Epidemiology of lung cancer

Lung cancer incidence is now decreasing in US men. Although rates continue to increase in women, the rate of increase is declining. Most lung cancer in men and women is attributable to cigarette smoking. Histologic patterns are consistent with smoking trends for gender, race, and age. Trends in adenocarcinoma may be related to an increase in exposure to tobacco-specific nitrosamines from low-tar cigarettes. Other risk factors, including exposure to residential radon, occupational exposures, diet, and family history, have been shown to increase risk of lung cancer independent of cigarette smoking. Recent research in molecular epidemiology has greatly increased our understanding of the mechanism of lung carcinogenesis and the interactions between exposure to lung carcinogens (smoking, occupational exposures, radon), diet, and heritable variations in susceptibility.     

Margin distance and other clinico-pathologic prognostic factors in vulvar carcinoma: a multivariate analysis

OBJECTIVES: To determine the importance of margin status and other prognostic factors associated with the recurrence and survival of patients with squamous cell vulvar carcinoma. METHODS: Data were analyzed using Kaplan-Meier methods and Cox proportional hazards regression. All slides were re-reviewed by two gynecologic pathologists. RESULTS: Ninety patients (median age: 69) were treated for vulvar carcinoma from 1984 to 2002, including 28 FIGO stage I, 20 stage II, 26 stage III and 16 with stage IV disease. Sixty-three (70%) patients underwent complete radical vulvectomies and 27 (30%) had modified radical vulvectomies. Nineteen (20%) patients received adjuvant radiotherapy. Five-year disease-specific survival rates were 100%, 100%, 86% and 29% for stages I-IV, respectively. None of the 30 patients with a pathologic margin distance >8 mm had local recurrence. Of the 53 women with tumor-free pathologic margin of <8 mm, 12 (23%) had a local recurrence. Moreover, women with >2 positive groin nodes had significantly higher recurrence risk compared to those with <2 metastatic groin nodes (p<0.001). On multivariate analysis, positive groin nodes and margin distance were important prognostic factors for recurrence. Moreover, stage, tumor size, margin distance, and depth of invasion were significant independent predictors for disease-specific survival. The median follow-up was 58 months (range: 2-188). CONCLUSIONS: Pathologic margin distance is an important predictor of local vulvar recurrence. Our data suggest that a > or =8-mm pathologic margin clearance leads to a high rate of loco-regional control.     

Race, gender, and health care service utilization and costs among Medicare elderly with psychiatric diagnoses

OBJECTIVE. To investigate race and gender differences in health care service utilization and costs among the Medicare elderly with psychiatric diagnoses. METHODS. The authors employ a 5% sample of Medicare beneficiaries from Tennessee (N = 33,680), and among those with a psychiatric diagnosis (n = 5,339), they examine health care service utilization and costs by race and gender. RESULTS. African Americans had significantly higher rates of diagnosis for dementia, organic psychosis, and schizophrenia, whereas Whites had significantly higher rates for mood and anxiety disorders. White and African American men have higher rates of utilization of emergency and inpatient services and lower rates of outpatient utilization compared to White women and African American women. African American men have significantly higher health care costs. DISCUSSION. The findings suggest that race and gender interact to influence service utilization and preventive care, thereby driving up costs of care, for elderly persons with psychiatric diagnoses.     

Somatic mutations and altered expression of the candidate tumor suppressors CSNK1 epsilon, DLG1, and EDD/hHYD in mammary ductal carcinoma

We report somatic mutations in three genes (CSNK1 epsilon, encoding the Ser/Thr kinase casein kinase I epsilon; DLG1, encoding a membrane-associated putative scaffolding protein; and EDD/hHYD, encoding a progestin induced putative ubiquitin-protein ligase) in mammary ductal carcinoma. These genes were suspected of playing a role in cancer because loss-of-function mutations in their Drosophila homologues cause excess tissue growth. Using DNA from 82 laser-microdissected tumor samples, followed by microsatellite analysis, denaturing HPLC and direct sequencing, we found multiple somatic point mutations in all three genes, and these mutations showed significant association with loss of heterozygosity of closely linked polymorphic microsatellite markers. For CSNK1 epsilon and DLG1, most of the mutations affected highly conserved residues, some were found repetitively in different patients, and no synonymous mutations were found, indicating that the observed mutations were selected in tumors and may be functionally significant. Immunohistochemical reactivity of each protein was reduced in poorly differentiated tumors, and there was a positive association between altered protein reactivity, loss of heterozygosity, and somatic mutations. There was a statistically significant association of hDlg staining with p53 and Ki67 reactivity, whereas CSK1 epsilon and EDD/hHYD staining levels were associated with progesterone receptor status. The results provide strong indications for a role of all three genes in mammary ductal carcinoma. They also justify additional studies of the functional significance of the changes, as well as a search for additional changes in these and other genes identified from studies on model systems.     

