p53 gene status as a predictor of tumor response to induction chemotherapy of patients with locoregionally advanced squamous cell carcinomas of the head and neck.

PURPOSE: To determine whether p53 gene status predicts tumor responses to platinum- and fluorouracil-based induction chemotherapy in locoregionally advanced squamous cell carcinomas of the head and neck. PATIENTS AND METHODS: Tumor responses of 105 patients were measured at the primary tumor site. Objective response and major response were defined by a 50% and 80% reduction in tumor size, respectively. All coding parts of p53 gene were directly sequenced. p53 expression in tumor cells was determined by immunohistochemistry. Human papillomavirus infection was detected by polymerase chain reaction. Odd ratios were adjusted by stepwise logistic regression analysis. RESULTS: p53 mutations, p53 expression, and tumor stage were sufficient to explain the variation in tumor responses to chemotherapy in multivariate models. p53 mutation was the only variable to significantly predict objective response (odds ratio, 0. 23; 95% confidence interval, 0.10 to 0.57; P =.002) and was the strongest predictor of major response (odds ratio, 0.29; 95% confidence interval, 0.11 to 0.74; P =.006). p53 expression (odds ratio, 0.39; 95% confidence interval, 0.16 to 0.98) and tumor stage (odds ratio, 0.31; 95% confidence interval, 0.10 to 0.96) also predicted major response. Specific mutations (contact mutations) accounted for much of the reduction in the risk of major response associated with overall mutations. In complementary analyses, p53 expression was weakly predictive of major response in the subgroup with wild-type p53, and p53 mutations also predicted histologic response. CONCLUSION: p53 gene mutations are strongly associated with a poor risk of both objective and major responses to chemotherapy. Contact mutations are associated with the lowest risk of major response to chemotherapy.

CFTR, MDR1, and MRP1 immunolocalization in normal human nasal respiratory mucosa.

CFTR (cystic fibrosis transmembrane conductance regulator), MDR1 (multidrug resistance), and MRP1 (multidrug resistance-associated protein), members of the ABC transporter superfamily, possess multiple functions, particularly Cl(-), anion, and glutathione conjugate transport and cell detoxification. They are also hypothesized to have a number of complementary functions. It is generally accepted that data obtained from nasal mucosa can be extrapolated to lower airway cell physiology. The aim of the present study was to investigate by immunohistochemistry the differential localization of CFTR, MDR1, and MRP1 in the normal mucosa of 10 human nasal turbinates. In ciliated epithelial cells, CFTR was inconstantly expressed at the apical cell surface, intense membranous labeling was observed for MDR1, and intense cytoplasmic labeling was observed for MRP1. In the glands, a higher level of expression was observed on serous cells, at the apical surface (for CFTR), on lateral membranes (for MDR1), and with an intracytoplasmic distribution (for MRP1). In conclusion, CFTR, MDR1 and MRP1 are expressed in the epithelium and glands of the nasal respiratory mucosa, but with different patterns of expression. These results suggest major roles for CFTR, MDR1, and MRP1 in serous glandular cells and a protective function for MDR1 and MRP1 in respiratory ciliated cells. (J Histochem Cytochem 48:1215-1222, 2000)

Conservative surgery in T3-T4 pharyngolaryngeal squamous cell carcinoma: an alternative to radiation therapy and to total laryngectomy for good responders to induction chemotherapy.

OBJECTIVE: To evaluate the possibility of preservation of the larynx after neoadjuvant chemotherapy by performing a conservative surgery instead of total laryngectomy initially planned, in patients with previously untreated laryngeal and piriform sinus squamous cell carcinoma (SCC). STUDY DESIGN: Retrospective study. METHODS: A total of 115 patients treated at Tenon Hospital with induction chemotherapy from 1985 to 1995, all with initial indication of radical surgery, were available for the study. The clinical tumor response was evaluated after three cycles of chemotherapy. According to this response, to preserve laryngeal functions, some patients had a modification of the treatment initially planned: radiation therapy essentially for complete responders, and conservative surgery for some partial responders. RESULTS: Of 69 patients with laryngeal cancer, 14 were treated by partial laryngectomy and 19 by radiation therapy; of 46 patients with piriform sinus cancer, 8 were treated by partial surgery and 12 by radiation therapy; the other patients were treated as was initially planned (total laryngectomy with partial pharyngectomy). Overall survival rates, estimated by the Kaplan-Meier method, were not statistically different between the three treatment groups. The laryngeal functions were preserved in 54% of the patients who were alive at 3 years. CONCLUSION: This report is a retrospective study, but these results suggest the possibility of using conservative surgery, instead of initially planned total laryngectomy, for good responders to induction chemotherapy with a small residual tumor.

