Survival of malignant mesothelioma and other rare thoracic cancers in Germany and the United States: A population-based study.

Evidence on survival of malignant mesothelioma (MM) and other rare thoracic cancers is limited due to the rarity of these cancer sites. Here, we provide a comprehensive overview of MM incidence and survival after MM and other rare thoracic cancers in Germany and the United States (US). Incidence was estimated from a German National Cancer Database and from the Surveillance, Epidemiology and End Results (SEER) 18 database for 2000-2014. Patients diagnosed in 1997-2013 with malignant epithelial tumors of the trachea (Etra), epithelial tumors of the thymus (Ethy) and MM were extracted from a German cancer survival database and from the SEER 13 database. Period analysis was employed to compute 5-year relative survival (RS). During 2000-2014, an annual average of 0.9 and 0.6 MM cases per 100,000 person-years was diagnosed in Germany and the US. Rates decreased in Germany and in the US. Patients with Ethy had highest 5-year RS with US patients surviving longer (69.1% compared to 63.7%, p = 0.02). Survival after Etra was comparable in both countries (Germany 33.6%, US 34.4%, p = 0.07). Survival in MM patients was poor overall (Germany 11.8%, US 12.1%, p < 0.01). Survival improvements were only observed in MM patients in Germany (10.8% [2002-2007] vs. 13.0% [2008-2013], p < 0.01). The lack of progress in survival for Etra and Ethy patients underlines the need of novel preventive, therapeutic and diagnostic approaches. MM incidence significantly decreased in Germany and in the US. Further monitoring of MM incidence is warranted given that a peak in incidence is expected in 2020-2030 in Western countries.

Recurrent respiratory papillomatosis arising in trachea not affecting larynx.

Recurrent respiratory papillomatosis (RRP) is an infrequent benign neoplasm commonly involving the upper respiratory tract with laryngeal predilection. The diagnosis and treatment of this disease are challenging due to its nonspecific clinical presentations and recurrent nature. We report here a rare juvenile case of RRP arising in the trachea without laryngeal lesions. Our experiences indicate that a high awareness of RRP and proper consideration in the right clinical context are prerequisites for early diagnosis, and a combination of multiple treatment modalities should be considered as a feasible treatment regimen.

Quantitative morphometry of respiratory tract epithelial cells as a tool for testing chemopreventive agent efficacy.

Previously, we developed a 30-day transformation assay (focus inhibition, FIA) of rat tracheal epithelial (RTE) cells to identify cancer preventive agents. This study reports nuclear density (ND) as a morphometric biomarker for efficacy evaluation of at an early stage before transformed foci appear. Positive (oltipraz, D-carvone, fumaric acid, and 2-amino-4-methylpyridine or 2-A-MPR) and negative agents (myristoleic acid, anethole trithione, hydrocortisone, and 3'-hydroxyflavanone), identified from FIA, were tested for their effect on ND. RTE cells plated for 24 h were treated with a carcinogen, benzo[a] pyrene (B[a]P) or plus a test agent. The data based on the number of nuclei in agent-treated and control cells at day 14 showed that all FIA-positive agents inhibited ND from 23-66% at 0.3-1000.0 microM and except for myristoleic acid, all of the FIA-negative compounds were also negative in the morphometry assay. As there is strong correlation between the FIA and morphometry data, morphometry analysis is useful for rapid screening of potential chemopreventive agents.

Inhibition by beta-carotene of upper respiratory tumorigenesis in hamsters receiving diethylnitrosamine followed by cigarette smoke exposure.

In recent intervention studies, beta-carotene failed to reduce or even increased the incidence of lung cancers in smokers. In the present investigation, the modifying effects of beta-carotene at various doses on the development of upper respiratory tract tumors were investigated in Syrian hamsters treated with diethylnitrosamine (DEN) and cigarette smoke. A total of 120 male 5-week-old hamsters were divided into 4 groups, each consisting of 30 animals. After a single subcutaneous (s.c.) injection of 100 mg/kg DEN, hamsters in groups 1-4 were respectively administered diets supplemented with beta-carotene at doses of 0.5%, 0.05%, 0.005% or 0% during experimental weeks 1 to 13, and simultaneously exposed to cigarette smoke. The duration of cigarette smoke exposure was 9 min twice a day, 5 days a week. Because of a marked reduction of body weight in group 1, the highest dose of beta-carotene was changed to 0.25% after 10 days. In all groups, epithelial hyperplasias and/or papillomas were induced in the larynx and trachea. However, the incidence and multiplicity of papillomas in group 1 were significantly (P < 0.05) lower than the group 4 values. Moreover, the beta-carotene treatments significantly (P < 0.05 or 0.01) reduced both the incidence and multiplicity of hyperplasias in a dose-dependent manner. The levels of retinol and beta-carotene in the serum, and the retinol level in the liver, were also elevated with dose dependence. Our results thus indicate that beta-carotene inhibits tumorigenesis, even at the high dose of 0.25%, under the present experimental conditions.

