Kathleen McMillan

A 585-nanometer pulsed dye laser treatment of laryngeal papillomas: Preliminary report†

Objectives/Hypothesis: Standard management of recurrent respiratory papillomatosis (RRP) currently consists of CO2 laser microsurgical ablation of papillomas. Because of the recurrent nature of this viral disease, patients are often faced with significant cumulative risk of soft tissue complications. As a minimally traumatic alternative to management of RRP, we have investigated the use of the 585‐nm pulsed dye laser (PDL) to cause regression of papillomas by selective eradication of the tumor microvasculature. Study Design: Nonrandomized prospective pilot study. Methods: Patients with laryngeal papillomas were treated with the PDL at fluences of 6 J/cm 2 (double pulses per irradiated site), 8 J/cm 2 (single pulses), and 10 J/cm 2 (single pulses), at noncritical areas within the larynx, using a specially designed micromanipulator. Lesions on the true cords were treated with the CO2 laser, using standard methodology. Results: Clinical examination of three patients treated to date showed that PDL treatment appeared to produce complete regression of papillomas. Unlike the sites of lesions treated by the CO2 laser, the epithelial surface at the PDL treatment sites was preserved intact. Conclusions: These preliminary results suggest the PDL may eradicate respiratory papillomas with minimal damage to normal laryngeal tissue. Further analysis of the ongoing study is required to demonstrate potential benefits of the technique.

Diagnosis of Head and Neck Precancerous Lesions in an Animal Model Using Fluorescence Spectroscopy

Laser‐induced fluorescence (LIF) of tissues depends on their biochemical and histomorphologic characteristics. LIF spectroscopic properties of 9,10‐dimethyl‐1,2‐benzanthracene (DMBA)‐induced precancerous and early cancerous lesions in a hamster buccal pouch mucosa model were studied. Fluorescence spectra from neoplastic lesions showed a characteristic fluorescence peak in the red region of the visible spectrum centered between 630 and 640 nm when excited with 410‐nm light. Using this as a diagnostic criterion, 45 of 49 lesions studied were correctly diagnosed, including early dysplastic lesions. Follow‐up study of four dysplastic lesions over 2 weeks revealed an increase in red fluorescence intensity. The findings of these experiments suggest that LIF spectroscopy may be a valuable noninvasive technique not only for early diagnosis of head and neck cancer, but also to probe a possible biochemical surrogate biomarker in the follow‐up of suspected lesions.

A new laser treatment for vocal cord papilloma--585-nm pulsed dye.

OBJECTIVES: Microvascular targeting with the 585-nm pulsed dye laser (PDL) may provide a new form of therapy to control symptoms caused by recurrent respiratory papillomatosis (RRP). METHODS: Ten patients with RRP underwent 13 procedures under general anesthesia with the 585-nm PDL. A micromanipulator (11 procedures) and a flexible nasolaryngoscope (2 procedures) were used to deliver the laser pulses. Patients were followed postoperatively according to protocol. RESULTS: Clinical examination revealed regression of papillomas in all patients. Seven patients had complete regression after PDL surgery, and 2 patients had partial response to treatment. One patient was lost to follow-up. No complications were present during this prospective nonrandomized pilot study. CONCLUSION: Patients treated with PDL experienced regression of their papillomas. PDL may provide patients with RRP with an alternative treatment without the risks associated with CO2 laser surgery. This procedure also has potential to be delivered on an outpatient basis with flexible fiberoptic laryngoscopes.

Tumor growth inhibition and regression induced by photothermal vascular targeting and angiogenesis inhibitor retinoic acid.

The effect of photothermal vascular targeting, alone and in combination with antiangiogenic therapy, was evaluated using tumors produced in mice by transplantation of KB cells. Tumor growth inhibition and regression followed vascular damage produced by pulsed dye laser (PDL) radiation. Administration of the antiangiogenic agent all-trans-retinoic acid (RA) was associated with smaller average tumor volumes in the presence and absence of PDL irradiation, but this effect was not statistically significant. The ability of PDL photothermal vascular targeting to cause regression of tumors without harming normal tissue may be a consequence of preferential damage to supplying vessels at the tumor periphery.

Atraumatic laser treatment for laryngeal papillomatosis

Ten to fifteen thousand new cases of recurrent respiratory papillomatosis (RRP) are diagnosed each year in the United States. RRP is caused by the human papillomavirus (HPV) and is characterized by recurrent, non-malignant, proliferative lesions of the larynx. Patients with RRP undergo numerous microsurgical procedures to remove laryngeal papilloma threatening airway patency and interfering with phonation. The standard surgical technique involves CO2 laser vaporization of laryngeal epithelium affected by the lesions, and requires general anesthesia. The pulsed dye laser operating at 585 nm has previously been demonstrated to be effective in clearing HPV lesions of the skin (verrucae). For treatment of RRP, the fiber- compatible pulsed dye laser radiation may be delivered under local anesthesia using a flexible intranasal laryngoscope. Potential advantages of the pulsed dye laser treatment over CO2 laser surgery include (1) reduced morbidity, especially a lower risk of laryngeal scarring; (2) lower cost; (3) reduced technical difficulty; and (4) reduced risk of viral dissemination or transmission. In vivo studies are underway to determine the effect of pulsed dye laser radiation on normal canine laryngeal tissue.

