Value of pre- and intraoperative diagnostic methods in suspected glottic neoplasia.

PURPOSE: To evaluate the individual and combined ability of videostroboscopy (VS), high-speed digital imaging (HSDI), enhanced endoscopy (EE) and saline infusion (SI) to predict neoplasia, defined as glottic precursor lesion (GPL) or T1a glottic cancer, in patients suspected for glottic neoplasia. METHODS: A nationwide prospective cohort study of patients treated by cordectomy for suspected GPL or T1a glottic cancer from August 1st 2016 to October 31st 2018 was conducted in the five Danish University Departments of Head and Neck surgery. Sensitivity, specificity, negative and positive predictive values, and area under Receiver Operating Curves (AUC-ROC) were calculated with 95% confidence intervals with respect to the histological diagnosis. Logistic regression with an imputation model for missing data was applied. RESULTS: 261 patients aged 34-91 years participated; 79 (30.3%) with non-neoplasia (i.e., inflammation, papilloma, hyperkeratosis) and 182 (69.7%) neoplasia, hereof 95 (36.4%) with GPL and 87 (33.3%) with T1a glottic cancer. Data from 188 VS, 60 HSDI, 100 preoperative EE, 209 intraoperative EE, and 234 SI were analyzed. In the complete case analysis the AUC-ROC of each diagnostic test was low, but increased when the tests were combined and especially if the combination included EE. However, multinomial logistic regression with imputation showed significant association (p < 0.05) only between age, male gender, and perpendicular vasculature in intraoperative EE, and the endpoint neoplasia. CONCLUSIONS: Intraoperative EE was the most accurate diagnostic method in detecting neoplasia. The prediction ability of methods applied preoperatively was more limited, but improved when test modalities were combined.

Microvascular density and hypoxia-inducible factor in intraepithelial vocal fold lesions.

OBJECTIVE: The promotion of neovascularisation is a crucial aspect of carcinogenesis. The study evaluates the microvascular density (MVD) and expression of hypoxia-induced factor (HIF-1α) in hypertrophic vocal fold (VF) lesions of different histopathological states including non-dysplastic, low-grade, high-grade dysplasia and invasive glottic cancer. MATERIALS AND METHODS: Histological specimens collected from patients diagnosed and treated in a single centre with different histological grades were immunohistochemically stained with CD31, CD34 and HIF-1α. Of the total number of 77 analysed VF specimens, 20 were non-dysplastic, 20 had low-grade dysplasia, 17 high-grade dysplasia and 20 were invasive cancers. RESULTS: The highest mean value for MVD evaluated with expression of CD31 (MVD CD31) was 21.23 ± 14.46 and identified in the low-grade dysplasia group. The average MVD CD31 was 13.74 ± 5.56 and 20.11 ± 9.28 in the high-grade dysplasia and invasive cancer group, respectively. The highest MVD evaluated with CD34 (MVD CD34) was revealed for invasive cancer 35.64 ± 17.21. The MVD CD34 was higher for low-grade than in high-grade dysplasia (25.87 ± 12.30 vs 24.65 ± 15.92, respectively). The expression of HIF-1α was strong or very strong in 60% of non-dysplastic lesions, 100% of low-grade dysplasia cases, 53% of high-grade dysplasia cases and 50% of invasive cancer cases. The comparison of MVD CD31 with MVD CD34 revealed a strong positive correlation (ρ value 0.727). The comparison of both MVD CD31 and MVD CD34 with HIF-1α resulted in no linear relationship (ρ value of 0.143 and 0.165, respectively). CONCLUSION: The stage of low-grade dysplasia in intraepithelial vocal fold lesions is related to significant advancement of angiogenesis together with the highest hypoxia level.

Pericytes in the Human Vocal Fold Mucosa.

