The Effect of Fibroblast Growth Factors in Grafted Fascia into the Vocal Fold of Rabbits

Abstract Introduction The human larynx is a very important organ for communication. Many conditions lead to scarring of the vocal folds, decreasing voice quality. Objective We aimed to determine whether fibroblast growth factors (FGFs) may influence tissue integration of grafted fascia into the vocal folds of an animal model. Methods This is an experimental animal study with 12 adult rabbits that were submitted to a grafting fragment obtained from superficial cervical fascia into the vocal fold lamina propria, bilaterally. The right vocal fold was injected with FGFs. The animals were sacrificed after 1 month or 12 months, depending on the group they were assigned to, and a histological analysis of their vocal folds was performed.We analyzed the histological changes (such as the presence of fibrosis and neovascularization) induced by the acute or chronic inflammatory reactions. Results The FGFs induced acute inflammatory changes in all animals after 1 month of the initial experiment. The presence of FGFs triggered more fibrosis than the expected due to the surgical procedure itself when compared with the control side of all animals after 12 months of the initial experiment. Conclusions Fibroblast growth factors alone do not represent a good therapeutic option in phonosurgery, since we observed higher levels of fibrosis in the vocal fold lamina propria. Further studies combining more substances may be necessary to elucidate the best option to be used in this kind of surgery. (AU)

Nasal septum ulcer as an isolated manifestation of histoplasmosis.

Histoplasmosis is an infection caused by the dimorphic fungus Histoplasma capsulatum, which is saprophyte of contaminated soil. In the immunocompetent host, the symptoms of histoplasmosis tend to be mild or even non-existent. In immunocompromised patients, the manifestations may be more severe and the disease manifests itself in a disseminated form, with high mortality rates. Isolated mucosal lesions are infrequent and the purpose of this report is to describe an unusual case of nasal septum ulcer as an isolated clinical manifestation of the disease.

The Effect of Fibroblast Growth Factors in Grafted Fascia into the Vocal Fold of Rabbits.

Introduction The human larynx is a very important organ for communication. Many conditions lead to scarring of the vocal folds, decreasing voice quality. Objective We aimed to determine whether fibroblast growth factors (FGFs) may influence tissue integration of grafted fascia into the vocal folds of an animal model. Methods This is an experimental animal study with 12 adult rabbits that were submitted to a grafting fragment obtained from superficial cervical fascia into the vocal fold lamina propria, bilaterally. The right vocal fold was injected with FGFs. The animals were sacrificed after 1 month or 12 months, depending on the group they were assigned to, and a histological analysis of their vocal folds was performed. We analyzed the histological changes (such as the presence of fibrosis and neovascularization) induced by the acute or chronic inflammatory reactions. Results The FGFs induced acute inflammatory changes in all animals after 1 month of the initial experiment. The presence of FGFs triggered more fibrosis than the expected due to the surgical procedure itself when compared with the control side of all animals after 12 months of the initial experiment. Conclusions Fibroblast growth factors alone do not represent a good therapeutic option in phonosurgery, since we observed higher levels of fibrosis in the vocal fold lamina propria. Further studies combining more substances may be necessary to elucidate the best option to be used in this kind of surgery.

Evaluation of the Grafted Fascia in the Vocal Fold of Dogs: A Histologic Study.

INTRODUCTION: There is no consensus on the ideal graft for medialization surgery of the vocal folds in the literature. One of the most favorable proposals is the use of autologous fascia, which seems limited by the lack of information regarding the integration of grafted tissue. Our study aims to evaluate the degree of fully engrafted fascia integration in the vocal fold lamina propria of dogs. MATERIALS AND METHODS: Fourteen adult mongrel dogs that underwent intravenous general anesthesia were selected and kept under spontaneous ventilation. A fascia lata fragment of 4 cm2 was obtained from the right leg of each dog. The dogs underwent laryngoscopy; a 3 mm incision was made in the vocal process, next to the vestibular process, and the fascia was grafted into the right vocal fold. The left vocal fold was used as a control. The animals were divided into two groups: group A, evaluated after 2 months of the procedure, and group B, evaluated after 6 months of the procedure. Histologic analysis was made semiquantitatively regarding the presence of inflammatory reaction, fibrosis, and neovascularization. RESULTS: Our final studied group comprised 12 dogs. Microscopic examination of the larynx revealed the absence of any detectable inflammation in the incision site. The lamina propria of the grafted vocal fold showed identifiable compact, thick, and eosinophilic collagen bands. The surrounding tissue showed thin collagen bands with some organization, similar to the contralateral vocal fold. CONCLUSION: The grafted fascia integrates into the vocal fold lamina propria and seems not to cause inflammatory reaction response.

