Gerardo Lopez-Guerra

Photoangiolytic laser treatment of early glottic cancer: a new management strategy.

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 Folkmans 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.

Microlaryngoscopic and office-based injection of bevacizumab (Avastin) to enhance 532-nm pulsed KTP laser treatment of glottal papillomatosis.

Objectives: Photoangiolytic lasers effectively treat glottal papillomatosis, but do not reliably prevent recurrence. Therefore, sublesional injections of the antiangiogenic agent bevacizumab (Avastin) were given to assess the effect on disease recurrence and phonatory function. Methods: A retrospective investigation was done in a pilot group of 10 adult patients with bilateral glottal papillomatosis who had prior angiolytic laser treatment with established patterns of recurrence. The patients underwent 5 bevacizumab injections (5 to 10 mg) into the diseased vocal folds along with 532-nm pulsed KTP laser photoangiolysis treatments 4 to 6 weeks apart. Their disease resolution was compared to findings from prior laser treatment alone, and objective measures of vocal function (acoustic, aerodynamic, Voice-Related Quality of Life survey) were obtained. Results: All 10 patients had a greater than 90% reduction in recurrence. Four of the 10 had resolution. Four of the 10 have limited recurrent or persistent disease, receive injections of bevacizumab at 8- to 12-week intervals, and have not required laser treatment. Two of the 10 have ongoing periodic office-based KTP laser treatment along with bevacizumab injections. No patient has required microlaryngeal surgery with general anesthesia, and all 10 have had substantial improvement in vocal function. Conclusions: This pilot investigation provides preliminary evidence that bevacizumab injections enhance photoangiolytic laser treatment of glottal papillomatosis while enhancing phonatory function. Coupling an antiangiogenesis agent with pulsed KTP laser photoangiolysis is conceptually promising, since the mechanisms of action are complementary.

Crosstalk between adipose-derived stem/stromal cells and vocal fold Fibroblasts in vitro

To explore adipose‐derived stem cell/fibroblast interactions as a potential remodeling pathway for vocal fold scar.

Assessment of canine vocal fold function after injection of a new biomaterial designed to treat phonatory mucosal scarring.

Objectives: Most cases of irresolvable hoarseness are due to deficiencies in the pliability and volume of the superficial lamina propria of the phonatory mucosa. By using a US Food and Drug Administration–approved polymer, polyethylene glycol (PEG), we created a novel hydrogel (PEG30) and investigated its effects on multiple vocal fold structural and functional parameters. Methods: We injected PEG30 unilaterally into 16 normal canine vocal folds with survival times of 1 to 4 months. High-speed videos of vocal fold vibration, induced by intratracheal airflow, and phonation threshold pressures were recorded at 4 time points per subject. Three-dimensional reconstruction analysis of 11.7 T magnetic resonance images and histologic analysis identified 3 cases wherein PEG30 injections were the most superficial, so as to maximally impact vibratory function. These cases were subjected to in-depth analyses. Results: High-speed video analysis of the 3 selected cases showed minimal to no reduction in the maximum vibratory amplitudes of vocal folds injected with PEG30 compared to the non-injected, contralateral vocal fold. All PEG30-injected vocal folds displayed mucosal wave activity with low average phonation threshold pressures. No significant inflammation was observed on microlaryngoscopic examination. Magnetic resonance imaging and histologic analyses revealed time-dependent resorption of the PEG30 hydrogel by phagocytosis with minimal tissue reaction or fibrosis. Conclusions: The PEG30 hydrogel is a promising biocompatible candidate biomaterial to restore form and function to deficient phonatory mucosa, while not mechanically impeding residual endogenous superficial lamina propria.

Real-Time Tracking of Vocal Fold Injections With Optical Coherence Tomography

Optical coherence tomography (OCT) is a promising new imaging modality that can help discern the layered microstructure of vocal folds. In the future, subepithelial injections of implants will improve vocal fold pliability where there is stiffness of phonatory mucosa. Using OCT both to delineate the depth of subepithelial injections real‐time and to serially image the implant over time would be valuable, and has not been demonstrated previously.

Thermal Damage during Thulium Laser Dissection of Laryngeal Soft Tissue is Reduced with Air Cooling: Ex vivo Calf Model Study

Objectives: The 2-μm-wavelength thulium laser has recently been shown to be an effective cutting instrument in endolaryngeal surgery, although there is increased thermal trauma as compared with the carbon dioxide laser. This study investigated temperature changes and thermal trauma during thulium laser dissection of laryngeal tissue, with and without air cooling, in an ex vivo model. Methods: A continuous-wave thulium laser (400-μm fiber, 4-W continuous power, 4-second duration) was used to incise 10 calf vocal folds. Paired cooled and uncooled cuts were made in each fold with a dermatologic cooling device. A thermistor inserted into the glottic subepithelium was used to measure tissue temperatures. Thermal damage was analyzed histologically by measuring the depth of the zone of lactate dehydrogenase inactivation surrounding the mucosal incision. Results: The initial vocal fold temperature averaged 24.3°C without cooling and 4.4°C with cooling. The peak temperature during cutting averaged 59.1°C without cooling and 28.0°C with cooling. The thermal damage zone surrounding the cooled incisions was approximately 27% less than that surrounding the uncooled incisions. Conclusions: Air cooling can reduce the extent of thermal trauma associated with thulium laser surgery of the vocal folds, and the high-temperature plume generated during laser cutting is effectively cleared.

