Long-term stimulation by implanted pacemaker enables non-atrophic treatment of bilateral vocal fold paresis in a human-like animal model.

A wide variety of treatments have been developed to improve respiratory function and quality of life in patients with bilateral vocal fold paresis (BVFP). One experimental method is the electrical activation of the posterior cricoarytenoid (PCA) muscle with a laryngeal pacemaker (LP) to open the vocal folds. We used an ovine (sheep) model of unilateral VFP to study the long-term effects of functional electrical stimulation on the PCA muscles. The left recurrent laryngeal nerve was cryo-damaged in all animals and an LP was implanted except for the controls. After a reinnervation phase of six months, animals were pooled into groups that received either no treatment, implantation of an LP only, or implantation of an LP and six months of stimulation with different duty cycles. Automated image analysis of fluorescently stained PCA cross-sections was performed to assess relevant muscle characteristics. We observed a fast-to-slow fibre type shift in response to nerve damage and stimulation, but no complete conversion to a slow-twitch-muscle. Fibre size, proportion of hybrid fibres, and intramuscular collagen content were not substantially altered by the stimulation. These results demonstrate that 30 Hz burst stimulation with duty cycles of 40% and 70% did not induce PCA atrophy or fibrosis. Thus, long-term stimulation with an LP is a promising approach for treating BVFP in humans without compromising muscle conditions.

Smart Artificial Soft Tissue - Application to a Hybrid Simulator for Training of Laryngeal Pacemaker Implantation.

Surgical simulators are safe and evolving educational tools for developing surgical skills. In particular, virtual and hybrid simulators are preferred due to their detailedness, customization and evaluation capabilities. To accelerate the revolution of a novel class of hybrid simulators, a Smart Artificial Soft Tissue is presented here, that determines the relative position of conductive surgical instruments in artificial soft tissue by inverse resistance mappings without the need for a fixed reference point. This is particularly beneficial for highly deformable structures when specific target regions need to be reached or avoided. The carbon-black-silicone composite used can be shaped almost arbitrarily and its elasticity can be tuned by modifying the silicone base material. Thus, objective positional feedback for haptically correct artificial soft tissue can be ensured. This is demonstrated by the development of a laryngeal phantom to simulate the implantation of laryngeal pacemaker electrodes. Apart from the position-detecting larynx phantom, the simulator uses a tablet computer for the virtual representation of the vocal folds' movements, in accordance with the electrical stimulation by the inserted electrodes. The possibility of displaying additional information about target regions and anatomy is intended to optimize the learning progress and illustrates the extensibility of hybrid surgical simulators.

Isolated Recovery of Adductor Muscle Function Following Bilateral Recurrent Laryngeal Nerve Injuries.

OBJECTIVES/HYPOTHESIS: The aim of this study was to analyze the phoniatric and respiratory outcomes of a subset of bilateral vocal cord paralysis (BVCP) patients who were all treated with unilateral endoscopic arytenoid abduction lateropexy (EAAL). EAAL is a nondestructive, minimally invasive glottis widening operation, which does not damage either the surgically treated or the contralateral vocal cord. Therefore, it does not impair the regeneration potential of the recurrent laryngeal nerve. STUDY DESIGN: Case series. METHODS: Ten out of 21 BVCP patients who were treated with EAAL showed signs of isolated adduction recovery at 1 year and were chosen for this study. Functional results (objective and subjective voice analysis, spirometric measurement) and vocal cord movements were assessed preoperatively, 1 week and 1 year after EAAL. Laryngeal electromyography was performed on the 12th postoperative month. RESULTS: The volitional adductor movement seen on laryngoscopy was corroborated by laryngeal electromyography evaluation. Peak inspiratory flow increased significantly after EAAL. Quality-of-life scores also showed high patient satisfaction. Shimmer showed consistent improvement along with harmonic-to-noise ratio and average maximal phonation time in parallel with the improving vocal cord movement. Complex voice analysis and subjective self-evaluation tests also demonstrated significant improvement. CONCLUSIONS: EAAL, as a minimally invasive, nondestructive airway widening technique, does not interfere with the potential regeneration process that can still occur after BVCP, allowing for laryngeal functional recovery. It is a safe and effective treatment for BVCP that allows a simple solution with good phonatory, swallowing, and respiratory benefits by unilateral passive and reversible vocal cord lateralization. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:2334-2340, 2019.

Laryngeal pacing in minipigs: in vivo test of a new minimal invasive transcricoidal electrode insertion method for functional electrical stimulation of the PCA.

