Treatment strategy in laryngeal chondrosarcoma: a multicenter study of 43 cases.

PURPOSE: Laryngeal chondrosarcoma is a rare tumor that mostly affects the cricoid cartilage. The aim of this study was to compare outcomes between the various treatments of this pathology as there are no official guidelines for this pathology. METHODS: A retrospective analysis of the pathology database of nine French tertiary care centers was conducted. Outcomes of patients treated by total laryngectomy were compared with those treated by more conservative approaches (endoscopic debulking, median thyrotomy, partial laryngectomy). Two Kaplan-Meier survival analyses were performed: one to assess the overall survival rate and the other to assess laryngeal preservation over time. RESULTS: A total of 43 patients were enrolled: 12 with total laryngectomy as the initial treatment, and 31 who initially underwent laryngeal-preserving treatment. With conservative treatment, laryngeal function was preserved in 96% and 75% of patients at 1 and 5 years, respectively. Conservative treatment did not reduce the overall survival rate. CONCLUSION: These results suggest that laryngeal preservation should be considered as the initial treatment in cases of laryngeal chondrosarcoma.

Quantified analysis of facial movement: A reference for clinical applications.

Most techniques for evaluating unilateral impairments in facial movement yield subjective measurements. The objective of the present study was to define a reference dataset and develop a visualization tool for clinical assessments. In this prospective study, a motion capture system was used to quantify facial movements in 30 healthy adults and 2 patients. We analyzed the displacements of 105 reflective markers placed on the participant's face during five movements (M1-M5). For each marker, the primary endpoint was the maximum amplitude of displacement from the static position (M0) in an analysis of variance. The measurement precision was 0.1 mm. Significant displacements of markers were identified for M1-M5, and displacement patterns were defined. The patients and age-matched healthy participants were compared with regard to the amplitude of displacement. We created a new type of radar plot to visually represent the diagnosis and facilitate effective communication between medical professionals. In proof-of-concept experiments, we collected quantitative data on patients with facial palsy and created a patient-specific radar plot. Our new protocol for clinical facial motion capture ("quantified analysis of facial movement," QAFM) was accurate and should thus facilitate the long-term clinical follow-up of patients with facial palsy. To take account of the limitations affecting the comparison with the healthy side, we created a dataset of healthy facial movements; our method might therefore be applicable to other conditions in which movements on one or both sides of the face are impaired. The patient-specific radar plot enables clinicians to read and understand the results rapidly.

The SELENOT mimetic PSELT promotes nerve regeneration by increasing axonal myelination in a facial nerve injury model in female rats.

Peripheral nerve injury (PNI) is frequent and many patients suffer lifelong disabilities in severe cases. Although the peripheral nervous system is able to regenerate, its potential is limited. In this study, we tested in a nerve regeneration model in rat the potential beneficial effect of a short mimetic peptide, named PSELT, which derives from SELENOT, an essential thioredoxin-like selenoprotein endowed with neuroprotective and antioxidant activities. For this purpose, the right facial nerve of female Long-Evans rats was axotomized then bridged with a free femoral vein interposition graft. PSELT (1 µM) was injected into the vein immediately and 48 h after the injury, and the effects observed were compared to those found after an end-to-end suture used as a gold standard treatment. Whisking behavior, electrophysiological potential, and histological analyses were performed 3 months after injury to determine the effects of these treatments. These analyses revealed that PSELT-treated animals exhibit a better motor recovery in terms of protraction amplitude and velocity of vibrissae compared to control and end-sutured nerve animal groups. Moreover, administration of PSELT following injury enhanced muscle innervation, axonal elongation, and myelination of newly formed nerve fibers. Altogether, these results indicate that a PSELT-based treatment is sufficient to enhance facial nerve myelination and regeneration and could represent a new therapeutic tool to treat PNI.

Comparison of the effects of two therapeutic strategies based on olfactory ensheathing cell transplantation and repetitive magnetic stimulation after spinal cord injury in female mice.

