Potential value of CT-based comprehensive nomogram in predicting occult lymph node metastasis of esophageal squamous cell paralaryngeal nerves: a two-center study.

PURPOSE: The aim of this study is to construct a combined model that integrates radiomics, clinical risk factors and machine learning algorithms to predict para-laryngeal lymph node metastasis in esophageal squamous cell carcinoma. METHODS: A retrospective study included 361 patients with esophageal squamous cell carcinoma from 2 centers. Radiomics features were extracted from the computed tomography scans. Logistic regression, k nearest neighbor, multilayer perceptron, light Gradient Boosting Machine, support vector machine, random forest algorithms were used to construct radiomics models. The receiver operating characteristic curve and The Hosmer-Lemeshow test were employed to select the better-performing model. Clinical risk factors were identified through univariate logistic regression analysis and multivariate logistic regression analysis and utilized to develop a clinical model. A combined model was then created by merging radiomics and clinical risk factors. The performance of the models was evaluated using ROC curve analysis, and the clinical value of the models was assessed using decision curve analysis. RESULTS: A total of 1024 radiomics features were extracted. Among the radiomics models, the KNN model demonstrated the optimal diagnostic capabilities and accuracy, with an area under the curve (AUC) of 0.84 in the training cohort and 0.62 in the internal test cohort. Furthermore, the combined model exhibited an AUC of 0.97 in the training cohort and 0.86 in the internal test cohort. CONCLUSION: A clinical-radiomics integrated nomogram can predict occult para-laryngeal lymph node metastasis in esophageal squamous cell carcinoma and provide guidance for personalized treatment.

Preservation of Internal Branch of Superior Laryngeal Nerve during Surgery for Hypopharyngeal Cancer.

OBJECTIVES: This study was performed to evaluate the significance of intraoperative preservation of the internal branch of the superior laryngeal nerve (ibSLN) during surgery for hypopharyngeal squamous cell carcinoma (HSCC). METHODS: Twelve patients with HSCC underwent surgery between January 2017 and December 2018. Sensation in the hypopharyngeal mucosa was tested using a flexible laryngeal endoscope on postoperative day 5. RESULTS: Surgeries were successfully performed in 10 patients with HSCC arising from the internal wall of the pyriform fossa and in 2 patients with HSCC arising from the posterior wall of the hypopharynx. The main trunk of the ibSLN was preserved in all patients. Testing of sensation in the hypopharyngeal mucosa revealed the presence of the cough reflex in all patients. All patients achieved a full normal oral diet at a median of 8.5 days (range, 6-11 days) and removal of the tracheal tube at a median of 10 days (range, 7-12 days). CONCLUSIONS: Our results showed that preservation of the ibSLN during surgery for HSCC is feasible and important in the recovery of sensation in the hypopharyngeal mucosa.

Development of a constant pressure perfused ex vivo model of the equine larynx.

Distal axonopathy is seen in a broad range of species including equine patients. In horses, this degenerative disorder of the recurrent laryngeal nerve is described as recurrent laryngeal neuropathy (RLN). The dysfunctional innervation of the cricoarytenoideus dorsalis muscle (CAD) leads to a loss of performance in affected horses. In general, ex vivo models of the larynx are rare and for equine patients, just one short report is available. To allow for testing new therapy approaches in an isolated organ model, we examined equine larynges in a constant pressure perfused setup. In order to check the vitality and functionality of the isolated larynx, the vessels´ reaction to norepinephrine (NE) and sodium nitroprusside (NP) as vasoactive agents was tested. Additionally, the contractility of the CAD was checked via electrical stimulation. To determine the extent of hypoxic alterations, lactate dehydrogenase (LDH) and lactate were measured and an immunofluorescent analysis of hypoxia-inducible factor (HIF-1α), a key transcription factor in hypoxia, was performed. For this, a hypoxia-induced cell culture for HIF-1α was developed. The application of NE led to an expected vasoconstriction while NP caused the expected vasodilation. During a perfusion period of 352 ±20.78 min, LDH values were in the reference range and lactate values slightly exceeded the reference range at the end of the perfusion. HIF-1α nuclear translocation could reliably be detected in the hypoxia-induced cell cultures, but not in sections of the perfused CAD. With the approach presented here, a solid basis for perfusing equine larynges was established and may serve as a tool for further investigations of equine larynx disorders as well as a transferrable model for other species.

