3191. Iodinated glycerol and thyroid dysfunction. Four cases and a review of the literature.
Iodinated glycerol (Organidin) has recently been shown to be a useful adjunct in the symptomatic treatment of patients with chronic obstructive pulmonary disease (COPD). Over an 18-month period, we saw four patients with significant thyroid dysfunction resulting from iodinated glycerol use. All were elderly patients with COPD who had been started on standard doses of iodinated glycerol 4 to 24 months earlier. None of the patients had histories of thyroid disease. Three of the patients had symptomatic thyrotoxicosis and one had severe hypothyroidism while taking iodinated glycerol. We review the literature on the mechanisms and management of iodine-induced thyroid dysfunction and conclude the following: (1) all iodine-containing drugs may adversely affect thyroid function; (2) these compounds should be prescribed with extreme caution to any patients with underlying thyroid disease; and (3) all patients receiving iodine-containing medications should be closely monitored for evidence of thyroid dysfunction.
3192. Infection of pulmonary artery catheters. Epidemiologic characteristics and multivariate analysis of risk factors.
Sixty-nine consecutive pulmonary artery catheters (PACs) were prospectively studied in a medical-surgical intensive care unit. Fifteen (21.7 percent) and two (2.9 percent) of the PACs were associated with colonization and bacteremia, respectively. These data represent an incidence of 4.98 and 0.66 episodes per 100 catheterization-days, respectively. Coagulase-negative staphylococci were the most common isolates. The source of the colonizing microorganism was the skin in 56 percent of cases, hubs in 28 percent, and unknown in 16 percent. From multivariate analysis, only more than 5 days of catheterization was significantly associated with a greater risk of colonization. Antimicrobial use was associated with negative cultures. The most useful method to diagnose colonization was the examination of both tip and intradermal segments. In addition, we suggest associate hub cultures when catheter-related bacteremia is suspected. These data may be useful in improving efficacy in the diagnosis and prevention of PAC-related infection.
3193. Chemoprophylaxis strategies in high-risk groups with an emphasis on lung cancer.
The incidence of lung cancer in the United States has stabilized in recent years, but it remains a major cause of death in the United States. Whereas the single most effective primary prevention of this disease would be to eliminate tobacco use from society, this is currently an unrealistic goal. Secondary prevention, however--that is, chemoprophylactic treatment of smokers, exsmokers, and others at risk--represents a viable option. Agents proven effective in both laboratory models and humans include vitamin A and its synthetic derivatives, the retinoids and the carotenoids. It is fairly easy to identify patients at risk of lung cancer compared with other cancers. Yet aside from patients who are under a physician's care and aware of their risk, it can be difficult to target individuals for chemoprophylactic treatment, especially those who are healthy but at high risk and not seeing a physician or other health care provider. Screening for the presence of predictive cellular and molecular changes may facilitate more accurate selection of individuals for chemoprophylactic treatment.
3194. The epidemiology of lung cancer.
Lung cancer rates and mortality have risen in epidemic proportions in the United States and other industrialized nations during the 20th century. Case-control and cohort studies performed in the 1950s and 1960s firmly established cigarette smoking as the single greatest risk factor for lung cancer. In the United States, overall lung cancer mortality rates in men and women rose progressively from the 1950s. Fortunately, lung cancer incidence and mortality are now declining in middle-aged men. Smoking has significantly increased lung cancer rates among women and is on the rise in developing countries. Environmental agents found in the home and workplace, including radon and asbestos, have also been shown to increase lung cancer risk in both smokers and nonsmokers. Government regulations have helped curtail quantities of these and other atmospheric carcinogens. Efforts to reduce lung cancer risk must be continued and their scope expanded in order to have a global impact on the incidence and mortality of this fatal malignancy.
3195. Chemoprevention strategies in lung carcinogenesis.
Chemoprevention entails using specific agents to suppress carcinogenesis and thereby prevent the development of primary or second primary cancers. Because the concept of chemoprevention in patients with or at risk of lung cancer is new, ongoing clinical trials are based on data from epidemiologic and preclinical research, as well as on results of chemoprevention studies in head and neck cancer. The latter studies have provided a model for such studies in lung cancer, considering the two diseases have a similar etiology and biology of field carcinogenesis. Beta-carotene, natural vitamin A, and the retinoids may be effective chemopreventive agents. However, chronic administration of such agents may be required to prevent the development of cancer. Results of chemoprevention trials in head and neck cancer have demonstrated effective inhibition of the development of second primary tumors with the synthetic retinoid 13-cis-retinoic acid; investigators are hopeful this will be repeated in patients with lung cancer. Results of ongoing phase III trials and continued advances in the epidemiologic and biologic study of lung carcinogenesis should contribute to future research in this area.
