BACKGROUNDThe survival of patients with head and neck squamous cell carcinoma (HNSCC) remains unaffected despite recent therapeutic advances. To reverse this trend, reliable and clinically applicable markers of tumor aggressiveness must be identified. One such marker may be the tumor‐associated macrophage content. The authors hypothesized that tumor‐associated macrophages contribute to HNSCC aggressiveness, and the objective of the current study was to prove this hypothesis using mRNA expression analysis and a large cohort of clinical specimens.METHODSOligonucleotide microarray analysis was performed on a prospective cohort of 20 patients with previously untreated oral cavity or oropharynx squamous cell carcinoma (OC/OP SCCA) and on normal oropharyngeal mucosa from 4 patients. After determining whether macrophage chemoattractants were produced by tumors, conditioned media from three HNSCC cell lines were used to quantify macrophage migration in an in vitro assay. A high‐density tissue microarray of 102 patients with previously untreated OC/OP SCCA was stained immunohistochemically for CD68 to identify tissue macrophages, and the results were correlated with clinicopathologic data and survival.RESULTSMonocyte chemoattractant protein 1 was up‐regulated significantly in tumors compared with normal mucosa (P = 0.0025; fold change = 1.89). All University of Michigan SCC tumor cell line conditioned media caused a significant increase in macrophage migration (P < 0.05). Tissue microarray data revealed that macrophage content of the primary tumor was associated strongly with lymph node metastasis (P < 0.0001), extracapsular lymph node spread (P = 0.0001), and advanced clinical disease stage (P = 0.0002). When it was evaluated along with other clinicopathologic data, the macrophage content was found to be an independent predictor of lymph node metastasis (P < 0.0001).CONCLUSIONSPrimary tumor macrophage content is a strong predictor of tumor aggressiveness in HNSCC. Cancer 2004. © 2004 American Cancer Society.

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Electromyographic monitoring of the RLN using a postcricoid surface electrode provides a safe, simple, and effective method for intraoperative monitoring during thyroid or parathyroid surgery. Further, evoked electromyography confirms RLN integrity at the conclusion of surgery.

Purpose: Survival rates for squamous cell carcinoma of the head and neck (SCCHN) have remained unchanged for several decades due to local tumor recurrences as well as regional and distant metastases. Recent evidence has shown that RhoC GTPase is overexpressed in stages III and IV regionally metastatic SCCHN compared with stages I and II localized disease. This study evaluated the expression of RhoC in head and neck carcinoma and investigated the prognostic use of this marker on a large cohort of previously untreated patients with SCCHN. Experimental Design: Standard Western blot techniques were used to evaluate RhoC protein expression in nine established head and neck cancer cell lines and in normal oral epithelium. In vivo expression of RhoC in metastatic and nonmetastatic SCCHN was investigated using immunohistochemical analysis on a tissue microarray composed of 113 independent tumor samples. RhoC expression was analyzed as it related to clinical and pathologic variables of interest. Results: Levels of RhoC protein were increased in the SCCHN cell lines compared with normal oral epithelium.The in vivo expression of RhoC correlated with advanced clinical stage and lymph node metastases for the entire patient cohort as well as in small primary tumors (T 1 and T 2 ). Conclusions:This study is the first to examine the expression of RhoC GTPase protein in SCCHN and normal squamous epithelium. It is clear from the results that RhoC is a specific marker of lymph node metastases in patients with this challenging form of carcinoma. RhoC levels seem to identify a subset of patients with early tumor stage primary tumors and high metastatic potential that might benefit from more aggressive therapy. Through continued investigation, blockade of RhoC activity may be a potential target in the development of novel strategies for treating metastases of head and neck cancer. Squamous cell carcinoma of the head and neck (SCCHN)accounts for >95% of all head and neck malignancies and is responsible for f40,000 incident cases yearly in the United States. Unfortunately, the majority of SCCHN patients present with advanced-stage disease (stages III and IV), requiring multimodality therapy. Even with combinations of chemotherapy, radiotherapy, and surgery, cure rates are only 30% for advanced-stage disease and have remained unchanged for decades. This poor survival is due mainly to the development of local tumor recurrences as well as regional and distant metastases. Novel molecular predictors of regional and distant metastatic potential at the time of diagnosis are needed to help guide clinical therapy decisions.Many of the factors necessary to convey the metastatic phenotype to cancer cells are controlled by the members of the Ras superfamily of small GTP-binding proteins. RhoC GTPase is a member of the Ras superfamily, and its activation results in the assembly of the actin-myosin contractile filaments into focal adhesion complexes that, ultimately, lead to cell polarity and facilitate motility (1 -3). Our laboratory has d...