Muscle activity and kinematics show different responses to recurrent laryngeal nerve lesion in mammal swallowing.

Understanding the interactions between neural and musculoskeletal systems is key to identifying mechanisms of functional failure. Mammalian swallowing is a complex, poorly understood motor process. Lesion of the recurrent laryngeal nerve, a sensory and motor nerve of the upper airway, results in airway protection failure (liquid entry into the airway) during swallowing through an unknown mechanism. We examined how muscle and kinematic changes after recurrent laryngeal nerve lesion relate to airway protection in eight infant pigs. We tested two hypotheses: 1) kinematics and muscle function will both change in response to lesion in swallows with and without airway protection failure, and 2) differences in both kinematics and muscle function will predict whether airway protection failure occurs in lesion and intact pigs. We recorded swallowing with high-speed videofluoroscopy and simultaneous electromyography of oropharyngeal muscles pre- and postrecurrent laryngeal nerve lesion. Lesion changed the relationship between airway protection and timing of tongue and hyoid movements. Changes in onset and duration of hyolaryngeal muscles postlesion were less associated with airway protection outcomes. The tongue and hyoid kinematics all predicted airway protection outcomes differently pre- and postlesion. Onset and duration of activity in only one infrahyoid and one suprahyoid muscle showed a change in predictive relationship pre- and postlesion. Kinematics of the tongue and hyoid more directly reflect changes in airway protections pre- and postlesion than muscle activation patterns. Identifying mechanisms of airway protection failure requires specific functional hypotheses that link neural motor outputs to muscle activation to specific movements.NEW & NOTEWORTHY Kinematic and muscle activity patterns of oropharyngeal structures used in swallowing show different patterns of response to lesion of the recurrent laryngeal nerve. Understanding how muscles act on structures to produce behavior is necessary to understand neural control.

The strap intermuscular approach can significantly increase the exposure rate of the external branch of the superior laryngeal nerve during thyroid surgery.

BACKGROUND: Avoiding injury to the external branch of the superior laryngeal nerve (EBSLN) is a major challenge during thyroid surgery. EBSLN injury can have an impact on the quality of life of patients. The aim of this study was to introduce the strap intermuscular approach, to dissect the EBSLN with two different approaches in thyroid surgery, to compare the differences between these two approaches, and to describe a way for surgeons to treat the upper thyroid gland to find the EBSLN. METHODS: A prospective study of hemithyroidectomy was performed. In total, 104 patients were included and randomly divided into two groups: one group used the traditional approach to expose and protect the EBSLN, and the other group used the strap intermuscular approach. We described the surgical procedure for the strap intermuscular approach and compared the differences in the rates of EBSLN exposure, injury, and classification to illustrate the advantages of the intermuscular approach in thyroid surgery. RESULTS: The exposure rate of the EBSLN was higher with the strap intermuscular approach than with the traditional approach (96.15% vs. 76.92%, p = 0.01), with an odds ratio (OR) and 95% confidence interval (CI) of 0.133 (0.028-0.630). The exposure rate of EBSLNs classified as type 1 was higher in the strap intermuscular approach than in the traditional approach (30.77% vs. 13.46%, p = 0.033), with an OR and 95% CI of 0.350 (0.130-0.942). CONCLUSIONS: The exposure rate of the EBSLN was significantly higher with the strap intermuscular approach method than with the traditional approach during thyroid surgery. This approach allows for better identification of the EBSLN during thyroidectomy.

A RAPGEF6 variant constitutes a major risk factor for laryngeal paralysis in dogs.