Methods of Fat Tissue Processing for Human Vocal Fold Injection: A Systematic Review.

OBJECTIVES: We analyzed different methods used to process autologous fat tissues for vocal fold injection (VFI). VFI is a safe procedure that preserves the folds' original elasticity and vibration properties and rarely triggers foreign-body reactions, but is often a temporary treatment due to fat reabsorption. To avoid it, selecting a technique that provides as many viable implantable adipocytes as possible is mandatory. STUDY DESIGN: This is a systematic review. METHODS: Data were collected from PubMed, Embase, Ovid, and Cochrane Library. Authors systematically reviewed databases for papers on autologous fat tissue processing methods involving human injections in vocal folds and vocalization outcomes that evolved the acoustic analysis of the voice before and after the surgical procedure, independently of the follow-up time. RESULTS: Nine out of the 517 articles met selection criteria for analysis. No standardized technique was found. CONCLUSION: There is no standardized technique for processing fat tissue for vocal fold injection. Further research is needed to point out the best available technique.

The Role of SPECT/CT Lymphoscintigraphy and Radioguided Sentinel Lymph Node Biopsy in Managing Papillary Thyroid Cancer.

IMPORTANCE: Single-photon emission computed tomography/computed tomography (SPECT/CT) and radioguided sentinel lymph node biopsy (rSLNB) are techniques that could potentially benefit surgeons and pathologists in the identification of sentinel lymph node (SLN) metastases in patients with papillary thyroid carcinoma (PTC). Evidence suggests that these novel techniques lead to substantial changes in PTC management by reducing understaging and of occult lymph node (LN) metastases and optimizing neck surgery by increasing the necessity of lateral lymphadenectomy and decreasing central lymphadenectomy. OBJECTIVES: To correlate the presence of LN metastases in PTC with clinical and pathological features using SPECT/CT and rSLNB. DESIGN, SETTING, AND PARTICIPANTS: For this prospective cohort study from June 2010 to November 2013, 42 patients with thyroid nodules suspicious for papillary carcinoma or classified as malignant on cytology examination without suspicion of lymph node metastases by clinical and ultrasound examinations were recruited from a single public medical institution. INTERVENTIONS: All 42 patients underwent preoperative lymphoscintigraphy after an ultrasound-guided peritumoral injection of Technetium Tc 99m nanocolloid. Cervical images were acquired with a SPECT/CT scanner 15 minutes after radiotracer injection. Approximately 2 hours after lymphoscintigraphy, the patients were submitted to intraoperative rSLNB using a handheld gamma probe. All SLNs identified were removed alongside with non-SLNs from the same compartment. Papillary thyroid carcinoma, SLNs and non-SLNs were submitted for histopathology and immunohistochemical analyses. RESULTS: Of the 42 patients initially enrolled, 37 were included in analysis, including 6 men and 31 women with a mean (range) age of 47 (22-83) years. Overall, T stage was as follows: T1, 23 patients (62.2%); T2, 8 patients (21.6%); and T3, 6 patients (16.2%). Sentinel lymph nodes were identified in 92% of the patients, and among these metastases were present in 17 patients (46%). The SLNs were false-negative in 3 patients. Metastases in the lateral compartment ocurred in 7 patients (18%). There was a significant association between LN metastases and tumor size (odds ratio, 1.06; 95% CI, 1.00-1.13; P = .02), with a Cohen d effect of 0.683 (medium to large effect). Overall, 17 patients (46%) with LN metastases had management changed because they were submitted to higher radioiodine ablation doses and closer clinical surveillance. CONCLUSIONS AND RELEVANCE: Radioguided SLNB is able to detect occult cervical lymph node metastases in patients with papillary thyroid carcinoma, and in 7 patients (18%) rSLNB detected lymph node metastases in the lateral compartments. The rSLNB technique lead to management change in 14 patients (37.8%).

Laryngeal Electromyography: Are the Results Reproducible?

UNLABELLED: Laryngeal electromyography (LEMG) is an auxiliary diagnostic technique that is used to study neurologic diseases that affect the larynx. This study aimed to verify the reproducibility and accordance of LEMG findings obtained by different approaches applied to the same intrinsic laryngeal muscle in patients with neurologic disorders of the larynx. STUDY DESIGN: This study is prospective, blind, randomized, and controlled. METHODS: Forty subjects (20 males and 20 females) aged between 21 and 78 years underwent LEMG of the thyroarytenoid muscles by different techniques, with a total of 120 insertion sites for analysis. The electrophysiological findings were grouped as follows: (1) equal LEMG findings; (2) different LEMG findings but in agreement on the same electromyographic pattern; and (3) different LEMG findings and in discord on the same electromyographic pattern. RESULTS: We found 5% discordance in the LEMG findings between the sites analyzed. CONCLUSIONS: LEMG is an important and useful technique, but caution must be taken to avoid misinterpretation and the wrong muscle approach.

