Exploring the Pathophysiology of Reinke's Edema: The Cellular Impact of Cigarette Smoke and Vibration.

OBJECTIVES: To explore the isolated or combined effects of cigarette smoke extract (CSE) and vibration on human vocal fold fibroblasts (hVFF) in an in vitro setting in order to elucidate their influence in the pathophysiology of Reinke's edema (RE). STUDY DESIGN: Immortalized hVFF were exposed to CSE or control medium under static or vibrational conditions. A phonomimetic bioreactor was used to deliver vibrational patterns to hVFF over a period of 5 days. METHODS: Cytotoxicity was quantified using a lactate dehydrogenase assay. We employed reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and Magnetic Luminex(R) assays (R&D Systems, Minneapolis, MN) to assess the influence on extracellular matrix production, fibrogenesis, inflammation, and angiogenesis. RESULTS: We observed significant changes induced by CSE alone (hyaluronic acid, matrix metalloproteinase 1, Interleukin-8, cyclooxygenase [COX]1, COX2, vascular endothelial growth factor [VEGF]D), as well as settings in which only the combination of CSE and vibration led to significant changes (transforming growth factor beta 1, VEGFA, VEGFC). Also, CSE-induced levels of COX2 were only significantly reduced when vibration was applied. CONCLUSION: We were able to explore the cellular effects of CSE and vibration on hVFF by employing a phonomimetic bioreactor. Whereas cigarette smoke is generally accepted as a risk factor for RE, the role of vibration remained unclear as it is difficult to study in humans. Our data showed that some genes and proteins in the pathophysiological context of RE were only affected when CSE in combination with vibration was applied. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E547-E554, 2021.

Reinke's Edema.

Reinke's edema (RE) is the polypoid degeneration of one or both vocal folds within Reinke's space. The viscoelastic properties of the mucosal folds are characteristically altered by the expansion of the subepithelial space. Most frequently, patients present with dysphonia, with women being more affected than men. The primary risk factor is tobacco use. Voice overuse and laryngopharyngeal reflux are also considered to be contributory. Although RE shares the same primary risk factor as malignancy, the risk of malignancy is low, and dysplasia is found only in 0% to 3% of cases. Treatment is focused on decrease of risk factors, such as implementation of smoking cessation, voice therapy, and reflux control. Surgical techniques aim to decrease redundant polypoid mucosa in order to improve voice and restore the glottic airway. Recurrence of RE is high.

Cigarette Smoke Exposure to Pig Larynx in an Inhalation Chamber.

OBJECTIVES: This study investigated the effects of cigarette smoke exposure on the pig larynx using an inhalation chamber. Specifically, we compared the effects of cigarette smoke exposure from either 3 cigarettes per day (3cd) or 15 cigarettes per day (15cd) for 20 days. STUDY DESIGN: In vivo prospective design. METHODS: Female pigs were exposed via an inhalation chamber to cigarette smoke (3R4F research cigarettes) from 3cd (n = 6) or 15cd (n = 6) for 20 days. Outcomes included histopathology of vocal fold and airway tissues; gene expression of interleukins, TNF-α, and VEGF; protein levels of TNF-α and IL-6; and number of coughs recorded in the chamber. RESULTS: Pigs exposed to cigarette smoke from 15cd exhibited mild vocal fold edema as compared to the 3cd group on histopathological evaluation. There was also minimal inflammation of nasal and tracheal tissue characterized by presence of more granulocytes in the 15cd group compared to the 3cd group. Cough frequency was significantly greater for the 15cd group compared to the 3cd group. CONCLUSIONS: A custom-designed large animal inhalation chamber successfully challenged pigs repeatedly, to varying levels of cigarette smoke. Future studies will combine such low levels of smoke exposure with other common challenges such as acid reflux to understand the multifactorial causation of laryngeal pathologies.

Inhalational injury and the larynx: A review.