Laryngeal paralysis (LP) is the inability to abduct the arytenoid cartilages during inspiration, resulting in a partial to complete airway obstruction and consequent respiratory distress. Different forms of LP with varying age of onset exist in dogs. Hereditary early onset forms were reported in several dog breeds. In most breeds, hereditary LP is associated with other neurologic pathologies. Using a genome-wide association study and haplotype analyses, we mapped a major genetic risk factor for an early onset LP in Miniature Bull Terriers to a ~1.3 Mb interval on chromosome 11. Whole genome sequencing of an affected Miniature Bull Terrier and comparison to 598 control genomes revealed a 36 bp insertion into exon 15 of the RAPGEF6 gene (c.1793_1794ins36). The imperfect genotype-phenotype correlation suggested a complex mode of inheritance with a major genetic risk factor involving a recessive risk allele. Homozygosity for the insertion was associated with a 10- to 17-fold increased risk for LP. The insertion allele was only found in Miniature Bull Terriers and Bull Terriers. It was absent from >1000 control dogs of other dog breeds. The insertion sequence contains a splice acceptor motif leading to aberrant splicing in transcripts originating from the mutant allele (r.1732_1780del). This leads to a frameshift and a premature stop codon, p.(Ile587ProfsTer5), removing 64% of the open reading frame. Our results suggest an important role of RAPGEF6 in laryngeal nerve function and provide new clues to its physiological significance.

Dental pulp-derived stem cell conditioned medium to regenerate peripheral nerves in a novel animal model of dysphagia.

In nerve regeneration studies, various animal models are used to assess nerve regeneration. However, because of the difficulties in functional nerve assessment, a visceral nerve injury model is yet to be established. The superior laryngeal nerve (SLN) plays an essential role in swallowing. Although a treatment for SLN injury following trauma and surgery is desirable, no such treatment is reported in the literature. We recently reported that stem cells derived from human exfoliated deciduous teeth (SHED) have a therapeutic effect on various tissues via macrophage polarization. Here, we established a novel animal model of SLN injury. Our model was characterized as having weight loss and drinking behavior changes. In addition, the SLN lesion caused a delay in the onset of the swallowing reflex and gain of laryngeal residue in the pharynx. Systemic administration of SHED-conditioned media (SHED-CM) promoted functional recovery of the SLN and significantly promoted axonal regeneration by converting of macrophages to the anti-inflammatory M2 phenotype. In addition, SHED-CM enhanced new blood vessel formation at the injury site. Our data suggest that the administration of SHED-CM may provide therapeutic benefits for SLN injury.

Immediate selective laryngeal reinnervation in vagal paraganglioma patients.

OBJECTIVE: This prospective case series aimed to present the outcomes of immediate selective laryngeal reinnervation. METHODS: Two middle-aged women with vagal paraganglioma undergoing an excision operation underwent immediate selective laryngeal reinnervation using the phrenic nerve and ansa cervicalis as the donor nerve. Multidimensional outcome measures were employed pre-operatively, and at 1, 6 and 12 months post-operatively. RESULTS: The voice handicap index-10 score improved from 23 (patient 1) and 18 (patient 2) at 1 month post-operation, to 5 (patient 1) and 1 (patient 2) at 12 months. The Eating Assessment Tool 10 score improved from 20 (patient 1) and 24 (patient 2) at 1 month post-operation, to 3 (patient 1) and 1 (patient 2) at 12 months. There was slight vocal fold abduction observed in patient one and no obvious abduction in patient two. CONCLUSION: Selective reinnervation is safe to perform following vagal paraganglioma excision conducted on the same side. Voice and swallowing improvements were demonstrated, but no significant vocal fold abduction was achieved.

[Clinical anatomic study on the segment and adjacent of tract of congenital pyriform sinus fistula].

Objective: To investigate the anatomic tract of congenital pyriform sinus fistula (CPSF). Methods: A total of 90 patients with CPSF undergoing open surgery between August, 2007 and March, 2017 at the Department of Guangdong General Hospital were retrospectively analyzed. Results: The tracts of all the fistulas actually walked far different from those of theoretical ones. A whole fistula may be divided into 4 segments according to adjacent anatomy of CPSF. The posterior inner segment to the thyroid cartilage was initial part of the fistula. It originated from the apex of pyriform sinus, then piercing out of the inferior constrictor of pharynx inferiorly near the inferior cornu of the thyroid cartilage (ICTC), and descended between the lateral branch of the superior laryngeal nerve and the recurrent laryngeal nerve. The ICTC segment was the second part of the fistula, firstly piercing out of the inferior constrictor of pharynx and/or cricothyroid muscle, and then entering into the upper pole of thyroid. The relationship between fistula and ICTC could be divided into three types: type A (medial inferior to ICTC) accounting for 42.2% (38/90); type B (penetrate ICTC) for 3.3% (3/90); and type C (lateral inferior to ICTC) for 54.5% (49/90). The internal segment in thyroid gland was the third part of fistula, walking into the thyroid gland and terminating at its upper pole (92.2%, 83/90) or deep cervical fascia near the upper pole of thyroid (7.8%, 7/90). The lateral inferior segment to thyroid gland was the last part of the fisula, most of which are iatrogenic pseudo fistula, and started from the lateral margin of thyroid gland. Conclusions: CPSF has a complicated pathway. Recognition of the tract and adjacent anatomy of CPSF will facilitate the dissection and resection of CPSF in open surgery.

