The Effects of Photobiomodulation on Vocal Fold Wound Healing: In Vivo and In Vitro Studies.

Background: Photobiomodulation (PBM) is increasingly used in dermatology and dentistry due to its benefit of promoting wound healing and relieving pain; however, there is no corresponding research report on the application of PBM to vocal fold wound healing. Objective: To assess the potential wound-healing effects of PBM on the vocal folds via in vivo and in vitro experiments. Materials and methods: In in vitro study, vocal fold fibroblasts (VFFs) were irradiated under a diode laser with wavelength of 635 nm at energy density of 8 J/cm2. The Cell Counting Kit-8 (CCK-8) assay was used to study the viability of VFFs, and the gene expressions of COL1A2, COL3A1, IL-6, HAS2, and COX-2 were investigated by real-time polymerase chain reaction (RT-PCR). In in vivo study, 15 rabbits were used. Lamina propria of the left vocal folds of 12 rabbits was unilaterally stripped, and 6 of them were treated with PBM. The remaining three rabbits served as normal controls. After 3 months, all animals were sacrificed to obtain histological results. We used laryngoscope to record images of the healing phase. Results: Irradiation with energy density of 8 J/cm2 resulted in a 2.8% increase in cell proliferation (p < 0.05). However, the difference between the experimental and the control group became larger after 48 and 72 h of subsequent irradiation. RT-PCR results showed that the expression of COL1A2, COL3A1, and HAS2 was higher, and the expression of IL-6 and COX-2 was lower. Histological examination showed that, compared with the injury group, hyaluronic acid (HA) increased significantly, collagen deposition decreased, and the configuration of collagen was more organized after PBM treatment. Conclusions: PBM can inhibit inflammatory reaction and promote the secretion of HA to decrease the deposition of collagen and regenerate vocal fold tissue without scar.

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.

The utility of the potassium titanyl phosphate laser in modulating vocal fold scar in a rat model.

OBJECTIVES/HYPOTHESIS: We hypothesize that the KTP laser has the potential to augment wound healing in a rat model, and this modality may serve as a therapeutic tool for the management of vocal fold fibrosis. STUDY DESIGN: Prospective, laboratory animal study. METHODS: Rats were subjected to either vocal fold injury ± KTP laser treatment at low energy to simulate clinically relevant endpoints. In addition, cohorts were subjected to therapeutic KTP laser alone. Endpoints included the analyses of gene expression data related to the acute inflammatory response and extracellular matrix deposition and organization. RESULTS: Therapeutic KTP treatment was associated with an additive effect on inflammatory gene expression in the context of the injured rat vocal fold mucosa. A similar additive effect was observed for matrix metalloproteinase gene expression, similar to data previously reported in the dermatology literature. However, histologically, the KTP had little effect on established vocal fold fibrosis. CONCLUSIONS: These data are the first to attempt to provide mechanistic insight into the clinical utility of angiolytic lasers for vocal fold scar. Similar to previous data obtained in the skin, it appears that these effects are mediated by MMPs.

Larynx preservation for patients with locally advanced laryngeal cancer.

A 53-year-old man presented with a 6-month history of mild hoarseness, with no associated pain, dysphagia, or stridor. At nasoendoscopy, a lesion was detected involving the whole length of the left vocal cord, with abnormal mucosa also seen in the right ventricle (Fig 1). The left vocal cord movement was impaired. There were no palpable neck nodes. Biopsy under anesthesia revealed moderately differentiated squamous cell carcinoma. He was a current smoker of 30 cigarettes per day (45 pack-year smoking history), and he consumed four standard drinks of alcohol per day. His Eastern Cooperative Oncology Group performance status was 1, and he had no significant comorbidities. Radiologic review of his outside computed tomography scan noted that it was of poor quality, and a magnetic resonance imaging scan was recommended, which showed low-volume T4a disease based on focal thyroid cartilage penetration (Fig 2). A positron emission tomography (PET) scan revealed no evidence of nodal or distant metastasis.

