Bilateral Selective Laryngeal Reinnervation for Bilateral Vocal Fold Paralysis in Children.

Importance: Bilateral vocal fold paralysis (BVFP) in pediatric patients is a challenging entity with multiple causes. Traditional approaches to managing BVFP include tracheostomy, arytenoidectomy, suture lateralization, cordotomy, and posterior cricoid enlargement. These interventions are used to create a stable airway but risk compromising voice quality. Objectives: To assess the use of bilateral selective laryngeal reinnervation (SLR) surgery to manage BVFP and restore dynamic function to the larynx in pediatric patients. Design, Setting, and Participants: In this case series performed at 2 tertiary care academic institutions, 8 pediatric patients underwent bilateral SLR to treat BVFP (5 patients with iatrogenic BVFP and 3 with congenital BVFP) from November 2004 to August 2018 with follow-up for at least 1.5 years. Interventions: Bilateral selective laryngeal reinnervation surgery. Main Outcomes and Measures: Flexible laryngoscopy findings, subjective and objective measures of voice quality, subjective swallowing function, and decannulation in patients who were previously dependent on a tracheostomy tube. Results: Participants included 6 boys and 2 girls with a median age of 9.3 (range, 2.2 to 18.0) years at the time of surgery. All 8 patients were decannulated; 6 patients had preoperative tracheostomies and 2 had perioperative tracheostomies. Voice quality, as measured using the GRBAS (grade, roughness, breathiness, asthenia, strain) scale, improved in 6 of 8 patients after reinnervation, and swallowing was not impaired in any patients. In 2 patients, GRBAS scale scores remained the same before and after surgery. Inspiratory vocal fold abduction was observed on both sides in 5 patients and on 1 side in 2 patients, with no active abduction observed in 1 patient. The follow-up period was more than 5 years in 7 of 8 patients and at least 1.5 years in all patients. Conclusions and Relevance: Bilateral SLR appears to be a promising treatment option for children with BVFP; it is currently the only option, to our knowledge, with the potential to restore abductor and adductor vocal fold movement. In patients with complete paralysis, this procedure may provide a strategy for airway management and restoration of the dynamic function of the larynx. It could be considered as a first-line technique before endolaryngeal or airway framework procedures, which carry a risk of compromising voice quality.

Should a neck dissection be performed on patients with cN0 adenoid cystic carcinoma? A REFCOR propensity score matching study.

BACKGROUND: Patterns of nodal involvement in adenoid cystic carcinoma (ACC) of the head and neck have not been sufficiently assessed to guide a decision of prophylactic neck dissection (ND). The objective of this study is to analyse the influence of ND on event-free survival (EFS) for patients with cN0 ACC. PATIENTS AND METHODS: A multicentre prospective study was conducted between 2009 and 2018. Patients presenting cN0 non-metastatic ACC on any site, and who received surgery on the tumour, were included. EFS was the main judgement criterion. A comparative survival analysis between the groups that received a ND versus those that did not was performed, using a propensity score. Analyses were carried out using the R software. RESULTS: Between 2009 and 2018, 322 patients with cN0 ACC were included, out of which 58% were female. The average age was 53 years. Tumours were in minor salivary glands in 58% of cases, and 52% had T3/T4 stages. ND was performed on 46% of patients. Out of them, seven had histological lymph node invasion, out of which six had tumour infiltration in the mucosa of oral cavity. After propensity score, the median EFS for N0 patients with ND was 72 months (95% Confidence Interval (CI) [48-81]), compared to 73 months (95% CI [52-85]) for patients without ND (HR = 1.33; 95% CI [0.82-2.16]; p = 0.2). CONCLUSION: ND of cN0 patients does not provide any benefit on EFS, which suggests that its application on such patients is not necessary.

Nonselective Reinnervation as a Primary or Salvage Treatment of Unilateral Vocal Fold Palsy.

