Facial plastic surgery Web site ethics.

Before the Internet can be used to its full potential in health care, several important barriers need to be overcome. These barriers include equitable access to information, imbalance between patient health literacy and the information provided, extreme variability in the quality of the content, the potential for commercial interests to influence content, and the need for preservation of personal privacy. Facial plastic surgeons have an obligation to use the Internet ethically and responsibly and to formulate the evolving guidelines for its use.

Chromosomal aneuploidy precedes morphological changes and supports multifocality in head and neck lesions.

OBJECTIVE: To identify chromosome changes associated with the transformation of dysplastic lesions and to verify evidence for multifocality in synchronous premalignant lesions associated with head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: Chromosomal aneuploidy was evaluated in sections of formalin-fixed, paraffin-embedded tissues from 16 patients with HNSCC, including sites with normal squamous mucosa, dysplasia (low- and high-grade), and invasive tumor. METHODS: A panel of 6 centromeric probes (chromosomes 1, 3, 7, 8, 9, and 17) was analyzed in dual-color fluorescence in situ hybridization assays, using matched hematoxylin-eosin-stained sections for histologic correlation. RESULTS: Imbalances for most of the targets tested were found in 20 of 24 invasive carcinoma sites, mainly represented by gain in copy number per cell. However, cell populations with chromosome losses and gains in multimodal patterns were concomitantly observed in a number of tumors, indicating a high degree of chromosome instability. The detection of chromosomal aneuploidy precedes the malignant transformation as indicated by findings of monosomy and trisomy in normal squamous mucosa, and in low-grade and high-grade dysplasia sites. Loss of chromosomes 3 and 17 prevailed in low-grade dysplasias, and gain of chromosomes 7 and 8 were prevalent in high-grade dysplasias. Synchronous low-grade and high-grade dysplastic lesions displayed discordant molecular signatures, suggesting a multifocal origin. CONCLUSIONS: The interphase fluorescence in-situ hybridization (FISH) assay with centromeric may detect early changes in the progression of dyplastic epithelia to invasive carcinoma and supports the field cancerization theory of multifocality.

eMedicine Otolaryngology: an online textbook for ENT specialists.

A new online publishing effort, eMedicine Otolaryngology-Facial Plastic Surgery (FPS), is a comprehensive textbook now being developed on the Internet (www.emedicine.com). This book is one of a series of 15 electronic textbooks written by a worldwide panel of authors and editors, and it is distributed free of charge to anyone with a computer and a modem. Advantages of online textbooks such as eMedicine Otolaryngology-FPS are that they provide readers with easy accessibility to reliable, up-to-date information, and they allow authors to quickly edit and revise editorial content and supplement traditional text with sound, graphics, and video. An ambitious undertaking, eMedicine Otolaryngology-FPS represents a significant advance in the way medical information is written, edited, and distributed. Although it is unlikely that electronic textbooks will replace traditional textbooks any time soon, these types of publishing efforts will continue to proliferate.

Recurrent psychogenic coma following tracheal stenosis repair.

Medication, intracranial hemorrhage, infarction, infection, hypoxia, organ failure, and nutritional deficiency may cause unconsciousness following successful emergence from anesthesia. A 39-year-old woman with a history of tracheal stenosis, depression, and anxiety had complete unconsciousness on 3 separate occasions following surgical repair of her tracheal stenosis. In each case, the patient's endotracheal tube had been removed; she was alert and oriented to person, time, and place; and she was admitted to the hospital for observation. Within a few hours after the tube was removed, the patient became abruptly unconscious for periods of 36, 18, and 30 hours. Each time, the results of cardiac, pulmonary, metabolic, and neurologic examinations and radiological studies were normal. We hypothesize that the patient's apparent comas were the result of an underlying conversion disorder precipitated by unresolved psychological conflict surrounding a long history of abuse in which she was repeatedly smothered by a pillow.

