Outcomes of laryngeal framework surgeries for unilateral vocal cord paralysis in the elderly patients.

OBJECTIVE: Laryngeal framework surgery is a widely accepted treatment for unilateral vocal fold paralysis with good functional outcomes. Recently, with the aging of the population, opportunities to perform this procedure in elderly patients have increased; however, the safety and efficacy of this procedure in elderly patients has not been established. Therefore, this study aimed to investigate the safety and functional outcomes of laryngeal framework surgery in elderly patients. METHODS: Between January 2008 and December 2017, 97 patients with unilateral vocal fold paralysis underwent laryngeal framework surgery, and 71 among them completed pre- and post-operative voice function evaluations. The clinical course of these 71 patients were retrospectively reviewed. RESULTS: Out of 71 patients, 35 were assigned to the younger group (< 65 years) and 36 to the elderly group (≥ 65 years). Complications included post-operative edema and submucosal hematoma that were safely managed in all cases, and no differences were identified between the groups. Significant improvements were observed in maximum phonation time (MPT), mean flow rate, alternating current/direct current ratio, pitch perturbation quotient, amplitude perturbation quotient, and noise-to-harmonic ratio in both groups, and multivariate analysis of variance revealed greater improvement in the younger group in MPT. CONCLUSION: Laryngeal framework surgeries for unilateral vocal fold paralysis are safe and effective, regardless of age. Better improvement was observed in the younger group in the MPT suggesting that the effects of laryngeal framework surgeries is more likely to be present in the younger group than in the elderly.

Complications including dysphagia following transoral non-robotic surgery for pharyngeal and laryngeal squamous cell carcinoma: A retrospective multicenter study.

OBJECTIVE: Transoral surgery is a minimally invasive treatment but may cause severe dysphagia at a lower rate than chemoradiotherapy. METHODS: We compared clinical information, surgical complications, and swallowing function in patients who underwent transoral nonrobotic surgery for laryngo-pharyngeal squamous cell carcinoma between 2015 and 2021 in a multicenter retrospective study. RESULTS: Six hundred and forty patients were included. Postoperative bleeding was observed in 20 cases (3.1%), and the risk factor was advanced T category. Postoperative laryngeal edema was observed in 13 cases (2.0%), and the risk factors were prior radiotherapy, advanced T stage, and concurrent neck dissection in patients with resected HPC. Dysphagia requiring nutritional support was observed in 29 cases (4.5%) at 1 month postoperatively and in 19 cases (3.0%) at 1 year postoperatively, respectively. The risk factors for long-term dysphagia were prior radiotherapy and advanced T category. Short-term risk factors for dysphagia were prior radiotherapy, advanced T category, and concurrent neck dissection, while long-term risk factors for dysphagia were only prior radiotherapy and advanced T category. CONCLUSION: Prior radiotherapy, advanced T stage, and concurrent neck dissection increased the incidence of postoperative laryngeal edema and short-term dysphagia, but concurrent neck dissection did not affect long-term dysphagia. Such features should be considered when considering the indication for transoral surgery and postoperative management.

Novel evaluation method for facial nerve palsy using 3D facial recognition system in iPhone.

OBJECTIVE: While subjective methods like the Yanagihara system and the House-Brackmann system are standard in evaluating facial paralysis, they are limited by intra- and inter-observer variability. Meanwhile, quantitative objective methods such as electroneurography and electromyography are time-consuming. Our aim was to introduce a swift, objective, and quantitative method for evaluating facial movements. METHODS: We developed an application software (app) that utilizes the facial recognition functionality of the iPhone (Apple Inc., Cupertino, USA) for facial movement evaluation. This app leverages the phone's front camera, infrared radiation, and infrared camera to provide detailed three-dimensional facial topology. It quantitatively compares left and right facial movements by region and displays the movement ratio of the affected side to the opposite side. Evaluations using the app were conducted on both normal and facial palsy subjects and were compared with conventional methods. RESULTS: Our app provided an intuitive user experience, completing evaluations in under a minute, and thus proving practical for regular use. Its evaluation scores correlated highly with the Yanagihara system, the House-Brackmann system, and electromyography. Furthermore, the app outperformed conventional methods in assessing detailed facial movements. CONCLUSION: Our novel iPhone app offers a valuable tool for the comprehensive and efficient evaluation of facial palsy.

