Benzo[a]pyrene up-regulates cyclooxygenase-2 gene expression in oral epithelial cells.

Cyclooxygenase may be important in the pathogenesis of smoking-related cancer because it activates carcinogens and catalyzes prostaglandin biosynthesis. We determined the effects of benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon in tobacco smoke, on cyclooxygenase-2 (Cox-2) mRNA, protein and synthesis of prostaglandin E2 (PGE2) in normal and transformed oral epithelial cells. Treatment with B[a]P caused a dose-dependent increase in production of PGE2, with a maximal increase of approximately 100%. Enhanced synthesis of PGE2 was associated with increased amounts of Cox-2 protein. B[a]P also caused a two-fold increase in Cox-2 mRNA in both normal and transformed cells. Transient transfections with a Cox-2 promoter construct showed that B[a]P-mediated induction of Cox-2 mRNA reflected increased transcription. Levels of Cox-1 were unaffected by B[a]P. B[e]P did not affect the synthesis of PGE2 or amounts of Cox-2. These data are important because B[a]P-mediated induction of Cox-2 may predispose to carcinogenesis by enhancing the production of mutagens and the synthesis of prostaglandins.

Cervicomediastinal thymic cysts.

Cervical thymic cysts are among the rarest congenital neck masses. They are probably more frequent than the number of cases reported as many of these lesions are asymptomatic and only discovered incidentally. The initial embryologic development of the thymus begins in the neck, followed by migration into the superior mediastinum. For this reason, extension of cervical thymic anomalies into the mediastinum is possible. Although it is the least common lateral cystic neck mass, it must be differentiated from other pediatric cystic neck masses, the majority of which are anomalies of the branchial system. Due to the possibility of mediastinal extension, the management of these lesions is different than other congenital neck masses. We report two cases of thymic anomalies with mediastinal extension and review the embryology, diagnosis, and management of cervicomediastinal thymic cysts.

Management of the neck in parotid carcinoma.

BACKGROUND: Management of the clinically negative neck remains a controversial issue in patients with carcinoma of the parotid gland. Our treatment policy has always been conservative, reserving lymphadenectomy for selected patients. METHODS: We retrospectively evaluated 121 patients with malignant tumors of the parotid gland who received their definitive treatment at the Memorial Sloan-Kettering Cancer Center between 1966 and 1988. RESULTS: A total of 35 neck dissections (ND) were performed, 14 of which involved removal of clinically positive nodes (radical in 10, modified in 2, and limited in 3). Twenty-one patients had an elective lymphadenectomy (radical in 14, modified in 2, and limited in 4), usually because of ominous histology or high T stage. In addition to histologically positive regional lymph nodes, facial nerve paralysis, gender, and advanced stage, the decision to perform a ND, whether elective or therapeutic, was significantly predictive of decreased survival (P < 0.001). In the majority of patients (86, or 65%), the neck was observed rather than treated electively, with no impact on overall survival. Only 4 of 121 patients developed neck recurrence following treatment, including 3 who had neck dissection as part of their initial management. CONCLUSIONS: These data support our policy of reserving elective ND only for those histologic diagnoses that carry the highest risk of nodal metastases, as well as for selected patients whose primary tumor resection might be facilitated by lymphadenectomy.

Evaluation of prevertebral muscle invasion by squamous cell carcinoma. Can computed tomography replace open neck exploration?

OBJECTIVE: To compare computed tomography (CT) with open neck exploration in determining prevertebral invasion by squamous cell carcinoma of the oropharynx or hypopharynx. DESIGN: Retrospective analysis using the findings at open neck exploration and results of histopathologic studies as the criterion standards. SETTING: Tertiary care referral center. PATIENTS: Twenty-nine of 40 patients with advanced squamous cell carcinoma of the oropharynx or hypopharynx treated between January 1, 1986, and December 31, 1994, were selected for analysis based on CT findings of posterolateral extension of the primary tumor placing the prevertebral muscle (PVM) at risk. All study patients had no previous therapy and underwent neck exploration to determine resectability. RESULTS: Overall accuracy of CT in predicting PVM status was 55.2%. The sensitivity of preoperative CT for PVM invasion was 50%; the specificity was 61%. Using an estimate of 21% for the prevalence of PVM invasion, the predictive value of a positive CT scan was 0.254 and the predictive value of a negative CT scan was 0.821. Open neck exploration correctly predicted PVM status in all cases. CONCLUSIONS: Open neck exploration is superior to CT to evaluate possible PVM invasion by squamous cell carcinoma of the oropharynx or hypopharynx. The predictive value of a negative CT scan for PVM invasion is high, so it may be useful in treatment planning. Patients with advanced squamous cell carcinoma of the oropharynx or hypopharynx at risk for PVM invasion who are otherwise surgical candidates should be considered for open neck exploration to determine resectability most accurately.