OBJECTIVE: To review and discuss the existing research on the pathophysiology, impact and management of inhalational injury on the larynx and lower respiratory tract. DATA SOURCES: A literature search was conducted on the PubMed, MedLine, Embase, Web of Science and Google Scholar databases based on the keywords "airway burn", "inhalational injury" and "larynx". REVIEW METHODS: Inclusion criteria included English language studies containing original and review data on airway injury. Data was reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. CONCLUSIONS: Abnormal laryngeal and lower airway findings are common in burns patients and the incidence tends to increase with severity of the burns. Most patients with abnormal findings remain dysphonic decades after the initial injury. Larynx, the inlet to the airway, is exposed to the most intense thermal damage and highest concentration of chemical in inhalational injury. Airway injury is common and may result in long term morbidity. Healing of this tissue architecture is prolonged and different from cutaneous burn. Many patients receive prolonged intubation for medical complications that arise due to the burn injury. The degree of subglottic damage, however, is more extensive and occurs sooner compared with those without inhalational injuries. IMPLICATIONS FOR PRACTICE: With advances in acute medical and surgical management of burn and inhalational injury, airway injury is an important secondary outcome with lasting impact. Awareness of these potential complications and early involvement of medical and allied health team are important steps in improving patient care. A multi-disciplinary approach to management will optimise the short and long-term morbidity management and ultimately our patients' quality of life.

Evaluation of upper esophageal sphincter in benign vocal lesions.

PURPOSE: To evaluate upper esophageal sphincter (UES) activity in patients with benign glottic lesions. METHODS: Twenty-three patients with benign vocal fold (VF) lesions scheduled for manometric evaluation were enrolled as the study group (SG); 20 healthy subjects without vocal pathology or dysphagia were included as the control group (CG). UES residual, basal, relaxation time and peak pharyngeal pressures were evaluated by manometry. The reflux symptom index (RSI) and reflux finding score (RFS) were used to estimate the clinical findings of laryngopharyngeal reflux, and the voice handicap index (VHI) was measured in both groups. The patients' data were compared using the Mann-Whitney test and t test. RESULTS: The diagnoses in the SG were vocal nodules, vocal polyps, vocal cysts, sulcus vocalis, or Reinke's edema. The evaluation scores (RSI, RFS, and VHI) were significantly higher in the SG than in the CG (P < 0.05). UES basal and relaxation pressures, relaxation time, and peak pharyngeal pressures did not differ between the SG and the CG (P > 0.05). CONCLUSION: UES manometric pressure was similar in patients with VF mucosal lesions and controls. Studies involving larger populations are necessary to confirm the manometric changes in the UES and to elucidate the pathogenesis of benign VF lesions.

[The clinical and functional condition of the larynx in the patients of the elder age group presenting with chronic oedematous polypoidal laryngitis]. / Kliniko-funktsional'noe sostoianie gortani u patsientov starshei vozrastnoi gruppy s khronicheskim otechno-polipoznym laringitom.

This article was designed to report the results of the evaluation of the clinical and functional condition of the larynx in the patients of the elder age group presenting with chronic oedematous polypoidal laryngitis before and after their surgical treatment. A total of 60 patients at the age from 60 to 72 years were available for the examination; all of them had a concomitant somatic or ENT pathology. The clinical and functional conditions of the larynx in the patients of the elder age group were studied, with special reference to those suffering from chronic oedematous polypoidal laryngitis before the surgical intervention, that determined the overall clinical picture of the disease characterized in the first place by the predominance of the severe polypoid process with the combination of the organic and functional laryngeal pathology. The specific clinical and functional features of the larynx were identified after the surgical treatment that exerted the appreciable influence on the postoperative course of the disease and the duration of dysphonia. The peculiarities of postoperative laryngitis are described. Its catarrhal form was diagnosed in 42% of the patients. The strong inflammatory reaction with exudation and formation of fibrin films was documented in 58% of the patients while 83% of them exhibited formation of the functional component of dysphonia that required the application of the additional therapeutic measures for the complete restoration of the vocal function taking into consideration the age-related alteration of the larynx together with the long-term postoperative observation of the patients.

