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The utility of the potassium titanyl phosphate (KTP) laser in modulating vocal fold scar in a rat model.
The Laryngoscope
Abstract
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.
Prospective, laboratory animal study.
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.
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.
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.
NA. Laryngoscope, 2013.
... As the same with previously obtained perspectives, it appears that the positive effect of angiolytic lasers are mediated by matrix metalloproteinase. The authors demonstrated that potassium-titanyl-phosphate (KTP) laser has the potential to augment wound healing in a rat VF injury model and utility of KTP laser may serve as a therapeutic tool for the management of VF fibrosis [131]. Recently, Zhang et al. demonstrated that KTP laser and Yttrium-Aluminum-Garnet (Nd:YAG) laser had positive effect in VF scars. ...
... of angiolytic lasers are mediated by matrix metalloproteinase. The authors demonstrated that potassium-titanyl-phosphate (KTP) laser has the potential to augment wound healing in a rat VF injury model and utility of KTP laser may serve as a therapeutic tool for the management of VF fibrosis [131]. Recently, Zhang et al. demonstrated that KTP laser and Yttrium-Aluminum-Garnet (Nd:YAG) laser had positive effect in VF scars. ...
Communication by voice depends on symmetrical vibrations within the vocal folds (VFs) and is indispensable for various occupations. VF scarring is one of the main reasons for permanent dysphonia and results from injury to the unique layered structure of the VFs. The increased collagen and decreased hyaluronic acid within VF scars lead to a loss of pliability of the VFs and significantly decreases their capacity to vibrate. As there is currently no definitive treatment for VF scarring, regenerative medicine and tissue engineering have become increasingly important research areas within otolaryngology. Several recent reviews have described the problem of VF scarring and various possible solutions, including tissue engineered cells and tissues, biomaterial implants, stem cells, growth factors, anti-inflammatory cytokines antifibrotic agents. Despite considerable research progress, these technical advances have not been established as routine clinical procedures. This review focuses on emerging techniques for restoring VF pliability using various approaches. We discuss our studies on interactions among adipose-derived stem/stromal cells, antifibrotic agents, and VF fibroblasts using an in vitro model. We also identify some obstacles to advances in research.
... In brief, these include transoral laryngeal surgery under flexible laryngo-videostroboscopy, 10 transnasal vocal fold polyppectomy, 11 steroid injection using various approaches, 12-16 and last but not least laser therapy. [17][18][19][20][21][22] Various types of laser have been used for office-based laryngeal surgery. In patients with vocal fold polyps, the emphasis has been on photoangiolytic lasers given their great affinity to hemoglobin. ...
... In patients with vocal fold polyps, the emphasis has been on photoangiolytic lasers given their great affinity to hemoglobin. [17][18][19][20][21][22] There are only a few reports in the literature on the application of thulium laser in treatment of vocal fold pathology in an office-based setting. [23][24][25] Thulium laser is a "diode-pumped solid state laser" with a wavelength of 2013 nm and a depth of penetration that does not exceed 0.2 mm. ...
Purpose:
To report the voice outcome measures of thulium laser therapy as an office procedure in patients with vocal fold polyps.
Method:
This is a retrospective chart review of all patients with vocal fold polyps who underwent office-based thulium laser treatment between November 2016 and December 2017. Demographic data were collected. Objective voice outcome measures included extent of resolution, type of closure, and mucosal wave characteristics. Also, subjective outcome measures were reported, namely, Voice Handicap Index-10.
Results:
A total of 20 patients were enrolled with a mean age of 50.95 ± 14.70 years. All patients had unilateral vocal fold polyps except for one who had bilateral polyps. Out of the 20 patients, 16 had complete regression of disease and 4 had partial regression. The number of patients with incomplete glottal closure decreased from 12 pretreatment to only 1 patient posttreatment, and the number of patients with impaired mucosal waves decreased from 13 to 5. There was also a significant decrease in the mean VHI-10 score before and after treatment (15.61 vs. 4.61 P value < 0.001).
Conclusion:
Thulium laser can be used as an office procedure for the treatment of vocal fold polyps.
... Additionally, PDL irradiation can inhibit vocal fold fibrosis in vivo [12]. However, Sheu et al. [13] reported that in the injured vocal fold mucosa, the KTP laser at therapeutic settings elicited a robust yet transient inflammatory response, in addition to increased MMP gene expression. However, these transient events appear to have little impact on the histological appearance of vocal fold scars. ...
... However, in this study, there was no significant difference in VEGFα gene expression between the laser and scar groups (P > 0.05). Sheu et al. [13] showed that the use of a KTP laser for the treatment of rat vocal fold scars resulted in a brief increase in MMP-1 and MMP-9 1 week after treatment, and there was no difference between the groups 4 weeks after treatment. In our study, MMP-13 gene expression between the laser and scar groups was not significantly different after 1 month of treatment (P > 0.05). ...
Purpose:
The objectives of this study were to observe the regulating effect of KTP laser and Nd:YAG laser in the repair of vocal fold scars.
Methods:
All rabbits were injured in the muscular layer with a sharp instrument, and then the vocal folds were treated with a KTP laser and a Nd:YAG laser at a power of 2, 4, 6 and 8 W 1 month after the injury. One month after treatment, the rabbits were killed and the throats were removed to detect changes in histology and gene expression of the vocal fold scar after laser therapy.
Results:
The best efficacy of all KTP laser treatment groups was the KTP laser 6 W group. Regarding the detection of gene expression, in the KTP laser 6 W and Nd:YAG laser 6 W groups, col-3A1 was decreased compared to the scar group (P < 0.05), and col-1A1 was decreased only in the KTP laser 6 W group (P < 0.05). TGF-β1 levels in the two groups were lower than in the scar group. There were also significant differences in the levels of IL-1β, COX-2 and TNF-α in the two laser groups compared with the scar group (P < 0.05).
Conclusion:
KTP laser and Nd:YAG laser treatments for vocal fold scars have particular therapeutic effects. The KTP laser may be better than the Nd:YAG laser for the regulation of vocal fold scars.
Level of evidence:
NA.
... Only a few articles came to our attention using a nonsystematic search. Vocal fold scar modulating effects of the KTP laser was the main area of interest 19,20 , but recently, the use of the novel blue light laser shows better results compared to the KTP laser 21 . ...
Purpose:
To present a detailed, reproducible, cost-efficient surgical model for controlled subepithelial endoscopic vocal fold injury in the rat model.
Methods:
Six male Sprague Dawley rats were enrolled in the experiment. The left vocal folds were used to carry out the injury model, and the right vocal fold served as control. After deep sedation, the rats were placed on a custom operating platform. The vocal fold injury by subepithelial stripping was carried out using custom-made microsurgical instruments under endoscopic guidance. Data were analyzed for procedural time and post-procedural pain. Microcomputed tomography (micro-CT) scan and histologic images were obtained to assess the length, area, and depth of injury to the vocal fold.
