An Airway Protection Program Revealed by Sweeping Genetic Control of Vagal Afferents.

Sensory neurons initiate defensive reflexes that ensure airway integrity. Dysfunction of laryngeal neurons is life-threatening, causing pulmonary aspiration, dysphagia, and choking, yet relevant sensory pathways remain poorly understood. Here, we discover rare throat-innervating neurons (∼100 neurons/mouse) that guard the airways against assault. We used genetic tools that broadly cover a vagal/glossopharyngeal sensory neuron atlas to map, ablate, and control specific afferent populations. Optogenetic activation of vagal P2RY1 neurons evokes a coordinated airway defense program-apnea, vocal fold adduction, swallowing, and expiratory reflexes. Ablation of vagal P2RY1 neurons eliminates protective responses to laryngeal water and acid challenge. Anatomical mapping revealed numerous laryngeal terminal types, with P2RY1 neurons forming corpuscular endings that appose laryngeal taste buds. Epithelial cells are primary airway sentinels that communicate with second-order P2RY1 neurons through ATP. These findings provide mechanistic insights into airway defense and a general molecular/genetic roadmap for internal organ sensation by the vagus nerve.

The Control of Vocal Pitch in Human Laryngeal Motor Cortex.

In speech, the highly flexible modulation of vocal pitch creates intonation patterns that speakers use to convey linguistic meaning. This human ability is unique among primates. Here, we used high-density cortical recordings directly from the human brain to determine the encoding of vocal pitch during natural speech. We found neural populations in bilateral dorsal laryngeal motor cortex (dLMC) that selectively encoded produced pitch but not non-laryngeal articulatory movements. This neural population controlled short pitch accents to express prosodic emphasis on a word in a sentence. Other larynx cortical representations controlling voicing and longer pitch phrase contours were found at separate sites. dLMC sites also encoded vocal pitch during a non-speech singing task. Finally, direct focal stimulation of dLMC evoked laryngeal movements and involuntary vocalization, confirming its causal role in feedforward control. Together, these results reveal the neural basis for the voluntary control of vocal pitch in human speech. VIDEO ABSTRACT.

Lentiviral expression of wild-type LAMA3A restores cell adhesion in airway basal cells from children with epidermolysis bullosa.

The hallmark of epidermolysis bullosa (EB) is fragile attachment of epithelia due to genetic variants in cell adhesion genes. We describe 16 EB patients treated in the ear, nose, and throat department of a tertiary pediatric hospital linked to the United Kingdom's national EB unit between 1992 and 2023. Patients suffered a high degree of morbidity and mortality from laryngotracheal stenosis. Variants in laminin subunit alpha-3 (LAMA3) were found in 10/15 patients where genotype was available. LAMA3 encodes a subunit of the laminin-332 heterotrimeric extracellular matrix protein complex and is expressed by airway epithelial basal stem cells. We investigated the benefit of restoring wild-type LAMA3 expression in primary EB patient-derived basal cell cultures. EB basal cells demonstrated weak adhesion to cell culture substrates, but could otherwise be expanded similarly to non-EB basal cells. In vitro lentiviral overexpression of LAMA3A in EB basal cells enabled them to differentiate in air-liquid interface cultures, producing cilia with normal ciliary beat frequency. Moreover, transduction restored cell adhesion to levels comparable to a non-EB donor culture. These data provide proof of concept for a combined cell and gene therapy approach to treat airway disease in LAMA3-affected EB.

Musculoskeletal morphogenesis supports the convergent evolution of bat laryngeal echolocation.

