Benign Laryngeal Diseases Research Articles

Identification and analysis of Nonlinear behaviors of vocal fold biomechanics during phonation to assess efficacy of surgery for benign laryngeal Diseases

BackgroundCurrent voice assessments focus on perceptive evaluation and acoustic analysis. The interaction of vocal tract pressure (PVT) and vocal fold (VF) vibrations are important for volume and pitch control. However, there are currently little non-invasive ways to measure PVT. Limited information has been provided by previous human trials, and interactions between PVT and VF vibrations and the potential clinical application remain unclear. Here, we propose a non-invasive method for monitoring the nonlinear characteristics of PVT and VF vibrations, analyze voices from pathological and healthy individuals, and evaluate treatment efficacy. MethodHealthy volunteers and patients with benign laryngeal lesions were recruited for this study. PVT was estimated using an airflow interruption method, VF vibrational frequency was calculated from accelerometer signals, and nonlinear relationships between PVT and VF vibrations were analyzed. Results from healthy volunteers and patients, as well as pre- and post-operation for the patients, were compared. ResultsFor healthy volunteers, nonlinearity was exhibited as an initial increase and then prompt decrease in vibrational frequency at the end of phonation, coinciding with PVT equilibrating with the subglottal pressure upon airflow interruption. For patients, nonlinearity was present throughout the phonation period pre-operatively, but showed a similar trend to healthy volunteers post-operatively. ConclusionThis novel method simultaneously monitors PVT and VF vibration and helps clarify the role of PVT. The results demonstrate differences in nonlinear characteristics between healthy volunteers and patients, and pre-/post-operation in patients. The method may serve as an analysis tool for clinicians to assess pathological phonation and treatment efficacy.

The prognostic role of coagulation markers in the progression and metastasis of laryngeal squamous cell carcinoma

BackgroundThe application of coagulation-related markers in laryngeal squamous cell carcinoma(LSCC) remains unclear. This study explored the prognostic role of coagulation markers in the progression and metastasis of LSCC.MethodsCoagulation markers of patients with LSCC receiving surgery in the Second Affiliated Hospital of Fujian Medical University in China, from January 2013 to May 2022 were retrospectively analyzed and compared with those of contemporary patients with benign laryngeal diseases. The relationship between clinicopathological features of LSCC and coagulation markers was analyzed with the chi-square and rank sum tests. The ROC curve analysis was utilized to evaluate the diagnostic efficacy of seven coagulation markers for LSCC and its different clinicopathological features, and to find the optimal cutoff value of each coagulation marker.Results303 patients with LSCC and 533 patients with benign laryngeal diseases were included in the present analysis. Compared to the control group, prothrombin time (PT) (p < 0.001), activated partial thromboplastin time (APTT) (p = 0.001), and Fib (p < 0.001) in patients with LSCC were significantly higher, while mean platelet volume (MPV) (p < 0.001) was significantly shorter. Significant increases were detected in PT (Z = 14.342, p = 0.002), Fib (Z = 25.985, p < 0.001), platelet count (PC) (Z = 12.768, p = 0.005), PCT (Z = 9.178, p = 0.027), MPV (F = 2.948, p = 0.033) in T4 stage. Fib had the highest prognostic value among the seven coagulation markers in different T stages (AUC = 0.676, p < 0.001), N stages (AUC = 0.717, p < 0.001), tumor stage (AUC = 0.665, p < 0.001), differentiation degree (AUC = 0.579, p = 0.022), and neurovascular invasion (AUC = 0.651, p = 0.007). Fib (Z = 25.832, p < 0.001), PC (Z = 23.842, p < 0.001), and PCT (Z = 20.15, p < 0.001) in N1 and N3 stages were significantly higher than in N0 stage. PT (Z = 12.174, p = 0.007), Fib (Z = 23.873, p < 0.001), PC (Z = 17.785, p < 0.001), and PCT (Z = 14.693, p = 0.002) were significantly higher in stage IV than in stage I and II. APTT (Z=-1.983, p = 0.047), Fib (Z=-2.68, p = 0.007), PC (Z=-2.723, p = 0.006), and PCT (Z=-2.592, p = 0.01) increased significantly when the tumor invaded neurovascular tissue.ConclusionsCoagulation markers have the potential to act as biomarkers for predicting pathological features of LSCC. The high level of Fib was helpful for the diagnosis of LSCC and the detection of advanced LSCC.Trial registrationNot applicable.