Results:
The mean procedural time was 112 s. The mean control vocal fold length was 0.96 ± 0.04 mm. The mean vocal fold injury length was 0.53 ± 0.04 mm. The mean vocal fold surface was 0.18 ± 0.01 mm2 with a mean lesion area of 0.05 ± 0.00 mm2. Mean vocal fold injury depth was 375.4 ± 42.8 μm. The lesion length to vocal fold length ratio was 0.55 ± 0.03, as well as lesion area to vocal fold surface area was 0.29 ± 0.02.
Conclusions:
Our described experimental vocal fold injury model in rats is found to be fast, safe, cost-efficient, and reproducible with a rapid learning curve.
... Because it is a solid-state laser, the pulse width of a KTP laser can be varied more easily than that of a PDL, and intravascular blood is heated more slowly, therefore minimizing collateral thermal injury. 23 Favorable outcomes have been reported with KTP laser for injured and scarred vocal folds by several authors 24,25 in animal models and the therapeutic effect was attributed to the up-regulation in extracellular matrixmetalloproteinase mediators and the creation of a sub-basement membrane plane of division from the laser effect. ...
Objective
This pilot study aims to evaluate the efficacy of 532 nm potassium titanyl phosphate (KTP) laser under topical anesthesia in patients with vocal fold scars.
Methods
A series of 18 patients with vocal fold scars of varying degrees were treated. The KTP laser was used under local anesthesia in the outpatient clinic. It was set to deliver 6 W of power using a continuous output mode. Close-to-contact mode was used for laser irradiation, and contact mode was used for ablation and excision of the lesions. Some of the patients received laser scar ablation on both vocal folds; the scarred vocal fold on one side and the hypertrophic vocal fold on the other. Parameters include glottic closure, amplitude, and mucosal wave pattern were measured using laryngeal stroboscopic examination. Aerodynamic and voice evaluations were carried out using maximum phonation time (MPT), jitter, shimmer, Voice Handicap Index questionnaire (VHI-30), and GRBAS scale.
Results
In total, 21 surgeries were performed on 18 patients. Glottic closure, amplitude, and mucosal wave pattern showed improvement 2 months postoperatively (P < .05). There was significant improvement in the postoperative scores for VHI-30, VHI-emotional sub-scale, VHI-physical sub-scale, and GRBAS (P < .05). There was no significant difference in the MPT and VHI-functional sub-scale before and after the operation (P > .05). Re-adhesion of the anterior commissure was observed in 2 patients with Type III scars.
Conclusion
The 532 nm KTP laser is an effective tool for the treatment of vocal fold scars. Further research is required to determine if serial laser applications could improve outcomes for this challenging condition.
Level of Evidence
Level IV
... 13,14 The mechanism of scar remodeling after the irradiation of angiolytic laser is manifested by a change in extracellular matrix metabolism due to the increased expression of matrix metalloproteinase and a decrease in the expression of TGF-β, known as a profibrotic mediator. 15 Our research was based on the hypothesis that angiolytic laser-assisted glottoplasty can induce the regeneration of defective superficial lamina propria in sulcus vocalis patients due to its scar remodeling ability. Although the current study did not analyze the histologic changes of the lesion in patients after angiolytic laserassisted glottoplasty, most patients showed significant improvement of the GRBAS and VHI scores until 6 months after the operation. ...
Objective
We have been performing glottoplasty using angiolytic laser, including pulsed dye laser (PDL) or potassium titanyl phosphate (KTP) laser, for the treatment of sulcus vocalis. In this study, we retrospectively reviewed the treatment results of sulcus vocalis patients who had undergone glottoplasty using angiolytic laser and evaluated the efficacy and safety of this surgical technique.
Methods
From January 2008 to April 2016, 79 patients with sulcus vocalis who underwent angiolytic LASER-assisted glottoplasty were enrolled in the study.
Results
Of the 79 patients who participated in this study, 55 were male, and 24 were female. PDL was used for glottoplasty in 68 patients, and KTP was used in the remaining 11 patients. Seventy-seven patients underwent surgery for bilateral vocal cord lesions, and only 2 patients underwent surgery for unilateral vocal cord lesion. After glottoplasty using angiolytic laser, most patients showed continuous improvement of the GRBAS (grade, roughness, breathiness, asthenia, strain) score and Voice Handicap Index score until 6 months after the operation. In addition, we observed improvement of objective voice indices such as noise to harmonic ratio, jitter, shimmer, and maximal phonation time postoperatively.
Conclusions
Based on these results, we confirmed the efficacy and safety of glottoplasty using angiolytic laser in sulcus vocalis patients. Further studies are needed to confirm appropriate laser settings such as frequency of treatments and total energy delivered to the lesion. Also, multi-institutional studies are needed to confirm the efficacy and safety of the operation.
... 3 More recently, use of the 585 nm Pulse Dye Laser or 532 nm Potassium Titanyl Phosphate (KTP) Laser has shown promise as newer scar modulators. 4,5 Current lamina propria replacements have had variable results. Rheological evaluation of hyaluronic acid (HA) and collagen injectables have shed light on their respective viscoelastic properties. ...
Objectives
Clinical indications for vocal fold injection augmentation (VFI) are expanding. Prior studies demonstrate the benefit of trial VFI for select causes of glottic insufficiency. No studies have examined trial VFI for glottic insufficiency resulting from true vocal fold (TVF) scar.
Methods
Retrospective chart review of patients who underwent trial VFI for a dominant pathology of TVF scar causing dysphonia. Patients who subsequently underwent durable augmentation were identified. The primary study outcome was the difference in Voice Handicap Index-10 (VHI-10) score from pretrial VFI to post-durable augmentation.
Results
Twenty-eight patients underwent trial VFI for TVF scar, 22 of whom reported a positive response. Fifteen of 22 subjects who underwent durable augmentation had viable data for analysis. Mean VHI-10 improved from 26.9 to 18.6 (P < .05), for a delta VHI-10 of 8.3, or 30.9% improvement. Twelve of the 15 (80%) showed a clinically significant improvement (delta VHI-10 >5).
Conclusions
A trial VFI is a potentially useful, low-risk procedure that appears to help the patient and clinician identify when global augmentation might improve the voice when vocal fold scar is present. Patients who reported successful trial VFI often demonstrated significant improvement in their VHI-10 after subsequent durable augmentation.
... In the rat vocal fold, Lin et al. examined the effects of PDL irradiation and demonstrated the alteration in inflammatory cytokine and ECM transcript expression both in vitro and in vivo [11]. Similar effects of KTP laser irradiation were also confirmed in injured rat VFs [12]. Angiolytic laser irradiation may provide phenotypic alteration of epithelial cells, in addition to photocoagulation of the microcirculation beneath the tumors. ...