Effect of the 532nm pulsed KTP laser in the treatment of Reinke's edema.

OBJECTIVES/HYPOTHESIS: To evaluate the effect and safety of the 532nm Pulsed Potassium-Titanyl-Phosphate (KTP) laser in the office-based treatment of patients with Reinke's edema using objective and subjective scaled outcome measures. STUDY DESIGN: Case Series. SETTING: Tertiary hospital center. SUBJECTS: Seven adult females undergoing in-office KTP laser treatment for Reinke's edema. METHODS: Participants were studied pre- and posttreatment. Vocal function was evaluated by objective aerodynamic and acoustic analysis. Subjective changes were evaluated using the GRBAS scale, Voice Handicap Index, and videostroboscopy. Histologic effects of the laser were investigated by comparing one patient treated with laser one year prior to excision, one treated with laser just prior to excision, and one control patient who underwent excision without prior laser treatment. RESULTS: At an average postoperative follow up of 17.8 weeks (range 5-78), maximum phonation time trended toward improvement. The median VHI score decreased from 37 to 26 (p=0.150). There was a reduction in each component of the GRBAS scoring and the median fundamental frequency increased from 162 to 186 (p=0.625). Stroboscopic findings demonstrated an intact posttreatment mucosal wave. Histologic comparison of the tissue effects of laser in three patients demonstrated changes in vocal fold vascularity but no acute or long-term damage to the overlying epithelium. CONCLUSION: Objective and subjective scaled measures suggest that treatment of Reinke's edema in the office with a 532nm KTP laser may result in improved voice. It appears safe with histologic preservation of the vocal fold vibratory epithelium and persistence of mucosal wave.

Pulse dye and other laser treatments for vocal scar.

PURPOSE OF REVIEW: Vocal fold scar is a challenging clinical problem, resulting in a spectrum of voice-related complaints. While there are a variety of treatment options available, it is rare to obtain outcomes similar to the perfectly normal voice. The pulsed dye and other lasers are an emerging treatment option for cutaneous scar and have shown promise for the treatment of vocal fold scarring. The purpose of this review is to summarize the theory, and describe clinical outcomes from both cutaneous and vocal fold scarring treated with lasers. RECENT FINDINGS: There are a growing number of papers in the literature substantiating the use of pulsed dye and other lasers used to treat cutaneous scars. Some experimental models describe potential mechanisms of laser effect, which include the development of a sub-basement membrane cleavage plane, as well as up-regulation of proteins which may actively modulate continued fibrosis. One prospective pilot study of 11 patients with vocal fold scarring treated with the pulsed dye laser has also shown statistically significant improvement in subjective and objective voice measures, as well as laryngeal stroboscopy findings after treatment. SUMMARY: The pulsed dye and other lasers have shown effectiveness and potential in treating cutaneous and vocal scarring.

Pulsed dye laser-induced inflammatory response and extracellular matrix turnover in rat vocal folds and vocal fold fibroblasts.

BACKGROUND AND OBJECTIVES: Disruption of the vocal fold extracellular matrix (ECM) can induce a profound and refractory dysphonia. Pulsed dye laser (PDL) irradiation has shown early promise as a treatment modality for disordered ECM in patients with chronic vocal fold scar; however, there are limited data addressing the mechanism by which this laser energy might induce cellular and extracellular changes in vocal fold tissues. In this study, we examined the inflammatory and ECM modulating effects of PDL irradiation on normal vocal fold tissues and cultured vocal fold fibroblasts (VFFs). STUDY DESIGN/MATERIALS AND METHODS: We evaluated the effects of 585 nm PDL irradiation on inflammatory cytokine and collagen/collagenase gene transcription in normal rat vocal folds in vivo (3-168 hours following delivery of approximately 39.46 J/cm(2) fluence) and VFFs in vitro (3-72 hours following delivery of 4.82 or 9.64 J/cm(2) fluence). We also examined morphological vocal fold tissue changes 3 hours, 1 week, and 1 month post-irradiation. RESULTS: PDL irradiation altered inflammatory cytokine and procollagen/collagenase expression at the transcript level, both in vitro and in vivo. Additionally, PDL irradiation induced an inflammatory repair process in vivo that was completed by 1 month with preservation of normal tissue morphology. CONCLUSIONS: PDL irradiation can modulate ECM turnover in phenotypically normal vocal folds. Additional work is required to determine if these findings extend to disordered ECM, such as is seen in vocal fold scar. Lasers Surg. Med. 41:585-594, 2009. (c) 2009 Wiley-Liss, Inc.

