The effect of galvanization and potassium iodide iontophoresis of the throat and larynx on thyroid parameters: a randomized controlled trial.

Few studies have assessed the application and side effects of potassium iodide (KI) iontophoresis. Using a double-blinded randomized controlled trial with a 1:1 parallel-group, we investigated the effect of galvanization and the KI iontophoresis in the throat and larynx on three thyroid parameters. A total of 50 healthy volunteers with normal TSH, FT3, and FT4 levels and lacking focal changes in the thyroid ultrasonography were subjected to 10 electrotherapy treatments. The TSH, FT3, and FT4 levels were determined prior to the 10 electrotherapeutic treatments (T1), 2-weeks after treatment (T2) and 6-months after treatment (T3). At T2 and T3, both groups had normal levels of TSH, FT3, and FT4. Regarding the change of TSH, FT3, and FT4 levels between T1 vs. T2 and T1 vs. T3, no significant differences between the galvanization and iontophoresis groups were found. However, both groups had lower levels of all three hormones at T3. Together, these data indicate that KI iontophoresis does not affect thyroid hormone levels in the short- nor long-term. Additional follow-up studies with larger groups are required to better confirm the safety of galvanization and iontophoresis procedures in the pharynx and larynx.Trial registration ClinicalTrials.gov (NCT04013308; URL: www.clinicaltrials.gov ). Day of first registration 09/07/2019.

The Effect of Antioxidant Agents on Cisplatin-Induced Laryngeal Histological Alterations in Rats.

The larynx-related adverse effects that depend on cisplatin decrease patient comfort and many antioxidants have been used to eliminate these side effects. We aimed to identify the laryngeal mucosal changes imposed by cisplatin and investigated whether antioxidants, and their healing effects on these changes, may help reduce laryngeal complications in patients resulting from adverse effects in the larynx. A rat model was designed to evaluate the effects of cisplatin on the larynx and the protective role of antioxidants. Single-dose cisplatin was given both intraperitoneally alone and additionally administered with p-coumaric acid, melatonin, resveratrol, vitamin D, and oleic acid over 5 days. Whole larynges were dissected and evaluated histologically, histochemically, and immunohistochemically. Varying degrees of mucosal changes cisplatin group, but neither erosion nor an ulcer was observed. Numerous variable histological effects of antioxidants were observed on cisplatin exposed laryngeal mucosa. The most obvious effects of cisplatin were edema. The results of the study showed that resveratrol was the most preventive antioxidant agent against cisplatin-dependent mucosal changes. The highest increase in the Ki67 index was in the oleic acid group. Vitamin D increased stromal cyclooxygenase-2 expression that may have an effect on increasing mucosal damage.

Routine restaging after primary non-surgical treatment of laryngeal squamous cell carcinoma-a review.

PURPOSE: Treatment of patients with laryngeal squamous cell carcinoma with radiotherapy or chemoradiation is an established alternative to laryngeal surgery in many cases, but particularly for advanced tumors without cartilage invasion. Imaging modalities face the challenge of distinguishing between posttherapeutic changes and residual disease in the complex anatomic subsite of the larynx. Guidelines concerning restaging of head and neck squamous cell carcinomas (HNSCC) are presented by the National Comprehensive Cancer Network (NCCN) and other national guidelines, but clearly defined recommendations for routine restaging particularly for laryngeal cancer are lacking. METHODS: A systematic search was carried out in PubMed to identify studies evaluating routine restaging methods after primary non-surgical treatment of laryngeal squamous cell carcinoma from 2009 to 2020. RESULTS: Only three studies were deemed eligible, as they included at least ≥50% patients with laryngeal squamous cell carcinoma and evaluated imaging modalities to detect residual cancer. The small number of studies in our review suggest restaging with fluoro-deoxy-glucose positron-emission tomography/computed tomography (FDG PET/CT) 3 months after initial treatment, followed by direct laryngoscopy with biopsy of the lesions identified by FDG PET/CT. CONCLUSION: Studies evaluating restaging methods after organ-preserving non-surgical treatment of laryngeal carcinoma are limited. As radiotherapy (RT), chemoradiotherapy (CRT), systemic therapy followed by RT and radioimmunotherapy are established alternatives to surgical treatment, particularly in advanced laryngeal cancers, further studies are needed to assess and compare different imaging modalities (e.g. PET/CT, MRI, CT, ultrasound) and clinical diagnostic tools (e.g., video laryngoscopy, direct laryngoscopy) to offer patients safe and efficient restaging strategies. PET or PET/CT 3 months after initial treatment followed by direct laryngoscopy with biopsy of the identified lesions has the potential to reduce the number of unnecessary laryngoscopies.