Hyaluronidase Injection in the Vocal Folds for Vocal Hemorrhage, Reinke Edema, and Hyaluronic Acid Overinjection: A Novel Application in the Larynx.

Hyaluronidase (HAase) injection into the vocal folds is an off-label use of an enzyme for liquefaction of hyaluronic acid (HA). HAase injection was performed in 14 cases in 13 patients. Office and operative injections of HAase were performed. The indications were five cases of overinjection of HA, six cases of Reinke edema and polypoid corditis, and three cases of acute vocal hemorrhage with early fusiform polyp formation. All the patients tolerated the HAase without complications. Significant voice improvements were noted between pre- and postinjection procedures as evaluated by a self-rating of voice by the Voice Handicap Index-10. A marked decrement in the mass on the side of the injection of HAase was noted in all groups successfully injected upon viewing by videostroboscopy. HAase prevented an additional operative phonosurgery in 10 patients. In conclusion, HAase injection can be used in the vocal folds with good effect in patients. The indications are polypoid corditis with overproduction of HA, acute vocal hemorrhage, and correction of iatrogenic HA overinjection.

"Cold-Steel" Phonosurgery of Reinke Edema Evaluated by the Multidimensional Voice Program.

OBJECTIVES: "Cold-steel" phonosurgery (PS) of Reinke edema is challenging, as the delicate structures of the vocal folds are difficult to preserve. This study aimed to evaluate the results of PS using the Multidimensional Voice Program (MDVP) . MATERIALS AND METHODS: From 2003 to 2007, 76 consecutive patients with Reinke edema were treated with PS for the first time. Reliable MDVP data were available in 37 female patients with both pre- and postoperative values in 14 patients. Voice quality and outcome after PS were evaluated by jitter, shimmer, soft phonation index, and fundamental frequency (f0) using MDVP, videostroboscopy, and a five-step voice outcome score. RESULTS: In the 14 patients, the mean f0 increased from 172 to 222 (P = 0.01), and jitter decreased from 2.03 to 1.17 (P = 0.04) 3 months postoperatively. Vocal fold grading based on videostroboscopy correlated significantly with jitter (P = 0.01). Patients with high preoperative values of jitter, shimmer, or soft phonation index had larger reductions than those with normal values. All had a postoperative reduction of the edemas. The mean voice outcome score increased postoperatively. None of the 37 patients reported complications, but seven patients were reoperated. Preoperatively, 95% of the 37 patients were smokers and only 9 (24%) changed smoking habits. Pre- or postoperative voice therapy was used in 23 (62%) patients. CONCLUSIONS: f0 and jitter by MDVP adequately reflected the postoperative voice improvement and reduction of the edema. Removal of large amounts of edematous tissue, many years of vocal abuse, and unchanged smoking habits may prevent optimal results.

Edema de Reinke obstructivo / Obstructive Reinke edema

Introducción: el edema de Reinke es la acumulación de fluidos en la capa externa de la lámina propia de las cuerdas vocales. Produce disfonía y raras veces obstrucción respiratoria. Las etiologías más frecuentes son el tabaquismo, el reflujo gastroesofágico y el mal uso y abuso vocal. Objetivos: determinar, mediante tratamiento quirúrgico, la tasa de resolución de la disnea inspiratoria severa provocada por edema de Reinke bilateral de cuerdas vocales. Diseño: estudio descriptivo y retrospectivo. Material y métodos: revisión de las historias clínicas electrónicas de todos los pacientes que consultaron y fueron tratados por disnea inspiratoria severa provocada por edema de Reinke bilateral de las cuerdas vocales, en el servicio de Otorrinolaringología del Hospital Italiano de Buenos Aires, entre febrero de 2007 y abril de 2015. Resultados: fueron tratados 4 pacientes de sexo femenino que consultaron por disnea inspiratoria severa. Fumaban más de 30 cigarrillos por día. La técnica quirúrgica consistió en resecar todo el edema polipoideo en forma bilateral, preservando el borde libre de las cuerdas vocales. Conclusiones: el edema de Reinke obstructivo es una patología infrecuente. La tasa de resolución de la disnea inspiratoria severa en las cuatro enfermas tratadas fue del100%. La resección total del edema y de la mucosa excedente, preservando un pequeño sector para que recubra el borde libre de la cuerda vocal (cordectomía vs. cordotomía), fue la técnica quirúrgica preferida. (AU)

