Pulsed-dye laser and retinoic acid delay progression of oral squamous cell carcinoma: a murine model.

OBJECTIVES/HYPOTHESIS: This study examined the role of the pulsed-dye laser (PDL) at 585 nm coupled with retinoic acid at therapeutic (5.0 mg/kg) and nontherapeutic (0.5 mg/kg) doses to delay the progression of cancer with a two-hit approach. The existing vasculature is selectively targeted by the laser, whereas retinoic acid inhibits future angiogenesis. STUDY DESIGN: Randomized, prospective study in a murine model. METHODS: Twenty-five athymic nude mice were inoculated with oral squamous cell cancers on six flank sites and randomly divided into five groups: 1) control subjects, 2) treatment with 0.5 mg/kg retinoic acid (RA 0.5), 3) treatment with 5.0 mg/kg retinoic acid (RA 5.0), 4) treatment with RA 0.5 + PDL, and 5) treatment with RA 5.0 + PDL. The PDL groups received irradiation after inoculation. The retinoic acid was administered daily. The tumors were counted and measured for 14 days. RESULTS: The control group developed visible tumors in 50% of the inoculation sites at 3 days compared with 3 days (RA 0.5) and 4 days (RA 5.0) for the retinoic acid groups and 9 days (RA 0.5 + PDL) and 10 days (RA 5.0 + PDL) for the laser treatment groups. There was no tumor growth until day 7 in the RA 5.0 + PDL group. The tumor volume was statistically different between the treatment groups. CONCLUSION: This study demonstrated the superiority of a single treatment with the PDL coupled with retinoic acid to delay the progression of cancer when compared with treatment with retinoic acid alone, thus introducing a novel strategy in cancer control.

Experimental CO2 laser myringotomy.

OBJECTIVE: The purpose of this study was to compare closure rates of CO2 laser myringotomies with those produced conventionally with a knife. STUDY DESIGN AND SETTING: We investigated closure rates in 3 experimental groups of chinchillas: (1) semicircular myringotomy in both ears either produced with a knife or CO2 laser; (2) CO2 laser myringotomy, round in one ear and kidney shaped in the other; (3) CO2 laser myringotomy, incisional in one ear and kidney shaped in the other. RESULTS: Patency of knife myringotomies was shorter (P < 0.01) than of similar laser myringotomies, means 10.0 and 21.8 days, respectively. The patency of kidney-shaped laser myringotomies was longer (P < 0.05) than of round ones. Incisional laser myringotomies remained open longer (P < 0.01) than round ones. CONCLUSION: Use of CO2 laser as well as certain geometries delay the closure of myringotomies. By allowing perforations of different shapes and sizes, CO2 laser myringotomy may become an alternative in the treatment of otitis media.

Anterior window laryngoplasty: a new anatomic approach for posterior glottic and subglottic stensosis.

This study explores the feasibility of an anterior thyroid window as a new approach for posterior glottic stenosis. An anterior window was made on the thyroid cartilage of human cadaver larynges, with its superior edge below the level of the vocal cords and an inferior pedicle composed of the inferior border of the thyroid cartilage attached to the cricothyroid membrane, which was left intact. By obtaining direct exposure of the posterior glottis and cricoarytenoid joints, mucosal graft suturing and exploration of the joints were easily achieved with an operating microscope. This study demonstrates the anatomic feasibility of an anterior window laryngoplasty as an alternative approach to treating posterior glottic stenosis while preserving the cartilage framework and avoiding the anterior commissure. This technique may improve endolaryngeal manipulation by providing a closer and more direct exposure than do endoscopic techniques, and by having fewer possible complications than traditional open techniques.

Optical-thermal simulation of tonsillar tissue irradiation.

BACKGROUND AND OBJECTIVE: Despite laser applications targetted toward tonsillar tissue, there has been no characterization of underlying optical and thermal events during laser irradiation of tonsillar tissue. STUDY DESIGN/MATERIALS AND METHODS: The optical properties of canine and human tonsils were determined at 805 nm (diode laser) and 1,064 nm (Nd:YAG laser). An optical-thermal simulation was developed to predict the temperature rise in irradiated human tonsils. RESULTS: The optical properties of human and canine tonsillar tissue are similar at both wavelengths. The optical-thermal simulation was validated and predicts that at 10 W and 1 minute of irradiation, the heat will be contained within the human tonsil. The diode laser causes more superficial heating than the Nd:YAG laser. CONCLUSIONS: The safety of irradiating human tonsils was shown. The diode laser is superior to the Nd:YAG laser because less heat affects collateral structures. The optical-thermal simulation detailed in this study can be used to predict the temperature rise in tissues undergoing irradiation.