Impact of clinicopathologic parameters on patient survival in carcinoma of the cervical esophagus.

BACKGROUND: The survival of patients with carcinoma of the cervical esophagus remains poor in spite of multimodality treatment and technical improvements in surgical resection and reconstruction. This study was undertaken to update our experience with cervical esophageal carcinoma and to identify factors that had an impact on patient survival and quality of life. PATIENTS AND METHODS: Clinical data encompassing 132 variables were collected on 67 patients with cervical esophageal carcinoma from 1980 to 1993. Statistical analysis was performed: independent Student's t-tests, Cox regression, Kaplan-Meier curves, and log rank analyses were used in the statistical evaluation. The mean age of the patients was 63 years (range 31 to 88). Dysphagia was the primary symptom in 86% of patients; 80% had received no prior treatment. The most common abnormal finding (21%) on physical examination was a neck mass. RESULTS: Curative resection was performed in 22 patients, 7 had palliative procedures, and 7 were found to be inoperable at exploration and received palliative treatment. Radiation with or without chemotherapy was definitive treatment for 10 patients, whereas 4 patients were treated with chemotherapy alone for cure, and 17 patients received palliative treatment. The mean survival following diagnosis was 17 months (range 1 to 96). Cumulative 5-year survival was 12%. CONCLUSIONS: Persistent disease, chemotherapy prior to presentation, and chemotherapy for cure remained as statistically significant parameters associated with decreased survival by multivariate analysis. There was a trend toward improved survival in patients treated with surgical resection.

Immunohistochemical detection of c-myc protein in head and neck tumors.

OBJECTIVES: To evaluate the correlation between the levels of immunohistochemically detectable c-myc protein in squamous cell carcinoma of the head and neck and clinicopathologic prognostic variables utilized in clinical practice. DESIGN: Cohort study. SETTING: University and Veterans Administration medical centers, Cincinnati, Ohio. PATIENTS OR OTHER PARTICIPANTS: Consecutive samples. INTERVENTION: Surgery for squamous cell carcinoma of the head and neck. MAIN OUTCOME MEASURE: Correlation between c-myc expression and tumor size, nodal involvement, clinical disease stage, and degree of differentiation. Hypothesis formulated after data collection. RESULTS: Significant negative correlation between the c-myc levels and the number of metastatic nodes (P = .0001) and clinical stage of disease (P = .05). No correlation with tumor size or degree of differentiation. CONCLUSIONS: Reduction or loss of c-myc oncoprotein might be associated with metastatic lymph node involvement and advanced stages of squamous cell carcinoma of the head and neck. Further studies are needed to substantiate preliminary findings.

Detection of P-glycoprotein with four monoclonal antibodies in normal and tumor tissues.

P-glycoprotein (Pgp), encoded by the multidrug-resistance gene (MDR1), is an active efflux pump for many structurally diverse lipophilic compounds. Using peroxidase-antiperoxidase immunohistochemistry technique and four anti-Pgp monoclonal antibodies directed against different epitopes of the molecule, we examined the distribution of Pgp in normal human tissues and squamous cell carcinomas of the head and neck. All four antibodies detected Pgp in bronchial cells, mammary ductal epithelium, gallbladder epithelium, epithelia of small and large intestine, bile canaliculi, dermal sweat glands, proximal tubules of kidney, endometrium, trophoblasts, adrenal gland, and capillaries of central nervous system, testis, and papillary dermis. Of the 23 head and neck squamous cell carcinomas, about 60% had detectable Pgp. It is possible that differences noticed between antibodies are due to cross-reactivity to proteins unrelated to MDR1. Care must be taken in interpreting staining results when only one or two monoclonal antibodies are used.

Detection of P-glycoprotein in squamous cell carcinomas of the head and neck.