Office-Based Procedures for the Diagnosis and Treatment of Laryngeal Pathology.

INTRODUCTION: Since the development of distal chip endoscopes with a working channel, diagnostic and therapeutic possibilities in the outpatient clinic in the management of laryngeal pathology have increased. Which of these office-based procedures are currently available, and their clinical indications and possible advantages, remains unclear. MATERIAL AND METHODS: Review of literature on office-based procedures in laryngology and head and neck oncology. RESULTS: Flexible endoscopic biopsy (FEB), vocal cord injection, and laser surgery are well-established office-based procedures that can be performed under topical anesthesia. These procedures demonstrate good patient tolerability and multiple advantages. CONCLUSION: Office-based procedures under topical anesthesia are currently an established method in the management of laryngeal pathology. These procedures offer medical and economic advantages compared with operating room-performed procedures. Furthermore, office-based procedures enhance the speed and timing of the diagnostic and therapeutic process.

[Local anesthesia in the children undergoing the fibroendoscopic study of the nasal cavity, nasopharynx, and larynx: are topical anesthetics needed?].

This prospective randomized study with double blind control was designed to evaluate the effectiveness of various anesthetic techniques employed prior to fibroendoscopy of the nose, nasopharynx, and larynx of the children. The study included 160 children at the age varying from 3 to 14 (mean 7.4±2.96) years randomly allocated to four statistically comparable groups matched for age and sex. The following preparations were used to treat the children prior to fibroendoscopy: physiological solution (group 1), a 0.05% xylometazoline solution (group 2), a 10% lidocaine solution (group 3), and a mixture of 0.05% xylometazoline and 10% lidocaine solutions (group 4). The evaluation of the tolerance to the pretreatment of the nasal cavity with lidocaine and lidocaine plus xylometazoline (groups 3 and 4) showed that it was significantly (p<0.05) worse than in groups 1 and 2. The subjective tolerance to fibroendoscopy as reported by the patients was on the average similar in the children of all four groups (p>0.05). The doctors found the tolerance of fibroendoscopy to be the worst following pretreatment with the physiological solution (group 1) and the best after pretreatment with a mixture of lidocaine and xylometazoline (group 4) (p=0.03). The children comprising groups 2 and 3 were not significantly different in terms of the tolerance to fibroendoscopy (p>0.05). It is concluded that the pretreatment of the nasal cavity of the children with a 10% lidocaine solution before fibroendoscopy has no advantage over the pretreatment with a 0.05% xylometazoline solution; at the same time, insuflation of lidocaine as an anesthetic induces more pronounced negative emotions compared with the application of 0.05% xylometazoline.

Comparison of Enk Fibreoptic Atomizer with translaryngeal injection for topical anaesthesia for awake fibreoptic intubation in patients at risk of secondary cervical injury: A randomised controlled trial.

