Cancer induction in the DMBA hamster cheek pouch: a modified technique using a promoter.

OBJECTIVE: To evaluate a modified method of carcinogenesis induction using the 9,10-dimethyl-1,2-benzanthracene (DMBA) sustained-release suture technique followed by arecaidine promotion in the hamster cheek pouch model. STUDY DESIGN: Prospective, controlled animal study. METHODS: Number 3-0 cotton sutures were impregnated with DMBA and coated with silicone elastomer. These sutures were placed in the cheek pouch of Syrian hamsters in the submucosal space to a length of approximately 1.5 cm. The suture placement was confirmed every 2 weeks and replaced if lost. After 12 weeks, the DMBA-coated sutures were removed. The cheek pouches were everted and painted with a solution of arecaidine three times weekly for up to an additional 4 weeks or until the tumor reached a size of 100 mm2. RESULTS: We placed sutures in 165 Syrian hamster cheek pouches. Of these, 133 hamsters (80.6%) produced squamous cell carcinomas that reached a size of 100 mm2 and then were randomly selected for treatment in a new drug trial. Twenty-six hamsters (15.8%) were found dead and 6 (3.6%) were killed because of severe inflammation. CONCLUSIONS: The DMBA hamster cheek pouch model is a reliable and efficient animal model for inducing squamous cell carcinoma and can be used to study upper aerodigestive tract tumors.

Rationale for intralesional valrubicin in chemoradiation of squamous cell carcinoma of the head and neck.

OBJECTIVES/HYPOTHESIS: With some advanced squamous cell carcinomas (SCCs) of the head and neck, chemoradiation therapy may obviate the need for surgical intervention. However, both modalities are known to produce organ toxicities, and tumor insensitivity remains problematic. Thus there is a clear need for the development of new treatment strategies. Accordingly, preclinical studies to evaluate the use of valrubicin, a contact-safe, mechanistically novel antitumor agent, combined with low-dose radiation for the therapy of SCC have been conducted. METHODS: The comparative in vitro antitumor activities of valrubicin with or without irradiation versus cisplatin were evaluated using human-derived sensitive and cisplatin-resistant SCC cell lines. A hamster cheek pouch model of SCC was used to assess the efficacy of weekly intratumoral valrubicin injections with and without concurrent low-dose irradiation. RESULTS: Valrubicin cytotoxicity was found to be comparable in both sensitive and platinum-resistant cell lines and superior to cisplatin. The addition of minimally cytotoxic cell irradiation (300-450 cGy) resulted in prolonged G2/M cell cycle arrest and a supraadditive increase in apoptotic cell death. In hamsters, once a week x 3 intratumoral drug injections (3, 6, or 9 mg) were growth inhibitory; however, when valrubicin (6 mg) was combined with minimally cytotoxic irradiation (150, 250, or 350 cGy) significant tumor shrinkage was observed. CONCLUSIONS: Valrubicin produces supra-additive effects against SCC when combined with low-dose irradiation. This effect appears to correlate with the ability of valrubicin, a cytoplasmic-localizing drug, to inhibit protein kinase C. Therapeutic use of valrubicin against SCC could provide for reduced radiation doses with consequent improved efficacy and reduction in host toxicity.

Arytenoid adduction: controlling vertical position.

In flaccid laryngeal paralysis, the vocal process (VP) is displaced laterally and superiorly. The arytenoid adduction procedure (AA) moves the VP medially and caudally, closing the glottic gap. However, clinical evidence suggests that the VP is more caudal after AA than in physiological phonation. The neurally intact arytenoid is supported by tonic and phonatory activity of the posterior cricoarytenoid muscle (PCA). We hypothesize that a posterior anchoring suture could replace PCA support, achieving a more natural VP location. Cadaver larynges were scanned with computed tomography at rest and after AA, alone or in combination with a second arytenoid suture anchored to either the posterior midline cricoid (PC) or the inferior thyroid cornu (IC). Each posterior suture reduced caudal displacement of the VP during AA, but the glottic gap was wider with the PC suture. In 3 patients undergoing AA for laryngeal paralysis, the IC suture improved arytenoid posture and voice quality.

Unilateral cricothyroid contraction and glottic configuration.

It is frequently stated that unilateral cricothyroid muscle (CT) paralysis can be diagnosed by physical examination, noting rotation of the glottis, and shortening and vertical displacement of the ipsilateral vocal fold. These signs, however, are inconsistently observed, and there is considerable controversy regarding the direction of glottic rotation. To determine the effects of CT contraction on three-dimensional glottic configuration, we performed computerized tomography on cadaver larynges before and after simulated CT contraction. Radiopaque makers were used to compute distances. Unilateral CT contraction equally increased the length of both membranous vocal folds, and rotated the posterior glottis less than 1 mm. CT contraction neither adducted the vocal processes, nor significantly their altered vertical level. These results suggest that unilateral CT paralysis cannot be diagnosed on the basis of any clinically apparent change in glottal configuration.

