Kosuke Uno

Comparative multidimensional assessment of laryngeal function and quality of life after radiotherapy and laser surgery for early glottic cancer

This study was designed to comparatively assess laryngeal function and quality of life (QOL) of patients after laser surgery (LS) or radiotherapy (RT) for early glottic cancer.

Harmonious Team Approach for Safe Airway Management -The Keio University Experience-

Surgical Tracheostomy (ST) has been a standard procedure for surgical airway management for a long time. Recently, Percutaneous Dilatational Tracheostomy (PDT) is getting more and more popular in the US and Europe in this field. In Japan, PDT is becoming well-known following the trend in other countries mainly due to its relatively easy procedure even for non-surgeons to secure the airway. However, part of the multidisciplinary participants in preparing/ performing tracheostomy and postoperative care do not have opportunities to understand the (contra) indications of PDT, or to precisely learn the technical difference between ST and PDT. Furthermore, instruction for use is hard to be strictly followed in diverse situations to potentially induce multiple accidents. In our institution, PDT was adopted under the collaboration between anesthesiologists and otolaryngologists in January 2008. However, at that time, responsibilities and roles of every participant engaged in the tracheostomy were not clarified, while multiple responsible decisions were necessary for harmonious procedure, e.g. necessity of tracheostomy for the candidate, timing to perform the procedure, selection of proper surgical procedure, and the place where the tracheostomy should be performed. Considering such a muddled situation, we organized a committee consisted of surgeons, anesthesiologists, nurses and administrative organizers to comprehend the recent complicated situations surrounding tracheostomy. The final purpose of organizing the committee was to build a unique intramural rule to prepare and perform elective tracheostomy safely and harmoniously. In this communication, multiple issues to produce the present confused situation for harmonious elective tracheostomy are summarized. We show our current intramural protocol for elective tracheostomy, delivered in July 2010, which clarifies the sequential role and responsibility of every multidisciplinary participant at each indispensable decision for safe procedure. Furthermore, current practice of tracheostomy in our institution, especially in the intensive care unit, was assessed.

Multidimensional vocal assessment after laser treatment for recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis (RRP) is a benign epithelial tumor that exhibits a high frequency of recurrence. This study assesses the vocal function after laser treatment for RRP, particularly in relation to the frequency of surgery.

Clinical Review of Globus Patients with a Focus on GERD Cases: ―胃食道逆流が関連した症例を中心に―

Globus sensation is a common symptom seen daily in ear-nose-throat (ENT) clinics. Globus is affected by multiple factors, and of these, gastroesophageal reflux disease (GERD), has been recognized as a relatively more manageable cause of globus than the other causes. However, we still commonly encounter globus patients with unclear backgrounds who require multiple diagnostic and therapeutic modalities. To provide an appropriate treatment approach and create favorable situations for these patients, we developed and applied an intramural algorithm to manage globus considering GERD, laryngeal allergy, and psychological problems as major factors of this pathology. 　Twenty-six patients with globus sensation who visited our voice clinic from June 2012 to March 2015 were enrolled in this study. All these patients had undergone general ENT examinations, including naso-pharyngo-laryngeal endoscopies and cervicothoracic computed tomographic scans. Upper gastrointestinal endoscopy revealed 2 cancers. Further study classified 23 patients into the GERD group and 1 patient into the allergy group. Proton pump inhibitor (PPI) therapy was successful in 11 patients of the GERD group (response rate, 47.2%). Improvement in subjective symptoms of globus were measured by the scores of questionnaires, including the F scale and Reflux Symptom Index. Significant improvement in these scores were observed 1 month after PPI prescription in the PPI-responder group in this study. Further assessment of medical history as well as the scores of questionnaires to measure the severity levels of depression (Self-rating Depression Scale) and anxiety (State-Trait Anxiety Inventory-Form JYZ, STAI) proved that relatively longer lasting symptoms (≥4 months) or relatively higher anxiety scores (STAI≥50 points) were predictive of PPI resistance. Our study results suggested that the pathology of globus is affected by multiple factors and that a multidisciplinary team approach is required for better management of this disease.

Postoperative Glottal Function and Voice-Related QOL after Type1 and Type2 Cordectomy against Laryngeal Leukoplakia

