Salvage treatment for recurrent squamous cell carcinoma of the oral cavity.

BACKGROUND: Squamous cell carcinoma (SCCA) of the oral cavity recurs with a frequency of 25%-48%, a fact that usually portends a poor prognosis. Recent studies have reported salvage cure rates as high as 67%. Investigators have also claimed that restaging recurrent tumors provides useful prognostic information, although this has not been demonstrated with tumors of the oral cavity. The purposes of this study were: (1) to report the patterns of recurrent SCCA of the oral cavity; (2) to examine the benefit of restaging oral cavity tumors, and (3) to compare different treatment modalities in the management of recurrent SCCA of the oral cavity. Materials and Methods Thirty-eight patients who developed recurrent SCCA of the oral cavity were reviewed. Salvage treatment consisted of surgery, chemotherapy, radiation therapy, or a combination of these modalities. Survival analysis was based on the stage of the primary and recurrent tumors and the type of salvage treatment received. RESULTS: The overall recurrence rate was 28%. Local recurrence was most common (58%) followed by locoregional (27%) and regional recurrence (16%). Patients who recurred more than 6 months after completion of their primary treatment had improved survival compared with those who recurred within 6 months of initial treatment. Individuals with stage I-II primary tumors had significantly improved salvage time and total survival time compared with those with stage III-IV primary tumors (p < 0.005 and p < 0.001). Conversely, the stage of the recurrent tumor was not predictive of either improved salvage time or total survival time. Patients who underwent salvage surgery had significantly improved salvage time and total survival time compared with those who received chemotherapy and/or radiation therapy (p < 0.001 and p < 0.002). The overall salvage cure rate was 21%. Neither the stage of the primary or recurrent tumors nor the type of salvage treatment received significantly correlated with an improved cure rate. However, the group of patients who underwent salvage surgery approached a statistically significant improvement in cure rate (p = 0.08). CONCLUSIONS: Squamous cell carcinoma of the oral cavity is most likely to recur at the primary site. The stage of the primary tumor is significantly correlated with survival even after recurrence, but the stage of the recurrent tumor is not significantly correlated with survival. Patients most likely to benefit from retreatment are those who (1) have primary tumors stage I-II, (2) recur greater than 6 months after their initial treatment, and (3) develop recurrences that are amenable to salvage surgery.

Well-differentiated thyroid carcinomas: p53 mutation status and microvessel density.

BACKGROUND: Risk-stratification schemes exist for well-differentiated thyroid carcinoma and include prognostic factors such as age, sex, extent of tumor, size of tumor, and presence of metastasis. Controversy continues, however, over the aggressiveness of initial surgical intervention because of anecdotal experiences of poor clinical outcomes in low-risk patients. Our objective is to determine the prognostic significance of two biologic tumor markers, the p53 gene mutation and CD34 microvessel density (MVD) count, in well-differentiated tumors of thyroid gland. METHODS: We selected 38 patients with well-differentiated thyroid carcinomas from the University of Illinois Tumor Registry. Patients had an average clinical follow-up of 10 years. Paraffin-embedded tumor specimens were available for all patients. Immunohistochemistry was performed to identify mutations of the p53 gene (Ab 1801) and to determine the MVD count (CD34). RESULTS: There were significant increases in MVD counts within thyroid tumor tissue, when compared with surrounding, normal thyroid tissue. There was no significant correlation noted, however, between increased MVD and histology or recurrence rates. There was a trend toward higher MVD counts in tumor specimens of patients initially seen with metastatic lymphadenopathy. The incidence of p53 mutation expression was 28%, and there was no correlation between p53 status and histology, sex, recurrence rate, or survival. CONCLUSIONS: This study supports the concept of tumor neovascularization but fails to correlate MVD with clinical behavior or pathologic features in well-differentiated thyroid carcinoma. Furthermore, we found that the p53 mutation status was not an independent prognosticator of tumor behavior in these lesions.

Human papillomavirus expression and p53 gene mutations in squamous cell carcinoma.