BACKGROUND: Two methods of topical anaesthesia for awake fibreoptic intubation (FOI) in patients at risk of secondary cervical injury were compared: the translaryngeal injection (TLI) technique and the Enk Fibreoptic Atomizer. OBJECTIVE: The objective of this study was to determine which system of topical anaesthesia provides the fastest and most comfortable awake FOI, using the oral approach. DESIGN: A randomised controlled study. SETTING: A single centre trial between 2009 and 2011. PATIENTS: One hundred and twenty patients (63 women, 57 men) who underwent neurosurgery of the spine at Klinikum St. Georg Leipzig were randomly allocated into two groups (group TLI, 61 patients; group ENK-ATOMIZER, 59 patients). Inclusion criteria were an American Society of Anesthesiology (ASA) physical status of 1 to 3, age 18 to 80 years, and those who met any one of three indications for FOI - cervical instability, predicted difficult airway, a BMI greater than 40 kg m(-2), and who gave written informed consent.Exclusion criteria were emergency awake FOI, mental disability/delirium, polytrauma and contraindication to TLI. INTERVENTIONS: Two anaesthesiologists experienced in both techniques performed all anaesthesia procedures within the study. MAIN OUTCOME MEASURES: The primary outcome was the timing sequence of awake FOI. The incidence of coughing/gagging, ease of tracheal tube placement, mucosal bleeding, cardiopulmonary stability and postoperative outcomes were also investigated. RESULTS: Awake FOI was significantly faster using the TLI technique (mean, 191 s; range, 123 to 447 s; SD, 83.5) than the Enk Fibreoptic Atomizer [mean, 430 s; range, 275 to 773 s; SD, 124.9; (P = 0.0001)]. Patients in group TLI exhibited significantly less gagging (P = 0.047) but more mucosal bleeding (P <  .001). CONCLUSION: Awake FOI using the TLI technique was faster and provided better topical anaesthesia with less gagging during endoscopic intubation. However, the TLI technique was also more invasive. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00948350.

Toxicological evaluation of aerosols of a tobacco extract formulation and nicotine formulation in acute and short-term inhalation studies.

A formulation of tobacco extract containing 4% nicotine (TE) and similar nicotine formulation containing vehicle and 4% nicotine (NF) were evaluated using animal inhalation assays. Two 4-h inhalation exposures at 1 and 2 mg/L aerosol exposure concentrations, respectively, of the tobacco extract with 4% nicotine formulation showed that the LC50 was greater than 2 mg/L, the maximum concentration tested. All inhalation exposures were conducted using the capillary aerosol generator (CAG). Increasing aerosol TPM concentrations (0, 10, 50, 200, 1000 mg/m(3) TE and 0, 50, 200, 500, 1000 mg/m(3) NF) were generated via the CAG and used to expose groups of male and female rats for 4-h per day for 14 days. In life monitors for potential effects included clinical observations, weekly body weights and food consumption. Post mortem evaluations included gross tissue findings, hematology, clinical chemistry, serum plasma and nicotine levels, absolute and normalized organ and tissue weights, and histopathology of target organs. Treatment-related changes were observed in body weights, hematology, clinical chemistry, organ weights and histopathological findings for TE at the 200 and 1000 mg/m(3) exposure levels, and in the 500 and 1000 mg/m(3) exposure groups for NF. Under the conditions of these studies, the no-observed-adverse-effect level in the rat was approximately 50 mg/m(3) for the TE aerosol-exposed groups, and approximately 200 mg/m(3) in the NF aerosol-exposed groups.

Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer.