Preliminary results of the use of indole-3-carbinol for recurrent respiratory papillomatosis.

OBJECTIVE: We report the preliminary results of a phase I trial using indole-3-carbinol for the treatment of recurrent respiratory papillomatosis. Indole-3-carbinol is a chemical that is found in high concentrations in cruciferous vegetables and has been shown to alter the growth pattern of recurrent respiratory papillomatosis cell cultures and to be effective in an in vivo animal model of recurrent respiratory papillomatosis. METHODS: Eighteen patients were treated with oral indole-3-carbinol and had a minimum follow-up of 8 months and a mean follow-up of 14.6 months. All patients received indole-3-carbinol, and outcome measures included a change in papilloma growth rate and the need for surgery during treatment compared with before treatment. All patients had serial examinations with videoendoscopy to document papilloma location and growth rate. RESULTS: Thirty-three percent (6 of 18) of the study patients had a cessation of their papilloma growth and have not required surgery since the start of the study. Six patients have had reduced papilloma growth rate, and 6 (33%) patients have shown no clinical response to indole-3-carbinol. Indole-3-carbinol affects the ratio of hydroxylation of estradiol; changes in the ratios of urinary 2-hydroxylation and 16-hydroxylation of estradiol caused by indole-3-carbinol correlated well with clinical response. No major complications or changes in the children's growth curve were noted. CONCLUSIONS: The preliminary results of treating recurrent respiratory papillomatosis with indole-3-carbinol holds promise. Longer follow-up of this patient group and a blinded, controlled trial are required. We conclude that indole-3-carbinol appears to be safe and well tolerated and may be an efficacious treatment for recurrent respiratory papillomatosis.

Fire in the operating room during tracheostomy.

BACKGROUND: Fire in the modern operating room is still a constant danger today despite the usual absence of the historically explosive anesthetic gases, cyclopropane, and ether. During a tracheostomy, three conditions are present that will support an explosive or combustive event: heat, fuel and oxygen. METHODS: We report three routine tracheostomy cases during which a fire was ignited. One patient had a minor burn during the cauterizing of a bleeding vessel. There was a visible flame in all cases and, in one case, the cloth drapes ignited. There were no serious airway injuries to any patients and all had a complete and uneventful recovery. We duplicated the same conditions in our laboratory. RESULTS: We discuss each case and give effective techniques to prevent ignition during surgery in the future. For our study, we reproduced flames in a cadaver trachea using halothane and the electrocautery in an oxygen-rich environment. We describe a protocol that has effectively prevented tracheostomy fires in our institution and may decrease the risk during other procedures as well. Also, we reviewed the literature to provide insight into the magnitude of the problem. CONCLUSIONS: High-oxygen concentration, the presence of fuels such as suture and tissue, and an igniting spark from the electrocautery device produce the proper conditions for a fire during tracheostomy. Taking the proper precautions can minimize if not eliminate this risk.

Changes in length and spatial orientation of the vocal fold with arytenoid adduction in cadaver larynges.

Videoendoscopy suggests that arytenoid adduction (AA) surgery not only medializes the paralyzed vocal fold, but increases the length of its membranous portion so that it more closely resembles the normal side. This could represent either real length change or out-of-plane rotation. Computed tomography scanning was performed on adult male cadaver larynges before and after the AA procedure to measure changes in length and spatial orientation of the vocal fold. Three-dimensional coordinates of radiopaque markers on the anterior commissure, posterior glottic midline, and vocal processes were determined. The distance between the vocal processes was 3.9 mm before, and 0.8 mm after AA. The mean vocal fold length was 12.4 mm before, and 13.4 mm after AA (p = .14). The vocal process moved consistently caudally, an average of 3.5 mm (p = .02). The data suggest that clinically apparent vocal fold length changes with AA could be an illusion due to vertical displacement of the vocal process, and not actual lengthening.

Human posterior cricoarytenoid muscle compartments. Anatomy and mechanics.