Interspecies analysis of the chemopreventive efficacy of dietary alpha-difluoromethylornithine.

The anticarcinogenic efficacy of the polyamine biosynthesis inhibitor, alpha-difluoromethylornithine (DFMO), was assessed in three rodent models of human epithelial cancer. In DMBA-induced female, Sprague-Dawley rats, DMFO treatment (3.2 or 6.4 g/kg diet) for 180 days significantly inhibited mammary carcinogenesis and reduced tumor-related intercurrent mortality compared to untreated controls. In male, C57BL/6x DBA/2F1 mice induced with N-butyl-N(4-hydroxybutyl)nitrosamine (OH-BBN), DFMO treatment (2 or 4 g/kg diet) concurrent with the period of carcinogen administration significantly reduced the incidence and severity of urinary bladder carcinomas. In methylnitrosourea (MNU)-induced male Syrian golden hamsters, DFMO (3.2 g/kg diet) numerically reduced the incidence and size of tracheal carcinoma relative to untreated controls. DFMO-mediated toxicity was not evident in any of the animals on study, although a slight reduction in mean body weight gain was evident in rats and mice.

Effect of three retinoids on tracheal carcinogenesis with N-methyl-N-nitrosourea in hamsters.

Male Syrian golden hamsters received 12 weekly intratracheal exposures to 0.5% N-methyl-N-nitrosourea with a special catheter. Following exposures, animals were randomized into 4 groups of 63 hamsters and placed on diets of lab meal or meal with 120 mg 13-cis-retinoid acid (CRA)/kg, 327 mg ethyl retinamide (ER)/kg, or 343 mg N-(2-hydroxyethyl)retinamide (HR)/kg for 6 months at which time all hamsters were killed. The observed incidences of tracheal epithelial neoplasms (No. of animals with tumors/total No. of animals) were 10/63 (lab meal), 22/61 (CRA), 24/63 (ER), and 17/62 (HR). The incidence of carcinomas (No. of animals with tumors/total No. of animals) were 4/63 (lab meal), 12/61 (CRA), 12/63 (ER), and 11/62 (HR). The weight loss and mortality relative to those in the group fed the lab meal were significantly in the group fed HR but not in the other retinoid-treated groups.

Effect of graded dietary levels of selenium on tracheal carcinomas induced by 1-methyl-1-nitrosourea.

An investigation was conducted to determine the effect of the dietary level of selenium on the induction of tracheal cancer by 1-methyl-1-nitrosourea (MNU). Male Syrian golden hamsters received intratracheal instilations of a 0.5% MNU solution once weekly for 12 weeks. Two weeks prior to the initiation of carcinogen treatment, animals were placed on a semisynthetic, 30% torula yeast diet to which either no selenium or 1 or 5 mg selenium/kg of diet as sodium selenite was added. Animals were maintained on their respective diets for the duration of the study which was terminated 195 days after the first MNU treatment. No significant differences among groups in the incidence of either benign lesions or carcinomas was observed and the distribution of tumor type was similar irrespective of selenium treatment. The results of this study indicate that selenium exerts no chemopreventive effect against MNU-induced tracheal carcinogenesis.

Elective irradiation of the lower cervical region in patients at high risk for recurrent cancer at the tracheal stoma.

The results of treatment for recurrent cancer at the tracheal stoma have been poor. From 1971 to 1976, elective postoperative irradiation of the neck was given to 26 high-risk patients with carcinoma of the larynx and hypopharynx. None of the 22 patients whose stomas were irradiated developed stomal or peristomal recurrence, while 2 of the 4 patients whose stomas were shielded had stomal recurrence. Elective irradiation of the tracheal stoma was effective in preventing stomal recurrence; we recommend inclusion of the stomal area in preoperative or postoperative irradiation to the lower cervical region for high-risk patients.

Prevention of tracheal stoma recurrences after total laryngectomy by postoperative irradiation.

Patients with advanced glottic cancer, in whom there is extensive subglottic disease and/or low cervical lymph node metastasis, have a high incidence of recurrence in and about the tracheal stoma. Stoma recurrences can be prevented by immediate postoperative megavoltage radiotherapy when the stoma is included in the irradiated volume.