The Effect of Noise on Deep Learning for Classification of Pathological Voice.

OBJECTIVE: This study aimed to evaluate the significance of background noise in machine learning models assessing the GRBAS scale for voice disorders. METHODS: A dataset of 1406 voice samples was collected from retrospective data, and a 5-layer 1D convolutional neural network (CNN) model was constructed using TensorFlow. The dataset was divided into training, validation, and test data. Gaussian noise was added to test samples at various intensities to assess the model's noise resilience. The model's performance was evaluated using accuracy, F1 score, and quadratic weighted Cohen's kappa score. RESULTS: The model's performance on the GRBAS scale generally declined with increasing noise intensities. For the G scale, accuracy dropped from 70.9% (original) to 8.5% (at the highest noise), F1 score from 69.2% to 1.3%, and Cohen's kappa from 0.679 to 0.0. Similar declines were observed for the remaining RBAS components. CONCLUSION: The model's performance was affected by background noise, with substantial decreases in evaluation metrics as noise levels intensified. Future research should explore noise-tolerant techniques, such as data augmentation, to improve the model's noise resilience in real-world settings. LEVEL OF EVIDENCE: This study evaluates a machine learning model using a single dataset without comparative controls. Given its non-comparative design and specific focus, it aligns with Level 4 evidence (Case-series) under the 2011 OCEBM guidelines Laryngoscope, 2024.

Impact of cervical lymph node metastasis on transoral surgery for hypopharyngeal squamous cell carcinoma: A retrospective multicenter study.

BACKGROUND: Hypopharyngeal carcinoma is likely to spread to the lymph nodes, but there is no established strategy for management in transoral surgery. METHODS: We compared oncologic and functional outcomes in a retrospective multicenter study of patients who underwent transoral surgery for hypopharyngeal carcinoma between 2015 and 2021. RESULTS: Two-hundred and thirty-two patients were included. Comparing patients with and without adjuvant radiotherapy, 3-year regional recurrence-free survival (RRFS) was not significantly different in pN2b and pN2c, but was significantly worse in pN3b without adjuvant radiotherapy. In patients without neck dissection, the 3-year RRFS was 85.6%, 76.8%, and 70.0% for T1, T2, and T3 primary lesions, respectively, and was significantly worse for T2 or higher (p = 0.035). CONCLUSIONS: In the absence of extracapsular invasion, regional control did not deteriorate without adjuvant therapy. If prophylactic neck dissection is not performed, careful follow-up is necessary if the primary lesion is T2 or greater.

Local recurrence and metachronous multiple cancers after transoral nonrobotic surgery for pharyngeal and laryngeal squamous cell carcinoma: A retrospective multicenter study.

BACKGROUND: Late laryngopharyngeal cancers after transoral surgery include not only local recurrences but also metachronous multiple cancers. METHODS: We compared clinical information, surgical outcomes, and late laryngopharyngeal cancers in patients who underwent transoral nonrobotic surgery for laryngopharyngeal squamous cell carcinoma without lymph node metastases between 2015 and 2021 in a multicenter retrospective study. RESULTS: Four hundred and fifty-seven patients were included. Positive surgical margins were found in 121 patients (26.5%). Twenty-two patients (4.8%) received additional treatment. Positive horizontal margins of invasive carcinoma (p = 0.003) and positive horizontal margins of carcinoma in situ only (p = 0.032) were independent risk factors for local recurrence, and prior radiotherapy (p = 0.001) for metachronous multiple cancers. Local control was significantly worse without additional treatment (p = 0.049), but there was no significant difference in survival. CONCLUSIONS: Patients with positive margins had an increased frequency of local recurrence, but salvage therapy was effective.

