Baseline data of oral and pharyngeal cancer before introducing an oral cancer prevention campaign in Germany.

OBJECTIVES: Oral and pharyngeal cancer is still a serious health problem with an annual incidence of about 13,000 in Germany. This study aimed at describing trends of incidence and mortality in Germany by age, sex, and sub-site as a baseline for an oral cancer prevention campaign. METHODS: Using data from the National Association of Population-based Cancer Registries, incidence rates for oral and pharyngeal cancer (ICD-10, C00-C14) from 2003 to 2011 and mortality rates from 1990 to 2012 were analysed by age, sex, and sub-site (C00-C06, C07-C08, C09-C14). Trends were described by annual percentage changes. RESULTS: Men are 2.5-times more likely than women to be diagnosed and 3-times more likely to die from this tumour. Incidence and mortality in women increased slightly during the last decade, while incidence and mortality in men remained stable at a high level. While a decline was observed for younger age groups, an increase was seen in the elderly. For some sub-sites a deviation from this overall pattern was observed. CONCLUSIONS: The decrease in this tumour in younger age groups is pleasing and may be attributed to public efforts in non-smoker protection in recent years. Further efforts are needed to counteract the increasing burden of disease in older age groups and in men.

Expression and function of CXCR4 in human salivary gland cancers.

Salivary gland cancers (SGCs) frequently metastasize to cervical lymph nodes and distant organs. Currently, the mechanisms responsible for the metastatic behavior of SGC cells are not fully understood. We previously demonstrated that the stromal cell-derived factor-1 (SDF-1; also known as CXCL12)/CXCR4 system is involved in the establishment of metastasis in oral squamous cell carcinoma. In the present study, we investigated the role of CXCR4 in the metastatic behavior of SGCs. We examined the expression of CXCR4 mRNA and protein in human SGC cell lines by quantitative RT-PCR and western blotting, respectively. The expression of CXCR4 mRNA and protein were frequently upregulated in 5 out of 6 SGC cell lines. Functional CXCR4 expression was demonstrated by the ability of these SGC cell lines to migrate toward an SDF-1 gradient. SDF-1 rapidly activated extracellular signal-regulated kinase (ERK)1/2 in SGC cell lines. Immunohistochemical analysis revealed that CXCR4 protein expression was detected in either the nucleus or cytoplasm of cancer cells in 16 out of 20 tissues of adenoid cystic carcinoma (ACC) and in 4 out of 6 tissues of mucoepidermoid carcinoma, which are representative of SGC. Furthermore, ACC cell lines exhibited dramatic metastasis to the lung following intravenous inoculation, whereas AMD3100, a CXCR4 antagonist, significantly inhibited lung metastasis of the cells, ameliorated body weight loss and improved the survival rate of tumor-bearing nude mice. These results indicate that CXCR4 expression contributes to the metastatic potential of SGCs.

MMTV-cre-mediated fur inactivation concomitant with PLAG1 proto-oncogene activation delays salivary gland tumorigenesis in mice.

Proprotein convertases are serine endoproteases implicated in the proteolytic processing of a large variety of regulatory proteins. An important role of proprotein convertases in tumorigenic processes has been suggested by various studies. In this study, the role of the proprotein convertase furin in PLAG1 proto-oncogene-induced salivary gland tumorigenesis was investigated. PLAG1 overexpression in salivary glands has previously been shown to result in salivary gland tumors in 100% of mice within 5 weeks after birth. MMTV-cre-mediated inactivation of fur without over-expression of PLAG1 caused smaller but histologically normal salivary glands. Moreover, the lymph nodes close to the salivary glands were enlarged, and histology showed that they had activated follicles. When genetic ablation of 1 or 2 alleles of fur and overexpression of the PLAG1 transgene were simultaneously achieved, a significant delay in tumorigenesis was observed. Collectively, these results suggest an important role for furin in PLAG1-induced salivary gland tumorigenesis in mice.

