Laryngeal spasm and tracheostomy after hydroxyapatite injection laryngoplasty.

INTRODUCTION: Adductor spasmodic dysphonia (Ad-SD) is usually treated by botulinum toxin injection into the thyroarytenoid muscles. In older patients, atrophy of these muscles is responsible for glottic leak, causing presbyphonia and is managed by vocal fold medialization using autologous fat or hydroxyapatite (HA). We report the first case of uncontrollable laryngeal spasm requiring tracheostomy after hydroxyapatite injection laryngoplasty in a patient with spasmodic dysphonia and presbyphonia. CASE REPORT: An 83-year-old man had been treated for Ad-SD by botulinum toxin injections every six months for 14 years. Due to severely disabling glottic leak, autologous fat injection laryngoplasty was then successfully performed. Six months later, following recurrence of severe hypophonia, hydroxyapatite injection was performed, subsequently complicated by immediate acute respiratory distress secondary to adductor laryngeal spasm requiring reintubation and tracheostomy. The postoperative course was marked by gradual recovery of vocal fold mobility with decannulation on day 12. DISCUSSION: This case allows a discussion of the possible pathophysiological mechanisms responsible for adductor laryngeal spasm. Vocal fold medialization procedures should be performed with caution in patients with Ad-SD.

Functional evaluation of mandibular reconstruction with bone free flap. A GETTEC study.

OBJECTIVES: To assess the functional results of oromandibular reconstruction by free bone flap, in terms of swallowing, speech and esthetics. MATERIALS AND METHODS: A transverse multicenter study included 134 patients reconstructed by free bone flap between 1998 and 2016, with more than 6 months' follow-up, in 9 centers. A standardized questionnaire collected data on patients and treatment. Study endpoints comprised: weight loss, mouth opening, gastrostomy dependence, type of feeding, and DHI score. The impact of patient baseline characteristics on these functional criteria was explored by uni/multivariate analysis. RESULTS: Ninety of the 134 patients had cancer. Fibula flap was mainly used (80%). 94% of reconstructions were primary successes. 71% of patients had pre- or post-operative radiation therapy. 88% had less than 50% lingual resection. 97% recovered oral feeding. 89% had intelligible speech. 86% judged their esthetic appearance as good/average. 9% had dental prosthetic rehabilitation. Radiation therapy and extensive lingual resection significantly impacted swallowing function (P=0.04 and P=0.03, respectively). Radiation therapy and oropharyngeal extension significantly increased gastrostomy dependence (P=0.04 and P=0.02, respectively). CONCLUSION: Oromandibular reconstruction by free bone flap enabled return to oral feeding in most cases. More than 80% of patients were satisfied with their result in terms of speech and esthetics. However, the rate of dental rehabilitation was low and the rate of complications was high.

Amyloidosis increase is not attenuated by long-term calorie restriction or related to neuron density in the prefrontal cortex of extremely aged rhesus macaques.

As human lifespan increases and the population ages, diseases of aging such as Alzheimer's disease (AD) are a major cause for concern. Although calorie restriction (CR) as an intervention has been shown to increase healthspan in many species, few studies have examined the effects of CR on brain aging in primates. Using postmortem tissue from a cohort of extremely aged rhesus monkeys (22-44 years old, average age 31.8 years) from a longitudinal CR study, we measured immunohistochemically labeled amyloid beta plaques in Brodmann areas 32 and 46 of the prefrontal cortex, areas that play key roles in cognitive processing, are sensitive to aging and, in humans, are also susceptible to AD pathogenesis. We also evaluated these areas for cortical neuron loss, which has not been observed in younger cohorts of aged monkeys. We found a significant increase in plaque density with age, but this was unaffected by diet. Moreover, there was no change in neuron density with age or treatment. These data suggest that even in the oldest-old rhesus macaques, amyloid beta plaques do not lead to overt neuron loss. Hence, the rhesus macaque serves as a pragmatic animal model for normative human aging but is not a complete model of the neurodegeneration of AD. This model of aging may instead prove most useful for determining how even the oldest monkeys are protected from AD, and this information may therefore yield valuable information for clinical AD treatments.