Spinal cord injury (SCI) is a debilitating condition, which leads to a permanent loss of functions below the injury site. The events which take place after SCI are characterized by cellular death, release of inhibitory factors, and inflammation. Many therapies have been studied to cure SCI, among them magnetic stimulation aims to reduce the secondary damages in particular by decreasing apoptosis, while, cellular transplantation promotes neuroregeneration by enhancing axonal regrowth. In the present study, we compared individually primary olfactory ensheathing cell (OEC) transplantation and repetitive trans-spinal magnetic stimulation (rTSMS) and then, we combined these two therapeutic approaches on tissue repair and functional recovery after SCI. To do so, SCIs were performed at Th10 level on female C57BL/6 mice, which were randomized into four groups: SCI, SCI + primary bOECs, SCI + STM, SCI + primary bulbar olfactory ensheathing cells (bOECs) + stimulation (STM). On these animals bioluminescence, immunohistological, and behavioral experiments were performed after SCI. Our results show that rTSMS has beneficial effect on the modulation of spinal scar by reducing fibrosis, demyelination, and microglial cell activation and by increasing the astroglial component of the scar, while, primary bOEC transplantation decreases microglial reactivity. At the opposite, locotronic experiments show that both treatments induce functional recovery. We did not observed any additional effect by combining the two therapeutic approaches. Taken together, the present study indicates that primary bOEC transplantation and rTSMS treatment act through different mechanisms after SCI to induce functional recovery. In our experimental paradigm, the combination of the two therapies does not induce any additional benefit.

European white paper: oropharyngeal dysphagia in head and neck cancer.

PURPOSE: To develop a European White Paper document on oropharyngeal dysphagia (OD) in head and neck cancer (HNC). There are wide variations in the management of OD associated with HNC across Europe. METHODS: Experts in the management of specific aspects of OD in HNC across Europe were delegated by their professional medical and multidisciplinary societies to contribute to this document. Evidence is based on systematic reviews, consensus-based position statements, and expert opinion. RESULTS: Twenty-four sections on HNC-specific OD topics. CONCLUSION: This European White Paper summarizes current best practice on management of OD in HNC, providing recommendations to support patients and health professionals. The body of literature and its level of evidence on diagnostics and treatment for OD in HNC remain poor. This is in the context of an expected increase in the prevalence of OD due to HNC in the near future. Contributing factors to increased prevalence include aging of our European population (including HNC patients) and an increase in human papillomavirus (HPV) related cancer, despite the introduction of HPV vaccination in various countries. We recommend timely implementation of OD screening in HNC patients while emphasizing the need for robust scientific research on the treatment of OD in HNC. Meanwhile, its management remains a challenge for European professional associations and policymakers.

Dual innervation may occur in a partially denervated muscle.

INTRODUCTION: With a view to simplifying surgical techniques for selective laryngeal reinnervation, we addressed the question of whether it is feasible to receive additional innervation by a partially denervated muscle using an infrahyoid muscle model. METHODS: In 90 rats (6 groups of 15), phrenic nerve transfer was used to reinnervate the sternothyroid muscle. In some cases, residual innervation by the original nerve was present. Three months later we performed electromyographic studies, contraction strength measurements, histologic assessment, and retrograde labeling. RESULTS: Muscles reinnervated by the phrenic nerve had a greater "dual-response" rate (in terms of nerve latency, contraction strength, and retrograde labeling) than muscles in the control groups. DISCUSSION: The phrenic nerve can impart its inspiratory properties to an initially denervated strap muscle-even when residual innervation is present. The preservation of contractile potential confirmed the feasibility of dual innervation in a previously injured muscle. Muscle Nerve 59:108-115, 2019.

Benefit of cetuximab addition to a platinum-fluorouracil-based chemotherapy according to KRAS-LCS6 variant in an unselected population of recurrent and/or metastatic head and neck cancers.

