Multimodal Evaluation of Voice Outcome in Early Glottic Cancers Treated With Definitive Radiotherapy.

Background/Aim: We employed a multimodal evaluation of voice outcome (MEVO) model to assess long-term voice outcome in early glottic cancer (EGC) patients treated with primary radiotherapy (RT). The model consisted of objective and subjective vocal evaluation during follow-up, by a dedicated Speech Pathologist and Speech Therapist. Patients and Methods: MEVO methodology includes Self-perception Voice Handicap Index (VHI-30), evaluation of parameters Grade (G), Roughness (R), Breathiness (B), Asthenia (A) and Strain (S) according to GRBAS scale, objective analysis and aerodynamics using the PRAAT software and laryngeal evaluation with videostroboscope (VS). Results: The MEVO methodology was described and tested on a sample of 10 EGCs submitted to definitive RT (total dose 66-70 Gy). Mean follow-up was 48.9 months (range=9-115). VHI was mild-moderate in 90% of patients; overall voice function (GRBAS) was normal-mildly impaired in 70% of patients; VS evaluation showed normal vocal cord motion in 90% of patients, but complete glottic closure in 60%. PRAAT scores confirmed these findings. Conclusion: A multidimensional voice evaluation is time consuming, but useful to objectify vocal impact of radiotherapy. The MEVO model allowed to quantify vocal dysfunction, showing a good objective vocal outcome.

Management of facial nerve in surgical treatment of previously untreated fisch class C tympanojugular paragangliomas: long-term results.

The aim of this study was to evaluate the long-term facial nerve outcome according to management of the facial nerve in patients undergoing surgery for Fisch class C tympanojugular paragangliomas. The study population consisted of 122 patients. The infratemporal type A approach was the most common surgical procedure. The facial nerve was left in place in 2 (1.6%) of the 122 patients, anteriorly rerouted in 97 (79.5%), anteriorly rerouted with segmental resection of the epineurium in 7 (5.7%), and sacrificed and reconstructed in 15 (12.3%). One patient underwent cross-face nerve grafting. At last follow-up, House-Brackmann grade I to II was achieved in 51.5% of patients who underwent anterior rerouting and in 28.5% of those who underwent anterior rerouting with resection of the epineurium. A House-Brackmann grade III was achieved in 73.3% of patients who underwent cable nerve graft interposition. The two patients in whom the facial nerve was left in place experienced grade I and grade III, respectively. The patient who underwent cross-face nerve grafting had grade III. Gross total resection was achieved in 105 cases (86%). Management of the facial nerve in tympanojugular paraganglioma surgery can be expected to ensure satisfactory facial function long-term outcome.

Infratemporal fossa approach type a with transcondylar-transtubercular extension for Fisch type C2 to C4 tympanojugular paragangliomas.

BACKGROUND: The classic infratemporal fossa type A approach (IFTA-A) permits superior and anterior exposure of the jugular foramen. The transcondylar-transtubercular extension facilitates posteroinferior and medial access to the jugular foramen. The purpose of this study was to present the IFTA-A with transcondylar-transtubercular extension and to assess its surgical results. METHODS: A review of patients with tympanojugular paraganglioma who underwent resection through the IFTA-A with transcondylar-transtubercular extension was performed. RESULTS: In all, 39 patients were included in the study. The average follow-up was 23.6 months. Gross total tumor removal was achieved in 87.2% of the cases and there was evidence of recurrence in 5.9% of this group. CONCLUSION: The transcondylar-transtubercular extension of the classic IFTA-A is aimed at making the excision of Fisch type C2 to C4 tympanojugular paragangliomas simpler and safer by drilling out one third of the lateral part of the occipital condyle and removing the jugular process and jugular tubercle.

Integrative genetic, epigenetic and pathological analysis of paraganglioma reveals complex dysregulation of NOTCH signaling.

Head and neck paragangliomas, rare neoplasms of the paraganglia composed of nests of neurosecretory and glial cells embedded in vascular stroma, provide a remarkable example of organoid tumor architecture. To identify genes and pathways commonly deregulated in head and neck paraganglioma, we integrated high-density genome-wide copy number variation (CNV) analysis with microRNA and immunomorphological studies. Gene-centric CNV analysis of 24 cases identified a list of 104 genes most significantly targeted by tumor-associated alterations. The "NOTCH signaling pathway" was the most significantly enriched term in the list (P = 0.002 after Bonferroni or Benjamini correction). Expression of the relevant NOTCH pathway proteins in sustentacular (glial), chief (neuroendocrine) and endothelial cells was confirmed by immunohistochemistry in 47 head and neck paraganglioma cases. There were no relationships between level and pattern of NOTCH1/JAG2 protein expression and germline mutation status in the SDH genes, implicated in paraganglioma predisposition, or the presence/absence of immunostaining for SDHB, a surrogate marker of SDH mutations. Interestingly, NOTCH upregulation was observed also in cases with no evidence of CNVs at NOTCH signaling genes, suggesting altered epigenetic modulation of this pathway. To address this issue we performed microarray-based microRNA expression analyses. Notably 5 microRNAs (miR-200a,b,c and miR-34b,c), including those most downregulated in the tumors, correlated to NOTCH signaling and directly targeted NOTCH1 in in vitro experiments using SH-SY5Y neuroblastoma cells. Furthermore, lentiviral transduction of miR-200s and miR-34s in patient-derived primary tympano-jugular paraganglioma cell cultures was associated with NOTCH1 downregulation and increased levels of markers of cell toxicity and cell death. Taken together, our results provide an integrated view of common molecular alterations associated with head and neck paraganglioma and reveal an essential role of NOTCH pathway deregulation in this tumor type.

