patients had only deficits of the horizontal and superior semicircular canals or their ampullary nerves. The implementation of C-VEMPs, O-VEMPs and vHIT in a vestibular diagnostic protocol has made possible to observe patients with ampullary VN, unidentifiable with other types of vestibular exams. The effect of age seems to have some impact on the recovery. When recovery firstly involves the utricular and saccular nerves and subsequently the ampullary nerves, it may be reasonable to expect a more favorable and successful outcome.

The clinical relevance of Ki-67 expression in laryngeal squamous cell carcinoma.

The aim of this study was to determine the prognostic value of Ki-67 immunostaining in patients affected by laryngeal squamous cell carcinoma. A systematic review was carried out in a tertiary university referral center. An appropriate string was run on PubMed to retrieve articles dealing with Ki-67 immunohistochemical staining and laryngeal squamous cell carcinoma. A double cross-check was performed on citations and full-text articles by two investigators independently to review all manuscripts and perform a comprehensive quality assessment. Of 85 abstracts identified, 18 articles were included. These studies reported on 1,342 patients with histological confirmed diagnosis of laryngeal squamous cell carcinoma. Most studies showed a statistical association between Ki-67 immunohistochemical expression and at least one of the clinical and histopathological parameters considered by the authors. Overall the studies analyzed suggested that the tumoral proliferative index was statistically connected respectively with T stage (2/18), N stage (4/18), grading (6/18), disease-free survival (10/18) and overall survival (4/18). Our review strongly suggests that immunohistochemical staining of Ki-67 correlates with tumoral aggressiveness and worse prognosis in patients affected by laryngeal squamous cell carcinoma. Further high-quality prospective studies should be carried out to confirm our finding and determine the eventual differences between cancers of specific laryngeal subsites.

Vestibular neurolabyrinthitis: a follow-up study with cervical and ocular vestibular evoked myogenic potentials and the video head impulse test.

OBJECTIVES: The aim of this study was to evaluate prospectively, in a group of patients affected by vestibular neurolabyrinthitis (VN), a diagnostic protocol including cervical vestibular evoked myogenic potentials (C-VEMPs), ocular vestibular evoked myogenic potentials (O-VEMPs), and the video head impulse test (vHIT). METHODS: The diagnosis of VN was based on the patient's clinical history, an absence of associated auditory or neurologic symptoms, and a neuro-otological examination with an evaluation of lateral semicircular canal function by use of the Fitzgerald-Hallpike caloric vestibular test and the ice test. RESULTS: In our series, 55% of the cases were superior and inferior VN, 40% were superior VN, and 5% were inferior VN. These cases, however, comprised different degrees of vestibular involvement, as the individual vestibular end organs have different prognoses. Four patients had only deficits of the horizontal and superior semicircular canals or their ampullary nerves. CONCLUSIONS: The implementation of C-VEMPs, O-VEMPs, and the vHIT in a vestibular diagnostic protocol has made it possible to observe patients with ampullary VN in a way that has not been feasible with other types of vestibular examinations. The age of the patient seems to have some impact on recovery from VN. When recovery occurs in the utricular and saccular nerves first and in the ampullary nerves subsequently, it may be reasonable to expect a more favorable outcome.

The role of antibiotic therapy and nasal packing in septoplasty.

Both systemic antibiotic therapy and nasal packing are used frequently in septoplasty. Nevertheless, there is still great disagreement among authors around the real advantages with regard to the efficacy of both of these procedures in septal surgery. The aim of the present review was to evaluate the more recent data published on this topic. One appropriate string was run on PubMed to retrieve articles dealing with the topics mentioned above. A double cross-check was performed on citations and full-text articles found using the selected inclusion and exclusion criteria. Overall, the articles we analyzed indicated the poor utility of routine antibiotic therapy and nasal packing during septoplasty, the latter procedure producing more complications than advantages. In conclusion, on the basis of the recent literature, the use of systemic antibiotic prophylaxis and nasal packing in septal surgery seems to be a non-rational procedure.

Improving the endoscopic endonasal transclival approach: the importance of a precise layer by layer reconstruction.