A prospective evaluation of postoperative swallowing function and dysphagia following endoscopic laryngopharyngeal surgery.

BACKGROUND: Endoscopic laryngopharyngeal surgery (ELPS) is a minimally invasive transoral surgery for superficial pharyngeal and laryngeal cancer, but dysphagia occasionally occurs post-treatment. We investigated dysphagia following ELPS and its risk factors. METHODS: Of the 145 patients who underwent ELPS, 92 were evaluated in this study using the Hyodo score, Functional Outcome Swallowing Scale, Eating Assessment Tool-10 along with the total scores for the three items of the method of intake, time, and food preoperatively and on postoperative 1, 3, and 6 months. We examined the 6-month trends of these values. Furthermore, the fasting period post-surgery, the need for swallowing rehabilitation by a speech therapist, and postoperative pneumonia episodes were set as outcomes reflecting the short-term swallowing function. We determined the associations between these outcomes and patient background factors. RESULTS: Postoperatively, the Hyodo score worsened at 1 month but recovered at 3 months. The Hyodo scores of all patients who underwent postcricoid ELPS did not worsen. The diameter of the resected specimen (DRS) was significantly associated with the need for swallowing rehabilitation and postoperative fasting time. A DRS ≥ 35 mm was considered the threshold for the need of swallowing rehabilitation, postoperative pneumonia, and prolonged postoperative fasting time. CONCLUSION: ELPS exerts a temporal and limited impact on the swallowing function, which recovers within 3 months in every swallowing evaluation. This necessitates additional care during the treatment of patients with mucosal defects ≥ 35 mm, owing to the significant association between the DRS and short-term swallowing function.

Intraoperative computed tomography imaging for laryngoplasty.

OBJECTIVES: Intraoperative cone beam computed tomography (CBCT) imaging has the potential to facilitate the surgical procedure. The current preliminary retrospective chart review investigated the benefits of intraoperative CBCT during laryngoplasty. METHOD: This study examined 26 cases that underwent intraoperative CBCT imaging during laryngoplasty, with one patient who counted twice due to first and revision surgery. The visual quality of structures of interest (glottal shape, thyroid cartilage, arytenoid cartilage, and implants) was determined using intraoperative CBCT during laryngoplasty. Each patient also underwent an aerodynamic assessment. RESULTS: CBCT provided unique information, such as surgical landmarks in severe scarring, the subglottal shape, and the rotation angle of the arytenoid cartilage during arytenoid adduction. Nonetheless, 26.9% (7 of 26) of cases were affected by motion artifact, due to the long acquisition time. When motion artifact-negative cases were evaluated, 100% of glottal shape and more than 89% of thyroid cartilage were well visualized. All arytenoids were well-visualized in patients ≥ 50 years of age and without motion artifact, while CBCT failed to visualize the arytenoids in 2 of 4 patients who were < 50 years, due to the lack of calcifications. After medialization surgery, the yields of improved maximal phonation times (MPTs) in the motion artifact-negative and -positive groups were 8.7 sec and 3.4 sec, respectively (p = 0.032; Welch's t test). This comparison indicates intraoperative CBCT would contribute in MPT improvement, if CBCT is taken in measurable quality. CONCLUSION: The potential benefits of intraoperative CBCT during laryngoplasty were demonstrated. A corollary, prospective study is warranted to further confirmation.

A case of long-term survival treated with three metastasectomies and two subsequent adjuvant nivolumab therapies for recurrent malignant melanoma of the esophagus.

