Usefulness of Intraoperative Narrow-Band Imaging in the Site Diagnosis of Respiratory Papillomatosis.

OBJECTIVE: Narrow-band imaging (NBI) is considered useful for detecting respiratory papillomatosis. However, the choice between preoperative and intraoperative NBI depends on the facility. We investigated the usefulness of NBI and determined whether preoperative NBI can replace intraoperative NBI with a comparable detection rate. METHODS: In this retrospective cohort study conducted at single a tertiary care center, patients with respiratory papillomatosis treated between 2017 and 2022 were enrolled. We systematically compared preoperative white light imaging (WLI) with preoperative and intraoperative NBI. The primary endpoints were the papilloma detection rate and lesion site assessed by the Derkay scoring system. The secondary endpoints were the risk factors for increased Derkay scores. RESULTS: The study included 127 patients with papilloma. Intraoperative NBI yielded significantly higher Derkay scores than preoperative WLI (p < 0.001) and preoperative NBI (p = 0.004). The papilloma detection rates of preoperative WLI and preoperative NBI were not significantly different. Intraoperative NBI detected more lesions than preoperative NBI in 37 of 127 (29%) patients; the overall number of additional lesions was 47 of 279 (17%). Compared with preoperative NBI, intraoperative NBI yielded significantly higher scores for the vocal cords (p = 0.005), false vocal cords (p = 0.010), and ventricle of the larynx (p < 0.001). Elevated Derkay scores were significantly associated with male sex (p = 0.012) and alcohol consumption (p = 0.007). CONCLUSION: Intraoperative NBI is more accurate in detecting papillomatous lesions, and preoperative NBI cannot replace intraoperative NBI. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1820-1824, 2024.

Inferior Surface Leukoplakia of Vocal Folds: Risk of Recurrence: A Preliminary Study.

OBJECTIVES: This study aimed to identify vocal fold leukoplakia (VFL) lesions on the inferior surface as a risk factor for recurrence. METHODS: This was a retrospective study with data collected from 2001 to 2018. The study comprised 37 patients with VFL, divided into the nonrecurrent and recurrent groups. We examined the clinicopathological characteristics and the surgical procedures performed in each patient. RESULTS: Among the 37 patients, 15 (40.5%) had residual (3) or recurrent (12) VFL. Of those patients with and without recurrence, 8 of 12 (66.7%) and 6 of 22 (27.3%), respectively, had inferior surface lesions of the vocal fold at the initial operation (P = .036). Recurrences were significantly higher in patients with inferior surface lesions. Other evaluated factors did not show significance for recurrence. CONCLUSION: The presence of VFL lesions on the inferior surface is a significant risk factor for recurrence.

Effect of a Single Injection of Basic Fibroblast Growth Factor into the Vocal Folds: A 36-Month Clinical Study.

OBJECTIVE: A single injection of basic fibroblast growth factor (bFGF) into the vocal folds of patients with glottal insufficiency has been shown to be effective for a few years. However, the long-term therapeutic effect of a single injection of bFGF into the vocal folds has yet to be demonstrated. In this study, the therapeutic effect of a single injection of bFGF into the vocal folds was investigated over several years by monitoring patients for 36 months following this treatment. METHODS: Nineteen patients with glottal insufficiency received injections of bFGF diluted to 20 µg/mL in the superficial layer of the lamina propria of the bilateral vocal folds. The following parameters were evaluated at preinjection baseline and 6, 12, 18, 24, and 36 months later, and statistical comparisons were performed. The parameters evaluated were: the Grade, Rough, Breathy, Asthenic, and Strained (GRBAS) scale score; maximum phonation time; acoustic analysis; and glottal wave analysis (GWA) and kymograph edge analysis (KEA) using high-speed digital imaging (HSDI). The amplitude perturbation quotient (APQ) and period perturbation quotient (PPQ) were measured by acoustic analysis. The mean minimum glottal area during vocalization and mean minimum distance between the vocal folds were measured by GWA. The amplitudes of the bilateral vocal folds were measured by KEA. RESULTS: Postinjection, the GRBAS scale score decreased from 6 months after injection, and maximum phonation time was prolonged. The mean minimum glottal area during vocalization and the mean minimum distance between the vocal folds calculated by GWA of HSDI decreased significantly after 6 months. These effects persisted until 36 months postinjection. APQ and PPQ derived from acoustic analysis tended to decrease, but not significantly. There was no clear change in the amplitudes of the bilateral vocal folds calculated by KEA of HSDI before and after injection. CONCLUSIONS: These results suggest that the effects of a single injection of bFGF into the vocal folds persist for 36 months.

