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.

Magnetic resonance imaging of the paranasal sinuses: incidental abnormalities and their relationship to patient symptoms.

OBJECTIVES: Magnetic resonance imaging (MRI) is able to demonstrate a wide range of abnormalities in the paranasal sinuses, which are often reported as incidental findings on scans performed for indications other than the evaluation of paranasal sinus pathology. However, the clinical significance of these findings remains undefined. We present a prospective study that determines the prevalence of abnormalities in the paranasal sinuses in a population undergoing MRI scans for suspected intracranial disease. These findings are correlated with clinical data pertaining to nasal and sinus symptoms. STUDY DESIGN: Prospective, cross-sectional study. METHODS: Patients undergoing MRI scans for suspected intracranial pathology were asked to complete a questionnaire pertaining to symptoms of nasal/sinus pathology. The T2-weighted scans of 86 patients (mean age = 51 years) were then reviewed for evidence of paranasal sinus pathology using a standardized method for evaluation and reporting of results. These results were then correlated with those obtained from the patient questionnaire. RESULTS: Radiologic abnormalities were found in the paranasal sinuses of 33 (38%) patients. Abnormalities were most commonly seen in the ethmoid sinuses (44.8%) followed by the maxillary (38%), sphenoid (14%), and frontal (3%) sinuses. Analysis of the clinical data revealed no significant relationship between the presence of clinical symptoms of nasal and sinus pathology and abnormalities on MRI scan. CONCLUSION: The assessment of inflammatory sinus pathology remains controversial. Based on the results of this study, incidental abnormalities of the paranasal sinuses detected on MRI scan do not appear to be related to clinical symptoms.

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.

Laryngeal contact granuloma.

OBJECTIVE: To report outcomes of treatment for laryngeal contact granuloma. STUDY DESIGN: Prospective treatment of 21 patients with laryngeal contact granulomas using proton-pump inhibitor (PPI) medication. METHODS: Patients were diagnosed and followed by office endoscopy and patient interview. RESULTS: Three patients did not tolerate PPI medication and were managed by treatment with type 2 histamine (H2) blockers. The lesion completely resolved in 14 of the 18 patients maintained on PPI medication, and significantly regressed in the other 4. Residual granulomas were surgically excised in one patient. Lesions resolved in two patients following injection of botulinum toxin into one thyroarytenoid muscle. One patient had a residual lesion, but symptoms were controlled by medication, and he declined treatment with botulinum toxin. Of the three patients treated with H2-blocker medication, the lesion resolved in only one. CONCLUSION: PPI medication is effective in the treatment of laryngeal contact granuloma, even in the absence of identifiable symptoms of gastroesophageal reflux.

Paroxysmal laryngospasm after laryngeal nerve injury.

OBJECTIVE: Describe a clinical syndrome of laryngeal hypersensitivity following laryngeal nerve injury. STUDY DESIGN: Retrospective review of six patients with laryngeal paralysis sustained during neck surgery who presented with paroxysms of coughing and stridor, progressing to brief episodes of complete airway occlusion. METHODS: Chart review. RESULTS: Superior laryngeal nerve blockade temporarily improved symptoms in four of five patients. Botulinum toxin relieved spasm in two of three patients and reduced symptoms in the third. Symptoms gradually diminished or resolved in four patients from 1 to 2.5 years later. One patient underwent arytenoidectomy and one patient has a tracheostomy. CONCLUSIONS: Patients with laryngeal injury may present with stridor and acute airway obstruction secondary to paroxysmal laryngospasm. The authors have found that superior laryngeal nerve blockade or botulinum toxin may be effective in temporary relief of symptoms.

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.