French consensus regarding precautions during tracheostomy and post-tracheostomy care in the context of COVID-19 pandemic.

Tracheostomy post-tracheostomy care are regarded as at high risk for contamination of health care professionals with the new coronavirus (SARS-CoV-2). Considering the rapid spread of the infection, all patients in France must be considered as potentially infected by the virus. Nevertheless, patients without clinical or radiological (CT scan) markers of COVID-19, and with negative nasopharyngeal sample within 24h of surgery, are at low risk of being infected. Instructions for personal protection include specific wound dressings and decontamination of all material used. The operating room should be ventilated after each tracheostomy and the pressure of the room should be neutral or negative. Percutaneous tracheostomy is to be preferred over surgical cervicotomy in order to reduce aerosolization and to avoid moving patients from the intensive care unit to the operating room. Ventilation must be optimized during the procedure, to limit patient oxygen desaturation. Drug assisted neuromuscular blockage is advised to reduce coughing during tracheostomy tube insertion. An experienced team is mandatory to secure and accelerate the procedure as well as to reduce risk of contamination.

French consensus on management of head and neck cancer surgery during COVID-19 pandemic.

In the context of the current pandemic, there is a need for specific advice concerning treatment of patients with Head and Neck cancers. The rule is to limit as much as possible the number of patients in order to reduce the risks of contamination by the SARS-Cov-2 virus for both patients and the caregivers, who are particularly exposed in ENT. The aim is to minimize the risk of loss of opportunity for patients and to anticipate the increased number of cancer patients to be treated at the end of the pandemic, taking into account the degree of urgency, the difficulty of the surgery, the risk of contaminating the caregivers (tracheotomy) and the local situation (whether or not the hospital and intensive care departments are overstretched).

[Vocal cord dyskinesia and/or asthma]. / Dyskinésie des cordes vocales et/ou asthme.

INTRODUCTION: Vocal cord dyskinesia or vocal cord dysfunction (VCD) is characterized by intermittent abnormal adduction of the vocal cords leading to airflow limitation at the level of the larynx, in the absence of local organic disease. It may occur in isolation or in association with asthma. The pathophysiology is complex and poorly understood. Wheeze, stridor or apparent upper airway obstruction are the most common symptoms. It occurs in a wide age range, more commonly in women, and diagnosis is often delayed and leads to unnecessary treatments (intubation, tracheostomy and high dose steroids). METHODS: A retrospective study of 15 cases of VCD (8 cases of isolated VCD and 7 cases of VCD with associated asthma) describing the main clinical features and the diagnosis strategy. RESULTS: Apparent upper airway obstruction, with or without associated asthma, requires an ear nose and throat examination with laryngoscopy to confirm the paradoxical adduction of the vocal cords during an acute episode of dyspnoea or during a provocation test with triggers like exercise or exposure to irritants, and for the purpose of differential diagnosis. CONCLUSIONS: VCD remains under-appreciated and misdiagnosed, often by mimicking asthma with which it can be associated. A delayed diagnosis by emergency specialists, pulmonologists and ear nose and throat surgeons leads to unnecessary treatments and morbidity before specific therapy can be given.

Induction chemotherapy before surgery for unresectable head and neck cancer.

OBJECTIVE: To preoperatively reduce tumour size in patients with locally advanced and/or non-resectable squamous cell carcinoma with induction chemotherapy in order to achieve surgical excision with clear margins and preserve quality of life. METHODOLOGY: In this study, 16 patients with locally advanced and/or non-resectable squamous cell carcinoma underwent induction chemotherapy with docetaxel, cisplatin, and 5-fluorouricil or paclitaxel, carboplatin, and cetuximab. RESULTS: Over 80% of patients responded to induction chemotherapy. Histological examination of the 14 surgical specimens showed a total absence of residual cancer cells in 37.5% of cases. CONCLUSION: Concurrent radiation and chemotherapy is the standard treatment for locally advanced head and neck squamous cell carcinoma; however, induction chemotherapy may be beneficial in select patients.