BACKGROUND. The endoscopic endonasal transclival approach (EETCA) is a minimally-invasive technique allowing a direct route to the base of implant of clival lesions with reduced brain and neurovascular manipulation. On the other hand, it is associated with potentially severe complications related to the difficulties in reconstructing large skull base defects with a high risk of postoperative cerebrospinal fluid (CSF) leakage. The aim of this paper is to describe a precise layer by layer reconstruction in the EETCA including the suture of the mucosa as an additional reinforcing layer between cranial and nasal cavity in order to speed up the healing process and reduce the incidence of CSF leak. METHODS. This closure technique was applied to the last six cases of EETCA used for clival meningiomas (2), clival chordomas (2), clival metastasis (1), and craniopharyngioma with clival extension (1). RESULTS. After a mean follow-up of 6 months we had no one case of postoperative CSF leakage or infections. Seriated outpatient endoscopic endonasal controls showed a fast healing process of nasopharyngeal mucosa with less patient discomfort. CONCLUSIONS. Our preliminary experience confirms the importance of a precise reconstruction of all anatomical layers violated during the surgical approach, including the nasopharygeal mucosa.

Predicting 60-Day Mortality in a Home-Care Service: Development of a New Inter-RAI 49-Frailty Index in Patients with Chronic Disease and without a Cancer Diagnosis.

OBJECTIVE: Frailty Index (FI) is used to define the level of frailty in various clinical settings. Fifteen- and 26-item FIs have been demonstrated to predict 1-year mortality and intensity of care in home care (HC) and palliative home care (PHC). The objective of this study was to develop a new FI to predict the 60-day risk of death or transition to a PHC service after the initiation of an HC service in patients with chronic disease and without a cancer diagnosis. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Patients 18 years and older followed in an HC service of a "Frailty Department-Local Palliative Care Network" from January 1, 2017, to October 31, 2021. METHODS: A 49-item FI (FI-49) was developed selecting variables within the standardized international Residential Assessment Instrument assessments (interRAI-HC) and compared to existing FIs with 15 and 26 variables. RESULTS: A total of 2099 patients were included in the study with a median age of 80.0 years (IQR: 72.0-86.0) and a predominantly female population (62.4%). Among these patients, 8% died or were transferred to PHC within the 60-day follow-up. The FI-49 demonstrated a higher ability to predict 60-day mortality (C index 0.8165, 95% CI 0.7848-0.8481) compared to the 26- and 15-item FI. An FI-49 cutoff of 0.33 was also selected to provide clinicians with a more practical approach (C-index of 0.7044, 95% CI 0.6796-0.7292). CONCLUSION AND IMPLICATION: The FI-49 is a good predictor of short-term mortality or transition to palliative care among older patients referred to an HC service. The automatic calculation of this tool could facilitate more appropriate care planning and the correct allocation of healthcare resources, especially considering the rapid ageing of the population.

AGO2-RIP-Seq reveals miR-34/miR-449 cluster targetome in sinonasal cancers.

Sinonasal tumours are heterogeneous malignancies, presenting different histological features and clinical behaviour. Many studies emphasize the role of specific miRNA in the development and progression of cancer, and their expression profiles could be used as prognostic biomarkers to predict the survival. Recently, using the next-generation sequencing (NGS)-based miRNome analysis the miR-34/miR-449 cluster was identified as miRNA superfamily involved in the pathogenesis of sinonasal cancers (SNCs). In the present study, we established an Argonaute-2 (AGO2): mRNA immunoprecipitation followed by high-throughput sequencing to analyse the regulatory role of miR-34/miR-449 in SNCs. Using this approach, we identified direct target genes (targetome), which were involved in regulation of RNA-DNA metabolic, transcript and epigenetic processes. In particular, the STK3, C9orf78 and STRN3 genes were the direct targets of both miR-34c and miR-449a, and their regulation are predictive of tumour progression. This study provides the first evidence that miR-34/miR-449 and their targets are deregulated in SNCs and could be proposed as valuable prognostic biomarkers.