In the management of laryngeal pre-cancerous lesions such as dysplasia or carcinoma in situ (CIS), it is important that lesion regression occur without any complications. As a minimally invasive treatment option, photocoagulation therapy using angiolytic lasers has been attracting attention. Therapeutic effects have been reported for this type of treatment, however, vocal function after treatment has not been well discussed. In this retrospective case series, we examined the therapeutic effects of photocoagulation therapy on laryngeal dysplasia and the impact on vocal function. Twenty-four patients with laryngeal dysplasia or CIS were treated with photocoagulation therapy using angiolytic lasers. Two patients were treated under general anesthesia, the remaining 22 patients were treated with topical anesthesia. Before and after treatment the extent of the lesion and vocal function was evaluated by endoscopic examination and acoustic and aerodynamic analyses, respectively. More than 50 % disease regression was observed in 20 of 24 patients. Acoustic and aerodynamic analyses revealed improvement in pitch perturbation quotient with no impairment in other parameters. Photocoagulation therapy using angiolytic lasers has proven to be feasible and safe for the treatment of laryngeal dysplasia.
... Previous investigators have suggested that the targeting of hypervascular tissue causes lesion regression by disrupting the blood supply, 5,6 although modulation of wound healing response may play an important role. 12,19 However, it is as yet unclear whether these hypotheses apply to KTP treatment of Reinke's edema. This disparity between energy delivered, immediate tissue effects, and long-term outcomes places critical import on using available classifications to more accurately and reliably assess and apply study outcomes in clinical practice. ...
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.
Vocal fold scar is an especially challenging problem for laryngologists. Etiologies include surgery, systemic diseases, and laryngeal trauma. Following injury there is increase in irregular collagen deposition in the lamina propria and decrease in elastin leading to alteration in the viscoelastic properties of the vocal fold. The resultant change in the landscape of the extracellular matrix constituents has adverse effect on voice quality. Affected patients present with change in voice quality including hoarseness, disturbances in pitch and volume, and voice fatigue. There are many treatment modalities including laryngeal framework surgery, vocal fold steroid injections, injection laryngoplasty, 5-fluorouracil injections, growth factor injections, and tissue engineering, among others.While lasers have been discussed more as causes of scar than they have as treatment, photoangiolytic lasers have been used to good effect and without reported adverse consequences. Blue laser has worked well and has advantages over the pulsed-KTP laser, which no longer is manufactured. This chapter highlights the role of laser therapy and its regenerative effect for vocal fold scar. Case presentations in this chapter illustrate its use for this application.KeywordsVocal fold scarDysphoniaPhono-surgeryOffice-basedLaser therapyBlue laser
Background:
Vocal fold (VF) scar can result from trauma, neoplasm, inflammatory processes, congenital causes, surgery and other etiologies. In general, once the vibratory margin of the VF has been scarred, it has not been possible to return VF function to normal; but often it can be improved. The drug 5-fluorouracil (5-FU) is a pyrimidine antimetabolic that has many clinical applications ranging from systemic chemotherapy to topical treatment of actinic keratosis and basal cell carcinoma of the skin. Local injection with 5-FU also has been used for hypertrophic scar and keloids. 5-FU was shown to have benefit in animal models of VF scar and subglottic stenosis.
Objectives:
The present study aimed to evaluate the effect of 5-FU injection on VF vibratory function in patients with VF scar. Outcomes of 5-FU injection were compared to controls injected with dexamethasone.
Methods:
Adult voice center patients who had undergone VF injection with dexamethasone or a series of three 5-FU injections for treatment of VF scar were included in the study. Postoperative outcomes included percentage of subjects demonstrating improvement after injection, change in scar size, glottic closure, and VF stiffness, as well as digital image analysis measurements of mucosal wave. Outcomes were compared between subjects who received 5-FU and those who received dexamethasone.
Results:
There were 58 VFs injected with 5-FU and 58 historical controls injected with dexamethasone. Baseline subject characteristics and etiology of scar did not differ significantly between the 5-FU and dexamethasone cohorts, except that scar size was greater in the 5-FU group and mucosal wave was worse at baseline. After a series of three 5-FU injections, 61.22% improved, 8.16% demonstrated no change, and 30.61% worsened. In the dexamethasone cohort, 51.06% improved, 0.00% demonstrated no change, and 48.94% worsened. The response differed significantly between the 5-FU and dexamethasone cohorts, with a greater proportion of subjects who underwent 5-FU injection demonstrating improvement postoperatively. In the 5-FU cohort, 32.76% of subjects previously had undergone and failed dexamethasone injection for VF scar: and within that group 84.21% improved, 5.26% demonstrated no change, and 10.53% worsened following 5-FU injection. On digital image analysis, the percent improvement in postoperative mucosal wave was significantly greater in the 5-FU cohort compared to the dexamethasone group, which demonstrated a worsening of mucosal wave.
Conclusions:
A series of three intralesional injections with 5-FU outperformed dexamethasone for improving mucosal wave in patients with VF scar. A prior failed trial of dexamethasone injection predicted a favorable response to 5-FU. Further research is encouraged to confirm or refute these findings.
The history of laser in laryngology dates back to the 1960s. Traditionally, it has been used in the operating room for the treatment of benign and malignant lesions of the larynx. Technical advances, such as the development of distal chip flexible endoscopes with a working channel and the ability to deliver lasers using glass fibers, have permitted increasing laser therapy in office-based surgery. Otolaryngologists are able to choose from a large spectrum of lasers ranging in frequency about 400 nm to 10, 000 nm. The choice of laser for office-based surgery depends on the mode of laser delivery and type of lesion to be treated. Lasers with high affinity for water, such as the carbon dioxide laser with a wavelength of 10,600 nm and thulium laser with a wavelength of 2013 nm, provide excellent cutting properties, while photoangiolytic lasers with affinity for oxyhemoglobin, such as the potassium titanyl phosphate (KTP) laser with a wavelength of 532 nm and the blue laser with a wavelength of 445 nm, provide better hemostatic properties with minimal injury to the overlying mucosa.Office-based laser therapy has been shown to be effective and safe in the treatment of laryngeal recurrent respiratory papillomatosis (RRP), vascular and other benign lesions of the vocal folds, vocal fold dysplasia, and early malignancy. Potential complications are infrequent and include primarily vocal fold hemorrhage, scar, and persistent edema which may lead rarely to airway obstruction. This chapter reviews the clinical application of office-based laser in the treatment of benign and premalignant lesions of the larynx. The limitations and complications of office-based laser therapy are discussed. This information is invaluable for otolaryngologists who elect to treat patients with various laryngeal diseases in the office.KeywordsOffice-based laser surgery Photoangiolytic lasers Diode lasers Recurrent respiratory papillomatosis Vocal fold benign lesions Vocal fold scar Vocal fold dysplasia
Objective
Glottoplasty using an angiolytic laser is an option for the surgical treatment of sulcus vocalis. In this study, we sought to evaluate the clinical outcomes of using a 532-nm diode laser in sulcus vocalis patients and to identify predictive factors of improved voice outcomes after angiolytic laser-assisted glottoplasty.