Pharmacology of the glucagon-like peptide-1 analog exenatide extended-release in healthy cats.

Exenatide extended-release (ER) is a microencapsulated formulation of the glucagon-like peptide 1-receptor agonist exenatide. It has a protracted pharmacokinetic profile that allows a once-weekly injection with comparable efficacy to insulin with an improved safety profile in type II diabetic people. Here, we studied the pharmacology of exenatide ER in 6 healthy cats. A single subcutaneous injection of exenatide ER (0.13 mg/kg) was administered on day 0. Exenatide concentrations were measured for 12 wk. A hyperglycemic clamp (target = 225 mg/dL) was performed on days -7 (clamp I) and 21 (clamp II) with measurements of insulin and glucagon concentrations. Glucose tolerance was defined as the amount of glucose required to maintain hyperglycemia during the clamp. Continuous glucose monitoring was performed on weeks 0, 2, and 6 after injection. Plasma concentrations of exenatide peaked at 1 h and 4 wk after injection. Comparing clamp I with clamp II, fasting blood glucose decreased (mean ± standard deviation = -11 ± 8 mg/dL, P = 0.02), glucose tolerance improved (median [range] +33% [4%-138%], P = 0.04), insulin concentrations increased (+36.5% [-9.9% to 274.1%], P = 0.02), and glucagon concentrations decreased (-4.7% [0%-12.1%], P = 0.005). Compared with preinjection values on continuous glucose monitoring, glucose concentrations decreased and the frequency of readings <50 mg/dL increased at 2 and 6 wk after injection of exenatide ER. This did not correspond to clinical hypoglycemia. No other side effects were observed throughout the study. Exenatide ER was safe and effective in improving glucose tolerance 3 wk after a single injection. Further evaluation is needed to determine its safety, efficacy, and duration of action in diabetic cats.

[Surgical treatement by intracapsular enucleation of cervical peripheral neural sheath tumors]. / Traitement chirurgical des tumeurs nerveuses périphériques bénignes cervicales par exérèse intracapsulaire.

Schwannomas and neurofibromas are benign tumors of the peripheral neural sheath tumors (PNST), representing 5% of soft tissue tumors. Cervical PNST are mainly located on the vagus nerve or in the sympathetic nervous system. The treatment is based on a tumor resection with preservation of nerve function. Classical surgery consists in total tumor removal after dissection of the nerve and is frequently complicated by nerve paralysis. The authors describe a simpler surgical technique consisting in a resection of the intracapsular enucleation of PNST that can limit the risk of nerve injury without increasing recidivism. The description of this surgical technique is illustrated by its use in a type I neurofibromatosis patient with a large vagal nerve neurofibroma.

Semi-free forearm flap for pharyngeal-esophageal reconstruction after radiation therapy.

Reconstruction of the pharynx and upper esophagus uses various procedures, including pedicled or free flap. Pharyngoplasty with free forearm flap provides excellent functional results. In radiation-related pharyngeal stenosis, recipient vascularization is often poor, especially in the venous system. The authors describe pharyngeal reconstruction with semi-free forearm flap, pedicled on the cephalic vein, to minimize the risk of venous thrombosis, which is the main factor of free forearm flap necrosis. Taking the case of a laryngectomy with complete pharyngeal stenosis after radiation therapy and iterative neck surgery, the technique of pharyngeal-esophageal reconstruction by semi-free forearm flap is described in a context of impaired vascularization.

How to replace codeine after tonsillectomy in children under 12 years of age? Guidelines of the French Oto-Rhino-Laryngology--Head and Neck Surgery Society (SFORL).

The authors present the guidelines of the French Oto-rhino-laryngology--Head and Neck Surgery Society (SFORL) regarding pain management in children and adults following tonsillectomy. A multidisciplinary work group was entrusted with a literature review. Guidelines were drawn up based on the articles retrieved and the group members' experience. They were read over by an editorial group independent of the work group. A coordination meeting drew up the final version. Guidelines were graded A, B or C or as professional agreement in decreasing order of level of evidence. At home, non-steroid anti-inflammatory drugs (NSAIDs) are recommended in association with paracetamol in elevated respiratory risk and especially obstructive sleep apnea syndrome; in elevated hemorrhagic risk (hemostasis disorder, surgical problems, etc.), tramadol is recommended. Two other treatment schedules (modified NSAIDs and corticosteroids) have not undergone dedicated study and should be assessed. Management of post-tonsillectomy pain in children is founded on individual risk/benefit analysis.