Effects of surgery on the relationship between subglottic pressure and fundamental frequency in vocal fold dynamics in patients with benign laryngeal diseases.

Subglottic pressure (Ps) and fundamental frequency (F0) play important roles in governing vocal fold (VF) dynamics. Theoretical description, model simulation, excised larynx and animal models have been used in previous studies, yet clinically applicable measurements are still lacking. This study aimed to evaluate the effects of surgery for benign laryngeal lesions by investigating the relationship between F0 and Ps. Patients with benign laryngeal lesions who underwent phonosurgery were prospectively recruited. Participants were instructed to sustain voicing the vowel /o/ at three incremental frequencies four semitones apart in the modal register (F01, F02, F03). F0 was estimated by VF vibration on the accelerometer. Ps change was achieved and measured using the airflow interruption method. Thirteen patients with a mean age (SD) of 43.5 (12.4) years were included. The change in F0 per unit change of Ps, which is the slope (Hz/kPa) of the regression line of the frequency-pressure data pairs, decreased as the tension of the VF increased. The slopes significantly increased after the operation for F01 and F02 (36.43 ± 14.68 preoperatively, 53.91 ± 30.71 postoperatively, p = 0.011 and 26.02 ± 10.71; 34.85 ± 17.92, p = 0.046, respectively). In addition, there was a significant decrease in phonation threshold pressure and improvements in the grade, roughness, breathiness, asthenia, strain scale, and the voice handicap inventory-10. The relationship between F0 and Ps may serve as an objective assessment of the outcomes in the treatment of benign laryngeal diseases with clinical relevance.

Characteristics of CO2 laser in benign laryngeal diseases

Laserele reprezintă o achiziţie relativ recentă în chirurgia la­­rin­­ge­lui. Utilizarea laserului CO2 a cunoscut o extindere ra­pi­dă în ceea ce priveşte abordarea unei largi varietăţi a pa­to­lo­giei laringiene, atât benigne, cât şi maligne, chirurgia en­do­sco­pi­că transorală cu ajutorul laserului sub microscopul ope­ra­tor devenind indicaţia de elecţie pentru multe dintre aces­te afec­ţiuni ale planului glotic. Lucrarea prezintă o serie de cazuri cli­ni­ce relevante şi situaţii particulare întâlnite care sus­ţin uti­li­ta­tea acestei tehnologii chirurgicale în rezolvarea cu suc­ces a celor mai frecvente leziuni benigne laringiene. Sunt evo­ca­te, co­men­tate şi subliniate cele mai importante aspecte pri­vind mo­da­li­tă­ţile de abord alese, detaliile chirurgicale şi par­ti­cu­la­ri­tă­ţile fie­cărui caz în parte, problemele întâmpinate, beneficiile şi de­za­van­tajele folosirii laserului CO2 în aceste tipuri de afec­ţiuni, so­lu­ţiile utilizate pentru eficientizarea rezultatelor pe ter­men lung şi îmbunătăţirea calităţii vieţii pacienţilor.

Clinical Applications of Office-Based Laryngeal Surgery With KTP Laser

The pulsed photoangiolytic 532-nm potassium-titanyl-phosphate (KTP) laser has emerged in recent years as an efficacious treatment modality for vocal fold lesions. It also has broadened the indications for other laryngeal laser surgery. Features of KTP laser that it is a fiber-based delivery system and its energy is selectively absorbed by oxyhemoglobin make it suitable for office-based laryngeal procedures. An office-based KTP laser surgery provides an alternative management option for benign laryngeal diseases and can be performed comfortably under flexible endoscopic guidance which is placed through the nose of a fully awake patient. Office-based laryngeal surgery with a KTP laser can alleviate the need for general anesthesia. However, there are some limitations to apply due to reduced visual precision and the fact that the vocal folds are moving during procedures. Clinicians should carefully weigh the advantages and disadvantages of office-based procedures before a treatment option is selected. Patient selection and standardized laser energy parameters may help in decreasing complications and improving the treatment results.