Otolaryngologic complications of the anterior approach to the cervical spine.

PURPOSE: To review current literature regarding otolaryngologic complications of the anterior approach to the cervical spine with the focus on the etiology, diagnosis, and treatment of these disorders. METHODS: A review of literature from the introduction of anterior cervical surgery (late 1950s) to the present was conducted by using computer databases and bibliographies of appropriate journal articles and texts. Key words included "anterior cervical surgery," "dysphagia," "surgical complications," and "hoarseness." CONCLUSION: Dysphagia and dysphonia are common conditions following anterior cervical fusion, and patients should be counseled on this risk preoperatively. The etiologies of these problems have not been clearly elucidated, and these complications are frequently underreported or ignored. Otolaryngologic consultation should be obtained for all patients with dysphagia or dysphonia that persists longer than 1 to 2 months, and consideration should be given to having all patients at risk (previously operated patients) evaluated both preoperatively and postoperatively.

Identification of individuals at high risk for head and neck carcinogenesis using chromosome aneuploidy detected by fluorescence in situ hybridization.

To visualize the accumulation of chromosome abnormalities in head and neck squamous cell carcinomas (HNSCC) and investigate the extension of the abnormal field, we applied the fluorescence in situ hybridization (FISH) technique to tumor cells and cells collected from a large extension of clinically normal buccal mucosa distant from the tumor in 10 patients. DNA probes specific for 14 human chromosomes (1, 2, 3, 6, 7, 8, 9, 10, 11, 12, 15, 17, X, and Y) were used in dual-target, dual-color FISH assays. Control specimens were collected from oral mucosa of 10 healthy non-smokers, in order to define the tolerance limits for abnormalities, and from 10 healthy smokers. Extensive aneuploidy was detected in most of tumor specimens, more frequently represented by chromosome gains than losses. Interestingly, the clinically normal distant oral regions displayed chromosomal aneuploidies in seven out of the 10 patients tested. These findings support the occurrence of field cancerization in HNSCC. In addition, interphase FISH is demonstrated as an effective technique for detecting chromosome aneuploidy associated with malignancy and a potential tool for non-invasive screening of individuals at high-risk for HNSCC.

Hypopharyngeal stenosis and dysphagia complicating toxic epidermal necrolysis.

Toxic epidermal necrolysis is a severe dermatologic disorder clinically characterized by the acute onset of erythema and tenderness of the skin. Destruction of the epidermal barrier results in significant morbidity and mortality. Large erosions of mucous membrane, including the mouth and oral mucosa, are typical of toxic epidermal necrolysis. After ingesting naproxen sodium (Aleve) and aspirin, a previously healthy 43-year-old woman developed toxic epidermal necrolysis that resulted in hypopharyngeal stenosis complicated by dysphagia and recurrent aspiration.

Malignancy detection by molecular cytogenetics in clinically normal mucosa adjacent to head and neck tumors.

OBJECTIVE: To identify the potential use of chromosome imbalances as biomarkers for tumorigenesis in head and neck squamous cell carcinoma (HNSCC) by fluorescence in situ hybridization (FISH). DESIGN: In this case-control study, chromosome copy numbers were assessed in dual-target, dual-color FISH assays using DNA probes specific for 14 human chromosomes (1, 2, 3, 6, 7, 8, 9, 10, 11, 12, 15, 17, X, and Y) applied to exfoliated epithelial cells. SETTING: University medical center. PATIENTS: We examined 20 cell brushings (from 10 primary tumors and 10 clinically normal margins) collected from 10 patients with HNSCC and compared these with cell brushings from the oral cavity of 10 nonsmoker and 10 smoker control subjects. INTERVENTION: None. MAIN OUTCOME MEASURE: Chromosomal aneuploidy. RESULTS: Specimens from nonsmokers displayed greater than 91% of cells with normal signals, indicating high analytical sensitivity for the probes. Specimens from smokers demonstrated large variability without significant imbalance (P>.05) compared with those from nonsmokers. Tumor specimens from patients with HNSCC displayed significant chromosomal imbalance (P<.05) for all probes except chromosome Y. Similar imbalance, although in lower frequency, was found in all clinically normal adjacent mucosa specimens. CONCLUSIONS: Interphase FISH demonstrated great applicability in detecting chromosome imbalance associated with malignancy in HNSCC and clinically normal adjacent cells, thereby detecting subclinical tumorigenesis. A panel of chromosome probes (chromosomes 3, 8, 9, and 10) is proposed as an efficient and sensitive additional tool for future routine screening of tumor margins and potential diagnosis of residual disease in HNSCC.