3196. Detection and localization of early lung cancer by imaging techniques.
Two new technologic developments may have a significant impact on the detection and localization of early lung cancer. These two developments work together in a complementary way. The first is a solid-state microscope that can be applied in the prescreening of sputum cytology specimens. The finding that malignancy-associated changes (MACs) are present in ostensibly normal bronchial epithelial cells may be used to improve the sensitivity of sputum cytology to detect cancer. Once abnormal or MAC cells are found, a second device, a fluorescence bronchoscope, can be employed to localize the source of the abnormal cells. Fluorescence bronchoscopy is also a potentially useful tool for procuring premalignant tissue for molecular biology studies and for monitoring the progress of patients in chemoprevention studies.
3197. Treatment of the elderly patient with small-cell lung cancer.
The population of the United States is gradually aging. Within a generation, over 20 percent of the population will be > 65 years of age. Since cancer is a disease of older persons, the incidence of malignancies of all types is expected to increase during the coming decades. In general, since older patients appear to tolerate chemotherapy less well than their younger counterparts, strategies that lessen toxicity and yet maintain efficacy are desperately needed. Recently, the use of single-agent oral etoposide has been shown to be an effective palliative therapy for older patients with small-cell lung cancer. Future studies will need to focus on the unique requirements of older patients in order to improve therapy in these individuals.
3198. Management of metastatic non-small-cell lung cancer and a consideration of cost.
The 12 percent five-year survival rate for patients with non-small-cell lung cancer (NSCLC) has not changed in several decades. However, four randomized trials have shown a modest increase in the mean survival time of patients with advanced NSCLC who received systemic chemotherapy vs best supportive care (BSC), and two others have demonstrated a statistically significant survival advantage (average increase, 12 weeks). Whereas the objective response rate to chemotherapy ranges from 30 to 40 percent, relief of cancer-related symptoms as well as improved performance status and weight gain typically occur in 70 percent of patients. Treatment-related adverse effects have been markedly reduced with new antiemetics. Concerns regarding costs have been lessened by the National Cancer Institute of Canada's observation that at least some chemotherapy regimens may be less costly than BSC. Direct-care costs of managing all stages of NSCLC in Canada were estimated at $102 million (1984 Canadian dollars), assuming that stage IV patients received only BSC. The average incremental cost of the most expensive chemotherapy would be $5,000 per case. If this cost were incurred by 50 percent of stage IV cases (good performance status, symptomatic patients), total care costs would be increased by about 10 percent ($10.5 million). This is less than half the cost of the introduction of neoadjuvant chemotherapy, which is rapidly being adopted as standard practice in the absence of data from randomized controlled clinical trials.
3199. Current and future therapy for malignant pleural effusion.
Several options are available for treatment of malignant pleural effusions in patients with non-small-cell lung cancer. Repeat thoracentesis may be appropriate for the patient with limited survival and a slowly recurrent effusion. Pleurodesis with a sclerosing agent administered via a chest tube is the most widely used therapy, though controversy exists as to which drug produces the best results. Pleuroperitoneal shunting remains an option for those patients whose lung is trapped by tumor. Video-assisted thoracoscopy is likely to change the treatment patterns of malignant pleural effusion. Thoracoscopic pleurectomy can be performed with minimal morbidity. Alternatively, sclerosing agents such as talc can be easily and uniformly introduced into the thoracic cavity under thoracoscopic control. Future therapy is likely to entail a diagnostic thoracentesis followed by a definitive thoracoscopic procedure.
3200. Innovations in multimodality therapy for lung cancer. Combined modality management of limited small-cell lung cancer.
Recent approaches to the treatment of limited small-cell lung cancer have combined local radiotherapy and systemic chemotherapy in an attempt to improve local control and inhibit distant metastases. Local control is a key indicator of the efficacy of radiotherapy administration in combined-modality regimens. However, even in combined-modality trials using high total radiotherapy doses, local failure rates have ranged from 30 to 50 percent. The components of radiotherapy administration--including dose, volume, fractionation, integration with chemotherapy (concurrent, alternating, or sequential), and timing (early or late administration)--are also important considerations. Hyperfractionation, or the administration of small fractions of radiation more than once daily (usually twice), and accelerated hyperfactionation, or the administration of three fourths of the standard radiation dose two to three times daily, have emerged as important concepts in radiotherapy. Although the optimal chemotherapy regimen for combined-modality treatment has not yet been established, use of cisplatin and etoposide combinations, which do not promote pulmonary, cardiac, or esophageal toxicity, have been particularly appropriate in patients with small-cell lung cancer.
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