The predominant site of pharyngeal lesions in patients with recurrent respiratory papillomatosis.

PURPOSE: Recurrent respiratory papillomatosis (RRP) is a disorder characterized by the frequent recurrence of benign neoplasms in the respiratory tract. Some patients with RRP develop laryngeal papilloma, while others present with extralaryngeal lesions in the nose, pharynx, and trachea. The present study aimed to determine the pharyngeal sites where RRP-related lesions develop more frequently. METHODS: We retrospectively reviewed the medical records of 127 patients treated at our department between January 2015 and December 2020. We compared the human papilloma virus (HPV) infection status and differences in tumor location between 41 patients with RRP and 86 patients with pharyngeal papilloma (PP). RESULTS: In the RRP group, extralaryngeal papillomata were observed in 10 patients, eight (19.5%) of whom presented with lesions in the inferior wall of the nasopharynx (IWoN). On the contrary, only one patient with PP (1.1%) developed papillomata in this region. IWoN papilloma was significantly more likely to arise in the RRP group than in the PP group (p = 0.0004). CONCLUSION: In RRP, pharyngeal lesions frequently arise in the IWoN, while this region remains largely unaffected in patients with PP.

Human Papillomavirus Vaccination as an Adjuvant Therapy for Recurrent Respiratory Papillomatosis: Additional Case Series.

Prevention of the recurrence of recurrent respiratory papillomatosis (RRP), a neoplasm of the respiratory tract, is a challenge. Human papillomavirus (HPV) vaccine has been expected to suppress the aggressiveness of RRP. However, there has been insufficient data to verify whether HPV vaccination can serve as an adjuvant therapy option for RRP. The aim of this study was to add our data on the efficacy of HPV vaccination for RRP to the academic discipline. Twenty-four RRP patients were treated with a combination therapy of surgery and three sessions of quadrivalent HPV vaccine. The patients' clinical courses, which were HPV infection status changes, intersurgical interval, and disease severity score (Derkay's site score), were statistically analyzed before and after combination therapy. Twelve of the 24 (52.5%) RRP patients who were HPV-DNA positive turned negative after the combination therapy. The mean of intersurgical interval was significantly extended from 6.85 ± 4.49 months to 30.5 ± 27.6 months after the therapy (P <0.01). The median of Derkay's score of the participants also significantly decreased from 7.5 (interquartile range, 5-12) to 1 (interquartile range, 0-4.25) after the therapy (P <0.01). Thus, combination therapy comprising of surgery and HPV vaccination can postpone the recurrence and lessen the severity of RRP.

Multi-Year Effect of Human Papillomavirus Vaccination on Recurrent Respiratory Papillomatosis.

OBJECTIVE: To examine whether human papilloma virus (HPV) vaccination in combination with surgical resection could suppress recurrence for an extended period of time in patients with recurrent respiratory papillomatosis (RRP). METHODS: In a prospective case series, data of patients who received combination therapy comprising surgery and quadrivalent HPV vaccination (Gardasil; Merck & Co., West Point, PA) were collected. Patients were followed up for RRP from March 2012 to July 2018 in an academic tertiary care center. The patients comprised 16 adults with RRP who were observed for >12 months after HPV vaccination, and whose HPV-DNA status was tested before and for >12 months after completion of combination therapy. The outcomes of this study were the severity score of larynx disease, tumor incidence rate, and relationship between this rate and HPV-DNA negative conversion after therapy. RESULTS: The severity score of laryngeal disease significantly decreased from before combination therapy to the time of final examination (P = 0.00045). The tumor incidence rate decreased to approximately 20% during the period from 12 to 47 months after HPV vaccination. Regarding HPV-DNA status in the final test results of each patient, 12 of 16 (75%) patients showed negative conversion; these 12 were significantly less likely to experience recurrence than patients who persistently tested positive for HPV-DNA during the period between 12 and 47 months after vaccination. CONCLUSION: HPV vaccination prevented recurrence associated with RRP surgery for 4 years in 80% of patients. This may be an effective adjuvant therapy, and HPV-DNA negative conversion after HPV vaccination might predict prevention of recurrence. LEVEL OF EVIDENCE: 2 Laryngoscope, 130:442-447, 2020.