OBJECTIVES: To determine the incidence of human papillomavirus (HPV) infection and p53 gene mutation expression in squamous cell carcinomas (SCCs) of the oral cavity and tonsils, to correlate the presence of HPV and p53 gene mutation with known clinical and pathological features of SCC, and to determine whether infection with HPV or the presence of p53 gene mutations are independent prognosticators of patient survival. DESIGN: To accomplish this goal, 58 patients with SCCs of the oral cavity and 42 patients with SCCs of the tonsils were randomly examined. The cases examined met the criteria of 5-year clinical follow-up, availability of complete staging information and treatment history, and the presence of paraffin-embedded tumor specimens. Immunohistochemical tests were performed to identify the mutant p53 protein. Human papillomavirus identification was accomplished with polymerase chain reaction, with confirmation via restriction fragment length polymorphisms. RESULTS: The incidence of p53 gene mutation expression for this series was 66%. Human papillomavirus infection was found in 11 patients (11%). There was a trend toward increased p53 gene mutation expression with advancing stage of tumor in the oral cavity cancer group, although this was less evident in the tonsil cancer population. The p53 gene mutation status was found not to correlate with the histological grade of the tumor, patient age or sex, recurrence rates, or survival status. Like p53 expression, there were no correlations found between the presence of HPV and age, sex, histological grade, or recurrence rates. However, a correlation did exist between HPV and survival status in the tonsil cancer group, with improved survival noted among patients with tonsil cancers infected with HPV compared with those not infected with HPV. A significant correlation existed with both p53 gene mutation status and HPV status with respect to alcohol and tobacco use. The presence of the p53 gene mutation positively correlated with increased tobacco and alcohol use, whereas infection with HPV predicted a significantly lower rate of alcohol and tobacco consumption. CONCLUSIONS: Human papillomavirus infection is an independent risk factor for the development of oral cavity and tonsil SCCs in those patients with a relatively low alcohol and tobacco use history. Conversely, there is a strong association between heavy alcohol and tobacco use and mutation of the p53 gene. Neither p53 gene mutation nor HPV infection serve as prognosticators of tumor behavior in SCCs of the oral cavity or tonsils, with the exception of improved survival noted among patients with tonsil cancers infected with HPV.

Prognostic indicators for squamous cell carcinoma of the oral cavity: a clinicopathologic correlation.

Fifty-three patients with T1 squamous cell cancer of the floor of mouth and ventral surface of the tongue with a known clinical outcome were retrospectively analyzed and arbitrarily divided into "aggressive" and "nonaggressive" groups based on their clinical behavior. Various host and tumor factors were then evaluated in an attempt to determine whether the tumor behavior could have been predicted. The paraffin-embedded tumor specimens were evaluated for tumor differentiation, tumor thickness and tumor invasion, microvessel density, and p53 expression. In addition, a composite morphologic grading score was obtained by combining cell differentiation, nuclear polymorphism, mitosis activity, depth of infiltration, type of infiltration, and lymphatic infiltration. No single technique appeared capable of identifying "aggressive" behavior, although possibly an evaluation of composite factors might show promise in the future.

Negative-pressure pulmonary edema in the otolaryngology patient.

It is estimated that 11% of all patients requiring active intervention for acute upper airway obstruction develop negative-pressure pulmonary edema. This pathologic process typically has a benign and rapidly resolving clinical course with the prompt use of mechanical ventilation and positive end expiratory pressure. A review of the literature, however, has revealed a morbidity and mortality rate of 11% to 40% in reported series. During the years 1991 through 1993, six patients were identified in whom negative-pressure pulmonary edema developed after various otolaryngologic procedures. Five (84%) of the six patients had complete resolution of the pulmonary edema within 24 hours, and the sixth patient progressed to prolonged mechanical ventilation and eventual death. In an effort to further understand the pathophysiology of this disease, a cardiac evaluation was performed by use of echocardiography on all six patients. In three of the six patients, studies revealed an underlying cardiac anomaly not previously identified by history or physical examination. Findings included one case of hypertrophic cardiomyopathy and two cases of pulmonary and tricuspid valvular insufficiency. This 50% incidence of cardiac anomalies is striking, in contrast to the less than 1% incidence of these anomalies in the general adult population. To our knowledge, this is the first study to implicate an underlying cardiac cause for the generation of negative-pressure pulmonary edema. On the basis of this study, we recommend that echocardiography be a part of the routine evaluation of all patients who manifest negative-pressure pulmonary edema.

Objective assessment of the breathe-right device during exercise in adult males.