OBJECTIVE: To document the presence and functional significance of distinct anatomical compartments in the human posterior cricoarytenoid muscle (PCA). DESIGN: Anatomic study of human cadaver larynges. SUBJECTS: Seventeen fresh larynges, harvested at autopsy from 8 men and 9 women, with no history of laryngeal disease or surgery. INTERVENTIONS: Twenty-three PCA muscles from 12 human cadaver larynges were dissected. Computed tomographic scanning and rigid body mechanical analysis were used to compute 3-dimensional motion with simulated individual contraction of PCA compartments in 5 fresh larynges. RESULTS: Discrete medial and lateral bellies with different orientations of muscle fibers were found in every muscle. The 2 bellies insert on opposing aspects of the muscular process of the arytenoid. Very little linear translation was effected by either muscle. The axes of rotation attributable to the 2 bellies differed significantly, with the medial belly effecting rotation about a more vertical axis. The axis of rotation for the lateral muscle belly was nearer the anterior posterior axis than that of the medial belly. CONCLUSIONS: These data indicate that PCA muscle contraction results in arytenoid rotation about a variable oblique axis without significant lateral gliding. There are 2 bellies within the human PCA muscle with differing mechanical actions on the cricoarytenoid joint.

Endoscopic laser medial arytenoidectomy versus total arytenoidectomy in the management of bilateral vocal fold paralysis.

Bilateral laryngeal paralysis can result in severe airway compromise. A widely accepted treatment is endoscopic laser total arytenoidectomy (TA); however, vocal results are usually poor. An alternative approach, resection of only the medial portion of the arytenoid (medial arytenoidectomy [MA]), has the potential for less vocal impairment, but may not provide a sufficient airway. Laryngeal resistance (LR) was measured in vivo and ex vivo in 12 adult mongrel dogs with bilateral laryngeal paralysis after TA, MA, or no surgery (controls). The LR was significantly lower than in controls in both TA and MA, but there was no significant difference between TA and MA. Glottic area was also significantly higher in both MA and TA compared to controls, but again, there was no significant difference between TA and MA. Phonation could be elicited in all controls and 2 of 4 dogs with MA, but no dogs with TA. Our results show that MA offers airway improvement similar to that with TA and also has the potential for better vocal function.

Assessing vocal function after chemoradiation for advanced laryngeal carcinoma.

OBJECTIVE: To identify objective parameters that could serve as valid indicators of vocal function in evaluating patients treated at multiple centers for head and neck cancer. DESIGN: Objective measures of voice were validated against functional outcome measures of voice and communication. SETTING: A multidisciplinary university-based ambulatory head and neck cancer clinic. SUBJECTS: Fifteen patients at varying posttreatment intervals after chemoradiation therapy for head and neck cancer and 5 volunteers with no cancer but with a history of heavy smoking and drinking. MAIN OUTCOME MEASURES: Acoustic and aerodynamic parameters were measured in patients with head and neck cancer after treatment with combined chemotherapy and irradiation and in control subjects. Communicative function was assessed by perceptual assessment of recorded voice samples, by a clinician-based communication score, and by patient self-rating of voice and communication. RESULTS: Both perceptual analysis and communication score were concordant with patient self-rating of voice and communication ability. Acoustic measures were abnormal in patients, and jitter scores correlated with listener ratings of perceived voice quality. However, acoustic measures did not relate to communication function, as assessed by either the patient or the clinician. Laryngeal resistance demonstrated a significant correlation with both patient and observer assessments of voice quality and communication function. Laryngeal resistance was on average twice as high in patients who complained of voice fatigue, but this difference was not statistically significant. CONCLUSIONS: Laryngeal resistance, determined during standardized phonation, is a reliable objective parameter of vocal function after chemoradiation therapy for head and neck cancer. A standardized clinician-based communication scale holds promise as a useful tool. Acoustic measures reflect the sound of the voice but not the ability to communicate effectively.

Three-dimensional motion of the arytenoid adduction procedure in cadaver larynges.

To determine whether variation in suture placement could improve the results of the arytenoid adduction procedure, a model was developed using fresh human cadaver larynges. Three-dimensional (3-D) motion of the arytenoid was determined by utilizing computed tomographic imaging with radiopaque markers on the apex and muscular and vocal processes. By utilizing principles previously applied to the study of rigid body mechanics for the carpal, knee, and tarsal joints, rotation and translation of the arytenoid about the axial, coronal, and sagittal axes were calculated. Subglottic airflow resistance was measured before and after the procedure. Posterior glottic closure was reproducibly achieved, as determined by computed tomographic imaging and airway resistance. Conflicting reports on cricoarytenoid joint mechanics can be attributed to reliance on trigonometric analysis of two-dimensional images, which results in errors in out-of-plane motion. This paper presents a useful model for obtaining detailed anatomic information describing arytenoid 3-D motion.