Estudo do estado de diferenciação da célula mioepitelial nas neoplasias de glândula salivar / Study of the myoepithelial cell differentiation state in salivary gland tumors

A célula mioepitelial (CM) nos tumores de glândula salivar apresenta-se em diferentes estágios de diferenciação. Sabe-se que em glândula normal ela expressa actina músculo específica (AME) e Citoqueratina (CK) 14. Por outro lado, é conhecida a participação dos componentes de matriz extracelular, dentre eles a laminina (LN), na morfogênese e citodiferenciação das estruturas glandulares. Em vista do exposto, nos propusemos a estudar os diferentes estágios de diferenciação da CM através da expressão da AME, da CK 14, bem como a participação da LN neste processo. Para tanto, utilizamos tumores onde se postulam a participação da CM: adenoma pleomórfico, mioepitelioma, adenoma de células basais e carcinoma adenóide cístico e submetemos os espécimes ao método imunohistoquímico da avidina-biotina. Nossos resultados mostraram que a presença da AME foi rara, assim como a CK 14 que só esteve presente em CM de estruturas ductiformes bem formadas. Já a LN esteve presente junto à CM, independentemente da expressão de CK 14 e de AME, e no estroma tanto de tumores diferenciados, como indiferenciados. Em conclusão, é possível identificar diferentes estágios de diferenciação mioepitelial através da expressão da CK 14 e da AME, mas parece não existir uma correlação da LN com a diferenciação da CM tumoral, pois ou essa ou sua precursora continua a secretar LN, mesmo que imperfeitamente após estímulo oncogênico

Distant metastases from salivary glands cancer.

Patients who present with malignant salivary glands should at their initial assessment have an X-ray of the chest to exclude the possibility of distant metastases. Patients who have other symptoms, bone pain etc., should be appropriately investigated. The likelihood of patients developing distant metastases is associated with high-grade tumors, most commonly adenoid cystic carcinoma, high-grade mucoepidermoid carcinoma, salivary duct carcinoma and tumors sited in the submandibular gland, posterior tongue and pharyngeal tumors. Patients who have had a high-grade tumor treated and survived without locoregional recurrence have the same risk of developing distant metastases as those patients who have locoregional recurrence. Other histological types of salivary tumors are associated with a lower risk of developing distant metastases but a real risk remains lifelong. It is recommended that all patients who have a malignant salivary gland tumor treated, any histology, should be followed up and clinically assessed at least once every 12 months for life.

Aumento do volume facial tardiamente diagnosticado como carcinoma adenóide cístico. Relato de Caso / Late diagnostic of facial edema caused by adenoid cystic carcinoma

O diagnóstico precoce de lesöes malignas da cavidade bucal é de fundamental importäncia para o prognóstico e qualidade de vida do portador do tumor. O cirurgiäo-dentista possui relevante papel na prevençäo do cäncer bucal. Os autores relatam caso de paciente do sexo masculino, branco, de 71 anos portador de carcinoma adenóide cístico, que estava sendo tratado por vários profissionais da área de saúde, como portador de abscesso odontogênico há 90 dias. O mesmo foi a óbito, cerca de 60 dias após o diagnóstico definitivo da lesäo

Estudio sobre los tumores malignos maxilofaciales / Study of maxillofacial malignant tumors

Se realizó un análisis durante el trienio 1994-1996 y se estudiaron los tumores malignos de la región maxilofacial tratados en el Servicio de Cirugía Maxilofacial de Artemisa. El sexo masculino fue más afectado que el femenino, los tumores de la piel fueron los más frecuentes, afectaron en elevado porcentaje a los pacientes de tez blanca, y el carcinoma basocelular fue el tipo histológico que más se observó. En cuanto a la localización más frecuente en la cavidad bucal fue el labio inferior, y el tipo histológico que más predominó fue el carcinoma epidermoide. El 3 porciento de todos los tumores encontrados correspondieron con metástasis, que debutaron por la zona bucofacial

Diet and the risk of salivary gland cancer.

