Elective neck dissection and survival in patients with squamous cell carcinoma of the oral cavity and oropharynx

OBJECTIVE/HYPOTHESIS: The utility of elective neck dissection in the management of patients with oral cavity and oropharyngeal cancer who present without neck metastases remains controversial. The study addressed the question of whether elective neck dissection improves regional control and survival in patients with squamous cell carcinoma of the oral cavity and oropharynx presenting with T1/T2 node-negative disease. STUDY DESIGN: A nonrandomized, uncontrolled retrospective chart review. METHODS: A nonrandomized, uncontrolled retrospective chart review was performed. Resection of the primary tumor was performed in all patients. The neck was observed in one group, and elective neck dissection was performed for patients in another group. RESULTS: The study data indicated that elective neck dissection significantly improves regional control and regional recurrence-free survival. Elective neck dissection when compared with observation of the neck did not improve overall survival. CONCLUSION: Elective neck dissection reduces regional recurrence and may extend disease-free survival.     

Nitric Oxide Improves Cisplatin Cytotoxicity in Head and Neck Squamous Cell Carcinoma

Objective To test whether nitric oxide (NO) enhances the cytotoxicity of cisplatin in a head and neck squamous cell carcinoma (HNSCC) cell line. Background Cisplatin is one of the most frequently used chemotherapeutic agents in the treatment of HNSCC. NO has been shown to play an important role in regulating tumor growth. Previous studies demonstrate that NO can enhance the cytotoxicity of cisplatin in Chinese hamster lung fibroblasts. In this report, we examined the in vitro interaction of NO and cisplatin in a HNSCC cell line. Materials and Methods CCL23 cells were pretreated with three different NO donors: PAPA/NO (t 1/2 = 15 min), DPTA/NO (t 1/2 = 3 h), and DETA/NO (t 1/2 = 20 h). The cells were rinsed and exposed for 6 hours to a culture medium containing cisplatin. Cell survival and LD₅₀ of cisplatin were calculated with and without NO pretreatment. Results PAPA/NO and DPTA/NO did not show any cytotoxic activity and did not change the LD₅₀ of cisplatin. DETA/NO when used alone resulted in 25.6% cell death at its peak dose (100 μM). Pretreatment with DETA/NO resulted in almost a threefold reduction of the LD₅₀ of cisplatin (6.8 vs. 2.4 μg/mL). Pretreatment with DETA/NO sensitized the HNSCC cells to subsequent cisplatin activity (two‐sided P = .00016). Conclusion Pretreatment of HNSCC cells with long‐acting NO donors enhances cisplatin activity. Short‐ and medium‐acting NO donors do not exert a toxic effect and do not augment the activity of cisplatin. NO agonists should be considered in the future as a possible adjunct to cisplatin in the treatment of HNSCC. Further studies with animal models are necessary to further clarify this relationship.     

XPD Polymorphisms and Risk of Squamous Cell Carcinoma of the Head and Neck in a Korean Sample

Objectives

XPD is a major player in nucleotide excision repair, which is one of the basic pathways of DNA repair. The objective of this study was to investigate the association of XPD single nucleotide polymorphisms (SNPs) and the risk of squamous cell carcinoma of the head and neck (SCCHN) in Koreans.

Methods

We performed XPD +23591G>A and +35931A>C genotyping in 290 SCCHN patients and 358 controls.

Results

The frequencies of the XPD +23591G>A (GG/GA/AA) genotypes were 89.0%/11.0%/0% in the patients and 90.3%/8.8%/0.9% in the controls, respectively. The odds ratio (OR) of the XPD +23591 GA genotype was 1.94 (0.92 to 4.08) in reference to the GG genotype. The frequencies of the XPD +35931A>C (AA/AC/CC) genotypes were 86.9%/12.0%/1.1% in the patients and 85.6%/13.8%/0.6% in the controls, respectively. The OR of the XPD +35931 AC and CC genotypes were 0.98 (0.51 to 1.88) and 2.68 (0.71 to 10.1), respectively, in reference to the AA genotype. On the subgroup analyses according to the smoking and drinking statuses, the SNPs and haplotypes of XPD showed no statistically significant association with the risk of SCCHN.