Methods
A total of 66 patients with sulcus vocalis who underwent laser-assisted glottoplasty with a 532-nm diode laser were included in this study.
Results
3 months after surgery, GRBAS scores, patient-reported outcome measures, fundamental frequency (F0), jitter percent, and noise-to-harmonic ratio decreased significantly, while cepstral peak prominence (CPP) of vowel and sentence production increased. Patients with auditory-perceptual improvements showed greater improvement in the Voice Handicap Index (VHI) scores, F0, and CPP of vowel and sentence production compared to those with no improvement. While young male patients with preoperatively high F0 were predicted to have favorable outcomes, the type of sulcus vocalis was not predictive of treatment outcomes. Patients treated with lower laser power showed better improvement in the VHI scores postoperatively than those who received higher laser power per vocal fold. Combined injection laryngoplasty with laser glottoplasty was effective in lowering the F0, especially in male patients with high F0.
Conclusion
A 532-nm diode laser is useful for treating sulcus vocalis. Young male patients and individuals with preoperatively high F0 showed better voice outcomes after laser glottoplasty. Laser power and combined injection laryngoplasty are considered to affect improvement in the VHI and lowering F0 after laser glottoplasty in sulcus vocalis.
There are several lasers available for office-based or suspension microlaryngoscopy laser procedures in the treatment of laryngeal diseases. Each has advantages and disadvantages given the depth of penetration per unit of power, absorption in water, spectral absorption characteristics, mode of delivery, safety, and cost. It is important to note that while the proper selection of indication of treatment based on a laser wavelength is critical, of equal importance is selecting the appropriate power setting, focal length (or spot size), and time of exposure. The photoangiolytic lasers precisely target hemoglobin within the microcirculation of the highly vascularized tissue and may have better hemostatic effects and preservation of surrounding normal tissue than the CO2 laser. Although the choice of laser is purely theoretical and cannot be accurately concluded which parameters of laser (wattage and pulse width) were best to use, photoangiolytic laser surgery is safe and effective for specific laryngeal lesions. In this review, indications for photoangiolytic laser procedures for various laryngeal diseases, laser settings and surgical techniques for specific laryngeal lesions including sulcus vocalis, laryngeal dysplasia, and recurrent respiratory papillomatosis will be introduced. Pros and cons of in-office laser surgery using photoangiolytic laser and flexible CO2 laser will also be addressed.
With fiber-based lasers that may be passed via the working channel of a flexible laryngoscope, in-office laser laryngeal surgery has become possible. The potassium-titanyl-phosphate laser has several features that make it ideal for laryngeal surgery, and it is now the laser of choice for in-office management of a variety of laryngeal lesions. Its applications have expanded significantly since its introduction, with reports of new indications continuing to appear in the literature. This article provides a comprehensive review of the indications and technical details of in-office potassium-titanyl-phosphate laser laryngeal surgery, and a summary of the existing literature regarding outcomes of these procedures.
The 532 nm pulsed KTP (potassium titanyl phosphate) laser and the 585 nm pulsed dye laser (PDL) are photoangiolytic lasers that have been demonstrated to be effective for managing vocal fold dysplasia. The putative mechanism of action is selective photoangiolysis of the sublesional microcirculation. On the basis of this experience, early glottic cancers were treated by selectively targeting the intralesional and sublesional microvasculature. This approach was derived from Folkman's concepts of neoplastic growth resulting from tumor angiogenesis. Staged microlaryngeal treatment was adopted, because it facilitated optimal functional results, and was considered safe, because early glottic cancer rarely metastasizes. Furthermore, intercurrent disease during conventional incremental radiotherapy is typical in treating early glottic cancer. A pilot group of 22 patients with early glottic cancer (13 T1, 9 T2) were treated with a fiber-based angiolytic laser. Eleven of the 22 had unilateral disease and were entirely treated by laser photoangiolysis as a sole modality. Eleven of the 22 had bilateral disease; 5 of the 11 were treated entirely (bilaterally) by laser photoangiolysis, and 6 of the 11 only underwent laser treatment of the less involved vocal fold, with conventional resection being done on the dominant side of the cancer. The initial 8 of the 22 were treated with the PDL, and the latter 14 of the 22 were treated with the pulsed KTP laser. No patient has cancer presently, and none have undergone posttreatment radiotherapy or open surgery. The mean follow-up is 27 months, 13 of the 22 patients have at least 2 years of follow-up, and the first patient was treated just over 5 years ago. Objective measures of vocal function revealed that photoangiolytic treatment of early glottic cancer resulted in significant postoperative improvements despite the fact that half of the patients had bilateral disease. Angiolytic lasers effectively involuted early glottic cancer, with microsurgically directed nonionizing radiation of the dense neoplastic blood supply resulting in complete tumor regression. This approach is conceptually attractive, because it is repeatable, it preserves all conventional cancer treatment options, and it results in excellent vocal function by improving phonatory mucosal wave vibration. Observations from this investigation suggest that this new and novel cancer treatment strategy is effective; however, larger patient cohorts, longer follow-up, and multi-institutional confirmation will be necessary to establish incontrovertible oncological efficacy.
As context is important to gene expression, so is the preprocessing of microarray to transcriptomics. Microarray data suffers from several normalization and significance problems. Arbitrary fold change (FC) cut-offs of >2 and significance p-values of <0.02 lead data collection to look only at genes which vary wildly amongst other genes. Therefore, questions arise as to whether the biology or the statistical cutoff are more important within the interpretation. In this paper, we reanalyzed a zebrafish (D. rerio) microarray data set using GeneSpring and different differential gene expression cut-offs and found the data interpretation was drastically different. Furthermore, despite the advances in microarray technology, the array captures a large portion of genes known but yet still leaving large voids in the number of genes assayed, such as leptin a pleiotropic hormone directly related to hypoxia-induced angiogenesis.
The data strongly suggests that the number of differentially expressed genes is more up-regulated than down-regulated, with many genes indicating conserved signalling to previously known functions. Recapitulated data from Marques et al. (2008) was similar but surprisingly different with some genes showing unexpected signalling which may be a product of tissue (heart) or that the intended response was transient.