BACKGROUND: The treatment strategy for metastatic lesions of primary malignant melanoma of the esophagus (PMME) is currently determined on a case-by-case basis, based on the National Comprehensive Cancer Network (NCCN) guidelines for cutaneous melanoma. The NCCN guidelines state that resection should be considered in patients with resectable metastatic recurrence. Herein, we report a case of long-term survival treated with three metastasectomies and two subsequent adjuvant nivolumab therapies for the metastatic recurrence of PMME. CASE PRESENTATION: A 65-year-old female patient with PMME underwent thoracoscopic subtotal esophagectomy, gastric tube reconstruction via the posterior mediastinal route, and cervical esophagogastric anastomosis. Histopathological examination of the resected specimen revealed that the tumor was PMME with tumor invasion into the muscularis propria and no lymph node metastasis. At the age of 68 years, she developed intestinal invagination due to jejunal metastasis of malignant melanoma and underwent resection of the jejunum. Histopathological examination of the resected specimen revealed two metastases of malignant melanoma in the jejunum and one metastasis to the mesenteric lymph node. At the age of 75 years, a recurrence of malignant melanoma was found in the cervical esophagus. She underwent thoracoscopic mobilization of the gastric tube and esophagus followed by cervical esophagectomy and reconstruction with a free jejunum flap. She received 24 courses of nivolumab therapy for 1 year as a postoperative adjuvant therapy. Subsequently, at the age of 78 years, an enlarged left cervical lymph node and a mass in the right lower lobe of the lung were found. She underwent left cervical lymph node dissection and thoracoscopic wedge resection of the right lung. Histopathological examination of the resected specimens revealed that both tumors were metastases of malignant melanoma. At age 79 years, she received eight courses of nivolumab therapy as a second postoperative adjuvant therapy, with no sign of recurrence in a 9-month follow-up period after the third metastasectomy. CONCLUSION: In cases of metastatic recurrence of PMME, aggressive resection of oligometastasis with postoperative adjuvant nivolumab therapy may result in long-term survival.

A retrospective analysis of revision framework surgeries for unilateral vocal fold paralysis / Análise retrospectiva das cirurgias de revisão do arcabouço laríngeo para paralisia unilateral de prega vocal

Abstract Introduction Revision framework surgeries might be required for unilateral vocal fold paralyses. However, outcomes and indications of revision surgeries have not been adequately documented. For a better understanding of indications for the procedure and to help in achieving better vocal outcomes, we performed a retrospective chart review of patients who underwent revision framework surgeries for unilateral vocal fold paralysis. Objectives This study aimed to present clinical features of patients who underwent revision framework surgeries for the treatment of unilateral vocal fold paralysis. Methods Of the 149 framework surgeries performed between October 2004 and October 2019, 21 revision framework surgeries were performed in 19 patients. Self-assessments by patients using the voice handicap index-10 questionnaire, and objective aerodynamic and acoustic assessments performed pre- and post-operatively were analyzed using the Wilcoxon's signed-rank test for paired comparisons. Results Undercorrection was indicated as reasons for revision surgeries in all cases. The revision techniques included type I thyroplasty, type IV thyroplasty, and arytenoid adduction, and revision surgeries were completed without any severe complication in all cases. Pre- and post-operative voice handicap index-10 scores were obtained in 12 cases, and other parameters were evaluated in 18 cases. Significant improvements were observed in voice handicap index-10 scores, maximum phonation time, mean flow rate, Current/Direct Current ratio, and pitch perturbation quotient. Conclusion Undercorrection was observed in all patients who underwent revision framework surgeries for unilateral vocal fold paralysis, and the initial assessment and planning are thought to be important in order to avoid revision surgeries. Revision surgeries were performed safely in all cases, and significantly improved vocal outcomes were observed, even after multiple procedures. Revision surgery should be considered for patients with unsatisfactory vocal functions after primary framework surgeries for unilateral vocal fold paralysis.