Histologic comparison of vocal fold microflap healing with sutures and glue.

OBJECTIVES/HYPOTHESIS: Improved voice quality is the expected outcome of microphonosurgery. To this end, the complex vibratory movement of the vocal folds must be preserved. Scarring of the vocal folds may compromise vocal outcome and is one of the most difficult to treat conditions. To minimize scar formation, a consensus exists on the need for maximum preservation of the epithelium and superficial lamina propria, and minimal exposure of vocal ligament. However, the need to cover the microflap defect is controversial. The aim of this study was to compare healing characteristics of microflap technique when the microflap is left to heal by second intention, when the defect is closed with sutures, and when it is covered with glue. STUDY DESIGN: Experimental animal study. MATERIAL AND METHODS: An experimental study comparing the three techniques was carried out on 37 New Zealand rabbits. Vocal fold healing was evaluated 7, 30, and 90 days after surgical intervention. Collagen concentration, inflammatory reaction, epithelium, and lamina propria thickness were evaluated. RESULTS: Collagen concentration significantly increased in all groups. After 7 days, epithelium thickness significantly increased and lamina propria thickness was not significantly altered. At 90 days, only the suture group showed no significant alteration in epithelium thickness. After 90 days, lamina propria thickness decreased, except in the fibrin glue group. No difference was seen in the number of inflammatory cells among the techniques. CONCLUSIONS: The use of microsutures or fibrin glue to close microflap defects did not consistently improve vocal fold healing nor produce better scarring results when compared to healing by second intention.

Impact of immunohistochemistry in sentinel lymph node biopsy in head and neck cancer.

To determine the sensitivity, specificity, negative predictive value (NPV) and accuracy of hematoxylin-eosin (HE) staining compared to immunohistochemistry (IHC) in sentinel lymph node (SLN) histological analyses of head and neck squamous cell carcinoma. The Clinical prospective study was carried out at Tertiary referral university hospital. Patients with oral, lip and oropharyngeal squamous cell carcinoma undergoing elective neck dissection with clinically and radiologically negative necks were included. All patients were submitted to computer tomography scan for the evaluation of lymphatic metastases. The surgical procedure consisted of tumor resection, SLN sampling and elective neck dissection. Negative SLNs via HE were then submitted for IHC analysis of cytokeratin AE1/AE3 and step serial section (SSS). The main outcome measures were the negative predictive value of conventional HE staining techniques in the diagnosis of lymphatic metastases with the SSS/IHC analysis. Of 46 patients undergoing 63 neck procedures, 53 were SLN negative and 10 were positive on HE analysis. Using SSS/IHC analysis of these 53 negative SLNs on HE, two (3.8 %) were found to be positive. For HE, the sensitivity, specificity, NPV and accuracy were 77, 100, 94, and 95 %, respectively. With subsequent analysis with SSS/IHC, these values increased to 92, 100, 98 and 98 %, respectively. SSS/IHC is important in SLN analysis as the false negative rate decreased significantly while increasing the inherent sensitivity of the analyses.

Cephalometric evaluation of the airway space and head posture in children with normal and atypical deglutition: correlations study.

UNLABELLED: Head posture has been related to pharyngeal space, especially in the syndrome of obstructive sleep apnea (OSA) in adults. However no studies were found that evaluated the possible correlation between head posture and pharyngeal airway space measured in children with atypical swallowing. The purpose of this study was to evaluate the possible correction between head posture and the measurement of pharyngeal space on radiographs of children who were in the period of mixed dentition who demonstrated atypical swallowing and in children with normal deglutition. A retrospective clinical study, using cephalometric analysis of lateral radiographs to obtain measures of the antero-posterior dimension of the pharyngeal airway space (PAS) and the angle formed between the base of the skull and the odontoid process (CC1) between two groups: the 55 radiographs experimental group (with atypical swallowing) and 55 radiographs of the control group (normal swallowing). The Spearman Coefficient of Correlation was used to evaluate the possible relationship between PAS and CC1 was used. Results indicated a positive correlation between measures of CC1 and PAS (r = 0357) only in the control group (normal swallowing). CONCLUSIONS: There is positive correlation between head posture and measure pharyngeal airway space (PAS) in the group of normal swallowing. This correlation was not observed in the experimental group (atypical swallowing).