Our analyses suggest that based on the chosen statistical or fold change cut-off; microarray analysis can provide essentially more than one answer, implying data interpretation as more of an art than a science, with follow up gene expression studies a must. Furthermore, gene chip annotation and development needs to maintain pace with not only new genomes being sequenced but also novel genes that are crucial to the overall gene chips interpretation.
Pathological cutaneous scars such as keloids and hypertrophic scars (HSs) are characterized by a diffuse redness that is caused by the overgrowth of capillary vessels due to chronic inflammation. Our group has been using long-pulsed, 1064-nm Nd:YAG laser in noncontact mode with low fluence and a submillisecond pulse duration to treat keloids and hypertrophic scars since 2006 with satisfactory results. The present study examined the efficacy of this approach in 22 Japanese patients with keloids (n = 16) or hypertrophic scars (n = 6) who were treated every 3 to 4 weeks. Treatment settings were as follows: 5 mm spot size diameter; 14 J/cm(2) energy density; 300 μs exposure time per pulse; and 10 Hz repetition rate. The responses of the pathological scars to the treatment were assessed by measuring their erythema, hypertrophy, hardness, itching, and pain or tenderness. Moreover, skin samples from 3 volunteer patients were subjected to histological evaluation and 5 patients underwent thermography during therapy. The average total scar assessment score dropped from 9.86 to 6.34. Hematoxylin and eosin staining and Elastica Masson-Goldner staining showed that laser treatment structurally changed the tissue collagen. This influence reached a depth of 0.5 to 1 mm. Electron microscopy revealed plasma protein leakage, proteoglycan particles, and a change in the collagen fiber fascicles. Further analyses revealed that noncontact mode Nd:YAG laser treatment is highly effective for keloids and hypertrophic scars regardless of patient age, the origin and multiplicity of scarring, the location of the scar(s), or the tension on the scar.
The 532 nm pulsed KTP (potassium titanyl phosphate) laser and the 585 nm pulsed dye laser (PDL) are photoangiolytic lasers that have been demonstrated to be effective for managing vocal fold dysplasia. The putative mechanism of action is selective photoangiolysis of the sublesional microcirculation. On the basis of this experience, early glottic cancers were treated by selectively targeting the intralesional and sublesional microvasculature. This approach was derived from Folkman's concepts of neoplastic growth resulting from tumor angiogenesis. Staged microlaryngeal treatment was adopted, because it facilitated optimal functional results, and was considered safe, because early glottic cancer rarely metastasizes. Furthermore, intercurrent disease during conventional incremental radiotherapy is typical in treating early glottic cancer. A pilot group of 22 patients with early glottic cancer (13 T1, 9 T2) were treated with a fiber-based angiolytic laser. Eleven of the 22 had unilateral disease and were entirely treated by laser photoangiolysis as a sole modality. Eleven of the 22 had bilateral disease; 5 of the 11 were treated entirely (bilaterally) by laser photoangiolysis, and 6 of the 11 only underwent laser treatment of the less involved vocal fold, with conventional resection being done on the dominant side of the cancer. The initial 8 of the 22 were treated with the PDL, and the latter 14 of the 22 were treated with the pulsed KTP laser. No patient has cancer presently, and none have undergone posttreatment radiotherapy or open surgery. The mean follow-up is 27 months, 13 of the 22 patients have at least 2 years of follow-up, and the first patient was treated just over 5 years ago. Objective measures of vocal function revealed that photoangiolytic treatment of early glottic cancer resulted in significant postoperative improvements despite the fact that half of the patients had bilateral disease. Angiolytic lasers effectively involuted early glottic cancer, with microsurgically directed nonionizing radiation of the dense neoplastic blood supply resulting in complete tumor regression. This approach is conceptually attractive, because it is repeatable, it preserves all conventional cancer treatment options, and it results in excellent vocal function by improving phonatory mucosal wave vibration. Observations from this investigation suggest that this new and novel cancer treatment strategy is effective; however, larger patient cohorts, longer follow-up, and multi-institutional confirmation will be necessary to establish incontrovertible oncological efficacy.
Despite increasing knowledge of wound healing and collagen metabolism, hypertrophic scars and keloid scars are difficult to eradicate. Median sternotomy scars are often hypertrophic or keloidal. We treated them with a 585 nm flashlamp-pumped pulsed-dye laser, which selectively injures cutaneous microvessels without inducing scars. 16 adult patients with hypertrophic or keloidal median sternotomy scars after heart surgery received two treatments to one half of their previously untreated scars every 6-8 weeks and were reviewed at 6 months. Symptoms and clinical, histological, photographic, and surface texture assessments were obtained for treated and untreated areas of scar and evaluated independently by two observers blind to the treatment and by digital image analysis of skin surface casts. There was a significant improvement in erythema, scar height, skin surface texture, and pruritus in laser-treated scar areas; this improvement persisted for at least 6 months.
Although used for treating vascular malformations, KTP (532 nm) lasers have not been used to treat microvascular lesions of the vocal fold. The efficiency of KTP laser operation in the continuous mode with a 0.4- or 0.6-mm beam (1- to 2-W aim for 3 to 7 seconds delivering a total energy of 3 to 7 J) was studied retrospectively in patients with microvascular lesions of the vocal fold (n = 14). The perceptual acoustic, phonatory function, and videolaryngostroboscopic data were evaluated before and after operation in 10 patients. At follow-up (mean, 7 months), the results were excellent in all patients. Their phonatory function (jitter, shimmer, grade, breathiness, and roughness) significantly improved (p < .01). The videolaryngostroboscopic rating showed significant improvement in the amplitude of vocal fold vibration and excursion of the mucosal wave (p < .05). No postoperative recurrence or complications were noted. The KTP laser operation is a useful, cost-effective, and time-saving procedure and can be considered as an option in management of patients with microvascular lesions of the vocal fold, particularly those with repeated hemorrhages. Because the operation is easy (compared to other surgical methods) and has no major side effects, the prospect of total patient recovery is excellent.
Objectives
Ectasias and varices of the vocal fold are microvascular lesions that are often due to chronic abuse of the voice, and are occasionally encountered in association with other disorders such as polyps, Reinke's edema, and hematoma. The KTP laser can be used for photocoagulation of small vascular lesions, because the laser beam is well absorbed by hemoglobin, and damage to the epithelium is minimal. The present pilot study examined how the KTP laser could be used for microvascular lesions and their associated lesions.
Methods
Twelve patients who had undergone phonomicrosurgery were enrolled in the present study. The microvascular lesions were treated by photocoagulation with the laser set at a low power of 1.5 W in the continuous mode, while preserving the epithelium, and associated lesions were then treated by microdissection with cold instruments. The postoperative phonatory function was assessed by maximum phonation time, a perceptual test rating (GRBAS scale), and stroboscopy.