1. The human vocal fold is a vibrating tissue and vascular structures in organs which have the capacity to vibrate require a specific structure suitable for vibration. 2. The structure of the blood vessels is unique at the vocal fold edge as a vibrating tissue, where only small vessels, including arterioles, venules, and capillaries, are present. The capillaries are distributed in the superficial layer of the lamina propria (Reinke's space). 3. The blood vessels enter the vocal fold edge from the anterior or posterior end of the membranous vocal fold and run essentially parallel to the vocal fold edge. 4. Many pericytes can be seen around the capillaries in the human vocal fold mucosa. The cell bodies of the pericytes attach to capillary endothelial cells, and the branching processes encircle the capillaries and attach to the capillary endothelial cells at the tips. The processes of pericytes are in close contact with endothelial cells, sharing a common basement membrane with them. The tips of the processes form intercellular tight junctions with endothelial cells. 5. The pericytes in the vocal fold mucosa appear to provide mechanical support and protection to the capillary walls, particularly during phonation. The pericytes also appear to regulate the diameter of the capillary during and after phonation. Pericytes are also thought to be critical cells in vascular biology and angiogenesis, especially in revascularization following vocal fold tissue injury. 6. At birth, pericytes have already encircled the capillaries in the newborn vocal fold mucosa. The pericytes appear ready to provide support and protection of the blood vessels just after birth. 7. Vascular structures and their permeability are related to the specific structures and specific diseases of the human vocal fold mucosa as a vibrating tissue.

Objective quantification of the vocal fold vascular pattern: comparison of narrow band imaging and white light endoscopy.

No clinical standard procedure has yet been defined to quantify the vascular pattern of vocal folds. Subjective classification trials have shown a lot of promise. Narrow band imaging (NBI) as an endoscopic imaging tool is useful, because it shows the vascular structure clearer than white light endoscopy (WL) alone. Endoscopic images of 74 human vocal folds (NBI and WL) were semi-automatically evaluated after image processing with respect to pixels of vessels and mucosa by the software MeVisLab. The ratios of vessel/mucosa pixels were compared. Using NBI, more vocal fold vessels are visible compared with WL alone (p = 0.000). There may be a difference between the right and left vocal folds due to the handedness of the examiner (p = 0.033) without any interaction between the method (NBI/WL) and the side (right/left) (p = 0.467). MeVisLab is a suitable tool for the objective quantification of the vessel/mucosa ratio for NBI and WL endoscopic images. NBI is an appropriate endoscopic tool for examination of diseases of vocal folds with changes in the vascular pattern. There is evidence that the handedness of the examiner may have an influence on the quality of the examination between the right and left vocal folds.

Proposal for a descriptive guideline of vascular changes in lesions of the vocal folds by the committee on endoscopic laryngeal imaging of the European Laryngological Society.

In the last decades new endoscopic tools have been developed to improve the diagnostic work-up of vocal fold lesions in addition to normal laryngoscopy, i.e., contact endoscopy, autofluorescence, narrow band imaging and others. Better contrasted and high definition images offer more details of the epithelial and superficial vascular structure of the vocal folds. Following these developments, particular vascular patterns come into focus during laryngoscopy. The present work aims at a systematic pathogenic description of superficial vascular changes of the vocal folds. Additionally, new nomenclature on vascular lesions of the vocal folds will be presented to harmonize the different terms in the literature. Superficial vascular changes can be divided into longitudinal and perpendicular. Unlike longitudinal vascular lesions, e.g., ectasia, meander and change of direction, perpendicular vascular lesions are characterized by different types of vascular loops. They are primarily observed in recurrent respiratory papillomatosis, and in pre-cancerous and cancerous lesions of the vocal folds. These vascular characteristics play a significant role in the differential diagnosis. Among different parameters, e.g., epithelial changes, increase of volume, stiffness of the vocal fold, vascular lesions play an increasing role in the diagnosis of pre- and cancerous lesions.

[Evaluation of a Classification Model of Horizontal Vascular Lesions of the Vocal Folds]. / Evaluation eines Klassifikationsmodells horizontaler Gefäßveränderungen der Stimmlippen.