Introduction: the Reinke edema is an accumulation of fluid in the outer layer of the lamina propria of the vocal cords. Causes dysphonia and rarely produces respiratory obstruction. Objectives: to determine the rate of resolution of the severe inspiratory dyspnea caused by bilateral Reinke edema of vocal cords with surgical treatment. Design: descriptive and retrospective study. Material and methods: review of the electronic medical records of all patients who consulted and were treated for severe inspiratory dyspnea caused by bilateral Reinke edema of the vocal chords in the Hospital Italiano de Buenos Aires between February 2007 and April 2015. Results: four women were treated, consulted for severe inspiratory dyspnea. Smoked more than 30 cigarettes per day. The surgical technique consisted in to resect all the bilateral polypoid edema, while preserving the free edge of the vocal cords. Conclusions: the obstructive Reinke edema is an infrequent pathology. The rate of resolution of the severe inspiratory dyspnea in the four patients treated was 100%. The total resection of the edema and mucosa excess, preserving a small sector to cover the free edge of the vocal cord (cordectomy vs cordotomy) was the preferred surgical technique. (AU)

Two rare cases of laryngeal intralymphatic histiocytosis.

We report two rare cases of intralymphatic histiocytosis causing, respectively, recurrent and persistent episodes of upper airway swelling and breathing difficulties. Case 1 was a 39-year-old man who was referred with recurrent upper airway swelling causing difficulty in breathing. A direct laryngoscopy was performed under general anesthesia due to minimal effect from treatment with antibiotics and anti-oedema medication. On examination, the larynx was found to be swollen and oedematous but not inflamed. Biopsies from the aryepiglottic folds showed intralymphatic histiocytosis. The patient was extensively examined but the only abnormal finding was a low CD4 count. The breathing difficulties fluctuated during the diagnostic process and settled after a year. Case 2 was a 35-year-old man who presented with persistent laryngeal swelling. Biopsies from the epiglottis showed intralymphatic histiocytosis. Extensive investigations were performed but discovered no abnormal findings. He received CO2 laser treatment twice and the swelling decreased. Intralymphatic histiocytosis is extremely rare in upper airway pathology. It is an important differential diagnosis in patients with recurrent and chronic laryngeal swelling and dyspnoea.

Laryngeal Side Effects of Tyrosine Kinase Inhibitors.

OBJECTIVES: Tyrosine kinase inhibitors (TKIs) are common targeted drugs, used in the treatment of hematological and solid malignancies. These drugs present a multitude of potential adverse effects. Laryngeal manifestations, including laryngeal edema, secondary to TKIs treatment have not been well studied, despite their potential lethality. METHODS: This cross-sectional study included adult patients (>18 years) treated with TKIs who were followed in a secondary medical center and underwent a voluntary otolaryngological examination, which included laryngeal fiber-optic laryngoscopy (FOL). FOL was independently performed by two senior otolaryngologists, and results were recorded and evaluated by two grading systems, to assess the degree of laryngeal edema. In addition, medical files were reviewed, and data collected included past medical history, signs and symptoms, physical examination, laboratory results, treatment type, and duration. RESULTS: Sixteen patients, aged 68.2 ± 13.6 years, were examined during October 2014 to December 2014. Of them, three (19%) were males. Eleven (68%) patients presented with varying degrees of laryngeal edema. A significant correlation was found between gastroesophageal reflux symptoms and laryngeal edema (P = 0.02). TKI treatment was stopped in one patient, because of symptomatic laryngeal edema, which completely resolved within 2 weeks. CONCLUSIONS: Laryngeal edema was common in our study group. This edema was most often not life threatening. Yet, because of the potential severity of this side effect, we propose a routine FOL examination of patients before commencing TKI treatment and a reevaluation performed during treatment.