Cancer of the major salivary glands is relatively rare, and little is known about its etiology. The only established risk factors are radiation exposure and a prior cancer. The role of diet in the development of salivary gland tumors has not been addressed previously. The results from a population-based case-control study conducted in the greater San Francisco-Monterey Bay area examining the association between dietary intake and salivary gland cancer risk are presented. Of 199 cases diagnosed with salivary gland tumors between 1989 and 1993, 150 (75%) were interviewed. Nine cases were subsequently excluded based on review of pathology specimens. Of 271 controls identified through random-digit dialing and the Health Care Finance Administration files, 191 (70%) were interviewed. Eight cases and seven controls who over- or underreported dietary intake were excluded from analysis. Vitamin C intake of > 200 mg/day compared with < or = 100 mg/day was associated with a 60% decrease in salivary gland cancer risk (odds ratio (OR) = 0.40, 95% confidence interval (CI) 0.22-0.70). Inverse associations observed for carotene, vitamin E, and fiber from fruits and vegetables were diminished when adjusted for vitamin C intake. Fiber from been sources was associated with a 51% decrease in risk after adjusting for vitamin C intake (OR = 0.49, 95% CI 0.26-0.92 for > 1.4 g/day compared with < or = 0.4 g/day). Cholesterol intake was associated with elevated risk (OR = 1.67, 95% CI 1.2-2.4 for a 10% increase in calories from cholesterol). These findings suggest that preventive strategies developed for common chronic diseases, such as increased consumption of fruits and vegetables and limiting foods high in cholesterol, also may be effective in preventing these rare tumors.

Diet and other risk factors for cancer of the salivary glands:a population-based case-control study.

A population-based case-control study of cancer of the salivary glands, involving interviews of 41 incident cases and 414 controls, was conducted in Shanghai. After adjustment for other risk factors, occupational exposure to silica dust was linked to a 2.5-fold increased risk of salivary-gland cancer. The risk was also significantly elevated among individuals who reported ever using kerosene as cooking fuel or having a prior history of head X-ray examinations. Dietary analyses revealed a significant protective effect of consumption of dark-yellow vegetables or liver, with about 70% reduced risk of salivary-gland cancer among individuals in the highest intake group of these foods. Our findings are consistent with previous observations on a possible role of environmental exposure and radiation in the etiology of salivary-gland cancer, and suggest that dietary factors may contribute to the development of this malignancy.

The influence of positive margins and nerve invasion in adenoid cystic carcinoma of the head and neck treated with surgery and radiation.

PURPOSE: Surgery is the primary treatment for adenoid cystic carcinomas arising from major and minor salivary glands of the head and neck. However, local recurrence is frequent because of the infiltrative growth pattern and perineural spread associated with these tumors. At UTMDACC, we have had a longstanding policy of using postoperative radiotherapy to reduce the risk of local recurrence and to avoid the need for radical surgery; this 30-year retrospective study analyzes the results of this combined modality approach. METHODS AND MATERIALS: Between 1962 and 1991, 198 patients ages 13-82 years, with adenoid cystic carcinomas of the head and neck, received postoperative radiotherapy for known or suspected microscopic residual disease following surgery. Distribution of primary sites was: parotid: 30 patients; submandibular/sublingual: 41 patients; lacrimal: 5 patients; and minor salivary glands: 122 patients. Eighty-three patients (42%) had microscopic positive margins and an additional 55 (28%) had close (< or = 5 mm) or uncertain margins. One hundred thirty-six patients (69%) had perineural spread with invasion of a major (named) nerve in 55 patients (28%). Using radiation techniques appropriate to the primary site, a median dose of 60 Gy (range 50-69 Gy) was delivered to the tumor bed. Follow-up ranged from 5-341 months (median, 93 months). All surviving patients had a minimum of 2 years follow-up. RESULTS: Twenty-three patients (12%) had local recurrences with 5-, 10-, and 15-year actuarial local control rates of 95%, 86%, and 79%, respectively. Fifteen of the 83 patients (18%) with positive margins developed local recurrences, compared to 5 of 55 patients (9%) with close or uncertain margins, and 3 of 60 patients (5%) with negative margins (p = 0.02). Patients with and without a major (named) nerve involved had crude failure rates of 18% (10 out of 55) and 9% (13 out of 143), respectively (p = 0.02). There was a trend toward better local control with increasing dose. This was significant in patients with positive margins, in whom crude control rates were 40 and 88% for doses of < 56 Gy and > or = 56 Gy, respectively (p = 0.006). Actuarial 5-, 10-, and 15-year freedom from relapse rates were 68%, 52%, and 45%, respectively. Base of skull and neck failures were uncommon with or without elective treatment, developing in 2 and 3% of patients, respectively. Distant metastases were the most common type of disease recurrence, developing in 74 patients (37%) of whom 62 (31%) were disease-free at the primary site. CONCLUSIONS: Excellent local control rates were obtained in this population using surgery and postoperative radiotherapy and we recommend this combined approach for most patients with adenoid cystic carcinomas of the head and neck. Perineural invasion was an adverse prognostic factor only when a major (named) nerve was involved. Microscopic positive margins was also an adverse prognostic factor, but even when present, local control was achieved in over 80% of our patients. We recommend a dose of 60 Gy to the tumor bed, supplemented to 66 Gy for patients with positive margins. Despite effective local therapy, one-third of patients fail systemically, and good treatment to address this problem is lacking.