Absence of p53 mutations in squamous carcinomas of the tongue in nonsmoking and nondrinking patients younger than 40 years.

BACKGROUND: Although carcinoma of the tongue usually occurs in patients older than 60 years, up to 4% of these tumors may occur in patients younger than 40 years. Many of the younger patients with this tumor have had no exposure or brief exposure to tobacco smoke or alcohol consumption, to which oral carcinoma is usually attributed. The molecular mechanism responsible for carcinogenesis in this group of patients is not known. OBJECTIVE: To assess the role of p53 gene mutation in oral carcinogenesis in a group of patients younger than 40 years with squamous carcinoma of the tongue. DESIGN: Squamous carcinoma cells were isolated from paraffin blocks by microdissection. DNA extracted from these cells was tested for the presence of p53 mutations by polymerase chain reaction and single-stranded conformational polymorphism analysis. Mutations identified by this procedure were directly sequenced. Sections of the tumors were also stained using an immunoperoxidase immunohistochemical technique for expression of p53 protein. SUBJECTS: Eleven patients were selected on the basis of 2 criteria: presence of squamous cell carcinoma and age younger than 40 years. Six of the 11 patients had no history of measurable tobacco or alcohol exposure. RESULTS: Two mutations were detected among 11 tumors by single-stranded conformational polymorphism analysis, one in exon 4 and a second in exon 7. The former mutation consisted of G:C to C:G (guanine:cytosine to cytosine:guanine) transition in codon 72 (CGC to CCC), which would have resulted in the substitution of a proline residue for arginine. With the immunoperoxidase immunohistochemical technique for p53 protein, strong, diffuse nuclear staining was observed only in this tumor. The second mutation was a G:C to A:T (guanine:cytosine to adenine:thymine) transition in codon 248 (CGG to CGA), which would have resulted in no amino acid change since both mutant and wildtype codon sequences encode arginine. Weaker and more variable anti-p53 immunostaining was noted in this and 4 other tumors. Five tumors were negative for p53 protein by the immunoperoxidase immunohistochemical technique. CONCLUSIONS: Our results suggest that p53 gene mutations are less frequent in squamous carcinomas occurring in nonsmoking young patients who do not drink alcohol than in young smokers or in the general population. Paucity of p53 mutations may be explained by the absence of exposure to tobacco smoke or alcohol. These data leave unanswered the question of the molecular mechanism responsible for oral carcinogenesis in this group of patients and suggest that this group may be a suitable population in which to study genetic susceptibility to aerodigestive carcinoma isolated from the confounding factors of tobacco and alcohol exposure.

Inhibition of proliferation and expression of T-antigen in SV40 large T-antigen gene-induced immortalized cells following transplantations.