The order Chiroptera (bats) is the second largest group of mammals. One of the essential adaptations that have allowed bats to dominate the night skies is laryngeal echolocation, where bats emit ultrasonic pulses and listen to the returned echo to produce high-resolution 'images' of their surroundings. There are two possible scenarios for the evolutionary origin of laryngeal echolocation in bats: (1) a single origin in a common ancestor followed by the secondary loss in Pteropodidae, or (2) two convergent origins in Rhinolophoidea and Yangochiroptera. Although data from palaeontological, anatomical, developmental and genomic studies of auditory apparatuses exist, they remain inconclusive concerning the evolutionary origin of bat laryngeal echolocation. Here we compared musculoskeletal morphogenesis of the larynx in several chiropteran lineages and found distinct laryngeal modifications in two echolocating lineages, rhinolophoids and yangochiropterans. Our findings support the second scenario that rhinolophoids and yangochiropterans convergently evolved advanced laryngeal echolocation through anatomical modifications of the larynx for ultrasonic sound generation and refinement of the auditory apparatuses for more detailed sound perception.

Immunohistochemical analysis and distribution of epithelial mast cells in the rat larynx and trachea.

Mast cells (MCs) in rat airways have been classified into two subtypes: epithelial MCs and connective tissue MCs (CTMCs). However, the immunohistochemical characteristics, cellular morphology, and distribution of epithelial MCs in the upper airways remain unclear. The present study investigated the morphological characteristics and distribution of epithelial MCs using 5-hydroxytryptamine (5-HT) and other immunohistochemical markers in sectioned or whole-mount preparations of the rat larynx and trachea. A double immunofluorescence analysis revealed the colocalization of 5-HT immunoreactivity with c-kit, a stem cell factor receptor commonly used as a MC marker, in both epithelial MCs and CTMCs. Dopa decarboxylase, an enzyme involved in 5-HT synthesis, was detected in both subtypes, suggesting their ability to synthesize and release 5-HT. Tryptase and histidine decarboxylase (a biosynthetic enzyme of histamine), which are well-known mediators of MCs, were exclusive to CTMCs. Epithelial MCs were pleomorphic with long cytoplasmic processes, whereas CTMCs were round and lacked cytoplasmic processes. The density of epithelial MCs was significantly higher in the glottis and cranial part of the trachea than in the epiglottis and other parts of the trachea. The present results showed that the morphology and immunohistochemical characteristics of epithelial MCs were different from those of CTMCs in the rat larynx and trachea, and variform epithelial MCs were predominantly located at the entrance of the upper airways. Epithelial MCs may release 5-HT to regulate innate immune responses by modulating epithelial cell functions at the entrance gate of the upper airways.

Postnatal changes in thyroid cartilage shape and cartilage matrix composition are not synchronized in Mus musculus.

The study was conducted to quantify laryngeal cartilage matrix composition and to investigate its relationship with cartilage shape in a mouse model. A sample of 30 mice (CD-1 mouse, Mus musculus) from five age groups (postnatal Days 2, 21, 90, 365, and 720) were used. Three-dimensional mouse laryngeal thyroid cartilage reconstructions were generated from contrast-enhanced micro-computed tomography (CT) image stacks. Cartilage matrix composition was estimated as Hounsfield units (HU). HU were determined by overlaying 3D reconstructions as masks on micro-CT image stacks and then measuring the attenuation. Cartilage shape was quantified with landmarks placed on the surface of the thyroid cartilage. Shape differences between the five age groups were analyzed using geometric morphometrics and multiparametric analysis of landmarks. The relationship between HU and shape was investigated with correlational analyses. Among five age groups, HU became higher in older animals. The shape of the thyroid cartilage changes with age throughout the entire life of a mouse. The changes in shape were not synchronized with changes in cartilage matrix composition. The thyroid cartilage of young and old M. musculus larynx showed a homogenous mineralization pattern. High-resolution contrast-enhanced micro-CT imaging makes the mouse larynx accessible for analysis of genetic and environmental factors affecting shape and matrix composition.

Anatomy and mechanisms of vocal production in harvest mice.