Mainstream Cigarette Smoke Impacts the Mouse Vocal Fold Epithelium and Mucus Barrier.

Cigarette smoke (CS) is a primary risk factor for the development of numerous benign and malignant laryngeal diseases. The epithelium and mucus lining the vocal folds (VF) are the first barriers against CS. The primary objective of this study was to investigate epithelial and mucus barrier changes in the mouse laryngeal mucosa upon exposure to subacute CS. The secondary objective was to compare mucus barrier changes in mice and human smokers and nonsmokers. Study Design Animal model. Mice were exposed to CS for 4 weeks for 4 hours (N=12, high dose [HD]) or 1 hour (N=12, low dose [LD]) per day. Air-exposed mice were used as a control group (N=10). Larynges were harvested and VF epithelial barrier integrity was evaluated including cellular proliferation and expression of cell junctions. We also investigated mucus production by examining mucus cell area and mucin expression in mice and human smokers and nonsmokers. HD CS increased VF epithelial cellular proliferation but did not alter the expression of cell junctions. HD CS also induced hypertrophy of the mucus-producing submucosal glands. However, only LD CS increased MUC5AC gene expression. MUC5AC staining appeared elevated in laryngeal specimens from smokers, but this was not significant as compared to nonsmokers. These findings help us identify potential adaptive mechanisms to CS exposure as well as set the foundation for further study of key aspects of epithelial and mucus barrier integrity that may be implicated in laryngeal disease development following prolonged smoking. NA Laryngoscope, 131:2530-2539, 2021.

Yaşlılarda Laringeal Skuamoz Hücreli Karsinomla Benign ve Premalign Laringeal Hastalıkların Ayrımında Nötrofil: Lenfosit Oranı, Trombosit: Lenfosit Oranı ve Sistemik İmmün-İnflamasyon İndeksi Değerlerini Kullanabilir miyiz?

Yaşlılarda Laringeal Skuamoz Hücreli Karsinomla Benign ve Premalign Laringeal Hastalıkların Ayrımında Nötrofil: Lenfosit Oranı, Trombosit: Lenfosit Oranı ve Sistemik İmmün-İnflamasyon İndeksi Değerlerini Kullanabilir miyiz?

Short-term whole body cigarette smoke exposure induces regional differences in cellular response in the mouse larynx.

The larynx is an essential organ in the respiratory tract and necessary for airway protection, respiration, and phonation. Cigarette smoking is a significant risk factor associated with benign and malignant laryngeal diseases. Despite this association, the underlying mechanisms by which cigarette smoke (CS) drives disease development are not well elucidated. In the current study, we developed a short-term murine whole body inhalation model to evaluate the first CS-induced cellular responses in the glottic [i.e. vocal fold (VF)] and subglottic regions of the larynx. Specifically, we investigated epithelial cell proliferation, cell death, surface topography, and mucus production, at various time points (1 day, 5 days, 10 days) after ∼ 2 h exposure to 3R4F cigarettes (Delivered dose: 5.6968 mg/kg per cigarette) and following cessation for 5 days after a 5 day CS exposure (CSE). CSE elevated levels of BrdU labeled proliferative cells and p63 labeled epithelial basal cells on day 1 in the VF. CSE increased proliferative cells in the subglottis at days 5, 10 and following cessation in the subglottis. Cleaved caspase-3 apoptotic activity was absent in VF at all time points and increased at day 1 in the subglottis. Evaluation of the VF surface by scanning electron microscopy (SEM) revealed significant epithelial microprojection damage at day 10 and early signs of necrosis at days 5 and 10 post-CSE. SEM visualizations additionally indicated the presence of deformed cilia at days 5 and 10 after CSE and post-cessation in the respiratory epithelium lined subglottis. In terms of mucin content, the impact of short-term CSE was observed only at day 10, with decreasing acidic mucin levels and increasing neutral mucin levels. Overall, these findings reveal regional differences in murine laryngeal cellular responses following short-term CSE and provide insight into potential mechanisms underlying CS-induced laryngeal disease development.