OBJECTIVE: There exists no valid classification of beginning vascular changes of the vocal folds. We tested an own classification model of visible beginning horizontal vascular changes. MATERIAL AND METHODS: 168 indirect endoscopic pictures (84 white light=WL and 84 Narrow Band Imaging=NBI) of vocal folds were presented to 3 different consultants for classification (graduation normal, slight, moderately, high-grade belonged to the vascular features ectasia, meander, convolute, frequency of the vessels, ramification, change in direction). The self-confidence was declared by the consultants with a numeric rating scale. RESULTS: A classification of beginning vascular changes of the vocal folds is possible, especially of ectasia, meander, convolute, frequency of the vessels, ramification, change in direction (p<0.0001). Significantly more vascular lesions can be detected by NBI than with white light endoscopy alone (p<0.0001). There are no significant differences (p=0.3529) in self-confidence of the classification. But it differs between the consultants highly significant (p<0.0001). The inexperienced classifier shows the highest growth in the learning curve. The intrarater- and interrater-variability differs only slightly between WL and NBI. CONCLUSIONS: Beginning horizontal changes of vocal fold vessels can be classified. Endoscopic NBI-pictures of the vocal folds demonstrate the beginning of vascular changes better compared to endoscopic white light pictures alone. The familiarity and expertise with the classification model and the endoscopic imaging technique affect the self-confidence of the evaluation.

[Vascular Lesions of Vocal Folds - Part 2: Perpendicular Vascular Lesions]. / Gefäßveränderungen der Stimmlippen - Teil 2: Perpendikuläre Gefäßveränderungen.

The present work aims at a systematic pathogenetic description of perpendicular vascular changes in the vocal folds. Unlike longitudinal vascular changes, like ectasia and meander, perpendicular vascular changes can be observed in bening lesions. They predominantly occur as typical vascular loops in exophytic lesions, especially in recurrent respiratory papillomatosis (RRP), pre-cancerous and cancerous diseases of the larynx and vocal folds. Neoangiogenesis is caused by an epithelial growth stimulus in the early phase of cancerous genesis. In RRP the VVC impress by a single, long vessel loop with a narrow angle turning point in the each single papilla of the papilloma. In pre- and cancerous lesions the vascular loop is located directly underneath the epithelium. During progressive tumor growth, vascular loops develop an increasingly irregular, convoluted, spirally shape. The arrangement of the vascular loops is primarily still symmetrical. In the preliminary stage of tumor development occurs by neoangiogenesis to a microvascular compression. In advanced vocal fold carcinoma the regular vascular vocal fold structure is destroyed. The various stages of tumor growth are also characterized by typical primary epithelial and secondary connective tissue changes. The characteristic triad of vascular, epithelial and connective tissue changes therefore plays an important role in differential diagnosis.

Dysphonia and vocal fold telangiectasia in hereditary hemorrhagic telangiectasia.

OBJECTIVE: This case report is the first documentation of dysphonia and vocal fold telangiectasia as a complication of hereditary hemorrhagic telangiectasia (HHT). METHODS: Case report of a 40-year-old man with HHT presenting with 2 years of worsening hoarseness. RESULTS: Hoarseness corresponded with a period of anticoagulation. Endoscopy revealed vocal fold scarring, vocal fold telangiectasias, and plica ventricular is suggestive of previous submucosal vocal fold hemorrhage and subsequent counterproductive compensation with ventricular phonation. CONCLUSION: Hereditary hemorrhagic telangiectasia may present as dysphonia with vocal fold telangiectasias and place patients at risk of vocal fold hemorrhage.

The effect of different angiolytic lasers on resolution of subepithelial mucosal hematoma in an animal model.

OBJECTIVE: Vocal fold hematoma is traditionally managed with a period of voice rest, in the order of weeks, to allow natural resolution. This study is designed to examine the efficacy and safety of a number of hemoglobin-avid (vascular) lasers when used in the setting of acute vocal fold hematoma. METHODS: Venous blood drawn from 4 white rabbits was used to create an array of subepithelial hematomas in the buccal cavities of each animal. Laser energy from I of 3 different lasers (532-nm pulsed potassium titanyl phosphate [KTP], 532-nm diode KTP, and 940-nm diode laser) was applied to each of the test hematomas at varying energy levels. Hematoma sites were photographed at days 0, 1, 5, 7, 9, and 12. Two animals were sacrificed on day 7 and the remainder on day 12. Histological evaluation of collateral tissue damage and residual hematoma was performed on biopsy specimens. RESULTS: Macroscopic and microscopic ulceration at laser-treated sites was mostly resolved by day 7. Inflammatory cell infiltrate was present in laser-treated and hematoma-only sites. Laser-treated samples showed alterations in vascularity. CONCLUSION: Hemoglobin-avid lasers may be beneficial in accelerating subepithelial hematoma resolution with a favorable tissue damage profile.