Characterizing mechanisms of vocal production provides important insight into the ecology of acoustic divergence. In this study, we characterized production mechanisms of two types of vocalizations emitted by western harvest mice (Reithrodontomys megalotis), a species uniquely positioned to inform trait evolution because it is a sister taxon to peromyscines (Peromyscus and Onychomys spp.), which use vocal fold vibrations to produce long-distance calls, but more ecologically and acoustically similar to baiomyines (Baiomys and Scotinomys spp.), which employ a whistle mechanism. We found that long-distance calls (∼10 kHz) were produced by airflow-induced vocal fold vibrations, whereas high-frequency quavers used in close-distance social interactions (∼80 kHz) were generated by a whistle mechanism. Both production mechanisms were facilitated by a characteristic laryngeal morphology. Our findings indicate that the use of vocal fold vibrations for long-distance communication is widespread in reithrodontomyines (Onychomys, Peromyscus, Reithrodontomys spp.) despite overlap in frequency content that characterizes baiomyine whistled vocalizations. The results illustrate how different production mechanisms shape acoustic variation in rodents and contribute to ecologically relevant communication distances.

Machine learning model to preoperatively predict T2/T3 staging of laryngeal and hypopharyngeal cancer based on the CT radiomic signature.

OBJECTIVES: To develop and assess a radiomics-based prediction model for distinguishing T2/T3 staging of laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) METHODS: A total of 118 patients with pathologically proven LHSCC were enrolled in this retrospective study. We performed feature processing based on 851 radiomic features derived from contrast-enhanced CT images and established multiple radiomic models by combining three feature selection methods and seven machine learning classifiers. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity were used to assess the performance of the models. The radiomic signature obtained from the optimal model and statistically significant morphological image characteristics were incorporated into the predictive nomogram. The performance of the nomogram was assessed by calibration curve and decision curve analysis. RESULTS: Using analysis of variance (ANOVA) feature selection and logistic regression (LR) classifier produced the best model. The AUCs of the training, validation, and test sets were 0.919, 0.857, and 0.817, respectively. A nomogram based on the model integrating the radiomic signature and a morphological imaging characteristic (suspicious thyroid cartilage invasion) exhibited C-indexes of 0.899 (95% confidence interval (CI) 0.843-0.955), fitting well in calibration curves (p > 0.05). Decision curve analysis further confirmed the clinical usefulness of the nomogram. CONCLUSIONS: The nomogram based on the radiomics model derived from contrast-enhanced CT images had good diagnostic performance for distinguishing T2/T3 staging of LHSCC. CLINICAL RELEVANCE STATEMENT: Accurate T2/T3 staging assessment of LHSCC aids in determining whether laryngectomy or laryngeal preservation therapy should be performed. The nomogram based on the radiomics model derived from contrast-enhanced CT images has the potential to predict the T2/T3 staging of LHSCC, which can provide a non-invasive and robust approach for guiding the optimization of clinical decision-making. KEY POINTS: • Combining analysis of variance with logistic regression yielded the optimal radiomic model. • A nomogram based on the CT-radiomic signature has good performance for differentiating T2 from T3 staging of laryngeal and hypopharyngeal squamous cell carcinoma. • It provides a non-invasive and robust approach for guiding the optimization of clinical decision-making.

An update on larynx cancer.

Answer questions and earn CME/CNE Laryngeal cancer remains one of the most common tumors of the respiratory tract. Fortunately, significant advancements have been made over the past decade in the treatment of laryngeal cancer. Although surgery has been the historical mainstay for localized disease and still is an integral part of treatment, nonsurgical options like radiation and systemic therapy have emerged as viable options. In addition, in the metastatic setting, novel agents are showing promise for this patient population. The care for patients with laryngeal cancer continues to evolve and truly requires a multidisciplinary team-based approach. Unique morbidities, such as loss of natural voice, respiration, and airway protection during swallowing, are observed with this disease and require special consideration. CA Cancer J Clin 2017;67:31-50. © 2016 American Cancer Society.

Diagnostic accuracy of post-mortem computed tomography for fractures of the hyoid-larynx complex.