Effects of early commercial air travel on graft healing rates after tympanoplasty.

OBJECTIVES: We sought to determine whether commercial air travel soon after tympanoplasty significantly affects graft healing rates. METHODS: We performed a retrospective analysis of 169 patients who underwent tympanoplasty from 1993 to 2009, comparing two groups of patients: 69 patients who flew 1 day after surgery and 100 who did not. The confounding factors analyzed were side of surgery, size of perforation, surgical approach, graft material, and grafting technique. The primary outcome measure analyzed was successful closure of the perforation at the first follow-up visit, at 4 weeks, evidenced by direct otoendoscopic examination. RESULTS: There was no significant difference in the confounding variables between the two groups. There was no significant difference in the primary outcome measure of graft healing rates between the two groups (p = 0.494). Additionally, the overall graft healing rates compared favorably with previously published data from other authors. CONCLUSIONS: Early commercial air travel after tympanoplasty does not significantly affect graft healing rates and should be considered a relatively safe option.

Management of vagal paragangliomas including application of internal carotid artery stenting.

BACKGROUND: The primary treatment of vagal paraganglioma (VP) includes 'wait and scan', surgery and radiotherapy. OBJECTIVES: To present the clinical findings, surgical treatment including application of internal carotid artery (ICA) stenting to facilitate surgery, and complications, as well as to review the literature and to discuss the decision-making process in the management of VP cases based on our experience and the literature. DESIGN: A retrospective case review of 22 cases with VP. SETTING: Quaternary neurotologic and skull base referral center. MATERIAL AND METHODS: The retrospective chart review identified 22 patients presenting with VP. Our indication for surgery was VP in younger patients, irrespective of the existence of vocal cord paralysis. Preoperative endovascular management of the ICA included permanent balloon occlusion (PBO) and stenting. The transcervical approach and the infratemporal fossa approach type A (ITFA) were used. RESULTS: Fifteen cases had multicentric paragangliomas, 5 cases bilateral tumors, 3 cases a genetic mutation, and 2 cases a positive family history. The most common symptoms were hoarseness, tinnitus and hearing loss. The surgical approaches commonly employed for excision were the transcervical approach (9 cases) and the ITFA (12 cases), whereas 1 case did not have surgery. Three cases had PBO and 7 had intracarotid stent insertion. Gross total removal was achieved in 19 cases, and 1 case had a recurrence. Eighteen cases had no dysphagia or were well compensated after surgery. There were no significant complications noted in our series. CONCLUSIONS: In younger patients with VP, surgery should be recommended. The proper preoperative endovascular intervention and surgical approach facilitates gross total tumor removal. In the management of bilateral or familial paragangliomas, careful and appropriate decision making is essential.

Management of complex tympanojugular paragangliomas including endovascular intervention.

OBJECTIVES/HYPOTHESIS: To identify complex cases of tympanojugular paraganglioma (TJP) and to analyze their management and surgical outcome. To present strategy and guidelines on how to deal with the perioperative complicating factors. STUDY DESIGN: Retrospective analysis. METHODS: We retrospectively studied 212 TJP patients to identify the complex cases and analyzed their management and surgical outcome. The criteria for complex TJP are: 1) very large size; 2) large intradural extension (IDE); 3) extension to the cavernous sinus, foramen magnum, and clivus; 4) significant involvement of the internal carotid artery (ICA); 5) a solitary ICA on the lesion side; 6) involvement of the vertebral artery; 7) dominant or unilateral sigmoid sinus on the lesion side; 8) bilateral or multiple paragangliomas; and 9) recurrence. RESULTS: Sixty patients were classified as complex. Forty-five patients had tumors with IDE. Twenty patients with tumor involving ICA underwent preoperative endovascular intervention. Two patients had a solitary ICA and two others unilateral sigmoid sinus on the lesion side. Thirteen patients had multicentric tumors, and three patients had bilateral ones. The main procedure was the infratemporal fossa approach type A. Total removal was achieved in 46 patients, and five of them experienced recurrence. CONCLUSIONS: It is essential to carefully investigate the hemodynamics of the brain in planning surgery. A proper preoperative endovascular intervention facilitates gross total tumor removal. In bilateral paragangliomas, lower cranial nerves' function should be preserved at least unilaterally. Staged removal is recommended for a tumor with a large intradural component.