[Vascular lesions of vocal folds--part 1: horizontal vascular lesions]. / Gefäßveränderungen der Stimmlippen - Teil 1: Horizontale Gefäßveränderungen.

BACKGROUND: In recent decades, the endoscopic methods and technologies for laryngeal examination have improved so much that not only epithelial changes, but also vascular changes are recognizable at earlier stages. When comparing newer and older literature, the associated increasingly differentiated descriptions of such visible vascular changes of the vocal folds lead to terminological blurring and shifts of meaning. This complicates the technical-scientific discourse. The aim of the present work is a theoretical and conceptual clarification of early vascular changes of vocal folds. RESULTS: Horizontal changes of benigne vascular diseases, e. g. vessel ectasia, meander, increasing number and branching of vessels, change of direction may develop in to manifest vascular lesions, like varicosis, polyps and in case of ruptures to haemorrhages of vocal folds. These beginning and reversible vascular changes, when early detected and discussed basing on etiological knowledge, may lead to more differentiated prognostic statements and adequate therapeutic decisions, e. g. phonosurgery, functional voice therapy, voice hygiene and voice rest. Vertical vascular changes, like vessel loops, occur primarily in laryngeal papilloma, pre-cancerous and cancerous changes of the vocal folds. Already in small cancerous lesions of the vocal folds the vascular architecture is completely destroyed.

Surgical Outcome of Potassium-Titanyl-Phosphate (KTP) Laser Photocoagulation for Vocal Fold Vascular Lesions.

INTRODUCTION: Laser technology is used in microscopic direct laryngeal surgery for a variety of indications. Lasers are categorized broadly as photoangiolytic or cutting/ablating lasers, based on the chromophores that absorb their energy. Photoangiolytic lasers such as the 532 nm Potassium-Titanyl-Phosphate (KTP) laser are absorbed selectively by the chromophore hemoglobin, facilitating controlled intravascular coagulation, with preservation of the overlying epithelium and adjacent tissue. Efficacy of the KTP laser has been demonstrated for incision, coagulation, and ablation in vocal fold (VF) surgery. OBJECTIVE: The purpose of the present study was to examine surgical outcomes following KTP laser photocoagulation for the management of VF vascular lesions. METHODS: Adult patients with sufficient data who had undergone KTP laser photocoagulation in the operating room for the treatment of VF vascular lesions were included in this retrospective study. Strobovideolaryngoscopy (SVL) video footage from all preoperative visits and all available postoperative visits was compiled and de-identified. Patients were followed up at days 1-7, 8-14, 30-60, and greater than 60 days after surgery. Three blinded physician evaluators reviewed and evaluated the SVL footage independently for postoperative outcome parameters. Postoperative SVL video footage was evaluated on a 5-point scale for surgical success (surgical objective score; 1 = failure and 5 = complete success). The average surgical objective score was 4.36, 4.04, 4.25, and 4.46 (out of 5) at postoperative visits 1-4, respectively. RESULTS: There were 60 cases (19 male and 41 female) included in the retrospective cohort. The average age was 42.42 ± 15.51 (range = 18-74). Fifty-one-point six seven percent of subjects were professional voice users (singers, teachers, public speakers, and others). All subjects were diagnosed preoperatively with VF vascular malformations and had undergone pulsed KTP laser photocoagulation. There were 40 bilateral cases and 20 unilateral cases, for a total of 100 VFs included in the study. Vascular malformation recurrence was identified in 3.00% and 10.00% of subjects at the third and fourth postoperative visits, retrospectively. The formation of new vascular malformations was identified in 0.00%, 1.00%, 6.00%, and 7.00% of subjects at postoperative visits 1-4, respectively. CONCLUSION: KTP laser photocoagulation is highly effective for the management of vocal fold vascular lesions. Presence of hemorrhage or edema does not affect the long-term surgical outcome. In relatively few cases, vascular lesion recurrence or formation of new vascular lesions may occur.