In order to improve nasal breathing during competition, many athletes recently have been wearing a spring-loaded, external nasal dilator referred to as the Breathe-Right device (BRD). Although there are many subjective claims that this device improves breathing during exercise, there are currently no controlled studies documenting its efficacy. To determine objectively whether the device improves the nasal airway, 20 subjects (10 Caucasian and 10 African-American) were studied during rest and after 15 minutes of exercise using anterior rhinomanometry and acoustic rhinometry to measure changes in airway resistance and minimal cross-sectional area, respectively. We found that the BRD exerts its main effect in the region of the nasal valve improving the airway an overall 21% in our group of subjects. This anatomic improvement in nasal airway resulted in an overall 27% reduction in nasal resistance in the Caucasian group. However, in the African-American group, a wider range of resistance changes was observed with application of the BRD with significant improvement in nasal resistance in some subjects but paradoxical worsening in others. In the African-American group as a whole, no significant change in nasal resistance occurred with application of the BRD. These measured differences are likely due to variations in nasal anatomy that exist not only between races but also between individuals within a given race. In addition, this study confirms the well known decongestant effects of exercise providing anatomic data with acoustic rhinometry not previously documented in the literature. Overall improvement in nasal airway seen with application of the BRD occurred independent of these exercise-related decongestant effects.

Long-term follow-up of tracheoesophageal puncture results.

Since its introduction by Blom and Singer in 1980, tracheoesophageal puncture with a voice prosthesis has become the most frequently recommended choice for speech rehabilitation of total laryngectomies. Many studies have reviewed the initial speech acquisition success rates following tracheoesophageal puncture; however, long-term follow-up in these initial successes has been lacking. In addition, factors predictive of long-term success with tracheoesophageal speech have not been defined. Over a 10-year period, we retrospectively reviewed all total laryngectomy patients, including those who have undergone primary or secondary tracheoesophageal puncture, at the University of Illinois Hospital and Clinics and the Westside Veterans Administration Hospitals. Survival in the total laryngectomy cohort of 202 patients ranged from 35% to 50%. Forty of these patients underwent tracheoesophageal puncture, in whom survival was 75%. Short-term success with tracheoesophageal speech was approximately 70% for our patients, while long-term success was achieved in 66%. Despite low socioeconomic status and relatively high alcoholism rates, successful maintenance of tracheoesophageal speech was achieved in the majority of cases. Tracheoesophageal speech should therefore be considered as a primary method of vocal rehabilitation in all patients undergoing total laryngectomy.

The role of toluidine blue in assessing margin status after resection of squamous cell carcinomas of the upper aerodigestive tract.

OBJECTIVE: To determine the efficacy of toluidine blue in assessing margin status after removal of squamous cell carcinomas of the upper aerodigestive tract. DESIGN: A prospective study of 50 consecutive patients undergoing surgical resection of squamous cell carcinomas of the upper aerodigestive tract was performed during February 1 to December 1, 1993. After tumor resection, toluidine blue was applied directly to the remaining unresected mucosa. The staining characteristics of the mucosa were then compared with those of frozen-section biopsy specimens of the margins and with the permanent histologic findings of the resected tumor specimen. RESULTS: In three cases, toluidine blue identified a positive margin, which was confirmed on frozen and permanent section. In six cases, false-positive staining was noted, which was most frequently related to traumatic handling of the mucosa during the resection. In no case was a positive margin found on histologic staining that failed to stain with toluidine blue. During routine staining of surrounding unresected mucosa, three cases of a second primary tumor that was not seen on routine evaluation before tumor removal were identified with toluidine blue. In one case, a second T1 oral cavity lesion was found, while in the other cases, separate pharyngeal lesions were identified. CONCLUSION: Based on these findings, it appears that toluidine blue improved the ability to assess margin status at the time of resection, and we advocate its use after resection of tumors to the upper aerodigestive tract.

Retrieval of p53 protein in paraffin-embedded head and neck tumor tissues.

OBJECTIVES: To improve the detection of p53 protein in formalin-fixed, paraffin-embedded head and neck tumor tissues. DESIGN: Cohort. SETTING: University and Veterans Administration medical centers. PATIENTS OR OTHER PARTICIPANTS: Retrospective samples. INTERVENTION: Surgery for head and neck carcinoma. MAIN OUTCOME MEASURES: Retrieval of p53 antigen. Hypothesis formulated after data collection. RESULTS: An antigen retrieval method facilitated the unmasking of previously inaccessible p53 antigenic determinants in formalin-fixed, paraffin-embedded tissues. This approach has made possible a much more reliable and sensitive immunohistochemical detection of p53 antigen. The procedure is simple, requiring only microwave heating of tissue sections to 100 degrees C in the presence of a zinc sulfate solution. CONCLUSIONS: Antigen retrieval method in formalin-fixed, paraffin-embedded tissue demonstrated a significant increase in p53 immunostaining.

Photodynamic therapy for cutaneous malignancies of the head and neck.

Photodynamic therapy is a modality that potentially could be most helpful in treating multicentric skin cancers. Although a number of reports are present in the literature relating to this treatment, the results are conflicting and confusing. This article summarizes the current literature and suggests future directions.