Post-mortem computed tomography (PMCT) is routinely used at many forensic institutions to guide the following autopsy and is especially useful for diagnosing fractures. This systematic review aims to investigate the sensitivity and specificity of a PMCT scan in fracture diagnosis of the hyoid-larynx complex (HLC) compared to traditional autopsy in cases involving traumatic neck injuries. We searched PubMed, SCOPUS and Web of Science and included papers with cases n ≥ 3 published between January 2000 and April 2023 reporting on PMCT and autopsy findings of fractures of the HLC. The search provided 259 results of which 10 were included. Overall sensitivity and specificity were 0.70 [0.59; 0.79] and 0.92 [0.80; 0.97] for hyoid bone fractures and 0.80 [0.62; 0.91] and 0.76 [0.63; 0.85] for the thyroid cartilage. The results show great variation, and a large range between studies. These results indicate that PMCT cannot replace autopsy in cases with HLC fractures. Future larger prospective studies are needed, examining fracture details, scan protocols and different slice thicknesses using uniform reporting.

Histology Atlas of the Developing Mouse Respiratory System From Prenatal Day 9.0 Through Postnatal Day 30.

Respiratory diseases are one of the leading causes of death and disability around the world. Mice are commonly used as models of human respiratory disease. Phenotypic analysis of mice with spontaneous, congenital, inherited, or treatment-related respiratory tract abnormalities requires investigators to discriminate normal anatomic features of the respiratory system from those that have been altered by disease. Many publications describe individual aspects of normal respiratory tract development, primarily focusing on morphogenesis of the trachea and lung. However, a single reference providing detailed low- and high-magnification, high-resolution images of routine hematoxylin and eosin (H&E)-stained sections depicting all major structures of the entire developing murine respiratory system does not exist. The purpose of this atlas is to correct this deficiency by establishing one concise reference of high-resolution color photomicrographs from whole-slide scans of H&E-stained tissue sections. The atlas has detailed descriptions and well-annotated images of the developing mouse upper and lower respiratory tracts emphasizing embryonic days (E) 9.0 to 18.5 and major early postnatal events. The selected images illustrate the main structures and events at key developmental stages and thus should help investigators both confirm the chronological age of mouse embryos and distinguish normal morphology as well as structural (cellular and organ) abnormalities.

Non-squamous Cancers of the Larynx.

PURPOSE OF REVIEW: Although non-squamous tumors of the larynx are really rare, they may not always be viewed from the same perspective in the multidisciplinary treatment approach once the diagnosis is made. In this review, non-squamous tumors of the larynx and current approaches in treatment will be discussed. RECENT FINDINGS: When the studies and meta-analyses presented in the last 5 years are evaluated, it is seen that these tumors usually show non-specific symptoms. Due to their submucosal location, the stage of the disease at the time of diagnosis is often advanced. In the literature, treatment may vary in these particular cases. The majority of non-squamous tumors of the larynx includes minor salivary gland tumors, neuroendocrine carcinomas, sarcomas, cartilage tumors, and malignant melanomas. Once treating a patient with these diagnoses, it should be kept in mind that the histopathological subtype is almost as important as the stage of the tumor.

Xevinapant plus radiotherapy in resected, high-risk, cisplatin-ineligible LA SCCHN: the phase III XRay Vision study design.

There is a significant unmet need and lack of treatment options for patients with resected, high-risk, cisplatin-ineligible locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). Xevinapant, a first-in-class, potent, oral, small-molecule IAP inhibitor, is thought to restore cancer cell sensitivity to chemotherapy and radiotherapy in clinical and preclinical studies. We describe the design of XRay Vision (NCT05386550), an international, randomized, double-blind, phase III study. Approximately 700 patients with resected, high-risk, cisplatin-ineligible LA SCCHN will be randomized 1:1 to receive 6 cycles of xevinapant or placebo, in combination with radiotherapy for the first 3 cycles. The primary end point is disease-free survival, and secondary end points include overall survival, health-related quality of life, and safety.