Normative Values and Interrelationship of MDVP Voice Analysis Parameters Before and After Endotracheal Intubation.

PURPOSE: The Multi-Dimensional Voice Program (MDVP) is used for assessment of voice quality. A simple procedure for MDVP recordings was used in a randomized clinical trial (RCT) on induced vocal fold trauma due to intubation. This secondary study compares the common MDVP parameters with other normative values for adults and investigates the correlation between these MDVP parameters in relation to the "standardized" trauma of endotracheal intubation. METHODS: Preoperative and postoperative assessments of vocal fold pathology with flexible videolaryngoscopy and voice analysis with MDVP using the best-of-three standardized recording were performed in 121 patients with normal voices included consecutively in the RCT. The procedures of anesthesia were standardized. RESULTS: The normative MDVP values of this study are consistently lower compared with most normative values presented in other studies. The preoperative to postoperative differences in jitter values (jitter and relative average perturbation) were closely correlated to the shimmer values for patients with postoperative vocal fold edemas. In the patients with edema, the preoperative to postoperative differences in jitter had a correlation coefficient of 0.95 (P < 0.0001) to the difference in shimmer, compared with a correlation coefficient of 0.39 (P < 0.0001) in the patients without edema. CONCLUSIONS: This study supports the use of the "Best-of-Three" procedures for precise and relevant MDVP parameter calculations. The MDVP parameters, with closely correlated changes in jitter and shimmer values, accurately reflect the induced vocal fold edema when using the preoperative to postoperative changes.

Angiotensin converting enzyme inhibitor-related angioedema: onset, presentation, and management.

OBJECTIVE: This study aimed to determine the duration of use, presentation, and management of angiotensin converting enzyme (ACE) inhibitor-related angioedema patients at an urban academic medical center. METHODS: Retrospective chart review. RESULTS: Eighty-eight patients who presented with ACE inhibitor-related angioedema between January 1, 2012, and December 31, 2012, were identified. They presented anywhere from 1 day to 20 years after starting an ACE inhibitor. About half the patients (50.7%) presented after taking an ACE inhibitor for at least 1 year. Fifty-five patients were female (62.5%). Twenty-eight patients (31.8%) had an airway intervention with 27 intubated and 1 requiring cricothyroidotomy. Six patients were intubated after more than 1 flexible laryngoscopy. The percentage of patients with involvement of the face, lips, tongue, floor of mouth, soft palate/uvula, and larynx were 12.5%, 60.2%, 39.7%, 6.8%, 17.0%, and 29.5%, respectively. Sixty-eight percent of patients with laryngeal edema were intubated. The majority of patients were treated with a corticosteroid and H1 and H2 receptor antagonists. CONCLUSION: Angioedema can occur at any time after starting ACE inhibitor use, with nearly half occurring after 1 year of use. Laryngeal involvement occurred in a minority of patients, but most of these patients were felt to require airway protection.

Analysis of Potassium Titanyl Phosphate Laser Settings and Voice Outcomes in the Treatment of Reinke's Edema.