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 CO(2) laser surgery. This procedure also has potential to be delivered on an outpatient basis with flexible fiberoptic laryngoscopes.

Mitomycin: effects on laryngeal and tracheal stenosis, benefits, and complications.

The management of laryngeal and tracheal stenosis continues to challenge us, despite advances in surgical techniques and better understanding of the wound healing process. Injury to the airway mucosa is the inciting event, regardless of the cause of the stenosis. Mitomycin-C is an antineoplastic antibiotic that acts as an alkylating agent by inhibiting DNA and protein synthesis. It can inhibit cell division, protein synthesis, and fibroblast proliferation. Topical application of mitomycin-C (0.4 mg/mL) was used as an adjuvant treatment in the endoscopic laser management of laryngeal and tracheal stenosis in 15 patients. Fourteen patients (93%) have shown improvement of their airway and resolution of their preoperative symptoms. After a mean follow-up of 18 months, no complication was noted with regard to the application of mitomycin-C. This study gives promising findings on the efficacy and safety of mitomycin-C as an adjuvant treatment in the management of selected cases of laryngeal and tracheal stenosis.

Bronchoscopic management of benign stenosis.

In summary, the use of laser technology in the airway for the treatment of benign lesions has become a standard therapeutic modality for the airway endoscopist. It is extremely important that endoscopists be well acquainted with the laser soft tissue interactions of the laser being used and the safety precautions associated with each individual wavelength. They should be conversant with the indications and contraindications and have the ability to use adjuvant therapeutic modalities, such as stents and medications. As usual, patient selection is one of the key factors related to successful management.

Optical-thermal simulation of human tonsillar tissue irradiation: clinical implications.

BACKGROUND AND OBJECTIVE: Mucosa intact laser tonsillar ablation is an alternative to conventional tonsillectomy. The efficacy of this procedure was demonstrated in canines, but establishing the safety of irradiating human tonsils is paramount. STUDY DESIGN/MATERIALS AND METHODS: An optical-thermal simulation of tonsillar tissue irradiation was previously developed, but the effect of varying parameters was not investigated. The tissue response to irradiation at 5-25 watts for 1 minute and 10 watts for 10 seconds to 162 seconds is simulated. RESULTS: At 15 watts and greater, the peak temperature is over 100 degrees C and the mucosal temperature is over 70 degrees C. At the depth of the tonsil, the temperature does not vary significantly. The peak temperature is at 1 mm. The radial temperature profile is not significantly altered by longer irradiation times. CONCLUSIONS: The optimal dosimetry parameters for irradiation of human tonsillar tissue at 805 nm with the MILTA technique is under 15 watts for approximately 1 minute.

Preliminary results of intraoperative mitomycin-C in the treatment and prevention of glottic and subglottic stenosis.

Mitomycin-C is an antineoplastic antibiotic that acts as an alkylating agent by inhibiting DNA and protein synthesis. It can inhibit cell division, protein synthesis, and fibroblast proliferation. The purpose of this pilot study is to investigate intraoperative applications of topical mitomycin-C in treatment and prevention of glottic and subglottic stenosis. Eight patients with posterior glottic and/or subglottic stenosis were treated with endoscopic CO2 laser excision followed by topical application of 0.5 cc of 0.4 mg mitomycin-C per milliliter of saline for 4 minutes at the surgical site. After mean follow-up of 15 months (10-20) all patients had clinical improvement of their airway and resolution of their preoperative symptoms. No complications were noted in this study. Although a longer follow-up and further controlled studies are needed, the use of topical mitomycin-C may prove useful in the treatment and prevention of subsequent restenosis and scar formation in the larynx and trachea.

Slow-release 5-fluorouracil and triamcinolone reduces subglottic stenosis in a rabbit model.

A previous pilot study suggested that a sustained-release conjugate that provided a slow release of 5-fluorouracil and triamcinolone acetonide injected into the tracheal and paratracheal tissues of rabbits at the time of subglottic surgery reduced the formation of subglottic stenosis. Our study was undertaken to confirm the effect. Ten milligrams of the compound suspended in hyaluronic acid was injected at the time of injury via a laryngofissure approach. The results showed that the control group had a mean stenosis of 52%, whereas the treated group had a mean stenosis of 32%. There was a significant difference between the treated and untreated groups (p = .003). It is hoped that this co-drug ultimately can be used in humans to reduce stenosis formation after laryngotracheal surgery and in other forms of otorhinolaryngological surgery.