Squamous cell carcinoma is the most common form of head and neck cancer (SCCHN) and includes cancers of the lips, mouth, throat, tongue and voice box. It is called 'locally advanced' when the cancer has spread to nearby areas but not to other parts of the body. Few treatment options are available for people with locally advanced SCCHN who have had surgery and are unable to receive a type of chemotherapy called cisplatin. Xevinapant is being developed as a possible new type of cancer treatment. It is a liquid that is taken by mouth or given through a feeding tube. Adding xevinapant to the standard treatment ­ called radiotherapy ­ aims to make radiotherapy more effective against the cancer. Researchers have started a large, international, phase III study called XRay Vision to see if adding xevinapant to radiotherapy can help stop the cancer from coming back after surgery and help people live longer. Clinical Trial Registration: NCT05386550 (ClinicalTrials.gov).

CT and MR anatomy of the larynx and hypopharynx.

Imaging of the larynx and hypopharynx is frequently requested to assess the extent of neoplasms beyond the field of view of endoscopic evaluation. The combination of optical and cross-sectional imaging allows tumors to be classified according to AJCC/UICC guidelines. A thorough understanding of laryngeal and hypopharyngeal anatomy is crucial to guide the radiological eye along the possible pathways of the spread of diseases and to guide differential diagnoses. Computed tomography (CT) has been the first cross-sectional imaging technique used to evaluate the larynx and hypopharynx; its spatial resolution combined with volumetric capability and the use of injectable contrast medium made CT the working horse in the assessment of neoplastic and inflammatory diseases. In the last two decades, magnetic resonance (MR) supported CT in the most challenging cases, when the optimal contrast resolution due to the multisequence portfolio is needed to assess the neoplastic involvement of laryngeal cartilages, paraglottic space(s), and extra laryngeal spread. The aim of this paper is to give a comprehensive radiological overview of larynx and hypopharynx complex anatomy, combining in vivo images, anatomical sections, and images of ex vivo specimens.

Occupational benzene exposure and risk of head and neck cancer: A systematic review and meta-analysis.

INTRODUCTION: Benzene, an aromatic hydrocarbon, is a well-known leukemogen. To date, the link between benzene exposure and solid cancers is under examination. Our objective is to perform a systematic review and meta-analysis to evaluate if the occupational exposure to benzene is associated with the incidence and mortality of head and neck cancers (HNCs). METHODS: We systematically reviewed the literature for pertinent cohort studies mentioned in the most recent IARC Monograph on benzene working exposure and other cohorts and case-controls identified via a literature search performed in PubMed, Scopus, and Embase, from their inception to March 2024. Stratified multilevel meta-analyses according to study design, cancer type, industrial sector, quality score of the articles, geographic region and risk of exposure bias were conducted. RESULTS: A total of 29 independent studies were included in our review and multilevel meta-analysis. The findings revealed a bordeline association between exposure to occupational benzene and incidence of HNCs RR = 1.27, 95% CI = 1.00-1.64, I2 level2 = 0%, I2level3 = 43.30%, P < 0.05). In addition, we found a significant increased overall risk of HNCs in females (RR = 1.68, 95% CI = 1.07-2.61; I2level2 = 0%, I2level3 = 0%, P = 0.433). Stratification analysis according to cancer sites showed a significant increase in risk of nose & sinuses cancers (RR = 3.72, 95% CI = 2.07-6.68; I2level2 = 34.13%, I2level3 = 0%, P = 0.17). European cohorts (RR = 1.31, 95% CI = 1.08-1.59, p < 0.01) and lower quality studies (RR = 1.39, 95% CI = 1.00-1.91; I2level2 = 0%, I2level3 = 45.94%, P < 0.001). No evidence of publication bias was found (Egger test P = 0.103). CONCLUSIONS: In conclusion, this systematic review and meta-analysis provide evidence that workers with occupational exposure to benzene might be at increased risk of HNCs, in particular for nose & sinuses cancer. However, it is essential to consider the limitations of the studies, particularly residual confounding, and the areas that need further study to improve our understanding of the subject.

