Extracellular vesicles secreted by cumulus cells contain microRNAs that are potential regulatory factors of mouse oocyte developmental competence.

The role of cumulus cells (CCs) in the acquisition of oocyte developmental competence is not yet fully understood. In a previous study, we matured cumulus-denuded fully-grown mouse oocytes to metaphase II (MII) on a feeder layer of CCs (FL-CCs) isolated from developmentally competent (FL-SN-CCs) or incompetent (FL-NSN-CCs) SN (surrounded nucleolus) or NSN (not surrounding nucleolus) oocytes, respectively. We observed that oocytes cultured on the former could develop into blastocysts, while those matured on the latter arrested at the 2-cell stage. To investigate the CC factors contributing to oocyte developmental competence, here we focused on the CCs' release into the medium of extracellular vesicles (EVs) and on their miRNA content. We found that, during the 15-h transition to MII, both FL-SN-CCs and FL-NSN-CCs release EVs that can be detected, by confocal microscopy, inside the zona pellucida (ZP) or the ooplasm. The majority of EVs are <200 nm in size, which is compatible with their ability to cross the ZP. Next-generation sequencing of the miRNome of FL-SN-CC versus FL-NSN-CC EVs highlighted 74 differentially expressed miRNAs, with 43 up- and 31 down-regulated. Although most of these miRNAs do not have known roles in the ovary, in silico functional analysis showed that seven of these miRNAs regulate 71 target genes with specific roles in meiosis resumption (N = 24), follicle growth (N = 23), fertilization (N = 1), and the acquisition of oocyte developmental competence (N = 23). Overall, our results indicate CC EVs as emerging candidates of the CC-to-oocyte communication axis and uncover a group of miRNAs as potential regulatory factors.

Novel cellular systems unveil mucosal melanoma initiating cells and a role for PI3K/Akt/mTOR pathway in mucosal melanoma fitness.

BACKGROUND: Mucosal Melanomas (MM) are highly aggressive neoplasms arising from mucosal melanocytes. Current treatments offer a limited survival benefit for patients with advanced MM; moreover, the lack of pre-clinical cellular systems has significantly limited the understanding of their immunobiology. METHODS: Five novel cell lines were obtained from patient-derived biopsies of MM arising in the sino-nasal mucosa and designated as SN-MM1-5. The morphology, ultrastructure and melanocytic identity of SN-MM cell lines were validated by transmission electron microscopy and immunohistochemistry. Moreover, in vivo tumorigenicity of SN-MM1-5 was tested by subcutaneous injection in NOD/SCID mice. Molecular characterization of SN-MM cell lines was performed by a mass-spectrometry proteomic approach, and their sensitivity to PI3K chemical inhibitor LY294002 was validated by Akt activation, measured by pAkt(Ser473) and pAkt(Thr308) in immunoblots, and MTS assay. RESULTS: This study reports the validation and functional characterization of five newly generated SN-MM cell lines. Compared to the normal counterpart, the proteomic profile of SN-MM is consistent with transformed melanocytes showing a heterogeneous degree of melanocytic differentiation and activation of cancer-related pathways. All SN-MM cell lines resulted tumorigenic in vivo and display recurrent structural variants according to aCGH analysis. Of relevance, the microscopic analysis of the corresponding xenotransplants allowed the identification of clusters of MITF-/CDH1-/CDH2 + /ZEB1 + /CD271 + cells, supporting the existence of melanoma-initiating cells also in MM, as confirmed in clinical samples. In vitro, SN-MM cell lines were sensitive to cisplatin, but not to temozolomide. Moreover, the proteomic analysis of SN-MM cell lines revealed that RICTOR, a subunit of mTORC2 complex, is the most significantly activated upstream regulator, suggesting a relevant role for the PI3K-Akt-mTOR pathway in these neoplasms. Consistently, phosphorylation of NDRG1 and Akt activation was observed in SN-MM, the latter being constitutive and sustained by PTEN loss in SN-MM2 and SN-MM3. The cell viability impairment induced by LY294002 confirmed a functional role for the PI3K-Akt-mTOR pathway in SN-MM cell lines. CONCLUSIONS: Overall, these novel and unique cellular systems represent relevant experimental tools for a better understanding of the biology of these neoplasms and, as an extension, to MM from other sites.