OBJECTIVES/HYPOTHESIS: Demonstration of voice improvement and long-term stability following nonselective unilateral laryngeal reinnervation (ULR) in patients with unilateral vocal fold paralysis (UVFP) and severe denervation. A subgroup of patients on whom ULR was performed as a salvage technique following unsuccessful medialization was analyzed separately. STUDY DESIGN: Prospective cohort study. METHODS: The ansa cervicalis-recurrent laryngeal nerve anastomosis technique was performed in all patients. Pre- and postoperative voice analysis included voice questionnaires, voice assessment by senior laryngologists using the Hirano Voice Scale, and computer-assisted voice analysis at defined time points over the course of 36 months. Laryngeal electromyography (LEMG) and spirometry were performed before and 1 year after ULR. RESULTS: Significant linear improvement of mean voice quality over time was observed in the majority of parameters measured in 48 ULR patients and in eight ULR salvage patients. LEMG 1 year after ULR showed new recruitment. Mean voice quality remained stable during follow-up in all ULR patients and in the ULR salvage group. CONCLUSIONS: Nonselective ULR in UVFP is a reliable and stable therapeutic option for patients with high expectations concerning voice quality. The effect is stable in long-term results. It is also a viable option for patients in whom conventional voice surgery failed to improve voice quality. We therefore propose ULR as salvage option in UVFP. LEVEL OF EVIDENCE: 2b Laryngoscope, 130:1756-1763, 2020.

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.

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.

Human Error in Throat Pack Management: Report of Two Cases.

Throat packs are frequently used after tracheal intubation during ear, nose, and throat surgery. We report 2 cases of complications related to throat packs retained at the end of surgery. Miscommunication between anesthesiology and surgery teams on throat pack management led to an upper gastrointestinal endoscopy examination under general anesthesia in the first case and to severe respiratory distress requiring tracheal reintubation in the second case. Our 2 case reports highlight the importance of good communication between anesthesiology and surgery teams and of standardized procedures and checklists for the management of throat packs to ensure patient safety.

[Swallowing disorders in the elderly]. / Troubles de la déglutition chez les sujets âgés.

Swallowing disorders in the elderly. Swallowing disorders are a common problem in the elderly with severe consequences in multiple cases. At the current time these disorders are poorly understood and under-diagnosed. Although physiological aging is accompanied by changes in the process of swallowing resulting in an increase of the occurrence of aspiration, these changes are not responsible for a swallowing disorder. There are multiple aetiologies specific for the elderly and, in some cases, may be treatable when systematic screening is imposed. This one is based on medical history and a physical examination. Then the diagnosis can be confirmed with the videofluoroscopy, the gold standard for swallowing disorders. The management of these disorders is based on preventive measures, education of the patient, his family and of health care professionals and rehabilitation.

Troubles de la déglutition chez les sujets âgés. Les troubles de la déglutition, problème fréquent dans la population âgée aux conséquences sévères, sont actuellement mal connus et sous-diagnostiqués. Le vieillissement physiologique s'accompagne de modifications de la déglutition favorisant la survenue de fausses routes. Les causes spécifiques au sujet âgé sont diverses et peuvent parfois être traitées, imposant leur dépistage systématique. Celui-ci repose sur l'interrogatoire associé à l'examen clinique. Le diagnostic des troubles de la déglutition peut être étayé par la vidéofluoroscopie, examen de référence. La prise en charge de ces troubles repose sur des mesures préventives, l'éducation du patient, de sa famille et des intervenants professionnels, et la rééducation.

Transplantation of olfactory ensheathing cells to evaluate functional recovery after peripheral nerve injury.