PURPOSE: To report the long-term results of the Intergroup Radiation Therapy Oncology Group 91-11 study evaluating the contribution of chemotherapy added to radiation therapy (RT) for larynx preservation. PATIENTS AND METHODS: Patients with stage III or IV glottic or supraglottic squamous cell cancer were randomly assigned to induction cisplatin/fluorouracil (PF) followed by RT (control arm), concomitant cisplatin/RT, or RT alone. The composite end point of laryngectomy-free survival (LFS) was the primary end point. RESULTS: Five hundred twenty patients were analyzed. Median follow-up for surviving patients is 10.8 years. Both chemotherapy regimens significantly improved LFS compared with RT alone (induction chemotherapy v RT alone: hazard ratio [HR], 0.75; 95% CI, 0.59 to 0.95; P = .02; concomitant chemotherapy v RT alone: HR, 0.78; 95% CI, 0.78 to 0.98; P = .03). Overall survival did not differ significantly, although there was a possibility of worse outcome with concomitant relative to induction chemotherapy (HR, 1.25; 95% CI, 0.98 to 1.61; P = .08). Concomitant cisplatin/RT significantly improved the larynx preservation rate over induction PF followed by RT (HR, 0.58; 95% CI, 0.37 to 0.89; P = .0050) and over RT alone (P < .001), whereas induction PF followed by RT was not better than treatment with RT alone (HR, 1.26; 95% CI, 0.88 to 1.82; P = .35). No difference in late effects was detected, but deaths not attributed to larynx cancer or treatment were higher with concomitant chemotherapy (30.8% v 20.8% with induction chemotherapy and 16.9% with RT alone). CONCLUSION: These 10-year results show that induction PF followed by RT and concomitant cisplatin/RT show similar efficacy for the composite end point of LFS. Locoregional control and larynx preservation were significantly improved with concomitant cisplatin/RT compared with the induction arm or RT alone. New strategies that improve organ preservation and function with less morbidity are needed.

Prospective trial of chemotherapy-enhanced accelerated radiotherapy for larynx preservation in patients with intermediate-volume hypopharyngeal cancer.

BACKGROUND: Altered fractionation radiotherapy (RT) improves locoregional control in head and neck cancer without aggravation of late adverse events. To improve successful larynx-preservation rates in patients with resectable, intermediate-volume hypopharyngeal cancer, a prospective trial of chemotherapy-enhanced accelerated RT was conducted. METHODS: Patients with T2 to T4 hypopharyngeal cancer received 40 Gray (Gy)/4 weeks to the entire neck followed by boost RT administering 30 Gy/2 weeks (1.5 Gy twice-daily fractionation). Cisplatin and 5-fluorouracil were administered concomitantly only during boost RT. RESULTS: Thirty-five patients were enrolled in this study. All patients completed this protocol as planned. After a median follow-up period for surviving patients of 59 months (24-90 months), overall survival and local control rates at 3 years were 91% (95% confidence interval, 81% to 100%), and 88% (79% to 99%), respectively. All surviving patients maintained normalcy of diets. CONCLUSION: This regimen was feasible with encouraging oncological and functional outcomes.

Traditional Chinese Medicine for treatment of laryngeal papillomatosis.

OBJECTIVE: The objective of this study was to assess the clinical effectiveness of Traditional Chinese Medicine (TCM) as an adjuvant therapy for recurrent respiratory papillomatosis. DESIGN: The design of this study was a case series. LOCATION AND SUBJECTS: Fifty-one (51) patients with laryngeal papillomatosis who were treated at Keio University Hospital between May 1981 and April 2008 were incorporated in this study. INTERVENTIONS: Individually formulated TCM was orally administered postsurgically to 20 patients with aggressive laryngeal papillomatosis requiring multiple laser ablations (at least biannually) because of frequent recurrence. Eight (8) patients were excluded because of discontinued visits or medication (6 patients), or malignant transformation of the lesion (2 patients). The remaining 12 patients were enrolled in this study. OUTCOME MEASURES: Retrospective chart review and review of the patients' recorded laryngeal images were performed. Clinical response to TCM was measured by the surgical necessity and Derkay's severity score for each patient, followed by statistical analyses. RESULTS: Surgeries were required statistically less often (p = 0.0029) after TCM administration compared with the pre-TCM period. Furthermore, Derkay's severity score was significantly lower (p = 0.022) at the patients' last visit compared with the score before TCM administration. CONCLUSIONS: TCM may be a useful adjuvant therapy to treat aggressive laryngeal papillomatosis. Further studies are necessary to clarify the pharmacological mechanism of TCM in the treatment of laryngeal papillomatosis.

