Tracheotomy in very low birth weight neonates: indications and outcomes.

OBJECTIVE/HYPOTHESIS: To review incidence of, indications for, and outcomes of tracheotomy in very low birth weight (VLBW) infants. STUDY DESIGN: Retrospective review in tertiary care hospital. METHODS: Eighteen VLBW (<1,500 g) infants with bronchopulmonary dysplasia undergoing tracheotomy in the neonatal intensive care unit between October 1997 and June 2002 were studied. Controls consisted of 36 VLBW infants undergoing intubation without tracheotomy, two per study infant, matched by gestational age and weight. Outcome measures included duration and number of intubation events, time to decannulation, complications, comorbidities, length of stay, and speech, language, and swallowing measures. RESULTS: Infants undergoing tracheotomy had an average duration of intubation of 128.8 days with a median number of 11.5 intubation events, both significantly greater than those of controls. Percentage of those with laryngotracheal stenosis was 44% of study infants had laryngotracheal stenosis compared to 1.6% in all intubated VLBW infants. The tracheotomy group had a significantly higher incidence of gastroesophageal reflux, pulmonary hypertension, and gastrostomy tube placement. The overall tracheotomy-related complication rate was 38.9%. Three were lost to follow-up, and five deaths occurred, two possibly tracheotomy-related. Six of ten were decannulated by an average time of 3.8 years, two of six after laryngotracheal reconstruction. Four of ten remained cannulated for a variety of reasons. Disorders of speech, language, and swallowing were common. CONCLUSIONS: When considering tracheotomy in VLBW infants, the total number of intubation events should be monitored as well as the total duration of intubation. The relatively high incidence of laryngotracheal stenosis argues for earlier endoscopy and possibly earlier tracheotomy in infants with developing stenoses.

Clinical implications of human papillomavirus infection.

Human papillomaviruses (HPV) are small DNA viruses associated with specific mucosal and epithelial lesions ranging from benign proliferative lesions to invasive carcinomas. Over 100 types of HPV have been identified, some of which are associated with benign lesions (low risk types) and others are associated with malignancies (high risk types). While the genome consists of 6 early genes and 2 late genes, the E6 and E7 genes have been most studied because they interact with p53 and Rb, respectively, thus contributing to the ability of HPV to mediate oncogenesis. Cervical carcinoma is the most common and most studied HPV-related malignancy. These lesions are thought to be originated from persistent high-risk type HPV infections which progress to well characterized precursor lesions and finally to carcinoma. This same HPV related progression has also been observed in other anogenital malignancies including anal, penile and vulvar carcinomas. Although the evidence is not as conclusive, HPV also likely plays a role in the development of a subset of squamous cell carcinomas of the head and neck as well as other cutaneous malignancies. While HPV infection is common, the progression to malignancy is relatively rare indicating a potential role for immune protection against persistent infection. This is supported by the fact that HPV infection and related malignancies are common in the immunosuppressed population. Thus, efforts have been placed on development of HPV vaccines to prevent and treat these common and diverse groups of HPV related malignancies.

Epstein-Barr virus detected in a head and neck squamous cell carcinoma cell line derived from an immunocompromised patient.

BACKGROUND: DNA tumor viruses potentially play a role in the development of squamous cell carcinoma of the head and neck (SCCHN). Human papillomavirus is found in up to 50% of SCCHN specimens, and Epstein-Barr virus (EBV) has been detected in nasopharyngeal carcinoma, Burkitt lymphoma, and other lymphomas. However, the role of EBV in nonnasopharyngeal SCCHN has not been thoroughly investigated. METHODS: Twenty-one SCCHN cell lines derived from tumors of various subsites were used to screen for EBV DNA as well as latent viral protein expression. The method of EBV DNA detection was polymerase chain reaction with 3 independent primer sets from distinct regions of the genome. Expression of the viral protein EBNA-1, critical for the maintenance of the viral episome, was monitored by immunofluorescence using an antibody specific for EBNA-1. In addition, 12 paraffin-embedded tumor specimens and adjacent normal tissues were analyzed by polymerase chain reaction. These tumor specimens were further characterized by immunohistochemistry with the use of a mouse monoclonal antibody that recognizes EBNA-1. RESULTS: Little or no EBV DNA was detected in 20 of 21 cell lines or in any of the tumor specimens, while detecting approximately 40 genome copies in a control reaction. Accordingly, these cell lines and specimens were negative for EBNA-1 expression. In 1 cell line derived from an immunosuppressed patient, EBV DNA was detected, and on further examination a small percentage of cells expressed EBNA-1 as shown by immunofluorescence. CONCLUSIONS: Although EBV may not be a major cofactor contributing to the proliferation of SCCHN, the limited initial evidence suggests that EBV may be involved in development of SCCHN in immunosuppressed patients.

Human papillomavirus and p53 mutational status as prognostic factors in head and neck carcinoma.

BACKGROUND: Mutations of the p53 tumor-suppressor gene are common in squamous cell carcinoma of the head and neck (SCCHN) and may portend a worse prognosis. Human papillomavirus (HPV) represents another potential prognostic factor for SCCHN. The oncogenic potential of HPV may be due to the ability of its E6 oncoprotein to promote degradation of wild-type p53 protein. We wish to determine whether there is a lower incidence of p53 mutations in HPV-positive versus HPV-negative tumors, and if HPV and/or p53 status has an impact on survival. METHODS: Thirty-two SCCHN specimens were analyzed for mutations of the p53 gene using single-strand conformational polymorphism (SSCP) analysis followed by DNA sequencing. The HPV status of all specimens was evaluated by use of polymerase chain reaction with HPV consensus primers and Southern blot hybridization. Pertinent clinical information was obtained from chart review. RESULTS: Nonsilent p53 mutations were present in 2 of 15 (13%) of HPV-positive tumors compared with 6 of 17 (35%) of HPV-negative tumors (p =.229; Fisher's exact test, odds ratio.28). A survival advantage was found between HPV-positive compared with HPV-negative specimens (p =.0264) and between p53 wild type compared with p53 mutant specimens (p =.01) by univariate log rank analysis. When stratified according to both HPV and p53 status, a statistically significant survival difference was observed largely because of a 100% survival for the HPV-positive/p53 wild-type group (p =.003). CONCLUSIONS: This preliminary study supports the notion that the presence of HPV confers a survival advantage among HNSCC patients, particularly when p53 is wild type.