Original Research: Aerosolized Lidocaine: Effective for Safer Arousal After Suspension Laryngoscopy

To examine the systemic and local effects of the lidocaine on the larynx and trachea which is applied after the end of the surgery and through various application methods. Randomized controlled prospective study. The study is composed of patients who underwent suspension laryngoscopy (SL) for benign laryngeal diseases (cysts, polyp, granuloma, etc) and American Society of Anesthesiologists (ASA) I, between January 2017 and January 2018. The patients were randomly divided into 3 groups. In the first group nothing is applied at the end of the surgery and called as control group, second group received 7 pufs of aerosolized 10% lidocaine solution (70 mg) over larynx and trachea and third group received cotton swaps that impregnated in 1 ml of 20 mg lidocaine solution over surgical area for 1 minutes. Operation and arousal times, heart rate and mean arterial blood pressure levels were noted and compared. Also laryngospasm, cough, and agitation scores were obtained during arousal. 64 patients were included in the study. Laryngospasm was not observed in any of the patients. In group 2 (aerosolized lidocaine group), patients' blood pressure remained similar while increased in other groups (P < 0.05). Agitation scores were significantly lower in group 2 compared to the other groups (P = 0.012). Cough reflex is observed less in group 2 but result was not statistically significant (P = 0.13) CONCLUSION: The usage of aerosolized lidocaine after suspension laryngoscopy is very effective in blocking the stimulation of superior laryngeal nerve and sympathetic nerves which were responsible for the pressor reflexes. The inhibition of these reflexes before or during arousal could secure a safer arousal.

A link between RelB expression and tumor progression in laryngeal cancer.

Laryngeal cancer is a frequent malignancy originating from the squamous vocal epithelium in a multi-stage fashion in response to environmental carcinogens. Although most cases can be cured by surgery and/or radiotherapy, advanced and relapsing disease is common, and biomarkers of such dismal cases are urgently needed. The cancer genome of laryngeal cancers was recently shown to feature a signature of aberrant nuclear factor (NF)-κB activation, but this finding has not been clinically exploited. We analyzed primary tumor samples of 96 well-documented and longitudinally followed patients covering the whole spectrum of laryngeal neoplasia, including 21 patients with benign laryngeal diseases, 15 patients with dysplasia, 43 patients with early-stage carcinoma, and 17 patients with locally advanced carcinoma, for immunoreactivity of RelA, RelB, P50, and P52/P100, the main NF-κB subunits that activate transcription. Results were cross-examined with indices of tumor progression and survival. Interestingly, RelB expression increased with tumor stage, grade, and local extent. Moreover, patients displaying high RelB immunoreactivity exhibited statistically significantly poorer survival compared with patients featuring low levels of RelB expression (P = 0.018 by log-rank test). Using Cox regression analyses and tumor stage, local extent, grade and RelA/RelB immunoreactivity, we develop a new score that can independently predict survival of patients with laryngeal cancer. Hence we provide a simple and affordable NF-κB-based test to predict prognosis in laryngeal cancer.