Preliminary clinical results of window partial laryngectomy: a combined endoscopic and open technique.

Endoscopic laser resection for anterior commissure glottic carcinoma is difficult, because of inadequate exposure and close proximity to the underlying cartilage. A technique combining endoscopic carbon dioxide laser incision and an external approach creating a window in the thyroid cartilage was initially tested in a canine study and then performed in 5 patients. All patients were men, with T1 or T2 glottic or supraglottic cancer involving the anterior commissure, and had failed radiation treatment. The true or false vocal fold tumors were excised along with the paraglottic space and adjacent cartilage, with preservation of the remaining thyroid framework. The reconstruction was accomplished with placement of a sternohyoid muscle flap, by use of either a bipedicled muscle flap with overlying skin or a unipedicled muscle flap with a graft of free mucosa. The graft was secured in place with fibrin glue and laser soldering. Follow-up ranged from 11 months to 4 years and included biopsies. All patients had voice recordings before and after surgery. A tracheostomy was avoided in all patients. The hospital stays were 4 to 13 days. The voice quality was good after surgery. One patient died of unrelated causes 18 months after his surgery without evidence of recurrence. The other patients are still alive with no evidence of disease. The only complication was subcutaneous neck emphysema in 1 patient that spontaneously resolved. The results showed a satisfactory anatomic reconstruction and acceptable functions. We believe that this new combined technique is oncologically sound, may overcome the limited access seen with the endoscopic technique and the excessive cartilage resection seen with external partial laryngectomy, avoids a tracheostomy, and shortens hospital stays.

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.

Jet ventilation in upper airway obstruction: description and model lung testing of a new jetting device.

UNLABELLED: Patients with critical upper airway stenosis require a tracheotomy for corrective surgery. We describe a new transtracheal device that permits safe ventilation of these patients without tracheotomy. It is based on a coaxial bicannular design that allows "push-pull" ventilation by jetting gas through the inner cannula and applying suction through the outer cannula. It further allows monitoring of airway pressure, tidal volume, and end-tidal CO2. The device was placed in the "trachea" of an artificial lung, and the preparation was made airtight by sealing the proximal end of the trachea. Tidal volumes and their associated pressures were measured simultaneously at different parts of the airway at several lung compliances and airway resistance settings while varying the jet and suction pressures. A large range of tidal volumes was achieved at safe airway pressures using clinically relevant airway resistance and lung compliance settings. Airway pressures measured through the device correlated well with pressures measured directly in the airways at the same time. Tidal volumes, measured through a Wright respirometer in the suction line, exceeded actual values at high suction settings and decreased below actual values at low suction settings. This new form of jet ventilation allowed efficient ventilation of the artificial lung with a totally occluded upper airway. IMPLICATIONS: Tracheotomy is required for surgery to relieve stridor because gas forced into the trachea at high pressures through a percutaneously placed needle (jetting) cannot be exhaled quickly enough for respiration. We describe a device that allows jetting in the stridorous patient by actively assisting expiration, thereby eliminating the tracheotomy requirement.

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/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, 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.

Sinus surgery: does mitomycin C reduce stenosis?

This experimental study investigates the effect of mitomycin C (MMC) on sinus mucosal healing. MMC has an antiproliferative action on fibroblasts. It is used in glaucoma surgery to prevent restenosis of fistulas. Antrostomies were drilled in rabbit maxillary sinuses. One side was used as a control and the other treated with MMC at a concentration of 0.04, 0.4, or 1 mg/mL. Two animals from each group were sacrificed at 1, 2, 4, and 12 weeks. The antrostomies in the control and 0.04-mg/mL groups had closed by 1 week; in the 0.4-mg/mL group by 4 weeks, and in the 1.0-mg/mL group by 12 weeks. Ciliary function was initially impaired but normalized within 1 week. Both light and scanning electron microscopy showed no permanent damage to the cilia. These results suggest that MMC can be used to delay closure of antrostomies in sinus surgery.

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.

Does slow-release 5-fluorouracil and triamcinolone reduce subglottic stenosis?