Objectives: Recent progress in phonomicrosurgical technique and equipment enabled one to precisely differentiate the subepithelial (type1) and subligamental (type2) cordectomy concept as needed. The purpose of this study was to compare postoperative glottal function and voice-related quality of life (QOL) between these 2 surgical concepts against laryngeal leukoplakia. Methods: From January 2007 to August 2013, 42 consecutive laryngeal leukoplakia patients had excisional biopsies using type1 procedures. Of these, cancer patients (n = 10) had additional type2 laser surgeries. Furthermore, some severe dysplasia/carcinoma in situ patients (n = 11) preferred additional type2 surgery aiming at relatively safe surgical margins. Sequential pre- and postoperative measurements of Grade, Roughness, Breathiness, Asthenia, Strain (GRBAS) scale and evaluations of laryngeal videostroboscopic images were performed. Acoustic measurements and voice-related QOLs (VHI and V-RQOL) were examined at the patients’ last visits. All data were compared between type1 and type2 groups. Results: Vocal quality was well-preserved in type1 group after surgery. Although immediate postoperative deterioration of GRBAS score was observed in type2 group, vocal recovery was obtained in 6 months to present no significant difference compared with type1 group. Impaired glottal closure and pliability were observed in both groups after surgery. While videostroboscopic findings of type1 group recovered to normal in 3 months, impaired glottal findings remained for 1 year in half of the type2 patients. Moreover, voice-related QOLs were significantly better in type1 group. Conclusions: Our study proved that advanced phonomicrosurgical technique and equipment could offer a well-preserved vocal quality even in the type2 group. However, subjective voice-related QOLs were better in the type1 group with superior videostroboscopic findings.

Unique Clinical Findings in Laryngeal Leukoplakia to Predict Serious Histopathology in Low-Risk Nonsmokers

Objectives: Although most of the laryngeal leukoplakias are temporal inflammatory lesions in non-smokers, some patients represent serious histopathologies to require careful management. The purpose of this study was to clarify unique clinical features of the patients who require cautious care in this low-risk group. Methods: One hundred fifty-four consecutive patients referred to our institution with laryngeal leukoplakia from June 2006 to May 2013. Of these, 24 patients without smoking history were incorporated in this study. Retrospective chart reviews and the re-evaluations of video-taped laryngeal images were performed. Sequential change of vocal quality (Grade, Roughness, Breathiness, Asthenia, Strain scale) was assessed in each patient. Timings to show improvements of laryngeal images were studied in the patients with spontaneous disappearances of leukoplakias (n = 12). Furthermore, excisional biopsies were performed on 12 patients and their histopathologies and vocal/stroboscopic characteristics were compared with each other. Results: Spontaneous disappearances of the lesions were observed 4.6 months after referral to our hospital on average, and these patients presented vocal quality of G1 or G0 at their first visits. Additionally, gradual recoveries in their glottal closure and/or pliability of diseased vocal folds were observed in this group. Furthermore, patients with histopathology of severe dysplasia/cancer presented with either (1) no improvement in their G2 voice for 1 month, (2) incomplete glottal closure coupled with abnormal pliability of diseased vocal folds for 1 month, or (3) abnormal pliability of diseased vocal folds for 4 months. Conclusions: Our analyses identified several specific findings to predict serious pathology in laryngeal leukoplakia patients without smoking history.

Sjögren's syndrome with paresis of the internal branch of the superior laryngeal nerve

A 46‐year‐old woman developed painful dysesthesia in her extremities and ataxic gait. She was diagnosed with Sjögrens syndrome, and her condition was diagnosed as sensory ataxic and painful neuropathy. Intravenous immunoglobulin therapy alleviated the ataxia and severe pain in her extremities. When she was 61‐years‐old, she developed dysphagia and dyspnea. Laryngoscopy showed tactile anesthesia on the epiglottis, indicating paresis of the superior laryngeal nerve. We considered that the primary cause of dysphagia was paresis of the internal branch of the superior laryngeal nerve, and carried out tracheostomy and high‐dose intravenous methylprednisolone therapy (1 g/day × 3 days). Her dysphagia and aspiration gradually improved without following oral steroid therapy. Our case is the first report of the internal branch of superior laryngeal nerve paresis as a possible cause of dysphagia and aspiration in a patient with Sjögrens syndrome. Additional cases of Sjögrens syndrome with dysphagia should be investigated to confirm our findings.

3D Measurement of Paralyzed Larynx in Japanese Using Cone Beam CT

Objectives: Precise measurement of human organs with an error by less than one millimeter was realized by cone beam computed tomography (CBCT) imaging technology. The purpose of this study was to measure the shape/size of paralyzed larynges in Japanese patients with multiple parameters using CBCT. Methods: Eighty-nine Japanese patients who referred to our institution with unilateral vocal fold paralysis from April 2007 to November 2011 were incorporated in this case series study. There were 54 males and 35 females, and the mean age was 59.9 years. Laryngeal CBCT images were taken in 2 conditions: 1) patients sitting relaxed (R image), and 2) patients applying pressure at their diaphragm (P image). Lengths of bilateral vocal folds, bilateral horizontal glottal angles, and sizes of gaps from a median plane of each larynx were measured in R images. Vertical gaps of bilateral vocal folds were measured in P images. Results: Mean lengths of non-diseased vocal folds (males, 18.5 mm; females, 12.9 mm) were significantly longer compared with diseased side (males, 17.7 mm; females, 12.4 mm) in both males ( P =0.011) and females (P = 0.001). Glottal angles were significantly wider in no diseased side (16.1°) compared with diseased side (9.4°, P = 0.0011). Vertical gaps were normalized with the lengths of non-diseased vocal folds with mean value of 0.057. Conclusions: Our study showed the first correct measurement of paralyzed larynx in live Japanese patients. These data will contribute to the improvement of diagnosis and surgical procedures for the patients with laryngeal paralysis in the future.