OBJECTIVES: To evaluate the benefit of cetuximab (Cx) addition to platinum-based and 5-fluorouracil chemotherapy (PFU) in unselected recurrent and/or metastatic head and neck cancer patients (R/MHNC) according to KRAS-LCS6 variant status. METHODS: All patients who received at least two PFU ± Cx cycles from 2004 to 2014 were retrospectively included into to two distinct study periods according to Cx implementation: patients treated by PFU alone before 2009 and those treated by PFU + Cx from 2009. Primary objective was to evaluate the progression-free survival (PFS) between the two groups. Secondary objectives were to analyze the overall survival (OS) between the two groups and the prognostic impact of KRAS-LCS6 variant. Factors associated with survival were determined by a Cox multivariate analysis including age, WHO performance status (PS), type of treatment, KRAS-LCS6 variant, Charlson's score and p16 status. RESULTS: Overall, 134 patients were included: 59 (44%) in PFU group and 75 (56%) in PFU + Cx group. Baseline characteristics were well balanced including 30% of patients with 2-3 PS. Median PFS was significantly improved in PFU + Cx group compared to PFU group (6.1 vs 4.4 months, respectively, HR 0.68, p = 0.02) and with a trend for better OS. A KRAS-LCS6 variant was found in 27 (25%) of samples without prognostic impact neither in whole population nor according to treatment. In multivariate analysis, addition of Cx to PFU was the only factor significantly associated with a better PFS (p = 0.01, HR 0.6). CONCLUSION: Our results suggest that PFU + Cx combination may be effective in unselected population of R/MHNC regardless the KRAS-LCS6 variant status.

Selective laryngeal reinnervation: can rerouting of the thyrohyoid nerve simplify the procedure by avoiding the use of a nerve graft?

PURPOSE: The objective of this study was to record the descriptive and metric anatomical characteristics of the thyrohyoid nerve with the aim of rerouting it in a selective laryngeal reinnervation procedure. METHODS: An anatomical study was performed on ten formalin-embalmed cadavers. The origin of the thyrohyoid nerve and the superior root of the ansa cervicalis, the location of the thyrohyoid nerve ending in the thyrohyoid muscle, and the recurrent laryngeal nerve were established. Then, a rerouting of the thyrohyoid nerve was performed. We measured the length of thyrohyoid nerve, the distance between the thyrohyoid nerve ending and the recurrent laryngeal nerve at the horizontal level of the cricothyroid joint before and after the rerouting, and the distance between the origin of the thyrohyoid nerve and the superior root of the ansa cervicalis. RESULTS: The thyrohyoid nerve was identified on both sides in all the cases. The average length of the thyrohyoid nerve was 27 mm. The end of the thyrohyoid nerve was found in 100% of the cases at the upper outer quarter of the thyrohyoid muscle. After the rerouting, an average reduction of 30% of the distance between the end of the thyroid nerve and the recurrent laryngeal nerve at the horizontal level of the cricothyroid joint was measured. CONCLUSION: The rerouting of the thyrohyoid nerve provided a reduction in the length of the nerve graft in laryngeal reinnervation. Moreover, the constancy of the thyrohyoid nerve and its characteristics make it a valuable anatomical base for laryngeal reinnervation and laryngeal innervated allotransplantation.

Lateral semicircular canal fistula in cholesteatoma: diagnosis and management.

The objective of this retrospective study was to present the authors' experience on the management of labyrinthine fistula secondary to cholesteatoma. 695 patients, who underwent tympanoplasty for cholesteatoma, in a University Hospital between 1993 and 2013 were reviewed, to select only those with labyrinthine fistulas. 42 patients (6%) had cholesteatoma complicated by fistula of the lateral semicircular canal (LSCC). The following data points were collected: symptoms, pre- and postoperative clinical signs, surgeon, CT scan diagnosis, fistula type, surgical technique, preoperative vestibular function and audiometric outcomes. Most frequent symptoms were unspecific, such as otorrhea, hearing loss and dizziness. However, preoperative high-resolution computed tomography predicted fistula in 88 %. Using the Dornhoffer and Milewski classification, 16 cases (38 %) were identified as stage 1, 22 (52 %) as stage II, and 4 (10 %) as stage III. The choice between open or closed surgical procedure was independent of the type of fistulae. The cholesteatoma matrix was completely removed from the fistula and immediately covered by autogenous material. In eight patients (19 %), the canal was drilled with a diamond burr before sealing with autologous tissue. After surgery, hearing was preserved or improved in 76 % of the patients. There was no statistically significant relationship between the extent of the labyrinthine fistula and the hearing outcome. In conclusion, a complete and nontraumatic removal of the matrix cholesteatoma over the fistula in a one-staged procedure and its sealing with bone dust and fascia temporalis, with sometimes exclusion of the LSCC, is a safe and effective procedure to treat labyrinthine fistula.