OBJECTIVE: Despite increased clinical utility of the 532-nm potassium titanyl phosphate (KTP) laser, no studies have examined outcomes for Reinke's edema (RE) as a function of laser parameters and initial treatment effects. Variability in delivery parameters, fiber-to-tissue distance, and immediate end-tissue effects limits universal application of existing study outcomes. We examine voice outcomes using standardized treatment classification, providing justification for laser parameter selection and immediate tissue effect in clinical use. METHODS: Retrospective review of 9 patients who underwent KTP laser treatment for RE. Demographics, RE severity, laser settings, total laser energy, and immediate tissue effects were correlated with quantified voice outcomes. RESULTS: An average of 157 joules (6-640 J) was delivered over a 0.369-second exposure time (0.1-0.9 seconds). Immediate tissue effects varied from nonablative treatment (type I and type II) to ablation without tissue removal (type III). Overall, Voice Handicap Index-10 (VHI-10) decreased by 8.23; improvement was most pronounced with type II treatments (delta VHI-10=12). No complications were encountered. CONCLUSION: Potassium titanyl phosphate laser can be safely and effectively used to improve voice in RE patients regardless of severity. This is the first study to provide detailed information on laser settings, energy delivery, and treatment effect in RE management; these results may guide clinical use of this modality, especially for novice laser surgeons.

Videolaryngoscopic assessment of laryngeal edema after arytenoid adduction.

OBJECTIVES/HYPOTHESIS: Arytenoid adduction (AA) as surgical treatment for unilateral vocal fold paralysis (UVFP) is associated with higher morbidity from airway complications due to postoperative laryngeal edema compared with other laryngeal framework surgeries. The aim of this study was to evaluate postoperative laryngeal edema after AA using a new videolaryngoscopic (VL) scoring assessment. STUDY DESIGN: Prospective case series. METHODS: Nineteen patients with UVFP (14 males and five females; mean age, 56 years) who were treated with AA alone or combined with ansa cervicalis (AA/AC) nerve anastomosis or nerve-muscle pedicle (AA/NMP) flap implantation were evaluated. Laryngeal edema was assessed by VL scoring for 10 days postoperatively. Degree of edema was scored in three subsites: the membranous vocal fold, arytenoid mound, and pyriform sinus on the operated side. Statistical significance was defined as P < .05. RESULTS: No patient experienced postoperative airway compromise. Interexaminer reliability was generally high (Spearman r > 0.75). The mean degree of edema increased steadily from postoperative day (POD) 1 to 3, peaking on POD 3 at all subsites. It then declined significantly from POD 3 to 7 (P < .05) and gradually through POD 10. The maximum degree of edema, maximum edema time, and operative time were not correlated significantly at any subsite. Maximum edema time and surgery type (AA vs. AA/AC or AA/NMP) were not correlated at any subsite. CONCLUSIONS: Inter-rater reliability for the proposed VL scoring was significant at all subsites. The VL findings suggest that AA alone or AA combined with reinnervation showed maximum laryngeal edema on POD 3 but added no significant morbidity.

The effects of cigarette smoke condensate on vocal fold transepithelial resistance and inflammatory signaling in vocal fold fibroblasts.

OBJECTIVES/HYPOTHESIS: In response to chronic cigarette smoke exposure, a subset of patients present with edematous vocal folds, characteristically referred to as Reinke's edema. This phenotype differs from the tissue changes associated with prolonged smoke exposure in the lower airway, and the mechanism underlying Reinke's edema remains poorly described. We hypothesize that the effects of smoke are diffuse and involve both the epithelium and mucosa. STUDY DESIGN: In vitro, ex vivo experiment. METHODS: Transepithelial resistance (R(T) ) was quantified in an ex vivo, viable, porcine vocal fold model. Excised tissue was exposed to cigarette smoke condensate (CSC) and R(T) was computed at baseline and 1 and 4 hours after exposure. In vitro, human vocal fold fibroblasts were exposed to CSC. Cyclooxygenase 2 (COX-2), microsomal prostaglandin E synthase-1, and 15-hydroxyprostaglandin dehydrogenase mRNA expression were assessed at 4 hours. Prostaglandin E2 (PGE2) synthesis was quantified via immunoassay following 24 hours of CSC exposure. RESULTS: CSC had no effect on R(T) . CSC did, however, induce COX-2 mRNA expression as well as its downstream lipid mediator PGE2. PGE2 metabolism appears to be regulated via both synthetic and degradative enzymes in response to cigarette smoke. CONCLUSIONS: In vitro, CSC initiates an inflammatory response in vocal fold fibroblasts. However, in isolation, the epithelial resistance is not altered by CSC, at least acutely. These data may suggest a role for the interaction between the inflammatory response in the mucosa and compromised epithelial barrier function, as has been shown in other tissues.