Comparative Assessment on Laryngeal Function after Radiotherapy and Laser Surgery against Early Glottic Cancer

Objectives: Comparatively assess the laryngeal function and quality of life (QOL) of the patients after laser surgery and radiotherapy against early glottic cancer. Methods: Sixty-seven patients with T1 glottic cancer treated in our institution with radiotherapy (RT, n=30) or CO2 laser surgery (LS, n=37) were incorporated in this retrospective cohort study. LSs were performed following the type II subligamental cordectomy concept. Patients in LS group were categorized into subgroups for further analyses. Twenty-seven patients had vaporization of the lesion with defocused mode, and a residual 10 patients had cancer excision with focused mode using relatively lower power (LS-EX group). GRBAS subjective voice assessment scale, maximum phonation time, and acoustic parameters were measured as vocal parameters. Voice-Related Quality of Life Measure and Voice Handicap Index were used to evaluate post-therapeutic QOL. Laryngeal videostroboscopic images were further examined to assess post-therapeutic laryngeal pliability. The mean follow-up period was 46 months. Results: Compared with their pre-therapeutic scores, worse GRBAS scores were observed at the end of the treatments in 20% and 60% of RT group and LS group respectively. Although these scores recovered 1 year after treatment, abnormal stroboscopic findings remained in 40% and 95% of RT group and LS group respectively. Interestingly, further subgroup analysis proved no significant difference of post-therapeutic vocal parameters and QOL between RT group and LS-EX group. Conclusions: Early glottic cancer could be treated with equivalent post-therapeutic laryngeal function and QOL with either radiotherapy or focused low power CO2 laser surgery.

Abstract 4039: miR-196a is a novel diagnostic biomarker and therapeutic target for laryngeal cancer

Head and neck cancer (HNC) is a major cause of cancer-related mortality and morbidity, comprising roughly 6% of all malignancies worldwide, and laryngeal cancer has the highest incidence in it. At present, laryngeal cancer is treated with surgery and/or (chemo)radiation, each of which can have devastating consequences on speech and swallowing function. Even with the combined treatment approaches as mentioned above, laryngeal cancers with advanced stages have poor prognosis, therefore in need of novel less invasive treatments against their high morbidity. However, although to date its relevance to smoking has been well documented, the molecular mechanism involved in laryngeal cancer development and its highly sensitive biomarkers remain to be known. Thus, we have focused on microRNAs (miRNAs) showing highly tissue-or disease-specific patterns as potential novel biomarkers or therapeutic targets with clinical applicability. In this study, to screen the miRNAs highly sensitive to laryngeal cancer as putative biomarkers, we first examined the expression of 723 human miRNAs in 8 laryngeal tissues (1 polyp, 2 dysplasias, 3 laryngeal cancers and 2 neighboring normal tissues matched to laryngeal cancers) using microarrays (Agilent Human miRNA V2). The result showed the up-regulation of 6 miRNAs and the down-regulation of 3 miRNAs in laryngeal cancer compared to others. Subsequently, to confirm these findings and quantitate cancer-specific miRNAs, we performed quantitative RT-PCR (qRT-PCR) analysis (TaqMan miRNA assays, Applied Biosystems) using 48 laryngeal tissue samples including 16 cancers on 5 miRNAs (miR-196a, miR-130b*, miR-133b, miR-375, miR-455-5p), which showed markedly differential expression in cancers compared with others on microarrays. The results were consistent with those from microarrays, especially when cancer samples were compared with matched laryngeal tissues as normal controls. Of the 5 miRNAs examined, miR-196a showed significant increase in cancers when compared to either benign tissues or dysplasias. Next, to examine the utility of miR-196a as a promising biomarker for laryngeal cancer, we performed qRT-PCR on miR-196a using 83 tissue samples and 68 serum samples and found that miR-196a could be very useful in diagnosing the disease. We also analyzed miR-196a expression in FFPE sections by in situ hybridization and the result showed its robust expression in cancers but barely detectable in benign tissues Finally, to explore whether miR-196a can promote tumor growth in vitro or in vivo, we treated human laryngeal cancer cells or xenografted nude mice, respectively, with either miR-196a inhibitor or negative control inhibitor, and found that miR-196a inhibition suppresses tumorigenic properties of laryngeal cancer. Together with these findings, our study provided the first demonstration of miR-196a as a putative diagnostic biomarker and therapeutic target for laryngeal cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4039.