Local control in medically inoperable lung cancer: an analysis of its importance in outcome and factors determining the probability of tumor eradication.

PURPOSE: For patients who are medically unable to tolerate a surgical resection for technically resectable non-small-cell lung carcinoma, radiation therapy is an acceptable alternative. We report on the effect of achieving local control of the primary tumor on survival end-points, and analyze factors that may influence local control. METHODS AND MATERIALS: We reviewed the records of 152 patients with medically inoperable non-small-cell lung carcinoma treated at our institutions. All patients had technically resectable lesions and no evidence of metastatic disease. Treatment was delivered using megavoltage irradiation to doses ranging from 45 to 75 Gy. RESULTS: For patients with tumors 3 cm or less, locally controlling the tumor significantly improved survival (p = .0371). Patients with T1 tumors had a higher probability of survival and disease-free-survival than patients with larger tumors if the primary tumor was locally controlled, but this survival advantage disappeared if the tumor was not controlled. Overall, patients with smaller tumors had a lower incidence of distant spread, but this association was maintained only when the primary tumor was controlled (36 month risk of 10%, 23%, and 57% for tumors < 3 cm, 3-4.9 cm, 5 cm or greater, respectively, p = .0027). For patients whose tumors were not controlled, there was no significant difference in the risk of distant dissemination by tumor size. Higher radiation doses influenced local control and metastatic spread. We observed no influence of the initial field size in the risk of local control and in the probability of survival. CONCLUSION: Radical radiation therapy is an effective treatment for small (T1 or < 3 cm) tumors when treated to doses of 65 Gy or more, and should be offered as an alternative to surgery in elderly or infirm patients. New therapeutic strategies to improve the local control rate should be considered for larger tumors, through the use of hyperfractionated treatment, endobronchial "boost" irradiation, and sensitizing chemotherapy agents.

Cigarette smoke alters plasma membrane fluidity of rat alveolar macrophages.

This study examined the effect of cigarette smoking on the fluidity of the rat alveolar macrophage plasma membrane. Rats were subjected to 8 wk of an in vivo smoke exposure protocol, after which their alveolar macrophages were harvested. Fluidity was assessed by measuring steady-state anisotropy of isolated plasma membranes as well as of lipid vesicles made from total lipid extracts of these plasma membranes. The smoke-exposed animals showed a significant decrease in fluidity in both intact plasma membranes (p less than 0.0001) and in their lipid vesicle preparations (p less than 0.0001). To assess the time course of these changes, lipid vesicles were prepared from total cellular lipid extracts of macrophages from paired rats, control and smoke-exposed, at 1 through 4 wk after initiation of exposure. Significant decreases in fluidity were observed as early as 2 wk after smoking was begun (p less than 0.001). To assess the reversibility of these changes, paired rats were exposed for 8 wk, then withdrawn for 8, 12, and 18 wk, after which fluidity was evaluated in lipid vesicles prepared from total cellular lipids. Even after 18 wk of smoking cessation, significant decreases in fluidity persisted (p less than 0.01). We conclude that cigarette smoking causes a decrease in plasma membrane fluidity of rat alveolar macrophages. This is due at least in part to a change in the lipid portion of the membrane. These alterations occur after a very brief period of smoke exposure and persist long after cessation of smoking.

The effect of whole virus influenza vaccination on theophylline pharmacokinetics.

The effect of whole virus influenza vaccination on theophylline pharmacokinetics was evaluated in 16 normal subjects. Because previous reports had suggested that influenza vaccine induces interferon production and may potentially depress hepatic metabolism of theophylline, serum interferon concentrations were monitored for 6 days after vaccination. Lymphocytes from 6 subjects were incubated in vitro with dilute whole virus vaccine (WVV) or dilute split virus vaccine (SVV) to assess their immunocompetence and the immunogenic potential of the 2 vaccine preparations. Additionally, influenza antibody response was monitored by prevaccination and postvaccination serum antibody titers in 11 subjects. No significant change in half-life, total body clearance, volume of distribution of maximal serum theophylline concentration compared to prevaccine values was observed at either 2 or 6 days after vaccination. No interferon production was detected in vivo up to 6 days after vaccination. In vitro lymphocyte interferon induction assay demonstrated mean interferon levels of 12,252 +/- 9,819 IU/ml for WVV and 888 +/- 1,180 IU/ml for SVV (p less than 0.05), demonstrating the immunocompetence of the subject's lymphocytes and confirming the greater immunogenic potential of WVV. Seven of 11 subjects (64%) showed a 4-fold rise in influenza antibody titer to at least one of the vaccine antigens. We conclude that whole virus influenza vaccine does not alter theophylline pharmacokinetics. In addition, it has greater immunogenic potential than split virus vaccine in vitro but does not induce significant interferon production in vivo. This study adds further evidence supporting the safety of the concomitant use of influenza vaccine in patients taking theophylline.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone pulmonary toxicity presenting as bilateral exudative pleural effusions.

Therapy with the antiarrhythmic drug amiodarone has been associated with drug-related side effects. In addition to pulmonary fibrosing alveolitis, anecdotal reports have alluded to incidental pleural involvement associated with amiodarone. We describe an unusual manifestation of amiodarone-induced pulmonary toxicity in a patient with bilateral exudative pleural effusions and toxic involvement of other organs. We review amiodarone-associated pleural reactions reported in the literature.

Foreign body aspiration associated with the use of an aerosol inhaler.

A 51-yr-old asthmatic carpenter aspirated a penny using a hand-held, self-pressurized aerosol device. The penny was extracted using a fiberoptic bronchoscope. Because no similar instances are reported in the medical literature, experimental systems were designed to test the likelihood of this event happening with a variety of nebulizers. Nickels , dimes , and pennies were tested for ejection potential and for aspiration likelihood. All inhalers, excepting that designed for Intal, were capable of accommodating dimes and pennies and ejecting them down simulated airways during inspiration. Nickels were accommodated by several inhalers but were not ejected during conventional inspiratory volumes and pressures.