Guidelines (short version) of the French Oto-Rhino-Laryngology--Head and Neck Surgery Society (SFORL) for the management of post-tonsillectomy pain in adults.

OBJECTIVES: The present clinical practice guidelines cover the entire field of management of post-tonsillectomy pain. Given the French and European regulatory restrictions on the use of codeine, an update appears necessary to clarify the management of post-tonsillectomy pain in adults. METHOD: A work group approached the issue of pain management, following the chronological pathway from initial consultation to postoperative period. As exhaustive a study of the literature as possible assessed the pain impact of the various surgical techniques and the efficacy of the various analgesia schedules. RESULTS: Guidelines on the management of post-tonsillectomy pain in adults were drawn up and graded, based on the levels of evidence of selected articles and on work group consensus. The guidelines stress the importance of patient information and seek to harmonize practice, reduce the risk of postoperative complications and above all improve control of post-tonsillectomy pain in adults.

[Constraints of the dentist are consistent with the results of an optimal irradiation with modulated intensity in N0 oropharyngeal cancer]. / Les contraintes du chirurgien dentiste sont compatibles avec les résultats d'une irradiation optimale avec modulation d'intensité dans les cancers de l'oropharynx de stade N0.

PURPOSE: We compared intensity-modulated radiotherapy and 3D-conformal irradiation in oropharyngeal cancers according to the requirement of dentists. MATERIAL AND METHODS: From the files of seven patients with cancer of the oropharynx, two dosimetry plannings for 3D-conformal radiotherapy and intensity-modulated radiotherapy with tomotherapy were performed. The dose distributions in the target volumes and organs at risk in relation to the dental sphere were compared. RESULTS: For the planning target volume of the primitive tumour sites, average values of V95%, D2%, D98% and of the conformal index were statistically in favour of tomotherapy. For the planning target volume of node areas, averages values of V95%, D2%, D98% were statistically in favour of tomotherapy. For ipsi- and controlateral parotide glands, average values of V15Gy, V26Gy, V30Gy, V40Gy were significantly lower for tomotherapy. For the submaxillary glands, average values of mean doses and V40Gy were statistically in favour of tomotherapy. For the buccal cavity, the average values of V45Gy were statistically in favour of tomotherapy. For ipsi- and controlateral masseter muscles, the average values of mean doses were statistically in favour of tomotherapy. For the ipsi- and controlateral temporomandibular joints, average values of mean doses and V60Gy were statistically in favour of tomotherapy. For mandibular bone, average values of mean doses and V40Gy, V50Gy, V60Gy and V70Gy were statistically in favour of tomotherapy. For maxillary bone, average values of V40Gy, V50Gy and V60Gy were statistically in favour of tomotherapy. CONCLUSION: The radiation oncologist can constrain the intensity-modulated radiotherapy dosimetry to the needs of dentists to prevent or improve dental care and quality of life.

Initial staging of squamous cell carcinoma of the oral cavity, larynx and pharynx (excluding nasopharynx). Part 2: Remote extension assessment and exploration for secondary synchronous locations outside of the upper aerodigestive tract. 2012 SFORL guidelines.

OBJECTIVES: This report presents the French Society of ORL (SFORL) guidelines for exploration for remote metastasis and synchronous second cancer in initial staging of head and neck squamous cell carcinoma. MATERIALS AND METHODS: An exhaustive literature review was analyzed by a multidisciplinary work-group. RESULTS: The thorax is the most frequent location of remote metastases and synchronous second cancer outside of the upper aerodigestive tract. Thoracic CT is recommended as first-line examination in all cases (grade B). 18-FDG PET/CT is recommended when the thoracic CT image is doubtful or in case of high metastatic risk (grade B), for the detection of non-pulmonary remote metastasis. Esophageal exploration is recommended in case of significant risk of synchronous esophageal cancer (hypopharyngeal or oropharyngeal tumor, chronic alcohol intoxication) (grade B). The reference examination is flexible endoscopy of the upper digestive tract (grade B). CONCLUSION: The present grade B recommendations rationalize the roles of the various first-line radiological and endoscopic examinations for remote metastasis and synchronous second cancer, so as to limit the number of examinations performed, thereby reducing the time needed for initial staging.