Olfactory-ensheathing cells promote physiological repair of injured recurrent laryngeal nerves and functional recovery of glottises in dogs.

The aim of this study was to investigate whether the transplantation of olfactory-ensheathing cells (OECs) could physiologically repair severely injured recurrent laryngeal nerve (RLN) in dogs. Adult Beagle dogs were surgically introduced with a 10-mm defect in the left RLN and transplanted with a nerve guide (NEUROLAC) containing dog olfactory mucosa-olfactory-ensheathing cells (OM-OECs) in matrigel. The effects of OM-OECs on the morphology, histology, and electrophysiology of the injured RLNs, glottis movement, and voice acoustics were comparatively studied. Two months after transplantation, the normal dogs (group N) had intact left RLNs that contained axons well organized as bundles, transmitted action potentials of high amplitudes without latent phases, and modulated glottis movement to produce normal voices. The RLN-damaged dogs transplanted with OM-OECs (group CTT) had pieces of nerves regenerated in the place of the defects, which contained fewer axons scattered in the internal nerve membrane and wrapped peripherally by the connective tissue, prevented the distal trunk of the defected RLN from shrinking, transmitted action potentials of lower amplitudes with latent phases, and modulated a slightly impaired glottis movement to produce voices with slight differences compared to the N dogs. The RLN-damaged dogs without OM-OECs (group NC) had no nerves generated at the defective or the damaged area, leading to a shrinkage in the enervated distal nerve trunks; a blockage in nerve pulse transit; a paralysis of the left vocal cords; an impaired glottis movement; and abnormal voices. Transplantation of OM-OECs promoted nerve regeneration, and the recoveries of glottises and voices in dogs with RLN injury.

Laryngeal nerve morbidity in 1.273 central node dissections for thyroid cancer.

AIM: We assess the prevalence and mechanism of recurrent laryngeal nerve (RLN) injury in central neck dissection (CND) for thyroid cancer. METHODS: CND with intraoperative neural monitoring was outlined in 1.273 nerves at risk (NAR). RLN lesions were stratified according to: timing (during thyroidectomy versus CND), segmental vs. diffuse injury, mechanism, severity, location, number of lymph nodes dissected and metastastatic. EMG parameters were recorded. RESULTS: 49/1.273NAR (3,8%) documented RLN palsy. 25 nerves were injured during thyroidectomy, 8 while CND. In 16 no precise moment or mechanism of injury was identified. A disrupted point could be identified in 19/25 (76%) and 7/8 (87%) respectively for thyroidectomy and CND steps. Diffuse injury, occurred in 24% and 12,5% respectively for thyroidectomy and CND. Nerves were injured in the all cervical nerve course without any major location for incidence for CND; for thyroidectomy most nerves were injured in the last 1 cm course. Traction (36%) was the leading cause of RLN injury for thyroidectomy. For solely CND, traction, entrapment and thermal injuries were equally frequent. Permanent vs. transient injuries were respectively 8% (4/49) and 92% (n.45/49), overall. Permanent lesions were equally distributed. CONCLUSIONS: During CND, RLN palsy still occurs with routine exposure of the nerve even combined with IONM. The incidence of nerve lesions during thyroidectomy is higher than that of CND.

Successful Prediction of a Left Nonrecurrent Laryngeal Nerve in a Patient With Right-Sided Aorta and Aberrant Left Subclavian Artery.