Results
The procedures were completed successfully in all cases. An exceptional case of a small hemorrhagic polyp allowed treatment with the laser only. The postoperative stroboscopic findings, maximum phonation time, and perceptual test rating all showed significant improvement compared with the preoperative state. No adverse effects, such as scarring or reduction of the mucosal wave, were observed in the current series.
Conclusions
KTP laser photocoagulation is a relatively simple and safe procedure for treating microvascular lesions of the vocal fold. It is not recommended for photocoagulation of hemorrhagic polyps or hematomas, because such lesions have little blood flow inside and thus photocoagulation is usually impossible or requires too much laser energy. However, photocoagulation of perimeter or feeding vessels of such disorders may facilitate the following procedure by avoiding unnecessary bleeding, as well as preventing recurrence of hemorrhagic lesions.
Objectives
Varices and ectasias in singers are typically the result of phonotraumatic shearing stresses and/or collision forces on the microcirculation within the superficial lamina propria. These lesions can be debilitating in performing vocalists because of the effect of recurrent hemorrhage and/or as a contributing factor to the morbidity of other mass lesions such as polyps, nodules, and cysts. Phonomicrosurgical treatment of performers is understandably approached with great trepidation, as the vocal liability of surgically disturbing the superficial lamina propria and epithelium must be balanced with the inherent detrimental vocal effect(s) of the lesion(s). Pulsed angiolytic lasers that emit radiation at high absorbance peaks of oxyhemoglobin were examined to determine whether they were an efficacious treatment approach for ectasias and varices based on these lasers' mechanisms of action and prior experience in phonomicrosurgery.
Methods
A prospective trial was done in 39 patients (40 procedures in 54 vocal folds) without complication to evaluate the effectiveness of a 585-nm pulsed dye laser (PDL; 25 cases) and a 532-nm pulsed KTP laser (15 cases) in a noncontact mode to treat 65 varices and 43 ectasias. Twenty-nine of 39 patients had varices and ectasias associated with other phonotraumatic mass lesions that required resection.
Results
All patients have resumed full vocal activities, and no patient has had a subsequent hemorrhage or vocal deterioration.
Conclusions
Both the 585-nm PDL and the 532-nm pulsed KTP laser were found to be efficacious and relatively safe treatment modalities for vascular abnormalities of the vocal folds in singers. Noncontact selective photoangiolysis of the aberrant vessels prevented future bleeding without substantial photothermal trauma to the overlying epithelium and surrounding delicate superficial lamina propria, thereby allowing for optimal postoperative mucosal pliability and glottal sound production. However, the pulsed KTP laser was substantially easier to use because of its enhanced hemostasis due to its longer pulse width. Vessel wall rupture was commonplace during use of the 585-nm PDL, but rarely occurred during photoangiolysis with the 532-nm pulsed KTP laser.
Objectives
Treatment of glottal papillomatosis and dysplasia was mirror-guided and done in surgeons' offices in the 19th century. It migrated to the operating room in the 20th century to accommodate direct laryngoscopic surgery, which required assistants to administer anesthesia and procedural support. The primary treatment goals, which are disease regression and voice restoration and/or maintenance, are tempered by the morbidity of general anesthesia and potential treatment-induced vocal deterioration. To obviate general anesthesia, office-based laser laryngeal surgery was first done in 2001 with the 585-nm pulsed dye laser (PDL), because it employs a fiber delivery system and its energy is selectively absorbed by oxyhemoglobin. Since then, this new angiolytic laser treatment paradigm has become a mainstay of management for many surgeons; however, there are a number of shortcomings of the PDL. To further develop this concept and address the limitations of the PDL, we used a 532-nm pulsed potassium titanyl phosphate (KTP) laser.
Methods
A prospective assessment was performed on 48 patients in 72 cases of recurrent glottal dysplasia (36) or papillomatosis (36). All individuals had previously undergone microlaryngoscopic management with histopathologic evaluation.
Results
Two dysplasia patients did not tolerate the procedure. Of the treatable dysplasia cases, there was follow-up in 29 of 34. Disease regression was at least 75% in 18 of 29 cases (62%), 50% to 75% in 7 of 29 (24%), and 25% to 50% in the remaining 4 of 29 (14%). Papilloma patients returned for treatment when symptoms recurred, so disease regression could not be assessed accurately. Similar to data obtained with the PDL, these data confirmed that dysplastic mucosa could normalize without resection.
Conclusions
Our observations revealed that the 532-nm pulsed KTP laser provided enhanced performance over the PDL laser in a number of ways. The ability to use smaller glass fibers precluded mechanical trauma to the channels of the flexible laryngoscopes and allowed for improved suctioning of secretions. Oxyhemoglobin absorbs energy better at 532 nm than at 585 nm, and the KTP laser can be delivered through a longer pulse width. These factors provide enhanced hemostasis and improved intralesional energy absorbance. Finally, unlike the PDL, the KTP laser is a solid-state laser and is not prone to mechanical failure.
Objectives
Vocal fold scarring is the major cause of voice disorders after voice surgery or laryngeal trauma. The role of inflammatory factors in vocal fold wound healing and fibrosis has not been adequately investigated. Scarless wound healing has been associated with decreased inflammatory responses. To understand scar formation and develop reliable treatments, it is necessary to control extracellular matrix production and inflammation. Thus, we examined the inflammation profile and extracellular matrix production in wounded vocal folds in the acute phase of wound healing.
Methods
Vocal fold stripping was performed on 30 Sprague-Dawley rats. Vocal fold tissue was collected at 5 time points (4, 8, 16, 24, and 72 hours). We examined the in vivo messenger RNA expression profile of inflammatory factors interleukin 1β, interferon γ, tumor necrosis factor a, nuclear factor Kβ, transforming growth factor β, and cyclooxygenase 2, as well as hyaluronic acid synthases 1 and 2, procollagen subtypes I and III, and elastin synthase in scarred vocal folds after injury, compared to normal vocal folds, using real-time reverse transcription-polymerase chain reaction.
Results
The inflammatory factors showed a time-dependent sequence of expression peaks, starting with interleukin 1β, nuclear factor Kβ, tumor necrosis factor a (4 and 8 hours), and transforming growth factor β (72 hours). Interferon y decreased at 24 hours. Correspondingly, hyaluronic acid synthase 1 expression peaked first (4 and 8 hours), whereas hyaluronic acid synthase 2 expression peaked at 16 hours and again at 72 hours. Procollagen I expression peaked at 72 hours, whereas procollagen III decreased from 8 to 16 hours but peaked at 72 hours. Cyclooxygenase 2 expression was elevated, whereas elastin expression remained constant.
Conclusions
The results show a clear profile of vocal fold inflammation with corresponding changes in extracellular matrix production.
BACKGROUND: Due to its potential effects on skin microcirculation and collagen metabolism, the 585 nm flashlamp-pumped pulsed dye laser has been proposed for treating abnormal scars. Indeed, one of the main problems with keloidal scars is their disfiguring erythematous color.