Hydrostatic intestinal edema induced signaling pathways: potential role of mechanical forces.

BACKGROUND: Hydrostatic intestinal edema initiates a signal transduction cascade that results in smooth muscle contractile dysfunction. Given the rapid and concurrent alterations in the mechanical properties of edematous intestine observed with the development of edema, we hypothesize that mechanical forces may serve as a stimulus for the activation of certain signaling cascades. We sought to examine whether isolated similar magnitude mechanical forces induced the same signal transduction cascades associated with edema. METHODS: The distal intestine from adult male Sprague Dawley rats was stretched longitudinally for 2 h to 123% its original length, which correlates with the interstitial stress found with edema. We compared wet-to-dry ratios, myeloperoxidase activity, nuclear signal transduction and activator of transcription (STAT)-3 and nuclear factor (NF)-kappa B DNA binding, STAT-3 phosphorylation, myosin light chain phosphorylation, baseline and maximally stimulated intestinal contractile strength, and inducible nitric oxide synthase (iNOS) and sodium hydrogen exchanger 1-3 messenger RNA (mRNA) in stretched and adjacent control segments of intestine. RESULTS: Mechanical stretch did not induce intestinal edema or an increase in myeloperoxidase activity. Nuclear STAT-3 DNA binding, STAT-3 phosphorylation, and nuclear NF-kappa B DNA binding were significantly increased in stretched seromuscular samples. Increased expression of sodium hydrogen exchanger 1 was found but not an increase in iNOS expression. Myosin light chain phosphorylation was significantly decreased in stretched intestine as was baseline and maximally stimulated intestinal contractile strength. CONCLUSION: Intestinal stretch, in the absence of edema/inflammatory/ischemic changes, leads to the activation of signaling pathways known to be altered in intestinal edema. Edema may initiate a mechanotransductive cascade that is responsible for the subsequent activation of various signaling cascades known to induce contractile dysfunction.

Cigarette smoke and reactive oxygen species metabolism: implications for the pathophysiology of Reinke's edema.

OBJECTIVE/HYPOTHESIS: Oxidative damage mediates the lower airway response to cigarette smoke (CS). In the vocal folds, the tissue phenotype is both distinct and largely uncharacterized. We sought to investigate the effects of CS on the oxidative status and fibroblast phenotype in the vocal folds. Specifically, we hypothesized that CS would induce a hypermetabolic fibroblast phenotype and altered oxidative metabolism potentially providing insight into the relationship among CS, Reinke's edema (RE), and malignancy. STUDY DESIGN: In vivo/in vitro. METHODS: Heme oxygenase (HO)-1 gene expression was examined in human tissue. In vitro, the effects of cigarette smoke condensate (CSC) on HO-1 gene expression and secretion was assayed. In addition, CS-mediated intracellular reactive oxygen species synthesis was quantified, and compared to the response in pulmonary fibroblasts (HFL). We then examined the effects of CSC on migration and proliferation in human vocal fold fibroblasts (HVOX). RESULTS: : HO-1 expression was approximately 4-fold higher in RE samples versus vocal fold polyps. CSC induced HO-1 gene expression and secretion in a time- and dose-dependent fashion in vitro. CSC also increased intracellular ROS in both HVOX and HFL. CSC decreased HVOX proliferation and migration in a dose-dependent manner. CONCLUSIONS: These data suggest that the fibroblast phenotype is influenced by smoke. Our data suggest that the antioxidant response in the vocal fold tissue may be one mechanism of chemoprotection, a putative explanation for the observation that RE rarely transforms to malignancy. In addition, CSC does not appear to induce a hypermetabolic fibroblast phenotype as expected.