Rat dopamine-producing nerve cells (1RB3AN27) and rat parotid acinar cells (2RSG) were immortalized by insertion of simian virus 40 (SV40) large T-antigen gene (LTa). Both of these cells divided and produced nuclear LTa in vitro. In order to assess the relationship between cell proliferation and expression of LTa in vivo, immortalized dopamine-producing nerve cells and parotid cells were grafted into the striatum and parotid gland of adult Sprague-Dawley rats, respectively. Grafted cells exhibited nuclear LTa at 1 day but not at 7 and 30 days after transplantation. At 30 days after transplantation, no tumor was found, and there was no evidence of cell division as determined by H and E staining. When the striatal areas containing the grafts were cultured, these cells did not express LTa at 4 days after plating; however, after 3 weeks, when most host cells were eliminated, the cultured grafted cells expressed LTa. After 3 months of culturing, only cells exhibiting LTa were present. These cells had the same morphology and divided with the same doubling time as 1RB3AN27 cells before grafting. Results suggest the presence of a LTa-inhibiting factor in vivo, and support the hypothesis that the expression of LTa is directly linked with proliferation of immortalized cells.

Transplantation of immortalized, nontumorigenic parotid acinar cells into the allogeneic rat parotid gland and oral submucosa.

The recent establishment of an immortalized clonal cell line of rat parotid acinar cells (2RSG) by transfecting isoproterenol-stimulated parotid cells with a plasmid vector, pSV3neo which carries the large T-antigen gene from SV40 virus, afforded the opportunity to develop a model for parotid acinar cell transplantation. Single cell suspensions of 2RSG cells labeled with a fluorescent tracer, DiI, were injected into the parotid gland or oral submucosa of allogeneic adult rats. The grafted cells survived and were functionally viable for at least 30 days. Histological sections revealed no evidence of infiltration of leukocytes or lymphocytes. Grafted cells did not form tumors. Results suggest that allogeneic parotid acinar cell transplantation is a feasible technique in the animal model.

Correlation of tumor markers p53, bcl-2, CD34, CD44H, CD44v6, and Ki-67 with survival and metastasis in laryngeal squamous cell carcinoma.

BACKGROUND: Recent basic discoveries about the biological significance of nuclear and cell-surface marker proteins have opened new areas of research into head and neck cancer. However, the clinical significance of these markers is not yet understood. OBJECTIVE: To perform a historical prospective study of 70 patients with squamous cell carcinoma of the larynx who were treated at our institution between 1979 and 1989 to correlate tumor marker expression with survival and metastasis. DESIGN: Archival tissue was immunohistochemically stained for the p53 tumor suppressor gene product, the inhibitor of apoptosis (bcl-2), the stem cell marker CD34, the cell adhesion molecules CD44H and CD44v6, and a marker of cellular proliferation (Ki-67). The slides were examined using a light microscope and scored according to intensity and percentage of cells labeled. The patients were stratified by tumor stage, and survival and metastatic data were correlated with staining scores. RESULTS: For the stage IV group, increased expression of p53 and decreased expression of CD44H and CD44v6 correlated with a decreased survival (P = .03, P = .03, and P = .02, respectively), and decreased expression of CD44H correlated with an increase in metastasis (P = .01). For all stages, excluding metastatic cases, increased p53 expression was consistent with a shorter survival (P < .03), while increased CD44v6 expression was consistent with a longer survival (P < .02). CONCLUSIONS: The present study suggests that a loss of cell proliferation control implied by overexpression of p53 and loss of cell adhesion implied by decreased expression of CD44 may be determinants of survival in patients with carcinoma of the larynx. The tumor markers bcl-2 and Ki-67 were not prognostic discriminators in this limited series. This study also indicates that the stem cell marker CD34 is rarely expressed by laryngeal carcinoma cells.

Dysphagia following head and neck cancer surgery.

Surgical resection of head and neck cancer results in predictable patterns of dysphagia and aspiration due to disruption of the anatomic structures of swallowing. Common procedures undertaken in the treatment of head and neck cancer include tracheostomy, glossectomy, mandibulectomy, surgery on the palate, total and partial laryngectomy, reconstruction of the pharynx and cervical esophagus, and surgery of the skull base. An overview is presented of normal swallowing physiology, as well as swallowing perturbations that are frequently encountered in postoperative head and neck cancer patients.