Salvage endoscopic nasopharyngectomy for recurrent nasopharyngeal carcinoma in a non-endemic area.

PURPOSE: To analyze oncological outcomes of endoscopic surgical treatment of locally recurrent EBV-related undifferentiated non-keratinizing nasopharyngeal carcinoma (uNK-NPC) in a non-endemic area. METHODS: Retrospective review of patients affected by recurrent uNK-NPC treated with nasopharyngeal endoscopic resection (NER) in a tertiary-care referral center from 2003 to 2022, by evaluating survival rates, prognostic factors, and follow-up strategies. RESULTS: The oncological outcomes of 41 patients were analyzed, over a mean follow-up period of 57 months. The 5-year overall, disease-specific, and disease-free survival of the cohort were 60.7% ± 8.9%, 69% ± 9%, and 39.7% ± 9.2%, respectively. The local (rT) and regional (rN) extension of recurrent disease, stage of disease, and status of resection margins appeared to significantly influence survivals. After a mean follow-up period of 21 months, a further recurrence after NER was observed in 36.6% of cases. Skull base osteonecrosis induced by previous irradiation and post-surgical bone remodeling represent the major challenges for early detection of further local relapses during postoperative follow-up. CONCLUSION: NER appeared as a safe and effective treatment for recurrent uNK-NPC. The adequate selection of patients eligible for NER is essential, to maximize the chances to cure and minimize the risk of local complications.

Surgical Approaches for Possible Positions of an Olfactory Implant to Stimulate the Olfactory Bulb.

INTRODUCTION: Current scientific developments seem to allow for an "olfactory implant" in analogy to cochlear implants. However, the position and surgical approaches for electrical stimulation of the olfactory system are unclear. METHODS: In a human anatomic cadaver study, we investigated different endoscopic approaches to electrically stimulate the olfactory bulb (OB) based on the following considerations: (1) the stimulating electrode should be close to the OB. (2) The surgical procedure should be as non-invasive and safe as possible and (3) as easy as possible for an experienced ENT surgeon. RESULTS: In summary, the endoscopic intracranial positioning of the electrode via a widened ostium of the fila olfactoria or a frontal sinus surgery like a Draf IIb procedure is a good option in terms of patients' risk, degree of difficulty for ENT surgeons, and position to the OB. Endoscopic intranasal positioning appeared to be the best option in terms of patient risk and the degree of difficulty for ENT surgeons. Although a bigger approach to the OB using a drill and the combined intranasal endoscopic and external approach enabled a close placement of the electrode to the OB, they do not seem relevant in practice due to their higher invasiveness. CONCLUSION: The study suggested that an intranasal positioning of a stimulating electrode is possible, with placements beneath the cribriform plate, extra- or intracranially, applying elegant surgical techniques with low or medium risk to the patient and a close placement to OB.

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

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

Functional outcomes and complications in refractory dysthyroid optic neuropathy management: Experience with 3 different surgical protocols.

INTRODUCTION: Dysthyroid optic neuropathy (DON) is the most severe complication of Graves' orbitopathy (GO) and its management may require decompression surgery. Clear recommendations do not exist about which surgery should be performed and how extended the decompression should be. In this paper we present our experience regarding the management of DON via 3 different surgical protocols: a modified extended orbital apex decompression, a 2 walls decompression (inferior and lateral) and a 3 walls decompression (inferior, lateral and medial) and evaluate the functional outcomes. METHODS: Retrospective evaluation of subjects affected by DON not responding to medical therapy has been performed. All patients were submitted to pre- and post-operative ophthalmologic evaluations and orbital and sinuses CT scan in order to evaluate functional and surgical outcomes. RESULTS: 27 patients were enrolled in the study. Surgical procedures were performed on 42 orbits. A statistically significant post-operative improvement was recorded in visual acuity, proptosis, color vision and fundus oculi evaluation for all groups. No patient developed major or minor complications after surgery. CONCLUSIONS: Extended endonasal approach and 3 walls decompression have been proved effective in the management of DON. The choice between them is done according to degree of proptosis, general status and eye-surface damages.

