Women with pathologic stage I, II, and III non-small cell lung cancer have better survival than men.

OBJECTIVE: Bronchogenic malignancy is the number one cause of cancer deaths in both men and women worldwide. National registry-based studies have shown gender disparity in clinicopathologic characteristics and in survival. This study evaluates the risk factors and trends of lung cancer between genders. METHODS: A prospective cohort of consecutive patients with non-small cell lung cancer (NSCLC) who were carefully clinically (all underwent dedicated positron emission tomography scans) and pathologically staged with stage I, II, or III disease underwent homogenous treatment algorithms and were followed up over a period of 7 years. Primary outcomes were 5-year survival and response to neoadjuvant therapy. RESULTS: There were 1,085 patients (671 men and 414 women). Groups were similar for race, pulmonary function, smoking history, comorbidities, neoadjuvant therapy, histology, and resection rates. Women were younger (p = 0.014), had a higher incidence of adenocarcinoma (p = 0.01), and presented at an earlier pathologic stage (p = 0.01) than men. The overall age-adjusted and stage-adjusted 5-year survival rate favored women (60% vs 50%, respectively; p < 0.001). Women had better stage-specific 5-year survival rates (stage I disease, 69% vs 64%, respectively [p = 0.034]; stage II disease, 60% vs 50%, respectively [p = 0.042]; and stage III disease, 46% vs 37%, respectively [p = 0.024]). Women who received neoadjuvant chemotherapy alone (n = 76) were more likely to be a complete or partial responder than men (n = 142; p = 0.025). CONCLUSIONS: Despite uniform staging and treatment, the 5-year survival rate of women with stage I to III NSCLC was better than men overall and at each stage. Women are more likely to have adenocarcinoma, to present with earlier stage disease, and to be younger. Interestingly, women respond better to neoadjuvant chemotherapy.

Improving the lung cancer resection rate in the US Department of Veterans Affairs Health System.

BACKGROUND: The optimal treatment for non-small-cell lung cancer (NSCLC) is surgical resection; however, most patients are ineligible because of advanced disease. Although resection rates of 25% have been reported nationally, rates in the Veterans Affairs (VA) system appear lower, perhaps because of limited access to specialized care. We hypothesized that, since the introduction of a specialized Lung Mass Clinic in 1999, the resection rate at the Birmingham VA Medical Center would be comparable with US benchmarks. We also sought to identify the medical and nonmedical factors that influenced the use of surgery. PATIENTS AND METHODS: We reviewed the electronic medical records of all veterans seen in the Lung Mass Clinic from 1999 to 2003 and identified patients with NSCLC. Demographics, comorbidities, diagnostic methods, times to diagnosis/resection, and postoperative survival were recorded. Reasons for non-resection were documented and tabulated, and differences between the resected and nonresected subgroups were examined. RESULTS: One hundred fifty-six patients with NSCLC were identified, and 31 (20%) underwent resection. There were no differences in age, ethnicity, or sex between those undergoing resection and those denied surgery. Patients who underwent resection were less likely to have chronic obstructive pulmonary disease and had better pulmonary function. Eighty-four percent of those who did not undergo resection had advanced disease, poor pulmonary function, or had refused therapy. Although the median time to resection was longer than expected (104 days), overall survival was comparable with other reports (65% at 3 years). CONCLUSION: Since the inception of the Lung Mass Clinic, the resection rate at Birmingham VA Medical Center has improved. The primary limitation to resection was late presentation and not preoperative delays.

A novel assay for the quantification of invasion from raft cultures of lung carcinomas.

Assays that conveniently quantify invasion of carcinoma cells in vitro have generally measured the passage of dissociated cells into a matrix. Although these assays have been helpful in identifying relative differences between different carcinoma cell lines or types, the requirement for dissociation overlooks the possible modulation of invasion by cell-cell interactions among carcinoma cells. Described here is a novel assay that quantifies invasion of a matrix placed above intact, multilayered raft cultures of lung carcinoma cell lines A549 and H520. The assay was performed by placing a porous membrane coated with matrix at the air interface of the raft cultures for varying lengths of time, after which the cells invading the matrix were enumerated. The numbers of cells invading increased in a relatively linear fashion from 24 to 72 h, and the absolute numbers within each cell line were reproducible with multiple sets of raft cultures prepared at different times. It was also found that this assay could quantify differences in invasion caused by changes in matrix composition. It is concluded that this assay can reproducibly quantify carcinoma cell invasion from three dimensional raft cultures.

Differential expression and biodistribution of cytokeratin 18 and desmoplakins in non-small cell lung carcinoma subtypes.

Adenocarcinoma (AC), squamous cell carcinoma (SCC) and adenosquamous carcinoma (ASC) of the lung are morphologically distinguished in part by cyto-architectural features. However, little is known about the relative expression and distribution of cyto-architectural proteins among AC, SCC and ASC. Initial microarray analysis revealed significant differences in expression of two cyto-architectural genes in AC, SCC and ASC. Desmoplakin (DP) 1 and 2, which link desmosomes to intermediate filaments, was strongly expressed in SCC relative to AC and ASC. Cytokeratin 18 (CK18), an intermediate filament that is commonly linked to desmoplakin, was strongly expressed in AC and ASC relative to SCC. Western blot analysis demonstrated that AC and ASC had abundant CK18 protein, whereas CK18 was weakly detected in SCC. DP 1 and 2 are strongly expressed in SCC and minimally expressed in AC and ASC. However, the ratio of one to the other is the same in SCC and AC, but DP2 is lost in ASC. Microscopic analysis with fluorescence-labeled antibodies for CK18 and DP 1 and 2 revealed abundant membrane localization of DP and minimal perinuclear localization of CK18 in SCC. In contrast, in both AC and ASC, the CK18 protein was diffusely distributed within the cytoplasm, and DP showed both membranous and cytoplasmic localization. In conclusion, the data here shows that AC, SCC and ASC each have specific patterns of DP 1 and 2 and CK18 gene expression, protein content and biodistribution.

Standardized guidelines for surveillance bronchoscopy reduce complications in lung transplant recipients.

BACKGROUND: The role of surveillance bronchoscopy in the care of lung transplant recipients remains controversial. Although there are no controlled studies to suggest a survival advantage, many transplant physicians support the practice. The procedure is generally safe but is associated with some complications. A review of practices at our institution revealed significant variation in patient preparation, management of risk related to the procedure, and in the technical aspects of the bronchoscopy itself. In an effort to minimize these differences and potentially improve outcomes, a standard set of procedural guidelines for all bronchoscopies was adopted in January 2000. METHODS: Reports from 1028 surveillance bronchoscopies performed in our outpatient facility from January 1999 to December 2001 were reviewed. Baseline patient data and procedure-related complications were identified. Specific complications recorded included oversedation, the need for prolonged supplemental oxygen, major and minor bleeding, pneumothorax, bronchospasm, vomiting, arrhythmia, hypotension and death. Differences between groups were analyzed using chi-square or Student's t-tests as appropriate. RESULTS: The incidence of complications after the introduction of the guidelines (2000 and 2001) was significantly lower than in the year prior (1999) (1.95% vs 6.45%, p < 0.001). The lower rate of adverse events was mainly a result of a reduction in the incidence of minor bleeding (0.28% vs 2.26% p = 0.006) and of sedation-related complications (0.97% vs 2.90%, p = 0.04). CONCLUSIONS: The use of a standardized set of guidelines for surveillance fiber-optic bronchoscopy reduces complication rates. Similar guidelines should be considered by transplant centers performing the procedure.