OBJECTIVE: To assess the efficacy of the 585 nm pulsed dye laser on the appearance of keloids.
METHODS: Eleven patients with skin phototypes II–IV and keloids were treated with the 585 nm pulsed dye laser. After one to three treatment sessions, clinical assessments of the scars were performed in combination with remittance spectroscopy measurements of the redness and melanin pigmentation. A group of nine keloids covered by silicone gel sheeting served as controls. Data were compared statistically.
RESULTS: During laser treatments, a discrete decrease in redness of the scars was clinically reported. However, this improvement was not confirmed by the objective spectrophotometric data. No side effects, especially hyperpigmentation, were disclosed. The keloids redness was not improved in the control group.
CONCLUSION: The 585 nm pulsed dye laser yields only minimal effects, if any, on the erythema of keloids. Similarly silicone gel sheeting does not modify the keloids redness.
Background and Objectives
Flashlamp pulsed-dye lasers (PDLs) has shown effectiveness in the treatment of keloids. In this study, we investigated whether PDL treatments decreased transforming growth factor-β1 (TGF-β1)—induction and up-regulation of matrix metalloproteinase (MMP) expression in keloid regression.Study Design/Materials and Methods
Keloid tissues obtained from 10 patients with intra-lesional or punch biopsies before and 7 days after PDL treatments [fluence per pulse was 10–18 J/cm2 (mean 14.0 J/cm2)]. Immunohistochemical (IHC) staining of TGF-β1 and MMP-1 and MMP-13 expressions in keloid tissue was performed. Western blot analysis of MMP-1 and MMP-13 expressions in extracellular matrix was evaluated.ResultsIHC staining indicated that expression of TGF-β1 was significantly reduced in keloid tissues after PDL irradiation. MMP-13 but not MMP-1 expression on IHC staining significantly increased in extracellular matrix of keloid tissues after PDL treatment. Western blot analysis also showed MMP-13 but not MMP-1 significant increased in keloid tissues after PDL treatment.Conclusions
Regression of keloids regressed after PDL treatments are associated with down-regulation of TGF-β1 expression and up-regulation of MMP-13 activity. Lasers Surg. Med. 36:38–42, 2005. © 2005 Wiley-Liss, Inc.
Ten patients with portwine stains (PWS) with test sites previously exposed to an argon laser were evaluated and subsequently treated with five pulsed dye (585 nm) laser treatments over a 10 month period. Clinical assessments, skin surface texture analyses using optical profilometry, and light microscopic histological evaluations were performed prior to commencement and at the end of the study in all ten patients. A change in the skin texture with return of skin markings approximating those of normal skin measured by optical profilometry was observed in the argon treated PWS skin following pulsed dye laser treatments. © 1993 Wiley-Liss, Inc.
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.
Although the potassium titanyl phosphate (KTP) laser is versatile, the variability in laser parameters for laryngeal pathologies and the lack of clinical efficacy data remain problematic. We provide preliminary data regarding these parameters for benign lesion regression. In addition, we describe a novel method for the quantification of the effects of the KTP laser on vocal fold (VF) lesions.
Retrospective chart review.
Images were captured from examinations before and after in-office KTP treatment in patients with a range of benign lesions. Laser settings were noted for each patient. Imaging software was then used to calculate a ratio of lesion area to VF length. Ten percent of images were requantified to determine inter-rater reliability.
Thirty-two patients underwent 47 procedures for lesions including hemorrhagic polyp, nonhemorrhagic polyp, vocal process granuloma, Reinke's edema, cyst/pseudocyst, leukoplakia, and squamous cell carcinoma in situ. No statistically significant differences were observed with regard to the laser parameters used as a function of lesion type. Regardless, by 1 month following treatment, all lesions had significantly decreased in size, except nonhemorrhagic polyps. Similar data were obtained at 2-month follow-up. We then compared the pre-KTP lesion size with the smallest lesion size quantified during the 1-year follow-up period. All lesions were significantly smaller, with the exception of Reinke's edema. Inter-rater reliability was quite good.
KTP laser effectively reduced VF lesion size, irrespective of the laser parameters used. In addition, our quantification method for lesion size appeared to be both viable and reliable.
The 532-nm KTP laser is clinically useful to induce benign vocal fold lesion regression without a fibrotic response. Previously, we described an in vivo model for KTP-induced injury in the rat larynx. This study uses this model to correlate the KTP-induced histologic and biochemical changes with the absence of long-term vocal fold fibrosis seen in clinical scenarios.
In vivo.
Unilateral vocal fold injury was induced via KTP laser at 10W (20mS pulse width) as described by our laboratory previously. Animals were subjected to serial endoscopic imaging from postoperative days 1 through 3. Animals were euthanized at 1 day, 4 weeks, and 12 weeks posttreatment and subjected to histologic analyses via hematoxylin and eosin and trichrome staining, as well as RT-PCR analyses for MMP-3, 9, transforming growth factor-beta (TGF-β), and COX-2 mRNA expression. Uninjured vocal folds were used as controls.
Our study revealed gross healing of the vocal fold mucosa by 3 days posttreatment, and an immediate, moderate inflammatory infiltrate with no subsequent ultrastructural changes on histology. MMP-3 and COX-2 expression increased transiently, although no changes were seen in expression of MMP-9, an MMP involved in extracellular matrix remodeling, or TGF-β, a profibrotic cytokine.
These data suggest that the KTP laser induces a modest inflammatory response, selective MMP expression, and no long-term fibrotic processes in a clinically relevant simulation.
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).
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.
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.
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.
Radiation therapy (RT) to the head and neck often results in damage to the vocal folds (VF) and surrounding structures. Characterization and treatment of these sequelae is limited, likely due to the lack of experimental models.
Larynges from rats exposed to 2 fractionation schedules (40 Gy total) were analyzed histologically. In vitro, reactive oxygen species (ROS) synthesis, and transcription of select genes associated with ROS, inflammation, and fibrosis were examined in VF fibroblasts after single-dose radiation.
Although radiation-induced histologic alterations are made to VF architecture, 1 fractionation schedule was accompanied by significant morbidity and mortality. In vitro, radiation increased ROS synthesis and inflammatory and profibrotic gene expression.
Our data suggest that hyperfractionated RT is more tolerable. Utilizing this model, RT-induced histologic aberrations are made to the VF mucosa. In addition, a relationship between radiation, ROS, and inflammatory and fibrotic gene expression was observed in vitro.
The potassium titanyl phosphate (KTP) laser is emerging as a potentially effective treatment for various vocal fold pathologies. To date, the precise mechanism(s) of action of this wavelength on the layered microarchitecture of the vocal fold remains unknown. The purpose of this study is to develop an in vivo model for the use of the KTP laser in the rat vocal fold and to characterize the potential of this model for future studies.