A summary of the Clinical Practice Guideline for the Diagnosis and Management of Voice Disorders, 2018 in Japan.

OBJECTIVE: To develop a summary of the first version of the Clinical Practice Guideline of Voice Disorders for Diagnosis, Management, and Treatment in Japan by the Clinical Practice Guideline Committee of the Japan Society of Logopedics and Phoniatrics and The Japan Laryngological Association. The 2018 recommendations, based on a review of the scientific literature, are intended to serve as clinical practice guidelines for the diagnosis, management, and treatment of voice disorders in Japan. METHODS: A summary of the original version of the Clinical Practice Guideline of Voice Disorders for Diagnosis, Management, and Treatment in Japan was described. Recommendations for the diagnosis, management, and treatment of voice disorders were prepared. Twelve clinical questions (CQs) regarding the diagnosis, management, treatment, and effectiveness of therapy for voice disorders were also prepared. RESULTS: A summary of the first version of the clinical practice guidelines for the diagnosis, management, and therapy of voice disorders was prepared and is presented. Additionally, answers to the 12 CQs on the diagnosis, management, treatment, and effectiveness of voice disorder therapy were prepared, and include evidence-based recommendations. CONCLUSION: These guidelines present a summary of the standard approaches for the diagnosis and treatment of voice disorders and relevant CQs that consider the medical environments in Japan. We hope that the guidelines will assist physicians in clinical settings for patients with voice disorders.

Gardasil Vaccination for Recurrent Laryngeal Papillomatosis in Adult Men Second Report: Negative Conversion of HPV in Laryngeal Secretions.

BACKGROUND: In our first report on antibody levels in middle-aged and older men with recurrent laryngeal papillomatosis (RLP), we reported increases in human papillomavirus (HPV) antibody levels similar to those seen in adult women and young men. We posited that HPV antibodies produced in laryngeal mucus by Gardasil would prevent postoperative reinfection in patients with RLP. STUDY DESIGN: This is a case series study. PURPOSE: The purpose of this study was to examine whether Gardasil injection effectively inhibits recurrence of RLP. Specifically, in this second report, whether HPV antibodies produced in laryngeal secretions by Gardasil are capable of causing negative conversion of HPV-DNA (deoxyribonucleic acid) in laryngeal mucosa was investigated. METHODS: A total of 11 patients for whom antibodies were measured in the first report were studied. Before vaccination and after 1 year Post-vaccination, HPV screening tests were performed on laryngeal secretions, and whether HPV-DNA negative conversion had occurred was evaluated. At the time of collection of laryngeal secretions, the presence or absence of laryngeal papillomas was examined. RESULTS: Before vaccination, all patients were HPV low-risk positive on laryngeal secretion screening tests. After vaccination, three patients were positive. Laryngeal papillomas remained in five patients. CONCLUSIONS: The HPV-DNA test showed negative conversion in eight of 11 (72.7%) patients after vaccination. Residual laryngeal papillomas were found in five of 11 (45.5%) patients. The serum HPV antibody titer did not differ significantly between the group in which laryngeal secretions showed HPV negative conversion and the group in which conversion did not occur. The serum antibody titer did not differ significantly as a function of whether there were residual tumors.

Human Papillomavirus Infection Status of Various Laryngeal Diseases in Japan: A Comprehensive Study.