Resumo Introdução As cirurgias de revisão do arcabouço laríngeo podem ser necessárias em casos de paralisia unilateral de prega vocal. Entretanto, os resultados e as indicações das cirurgias de revisão não têm sido documentados de forma adequada. Para melhor compreensão das indicações do procedimento e para auxiliar na obtenção de melhores resultados vocais, fizemos uma revisão retrospectiva dos prontuários de pacientes submetidos a cirurgias de revisão do arcabouço laríngeo em paralisia unilateral de prega vocal. Objetivos Apresentar as características clínicas de pacientes submetidos a cirurgias de revisão do arcabouço laríngeo para tratamento de paralisia unilateral de prega vocal. Método Das 149 cirurgias de revisão do arcabouço laríngeo feitas entre outubro de 2004 e outubro de 2019, 21 cirurgias de revisão do arcabouço laríngeo foram feitas em 19 pacientes. As autoavaliações feitas pelos pacientes com o questionário voice handicap index‐10 e avaliações aerodinâmicas e acústicas objetivas feitas no pré e pós‐operatório foram analisadas com o teste de postos sinalizados de Wilcoxon para comparações pareadas. Resultados A hipocorreção foi apontada como o motivo das cirurgias de revisão em todos os casos. As técnicas de revisão incluíram tireoplastia tipo I, tireoplastia tipo IV e adução de aritenoide. As cirurgias de revisão foram feitas sem qualquer complicação grave em todos os casos. Os escores do questionário voice handicap index‐10 pré e pós‐operatórios foram obtidos em 12 casos e outros parâmetros foram avaliados em 18 casos. Melhorias significativas foram observadas nos escores do questionário, no tempo máximo de fonação, taxa de fluxo médio, relação antes/depois e no quociente de perturbação do pitch. Conclusão Hipocorreção foi observada em todos os pacientes submetidos a cirurgias de revisão do arcabouço laríngeo para paralisia unilateral de prega vocal e a avaliação inicial e o planejamento são considerados importantes para evitar cirurgias de revisão. As cirurgias de revisão foram feitas com segurança em todos os casos e melhoria significativa dos resultados vocais foi observada mesmo após múltiplos procedimentos. A cirurgia de revisão deve ser considerada para pacientes com funções vocais insatisfatórias após cirurgia primária do arcabouço laríngeo para paralisia unilateral de prega vocal.

Classification of Voice Disorders Using a One-Dimensional Convolutional Neural Network.

OBJECTIVES: Auditory-perceptual voice analysis is a standard method for quantifying pathological voice quality, but perceptual ratings are based on subjective evaluations and therefore may vary among examiners. Although many acoustic metrics have been studied for potential use in the objective evaluation of pathological voices, the interpretation of acoustic metrics in individual cases is difficult and the technique is not widely used by clinicians. The aim of this study was to establish standardized methods to discriminate grade, roughness, breathiness, asthenia, strain (GRBAS) scale scores of pathological voices directly using one-dimensional convolutional neural network (1D-CNN) models. METHODS: We constructed an original dataset utilizing 1,377 voice samples of sustained phonation of the vowel /a/. Each voice sample was rated by three experts according to the GRBAS scale and the median values were used as the correct answer label. We designed an end-to-end 1D-CNN model with a raw voice waveform input having a frame width of 9,600 samples. The models were trained with our original dataset for each GRBAS category individually and the model performance was tested by the five-fold cross validation method. RESULTS: The accuracy, F1 score, and quadratic weighted Cohen's kappa for the testing dataset were determined. The metrics for the G scale showed the most balanced model performance, with high accuracy (0.771) and substantial agreement (kappa = 0.710). The model for the R scale had relatively high accuracy (0.765) and F1 score (0.743) with moderate agreement (kappa = 0.536). The accuracy (0.883) and the F1 score (0.865) for the S scale were the highest among the five categories, whereas the Cohen's kappa was the lowest (0.190). CONCLUSIONS: The end-to-end 1D-CNN models can evaluate overall pathological voice quality with a reliability comparable to human evaluations. The efficiency with which the machine learning models can be trained and evaluated is closely related to the dataset quality.

A retrospective analysis of revision framework surgeries for unilateral vocal fold paralysis.