The preclinical toxicology of salmeterol hydroxynaphthoate.

An extensive toxicology programme on salmeterol hydroxynaphthoate (Serevent), a marketed long-acting beta(2)-adrenoceptor agonist, has been carried out. The studies evaluated both the local (respiratory tract) and systemic tolerance to single and repeated dosing, effects on all stages of reproduction, as well as the genotoxic and oncogenic potential. High acute doses were well tolerated and caused no specific target organ toxicity. In repeat dose studies, animals tolerated salmeterol very well both locally and systemically. No significant effects on the respiratory tract of dogs were seen and only minor laryngeal changes, typical of those occurring with many inhaled medicines, were noted in rats. The high systemic concentrations achieved resulted in a number of changes that are considered to be the result of excessive and prolonged beta( 2)-adrenoceptor stimulation. These included tachycardia, skeletal muscle hypertrophy and minor haematological and blood biochemical changes in general toxicity studies, foetal effects in rabbit organogenesis studies and increased incidences of smooth muscle tumours of the mesovarium in the rat and of the uterus in the mouse oncogenicity studies. Salmeterol showed no evidence of any genotoxic potential. Results of the extensive toxicology programme provide good assurance of the safety for the inhaled use of salmeterol in patients; this has ben confirmed by many years of clinical experience during its development and marketing.

Secretory response induced by essential oils on airway surface fluid: a pharmacological MRI study.

Using pharmacological magnetic resonance imaging, we have performed an in vivo evaluation of the secretory response induced by essential oils in the rat airway. Aim of the work was to establish a computerized method to assess the efficacy of volatile compounds in spatially localized areas without the bias derived by subjective evaluation. Magnetic resonance experiments were carried out using a 4.7 T horizontal magnet. In the trachea, airway surface fluid was easily identified for its high intensity signal. The tracheal glands were also easily visible. The oesophageal lumen was usually collapsed and was identifiable only in the presence of intraluminal liquid. Scotch pine essential oil inhalation significantly increased the surface fluid in the middle portion of the trachea and the increase was visible at both 5 and 10 min. A lesser secretory response was detected after rosemary essential oil inhalation even though the response was significant with respect to the control in particular at 10 min. No secretory response was detected after peppermint essential oil inhalation both at 5 and 10 min. The data obtained in the present work demonstrate a chemically induced airway secretion. The availability of a pharmacological magnetic resonance imaging approach opens new perspectives to test the action of volatile compounds on the airway.

Laryngeal injuries and intubating conditions with or without muscular relaxation: an equivalence study.

PURPOSE: The need for muscular relaxation to improve intubating conditions and to reduce the incidence of laryngeal morbidity is still controversial. The aim of this study was to determine the incidence of symptomatic laryngeal injuries (SLI) and of acceptable intubating conditions (including both good and excellent conditions), both with and without cisatracurium during induction of anesthesia, along with moderate doses of remifentanil and propofol. METHODS: In this prospective, randomized double-blind equivalence trial, the intubating conditions were compared in 130 ASA I or II female patients. All subjects received remifentanil 2 microg x kg(-1) i.v. and propofol 2.5 mg x kg(-1) i.v., with either cisatracurium 0.15 mg x kg(-1) i.v. (group Cisatracturium), or saline (group Placebo). Tracheal intubating conditions were assessed with the Copenhagen Score. A systematic screening for postoperative hoarseness and sore throat was performed 24 and 48 hr after anesthesia, followed by a nasofibroscopic examination when laryngeal symptoms persisted at 48 hr. RESULTS: Twenty-four hr after anesthesia, the incidence of postoperative hoarseness and sore throat in the Cisatracurium and Placebo groups was 26.5% and 21.5%, respectively, and 48 hr after anesthesia, the incidence was 7.8% and 6.1%, respectively (P = 0.32 and P = 0.50 between groups, respectively). In the clinically evaluable population, the incidence of SLI, assessed at 48 hr by nasofibroscopy, was equivalent in both groups, 1.6% vs 1.5% in group Placebo and group Cisatracurium, respectively (P < 0.001 for equivalence test), as was the occurrence of acceptable intubating conditions (95.4% vs 100%, P < 0.05 for equivalence test). However, the occurrence of excellent intubating conditions was more frequent in group Cisatracurium than in group Placebo (P = 0.0003). CONCLUSION: Following induction of anesthesia with propofol and moderate-dose remifentanil, cisatracurium did not confer a higher rate of good-to-excellent conditions for tracheal intubation, nor did muscle relaxation with cisatracurium decrease the rate of SLI after tracheal intubation.