OBJECTIVE: The aim of our study was to clarify the human papillomavirus (HPV) infection status of various laryngeal diseases in Tokyo, Japan. STUDY DESIGN: This is a retrospective study. METHODS: A total of 144 patients who underwent surgical resection for various laryngeal lesions were enrolled in this study. These subjects were categorized into four groups based on lesion type: non-neoplastic, 44; precancerous, 29; cancer, 35; and papilloma, 36. To determine the rate of HPV infection, laryngeal secretions and resected tissue from our study participants were examined by liquid-phase hybridization (LPH) and consensus primer-directed polymerase chain reaction (PCR). RESULTS: The LPH for low-risk HPV was applied to all 144 patients, and that for high-risk HPV was additionally applied to 121 of the 144 patients. The PCR was applied to 94 of the 144 patients. The LPH detected low-risk HPV-DNA in 23 patients (1 cancer and 22 papillomas) and high-risk HPV-DNA in 3 patients (1 cancer and 2 papillomas). The PCR detected HPV-6 and HPV-11 in the papilloma group, whereas it detected HPV-31 in one patient with laryngeal cancer and one patient with precancerous lesion. Both the LPH and the PCR revealed the HPV infection rate in the non-neoplastic group to be 0%. CONCLUSIONS: Although we found no significant difference in the HPV-DNA positive rates of laryngeal cancer and precancerous lesions in the non-neoplastic group, the positive rates were significantly smaller in this group than in the papilloma group. In the Tokyo area, HPV had little or no association with laryngeal cancer, precancerous lesions, and non-neoplastic lesions in the larynx.

Gardasil Vaccination for Recurrent Laryngeal Papillomatosis in Adult Men: First Report: Changes in HPV Antibody Titer.

BACKGROUND: Patients with human papillomavirus (HPV) DNA-positive recurrent laryngeal papillomatosis commonly have repeated recurrences following surgery. The reason is suspected to be a mechanism by which latent HPV infection in the surrounding healthy mucosa reinfects the surgical site. It may be that production of HPV antibodies in the laryngeal mucosa with Gardasil injection could inhibit postoperative recurrence. STUDY DESIGN: This is a case series study. PURPOSE: The purpose of this study was to examine whether Gardasil injection effectively inhibits recurrence. However, as a first report, we describe the antibody titers before and after vaccination. METHODS: Gardasil was injected in 12 men (aged 32-74 years; mean age 47.9 years) with HPV-positive laryngeal papillomatosis. Serum antibody titers of HPV-6, -11, -16, and -18 were measured by a competitive Luminex-based immunoassay before the vaccination and 7 months after the start of the vaccination. RESULTS: Each of the antibody titers was very low before vaccination, and they rose in all patients after the vaccination. CONCLUSIONS: This finding demonstrates that antibody titers increase with Gardasil injection in post-adolescent males.

THE DISPERSION OF HERBACEOUS PLANT POLLEN IN ITO CITY, SHIZUOKA.

BACKGROUND: Airborne pollen was examined in Ito City, Shizuoka for the purpose of treatment and prophylaxis pollen allergies because the patients with pollen allergy to herbaceous plants have recently increased. METHODS: Setting up a Durham's sampler, we measured airborne pollen identified and classified: Poaceae, Polygonaceae, Amaranthaceae, Urticaceae, Cannabaceae, Ambrosia and Artemisia indica.We studied whether each airborne pollen count has something to do with weather condition (2004-2015). RESULTS: Average total airborne Poaceae pollen count and standard deviation from January to June was 19.4±5.5 cells/cm(2), average total airborne Polygonaceae pollen count and standard deviation from April to September was 11.6±13.4 cells/cm(2). Airborne Poaceae, Amaranthaceae, Cannabaceae, Uriticaceae. Ambrosia and Artamisia indica pollen count from July to Deccember in order: 34.0±15.5 cells/cm(2), 1.3±1.1 cells/cm(2), 8.7±6.4cells/cm(2), 4.9±6.4 cells/cm(2), 10.5±7.8 cells/cm(2), and 13.6±16.3 cells/cm(2).Cannabaceae admitted that its airborne pollen count has negative correlation to the rainfall.Artemisia indica admitted that its airborne pollen count has negative correlation to the average temperature. CONCLUSION: Herbaceous plants pollen doesn't cause allergies because it is much less than tree pollen in ItoCity.It is thought that the diversity of the plants keep the people from having a serious allergy to pollen with awarm weather in this area.