BACKGROUND: Left nonrecurrent laryngeal nerve (LNRLN) is an extremely rare anatomic variant. The development of such anatomic variation requires the regression of both the fourth (aortic arch) and sixth (ductus arteriosus, DA) arches on the left side. Preoperative prediction of this variant is difficult but might reduce risk of nerve injury. METHODS: A 34-year-old female was indicated for thyroidectomy for a 2.4 cm follicular neoplasm and Graves' disease. Due to a positive medical history of 22q11.2 microdeletion and unexplained left vocal cord paralysis, a preoperative chest computed tomography (CT) scan was obtained and revealed a right-sided aorta (RSA) and aberrant left subclavian artery (ALSA) without Kommerell's diverticulum. A left-sided NRLN was then highly suspected. RESULTS: Thyroidectomy was performed under general anesthesia with the utilization of intraoperative laryngeal nerve monitoring. A LNRLN was confirmed intraoperatively. CONCLUSIONS: Right-sided aorta and ALSA indicate embryologic regression of the left fourth primitive aortic arch. The absence of Kommerell's diverticulum at the origin of the ALSA indicates the lack of high-pressure blood flow from the pulmonary artery to the ALSA through the ductus arteriosus during embryogenesis, suggesting the embryologic regression of the left sixth primitive aortic arch. The presence of all 3 radiologic features thus highly suggests the possibility of a LNRLN.

Laryngeal Neuropathy in Adult Goats With Copper Deficiency.

The aim of this study was to elucidate the cause of a neurological syndrome characterized by stridor in adult goats with clinical signs of copper deficiency. The main clinical signs consisted of apathy, emaciation, pale mucous membranes, mucous nasal discharge, dyspnea, severe achromotrichia, diffuse alopecia, torpor, ataxia, and stridor. When the goats were forced to move, the stridor increased. In a herd of 194 Toggenburg goats, 10 adult goats with clinical signs of copper deficiency were removed from the herd and divided into 2 groups: group 1, which consisted of 4 nannies and 1 buck with stridor, and group 2, which consisted of 4 nannies and 1 buck without stridor. Group 3, used as a control, consisted of 5 adult goats from another flock without any clinical signs of disease. The mean serum copper concentrations were 1.3 ± 0.3 µmol/L in group 1, 8.1 ± 1.1 µmol/L in group 2, and 11.3 ± 2.2 µmol/L in group 3. The mean serum iron concentrations were 42.3 ± 14.2 µmol/L in group 1, 39.1 ± 8.2 µmol/L in group 2, and 20.6 ± 6.1 µmol/L in group 3. The main histological lesions in goats from group 1 were axonal degeneration of the recurrent laryngeal nerves and atrophy of the muscles of vocal folds and of the dorsal cricoarytenoid and right and left cricothyroid muscles. Goats with ataxia had neuronal degeneration and necrosis of cerebellar Purkinje cells and of the cranial cervical ganglion. We concluded that the stridor was caused by axonal degeneration of the recurrent laryngeal nerves due to the severe copper deficiency.

Is intraoperative neural monitoring necessary for exploration of the superior laryngeal nerve?

BACKGROUND: We aimed to evaluate the contribution of intraoperative neuromonitoring to the visual and functional identification of the external branch of the superior laryngeal nerve and the effect on postoperative voice changes. METHODS: The prospective data of 221 patients (183 women, 38 men) who underwent thyroid operation with intraoperative neuromonitoring for exploration of the external branch of the superior laryngeal nerve were evaluated retrospectively. The surface endotracheal tube-based Medtronic NIM3 (Medtronic, Jacksonville, FL) intraoperative neuromonitoring device was used. The function of the external branch of the superior laryngeal nerve was evaluated by cricothyroid muscle twitch. Additionally, the contribution of the external branch of the superior laryngeal nerve to vocal cord adduction was evaluated using electromyographic records. RESULTS: A total of 374 (95.2%) of 393 external branch of the superior laryngeal nerves were identified; 145 (36.9%) external branch of the superior laryngeal nerves were identified visually before being stimulated with a probe, and 130 (33.1%) external branch of the superior laryngeal nerves were identified visually after being identified with a probe. Although 99 (25.2%) external branch of the superior laryngeal nerves were identified with a probe, they were not visualized. Intraoperative neuromonitoring provided meaningful contributions to visual (P = .001) and functional (P = .001) identification of the external branch of the superior laryngeal nerve. Positive electromyographic responses were recorded from 257 external branch of the superior laryngeal nerves (68.7%). After the patients with recurrent laryngeal nerve palsy were excluded, voice changes were detected in 6 (3.3%) of 184 patients with identified external branch of the superior laryngeal nerves and 3 (20%) of 15 patients in whom at least 1 external branch of the superior laryngeal nerve could not be identified with intraoperative neuromonitoring. CONCLUSION: Intraoperative neuromonitoring provided an important contribution to the visual and functional identification of the external branch of the superior laryngeal nerve. Intraoperative neuromonitoring is a helpful adjunct for identifying the external branch of the superior laryngeal nerve.

