Home and workplace smoking bans in Italy, Ireland, Sweden, France and the Czech Republic.

The purpose of this study was to report predictors and prevalence of home and workplace smoking bans in five European countries. We conducted a population-based telephone survey of 4,977 females, ascertaining factors associated with smoking bans. Odds ratios and 95% confidence intervals were derived using unconditional logistic regression. A complete home smoking ban was reported by 59.5% of French, 63.5% of Irish, 61.3% of Italian, 74.4% of Czech and 87.0% of Swedish females. Home smoking bans were associated with younger age and being bothered by secondhand smoke, and among smokers, inversely associated with greater tobacco dependence. Among nonsmokers, bans were also related to believing smoking is harmful (OR 1.20, 95% CI 1.11-1.30) and having parents who smoke (OR 0.62, 95% CI 0.52-0.73). Workplace bans were reported by 92.6% of French, 96.5% of Irish, 77.9% of Italian, 79.1% of Czech and 88.1% of Swedish females. Workplace smoking bans were reported less often among those in technical positions (OR 0.64, 95% CI 0.50-0.82) and among skilled workers (OR 0.53, 95% CI 0.32-0.88) than among professional workers. Workplace smoking bans are in place for most workers in these countries. Having a home smoking ban was based on smoking behaviour, demographics, beliefs and personal preference.

Metabolic gene polymorphism frequencies in control populations.

Using the International Project on Genetic Susceptibility to Environmental Carcinogens (GSEC) database containing information on over 15,000 control (noncancer) subjects, the allele and genotype frequencies for many of the more commonly studied metabolic genes (CYP1A1, CYP2E1, CYP2D6, GSTM1, GSTT1, NAT2, GSTP, and EPHX) in the human population were determined. Major and significant differences in these frequencies were observed between Caucasians (n = 12,525), Asians (n = 2,136), and Africans and African Americans (n = 996), and some, but much less, heterogeneity was observed within Caucasian populations from different countries. No differences in allele frequencies were seen by age, sex, or type of controls (hospital patients versus population controls). No examples of linkage disequilibrium between the different loci were detected based on comparison of observed and expected frequencies for combinations of specific alleles.

Gender differences in genetic susceptibility for lung cancer.

In contrast to men, the incidence of lung cancer among women has increased over the past decade. The basis for this increase among female smokers remains unknown. Surgical patients with a diagnosis of lung cancer and control subjects without a history of malignancy completed a smoking questionnaire and donated a blood sample. DNA was extracted from peripheral mononuclear cells and genotyped for polymorphisms in cytochrome P450 1A1 (CYP1A1) (exon 7) and glutathione S-transferase M1 (GSTM1) (null). No gender differences in either age at diagnosis or histological subtype were observed among lung cancer patients. In both patients (n = 180) and controls (n = 163), females smoked significantly less than males. The pack-year history associated with adenocarcinoma was smaller than that for squamous cell carcinoma. No significant association was observed between the GSTM1 null genotype and cancer risk. However, women had a larger cancer risk than men (odds ratio 4.98 vs. 1.37) if they possessed the mutant CYP1A1 genotype. Female cancer patients were significantly more likely than female controls to have both the CYP1A1 mutation and GSTM1 null genotype. The combined variant genotypes conferred an odds ratio of 6.54 for lung cancer in women versus 2.36 for men, independent of age or smoking history. These data suggest that polymorphisms in CYP1A1 and GSTM1 contribute to the increased risk of females for lung cancer.

Prognostic value of positive pleural lavage in patients with lung cancer resection.

BACKGROUND: Despite an early stage, lung cancer patients often have a poor survival, suggesting inaccurate staging. A pleural lavage demonstrating malignant cells at the time of operation may predict a poorer survival, particularly in patients with otherwise early disease. METHODS: Patients, with no preoperative evidence of pleural effusions and undergoing a surgical resection with curative intent, had a preresectional and postresectional lavage to be evaluated by cytology. RESULTS: Fourteen percent of patients with stage I disease had malignant cells in their preresectional lavage and had a significantly shorter survival than stage I patients with a negative lavage. Positivity of preresectional lavage was not correlated with nodal status, pleural or lymphatic involvement, or histologic findings. CONCLUSIONS: Preoperative pleural lavage should become a standard technique intraoperatively to better characterize and stage patients undergoing lung cancer resections. Patients with malignant cells in their preoperative lavage should be upstaged.