Cephalometric evaluation of the oropharyngeal space in children with atypical deglutition.

UNLABELLED: For several factors, not yet fully explained until now, infant deglutition may persist after changing the primary teeth and such swallowing is classified as atypical swallowing. Possible causes: finger sucking, bottle feeding, sucking the tongue and mouth breathing. There is no consensus about the etiology of atypical deglutition. OBJECTIVE: The aim of this study was to compare the oropharyngeal space in side-view radiographs of children with atypical deglutition and normal deglutition. METHODS: Retrospective study, by means of cephalometric analysis of side-view radiographs, measuring the anteroposterior distance of the lumen of the airway in two groups: 55 cephalograms from the experimental group (with atypical deglutition) and 55 side-view radiographs from the control group (normal deglutition). Measurements from the groups were compared using Mann-Whitney U test and a p value <0.05 was considered as an indication of statistical significance. RESULTS: The median in the control group was 10 mm and in the experimental group it was 7 mm, with a statistically significant difference (p <0.001). CONCLUSION: The oropharyngeal space is reduced in the group with atypical deglutition.

Cephalometric evaluation of the airway space and hyoid bone in children with atypical deglutition: correlations study / Evaluación cefalométrica del espacio de las vías respiratorias y hueso hioides en niños con deglución atípica: estudio correlacional

Although there is a close relationship between swallowing and breathing are no studies that relate to atypical swallowing radiographic anatomy of the airway space and its possible correlation with the radiographic position of the hyoid bone. The aim was to evaluate the possible correlation with the radiographic position of the hyoid bone and airway space in lateral radiographs of children with atypical deglutition. Using cephalometric analysis on lateral teleradiographs, the distances of H-MP (hyoid to mandibular plane) and H-T (hyoid to tuber) were Spearman's correlation analysis was performed with PAS (airway space) in two groups: the experimental group with atypical deglutition and the control group normal deglutition. Both groups included subjects in mixed dentition stage. Thevariable T-H had statistically significant correlation with PAS (0.0286) and the variable MP-H had significant correlation with variable PAS (0.0053). Ourresults show that advanced positive correlation of the radiographic position of the hyoid bone to the airway space only in the group of normal swallowing. The lower airway in patients with atypical swallowing, causing changes in tongue posture which leads to change in the position of the hyoid bone.

Aunque existe una estrecha relación entre la deglución y la respiración, no se dispone de estudios que relacionen la anatomía radiográfica atípica de deglución del espacio de la vía aérea y su posible correlación con la posición radiológica del hueso hioides. El objetivo fue evaluar la posible correlación de la posición radiológica del hueso hioides y las vías aéreas en radiografías laterales de niños con deglución atípica. Utilizando el análisis cefalométrico sobre telerradiografías laterales, fueron analizadas las correlaciones entre las distancias H-MP (hueso hioides al plano mandibular) y HT (hioides al tubérculo) y el PAS (espacio de la vía aérea) en dos grupos: el grupo experimental con la deglución atípica y el grupo control con deglución normal. Ambos grupos estaban en etapa de dentición mixta. Las variables HT y MP-H tuvieron una correlación estadísticamente significativa con la variable PAS, 0,0286 y 0,0053 respectivamente. Nuestros resultados muestran que la correlación positiva de la situación radiológica avanzada del hueso hioides al espacio de las vías respiratorias sólo se observa en el grupo de deglución normal. La vía respiratoria inferior en los pacientes con deglución atípica provoca cambios en la postura de la lengua, lo que conduce a un cambio en la posición del hueso hioides.

Levels and patterns of expression of hypoxia-inducible factor-1α, vascular endothelial growth factor, glucose transporter-1 and CD105 in adenoid cystic carcinomas with high-grade transformation.

AIMS: To compare the expression of proteins regulated by hypoxia between adenoid cystic carcinoma (ACC) with and without high-grade transformation (HGT). METHODS AND RESULTS: In eight ACC-HGT and 18 ACC without HGT, expression of hypoxia-inducible factor-1 (HIF-1α), vascular endothelial growth factor (VEGF), glucose transporter-1 (GLUT-1) and microvascular density (MVD) by CD105 (a hypoxia-inducible protein expressed in angiogenic endothelial cells) was determined. Expression levels of HIF-1α and VEGF as well as CD105-MVD did not differ significantly between: (i) transformed and conventional areas (TA and CA, respectively) of ACC-HGT, (ii) CA and ordinary ACC. HIF-1α was detected in 100% of cases and presented a diffuse expression pattern. No significant association was found between levels of HIF-1α expression and tumour size, metastasis and recurrence. GLUT-1 showed a prostromal expression pattern and was observed exclusively in TA (three of six cases) and in only three of 14 ACC. CONCLUSIONS: Both the absence of significant alterations in levels of expression of HIF-1α, VEGF and CD105 and the patterns of expression of HIF-1α and GLUT-1 suggest that hypoxia may not play a key role in the process of high-grade transformation of ACC. Although HIF-1α expression is a common finding in ACC, it cannot be used as a marker of tumour aggressiveness.