In vivo survival surgery.
A model for videoendoscopic visualization and injury to the rat vocal fold was established using a microlaryngoscope and rigid telescope. Unilateral vocal fold injury was induced with the KTP laser at 10 Watts (W) 20 milliseconds (ms) pulse width. Animals were euthanized at 1 day post-treatment. Larynges were subjected to gross visual analysis and histological analyses via hematoxylin and eosin and trichrome staining.
Consistent endoscopic visualization and injury was obtained without significant operative morbidity or mortality. The KTP laser caused superficial blanching and minor edema in the vocal fold, which resolved grossly by 24 hours postinjury. A modest inflammatory cell infiltrate was observed 1 day following injury. However, no remarkable alterations to the vocal fold microarchitecture were observed in the acute period.
We propose that this novel model simulates the clinical scenario of laser use for the vocal folds. Use of this model will allow us to further characterize effects, mechanisms, and therapeutic efficacy of this wavelength.
Fifteen patients with erythematous/hypertrophic scars and 11 patients with postinflammatory hyperpigmentation were treated with a flashlamp pumped pulsed-dye laser at 585 nm or a flashlamp pulsed-dye laser at 510 nm. An average of 1.8 treatments resulted in an average improvement of 77 percent. Forty-seven percent of the patients had 100 percent improvement after one to three treatments. Eleven patients with postinflammatory hyperpigmentation were treated with the flashlamp pumped pulsed-dye laser at 510 nm with a pulse width of 300 ns. There was an average of 80 percent improvement with 1.45 treatments. Forty-five percent of the patients had 100 percent improvement after one or two treatments. The pathophysiology of postoperative scarring is reviewed. Theoretical reasons for the efficacy of laser treatment are detailed.
This article explains the basic principles of lasers from their historical beginnings to their use specifically in otolaryngology. The operation of the laser is shown in clear, easy-to-understand steps with the basics of laser delivery, laser optics, and laser-tissue interactions also presented. This article aims to give the surgeon enough information and understanding to help in deciding which laser to use for which purpose.
Due to its potential effects on skin microcirculation and collagen metabolism, the 585 nm flashlamp-pumped pulsed dye laser has been proposed for treating abnormal scars. Indeed, one of the main problems with keloidal scars is their disfiguring erythematous color.
To assess the efficacy of the 585 nm pulsed dye laser on the appearance of keloids.
Eleven patients with skin phototypes II-IV and keloids were treated with the 585 nm pulsed dye laser. After one to three treatment sessions, clinical assessments of the scars were performed in combination with remittance spectroscopy measurements of the redness and melanin pigmentation. A group of nine keloids covered by silicone gel sheeting served as controls. Data were compared statistically.
During laser treatments, a discrete decrease in redness of the scars was clinically reported. However, this improvement was not confirmed by the objective spectrophotometric data. No side effects, especially hyperpigmentation, were disclosed. The keloids redness was not improved in the control group.
The 585 nm pulsed dye laser yields only minimal effects, if any, on the erythema of keloids. Similarly silicone gel sheeting does not modify the keloids redness.
Keloid scars have been treated in many ways, with varying success. A wide variety of treatments, all in current usage, indicate that no treatment has been shown to be markedly superior to the others. Following the successful treatment of scars using the pulsed dye laser, and with the more traditional intralesional steroid injection, a pilot study was undertaken using a combination of these treatments.
Recalcitrant keloid scars of 10 patients were managed with a combined treatment modality of pulsed dye laser (PDL) and intralesional steroid.
Seven of the patients benefited in terms of the raised nature of the scars being improved by 60%, erythema improved by 40%, and pain/itching by 75%. Three of the patients, who had presternal scars, had no benefit.
Pretreatment with PDL facilitated steroid injection by making the scar oedematous and therefore softer. In addition, we speculate that the benefits of this combined modality are summative, not just adjunctive. This study demonstrates that this treatment is effective for the treatment of keloid scars when other treatments have been unsuccessful.
Keloids and hypertrophic scars are benign growths of dermal collagen that usually cause major physical, psychological, and cosmetic problems.
In this 12-week single-blinded clinical trial, 69 patients were randomly assigned into three study groups. In Group 1, intralesional triamcinolone acetonide (TAC, 10 mg/mL) was injected at weekly intervals for a total of 8 weeks. In Group 2 [TAC+5-fluorouracil (5-FU)], 0.1 mL of 40 mg/mL TAC was added to 0.9 mL of 5-FU (50 mg/mL). This combination was injected weekly for 8 weeks. In Group 3, in addition to weekly TAC+5-FU injection for 8 weeks, lesions were irradiated by 585-nm flashlamp-pumped pulsed-dye laser (PDL, 5-7.5 J/cm2) at the 1st, 4th, and 8th weeks. Lesions were assessed for erythema, pruritus, pliability, height, length, and width.
Sixty patients completed the study. At the 8- and 12-week follow-up visits, all groups showed an acceptable improvement in nearly all measures, but in comparison between groups, these were statistically more significant in the TAC+5-FU and TAC+5-FU+PDL groups (p<.05 for all). At the end of the study, the erythema score was significantly lower, and itch reduction was statistically higher in the TAC+5-FU+PDL group (p<.05 for both). Good to excellent improvements (>50% improvement) were reported by the patients as follows: 20% in Group 1, 55% in Group 2, and 75% in Group 3, all of which were significantly different (p<.05). Good to excellent responses were reported by the blinded observer as follows: 15% in Group 1, 40% in Group 2, and 70% in Group 3. Their differences were statistically significant (p<.05). Atrophy and telangiectasia were seen in 37% of patients in TAC group.
Overall efficacy of TAC+5-FU was comparable with TAC+5-FU+PDL, but the TAC+5-FU+PDL combination was more acceptable by the patients and produced better results. Its effect on lightening of the lesion was promising. The TAC+5-FU+PDL combination seems to be the best approach for treatment of keloid and hypertrophic scars.
Statistical methods have proven invaluable tools for enhancing the quality of microarray analysis. In this study, we used different methods such as significance analysis of microarrays (SAM) and Bayesian analysis of gene expression levels (BAGEL), to analyze the same set of raw data in an attempt to maximize the chance of identifying genes whose expression were significantly altered in gastric cancers. In addition, we examined the utility of an additional set of reference in controlling the variances and enhancing the quality of the results. Our results showed that BAGEL has the advantage of detecting small yet statistically significant differences, which might be of biological significance. Furthermore, introducing an additional control into the BAGEL, we were able to minimize the influence of the variances and significantly reduce number of potential false positive hits. BAGEL incorporates a novel control significantly improve the sensitivity and specificity of gene expression profiling analysis.
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