Inhibition of lysyl oxidase stimulates TGF-ß signaling and metalloproteinases-2 and -9 expression and contributes to the disruption of ascending aorta in rats: protection by propylthiouracil.

Mutations in lysyl oxidase (LOX) genes cause severe vascular anomalies in mice and humans. LOX activity can be irreversibly inhibited by the administration of ß-aminoproprionitrile (BAPN). We investigated the mechanisms underlying the damage to the ascending thoracic aorta induced by LOX deficiency and evaluated whether 6-propylthiouracil (PTU) can afford protection in rats. BAPN administration caused disruption of the ascending aortic wall, increased the number of apoptotic cells, stimulated TGF-ß signaling (increase of nuclear p-SMAD2 staining), and up-regulated the expression of metalloproteinases-2 and -9. In BAPN-treated animals, PTU reduced apoptosis, p-SMAD2 staining, MMP-2, and -9 expression, and markedly decreased the damage to the aortic wall. Our results suggest that, as in some heritable vascular diseases, enhanced TGF-ß signaling and upregulation of MMP-2 and -9 can contribute to the pathogenesis of ascending aorta damage caused by LOX deficiency. We have also shown that PTU, a drug already in clinical use, protects against the effects of LOX inhibition. MMP-2 and -9 might be potential targets of new therapeutic strategies for the treatment of vascular diseases caused by LOX deficiency.

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

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

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

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

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

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

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

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

IVM of mouse fully grown germinal vesicle oocytes upon a feeder layer of selected cumulus cells enhances their developmental competence.

In the ovary, acquisition of oocyte developmental competence depends on a bidirectional exchange between the gamete and its companion cumulus cells (CCs). In this study we investigated the contribution of CCs surrounding oocytes of known developmental competence or incompetence to the acquisition of oocyte developmental competence. To this end, feeder layers of CCs (FL-CCs) were prepared using CCs isolated either from: (1) developmentally competent mouse oocytes whose nucleolus was surrounded by a chromatin ring (FL-SN-CCs); or (2) developmentally incompetent mouse oocytes whose nucleolus was not surrounded by a chromatin ring (FL-NSN-CCs). Denuded, fully grown oocytes (DOs) were matured to the MII stage on either FL-SN-CCs or FL-NSN-CCs, inseminated with spermatozoa and cultured throughout preimplantation development. FL-SN-CCs significantly improved the acquisition of oocyte developmental competence, with a blastocyst development rate equal to that for maturation of intact cumulus-oocyte-complexes. In contrast, DOs matured on FL-NSN-CCs or in the absence of CCs exhibited developmental failure, with embryos arresting at either the 4-cell or morula stage. These results set a culture platform to further improve the protocols for the maturation of DOs and to unravel the molecules involved in the cross-talk between the gamete and its companion CCs during the germinal vesicle to MII transition.

Endoscopic Endonasal Approaches for Treatment of Craniovertebral Junction Tumours.

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

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

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

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

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

Radiological and clinical interpretation of the patients with CSF leaks developed during or after endoscopic sinus surgery.

Cerebrospinal fluid (CSF) leaks associated with endoscopic sinus surgery (ESS) are a rare complication related to anatomical and technical factors. The anatomical variations at skull base level are imperative to be detected preoperatively by CT scan to avoid this complication. Identifying the factors playing a role in the incidence of the CSF leaks during and after ESS and the common leak sites. A retrospective review of 24 patients presented with incidental CSF leaks, gathered from 1999 to 2016 was performed. Images interpretation of the skull base area was done using four parameters includes Keros classification, skull base slope, fovea plane and maxillary ethmoid height ratio (MER). Each parameter is classified into three types according to the anatomical configuration, then these parameters scores categorized according to the level of the safety into a level I, II and III, all levels were correlated with each other and with the site of leakage. It was found that the major group presented with the level I and the least group with level III safety, with an evidence of the most unsafe anatomical variation was the least relevant. Parameters measurements revealed that the larger group of the anatomical variation type III was in the MER and the commonest leak site was in the posterior ethmoidal roof. CT scan study of the skull base is crucial in delineating the variations and be a roadmap to proceed safely through the dissection remembering that incidental CSF leaks are multifactorial in etiology.

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

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

Endoscopic Treatment of Ewing Sarcoma of the Sinonasal Tract.

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

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

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