Microstructure of the vocal fold in elderly humans.

Significant changes in the voice occur after the age of 50 years. Changes in the structure of the vocal fold (VF) can interfere with the voice. The aim of this study is to investigate the structure of the VF of elderly people that may contribute to the tendency of the human voice to deteriorate. Larynges were obtained from eight embalmed cadavers aged 72-98 years. The middle portion of each vocal fold was removed and placed in 4% buffered formalin. Tissue blocks were then processed and embedded in wax. Four to six micron coronal sections were cut and stained with Haematoxylin and Eosin (H&E), Masson's Trichrome (MTS), Elastin van Gieson (EVG), Herovici (HERO), picrosirius and CD31 immunohistochemical marker in order to study the collagen fibers, elastic fibers and microvasculature of the VF. The maturity of collagen fibers within the VF were noted to increase from the superficial to the deep layer of the lamina propria (LP). Contrary to current literature, the amount of elastic fibers was sparse in the superficial layer of the LP in the vocal tissue of elderly cadavers. Numerous cross-sectioned blood vessels were seen in the lamina propria near the free edge, and near the superior and inferior surfaces of the VF. The presence of lymphatic vessels was confirmed in the VF of elderly subjects. This study revealed that the collagenous component of the deep layer of the VF LP was made up of mature fibers whilst immature collagen fibers made up the superficial layer of the LP. There was a notable scarcity of elastic fibers in the superficial layer of the LP. Lymphatics were seen and were orientated differently in the geriatric vocal folds.

Effects of 445-nm Laser on Vessels of Chick Chorioallantoic Membrane with Implications to Microlaryngeal Laser Surgery.

OBJECTIVE: Previous research has shown that effective application of angiolytic lasers in microlaryngeal surgery is determined by wavelength, pulse width (PW), and fluence. Recently, a 445-nm (blue) laser (BL) has been developed with a potentially greater hemoglobin absorption than previous lasers. The chick chorioallantoic membrane (CAM) represents a suitable model for testing various settings to find out the most optimal settings of this laser. This study used the CAM model to examine whether successful photoangiolytic effects could be obtained using BL. METHODS: Seven hundred and ninety three third-order vascular segments of viable CAM were irradiated using BL via 400-µm diameter fiber, 1 pulse/second, with PW and power varied systematically at standardized fiber-to-vessel distances of 1 and 3 mm. Outcome measures including vessel ablation rate (AR), rupture rate (RR), and visible tissue effects were analyzed using Chi-square test. RESULTS: Energy levels of 400, 540, and 600 mJ (per pulse) were most effective for vessel ablation. A working distance of 3 mm resulted in higher ablation and less vessel rupture compared with 1 mm at these optimal energy levels. At 3 mm, a longer PW resulted in higher AR. At 1 mm, AR increased with shorter PW and higher power. The 1-mm working distance resulted in lower tissue effects than 3 mm. CONCLUSION: Findings in this study showed that BL was effective in vessel ablation using relevant combination of working distance, PW, and energy levels. To obtain high AR, longer working distance plus longer PW was required and if working distance was reduced, shorter PW should be set. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E1950-E1956, 2021.

Narrow band imaging and high definition television in the assessment of laryngeal cancer: a prospective study on 279 patients.

Narrow band imaging (NBI) is an optical technique in which a filtered light reveals superficial carcinomas in view of their neoangiogenic pattern. The accuracy of NBI is implemented by combining it with a high definition television (HDTV) camera. The aim of this study was to prospectively evaluate the diagnostic gain of NBI and HDTV in the assessment of laryngeal squamous cell carcinoma (LSCC). Between April 2007 and December 2008, we analyzed by NBI with or without HDTV 279 patients divided in two groups: Group A included 96 patients affected by LSCC and Group B included 183 subjects under follow-up after treatment for the same disease. Overall, 50 of 279 patients (18%) showed "suspicious" NBI findings histologically confirmed as neoplastic. The sensitivity, specificity, accuracy, positive and negative predictive rates of flexible NBI, HDTV with white light, and HDTV with NBI in both groups confirmed the value of these two technologies. In the pre- and intraoperative settings, NBI with or without HDTV provided better definition of tumor staging and surgical margins. NBI has also a role in the postoperative setting, due to its ability in early detection of persistences, recurrences, and metachronous tumors.