Comparison of diffusion ranges at different local anesthetic volumes during superior laryngeal nerve block.

OBJECTIVES: Ultrasound-guided superior laryngeal nerve (SLN) block is a practical and painless approach to avoid the hemodynamic stress response during endotracheal intubation and relieve sore throat after laryngeal surgery. The main purpose of this study was to establish an optimal dosage of local anesthetic when performing SLN block to help anesthetists balance analgesia and side effects. METHODS: Twenty fresh larynx specimens were obtained immediately after resection and then injected with 2-, 3-, 4-, or 5- mL of a lidocaine-blue dye mixture at bilateral SLN puncture sites. Superficial areas of deposited blue dye were measured. Dye leakage and surrounding dyed tissue were recorded. Another 40 patients were included in the ultrasound investigation. Distances between the internal branch of the SLN (iSLN) and adjacent structures were calculated. RESULTS: The dye spread area was greater with the administration of larger doses, especially to the visceral space. A 2- or 3-mL injection of local anesthetic was sufficient to infiltrate the SLN gap. A higher incidence of dye leaking out of the thyrohyoid membrane and anterior epiglottis space was observed; furthermore, there was substantially more dyed hyoid/thyroid cartilage with 4 and 5 mL of injected dye mixture than 2 mL. There was no significant difference between the specimen and ultrasound measurements of for length of iSLN-adjacent structures. CONCLUSIONS: In the Chinese population, 2- or 3- mL of local anesthetic is a safe dose during SLN block. A larger volume could overflow from the cavity to cause complications. The thyrohyoid membrane combined with the superior laryngeal artery is a reliable target for positioning the iSLN during ultrasound-guided regional anesthesia.

Mechanisms of Swallowing, Speech and Voice Disorders in Parkinson's Disease: Literature Review with Our First Evidence for the Periperal Nervous System Involvement.

The majority of patients with Parkinson's disease (PD) develop swallowing, speech, and voice (SSV) disorders. Importantly, swallowing difficulty or dysphagia and related aspiration are life-threatening conditions for PD patients. Although PD treatments have significant therapeutic effects on limb motor function, their effects on SSV disorders are less impressive. A large gap in our knowledge is that the mechanisms of SSV disorders in PD are poorly understood. PD was long considered to be a central nervous system disorder caused by the death of dopaminergic neurons in the basal ganglia. Aggregates of phosphorylated α-synuclein (PAS) underlie PD pathology. SSV disorders were thought to be caused by the same dopaminergic problem as those causing impaired limb movement; however, there is little evidence to support this. The pharynx, larynx, and tongue play a critical role in performing upper airway (UA) motor tasks and their dysfunction results in disordered SSV. This review aims to provide an overview on the neuromuscular organization patterns, functions of the UA structures, clinical features of SSV disorders, and gaps in knowledge regarding the pathophysiology underlying SSV disorders in PD, and evidence supporting the hypothesis that SSV disorders in PD could be associated, at least in part, with PAS damage to the peripheral nervous system controlling the UA structures. Determining the presence and distribution of PAS lesions in the pharynx, larynx, and tongue will facilitate the identification of peripheral therapeutic targets and set a foundation for the development of new therapies to treat SSV disorders in PD.

Non-adherence to recommended adjuvant radiation after total laryngectomy.

OBJECTIVES: Investigate trends and associated factors in guideline adherence to adjuvant radiation therapy in locally advanced laryngeal and hypopharyngeal cancer after primary total laryngectomy (TL). METHODS: Previously untreated, non-metastatic patients who underwent TL for pathologic T4 larynx or hypopharynx squamous cell carcinoma (SCC) were queried using the National Cancer Database (NCDB). Patients were excluded if they had regional or distant metastasis or positive margins. Patient characteristics were evaluated for association with non-adherence to adjuvant radiation by logistic regression analysis. Association between non-adherence and overall survival (OS) was investigated by Cox proportional hazard analysis. RESULTS: Among 2823 eligible T4 N0 patients, 841 (29.8 %) did not receive adjuvant radiation. Associated factors include increasing age, a Charlson Comorbidity Index of 2, greater per-mile distance to treatment center, and treatment at an academic cancer center. Delivery of adjuvant radiation was associated with improved OS on multivariable (HR 0.82, 95 % CI 0.72-0.93) analysis. CONCLUSIONS: Within the NCDB, non-adherence to adjuvant radiation treatment after TL for pathologically T4 N0 larynx and hypopharynx SCC is common. Older patients with more comorbidities and greater travel distance may be at higher risk for non-adherence. Treatment at an academic cancer center is associated with non-adherence to recommended adjuvant radiation. Lack of adjuvant radiation is associated with worse overall survival.