INTRODUCTION: Revision framework surgeries might be required for unilateral vocal fold paralyses. However, outcomes and indications of revision surgeries have not been adequately documented. For a better understanding of indications for the procedure and to help in achieving better vocal outcomes, we performed a retrospective chart review of patients who underwent revision framework surgeries for unilateral vocal fold paralysis. OBJECTIVES: This study aimed to present clinical features of patients who underwent revision framework surgeries for the treatment of unilateral vocal fold paralysis. METHODS: Of the 149 framework surgeries performed between October 2004 and October 2019, 21 revision framework surgeries were performed in 19 patients. Self-assessments by patients using the voice handicap index-10 questionnaire, and objective aerodynamic and acoustic assessments performed pre- and post-operatively were analyzed using the Wilcoxon's signed-rank test for paired comparisons. RESULTS: Undercorrection was indicated as reasons for revision surgeries in all cases. The revision techniques included type I thyroplasty, type IV thyroplasty, and arytenoid adduction, and revision surgeries were completed without any severe complication in all cases. Pre- and post-operative voice handicap index-10 scores were obtained in 12 cases, and other parameters were evaluated in 18 cases. Significant improvements were observed in voice handicap index-10 scores, maximum phonation time, mean flow rate, Current/Direct Current ratio, and pitch perturbation quotient. CONCLUSION: Undercorrection was observed in all patients who underwent revision framework surgeries for unilateral vocal fold paralysis, and the initial assessment and planning are thought to be important in order to avoid revision surgeries. Revision surgeries were performed safely in all cases, and significantly improved vocal outcomes were observed, even after multiple procedures. Revision surgery should be considered for patients with unsatisfactory vocal functions after primary framework surgeries for unilateral vocal fold paralysis.

A case of double inferior vena cava with the connection to sacral venous plexus.

Double inferior vena cava (IVC) is known as a variation in which the additional IVC is found on the left side of the abdominal aorta. Their developmental process has been well documented, but the venous development around the lumbosacral region is controversial. In the present double IVC case, the left IVC entered the left renal vein at the L2 level, and the renal veins on each side flowed into the right IVC at the L1 level. The internal and external iliac veins were merged at the S1 level on each side. Besides, a venous communication (3-mm-width) was found horizontally between the internal iliac veins near their origin at the S1 level. It had also an extra narrow branch (1-mm-width), which ran obliquely upward and reached the left IVC at the level of L5. The median sacral artery (MSA) ran at the ventral side of the horizontal communication but at the dorsal side of its extra oblique branch. These results suggest that the oblique branch is a remnant of the anastomosis between the right and left posterior cardinal veins. Furthermore, the horizontal vein corresponds to the sacral venous plexus, suggesting that the anastomosis can be formed between the IVC and sacral venous plexus.

Development and Validation of the Japanese Version of the Consensus Auditory-Perceptual Evaluation of Voice.

PURPOSE: Auditory-perceptual evaluation is essential for the assessment of voice quality. The Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) provides a standardized protocol and assessment form for clinicians to analyze the voice quality and has been adapted into several different languages. The aims of this study were to develop the Japanese version of the CAPE-V and to investigate its reliability and validity. METHOD: The Japanese CAPE-V consisted of the same three speech contexts (vowels, sentences, and conversation) as developed in the original English version. The sentences were designed according to the concepts of the original version and reviewed by Japanese phoneticians. To validate the usefulness of the Japanese CAPE-V, voices of 173 Japanese-speaking subjects (76 subjects with dysphonia and 97 without voice complaints) were evaluated by five experienced judges, according to the Japanese CAPE-V as well as the GRBAS (Grade, Roughness, Breathiness, Asthenia, Strain) scale. RESULTS: The Japanese CAPE-V provided a high interrater reliability (intraclass correlation coefficients [ICCs] > .85 for all the parameters) as well as a high intrarater reliability (ICCs > .85 for all the parameters). In addition, overall severity, roughness, and breathiness in the Japanese CAPE-V were highly correlated with the corresponding dimensions in the GRBAS scale, having Spearman correlation coefficients greater than .8. CONCLUSION: This study demonstrated the reliability and validity of the newly developed Japanese CAPE-V as an auditory-perceptual evaluation instrument.