Visible Vessels of Vocal Folds: Can they have a Diagnostic Role?

BACKGROUND: Challenges in visual identification of laryngeal disorders lead researchers to investigate new opportunities to help clinical examination. This paper presents an efficient and simple method which extracts and assesses blood vessels on vocal fold tissue in order to serve medical diagnosis. METHODS: The proposed vessel segmentation approach has been designed in order to overcome difficulties raised by design specifications of videolaryngostroboscopy and anatomic structure of vocal fold vasculature. The limited number of medical studies on vocal fold vasculature point out that the direction of blood vessels and amount of vasculature are discriminative features for vocal fold disorders. Therefore, we extracted the features of vessels on the basis of these studies. We represent vessels as vascular vectors and suggest a vector field based measurement that quantifies the orientation pattern of blood vessels towards vocal fold pathologies. RESULTS: In order to demonstrate the relationship between vessel structure and vocal fold disorders, we performed classification of vocal fold disorders by using only vessel features. A binary tree of Support Vector Machine (SVM) has been exploited for classification. Average recall of proposed vessel extraction method was calculated as 0.82 while healthy, sulcus vocalis, laryngitis classification accuracy of 0.75 was achieved. CONCLUSION: Obtained success rates showed the efficiency of vocal fold vessels in serving as an indicator of laryngeal diseases.

Vocal nodules and edema may be due to vibration-induced rises in capillary pressure.

HYPOTHESIS: Vocal fold vibration may physically raise intravascular pressure to levels high enough to damage capillaries and result in leakage of erythrocytes. This type of injury is commonly seen in benign vocal fold lesions and is not well explained. STUDY DESIGN: Theoretical, retrospective. METHODS: The relationship of intravascular pressure to vibration frequency and amplitude is derived and confirmed with a physical blood vessel model, then applied to published human measurements to estimate human intravascular pressures. RESULTS: Vocal fold intravascular pressure is predicted to have a quadratic dependence on both frequency and amplitude. During speaking, the pressure may rise to over 20 cmH2O, and may reach levels far higher for screaming and singing. Such pressure magnitudes are known to trigger inflammatory cascades and can lead to fluid leakage. They also have the potential for pharmacologic control with beta-agonists. CONCLUSIONS: Intravascular pressure likely rises significantly during vocal fold vibration and may lead to the type of injury seen in benign vocal fold lesions. The results support voice therapy aimed at reducing vibratory amplitude. More vibratory amplitude measurements need to be performed in a wider range of subjects before the full range of human vocal fold vascular pressures can be estimated.

Permeability and Weibel-Palade Bodies of the Blood Vessels in the Human Vocal Fold Mucosa.

OBJECTIVES: Transendothelial exchange and permeability of the capillaries in Reinke space (the superficial layer of the lamina propria) of the vocal fold mucosa affect physiological and pathological conditions of the human vocal fold mucosa. The mechanism of permeability and Weibel-Palade bodies of the blood vessels in the human vocal fold mucosa were investigated using electron microscopy. STUDY DESIGN: Histologic analysis of the human vocal fold. METHODS: Six normal human vocal folds (three adults and three newborns) obtained from autopsy cases and three human vocal folds with Reinke edema from surgical specimens were investigated under transmission electron microscopy. RESULTS: There were three possible capillary wall transport systems related to the permeability of the blood vessels in the vocal fold mucosa: 1) Fenestra transport, plasma exuded from the capillaries into surrounding tissue via the fenestration with or without a diaphragm; 2) vesicular transport (transcellular transport via vesicles), the use of vesicles to ferry fluid and solutes across endothelial cells; and 3) junctional transport (intercellular transport), molecules passed through intercellular gaps between endothelial cells. Weibel-Palade bodies were present in the cytoplasm of endothelial cells both in adults and newborns. They were present in high numbers in the cytoplasm of endothelial cells, with intercellular transport in the vocal folds with Reinke edema. CONCLUSION: There were three types of mechanisms for the permeability of the blood vessels in the human vocal fold mucosa. Some physiologically active substances, such as histamine produced by Weibel-Palade bodies, may adversely influence the permeability of the blood vessels. LEVEL OF EVIDENCE: NA. Laryngoscope, 2588-2592, 2018.