Double-blind study on the effects of topical anesthesia on laryngeal secretions.

The application of topical anesthesia to the oropharynx is a common clinical practice during oral and nasal laryngoscopy. Clinically, questions have been raised about whether topical anesthesia alters laryngeal secretions, which distorts clinical impressions. A double-blind, placebo controlled design was employed to address this issue. Ten premenopausal women with healthy vocal folds and 10 premenopausal women with phonotraumatic lesions underwent oral videolaryngoscopic examinations on subsequent days under both anesthesia and placebo conditions, in counterbalanced order. Video segments were rated by three judges. Dependent variables were balling and pooling of secretions, as previously described in the literature. Statistical analyses failed to reveal any clear effect of topical anesthesia on either secretion balling or pooling for the collapsed data set, but one cannot exclude changes in individual cases. Moreover, there was no evidence that secretions were differentially affected by anesthesia across subject groups. Null results in this data set replicate and extend previously reported findings by other authors. An incidental but potentially interesting finding was that the order of treatment condition (anesthesia versus placebo first) seemed relevant for secretions: Subjects who received the anesthesia condition first tended to show more secretion balling in general, as compared with subjects who received the placebo condition first. Speculation is entertained regarding possible physiological pathways for these incidental findings, which could be relevant for some clinical practice.

Toluene diisocyanate exposure induces laryngo-tracheal eosinophilia, which can be ameliorated by supplementation with antioxidant vitamins in guinea pigs.

OBJECTIVE: Toluene diisocyanate (TDI)-induced asthma is a common cause of occupational lung disease. In addition, a sore throat is one of the complaints of TDI-exposed workers. The aim of the present study was to determine whether TDI exposure induces laryngeal and/or tracheal lesions in experimental animals. MATERIAL AND METHODS: Guinea pigs underwent naris application of TDI three times, and their respiratory tracts were then examined using light and electron microscopy. Some animals simultaneously received vitamins C and E. which function as antioxidant agents. RESULTS: When TDI-treated animals showed the clinical sign of labored breathing, many eosinophils had appeared in the lamina propria and mucosa of both the larynx and trachea, which finally infiltrated the tract lumen through the ruptured epithelium. Laryngo-tracheal inflammation was more severe than that observed in the lungs. However, supplementation with antioxidant vitamins in TDI-treated animals ameliorated the respiratory eosinophilia. CONCLUSION: Naris application of TDI induced laryngotracheitis. which was significantly suppressed by the antioxidant vitamins, This implies a preventive effect of the vitamins on this occupational disease.

Effects of testosterone replacement on a male professional singer.

Testosterone has been known to play an important role in the development of the postpubertal male voice for many centuries. In fact, the prevention of pubertal development of the voice by castrating young male singers was a well-known practice, especially in Italy beginning in the sixteenth century. The "castrati" were well known for their clear, high-pitched voices. Because of the resulting small larynx and vocal folds, castrati apparently produced a distinctive resonance as well as the high pitch, which cannot be matched even by the counter tenors of today. Busy voice labs occasionally see males with sex hormone deficiencies secondary to chromosomal or gonadal problems. This is a presentation of an unusual patient who was a trained tenor singer and was found to have hypogonadism on a premarital health examination. Administration of replacement testosterone resulted in significant vocal register and voice quality changes.