Titanium prosthesis or autologous incus for total ossicular reconstruction in the absence of the stapes suprastructure and presence of mobile footplate.

The purpose of this study was to compare the hearing results after total ossicular replacement with a titanium prosthesis or autologous incus in the absence of stapes suprastructure and presence of mobile footplate as a retrospective medical record review in a tertiary referral center setting. There were 49 patients who had total ossicular reconstruction (titanium prosthesis, 40 patients; autologous incus, 9 patients). Medical records were reviewed after total ossicular replacement. Air-bone gap at 1 and 2 years after surgery were determined with the 4-frequency average (0.5, 1, 2, and 4 kHz) and the American Academy of Otolaryngology-Head and Neck Surgery 4-frequency average (0.5, 1, 2, and 3 kHz). The number of patients who had air-bone gap <20 dB was determined. For comparisons that were based on American Academy of Otolaryngology-Head and Neck Surgery 4-frequency average, mean air-bone gap at 2 years after surgery was significantly smaller for the titanium prosthesis (21 dB) than autologous incus group (31 dB; P ≤ 0.03); the frequency of patients who had air-bone gap <20 dB at 1 or 2 years after surgery was significantly greater for the titanium prosthesis (1 year, 40%; 2 years, 56%) than autologous incus group [1 year, 0% (P ≤ 0.03); 2 years, 0% (P ≤ 0.04)]. Titanium prosthesis ossiculoplasty gave better results than autologous incus in the absence of the stapes suprastructure and presence of a mobile footplate.

Recurrent Laryngeal Nerve Intraoperative Neuromonitoring Indications in Non-Thyroid and Non-Parathyroid Surgery.

Introperative nerve monitoring (IONM) of the recurrent laryngeal nerve (RLN) is a well-established technique to aid in thyroid/parathyroid surgery. However, there is little evidence to support its use in non-thyroid or non-parathyroid surgery. The aim of this paper was to review the current evidence regarding the use of IONM in non-thyroid/non-parathyroid surgery in the head and neck and thorax. A literature search was performed from their inception up to January 2024, including the term "recurrent laryngeal nerve monitoring". IONM in non-thyroid/non-parathyroid surgery has mainly been previously described in oesophageal surgery and in tracheal resections. However, there is little published evidence on the role of IONM with other resections in the vicinity of the RLN. Current evidence is low-level for the use of RLN IONM in non-thyroid/non-parathyroid surgery. However, clinicians should consider its use in surgery for pathologies where the RLN is exposed and could be injured.

Preoperative computed tomography scan may fail to predict perilymphatic gusher.

OBJECTIVES: A stapes gusher is a very rare event in ear surgery, but the consequences for hearing can be dramatic. It can usually be predicted by characteristic radiologic abnormalities. We report 2 cases of gusher without any abnormalities seen on the preoperative computed tomography scans. METHODS: The first case was in a 30-year-old man with a bilateral mixed hearing loss. The gusher occurred after a stapedotomy performed with a microdrill. The oval window was plugged with a vein graft, and a fluoroplastic piston was inserted. The second case was in a 39-year-old woman with a family history of hearing loss who presented with a bilateral mixed hearing loss. The footplate was fractured during the stapedotomy drilling and was covered with a temporalis fascia graft that was fixed with a fluoroplastic piston. RESULTS: The first patient had no cerebrospinal fluid leakage and no vertigo or tinnitus. He did have a sensorineural hearing loss. The second patient had dizziness and tinnitus. Postoperative magnetic resonance imaging scans were performed, but again no features were identified that might have predicted these cases. CONCLUSIONS: Surgeons should be reminded that a preoperative computed tomography scan may fail to detect the risk of a perilymphatic gusher.

Longitudinal Vocal Outcomes and Voice-Related Quality of Life After Selective Bilateral Laryngeal Reinnervation: A Case Study.