Kidney metastases.

Renal cell carcinoma is not common malignancy. Unfortunately, it remains difficult to cure, with small improvements being made in chemo/immunotherapeutic areas. Surgery remains the most successful approach for curative treatment in both primary and metastatic disease. Prospective studies are critically needed to definitively determine appropriate prognostic indicators for operation.

Pleural cytologies in lung cancer without pleural effusions.

BACKGROUND: Malignant pleural effusions significantly increase the stage of lung cancer with attendant worsening of prognosis. There is a paucity of literature evaluating malignant pleural lavage cytology in patients without pleural effusions. We propose to determine the incidence of malignant pleural cytologies in patients without pleural effusions who undergo curative resection for lung cancer and to identify any predictive risk factors for positive cytology. METHODS: Seventy-eight patients underwent curative resection for lung cancer. Lavage was performed before lung manipulation and after resection and cytologically evaluated. RESULTS: Twelve pneumonectomies, 64 lobectomies, and 2 wedge resections were performed on 40 men and 38 women with an average age of 65.7 years. Fourteen percent had positive lavage cytology before lung resection with an 11% (6 of 53) incidence in stage I. A significant correlation to adenocarcinoma compared with squamous cell was found (p = 0.03) but not to stage, T or N status, grade, pleural invasion, or preoperative transthoracic needle biopsy. CONCLUSIONS: The incidence of positive pleural cytology in otherwise stage I patients is disconcertingly high. Positive cytology may be a prognosticator of a more aggressive tumor biology.

Regional lymph node classification for lung cancer staging.

Recommendations for classifying regional lymph node stations for lung cancer staging have been adopted by the American Joint Committee on Cancer (AJCC) and the Union Internationale Contre le Cancer. The objective was to unify the two systems that have been in common use for the past 10 years; that is, the schema advocated by the AJCC, adapted from the work of Tsuguo Naruke, and the schema advocated by the American Thoracic Society and the North American Lung Cancer Study Group. Anatomic landmarks for 14 hilar, intrapulmonary, and mediastinal lymph node stations are designated. This classification provides for consistent, reproducible, lymph node mapping that is compatible with the international staging system for lung cancer. It is applicable for clinical and surgical-pathologic staging.

Clinical-pathologic analysis of 40 patients with large cell neuroendocrine carcinoma of the lung.

BACKGROUND: The identification, classification, and appropriate treatment of patients with pulmonary carcinomas demonstrating neuroendocrine differentiation remains controversial. METHODS: Patients undergoing resection of lung cancer at Washington University since 1986 were reviewed to identify all large cell neuroendocrine carcinomas. Cases were segregated into large, small, or mixed cell categories, and graded as moderate ("atypical carcinoid") or poorly differentiated (all higher grade lesions). All patients' charts were reviewed and referring physicians contacted to ascertain cancer treatment after resection and follow-up status. RESULTS: Forty patients were identified with large cell neuroendocrine carcinoma: 8 moderate and 32 high-grade. Average follow-up was 19.8 months. Stage distribution was as follows: I, 25; II, 6; III, 6; and VI, 3. Fifteen patients have no evidence of disease, 15 are dead of disease, and 6 are alive with disease. Five-year survival of the stage I patients is 18%; all-stage 5-year survival is 13%. Of the 15 patients who died of their disease, 80% had stage I or II disease. Postoperative chemotherapy, radiation therapy, or both were given to 9 of 26 patient in stage I, with six deaths (67%). Six of 17 patients (35%) with stage I disease died after no postoperative intervention. CONCLUSIONS: Large cell neuroendocrine carcinomas identified by histologic examination have a remarkably poor prognosis even in very early stage disease. Adjuvant therapy did not improve survival.

Results of a trial with topotecan dose escalation and concurrent thoracic radiation therapy for locally advanced, inoperable nonsmall cell lung cancer.