OK-432 injection therapy for cystadenocarcinoma of the parotid gland: A case report.

OK-432 is an immunomodulator that has been reported to be efficacious as an injection therapy for cervical lymphomas and ranulas. We performed OK-432 injection therapy to treat a cystadenocarcinoma of the parotid gland in a 72-year-old man. The 50 × 46-mm tumor was located in the deep lobe of the gland. The tumor had compressed the glossopharyngeal, vagus, and hypoglossal nerves, causing neurally mediated syncope, hoarseness, dysphagia, and dysarthria. A concentration of 5 KE/2 ml of OK-432 was injected. Within 2 months, the cyst had disappeared; no recurrence was apparent during 59 months of follow-up. To the best of our knowledge, no previous report has described injection of OK-432 for malignant cystic disease. We describe the injection method, injection dose, and postinjection course in the hope that this information will prove useful for future applications against malignant cystic disease.

High Prevalence of Laryngopharyngeal Reflux Disease in Patients With Lumbar Kyphosis.

OBJECTIVE: To evaluate the relationship between laryngopharyngeal reflux disease and presence of lumbar kyphosis. STUDY DESIGN: A cross-sectional study. METHODS: We included 20 patients with lumbar kyphosis and 31 control subjects. A diagnosis of laryngopharyngeal reflux disease and gastroesophageal reflux disease was made if the Reflux Symptom Index score was ≥13 and if the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease was ≥8, respectively. We compared the prevalence of the two reflux diseases, frequent reflux symptoms, and demographic factors between the two groups. RESULTS: There was no significant difference in demographic factors between the two groups. Five (25%) of 20 patients with lumbar kyphosis had a Reflux Symptom Index ≥13 compared with one (3.2%) of 31 controls. Seven (35.0%) of 20 patients had a Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease ≥8 compared with three (9.7%) of 31 controls. A comparison of the prevalence of laryngopharyngeal reflux disease and gastroesophageal reflux disease showed a significant difference between patients with kyphosis and controls (P value = 0.029 and 0.036, respectively). In Reflux Symptom Index, heartburn, hoarseness, and a swallowing problem were significantly frequent symptoms in the kyphosis group compared with the control group. CONCLUSIONS: The prevalence of laryngopharyngeal reflux disease and gastroesophageal reflux disease was significantly higher in patients with lumbar kyphosis than in controls. Therefore, otolaryngologists and orthopedic surgeons should be aware that patients with lumbar kyphosis are likely to have gastroesophageal reflux disease and also laryngopharyngeal reflux disease.

Efficacy of a Single Dose of Basic Fibroblast Growth Factor: Clinical Observation for 1 Year.

OBJECTIVE: Basic fibroblast growth factor promotes wound healing by accelerating healthy granulation and epithelialization. However, the duration of the effects of a single intracordal injection of basic fibroblast growth factor has not been established, and administration intervals and timing have yet to be standardized. Here, we administered a single injection to patients with insufficient glottic closure and conducted follow-up examinations with high-speed digital imaging to determine the duration of the treatment response. STUDY DESIGN: Case series. METHODS: For treatment, 20 µg/mL recombinant human basic fibroblast growth factor was injected into two vocal cords. The following examinations were performed before the procedure and at 3-month intervals for 12 months starting at 1 month postinjection: Grade, Roughness, Breathiness, Asthenia, and Strain (GRBAS) scale assessment, maximum phonation time, acoustic analysis, high-speed digital imaging, glottal wave analysis, and kymographic analysis. RESULTS: Postinjection, the GRBAS scale score decreased, and the maximum phonation time was prolonged. In addition, the mean minimum glottal area and mean minimum glottal distance decreased. These changes were significant at 12 months postinjection compared with preinjection. However, there were no significant changes in the vibrations of the vocal cord margins. CONCLUSIONS: The intracordal injection of basic fibroblast growth factor improved insufficient glottic closure without reducing the vibrations of the vocal cord margins. This effect remained evident at 12 months postinjection. A single injection can be expected to yield a sufficient and persistent long-term effect.

The effect of compound nasal surgery on obstructive sleep apnea syndrome.