The use of the pulse dye laser in the treatment of vocal fold scar: a preliminary study.

OBJECTIVES/HYPOTHESIS: Dysphonia due to vocal fold scarring is a challenging problem to the laryngologist. Vocal fold scarring after radiation, phonosurgery, and laser cordectomy causes moderate to severe dysphonia. Surgical attempts at scar removal and voice restoration have limited success. Pulsed dye laser (PDL) treatment has been shown to be effective in softening scarred skin by serial office treatments. The objective of this preliminary study was to evaluate the use of the PDL in the management of patients with established vocal fold scar. STUDY DESIGN: This is an Institutional Review Board-approved prospective study involving 11 patients. The causes of scarring were phonosurgery (n = 7), radiation (n = 2), and partial laryngectomy (n = 2). The subjects were evaluated pre- and postprocedure using the voice handicap index (VHI), laryngeal stroboscopy rating, voice recordings with acoustic and aerodynamic analysis, and self-evaluation. METHODS: The PDL was applied with the fiberoptic delivery system by three treatments at 1-month intervals in the office setting. Each treatment endpoint was blanching of the treatment site. RESULTS: : There were three women and eight men in our study group. Ten of 11 patients subjectively improved by self-rating. No patients were worse. VHI improved from 48.44 pretreatment to 35.55 at 6 months posttreatment (P < .05). The jitter at 6 months improved from 2.230% to 1.654% (P = NS) and shimmer improved from 3.679% to 3.196% (P = NS). The noise to harmonic ration improved from 0.1428 to 0.1316 (P = NS). The mean phonotory flow went from 0.177 to 0.254 L/S (P < .05). Three raters blinded to treatment sequence rated the posttreatment stroboscopy findings as better than pretreatment in a forced choice comparison, kappa score 0.903. CONCLUSION: PDL is a safe and potentially promising treatment for established vocal fold scar. Subjectively, no patients were worse and 10 of 11 patients reported improved voice. There was improvement in the VHI, acoustic measures of shimmer and jitter, and stroboscopy findings. Further study using this approach in a larger cohort seems to be warranted.

Retrospective analysis: concurrent chemoradiotherapy using protracted continuous infusion of low-dose cisplatin and 5-fluorouracil for T2N0 glottic cancer.

PURPOSE: Treatment with conventional radiotherapy alone for local control of T2 glottic cancer (T2GC) is insufficient. To improve local control of T2GC, we have simultaneously administered continuous intravenous infusions of low-dose cisplatin and 5-fluorouracil (5-FU) in combination with irradiation. MATERIALS AND METHODS: We performed this combination therapy in a total of 11 consecutive patients with previously untreated invasive squamous cell carcinoma (T2GC). Cisplatin was administered at 4 mg/m2/day and 5-FU at 200 mg/m2/day for 120 h, except during weekends, beginning on the day irradiation with a once-daily fraction at 2 Gy was started. RESULTS: An initial local control rate of the primary tumor was achieved in 10 of the 11 patients (91%), and ultimate laryngeal preservation by cordectomy was achieved in all cases. Regarding adverse reactions, grade 3 or 4 hemotoxicity did not develop in any of the patients. Grade 3 laryngitis was observed in four patients (36%), but none of these patients required interruption of treatment owing to acute laryngeal reactions. CONCLUSION: Instead of radiotherapy alone, this combination chemoradiotherapy is suggested with the possibility of improving local control of T2GCs.