Helicobacter pylori infection in laryngeal diseases

Clinical studies have shown that Helicobacter pylori can be found not only in the mucosa of the stomach, but in the pharyngeal and laryngeal regions as well. The aim of this prospective case-control study was to identify H. pylori infection in the biopsy material from the larynx of the patients suffering from benign laryngeal diseases (vocal fold polyps, laryngitis) and laryngeal cancer and to investigate the possible relationships between the laryngeal H. pylori and patients' socio-demographic data and laryngopharyngeal reflux. The results of the biopsy material from 67 adult patients treated for benign laryngeal diseases and laryngeal cancer and 11 individuals of the control group revealed that H. pylori infection could be identified in more than one-third of the patients. In the majority of cases H. pylori was found in the patients with chronic laryngitis (45.5%) and laryngeal cancer (46.2%). The findings of these sub-groups significantly differed from those of the control group (9.1%) (p < 0.05). No significant relationships between H. pylori infection found in the laryngeal region and patients' demographic data, their unhealthy habits and reflux-related symptoms or signs were obtained. It could be concluded that H. pylori can colonize in the larynx of patients with benign laryngeal diseases and laryngeal cancer. To clarify the role of H. pylori as a risk factor for laryngeal diseases further research is needed.

Multidetector computed tomography in nonmalignant laryngeal disease

Multidetector computed tomography (MDCT) is the examination of choice for laryngeal imaging in benign and malignant lesions. This review gives an overview of the MDCT scanning technique and discusses the advantages and disadvantages in investigation of benign lesions of the larynx. MDCT is not the primary diagnostic method for benign lesions on the vocal folds. However, CT is indispensable for the diagnostic investigation of immobility of the vocal fold, for laryngoceles, and for laryngeal trauma, and may allow the exact delineation of extension and nature of benign laryngeal disease. The improved spatial resolution with consecutive high-quality two-dimensional (2D) and three-dimensional (3D) reconstructions using thin-slice MDCT allows a better detection of laryngeal anatomic structures and benign pathologies. The investigation of choice in diagnosing the cause of hoarseness is laryngoscopy and/or laryngostroboscopy, respectively. Nevertheless, thin-slice MDCT with multiplanar 2D and 3D volume-rendered reconstructions is essential for exact anatomic definition and extension and diagnosis of subtle benign laryngeal diseases.

Detection of Helicobacter pylori and cagA Gene in Nasal Polyps and Benign Laryngeal Diseases

Helicobacter pylori is the most common etiological factor of chronic infection worldwide. It has also been found in human dental plaques, mouth, saliva, tonsils and adenoid tissue, medial ear or nasal polyps and sinuses mucosa, as well in several benign and malignant lesions of the larynx and pharynx. The aim of the study was to investigate the association of H. pylori colonization in chronic rhinosinusitis and benign laryngeal diseases. The prospective, controlled study involved a series of 30 patients with nasal polyps and normal nasal mucosa and 30 patients with benign laryngeal diseases. Samples of 10-15 mg obtained from fresh tissues were used for nucleic acid purification. All samples were subjected to H. pylori ureA detection by the PCR H. pylori diagnostic test. Samples that were positive for ureA H. pylori gene were evaluated for cagA H. pylori gene. H. pylori DNA (ureA gene) was detected in all patients with nasal polyps, concha bullosa and laryngeal diseases. Presence of H. pylori cagA gene was identified in 7 (23.3%) of 30 patients of H. pylori-positive larynx samples and no positive result was observed in nasal polyps and concha bullosa. Our results reveal the presence of H. pylori DNA in nasal polyps, concha bullosa and benign larynx diseases. cagA-positive H. pylori was observed only in laryngeal tissues. These results may have implications for a possible role of H. pylori in laryngeal diseases.