11.7 Tesla magnetic resonance microimaging of laryngeal tissue architecture

High‐resolution imaging of vocal folds that distinguishes vocal fold (VF) layered microstructure and VF implants would provide a key experimental tool for translational research investigating biomaterial‐based interventions to treat vocal fold scar. To establish proof of concept, we studied whether 11.7 Tesla (T) magnetic resonance (MR) microimaging provides the needed resolution to resolve vocal fold tissue architecture.

Comparison of Effects of 2 Harvesting Methods on Fat Autograft

Objectives/Hypothesis: Fat preparation for vocal‐fold injection medialization is typically done by scraping of excised fat or by lipo‐aspiration; however, lipo‐aspiration is substantially more efficient. Considering this, we compared viability of fat tissues obtained by these two techniques. We also examined whether basic fibroblast growth factor (bFGF) would increase cell proliferation in samples harvested by these methods.

Posterior glottic diastasis: mechanically deceptive and often overlooked.

Dysphonia secondary to posterior glottic aerodynamic incompetence can often be recognizable acoustically, but difficult to document visually. This mechanical impairment in posterior glottic closure is the result of injury caused by airway instrumentation. The difficulty of recognition of this entity is due to posterior supraglottic soft tissue that obscures the complete view during posterior glottic adduction, the lack of a structural organization of the cricoarytenoid region injury that leads to this disorder, and the lack of nomenclature. A retrospective assessment was done on 3 patients who underwent surgical reconstruction to correct posterior phonatory incompetence subsequent to laryngotracheal intubation. All 3 had sustained an injury to the cricoarytenoid joints, and 2 of the 3 had undergone paraglottic space medialization laryngoplasty that failed to solve the posterior glottic insufficiency. New procedures were designed and performed in these patients to correct the posterior glottic incompetence and are described: Laryngofissure and partial posterior cricoid resection, endoscopic pharyngoepiglottic-aryepiglottic fold advancement-rotation flap with interarytenoid interposition, and interarytenoid submucosal implant augmentation. Although the academic literature is replete with reports describing stenosis resulting from impaired cricoarytenoid joint abduction, the term glottic diastasis provides nomenclature for the inability to normally adduct the arytenoid cartilages. The initial experience with surgical reconstruction is preliminary, but encouraging.

Salvage Endoscopic Angiolytic KTP Laser Treatment of Early Glottic Cancer after Failed Radiotherapy

Objectives: Management of early glottic cancer subsequent to failed radiotherapy is challenging, especially in balancing oncological control and function preservation. Patients frequently have been incentivized against surgical management and thus have undergone radiotherapy as initial treatment. This history compounds the difficulty of discussions about surgical management after recurrence. Typically, endoscopic salvage has less morbidity than transcervical partial laryngectomy and is clearly desirable over total laryngectomy. However, there are appropriate concerns about the efficacy of endoscopic salvage and the overarching impact on larynx preservation and survival. Given our success with endoscopic angiolytic KTP laser treatment of previously nonirradiated T1 and T2 glottic cancers, we examined our results from treating similar-sized lesions after failed radiotherapy. Methods: We performed a retrospective chart review of 20 patients from our cancer database who had undergone failed radiation therapy elsewhere for early glottic cancer and then underwent endoscopic angiolytic KTP laser treatment. Results: Analysis of the geographic tumor recurrence of the 20 patients revealed T1a N0 M0 cancer in 4 patients, T1b N0 M0 cancer in 1 patient, T2a N0 M0 cancer in 1 patient, and T2b N0 M0 cancer in 14 patients. After KTP laser salvage treatment, 4 patients (20%) had local recurrence (all T2b) and required subsequent total laryngectomy, and 3 of these patients (15%) ultimately died of disease. The remaining 16 patients (80%) were free of disease at least 2 years after endoscopic salvage (average follow-up, 39 months). Conclusions: Our investigation provides preliminary evidence that angiolytic KTP laser salvage treatment of early glottic cancer is an effective treatment after failed irradiation. Studies with larger cohorts and longer follow-up will be necessary to establish incontrovertible evidence of its efficacy.