The surgical management of subglottic stenosis may be complicated by reformation of strictures. A slow-release combination of 5-fluorouracil, which has an antiproliferative effect on fibroblasts, and the corticosteroid triamcinolone acetonide has been used experimentally to control scar production in ophthalmic operations. This study was performed to determine if this material also can be used to reduce formation of subglottic stenosis. Subglottic stenosis was induced in rabbits by means of injury to the subglottic mucosa and submucosa. A suspension of the compound at a concentration of 2.5 mg/ml or 12.5 mg/ml was injected into the adjacent soft tissues. A control group of rabbits received the same volume of the suspension fluid but no compound. Two rabbits from each group were killed 1, 2, and 12 weeks postoperatively. No stenosis was seen at 1 or 2 weeks, but at 12 weeks the rate of formation of subglottic stenosis was decreased to a mean of 15.20% in the experimental groups compared with 47.37% in the control group. There were no indications of local or systemic toxicity. The promising results from this preliminary study suggest that use of this compound may reduce restenosis among patients treated surgically for subglottic stenosis. Further studies are being conducted.

Brain tissue response to Holmium:YAG laser irradiation.

OBJECTIVE: To evaluate the usefulness of pulsed infrared solid-state Holmium:Yttrium-Aluminum-Garnet (Ho:YAG) laser in neurosurgery, acute responses of brain tissue to Ho:YAG irradiation and to investigate the healing processes in rats and rabbits. METHODS: Animals were divided into groups according to different survival time and laser irradiation mode. Craniotomy was made and laser energy was delivered to the brain surface by two irradiation modes: 1) contact mode with the fiber in contact with the brain surface; and 2) non-contact mode with the fiber tip 5 mm above the brain surface. Gross observations were made and histological changes were studied. RESULTS: Acute responses were studied on rats' brain. The contact mode produced a crater lined with less than 1 mm thick thermally coagulated layer of brain tissue. The non-contact mode effectively vaporized the brain tissue even with water irrigation. Good homeostatic effect was achieved. The shock waves generated by the pulsed delivery of laser energy, however, impacted on the brain resulting in debris spreading and brain vibration. The healing processes were studied on rabbits' brain one day to six weeks after irradiation. The lesions produced by the contact mode were narrow and sharply defined. With the non-contact mode, the thickness of the coagulated layer at the bottom of the crater varied between 0.8 and 1.1 mm. CONCLUSIONS: Ho:YAG laser should be a clinically useful tool in neurosurgery because of its good ablation effect, shallow penetration and convenient optic fiber transmission system. Meanwhile, a continuously waved Ho:YAG laser is desired to reduce the shock wave impact.

Kaposi's sarcoma of the larynx.

Kaposi's sarcoma (KS) is a neoplastic vascular disorder, classically arising in the skin of the lower extremities. As a consequence of the acquired immunodeficiency syndrome (AIDS) epidemic, an increasing number of patients have been found to have KS. In AIDS patients, KS appears to exhibit a more diffuse nature and frequently affects the head and neck. Mucosal lesions are most often seen, commonly involving the oral cavity. Only rare cases of laryngeal involvement have been recorded in the literature. We report 2 cases of KS of the supraglottic larynx. Our first patient, an elderly man of Mediterranean descent, complained of voice change and throat discomfort. Endoscopy with biopsy for diagnosis allowed conservative treatment with chemotherapy. Our second patient was a younger man with AIDS who presented with symptoms of airway obstruction. Management with carbon dioxide laser epiglottectomy was successful in relieving that patient's symptoms. Although rare, KS may present in both healthy and immunocompromised patients, and must be considered in the differential diagnosis of all violaceous lesions of the larynx.

Autofluorescence characteristics of oral mucosa.

BACKGROUND: The fluorescence characteristics of tissues depend upon their biochemical composition and histomorphological architecture, both of which undergo a change during malignant transformation. These changes are detectable as an alteration in the fluorescence spectral profile of the tissues. METHODS: Biopsy specimens from clinically suspicious lesions and normal-appearing oral mucosa were obtained from patients. Fluorescence spectroscopic measurements were obtained to study the differences between normal and dysplastic tissues and to determine the most appropriate excitation wavelength(s) for exploiting these differences. RESULTS: Fluorescence spectra from a total of 12 histologically normal (healthy mucosa or benign lesions) and ten abnormal (dysplastic or malignant) tissue samples were compared. Significant spectral differences were seen between the two groups. These differences were most marked at the excitation wavelength of 410 nm. Using this wavelength, fluorescence correctly diagnosed 20 of 22 samples studied. CONCLUSIONS: This technique accurately differentiates normal from abnormal tissues in vitro and has the potential applications for in vivo use as a noninvasive diagnostic tool.