喉頭癌発症におけるヒト乳頭腫ウイルス（ＨＰＶ）の発現と喉頭局所免疫の関与

The aim of this study is to clarify the local immune status in the larynx affected by infection or carcinogenesis associated with HPV. Cytological samples for the detection of HPV and laryngeal secretions for the collection of immunoglobulin (Ig) were obtained from 31 patients with laryngeal diseases during microscopic surgery of the larynx. Histological results were as follows: 12 patients with squamous cell carcinomas, 4 with laryngeal papillomas and 15 with other benign laryngeal diseases. HPV-DNA testing from cytological samples was performed with the Hybrid Capture 2 assay method. High risk HPV-DNA was detected in 25% (3⁄12 cases) of laryngeal cancers. Low risk type was detected in three laryngeal papillomas only. The mean IgM, IgG, IgA and secretory IgA concentrations in HPV-DNA positive cases were more than double compared to respective concentrations in HPV-DNA negative cases. In particular, a significant difference was observed between the concentrations of secretory IgA of the two groups. A comparison of laryngeal cancer and benign laryngeal diseases revealed that patients with laryngeal cancer had a higher concentration in each Ig isotype in laryngeal secretions than patients with benign laryngeal diseases. When the mean concentrations of each antibody isotype in the 12 cases with laryngeal cancer were compared between HPV-DNA positive (3 patients) and HPV-DNA negative (9 patients), the mean IgM, IgG, IgA, secretory IgA concentrations in HPV-DNA positive cancer showed a tendency to be higher than those in HPV-DNA negative cancer. Our results suggest that the local immune response in the larynx is activated by infection or carcinogenesis caused by HPV. It is strongly considered that secretory IgA activity inhibits infection or proliferation of HPV in the larynx.

頭頸部癌患者の機能評価

During the last three decades, we have experienced a dramatic paradigm shift in the treatment of head and neck cancers. Instead of wide resection, concomitant chemoradiotherapy or conservative surgery are increasingly applied with radical intent in the treatment of advanced cancers for the purpose of organ preservation. Indeed, now, larynx and/or pharynx are preserved in much more cases than before with satisfactory oncological results. However, it is still questionable whether preserved organs functionate as expected. In this article, we introduce tools for evaluating the functional results of the patients with head and neck cancers. The University of Washington Head and Neck Measure and Medical Outcomes Short Form 36 are representative questionnaire to measure the general status of the patients with head and neck cancer. Voice Handicap Index-10 and Voice-Related Quality of Life are originally developed for benign laryngeal diseases, but also useful for laryngeal cancers. Blowing test, which has been used to evaluate the velopharyngeal function of the patients with cleft palate, is proved to be useful for patients with oral and oropharyngeal cancers. To evaluate the quality of life after neck dissection, the Japanese Clinical Study Group on Standardization of Treatment for Lymph Node Metastasis of Head and Neck Cancer has developed a self-administered neck dissection questionnaire (NDQ) and Arm Abduction Test (AAT).

양성후두질환에서 후두미세수술 전후 음성의 비교분석

Background and Objective: In benign laryngeal diseases, voice quality is major concern to both patients and clinicians. The purpose of this study is to identify the acoustic parameters that can represent preoperative pathologic and postoperative improved voice and to investigate quantitative changes of them. Using these data, We intend to disclose the mechanisms of voice change and apply to programs that can predict postoperative voice using preoperative voice data. Material and Methods: We examined 47 patients who experienced laryngeal microsurgery due to pathologic voice with benign laryngeal diseases and 50 normal controls. The voice was analysed by Multi-Dimensional Voice Program in Computerized Speech Lab 4300 B. Results: All preoperative parameter’s values except NHR and VTI were higher than control group. Among them, the values of frequency and amplitude perturbation related parameters increased most highly. Most parameter

Cytologic diagnosis of laryngeal diseases

The cytology of laryngeal diseases including 25 cases of laryngeal carcinoma, 15 cases of vocal cord polyp, 8 cases of chronic laryngitis and 2 cases of laryngeal leukoplakia were studied.The results were as follows;1. The over all correct diagnostic rate in this series of patients was 77.6%.2. The accuracy of cytological diagnosis in laryngeal carcinomas was 76.0% and the false negative rate was 24.0%.3. All benign laryngeal diseases were proved cytologically benign and the false positive was none.4. The laryngeal cytology under direct laryngoscopy were superior to the cytology under indirect laryngoscopy.5. The false negative diagnosis were derived by the paucity of malignant cells and epithelial cells in the specimen.6. The exfolliative cytology was proved to be a usefll method for the diagnosis of laryngeal diseases.7. The accuracy of laryngeal cytology should be improved with the use of direct laryngoscopy, especially with fiberlaryngoscopy.