Olfactory ensheathing cells (OECs) are neural crest cells which allow growth and regrowth of the primary olfactory neurons. Indeed, the primary olfactory system is characterized by its ability to give rise to new neurons even in adult animals. This particular ability is partly due to the presence of OECs which create a favorable microenvironment for neurogenesis. This property of OECs has been used for cellular transplantation such as in spinal cord injury models. Although the peripheral nervous system has a greater capacity to regenerate after nerve injury than the central nervous system, complete sections induce misrouting during axonal regrowth in particular after facial of laryngeal nerve transection. Specifically, full sectioning of the recurrent laryngeal nerve (RLN) induces aberrant axonal regrowth resulting in synkinesis of the vocal cords. In this specific model, we showed that OECs transplantation efficiently increases axonal regrowth. OECs are constituted of several subpopulations present in both the olfactory mucosa (OM-OECs) and the olfactory bulbs (OB-OECs). We present here a model of cellular transplantation based on the use of these different subpopulations of OECs in a RLN injury model. Using this paradigm, primary cultures of OB-OECs and OM-OECs were transplanted in Matrigel after section and anastomosis of the RLN. Two months after surgery, we evaluated transplanted animals by complementary analyses based on videolaryngoscopy, electromyography (EMG), and histological studies. First, videolaryngoscopy allowed us to evaluate laryngeal functions, in particular muscular cocontractions phenomena. Then, EMG analyses demonstrated richness and synchronization of muscular activities. Finally, histological studies based on toluidine blue staining allowed the quantification of the number and profile of myelinated fibers. All together, we describe here how to isolate, culture, identify and transplant OECs from OM and OB after RLN section-anastomosis and how to evaluate and analyze the efficiency of these transplanted cells on axonal regrowth and laryngeal functions.

Potential of olfactory ensheathing cells from different sources for spinal cord repair.

Spinal cord injury (SCI) induces a permanent disability in patients. To this day no curative treatment can be proposed to restore lost functions. Therefore, extensive experimental studies have been conducted to induce recovery after SCI. One of the most promising therapies is based on the use of olfactory ensheathing cells (OECs). OECs can be obtained from either the olfactory bulbs (OB-OECs) or from olfactory mucosa (OM-OECs), involving a less invasive approach for autotransplantation. However the vast majority of experimental transplantations have been focusing on OB-OECs although the OM represents a more accessible source of OECs. Importantly, the ability of OM-OECs in comparison to OB-OECs to induce spinal cord recovery in the same lesion paradigm has never been described. We here present data using a multiparametric approach, based on electrophysiological, behavioral, histological and magnetic resonance imaging experiments on the repair potential of OB-OECs and OM-OECs from either primary or purified cultures after a severe model of SCI. Our data demonstrate that transplantation of OECs obtained from OB or OM induces electrophysiological and functional recovery, reduces astrocyte reactivity and glial scar formation and improves axonal regrowth. We also show that the purification step is essential for OM-OECs while not required for OB-OECs. Altogether, our study strongly indicates that transplantation of OECs from OM represents the best benefit/risk ratio according to the safety of access of OM and the results induced by transplantations of OM-OECs. Indeed, purified OM-OECs in addition to induce recovery can integrate and survive up to 60 days into the spinal cord. Therefore, our results provide strong support for these cells as a viable therapy for SCI.

Co-transplantation of olfactory ensheathing cells from mucosa and bulb origin enhances functional recovery after peripheral nerve lesion.

Olfactory ensheathing cells (OECs) represent an interesting candidate for cell therapy and could be obtained from olfactory mucosa (OM-OECs) or olfactory bulbs (OB-OECs). Recent reports suggest that, depending on their origin, OECs display different functional properties. We show here the complementary and additive effects of co-transplanting OM-OECs and OB-OECs after lesion of a peripheral nerve. For this, a selective motor denervation of the laryngeal muscles was performed by a section/anastomosis of the recurrent laryngeal nerve (RLN). Two months after surgery, recovery of the laryngeal movements and synkinesis phenonema were analyzed by videolaryngoscopy. To complete these assessments, measure of latency and potential duration were determined by electrophysiological recordings and myelinated nerve fiber profiles were defined based on toluidine blue staining. To explain some of the mechanisms involved, tracking of GFP positive OECs was performed. It appears that transplantation of OM-OECs or OB-OECs displayed opposite abilities to improve functional recovery. Indeed, OM-OECs increased recuperation of laryngeal muscles activities without appropriate functional recovery. In contrast, OB-OECs induced some functional recovery by enhancing axonal regrowth. Importantly, co-transplantation of OM-OECs and OB-OECs supported a major functional recovery, with reduction of synkinesis phenomena. This study is the first which clearly demonstrates the complementary and additive properties of OECs obtained from olfactory mucosa and olfactory bulb to improve functional recovery after transplantation in a nerve lesion model.