Initial staging of squamous cell carcinoma of the oral cavity, larynx and pharynx (excluding nasopharynx). Part I: Locoregional extension assessment: 2012 SFORL guidelines.

OBJECTIVES: To set out good practice guidelines for locoregional extension assessment of squamous cell carcinoma of the head and neck (excluding nasopharynx, nasal cavities and sinuses). MATERIALS AND METHODS: A critical multidisciplinary review of the literature on locoregional extension assessment of squamous cell carcinoma of the head and neck was conducted, applying levels of evidence in line with the French health authority's (HAS) literature analysis guide of January 2000. CONCLUSION: Based on the levels of evidence of the selected articles and on work-group consensus, graded guidelines are set out for clinical, endoscopic and imaging locoregional extension assessment of head and neck cancer.

CXCR4 activation maintains a stem cell population in tamoxifen-resistant breast cancer cells through AhR signalling.

BACKGROUND: Tamoxifen is commonly used for breast cancer therapy. However, tamoxifen resistance is an important clinical problem. Continuous treatment with conventional therapy may contribute to cancer progression in recurring cancers through the accumulation of drug-resistant cancer progenitors. METHODS: To investigate signalling mechanisms important for the maintenance and viability of drug-resistant cancer progenitors, we used microarray analysis, PCR array for genes involved in cancer drug resistance and metabolism, flow cytometry, soft agar colony formation assay, in vivo tumourigenicity assay and immunohistochemical analysis using tamoxifen-sensitive and tamoxifen-resistant breast cancer MCF7 cells. RESULTS: Downregulation of CXCR4 signalling by small molecule antagonist AMD3100 specifically inhibits growth of progenitor cell population in MCF7(TAM-R) cells both in vitro and in vivo. Microarray analysis revealed aryl hydrocarbon receptor (AhR) signalling as one of the top networks that is differentially regulated in MCF7(TAM-R) and MCF7 xenograft tumours treated with AMD3100. Further, small molecule antagonists of AhR signalling specifically inhibit the progenitor population in MCF7(TAM-R) cells and growth of MCF7(TAM-R) xenografts in vivo. CONCLUSION: The chemokine receptor CXCR4 maintains a cancer progenitor population in tamoxifen-resistant MCF7 cells through AhR signalling and could be a putative target for the treatment of tamoxifen-resistant breast cancers.

Vocal fold cancer.

Ninety percent of vocal fold cancers take the form of squamous cell carcinoma. Since the 1980s, incidence in France has been constantly falling in males while increasing in females. The main risk factor is smoking, alcohol being less implicated than in other laryngeal or extralaryngeal locations. Vocal fold squamous cell carcinoma generally develops on healthy mucosa, although primary precancerous lesions such as leukoplakia or papillomatous keratosis are also frequent. The tumor usually originates in the non-lymphophilic mucosal free edge of the vocal fold then invades the various anatomic subunits of the larynx, acquiring lymph-node metastatic potential. Dysphonia is the first presenting symptom, initially caused by defective mucosal vibration and then by impaired mobility and finally fixation of the vocal fold. Extension, risk factor and pretreatment assessments are as in other upper-aerodigestive-tract cancer locations. The possibilities of laryngoscopic exposure and the tumor limits, however, need to be precisely determined if transoral resection is to be considered. For small tumors, surgery or exclusive radiation therapy can be suggested to the patient as part of an individual treatment plan, each having its advantages and drawbacks. Cutting-edge teams report 5-year local control rates of 85-95% in T1-class tumor and 60-90% in T2. Whatever the treatment option, smoking cessation, close surveillance and cardiovascular prevention enable screening of other oncologic locations and limit onset of the other pathologies implicated in most deaths.