Menstrual Cycle, Vocal Performance, and Laryngeal Vascular Appearance: An Observational Study on 17 Subjects.

OBJECTIVE: To assess the anatomical and functional features of the vocal folds during different phases of the female menstrual cycle. METHODS: An observational study of 17 healthy fertile female volunteers not using hormonal contraception was carried out. Each volunteer underwent two examinations: first, during the early days of the menstrual cycle when progesterone levels are low (p-depletion), and second, during premenstruation when progesterone levels are high (p-peak). The workup included blood hormone levels, Voice Handicap Index, acoustic analysis, rigid telescopy, stroboscopy, and narrow band imaging. The videos were evaluated by blinded observers. RESULTS: The participants' mean age was 31.7 ± 5.6 (range 23-43). Progesterone levels were 13- to 45-fold higher in p-peak relative to p-depletion. No significant differences were detected in Voice Handicap Index scores, stroboscopic reports, or acoustic analysis between p-peak and p-depletion examinations. Analyzing the rigid telescopy and narrow band imaging videos, the observers tended to estimate the different laryngeal subsites more vascularized during the p-peak examination. Moreover, this tendency was significantly correlated with blood progesterone levels during the p-depletion examinations; the lower the blood progesterone levels were during p-depletion, the higher the probability for the observers to estimate the p-peak examinations more vascularized (P value = 0.024). CONCLUSIONS: Alterations in laryngeal vascular characteristics are evident throughout the menstrual cycle and may suggest increased congestion during premenstrual days. Variations in progesterone levels during the menstrual cycle correlate with laryngeal vascular changes. Hormone-related alterations in vocal folds' vascularity may have a role in the variability of vocal performance in certain women.

Effects of 532 nm pulsed-KTP laser parameters on vessel ablation in the avian chorioallantoic membrane: implications for vocal fold mucosa.

OBJECTIVES: Selective vascular ablation (photoangiolysis) using pulsed lasers that target hemoglobin is an effective treatment strategy for many vocal fold lesions. However, vessel rupture with extravasation of blood reduces selectivity for vessels, which is frequently observed with the 0.45-ms, 585-nm pulsed dye laser. Previous studies have shown that vessel rupture is the result of vaporization of blood, an event that varies with laser pulse width and pulse fluence (energy per unit area). Clinical observations using a 532-nm wavelength pulsed potassium-titanyl-phosphate (KTP) laser revealed less laser-induced hemorrhage than the pulsed dye laser. This study investigated settings for the pulsed KTP laser to achieve selective vessel destruction without rupture using the avian chorioallantoic membrane under conditions similar to flexible laryngoscopic delivery of the laser in clinical practice. STUDY DESIGN: The chick chorioallantoic membrane offers convenient access to many small blood vessels similar in size to those targeted in human vocal fold. Using a 532-nm pulsed KTP laser, pulse width, pulse energy, and working distance from the optical delivery fiber were varied to assess influence on the ability to achieve vessel coagulation without vessel wall rupture. METHODS: Third-order vessels (n = 135) were irradiated: Energy (471-550 mJ), pulse width (10, 15, 30 ms), and fiber-to-tissue distance (1 mm, 3 mm) were varied systematically. RESULTS: Selective vessel destruction without vessel wall rupture was more often achieved by increasing pulse width, increasing the fiber-to-tissue distance, and decreasing energy. Vessel destruction without rupture was consistently achieved using 15- or 30-ms pulses with a fiber-to-tissue distance of 3 mm (pulse fluence of 13-16 J/cm). CONCLUSIONS: This study substantiates our clinical observation that a 532-nm pulsed KTP laser was effective for ablating microcirculation while minimizing vessel wall rupture and hemorrhage.