Avaliação cefalométrica do espaço orofaríngeo em crianças com deglutição atípica / Cephalometric evaluation of the oropharyngeal space in children with atypical deglutition

Por diversos fatores, ainda não explicados completamente até hoje, pode haver a permanência da deglutição infantil após a troca dos dentes decíduos e esta deglutição é classificada como deglutição atípica. Entre as causas possíveis: sucção do dedo, alimentação por mamadeira, sucção da língua e respiração oral. Não há consenso sobre a etiologia da deglutição atípica. OBJETIVO: O objetivo deste estudo foi comparar o espaço orofaríngeo em telerradiografias laterais de crianças com deglutição atípica e deglutição normal. MATERIAL E MÉODOS: Neste estudo clínico retrospectivo, por meio de análise cefalométrica em telerradiografias laterais foi mensurada a dimensão ântero-posterior da luz de via aérea em dois grupos: 55 telerradiografias do grupo experimental (com deglutição atípica) e 55 telerradiografias do grupo controle (deglutição normal). Tais medidas lineares foram submetidas ao teste estatístico Mann-Whitney com nível de significância de 5 por cento. RESULTADOS: A mediana no grupo controle foi de 10 mm e do grupo experimental foi de 7 mm, com diferença estatisticamente significativa (p-valor < 0,001). CONCLUSÃO: O espaço orofaríngeo está diminuído no grupo de deglutição atípica.

For several factors, not yet fully explained until now, infant deglutition may persist after changing the primary teeth and such swallowing is classified as atypical swallowing. Possible causes: finger sucking, bottle feeding, sucking the tongue and mouth breathing. There is no consensus about the etiology of atypical deglutition. OBJECTIVE: The aim of this study was to compare the oropharyngeal space in side-view radiographs of children with atypical deglutition and normal deglutition. METHODS: Retrospective study, by means of cephalometric analysis of side-view radiographs, measuring the anteroposterior distance of the lumen of the airway in two groups: 55 cephalograms from the experimental group (with atypical deglutition) and 55 side-view radiographs from the control group (normal deglutition). Measurements from the groups were compared using Mann-Whitney U test and a p value <0.05 was considered as an indication of statistical significance. RESULTS: The median in the control group was 10 mm and in the experimental group it was 7 mm, with a statistically significant difference (p <0.001). CONCLUSION: The oropharyngeal space is reduced in the group with atypical deglutition.

Radiographic position of the hyoid bone in children with atypical deglutition.

The persistence of childlike deglutition after the replacement of deciduous teeth is described as atypical deglutition. This condition has been attributed to sucking action without nutritive purposes, use of a feeding bottle, oral respiration, and anatomical abnormalities. Among the possible anatomical alterations, the hyoid bone, as a result of being the origin or the insertion of several muscles involved in swallowing, may have its position altered in cases of atypical deglutition. The aim of the present study was to evaluate the position of the hyoid bone using lateral teleradiographs, among patients with atypical deglutition during the stage of mixed dentition. Using cephalometric analysis on lateral teleradiographs, the distances of H-MP (hyoid to mandibular plane) and H-T (hyoid to tuber) were measured in two groups: the experimental group with atypical deglutition and the control group normal deglutition. Both groups included subjects in mixed dentition stage. Measurements from the groups were compared using Mann-Whitney U-test and a P-value <0.05 was considered as an indication of statistical significance. The average distance of the H-MP variable was 11.69 mm for the control group and 16.14 mm for the experimental group, with a statistically significant difference (P = 0.016). The average distance of the H-T variable was 2.26 mm for the control group and -5.89 mm for the experimental group, with significant difference (P < 0.001). There was no correlation among the variables studied. Cephalometric analysis of the H-MP distance revealed a mean difference of approximately 5 mm between the two groups, and the difference was more than 7 mm for H-T distance. Distances of H-MP and H-T based on radiographic measurements were greater in individuals with atypical deglutition than in control group and there was no correlation between these two parameters.