Impact of revised stage classification of lung cancer on survival: a military experience.

STUDY OBJECTIVES: This report reviews results of surgical management of lung cancer at a military medical center using the revised 1997 stage classification and determines the impact of the revised system on survival rates. It also compares our results with the recent reports from Japan and from a large, multinational study involving several institutions. DESIGN: Retrospective review. SETTING: Department of Cardiothoracic Surgery, Walter Reed Army Medical Center (WRAMC), Washington, DC. PATIENTS OR PARTICIPANTS: Active military members, their dependents, and eligible retired military members who were admitted to WRAMC for surgical treatment of lung cancer between January 1984 and December 1996. METHODS: Records of all patients who had surgical resection with intent to cure were reviewed. Data extracted included clinical and pathologic stages according to the 1997 revised stage classification. Survival probabilities for the stages were calculated by the Kaplan-Meier actuarial method. The log rank test was used to compare survival rates between stages and stage subsets. A p value < 0.05 was considered statistically significant. MEASUREMENTS AND RESULTS: Five hundred fifty-two of the 1,398 patients with primary lung cancers underwent curative surgical resection (39.5%). The operative mortality was 2%. Using the revised 1997 stage classification, the survival rate for stage IA was 77%; IB, 62%; IIA, 57%; IIB, 47%; IIIA, 28%; IIIB, 20%; and IV, 0%. The overall actuarial 5-year and 10-year survival rates were 58% and 45%, respectively (median survival, 3.3 years; mean survival 3.9+/-0.1 years). CONCLUSIONS: Our results confirm the justification for the recent revisions in the staging system of lung cancer; however, there are still discrepancies that cannot be explained.

Incorporation of bromodeoxyuridine (BrdU) in the bronchiolar-alveolar regions of the lungs following two inhalation exposures to chrysotile asbestos in strain A/J mice.

We have been studying early fibroproliferative events in the lungs of rodents exposed to aerosols of asbestos fibers. In the experiments presented here, incorporation of bromodeoxyuridine (BrdU) in the bronchiolar/alveolar (B/A) regions of the lungs in mice was assessed following two consecutive exposures to chrysotile asbestos. Six to 8-week-old male strain A/J mice, a strain with a high spontaneous incidence of B/A tumors, were exposed to inhaled asbestos fibers for two consecutive days (3 hours/day). A group of mice was also given an intraperitoneal injection of urethane, a known lung carcinogen in A/J mice, 48 h after initial inhalation exposure to asbestos. The groups of mice exposed to asbestos had significantly (p <0.05) increased incorporation of BrdU in the nuclei of epithelial and interstitial cells in the B/A regions of the lung at 48 h, 72 h, and 2 weeks after initial exposure. By 1 month, the labeling indices in mice exposed to asbestos were not statistically significantly different from the controls; however, in the regions of the first alveolar duct bifurcations (ALDB), the primary site of initial asbestos deposition, there continued to be detectable labeling of the epithelial and interstitial cells. Because of considerable variability from duct to duct, there were no statistically significant differences between the asbestos-exposed mice and control groups at 3 months. We conclude that in A/J mice the initial proliferative response observed in the B/A regions of the lung after two 3-h inhalation exposures to asbestos is significantly prolonged through 2 weeks post-exposure. In addition, there was measurable labeling above control values in the epithelial and interstitial cells of the first alveolar duct bifurcations up to 3 months after exposure. Urethane had no apparent effect on the incorporation of BrdU into any cells of the B/A regions of the lung when administered after inhalation exposure to asbestos. Furthermore, although the A/J strain is highly susceptible to lung tumor formation, the unexposed control A/J mice showed no spontaneous increases in cell proliferation.

From puffins to plankton: a DNA-based analysis of a seabird food chain in the northern Gulf of Maine.

The predator-prey interactions within food chains are used to both characterize and understand ecosystems. Conventional methods of constructing food chains from visual identification of prey in predator diet can suffer from poor taxonomic resolution, misidentification, and bias against small or completely digestible prey. Next-generation sequencing (NGS) technology has become a powerful tool for diet reconstruction through barcoding of DNA in stomach content or fecal samples. Here we use multi-locus (16S and CO1) next-generation sequencing of DNA barcodes on the feces of Atlantic puffin (Fratercula arctica) chicks (n=65) and adults (n=64) and the stomach contents of their main prey, Atlantic herring (Clupea harengus, n=44) to investigate a previously studied food chain. We compared conventional and molecular-derived chick diet, tested the similarity between the diets of puffin adults and chicks, and determined whether herring prey can be detected in puffin diet samples. There was high variability in the coverage of prey groups between 16S and CO1 markers. We identified more unique prey with our 16S compared to CO1 barcoding markers (51 and 39 taxa respectively) with only 12 taxa identified by both genes. We found no significant difference between the 16S-identified diets of puffin adults (n=17) and chicks (n=41). Our molecular method is more taxonomically resolved and detected chick prey at higher frequencies than conventional field observations. Many likely planktonic prey of herring were detected in feces from puffin adults and chicks, highlighting the impact secondary consumption may have on the interpretation of molecular dietary analysis. This study represents the first simultaneous molecular investigation into the diet of multiple components of a food chain and highlights the utility of a multi-locus approach to diet reconstruction that is broadly applicable to food web analysis.

Predominant p53 G-->A transition mutation and enhanced cell proliferation in uterine sarcomas of CBA mice treated with 1,2-dimethylhydrazine.

Mouse uterine tumors were examined for genetic alterations in the ras proto-oncogene and p53 tumor suppressor gene and for other biologically relevant immunohistochemical markers that may increase our understanding of the events that occur in uterine cancer. Fourteen dimethylhydrazine (DMH)-induced uterine sarcomas, including 3 primary malignant fibrous histiocytomas (MFH), 7 transplanted MFH, 3 stromal sarcomas, and 1 undifferentiated sarcoma, were first screened by immunohistochemistry for p53 missense mutations, followed by single strand conformation polymorphism analysis and DNA sequencing for the identification of point mutations. There was 100% correlation between p53 protein immunopositivity and subsequent detection of p53 mutations in DMH-induced malignant fibrous histiocytomas. All MFH had a characteristic p53 G:C-->A:T transition mutation, consistent with O6-methylguanine mispairing with thymine, the most common DNA lesion caused by alkylating agents. DMH-induced uterine MFH with p53 mutations also had a higher proliferative rate (qualitatively evaluated by immunohistochemical detection of proliferating cell nuclear antigen) when compared with other DMH-induced sarcomas. Uterine sarcomas were further evaluated for biological end points, such as estrogen receptor and desmin. Neoplastic cells from stromal sarcomas (SS), undifferentiated sarcomas (US), and MFH did not stain for desmin. The estrogen receptor was detected in normal uteri and a small portion of MFH, SS, and US. Our data suggest that DMH-induced uterine sarcomas are not consistent with smooth muscle cell origin and that a subset of these tumors, specifically DMH-induced malignant fibrous histiocytomas, have unique p53 G:C-->A:T transitions and a high proliferative rate.