Effects of excess vitamin A and canthaxanthin on salivary gland tumors.

The effects of feeding semipurified diets supplemented with excess retinyl palmitate (20,000 and 100,000 IU/kg), beta-carotene (250 mg/kg), and canthaxanthin (250 mg/kg) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced salivary gland tumors were studied in rats. None of the dietary supplements had a significant effect on tumor incidence. Tumor weights, however, tended to be lower in rats fed the dietary supplements compared with the controls. The incidence of tumor-bearing rats with large tumors was significantly lower in rats fed canthaxanthin than in the control rats. At termination of the experiment, the levels of vitamin A were higher in plasma, liver, normal salivary glands, and the tumor of rats fed diets supplemented with the higher level of retinyl palmitate. Feeding the canthaxanthin-supplemented diet had the opposite effect on tissue and plasma vitamin A levels. beta-Carotene supplementation was associated with higher vitamin A concentrations in the liver but not in plasma, salivary glands, or the tumor. The levels of beta-carotene were increased in tissues and plasma of rats fed the beta-carotene-supplemented diet. The results suggest that in this experimental model, the diet-induced modification of tissue or plasma vitamin A levels did not have an effect on tumor incidence.

The effect of different levels of dietary beta-carotene on DMBA-induced salivary gland tumors.

Different levels of beta-carotene (0, 5, 25, 125, and 250 mg/kg diet) were tested for their chemoprevention effects using 9,10-dimethyl-1,2-benzanthracene-induced salivary gland tumor model in rats. Tumor incidence and tumor weights were slightly lower in rats fed diets supplemented with 25 mg or more beta-carotene/kg diet. Hepatic vitamin A and beta-carotene levels were increased in a dose-dependent fashion, reaching a plateau at 125 mg beta-carotene/kg diet. In plasma, beta-carotene concentrations were also increased with an increase in dietary beta-carotene. Vitamin A levels in plasma were not affected. The normal salivary glands had higher concentrations of beta-carotene than did the tumors. The results suggest that the decreases in tumor incidence and tumor weight may be related to the increase in plasma and tissue levels of beta-carotene as a result of feeding high levels of beta-carotene.

Chemopreventive effects of beta-carotene and 13-cis-retinoic acid on salivary gland tumors.

The chemopreventive effects of beta-carotene and 13-cis-retinoic acid (RA) on chemically induced salivary gland tumors were studied in rats. Young male Sprague-Dawley rats were injected in one of the submandibular salivary glands with 1 mg of dimethylbenzanthracene (DMBA) dissolved in olive oil. The contralateral gland was injected with the vehicle alone. Rats were divided into four groups and were fed ad libitum a semisynthetic diet supplemented with 0 or 100 mg beta-carotene/kg diet, or 20 or 100 mg RA/kg diet. Rats were killed at 22 weeks after the DMBA treatment, and tumors were examined histologically. Tumors were generally found to be squamous cell carcinomas or poorly differentiated neoplasms resembling squamous cell carcinomas. The tumor incidence was slightly lower in rats fed the diet supplemented with beta-carotene. RA had no appreciable effect on tumor incidence. A high activity of gamma-glutamyl transpeptidase was histochemically demonstrated in the tumors. There were some mortalities in the beta-carotene and RA supplemented groups, especially in the group fed high levels of RA. This mortality appeared to be related to vitamin K becoming somewhat limited.