Transplantation of olfactory ensheathing cells promotes axonal regeneration and functional recovery of peripheral nerve lesion in rats.

INTRODUCTION: Olfactory ensheathing cells (OECs) hold promise for cell therapy because they may promote regeneration of the central nervous system. However, OECs have been less studied after peripheral nerve injury (PNI). The purpose of this investigation was to determine the effect of OEC transplantation on a severe sciatic nerve (SN) lesion. METHODS: OECs were injected in rats after section and 2-cm resection of the SN. RESULTS: Three months after therapy, muscle strength and morphometric studies showed complete restoration of the contractile properties of the gastrocnemius and complete repair of the SN. Immunohistochemistry and RT-PCR studies indicated an increase in the presence of neurotrophic factors. Interestingly, tracking of green fluorescent protein (GFP)-positive OECs showed that no OECs were present in the SN. DISCUSSION: Our results demonstrate that, after severe PNI, OECs have remarkable potential for nerve regeneration by creating a favorable microenvironment.

Effects of chronic aspirations on breathing pattern and ventilatory drive in vagatomized rats.

The aim of this study was to test the hypothesis that aspirations induced by unilateral vagotomy destabilise ventilatory pattern during swallowing. The study was carried out on 15 Wistar rats (2-3 months, 290-350 g) using whole-body plethysmography and video recordings, before and after unilateral vagotomy. The rats were given water ad libitum via a baby bottle fitted with a nipple. The experiment was continued until rest ventilation and swallowing periods were identified on the video recordings. Following the sectioning of the right vagus nerve, all the rats presented bronchial aspirations and unilateral vocal cord paralysis in the aperture position. After the vagotomy there were no changes at rest of the ventilatory variables compared to healthy controls. In healthy animals during swallowing, we observed a decrease in total ventilatory time (TTOT), a decrease in inspiratory time (TI) (p < 0.001), a decrease in expiratory time (TE) (p < 0.001), no change in tidal volume (VT) and an increase in mean inspiratory time (VT/TI) (p < 0.001) compared to the rest period. Animals with chronic aspiration presented during swallowing an increase in TTOT (p < 0.001), TI (p < 0.01), and TE (p < 0.001), no change in VT and a decrease of VT/TI (p < 0.001) and a modification of ventilatory pattern. In conclusion, our results confirmed that swallowing modifies ventilation in healthy animals and that chronic aspiration decreases ventilatory drive and modifies ventilatory pattern during swallowing.

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.

Comparative gene expression profiling of olfactory ensheathing cells from olfactory bulb and olfactory mucosa.

Olfactory ensheathing cells (OEC) have the ability to promote regeneration in the nervous system. Hence, they hold promise for cell therapy. Most of the experimental studies have investigated the role of OECs taken from olfactory bulb (OB). However, for a clinical human application, olfactory mucosa (OM) seems to be the only acceptable source for OECs. Many studies have compared the distinct ability of OECs from OB and OM to improve functional nerve regeneration after lesion of the nervous system. Nevertheless, the two populations of OECs may differ in several points, which might affect all fate after transplantation in vivo. We report here the first study which compares gene expression profiling between these two populations of OECs. It appears that OB-OECs and OM-OECs display distinct gene expression pattern, which suggest that they may be implicated in different physiological processes. Notably, OM-OECs overexpress genes characteristic of wound healing and regulation of extra cellular matrix. In contrast, OB-OECs gene profile suggests a prominent role in nervous system development. Hence, OB-OECs and OM-OECs fundamentally differ in their gene expression pattern, which may represent a crucial point for future clinical application.

Vagal paraganglioma of the neck: a case report.

Vagal paragangliomas are rare in the head and neck. Complementary use of computed tomography and magnetic resonance imaging can facilitate the diagnosis and help determine the best management approach. Most paragangliomas should be treated with surgery. We report a case of vagal paraganglioma of the neck in a 50-year-old man. The patient was treated with superficial parotidectomy via a transcervical approach. No postoperative morbidity was noted, and at 3 years of follow-up, he was free of disease.