BACKGROUND: Nasal surgery often fails to ameliorate the symptoms of obstructive sleep apnea syndrome (OSAS). We developed a compound nasal surgery (CNS) method that consists of septoplasty combined with submucosal inferior turbinectomy and posterior nasal neurectomy to ensure low nasal resistance during sleep. OBJECTIVE: To clarify the effect of CNS on OSAS, pre- and postoperative changes in sleep-related events were studied by using polysomnography, the Epworth sleepiness scale (ESS), the visual analog scale for snoring, and health-related quality of life (QOL). METHODS: Forty-five consecutive patients with OSAS and with nasal problems underwent CNS. Three months later, the postoperative effect on OSAS was assessed by using polysomnography findings, daytime sleepiness by the ESS, nasal allergy symptoms, and health-related QOL. Snoring was assessed by the family by using a visual analog scale. RESULTS: The indices of apnea, apnea-hypopnea, oxygen desaturation, and arousal; the ESS; allergic symptom score; health-related QOL; and snoring on a visual analog scale were all significantly improved. CONCLUSIONS: CNS improves OSAS events without any pharyngeal surgical procedure in selected patients. If high nasal resistance associated with OSAS is present, then CNS should thus be considered.

Patients' perceptions of vocal problems: results from a survey in the Tokyo area.

Laryngoscopy in cases of sulcus vocalis reveals bowed vocal folds, resulting in a spindle-shaped chink with glottal incompetence. The anatomic and functional problems and resulting incomplete glottal closure during phonation lead to the presenting symptoms of breathy hoarseness, decrease in maximum phonation time (MPT), and vocal fatigue. These symptoms, however, have been reported from the physician's viewpoint, not the patient's. Furthermore, no standardized guidelines for the treatment of sulcus vocalis have been established. Because the general attitude toward sulcus vocalis appears to have become 'It is only a vocal problem and does not significantly affect the patient's well-being,' knowledge of sulcus vocalis has decreased and knowledge about choices of therapy remain limited. We therefore conducted an epidemiological questionnaire survey on this pathological condition in voice clinics in seven hospitals in the Tokyo area to establish preliminary guidelines for the management of sulcus vocalis, in reference to the opinion of the patients. Here we report the summary of our preliminary study 'a survey for sulcus vocalis' and suggest guidelines for the management of such pathological conditions. Although these management guidelines may result in improvement in the symptoms of sulcus vocalis, patients and physicians should be aware that treatment of this condition is difficult and improvement is not guaranteed.

Assessment of human papilloma virus infection in adult laryngeal papilloma using a screening test.

OBJECTIVES: Human papilloma virus (HPV) infection is involved in both juvenile and adult laryngeal papilloma. We wished to determine which types of adult laryngeal papilloma were clinically related to HPV infection. We hypothesized that multiple-site and recurrent papillomas would have a strong relationship to HPV and conducted the present study to test this hypothesis. METHODS: Thirteen male patients with adult laryngeal papilloma who underwent resection of papilloma between August 2006 and September 2009 were studied. We examined the relationships between whether the tumor was solitary or multiple, presence or absence of recurrence after surgery, and HPV infection. High-risk HPV types (HPV-DNA types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) and low-risk HPV types (6, 11, 42, 43, and 44) were tested by a liquid-phase hybridization method. In addition, HPV typing was performed for patients positive for low-risk HPV types. Twenty patients with laryngeal carcinoma or laryngeal leukoplakia were enrolled as the control group. RESULTS: In the laryngeal papilloma group, all patients tested were negative for high-risk HPV and 69.2% were positive for low-risk HPV. Typing performed for seven of the patients who tested positive for low-risk HPV showed that one patient was positive for HPV-11, whereas the remaining six patients were positive for HPV-6. All patients with recurrent laryngeal papillomatosis (RLP) were positive for low-risk HPV. All patients who were positive for low-risk HPV had RLP. Tumor samples from repeat operations were positive for low-risk HPV in all patients tested. HPV was not detected in the control group. CONCLUSIONS: The relationship between RLP and low-risk HPV was strong, with all cases that were positive for low-risk HPV showing recurrence. Tumor tissue resected at the time of repeat surgery was positive for low-risk HPV in all cases tested.