Steroids and risk factors for airway compromise in multilevel cervical corpectomy patients: a prospective, randomized, double-blind study.

STUDY DESIGN: Prospective, randomized, double-blind study. OBJECTIVE: To evaluate intravenous corticosteroids in preventing delayed extubation after multilevel corpectomy and strut graft reconstructive procedures and to identify risk factors for delayed extubation in these patients. SUMMARY OF BACKGROUND DATA: We performed a prospective, randomized double-blind study in patients undergoing multilevel cervical corpectomy procedures. Our hypothesis was that high-dose perioperative steroids would decrease edema and thus decrease the incidence of delayed extubation. METHODS: We studied patients undergoing 2- or 3-level anterior cervical corpectomy procedures with anterior strut graft reconstruction. Sixty-six patients were randomized to receive 3 doses of either intravenous dexamethasone (n = 35) or saline (n = 31). The first dose was given before the incision, with subsequent doses given 8 and 16 hours later. Patients remained intubated until postoperative day 1, at which time a cuff leak test was performed by the anesthesiology attending. If a leak was present, the patient was extubated. If not, the test was repeated each postoperative day until a leak was present, indicating a patent airway. RESULTS: Five of 35 (14%) in the steroid group and 6 of 31 (19%) in the saline group required delayed extubation (P = 0.22). There were no statistical differences in preoperative parameters of age, gender, diagnosis, smoking history, BMI, number of operative levels, or preoperative American Society of Anesthesiologists rating between the 2 groups. Similarly there were no differences between the groups for duration of anesthesia, intraoperative colloids or crystalloids, intraoperative blood loss, or intraoperative urine output. The data for both groups were pooled to evaluate risk factors for delayed extubation. The only statistically significant risk factor for delayed extubation in this study was female gender (P = 0.0001). CONCLUSION: Based on our data, we cannot recommend intravenous dexamethasone for prevention of delayed extubation after multilevel anterior cervical corpectomy and strut grafting procedures.

Significance of laryngeal edema after partial laryngectomy and radiotherapy in supraglottic cancer.

OBJECTIVE: To evaluate the impact of the presence of laryngeal edema on outcome and the other potential prognostic factors in patients with supraglottic larynx carcinoma treated with radiotherapy after partial laryngectomy. DESIGN: A retrospective analysis. SETTING: Cerrahpasa Medical Faculty, Istanbul University. METHODS: Seventy-nine patients with supraglottic carcinoma of the larynx were treated with radiotherapy after partial laryngectomy between January 1980 and July 2003. Neck dissection was not performed in 46 patients. The median follow-up time was 64 months. MAIN OUTCOME MEASURES: The effect of laryngeal edema grade on local control, disease-free, and actuarial survival rates. RESULTS: The 5-year locoregional progression-free and overall survival rates were 86% and 75%, respectively. In univariate analysis, histologically positive neck disease reduced regional (p = .0045) and disease-free survival (p = .01). Patients with edema grade III-IV had lower local control (p = .0004), disease-free (p = .0034), and actuarial survival (p = .0041) rates. In the multivariate analysis, a significant negative association of laryngeal edema with local control (p = .012), disease-free survival (p = .002), and actuarial survival (p = .003) was found. Nodal status was a significant prognostic factor for disease-free survival (p = .027). Grade III-IV laryngeal edema was observed in 17 patients. Owing to laryngeal edema, tracheostomy dependence and total laryngectomy were required in three patients and one patient, respectively. CONCLUSION: Radiotherapy after partial laryngectomy can be performed in patients with poor prognostic factors with reasonable complication rates. However, in the presence of grade III-IV laryngeal edema, tumour recurrence should be suspected, and these patients have to be managed with close follow-up and further evaluation to improve outcome.