One established mechanism of multidrug resistance is elevated expression of P-glycoprotein. The expression of P-glycoprotein by immunohistochemistry was examined in squamous cell carcinomas of the head and neck using a newly developed monoclonal antibody, UIC2, which is specific to the human MDR1 gene product and recognizes an external epitope of the protein. P-glycoprotein was detected in 60% of the samples. MDR1 expression was compared with clinical response to chemotherapy in eight patients who received MDR1-dependent drugs and response was accurately predicted in seven (89%) of eight patients. Positive P-glycoprotein staining correlated with the degree of tumor differentiation, but not with other clinical factors. Therefore, analyzing the expression of P-glycoprotein may play a role when planning chemotherapeutic regimens for patients with head and neck cancer and may be an additional prognostic and diagnostic tool in these patients.

Expression of c-erbB-2 gene in human head and neck carcinoma.

The c-erbB-2 oncoprotein is a transmembrane protein the presence of which has been associated with poor prognosis in several human neoplasms. However, there has been no comprehensive assessment of its value as a potential prognostic marker in head and neck squamous cell carcinoma. Archival specimens from 93 patients, treated surgically for squamous cell carcinoma of the head and neck between 1981 and 1989, were analyzed by immunohistochemistry using an anti-c-erbB-2 monoclonal antibody; of these, 43 (46%) were positive for c-erbB-2 staining. The majority of stained specimens (41%) displayed staining predominantly at the cell surface, while mixed membrane and cytoplasmic staining was less common (9%). Only 4% shared exclusively cytoplasmic staining. Since the specimens were archival, the cytoplasmic staining is probably a consequence of variable handling and/or fixation at the time of tissue removal. Therefore, only cases exhibiting distinct cell surface membrane staining in more than 10% of tumor cells were regarded as positive. There is a definite association between immunohistochemical detection of c-erbB-2 and head and neck squamous cell carcinoma, since almost half of the tumor specimens manifested detectable c-erbB-2 protein. However, this association could not be extended to a predicted disease progression or outcome, since there was no significant correlation between c-erbB-2 staining and tumor size, stage of disease, histologic differentiation, lymph node status or patient survival.

Improved immunohistochemical detection of p53 protein in paraffin--embedded tissues reveals elevated levels in most head and neck and lung carcinomas: correlation with clinicopathological parameters.

We have analyzed the expression of the p53 tumor suppressor gene in paraffin-embedded sections of normal and malignant head and neck and lung tumors by immunohistochemistry using the PAb 1801 monoclonal antibody (MAb). The PAb 1801 does not consistently detect its p53 epitope in tissue fixed in 10% buffered formaldehyde. However, the antibody is effective in AMeX-fixed specimens, thereby permitting the improved morphologic localization of p53 phosphoprotein in paraffin embedded tissue. Of 33 primary head and neck carcinomas analyzed from AMeX-fixed, paraffin-embedded sections, 21 (64%) showed heterogeneous staining with PAb 1801. All 33 normal samples of head and neck tissues were negative. Similarly, 13 out of 20 lung carcinomas (65%) showed heterogeneous staining while none of normal lung tissues were positive. The data indicate a strong positive correlation between p53 detection by PAb 1801 and carcinomas of the head and neck and of lung. However, there was no obvious correlation between p53 staining and the number of involved nodes, the stage of disease or the degree of differentiation in these carcinomas.

Embryonal sarcoma of the liver in an adult treated with preoperative chemotherapy, radiation therapy, and hepatic lobectomy.

A rare case of embryonal sarcoma of the liver in a 28-year-old man is reported. The patient was treated preoperatively with a combination of chemotherapy and radiation therapy. Complete surgical resection, 4.5 months after diagnosis, consisted of a left hepatic lobectomy. No viable tumor was found in the operative specimen. The patient was disease-free 20 months postoperatively.

Murder and assault arrests of White House cases: clinical and demographic correlates of violence subsequent to civil commitment.

The authors studied arrest records and clinical data on 217 persons formerly hospitalized as "White House Cases" because they were psychotically preoccupied with prominent political figures. Prior arrest for violent crime was the variable most strongly associated with arrest for violent crime after hospital discharge. Male gender and a history of weapons possession were also correlated with future violence. For those with prior violent crime arrests, hospital incidents requiring seclusion were also associated with later violence. For those without prior arrests, subsequent violence was associated with threats, living outside Washington, and command hallucinations. For those previously arrested for nonviolent crimes, only persecutory delusions were associated with later violence.