PURPOSE: To conduct a dose escalation clinical study with topotecan and concurrent standard dose thoracic irradiation to assess its feasibility and toxicity in the treatment of patients with locally advanced, inoperable nonsmall cell lung cancer (NSCLCA). METHODS AND MATERIALS: Between April 1993 and August 1994, 12 patients with inoperable, loco-regionally advanced NSCLCA were entered in a prospective dose escalation trial and assigned to receive concurrent thoracic radiotherapy and topotecan. Patients received thoracic irradiation to a total tumor dose of 60 Gy in 30 fractions. Initial fields were to encompass the gross disease plus the mediastinum. Topotecan was delivered by bolus injection days 1 through 5, and days 22 through 26, beginning on the same day as the radiation therapy. The initial dose level was 0.5 mg/m2. Two additional dose levels of 0.75 mg/m2 and 1.0 mg/m2 were tested. RESULTS: Six patients were accessioned to the 0.5 mg/m2 dose level, three patients to the 0.75 mg/m2 dose level, and three patients to the 1.0 mg/m2 dose level. At the 0.5 mg/m2 dose level, zero of six patients had > or = Grade 4 hematologic toxicity. One of the six had Grade 3 esophagitis. At the 0.75 mg/m2 dose level, two of three patients had > or = Grade 3 nonhematologic toxicity including anorexia, fatigue, nausea, vomiting, and weakness; zero patients experienced > or = Grade 4 hematologic toxicity. At the 1.0 mg/m2 dose level one of three patients had > or = Grade 3 esophagitis, and two of three patients experienced Grade 4 neutropenia. With a follow-up of 12 to 24 months, two patients are alive and free of disease, three patients are alive with disease (two with distant metastasis, one with local disease and distant metastasis), and the remaining seven patients are dead of disease. CONCLUSIONS: The combination of topotecan and thoracic radiotherapy for nonsmall lung cancer, in the manner given by this protocol, could be safely given at a dose level of only 0.5 mg/m2 days 1 to 5 and 22 to 26 with 60 Gy of external beam radiotherapy. Higher doses of topotecan were associated with high hematologic and gastrointestinal toxicity. Distant metastasis was the primary pattern of failure.

Experiences of women in cardiothoracic surgery. A gender comparison.

OBJECTIVE: To assess the career and practice experiences of cardiothoracic surgeons, with references to gender similarities and differences. DESIGN: Four-step mailed 115-question survey. SUBJECTS: All identified women, and a cohort of men, certified by the American Board of Thoracic Surgery. MAIN OUTCOME MEASURES: Academic rank, career background, salary, perceptions and experiences of harassment or discrimination, and personal life characteristics. RESULTS: No differences were found in training backgrounds. More men (64%) than women (52%) were in university practices. Comparable proportions of men and women were assistant professors (27%), but more men (27%) than women (13.6%) were full professors. Fifty-eight percent of women and 21% of men reported salaries of less than $250000; 62% of men and 32% of women had incomes over $350000. Career satisfaction was comparable between genders; however, women perceived the promotion process as unfair and unrelated to academic rank. Both genders encouraged men toward a surgical career; men were less likely than women to encourage women to pursue a surgical career (P < .01). Women, much more than men, believed that discrimination hindered their career development (P < .001). Characteristics of personal life were also considerably different between the genders. CONCLUSION: Although practice and training parameters for male and female cardiothoracic surgeons are comparable, work experiences, personal life, and career rewards such as salary and promotion, and perception of discrimination are different.

Smoking cessation and lung cancer resection.