Functional electrical stimulation (FES) of the posterior cricoarytenoid muscle (PCA) to restore respiratory function of the larynx may become an option for the treatment of bilateral recurrent laryngeal nerve paralysis (RLNP) in the near future. The feasibility of this has been shown in several animal trials and in a human pilot study. The common open surgical inferolateral approach for electrode insertion into the PCA for FES has a risk of damaging the recurrent laryngeal nerve (RLN) and may result in postoperative swelling and scaring of the larynx. Therefore, a minimal invasive electrode insertion technique is needed. A new miniaturized bipolar spiral tip electrode and a new electrical stimulatable insertion needle were tested in a short-term trial for an endoscopically guided and functionally controlled transcricoidal electrode insertion in eight Göttingen minipigs with bilateral normal RLN function. The feasibility of this technique was evaluated and the achieved positions of the electrodes in the PCA were analyzed using intraoperative stimulation threshold data and 3D-CT reconstructions. In seven cases it was possible to place two well-performing electrodes into the PCA. They were positioned one on either side. In one animal no functioning electrode position could be achieved because the PCA was missed. Thresholds of the electrode tips varied between 0.2 and 2.5 mA (mean 0.71 mA). In any case maximal glottal opening could be reached before adductors were co-activated. The majority of electrodes were placed into the central lower part of the PCA with no apparent correlation between threshold and electrode position. Surgical trauma might be further reduced by using endoscopy via a laryngeal mask avoiding the temporary tracheostomy used in this trial. If the implanted electrodes remain stable in long-term tests, we suggest that this method could soon be transferred into human application.

Large-scale association study identifies ICAM gene region as breast and prostate cancer susceptibility locus.

We conducted a large-scale association study to identify genes that influence nonfamilial breast cancer risk using a collection of German cases and matched controls and >25,000 single nucleotide polymorphisms located within 16,000 genes. One of the candidate loci identified was located on chromosome 19p13.2 [odds ratio (OR) = 1.5, P = 0.001]. The effect was substantially stronger in the subset of cases with reported family history of breast cancer (OR = 3.4, P = 0.001). The finding was subsequently replicated in two independent collections (combined OR = 1.4, P < 0.001) and was also associated with predisposition to prostate cancer in an independent sample set of prostate cancer cases and matched controls (OR = 1.4, P = 0.002). High-density single nucleotide polymorphism mapping showed that the extent of association spans 20 kb and includes the intercellular adhesion molecule genes ICAM1, ICAM4, and ICAM5. Although genetic variants in ICAM5 showed the strongest association with disease status, ICAM1 is expressed at highest levels in normal and tumor breast tissue. A variant in ICAM5 was also associated with disease progression and prognosis. Because ICAMs are suitable targets for antibodies and small molecules, these findings may not only provide diagnostic and prognostic markers but also new therapeutic opportunities in breast and prostate cancer.

[Testing the sense of smell using validated procedures]. / Die Prüfung des Riechvermögens mit validierten Verfahren.

There is a growing interest into the investigation of smell disorders in both research and clinical practice. For psychophysical ("subjective") investigations related to the sense of smell a variety of test kits are available, namely the various "Sniffin' Sticks" kits, the UPSIT (University of Pennsylvania Smell Identification Test) or the CCSIT (Cross-Cultural Smell Identification Test). Recording of olfactory evoked potentials (OEPs) and respiration olfactometry can be used for diagnosing smell dysfunctions in a more objective way.

[Testing the sense of taste using validated procedures]. / Die Prüfung des Schmeckvermögens mit validierten Verfahren.

Psychophysical tests related to the sense of taste are usually less complex than those of the sense of smell. In addition to global tests a regional examination of the sense of taste might be indicated to search for nerve lesions. There are numerous validated psychophysical tests available based on the administration of liquid or solid substrates. The use of electrical currents (electrogustometry) is especially feasible for a rapid regional testing. The registration of gustatory event-related potentials to objectify results from psychophysical examination is possible although limited to a few centers world-wide.

Hemangiopericytoma: a rare head and neck tumor.

Among the rare malignant tumors of the paranasal sinuses and the middle ear, the hemangiopericytoma represents a very rare tumor entity. Reviewing four cases treated in our ENT department, we present here our experiences with this tumor. Inpatient and outpatient medical records from 1976 to 2001 were evaluated retrospectively. For the whole period we found four patients, three women and one man, who were treated with the diagnosis of hemangiopericytoma. Three tumors were localized in the paranasal sinuses (two in the maxillary sinus, one in the frontal sinus) and one in the middle ear. While the two tumors of the maxillary sinus and the tumor of the middle ear were treated only by surgery, the patient with the tumor of the frontal sinus also received postoperative irradiation because of an endocranial infiltration. This patient was the only one who developed an endocranial recurrence 14 years later on the opposite site, which again was treated with a combination of surgery and radiotherapy. The hemangiopericytoma as a very rare tumor in the paranasal sinuses and the middle ear should be treated with surgery. In our view, an adjuvant radiotherapy is indicated only in selected individual cases.

Headache as an unusual presenting symptom of retropharyngeal ganglioneuroma.

Ganglioneuromas are rare benign neurogenous neoplasms. The clinical symptoms of ganglioneuromas of the neck are usually mild and non-specific and definitive diagnosis requires a histological examination. We present the case of a 35-year-old female who complained of retroauricular pain as her first symptom and who was initially diagnosed with migraine. ENT examination revealed a bulging of the left pharyngeal wall. Fine-needle aspiration biopsy was misleading in terms of diagnosis. Histology after extirpation showed a ganglioneuroma. Ganglion cell differentiation was proven using the new intermediate filament class alpha-internexin immunohistochemical staining technique. Headache is an uncharacteristic symptom of ganglioneuroma and an interdisciplinary approach is required to find a possible cause. Periauricular pain without abnormal otoscopic findings should lead the otorhinolaryngologist to consider a retropharyngeal condition, especially if combined with dysphagia. Complete resection of the tumor using modern microsurgical techniques is the best way to extract ganglioneuroma today.