Faculty Bibliography

In this study, we investigated the role of the peripheral endothelin-1 (ET-1) concentration in a cancer pain model. To test the hypothesis that the concentration of ET-1 in the tumor microenvironment is important in determining the level of cancer pain we used two cancer pain mouse models that differed significantly in production of ET-1. The two mouse cancer models were produced by injection of cells derived from a human oral squamous cell carcinoma (SCC) and melanoma into the hind paw of female mice. Pain, as indicated by reduction in withdrawal thresholds in response to mechanical stimulation, was significantly greater in the SCC group than the melanoma group. The peripheral concentration of ET-1 within the cancer microenvironment was significantly greater in the SCC group. Intra-tumor expression of both ET-1 mRNA and ET-1 protein were significantly higher in the SCC model compared to the melanoma model. ET receptor antagonism was effective as an analgesic for cancer pain in the SCC model only. To address the potential confounding factor of tumor volume we evaluated the contribution of tumor volume to cancer pain in the two models. The mean volumes of the tumors in the melanoma group were significantly greater than the tumors in the SCC group. In both groups, the pain level correlated with tumor volume, but the correlation was stronger in the melanoma group. We conclude that ET-1 concentration is a determinant of the level of pain in a cancer pain mouse model and it is a more important factor than tumor volume in producing cancer pain. These results suggest that future treatment regimens for cancer pain directed at ET-1 receptor antagonism show promise and may be tumor type specific

PURPOSE: Squamous cell carcinomas of the hard palate, maxillary gingiva, and maxillary alveolus occur at relatively low rates compared with squamous cell carcinomas in other oral sites. There is little within the surgical literature to guide treatment for maxillary squamous cell carcinoma. To date, only 1 other group has addressed neck management in the oral maxillary squamous cell carcinoma patient presenting with a clinically negative neck. Adequate characterization of maxillary gingival carcinoma behavior with respect to regional cervical metastasis is wanting. PATIENTS AND METHODS: We present a retrospective review of our own clinical experience as well as a review of the existing literature. RESULTS: In our University of California San Francisco patient group, cervical disease was detected in 20% of those individuals with maxillary squamous cell carcinoma presenting for initial consultation. After ablative surgery, those individuals who presented with clinically negative necks had a 21.4% rate of regional node metastasis. Ultimately, 50% of our patients with squamous cell carcinomas of the palate, maxillary gingiva, and maxillary alveolus developed regional or metastatic distant disease; 42.9% of the patients manifested disease to the cervical lymph nodes alone. CONCLUSIONS: The cases of oral maxillary squamous cell carcinomas reviewed herein exhibit aggressive regional metastatic behavior comparable to that of such carcinomas of the tongue, floor of the mouth, and mandibular gingiva. Based on the findings presented herein, we recommend selective neck dissection in the setting of a clinically negative neck as a primary management strategy for patients with oral maxillary squamous cell carcinomas involving the palate, maxillary gingiva, and maxillary alveolus

We investigated the cannabinoid receptor (CBr) agonists Win55,212-2 (non-selective) and AM1241 (CBr2 selective) and the peripheral receptor (CBr1) in carcinoma-induced pain using a mouse model. Tumors were induced in the hind paw of female mice by local injection of a human oral squamous cell carcinoma (SCC). Significant pain, as indicated by reduction in withdrawal thresholds in response to mechanical stimulation, began at 4 days after SCC inoculation and lasted to 18 days. Local administration of Win55,212-2 (10 mg/kg) and AM1241 (10 mg/kg) significantly elevated withdrawal thresholds, indicating an antinociceptive effect. Ipsilateral expression of CBr1 protein in L5 DRG was significantly upregulated compared to ipsilateral L4 DRG and in normal tissue. These findings support the suggestion that cannabinoids are capable of producing antinociception in carcinoma-induced pain

PURPOSE: Resecting oral squamous cell carcinoma (SCC) with an appropriate margin of uninvolved tissue is critical in preventing local recurrence and making the decision regarding postoperative radiation therapy. This task can be difficult due to the discrepancy between margins measured intraoperatively and those measured microscopically by the pathologist after specimen processing. The goal of this study is to quantify and compare the amount of margin discrepancy observed based on tumor location and staging. MATERIALS AND METHODS: Forty-one patients who underwent resective surgery with curative intent for primary oral SCC were included in this study. All patients underwent resection of the tumor with a measured 1 cm margin by one attending surgeon. Specimens were then submitted for processing and reviewing and histopathologic margins were measured. The closest histopathologic margin was compared with the in situ margin (1 cm) to determine percentage discrepancy. Percent discrepancies were grouped by locations (buccal mucosa, mandibular alveolar ridge, and retromolar trigone in group 1; maxillary alveolar ridge and palate in group 2; and oral tongue in group 3) and analyzed. Percent discrepancies grouped by stages T1/T2 or T3/T4 were compared. RESULTS: The mean discrepancy for all patients was a statistically significant 59.02% (P < .0001). The mean discrepancy was 71.90% for group 1, 53.33% for group 2, and 42.14% for group 3 (P = .0133). The mean discrepancy in T1/T2 tumors was 51.48% and in T3/T4 tumors was 75.00% (P = .0264). CONCLUSIONS: Oral SCC margin discrepancies after resection and specimen processing are highly significant. Tumors located in the buccal mucosa, retromolar trigone, and mandibular alveolar ridge show significantly greater discrepancies than tumors of the maxilla or oral tongue. Late stage tumors also show significantly greater margin discrepancies. These findings suggest that it might be prudent to consider oral site and staging when outlining margins to ensure adequacy of resection