STUDY OBJECTIVE: This study was designed to examine the extent of smoking cessation prior to thoracotomy for resection of a pulmonary malignancy and the recidivism rate. DESIGN: Prospective, longitudinal study. PATIENTS: All patients presenting to the General Thoracic Clinic. RESULTS: The study included 362 patients, with an average age of 64.7 years; 95% with a smoking history were followed up for an average of 17.5 months. Five surgeons in the same practice group performed the procedures: pneumonectomy, 45; lobectomy, 288; and lesser resections, 29. Forty-two percent of patients had quit prior to 1 year; 6% quit 3 months to 1 year; 15% quit between 2 weeks to 3 months; 12% quit at 2 weeks; and 19% continued to smoke up to surgery. Postoperatively, 86% of previously smoking patients were nonsmoking; 13% of patients started smoking again. Of the restarted smoking patients, 61% had never quit preoperatively. Only 59% of smoking patients admitted that a physician had ever told them to stop smoking; however, 89% of patients who were smoking postoperatively acknowledged physician advice to stop smoking. CONCLUSIONS: Long-term smoking cessation occurs in a large proportion of patients after resection of lung cancer. The longer the patient is nonsmoking preoperatively, the more likely he or she is to remain nonsmoking postoperatively. Conversely, patients who do not quit preoperatively are at significant risk of continuing to smoke postoperatively.

Effects of inflation volume during lung preservation on pulmonary capillary permeability.

UNLABELLED: The degree of lung allograft inflation during harvest and storage may affect posttransplantation function. High volume ventilation causes pulmonary vascular injury and increased pulmonary capillary permeability. However, the effect of lung inflation on pulmonary capillary permeability after hypothermic flush and storage is unknown. The current study was designed to examine the effects of hyperinflation and hypoinflation during preservation on pulmonary vascular permeability. METHODS: An isolated, ex vivo rabbit lung gravimetric model without the confounding effects of reperfusion was used to determine post pulmonary capillary filtration coefficients (Kf). New Zealand White rabbits (2.75 to 3.15 kg) were intubated and lungs ventilated with room air (tidal volume 25 ml). After sternotomy and heparinization, the pulmonary artery was flushed with low potassium dextran-1% glucose solution (200 ml). The heart-lung block was then excised. Two studies were conducted. For measurement of changes in airway pressure and lung volume during preservation, lungs were inflated to one of four storage volumes (12, 25, 40, 55 ml) with room air, 100% O2, or 100% N2 and stored at 10 degrees C in a sealed container filled with saline solution. During preservation, lung volume and airway pressure were measured at 3, 6, 12 and 24 hours. In the Kf study, lungs were inflated with 100% O2, 50% O2 (with 50% N2), or room air and preserved. After 24 hours of preservation at 10 degrees C, the heart-lung block was suspended from a strain-gauge force transducer and the lungs were ventilated with room air. The pulmonary artery was connected to a reservoir of hetastarch solution (6% hetastarch with 0.9% saline solution). Lung weight gain, airway pressure, pulmonary artery pressure, and left atrial pressure were measured continuously. After a brief flush with hetastarch solution, the reservoir was then elevated to achieve 1.0 to 1.5 mm Hg increments in pulmonary artery pressure. RESULTS: The slope of subsequent steady-state lung weight gain was used to determine the Kf. The current study demonstrated the following: (1) changes in lung volume and airway pressure during storage increased with intraalveolar O2 concentration, (2) irrespective of inflation, fraction of inspired oxygen, hyperinflation during lung preservation increased the Kf in a volume-dependent fashion; (3) Kf was increased in lungs stored hypoinflated with room air; and (4) at any inflation volume, the Kf was significantly increased with 100% O2 inflation after 24 hours of preservation. CONCLUSION: These results suggest that storage at high lung volume or high inspired oxygen fraction increases pulmonary capillary permeability.

Surgical management of lung metastases: selection factors and results.

Lung parenchyma is the most common site of metastases from either carcinomas or sarcomas. Depending on the status of the original primary, resection of lung metastases may be curative. Multiple variables must be considered when deciding whether or not to operate on a patient with metastatic disease to the lung: The primary site must be evaluated; the lungs should be the only site of metastatic disease; the patient must be able to withstand the resection; and total removal of all disease must be possible. Other characteristics may be important to consider, such as the number of nodules and disease-free interval, and these factors may vary from histology to histology. However, if feasible, surgical resection remains the most important treatment modality for patients with pulmonary metastases.

Free radical-mediated vascular injury in lungs preserved at moderate hypothermia.