Dairy nutrition management: Assessing a comprehensive continuing education program for veterinary practitioners.

The purpose of this study was to assess the effectiveness of a team-based educational program designed to enhance the flow of applied, research-based, nutrition information to dairy veterinarians. A comprehensive dairy cattle nutrition curriculum was developed and participants from 11 veterinary practices located in 5 states (IN, NY, PA, NM, and OH), serving an estimated 186,150 dairy cattle in 469 herds, attended the 2 advanced nutrition modules (∼2.5 d each and ∼40 h of learning) held in 2009. Nutrients, feeding transition cows, calves, and heifers, dry matter intake, feed storage, metabolic diseases, evaluating cows (scoring body condition, manure, and lameness), metabolic blood profiles, and feeding behavior were discussed. Educational materials were delivered through in-class lectures, followed by case-based learning and group discussions. A farm visit and out-of-class assignments were also implemented. Attendees were assessed using pre- and post-tests of knowledge to determine the level of knowledge gained in both nutrition modules. Participants evaluated the program and provided feedback at the conclusion of each module. Veterinarians (100%) reported that the overall program, presentations, and discussions were useful. Attendees found the presented information relevant for their work (agree=60% and strongly agree=40%) and of great immediate use to them (neutral=6.5%, agree=56%, and strongly agree=37.5%). The presented materials and the implemented educational delivery methods substantially increased the knowledge level of the attendees (16.9% points increase from pre-test to post-test scores). Importance of feed particle size, ration evaluation, interpreting feed analysis, balancing carbohydrate components, and metabolic profiling in fresh cows were listed as learned concepts that participants could apply in their practices. Results suggested that both nutrition modules were relevant and effective, offering new information with immediate field application. This program has important implications for dairy veterinarians because they serve as a vital source of information for dairy producers.

Wegener's granulomatosis of the temporal bone and skull base that mimicked an inflammatory myofibroblastic tumour: a case report.

OBJECTIVE: To compare two potential diagnoses of a temporal bone pseudotumour: an inflammatory myofibroblastic tumour and Wegener's granulomatosis. METHODOLOGY: A case of Wegener's granulomatosis that mimicked an inflammatory myofibroblastic tumour is reported. The clinical presentation, staging of the disease, histology, and follow-up are analysed. RESULTS: Histopathology of the temporal bone failed to provide an accurate diagnosis, even after immunocytochemical analyses. The diagnosis of Wegener's granulomatosis was suspected after biopsy of a pulmonary mass and was confirmed by the presence of anti-neutrophil cytoplasmic antibodies in blood samples. CONCLUSION: Irrespective of the aetiology, a pseudotumour of the temporal bone should always be investigated by biology and radiology. Radiological investigations will allow staging of the disease and specific localisation for biopsies.

[Replacement of the trachea using surgical reconstruction: current state of research]. / Remplacement de trachée par reconstructions chirurgicales: état actuel de la recherche.

OBJECTIVE: To review the main studies and the recent surgical procedures in tracheal reconstruction. MATERIAL AND METHOD: The literature search was conducted using the key words "tracheal reconstruction", "grafts", and "tissue engineering" and by selecting references from the articles reviewed as well as the experience of the authors in this field. RESULTS: Surgical reconstruction for tracheal replacement without using biomaterials involves tissue grafts (auto- or allografts) and tissue engineering. Among the many procedures already described, three new techniques have emerged these past few years employing autologous mesenchymal stem-cell-derived chondrocytes, autologous cultured epithelial cells, and a matrix derived from tracheal graft; costal cartilage, recipient mucosa, and local or free flaps, and an aortic graft. These procedures have been proposed in humans with apparently good results but with a still limited follow-up. CONCLUSIONS: Tracheal reconstruction techniques have recently progressed and replacing a long segment of trachea can be envisaged for the future. Moreover, these reconstructions, in conjunction with biomaterial development, would facilitate the design and the implantation of a laryngeal prosthesis.