Intraoperative lymph node mapping and sentinel lymph node biopsy have proven beneficial techniques in staging adult patients with melanoma of the head and neck, where there is great variability in lymphatic drainage. This technique has also been applied to pediatric patients with truncal cutaneous melanomas in an effort to determine nodal status without the morbidity associated with complete lymph node dissection. Nevertheless, the utility of sentinel lymph node biopsy in head and neck melanoma in the pediatric population has not been established. The objective of the authors' study was to determine the clinical utility of intraoperative lymph node mapping and sentinel lymph node biopsy of head and neck melanoma in the pediatric population. The authors reviewed the records of seven pediatric patients with head and neck melanoma or borderline melanocytic proliferations of unknown biologic potential who underwent intraoperative lymph node mapping and sentinel lymph node biopsy between 1998 and 2001. All sentinel lymph node specimens were examined by a melanoma dermatopathologist for the presence of metastatic melanoma. The mean operative time for each case was 3 hours, 8 minutes (range, 2 hours, 15 minutes to 3 hours, 50 minutes). All seven pediatric patients who underwent extirpation of a primary head and neck melanoma and preoperative lymphoscintigraphy had unique and identifiable basins of drainage to regional nodal groups. Four of seven patients had at least one positive sentinel lymph node. Overall, five of 19 sentinel nodes (26 percent) resected had evidence of metastatic melanoma. Of the patients with positive sentinel lymph nodes, two of the primary lesions were diagnosed as melanoma while two were initially considered atypical melanocytic proliferations of uncertain biologic potential with melanoma in the differential diagnosis. Sentinel lymph nodes in pediatric patients with melanoma of the head and neck can be successfully mapped and biopsied, as in adult patients. In addition, this procedure can provide critical diagnostic information for those pediatric patients with diagnostically challenging, controversial, or borderline melanocytic lesions.

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To assess the effect of tetrathiomolybdate on cytokine expression, angiogenesis, and tumor growth rate in human squamous cell carcinoma (SCC). Design: Three human SCC cell lines were used in this study for both in vitro and in vivo investigations. Conditioned media from untreated and tetrathiomolybdatetreated cell lines were compared with regard to cytokine levels, endothelial cell chemotaxis, endothelial cell tubule formation, and migration and the ability to induce angiogenesis in a rat aortic ring array. In vivo UM-SCC-38 was seeded onto tissue-engineered scaffolds and surgically implanted into the flanks of immunodeficient mice. Tumor growth rates and the level of angiogenesis were compared after 2 weeks of therapy. Setting: A tertiary care facility. Results: In this study, we demonstrate that tetrathiomolybdate significantly decreases the secretion of interleukin 6 and basic fibroblast growth factor by head and neck SCC (HNSCC) cell lines in vitro. Furthermore, we demonstrate that tetrathiomolybdate significantly decreases the secretion of interleukin 6 and basic fibro-blast growth factor by HNSCC cell lines in vitro. Furthermore, tetrathiomolybdate treatment of HNSCC cell lines results in significantly decreased endothelial cell chemotaxis, tubule formation, and neovascularization in a rat aortic ring assay. This in vitro evidence of decreased angiogenesis by tetrathiomolybdate is confirmed in vivo by using a severe combined immunodeficiency disorder mouse model in which tetrathiomolybdate therapy is shown to prevent human blood vessel formation. Finally, human HNSCC implanted into immunodeficient mice grow to a much larger size in untreated mice compared with those treated with 0.7 mL/kg per day of oral tetrathiomolybdate. Conclusions: These findings illustrate the ability of tetrathiomolybdate to down-regulate proinflammatory and proangiogenic cytokines in HNSCC. These observations are potentially exciting from a clinical perspective because a global decrease in these cytokines may decrease tumor aggressiveness and reverse the resistance to chemotherapy and radiation therapy seen in this tumor type.

Arnica montana seems to accelerate postoperative healing, with quicker resolution of the extent and the intensity of ecchymosis after osteotomies in rhinoplasty surgery, which may dramatically affect patient satisfaction.