BACKGROUND: Early allograft dysfunction remains a frequently encountered problem in clinical lung transplantation. Lung ischemia-reperfusion injury is associated with increased vascular permeability, which may be due in part to oxygen (O2) free radicals. However, it is not clear whether O2 free radicals are produced during ischemia under storage conditions in clinical lung transplantation. METHODS: Using an isolated ex vivo rabbit lung model, we studied the effects of preservation temperature on pulmonary capillary filtration coefficient (Kf) and lipid peroxidation in rabbit lungs inflated with 100% O2 after preservation with or without the O2 free radical scavenger dimethylthiourea. New Zealand white rabbits weighing 2.7 to 3.1 kg were intubated and ventilated with room air or 100% O2 (tidal volume = 25 mL). After heparinization and sternotomy, the pulmonary artery was flushed with low-potassium-dextran-1% glucose solution (200 mL). The heart-lung block was excised, submerged, and stored for 24 hours at 1 degree or 10 degrees C. After 24-hour preservation, the heart-lung block was suspended from a strain-gauge force transducer and ventilated with room air. The pulmonary artery cannula was connected to a reservoir of hetastarch solution. The lungs were flushed briefly with the hetastarch solution, and the reservoir was raised sequentially at 8-minute intervals to achieve 1.0 to 1.5 mm Hg increments in pulmonary artery pressure. Lung weight gain, airway pressure, pulmonary artery pressure, and left atrial pressure were measured continuously. The slope of steady-state lung weight gain was used to determine Kf (g.min-1.cm H2O-1 x 100 g-1 wet weight). RESULTS: Twenty-four-hour lung preservation at both 1 degree and 10 degrees C increased Kf. A similar increase in Kf was observed in lungs stored at 1 degree C while inflated with 100% O2. However, a significant increase in Kf was observed when lungs inflated with 100% O2 were stored at 10 degrees C. This increase in Kf was ameliorated by dimethylthiourea. Thiobarbituric acid-reactive substance levels were increased in lungs stored at 10 degrees C while inflated with 100% O2. This finding was eliminated by dimethylthiourea. CONCLUSIONS: These results indicate that free radical injury occurs during the ischemic phase when lungs are stored at moderate hypothermia while inflated with 100% O2.

Expression of bcl-2 protein in stage T1N0M0 non-small cell lung carcinoma.

The bcl-2 gene product (bcl-2 protein, BCLP) prevents apoptotic cell death. Via a 14;18 chromosomal translocation, BCLP is overexpressed in most follicular lymphomas as well as some other non-Hodgkin's lymphomas, and it has also been documented in other nonlymphomatous malignancies. To address the possible prognostic value of this marker in predefined subsets of non-small cell lung carcinoma (NSCLC), the authors studied 126 T1N0M0 cases seen between the years 1986 to 1991 at our institution. Patients were treated by lobectomy (105 cases) or wedge excision (21 cases) with negative margins; neuroendocrine carcinomas of all grades were specifically excluded. The mean follow-up period was 39 months. Immunostaining for BCLP was done using a monoclonal antibody (clone no. 124; DAKO, Carpinteria, CA), and the avidin-biotin-peroxidase complex (ABC) technique. The study cases included 73 adenocarcinomas (ACs) as well as 40 squamous cell (SCC), five adenosquamous (ASC), and eight large cell/poorly differentiated (LCC) carcinomas. As assessed with the Kaplan-Meier method, overall survival was 64% at 5 years (66% AC vs 59% SC). BCLP was detected in 47 of 126 cases (37%) including 32 AC (44%), 10 SCC 925%), two ASC (40%), and three LCC (38%). No significant difference in 5-year survival was noted in a comparison of all cases with BCLP expression (63%) and those without (59%). There was, however, a significant difference in the survival of grade 1 BCLP(+) cases, when compared with grade 2 or 3 BCLP(+) cases (P = .01). A nonstatistically significant trend toward increased survival was observed in BCLP(+) SCC cases (66% 5-year survival in BCLP[+] vs 45% in BCLP[-] [P = .11]). Proportional hazards analysis failed to disclose significant independent risk factors. These data suggest that bcl-2 protein immunoreactivity has limited prognostic value in the pathological evaluation of NSCLC.