PURPOSE: Bilateral vocal fold paralysis (BVFP) is a severe disorder that can result in respiratory, swallowing, and voice-related problems. Most surgical treatments do not restore laryngeal function and often need to compromise voice quality to preserve respiratory function. Laryngeal reinnervation (LR) may offer a solution to this problem, but literature on longitudinal outcomes of this procedure is scarce. This study aims to report the longitudinal vocal outcomes of BVFP after LR and subsequent voice therapy. METHOD: The case of a 23-year-old man with BVFP after a traumatic dissection of both recurrent laryngeal nerves is described. Selective bilateral LR of both adductors and abductors was performed 5 months after the onset of BVFP. Voice therapy was provided after the LR procedure. Multidimensional voice assessments, including acoustic, perceptual, and patient-reported outcome measures (PROMs), were conducted 2, 5, 6.5, 8, and 31 months after LR. RESULTS: An improvement of vocal capabilities and voice quality was noticed 6.5 months after LR, after 4.5 months of voice therapy, with normative values after 2.5 years. PROMs showed an improvement of voice-related quality of life, but some limitations to activities of daily living were still present. Inspiratory arytenoid abduction was not observed on laryngeal videostroboscopic findings in this patient, but tracheostomy was not required. CONCLUSIONS: Voice therapy after LR helps establish healthy and efficient voice use without increasing compensatory hyperfunctional behavior. More research is needed to examine potential merits of voice therapy in the rehabilitation of vocal and respiratory functions after LR.

Management of 80 sinonasal undifferentiated carcinomas. Retrospective multicentre study of the French Network of Rare Head and Neck Cancers (REFCOR).

OBJECTIVES: Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive disease requiring multimodal treatment, and multiple new entities once included in the spectrum of SNUC, such as SWI/SNF-deficient carcinomas, are emerging. We aimed to provide new data regarding the role of chemotherapy and surgery and the prognostic factors of disease-free survival. METHODS: This study was based on data from the REFCOR database and included patients with SNUC treated with curative intent from 2007 to 2021 across 22 centres in France. RESULTS: A total of 80 patients were included in the analysis. Among the entire cohort, the 5-year disease-free survival (DFS) and overall survival (OS) rates were 58% and 63%, respectively. Of 100% of the patients treated with irradiation, 29% underwent surgery, 56% neoadjuvant chemotherapy (82% had either a partial or a complete response) and 76% chemoradiotherapy. No treatment modality was associated with a better OS or DFS, including surgery (p = 0.34). There was a trend for a better DFS for the patients treated with chemotherapy (neoadjuvant or concomitant, p = 0.062). Overall survival at 3 years was 58% for SWI/SNF deficient group and 86% for non deficient group (p = 0.14). The locoregional relapse rate without distant metastases was 21% in the exclusive radiotherapy group and 26% in the surgery group. Grade 3 or higher toxicities concerned 9%, 32% and 29% of patients for surgery, radiotherapy and chemotherapy respectively. CONCLUSION: In the management of localised SNUC among all patients treated with irradiation, surgery yielded no benefit, whereas the addition of chemotherapy tended to improve disease-free survival.

Isolation, characterization, and genetic profiling of subpopulations of olfactory ensheathing cells from the olfactory bulb.

Olfactory ensheathing cells (OECs) play a crucial role during neurogenesis of primary olfactory neurons. Transplantation of OECs is considered as a promising new therapy for central nervous system repair. Nevertheless, OECs are constituted of distinct subpopulations and their role during neurogenesis is not clearly understood. In particular, OECs from the olfactory bulb (OB) constitute a heterogeneous, but not yet isolated and characterized, population of cells. In our study, flow cytometry analyses of primary OB cultures, based on cell surface expression of low-affinity nerve growth factor receptor (p75), reveal the presence of two distinct populations of OECs. Indeed, some of them express a high level of p75 (P75High) and the other a low level of p75 (P75Low). Effects of OB microenvironment were assessed, and we were able to show that fibroblasts mediate the induction of these two populations through the secretion of soluble factors. To characterize P75High and P75Low OECs, cells were sorted based on their differential expression of p75. Microarray analyses revealed that P75High OECs overexpress genes implicated in modulation of extracellular matrix and cell sorting, whereas P75Low OECs overexpress genes involved in regulation of the inflammatory response and axonal guidance. These results permit, for the first time, to isolate the two distinct subpopulations of OECs from OB, and suggest their specific role during neurogenesis.

"Virtual" lesioning of the human oropharyngeal motor cortex: a videofluoroscopic study.