Human papillomavirus in head and neck squamous cell carcinomas in nonsmokers.

OBJECTIVE: To establish relationships between smoking status and human papillomavirus in head and neck squamous cell carcinomas. DESIGN: Human papillomavirus was detected in paraffin-embedded samples using E6-directed consensus primers and type-specific oligonucleotide probes. Patients were classified as smokers and nonsmokers. Alcohol use was also recorded. Data were analyzed by means of the Fisher exact test. Sequence analysis of exons 5 to 8 of the p53 gene was performed in tumor samples from nonsmokers. SETTING: Academic medical center in Paris, France. PATIENTS: One hundred eighty-seven consecutive patients with head and neck squamous cell carcinoma. RESULTS: The overall prevalence of human papillomaviral infection was 10.7%. Human papillomavirus occurred more frequently (P = .02) in oropharyngeal squamous cell carcinoma (18.6%) than in other locations (6.1%). There were 10 nonsmokers (5%). The 50% incidence of human papillomavirus in nonsmokers (95% confidence interval, 19%-81%) differed significantly from the 8.5% incidence in smokers (95% confidence interval, 5%-14%; P = .003). No occupational risk factor was recorded in nonsmokers. None of these patients had p53 gene mutations in cancer cells. CONCLUSION: These findings suggest that human papillomavirus may play a role in head and neck squamous cell carcinomas in nonsmokers.

The "sign of the rising tide" during swallowing fiberoscopy: a specific manifestation of Zenker's diverticulum.

Pooling of secretions in the hypopharynx is a common sign of an impaired upper esophageal sphincter. Until now, no specific manifestation, observed by flexible laryngoscopy, of Zenker's diverticulum has been reported. Direct visualization of the diverticulum can be missed during flexible laryngoscopic examination. In this series of 12 patients with hypopharyngeal diverticulum, we have described a manifestation of Zenker's diverticulum obtained on videofiberoscopy during cream swallowing. We have called it the "sign of the rising tide" because it describes the backup of cream visible in the hypopharynx as a wave after its complete disappearance. Barium swallow study is necessary to confirm the presumptive diagnosis. This relevant manifestation seems to be specific for Zenker's diverticulum, since it is not observed in other upper esophageal sphincter disorders, and it disappears when surgical treatment is successful.

Use of a coincidence gamma camera to detect primary tumor with 18fluoro-2-deoxy-glucose in cervical lymph node metastases from an unknown origin.

This study was performed to evaluate the ability of a dual-head gamma camera with 18fluoro-2-deoxy-glucose coincidence detection emission tomography (FDG-CDET) to detect primary tumors in patients with cervical lymph node metastases of head and neck squamous cell carcinoma from an unknown origin. From 60 patients with untreated head and neck squamous cell carcinoma, we selected 4 in whom no evidence of the primary's origin was found by the conventional methods used for the evaluation of head and neck tumors. In addition to the panendoscopy, chest radiography, a computed tomography (CT) scan, and FDG-CDET were performed. Both FDG-CDET and the CT scan located cervical lymph node metastases. In addition, FDG-CDET located the primary tumor in 3 of the 4 patients, and the tumors were confirmed with histopathologic findings. In contrast, the CT scan detected the primary tumor in none of them. FDG tomography performed on a coincidence gamma camera appears to be a successful new tool in detecting occult primary tumors in head and neck carcinoma, and is useful in guiding endoscopic biopsies. It has, further, the important potential ability to detect distant metastases on whole body images.

Osteoradionecrosis of the hyoid bone: a report of 3 cases.

PURPOSE: Osteonecrosis of the hyoid bone is an uncommon disease that has only been described occasionally in the literature. MATERIALS AND METHODS: We report 3 cases of osteonecrosis of the hyoid bone after radiation therapy for carcinoma at various sites in the head and neck region. RESULTS: Imaging computed tomography (CT) scans were performed for all 3 cases and did aid in the diagnosis. In 1 case, a 201thallium scintigraphy and a bone scan (99mtechnetium-diphosphonate) were performed and this confirmed the diagnosis of osteoradionecrosis. CONCLUSION: Osteoradionecrosis of the hyoid bone may be misdiagnosed as recurrent neoplasm. Although recurrent or persistent neoplastic disease must initially be ruled out, it is subsequently important to correctly identify osteonecrosis of the hyoid bone, because its surgical treatment is simple and the prognosis is good.