Conclusion

The results of this study suggest that the XPD +23591G>A and +35931A>C SNPs are not associated with the risk of SCCHN in Koreans; however, a further study with a larger number of subjects is necessary to verify this conclusion.     

头颈部中晚期鳞癌大剂量滴注化疗的应用

对３６例初治头颈部中晚期鳞癌患者进行前瞻性随机对照研究。第一组（２０例）为大剂量顺铂（ｐＤＤ）加５－氟脲嘧啶（５－Ｆｕ）１２０小时连续滴注组（连续组）。另一组（１６例）为ＰＤＤ加５－Ｆｕ常规点滴组（常规组）。连续组和常规组有效率分别为９０．０％（完全缓解２０％，部分缓解７０％）和４３．８％（完全缓解６，３％，部分缓解３７．５％），差异有非常显著性意义（Ｐ＝０．００３９）。二组副作用相似且临床可接受（各项Ｐ值均大于０．０５）。认为２～３段大剂量ＰＤＤ＋５－Ｆｕ１２０小时连续滴注化疗是高度有效和安全的。     

Upper neck (level II) dissection for N0 neck supraglottic carcinoma

OBJECTIVES: Elective neck dissection for the N0 neck in head and neck surgery is still controversial. This prospective nonrandomized study of N0 supraglottic carcinoma was designed to find an appropriate method of neck management. STUDY DESIGN: Anatomical studies show that the first echelon of lymphatic drainage from the supraglottic larynx is toward the upper jugular nodes (level II). An upper neck dissection (UND) was applied and all the lymph nodes were sent for frozen section. If the subclinical metastasis was found, a modified neck dissection was performed. If the nodes harbored no foci of cancer, the patients were observed after surgery on the supraglottic lesions. METHODS: Patient records of 142 patients with supraglottic laryngeal cancer (T1-4N0M0) were reviewed, with special attention paid to neck recurrences and survival rates. The cases were treated between 1976 and 1990 and all were observed for at least 5 years after the operation or until the time of death. RESULTS: The UND specimens of 142 patients were negative for metastasis. The 5-year survival rate for this group after surgery was 80.8%, according to the life table analysis. Fifteen of the 142 patients (10.6%) had neck recurrences during the period of observation within 5 years. The recurrence rate of this series with limited dissection on the neck was comparable with those reported in the literature after neck dissection, either radical or modified. CONCLUSIONS: There is no need for a comprehensive neck dissection for N0 supraglottic laryngeal cancer. A selective neck dissection such as UND (level II) or a supraomohyoid neck dissection (sparing the submandibular region) of level II and III will serve the purpose of radical neck treatment for the supraglottic cancer.     

Ethanol Decreases Negative Cell-cycle-regulating Proteins in a Head and Neck Squamous Cell Carcinoma Cell Line

Epidemiologic studies have provided evidence of an alcohol-associated increased risk of upper aerodigestive tract cancers. Recently we reported ethanol-induced proliferation in a squamous cell carcinoma of the head and neck (SCCHN) cell line, but the underlying mechanisms are unknown. In order to further clarify these findings, major G0/G1-regulating proteins were investigated in the present study. Synchronized cells of a SCCHN line (JP-PA) and a human immortalized keratinocyte line (HaCaT)--used as a control--were cultured with or without 10 -3 M ethanol for up to 96 h. At distinct time intervals the expression of cyclin D1 and the inhibitors p16, p18, p19 and p21 were determined by Western blot analyses. In both lines ethanol had no influence on the protein expression of cyclin D1. In contrast, distinct downregulations of p21, p18 and p19 were detectable at the protein level. The p16 protein was not expressed in the SCCHN line and was unchanged in the control line after the addition of ethanol. In these in vitro experiments the marked downregulation of important cell-cycle inhibitors may accelerate progression from the G1 to the S phase of the cell cycle. The relevance of our findings to in vivo conditions remains speculative, but the observed mechanisms of significantly reduced expression of cell-cycle inhibitor proteins may be involved in the carcinogenesis of head and neck malignancies.