Neuralgia del nervio laríngeo superior: a propósito de un caso de difícil control / Refractory neuralgia of the superior laryngeal nerve: A case study

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Surgical treatment of superior laryngeal neuralgia: A case report and review of the literature.

Superior laryngeal (SL) neuralgia is paroxysmal pain above the thyrohyoid membrane. We present a case of SL neuralgia that was resistant to conservative treatment and eventually required surgical intervention. The patient was a 39-year-old woman with a 5-year history of debilitating pain above the thyroid cartilage. After having undergone different imaging scans with negative results, she tried various treatments (e.g., antibiotics, analgesics, stellate ganglion block, radiofrequency SL neurotomy, and stereotactic radiosurgery), all of which were ineffective. Finally, she underwent bilateral surgical SL neurotomy. Postoperatively, she immediately noticed a significant alleviation of her pain. Her postoperative course was completely uneventful, as she experienced no dysphagia or dysphonia, even transiently. One month later, she no longer required regular painkillers, and at 14 months, she remained essentially pain-free. While medical management remains the treatment of choice for SL neuralgia, we recommend that refractory cases be treated initially with a neural block with local anesthesia. Patients who do not respond are candidates for surgery. We consider selective peripheral SL neurotomy to be safe and effective when performed by experienced hands. We also discuss the difficulties of managing SL neuralgia.

The nonrecurrent laryngeal nerve: A clinical anatomic mapping with regard to intraoperative neuromonitoring.

BACKGROUND: We investigated the nonrecurrent inferior laryngeal nerve (nrILN), an important variant in the course of the inferior laryngeal nerve (ILN; 0.5-6.0%). Its importance was demonstrated in a clinical case as well as in cadaver specimens, and the pattern was identified with intraoperative neuromonitoring (IONM). METHODS: The ILN and the presence of an nrILN were investigated in 36 formaldehyde-embalmed specimens. Our anatomic findings showed differences in the anatomic course of the ILN and thus produced possible explanations for different IONM signals that would correlate with differences in the anatomic course of the ILN. Preoperative ultrasonographic evaluation of the brachiocephalic trunk and the recurrent laryngeal nerve were used for the exclusion or identification of an nrILN, respectively. RESULTS: We found 2 nrILNs (ascending, horizontal; 6%) in the anatomic specimens. These 2 specimens each showed an aberrant right subclavian artery (lusorial artery) and were, therefore, associated with the absence of a brachiocephalic trunk. The intraoperative case displayed a descending nrILN. Signals derived from the vagus nerve were positive if derived proximal to and negative if derived distal to the branching of an nrILN. By ultrasonographic identification of a normal brachiocephalic trunk, an nrILN could be excluded. CONCLUSION: Surgeons need a working knowledge about nrILNs to avoid recurrent nerve palsy and should be familiar with all the possible course variations in the ILN when IONM signals are absent with vagal stimulation. Moreover, endocrine surgeons need to be able to interpret correctly negative as well as positive signals. Preoperative ultrasonography should ideally be performed, because the presence of a normal brachiocephalic trunk is a quick method to exclude or identify a nrILN.

Síndrome de Ortner y disfagia por aurícula izquierda gigante en el paciente anciano / Dysphagia and Ortner syndrome due to a giant left atrium in the elderly

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