OBJECTIVES: This study capitalizes on the unique molecular and developmental similarities between the auditory organs of Drosophila and mammals, to investigate genes implicated in human syndromic and nonsyndromic hearing loss in a genetically tractable experimental animal model, the fruit fly Drosophila. METHODS: The Drosophila counterparts of 3 human deafness genes (DIAPH1/DFNA1, ESPN/DFNB36, and TMHS/DF-NB67) were identified by sequence similarity. An electrophysiological assay was used to record sound-evoked potentials in response to an acoustic stimulus, the Drosophila courtship song. RESULTS: Flies with mutations affecting the diaphanous,forked, and CG12026/TMHS genes displayed significant reductions in the amplitude of sound-evoked potentials compared to wild-type flies (p < 0.05 to p < 0.005). The mean responses were reduced from approximately 500 to 600 microV in wild-type flies to approximately 100 to 300 microV in most mutant flies. CONCLUSIONS: The identification of significant auditory dysfunction in Drosophila orthologs of human deafness genes will facilitate exploration of the molecular biochemistry of auditory mechanosensation. This may eventually allow for novel diagnostic and therapeutic approaches to human hereditary hearing loss

BACKGROUND: Several unique complications of thyroidectomy exist because of its regional anatomy; they are well studied and reported. A majority of thyroidectomy patients report vague upper aerodigestive tract complaints. Despite this, no formal assessment of the integrity of the internal branch of the superior laryngeal nerve after thyroidectomy exists in the literature. METHODS: Thirty three patients undergoing thyroidectomy were prospectively evaluated with preoperative and postoperative laryngopharyngeal sensory testing. RESULTS: Preoperatively, 16 patients (49%) reported dysphagia, and 19 (58%) complained of globus sensation. Postoperatively, 24 (73%) patients complained of dysphagia, and 25 (76%) reported globus sensation. Preoperative sensory testing showed a mean sensory threshold of 2.79 +/- 0.51 mm Hg. The mean change in thresholds postoperatively was trivial (0.07 +/- 0.29 mm Hg), and did not differ significantly from zero (p = .19). CONCLUSIONS: Although most patients report significant difficulty swallowing after thyroidectomy, the sensory nerve to the laryngopharynx remains intact and is not at risk during thyroid surgery

OBJECTIVES: To provide comprehensive temporal trend analysis of 5-year relative survival rates of laryngeal cancer using the Surveillance, Epidemiology, and End Results database; and to expand on prior reports by including inclusion of laryngeal tumor location, stage, age at diagnosis, treatment strategy, and histologic grade. DESIGN: Retrospective cohort analysis using the Surveillance, Epidemiology, and End Results database of the National Cancer Institute. The Surveillance, Epidemiology, and End Results data were used to design 5 cohorts of patients with laryngeal cancer: 1977-1978, 1983-1984, 1989-1990, 1995-1996, and 2001-2002. Five-year survival rates were analyzed according to tumor site, stage, and grade; age at diagnosis; and treatment strategy. The joinpoint regression model was used to assess survival trends and their statistical significance. RESULTS: Among patients with supraglottic cancer, 5-year relative survival rates for distant disease worsened over time while rates for local and regional disease did not change (P = .01 and P > .05, respectively). For localized glottic cancer, survival remained stable from 1977-1978 to 2001-2002. However, patients with regional and distant glottic cancer demonstrated a significant decrease in survival in the past 3 decades (P < .001). This trend was independent of treatment strategy. Finally, the proportion of well-differentiated tumors in patients with regional laryngeal cancer decreased over time (P < .001 for supraglottic and P = .007 for glottic). CONCLUSIONS: A decreasing 5-year survival trend was found among patients with glottic cancer who had regional disease and in all patients with distant disease. Histopathologic trends not previously reported in those with laryngeal cancer seem to parallel those seen in other tobacco-related cancers. These trends may reflect the effect of birth cohorts and implicate the relationship between carcinogenic exposure and host factors, rather than the influence of treatment

The purpose of this article is to discuss the most significant oral health and related problems experienced by women, and to provide a Nurse's Plan of Action to respond to these largely preventable diseases. Oral health is integral to women's overall health and well-being, with poor oral health being associated with cancer, heart disease, diabetes, depression, and the birth of preterm, low-birthweight babies. Poor nutrition and lifestyle, principally tobacco and heavy alcohol use, can further increase the risk for oral diseases. Disparities are evident in women's reported poor access of regular dental care related to lack of dental insurance and low income. These facts are disturbing because most oral diseases are preventable. The Surgeon General's report on oral health in America (U.S. Department of Health and Human Services, 2000) and, more recently, the 'National Call to Action to Promote Oral Health' (U.S. Department of Health and Human Services, 2003) emphasized the need for partnerships of key stakeholders, including nurses, to get involved in oral disease prevention. Nurses are in an ideal position to provide health promotion education and screening across the multitude of settings in which they work regarding oral health and risk factors for oral disease. Nursing interventions aimed at promoting healthy outcomes and preventing disease should include a focus on oral health