Characterization of tissue ablation with a continuous wave holmium laser

The pulsed holmium laser is a promising tool for tissue ablation but possesses some limitations. For example, it is capable of producing significant mechanical damage in certain tissues in the form of fissures and fractures. Because longer pulse durations should reduce mechanical damage, this study examined the tissue effects produced by a prototype continuous wave holmium laser.

Inhibition and regression of tumors in hamster DMBA model following laser microvascular targeting

Vascular targeting is a recent approach to cancer therapy that aims at damaging tumor vasculature to induce tumor cell hypoxia and subsequent cell death. Squamous cell cancer arises in the superficial mucosal and cutaneous epithelial layers, and tumor microvasculature therefore may be particularly well suited for targeting by selective photothermolysis. An initial evaluation of the effect of selective eradication of microvasculature on tumor development was undertaken here using the chemically-induced hamster cheek pouch model and a 585 nm pulsed dye laser. In a first group of 6 hamsters, progression of premalignant mucosal lesions was compared between control and laser treatment groups, and laser-induced regression of established tumors was evaluated. In a second group of 12 hamsters, the number of laser treatments required to produce complete regression of tumors of the buccal mucosa was determined. The effect of the laser on tumors appearing on the skin in these animals was also investigated. These experiments showed that laser treatment inhibited tumor development and caused complete regression of established tumors 10 mm3 or smaller. Photothermal microvascular targeting may be useful in treating dyplasia and early tumors of the upper aerodigestive tract and skin, with fewer adverse sequelae than existing modalities.

Pulsed dye laser application in ablation of vascular ectasias of the larynx: a preliminary animal study

Vascular ectasias (dilatation) and vascular lesions of the larynx are difficult to treat with exciting modalities. Varix (enlarged vessel) of the vocal folds, vocal fold hemorrhage, vascular polyp, hemangioma, intubation or contact granuloma are common problems which disturb voice. Current applications of CO2 laser and cautery often damage the delicate vocal fold cover. The 585 nm dermatologic pulsed dye laser may be an ideal substitute. Two adult canines were examined under anesthesia via microlaryngoscopy technique. Pulsed dye laser (SPTL-1a, Candela Laser Corp., Wayland, MA) energy was delivered via the micromanipulator with the 3.1-mm spot size in single pulses of 6, 8, and 10 Joules/cm2 and applied to the vessels of the vocal folds, epiglottis, and arytenoid cartilage. Endoscopic examination was carried out immediately after the treatment and at 4 weeks postoperatively. The animals were sacrificed at 3 weeks, larynges excised, and whole organ laryngeal section were prepared for histology. Pulsed dye laser thrombosed vessels of the vocal fold using 6 or 8 Joules/cm2. Vascular break and leakage occurred at 10 Joules/cm2. Follow up examination showed excellent vessel obliteration or thrombosis without scarring or injury to the overlying tissues. Histologic examination shows vascular thrombosis without inflammation and fibrosis in the vocal fold cover. Pulsed dye laser may have promise in treatment of vascular lesions of the larynx and upper airway.

Laser soft-palate stiffening

Preliminary animal model experiments have been performed to test the feasibility of a new treatment for snoring. Current surgical treatments for snoring at the palatal level involve either excision of tissue to shorten the palate, or interstitial ablation of the palate to induce fibrosis and stiffening. Both shortening and stiffening of the palate are believed to be effective in reducing snoring. Mucosal surface damage and delayed tissue sloughing are the cause of considerable pain for the patient. In the new treatment proposed here, palatal stiffening with mucosal preservation is accomplished by combining evaporative cooling at the tissue surface with laser irradiation to heat subsurface tissue layers. The surface is cooled using a timed spray of tetrafluoroethane immediately prior to each pulse from a 1.54 micrometer erbium glass laser. In vivo experiments demonstrate that the technique causes significant shrinkage and decreased elasticity in hamster skin, with no tissue sloughing. In vitro experiments with canine soft palates show that laser-induced thermal damage zones ranged from approximately 0.75 to 1.75 mm below the surface, depending on laser parameters. These results suggest that the noninvasive laser technique may produce palatal stiffening with protection of the mucosal surface, for treatment of snoring with minimal morbidity.

Preliminary clinical results of pulsed dye laser therapy for recurrent respiratory papillomatosis

Recurrent respiratory papillomatosis (RRP) is a viral disease characterized by the growth of benign tumors on the vocal cords. Standard management of RRP currently consists of CO2 laser microsurgical ablation of the papillomas. Because of the recurrent nature of this disease, patients are often faced with significant cumulative risk of soft tissue complications such as vocal cord scarring. As a minimally traumatic alternative to management of RRP, we have investigated the use of the 585 nm pulsed dye laser (PDL) to cause regression of the papillomas by selective eradication of the tumor microvasculature. Three patients have been treated with the PDL at fluences of 6 J/cm2 (double pulses per irradiated site), 8 J/cm2 (single pulses), and 10 J/cm2 (single pulses), at noncritical areas within the larynx, using a specially designed micromanipulator. Lesions on the true cords were treated with the CO2 laser. Clinical examination showed that PDL treatment appeared to produce complete regression of papillomas. Unlike the sites of lesions treated by the CO2 laser, the epithelial surface at the PDL treatment sites was preserved intact. The presumed mechanism for papilloma regression following PDL treatment involves acute or chronic localized hypoxia caused by loss of tumor microvasculature.