Cell type specificity of lung cancer associated with arsenic ingestion.

Arsenic is a well-documented human carcinogen. Previous studies on urinary bladder and skin cancers have shown that arsenic can cause specific cell types of malignancy. To evaluate whether this is also true for lung cancers, we conducted a study on 243 townships in Taiwan. We identified patients through the National Cancer Registry Program and compared the proportion of each major cell type between an endemic area of arsenic intoxication with exposures through drinking water, which includes 5 of the townships and the other 238 townships. To control for gender and age, we analyzed data on men and women separately and divided patients into four age groups. A total of 37,290 lung cancer patients, including 26,850 men and 10,440 women, was diagnosed between January 1, 1980 and December 31, 1999 in study townships. Patients from the endemic area had higher proportions of squamous cell and small cell carcinomas, but a lower proportion of adenocarcinomas. These findings were similar across all age groups in both genders, although the lack of data on smoking is a limitation of our study. The results suggested that the carcinogenicity of arsenic on lungs is also cell type-specific: squamous cell and small cell carcinomas appeared to be related to arsenic ingestion, but not adenocarcinoma. Whereas data in the literature are limited, the association between adenocarcinoma and arsenic exposures through inhalation appeared to be stronger than that of squamous cell carcinoma. Therefore, we speculate that arsenic may give rise to different mechanisms in the development of lung cancers through different exposure routes.

Chronic obstructive lung disease: from structure to pathology.

Chronic obstructive pulmonary disease (COPD) is a complex disease characterized by progressive and irreversible airway obstruction and ubiquitous chronic inflammation in the lung. It is the end result of accumulated damage to many parts of the lung by many types of noxious agents, a destructive exhaustion of the lung reserve. Recent increases in the incidence of COPD have occurred mainly in older age groups, in non-smokers, and in females. Pathologically, COPD is characterized by chronic inflammation which perpetuates and accumulates locally. Discrete areas interact with each other, in the locus resistentia minoris (LRM), the sites of weak resistance of the lung, suggesting that insidious destruction with exhaustion of pulmonary reserves is still the main culprit of COPD. Traditional treatments of COPD are useful in symptomatic control but do not prevent progression of the disease. Prevention is still the best way to manage COPD. New pharmaceutical agents and bioengineered products using molecular or genetic techniques to block inflammatory mediators or their receptors may contain the inflammatory and noxious agents in the LRM and prevent their propagation. Methodologies involving structural approaches, such as devices to estimate the status of airways and associated vessels and the remaining lung reserve, creation of collateral or bypass ventilation pathways, and reduction of volume of over-inflated areas may be effective. The balance between exposure and clearance, injury and repair, ultimately decides how quickly the great reserves of the lung are depleted.

Successful treatment of multifocal bronchioloalveolar cell carcinoma with ZD1839 (Iressa) in two patients.

Multifocal bronchioloalveolar cell carcinoma (BAC) is a rare condition that often presents as bilateral lung infiltrates unsuitable for surgical and radiological treatment, with poor response to conventional chemotherapies. Epidermal growth factor receptor (EGFR) pathways are closely related to the proliferation and metastasis of cancer cells. ZD1839 (Iressa) is a quinazoline-derived, orally active, selective inhibitor of the EGFR tyrosine kinase that shows promising effects in the treatment of non-small cell lung cancer. We report 2 cases of multifocal BAC successfully treated with ZD1839. Both patients had advanced disease, and had productive cough for more than 1 year. After the diagnosis of BAC, the first patient received chemotherapy, but was unresponsive. Within 2 weeks of starting treatment with ZD1839 250 mg per day, the amount of bronchorrhea decreased. Two months after the start of ZD1839 treatment, image study showed a marked decrease of lung infiltrates. The second patient developed respiratory failure after an operation on the spine. He received ZD1839 250 mg daily via nasogastric tube. Two weeks after the start of treatment, his dyspnea had improved and he was weaned from the mechanical ventilator. The side effects of ZD1839 treatment in these 2 patients consisted only of dry skin and acne over the face, trunk, and periungual areas. Although the precise mechanisms of the antitumor effects of ZD1839 remain unclear, these results suggest a role for the agent in the management of patients with advanced multifocal BAC.

Combined intrapleural and intravenous chemotherapy, and pulmonary irradiation, for treatment of patients with lung cancer presenting with malignant pleural effusion. A pilot study.

OBJECTIVES: Patients with non-small-cell lung cancer (NSCLC) and malignant pleural effusion (MPE) are difficult to manage clinically and have a short life expectancy. In this pilot study, we designed a protocol of combined intrapleural (i.p.) and intravenous (i.v.) chemotherapy and pulmonary irradiation to enhance local as well as systemic control of the disease. METHODS: From April 1998 to April 2000, 27 patients with NSCLC and symptomatic MPE were eligible for the study. Patients received pre-radiation chemotherapy (cisplatin 60 mg/m(2) i.p. on day 1; gemcitabine 1,000 mg/m(2) i.v. on days 1, 8, and 15, q4week x 3) after surgical implantation of i.p. and i.v. port-A, followed by radiotherapy (7,020 cGy/39fr), and, finally, post-radiation chemotherapy (docetaxel 60 mg/m(2) q3week x 3-6 i.v.). RESULTS: Grade 1/2 nausea/vomiting and impaired renal function were more common from pre-radiation than post-radiation chemotherapy; however, grade 3/4 toxicities from pre-radiation chemotherapy were minimal. Conversely, grade 3/4 leukopenia and grade 1/2 alopecia, diarrhea, elevation of SGOT/SGPT, and sensory impairment were more common following post-radiation chemotherapy. Only two patients experienced recurrence of pleural effusion. The overall response rate was 55% with 7% complete remission, 48% partial remission, 22% stable disease, and 22% progressive disease. The median failure-free and overall survival was 8 and 16 months, respectively. The one-year survival rate was 63% (95% confidence interval, 45-80%). CONCLUSIONS: We conclude that the combination of i.p. and i.v. chemotherapy and pulmonary irradiation is feasible and should be tested in a larger clinical trial to determine whether survival can be improved for this cohort of patients.