Association of prealbumin with complications after total laryngectomy with free flap reconstruction.

OBJECTIVE: Malnutrition is an important risk factor for patient surgical outcomes. This is especially true for head and neck cancer (HNC) patients receiving a total laryngectomy with free flap reconstruction (TLwFFR). Preoperative prealbumin and albumin values have both been used to indicate poor nutrition. This study aims to identify the prognostic value of preoperative prealbumin and albumin levels with wound healing complications in HNC patients after TLwFFR. METHODS: A retrospective review was conducted in all HNC patients who underwent TLwFFR from 2016 to 2022 at a tertiary-care institution. Patients with either preoperative (within 1 month of surgery) prealbumin or albumin lab values were included. Low preoperative prealbumin (low prealbumin) levels and low preoperative albumin (low albumin) levels were defined as ≤20 mg/dL and <3.4 g/dL, respectively. Outcomes collected included all wound healing complications (infection, wound dehiscence, pharyngocutaneous fistula). The association between prealbumin and albumin with outcomes were analyzed using multivariable logistic regression. RESULTS: A total of 83 patients met the inclusion criteria. The mean age at surgery was 61.6 ± 9.3. The overall wound healing complication rate was 33.7 %. There was an association between low prealbumin levels and any wound healing complication. On multivariate analysis, low prealbumin levels were associated with postoperative wound healing complications (OR, 4.7; CI 1.3-17.0. P = 0.02) after controlling for low albumin level, age, smoking, and preoperative radiation. CONCLUSIONS: Low prealbumin levels were associated with wound healing complications in TLwFFR patients. Consideration of consistent prealbumin testing with nutritional intervention may reduce wound healing complications.

Features related to temporary tracheotomy in patients undergoing Transoral Robotic Surgery (TORS) for supraglottic squamous cell cancer of the larynx: A systematic review.

OBJECTIVE: The aim of this systematic review is to assess a relation between demographical, clinical and tumoral features and the need for a prophylactic tracheotomy during TORS procedure in patients affected by supraglottic laryngeal cancer. METHODS: PRISMA 2020 guidelines were applied in this systematic literature review. A computerized search was performed using the Embase/Pubmed, Scopus and Cochrane database, for articles published from 2007 to December 2023. A statistical univariate analysis including selected papers with low or intermediate risk of bias was performed. RESULTS: Through a study selection process 8 full texts were eligible for statistical univariate analysis. The most relevant factor related to a prophylactic tracheotomy was a contextual bilateral cervical nodes dissection, which increased the need for a tracheotomy of about 3 times. Other factors contribute with a minor impact, such as a patients age >60 years at the time of the diagnosis, a cervical lymph node metastasis and a false vocal fold involvement. Each ones increase by 20-70 % the need for a tracheotomy. However, this rate is decreased by about 60 % by the epiglottis involvement. CONCLUSIONS: The prophylactic tracheotomy is considered a temporary protection strategy to achieve a valid recovery after TORS procedure. However, there are no guidelines regarding its routinely use. Only 25 % of patients undergone tracheotomy during TORS to treat supraglottic laryngeal cancer. These preliminary results may add more significant evidence regarding the use of tracheotomy during the TORS procedure, in order possibly to help the surgeon decide preoperatively whether to perform it or not.