OBJECTIVE: To use focal cortical inhibition and create a "virtual" lesion in the oropharyngeal motor cortex in healthy subjects to determine whether this provokes swallowing dysfunction. DESIGN: Intervention study: before and after cortical stimulation. SETTING: Tertiary care center. PARTICIPANTS: Healthy adult volunteers (N=9; age range, 21-44y) participated in the study. INTERVENTIONS: Active or sham 1-Hz repetitive transcranial magnetic stimulation (rTMS) over the cortical sites in each hemisphere evoking the largest mylohyoid motor-evoked potentials (mMEPs) to single pulse transcranial magnetic stimulation. MAIN OUTCOME MEASURES: Videofluoroscopic assessment was performed before and 5, 30, and 60 minutes after rTMS. RESULTS: The motor threshold was 83%±10% for the hemisphere with the larger mMEP (dominant) and 92%±9% for the hemisphere with the smaller mMEP (nondominant). When rTMS was performed over the dominant hemisphere, there was a decrease in oral transit time (P=.05), an increase in swallow reaction time (P=.0001), but no change of pharyngeal transit time or laryngeal closure duration. When rTMS was performed on the nondominant hemisphere, there was also a decrease in oral transit time (P=.05), but no change in any of the other swallowing measures. Neither active intervention produced any signs of aspiration or penetration. Sham stimulation had no effect. CONCLUSIONS: Inhibiting the human oropharyngeal motor cortex using rTMS transiently modifies swallowing behavior in a way reminiscent to that seen in stroke patients.

A New Animal Model of Laryngeal Transplantation.

Only three laryngeal transplants have been described in the literature to date, and none of the techniques has enabled a completely satisfactory functional result to be obtained. This article presents a new model of laryngeal transplantation, with quality of revascularisation of the transplant being the principal objective and optimisation of the various steps of the procedure, with the integration of a new reinnervation technique as a secondary objective. We present a preclinical animal study. Three pig larynges removed in vivo underwent allotransplantation according to the same protocol. The quality of the revascularisation was examined immediately after the surgery as well as by endoscopy for one animal on the fourth day after the operation. The mean time of cold ischaemia was 3 h 15 min. The anaesthetic tolerance of the pigs was excellent. Revascularisation was achieved and judged to be excellent for the three transplants immediately after the operation and the endoscopy performed for one pig on the fourth day after the operation confirmed this result. The anatomical similarities also enabled the application and integration of an innovative technique of laryngeal reinnervation into the various phases of the operation. We describe a reliable and reproducible animal model for laryngeal transplantation. Its application in humans can be envisaged.

Efficiency of laryngeal motor nerve repair is greater with bulbar than with mucosal olfactory ensheathing cells.

The real ability of OECs provided by olfactory mucosa cultures (OM-OECs) and those from olfactory bulb cultures (OB-OECs) must be better characterized in order to propose their future clinical application. Therefore, we used a lesion of the vagus nerve (VN), which constitutes a severe motor denervation due to long distance of the muscular targets (4.5 cm). We performed a section/anastomosis surgery of the VN, at the third tracheal ring. Then, OM-OECs and OB-OECs were injected in matrigel around the lesion site. Three months after surgery, laryngeal muscle activity, synkinesis phenomena and latency were evaluated by videolaryngoscopy and electromyography recordings. To complete these procedures, axonal morphometric study of the right recurrent nerve was performed to assess axonal regrowth and tracking of green fluorescent protein positive cells was performed. Recurrent nerve is the motor branch innervating the laryngeal muscles, and is located distally to the lesion, near the muscular targets (0.7 cm). These analyses permitted to compare the ability of these two populations to improve functional recovery and axonal regrowth. Our results show that, OM-OECs improved electrical muscular activity and nervous conduction with significant tissue healing but induced aberrant movement and poor functional recovery. In contrast, OB-OECs induced a partial functional recovery associated with an increase in the number of myelinated fibers and nervous conduction. Our study suggests that, as recently reported in a microarray study, OM-OECs and OB-OECs express different properties. In particular, OM-OECs could regulate inflammation processes and extracellular matrix formation but have a poor regeneration potential, whereas, OB-OECs could improve functional recovery by inducing targeted axonal regrowth.