Objective Assessment of Pathological Voice Using Artificial Intelligence Based on the GRBAS Scale.

OBJECTIVES: The validity and reliability of the psychological assessment of auditory perceptions, as typified by the grade, roughness, breathiness, asthenia, and strain (GRBAS) scale, have been widely recognized. However, due to their subjective nature, inter- and intra-examiner reliability are unavoidable. In this study, we aimed to add objectivity to the GRBAS scale using artificial intelligence and to compare the accuracy of two methods-one based on Google's TensorFlow and another based on Apple's Core ML. METHODS: The GRBAS scale of 1,377 vowel samples was evaluated and used as training data to create a machine learning model. We used TensorFlow and Apple's Create ML to create two machine learning models and examined the difference in their accuracies for classifying the severity of pathological Voice data based on the GRBAS scale. RESULTS: Absolute comparisons are difficult to make because of the difference in methods; however, both training models could objectively evaluate GRBAS scales and were statistically correlated in G and B. CONCLUSION: While TensorFlow requires creation of a training model from scratch, Create ML is a relatively easy way to create a training model for voice by adding training data for GRBAS scales to an existing training model for sounds. Although the data handling and learning methods are different, both models performed well. Findings from this study could be used for medical screening purposes, and there is the potential to change the clinical approach to voice diagnostics in the future.

Real-Time Acoustic Voice Analysis Using a Handheld Device Running Android Operating System.

OBJECTIVES: We developed a highly accessible acoustic voice analysis system (VArt) using a handheld device running Android operating system. To provide stable and reliable analysis using readily obtainable equipment under unfavorable conditions, we modified the fundamental frequency (F0) extraction algorithm and designed an intuitive user interface representing a new hoarseness index (real-time Ra: Rart), which is a derivative of harmonics-to-noise ratio developed by Kojima and Shoji (Ra2). Since Rart continues to display analysis results in real time, unlike conventional acoustic analysis, it can be used for evaluation such as during phonosurgery and speech therapy. We evaluated the agreement between the earlier version of acoustic voice analysis software (VA) running on a Windows personal computer and VArt running on a handheld device. METHODS: F0, Ra2, and Rart were measured in voice samples of sustained vowel phonation /a/ from 10 healthy volunteers and 22 patients with voice disorders using VA running on a Windows personal computer and VArt running on two types of handheld devices in a sound-treated room or in a medical examination room. Intraclass correlation coefficients were calculated for both systems under both conditions. RESULTS: All of the comparisons were highly correlated. CONCLUSIONS: Measurements obtained using our newly developed VArt were highly consistent with those using VA, indicating high reliability. Moreover, the new system increases the clinical feasibility of acoustic voice analysis.

Adrenal insufficiency following nivolumab therapy in patients with recurrent or metastatic head and neck cancer.

Nivolumab, an anti-programmed cell death-1 monoclonal antibody, is currently used to treat many types of advanced cancers including recurrent and metastatic head and neck cancer. However, there are increasing reports concerning immune-related adverse events related to nivolumab therapy. Here, we report three patients who presented with adrenal insufficiency following nivolumab therapy. Two were diagnosed as having isolated adrenocorticotropic hormone (ACTH) deficiency and one was diagnosed as having primary adrenal insufficiency. All three patients complained of progressive fatigue and appetite loss, so we measured their blood cortisol and ACTH levels and diagnosed them as having adrenal deficiency. Treatment with nivolumab was discontinued for all three patients, and replacement therapy using hydrocortisone was successful after a few days in all cases. Two patients subsequently resumed nivolumab therapy because their general condition had improved. Complaints of fatigue and appetite loss during cancer treatment are common and tend to be regarded as unimportant. Although adrenal insufficiency due to nivolumab is relatively rare, complaints of these symptoms could lead to the detection of adrenal insufficiency at an early stage. The present report highlights the importance of the early recognition of adrenal insufficiency.