The clinicopathological spectrum of olfactory neuroblastoma and sinonasal neuroendocrine neoplasms: Refinements in diagnostic criteria and impact of multimodal treatments on survival.

OBJECTIVES: To provide a comprehensive review of the clinical and histopathological features of olfactory neuroblastoma (ONB) and other sinonasal neuroendocrine neoplasms (NENs), in order to refine diagnostic criteria, analyze treatment outcomes, and identify prognostic factors. METHODS: Data from an Italian multi-institutional database were analyzed. Patients were treated surgically via a minimally-invasive endoscopic approach followed by adjuvant radiotherapy or radiochemotherapy. Neoadjuvant cisplatin/etoposide chemotherapy was administered in cases of poorly-differentiated tumors. A centralized pathology review was performed in all cases. Patients were prospectively observed for survival. Overall (OS) and Disease-free survival (DFS) estimates were determined from Kaplan-Meier analysis and compared using the log-rank test. Statistically significant variables were entered in a multivariate Cox regression model. RESULTS: 98 patients with a median follow-up of 53months were included. Morphology review and the incorporation of cytokeratin 8/18 in the immunohistochemical panel modified the final diagnosis in 8/98 (8.2%) cases. The neoplasms were ultimately classified into four groups with different immunohistochemical profiles and clinical behaviors: ONB in 67 cases (5-year-OS, 91.6%); NEC (poorly-differentiated neuroendocrine carcinoma) in 22 cases (5-year-OS, 42.6%); MiNEN (mixed neuroendocrine/non-neuroendocrine neoplasm) in five cases (5-year-OS, 0%,0/5 cases); and NET (well-differentiated neuroendocrine tumor) in four cases (5-year-OS, 50%, 2/4 cases). Hyams grade and Ki67 index were independent prognostic factors for ONB. Neoadjuvant chemotherapy appeared to be associated with improved OS and DFS for NEC, independent of other clinicopathological variables. CONCLUSIONS: Induction chemotherapy improves survival outcomes in patients affected by poorly-differentiated tumors. Recent advances in histopathological diagnosis, including CK8/18 staining, allow to plan the most appropriate range of multimodal treatments.

Usefulness of three-dimensional computed tomographic anatomy in endoscopic frontal recess surgery.

PURPOSE: The endoscopic bidimensional vision offered by the endoscope during endoscopic sinus surgery involves difficulty in visualizing surgical field depth which makes it difficult to learn this surgical technique and makes it necessary for the endoscopic surgeon to mentally create a three-dimensional (3D) picture of the paranasal sinuses anatomy. In particular, frontal recess surgery requires good knowledge of its anatomic position, also since it is necessary to use angled endoscopes, which distort the view, and angular instruments which are difficult to use. Purpose of this project is to offer to the endoscopic surgeon a detailed 3D model of the nose and paranasal sinuses with particular attention to the frontal recess. METHODS: A 3D reconstruction of the frontal recess and its related structures, starting from computer tomography scans of the human skull, was realized using a professional 3D graphics software. RESULTS: A detailed reconstruction of the main structures which contribute to form the frontal recess was obtained. Particular attention was paid when reproducing the agger nasi cells, uncinate process, ethmoidal bulla, anterior ethmoidal cells, frontoethmoidal cells and their anatomic variants. CONCLUSIONS: This is the first experience reported in literature regarding this new technique of iconographic didactics applied to endoscopic sinus surgery. It represents a new frontier, which surpasses and integrates the previous didactic techniques to help the surgeon to mentally create a 3D image of the paranasal sinuses.

Endonasal endoscopic approach for removal of intraorbital cavernous hemangioma in childhood.

BACKGROUND: Orbital cavernous hemangiomas are the most common primary benign orbital tumors in adults. Although a rudimentary lesion may be present at birth, cavernous hemangiomas do not usually become symptomatic until the third to fifth decade of life and lesions occurring in pediatric age are quite rare. Surgical treatment is indicated in symptomatic cases, and surgical approach is planned according to the localization of the tumor in the orbit. METHODS AND RESULTS: We described the first case of pediatric intraorbital extraconal cavernous hemangioma, treated successfully by a pure endoscopic endonasal approach, and demonstrated the minimal invasiveness of this approach, without skin incision and neurovascular retraction. Review of the literature, surgical technique, pitfalls, and differences from previous reports are discussed. CONCLUSION: Endoscopic transnasal approaches can now be considered as an alternative option to traditional external approaches in the management of medial and inferior orbital lesions in childhood.

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.