Viability of limbal epithelium after anterior lamellar harvesting using a microkeratome

OBJECTIVE: To determine the viability in cold eye bank storage of different layers of central and limbal corneal epithelium, including the limbal basal stem cell population, on days 0, 3, 6, and 9 after harvest using a large diameter microkeratome system. METHODS: Twenty-two human whole globes not suitable for transplantation were obtained from an eye bank (San Diego Eye Bank, San Diego, California) and used for study. Large-diameter anterior corneal discs were prepared using a large diameter microkeratome and stained with calcein AM and an ethidium homodimer to differentiate live from dead cells, respectively. A laser confocal microscope and digital imaging were used to distinguish live (green) from dead (red) cells. Central and limbal epithelial regions were isolated and the middle and basal epithelial sections were cell counted by 3 independent observers. These sections were stored up to 9 days at 4 degrees C in an eye bank corneal storage medium. Differences were tested using nonparametric methods. MAIN OUTCOME MEASURES: The percentage of live cells in each of these epithelial layers was determined for up to 9 days in cold eye bank corneal storage medium. RESULTS: At all time points studied, the better protected basal epithelial layers displayed greater mean viability than the overlying middle epithelial layers. However, the difference was not statistically significant on all days. When comparing the basal epithelial viability of the limbal and central regions, after day 0 in 4 degrees C cold organ culture, the observed viability of the limbal basal epithelium, the purported location of the limbal epithelial stem cell region, was significantly greater than that of the central epithelium. On day 0, median limbal basal versus central basal epithelial viability were 100% (range, 71.7-100%) versus 98.4% (range, 88.9-100%) (P>0.05); on day 3, 100% (range, 64.3-100%) versus 63.4% (range, 13.6-95.5%) (P<0.0005); on day 6, 95.0% (range, 35.0-100%) versus 28.0% (range, 0-92.0%) (P<0.0005); and on day 9, 95.0% (range, 3.7-100%) versus 68.6% (range, 0-100%) (P<0.0005). CONCLUSIONS: After microkeratome harvesting, the limbal basal epithelium is significantly longer lived in cold eye bank storage than central basal epithelium and the middle layers of limbal and central epithelium. This longevity not only bodes well for organ storage of limbal grafts, but also confirms the hardiness of the stem cell region.     

Association between promyelocyte protein and small ubiquitin-like modifier protein and the progression of cervical neoplasia

OBJECTIVE: To examine the association between the size and number of promyelocyte protein-containing nuclear bodies, their colocalization with the small ubiquitin-like modifier protein, and existing histopathologic staging of cervical neoplasia progressing toward squamous cell carcinoma. METHODS: Fluorescence-based immunodetection of the promyelocyte protein and the small ubiquitin-like modifier protein was performed on paraffin-embedded and histopathologically graded human uterine cervical tissues. Quantitative measurements of the size and number of the promyelocyte protein-containing nuclear bodies were made and statistically analyzed. RESULTS: We found that promyelocyte protein-containing nuclear bodies exhibit changes in both size and number throughout the continuum of cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma. An increase in number and size of the bodies occurs with progression from normal to CIN I/CIN II. In CIN III, two new subcategories of nuclear body are present with distinctly different promyelocyte protein patterns, with the type B CIN III losing the small ubiquitin-like modifier protein partnership. In squamous cell carcinoma, we see the loss of this colocalization in both well and poorly differentiated tumors, with a distinctly different promyelocyte protein pattern. Well-differentiated tumors have bigger nuclear bodies that are more numerous than those of the poorly differentiated tumors. CONCLUSION: These data support the use of promyelocyte and small ubiquitin-like modifier proteins as a cytodiagnostic marker that parallels cervical cancer progression.