Background Uncontrolled studies suggest that a combination of chemotherapy and radiotherapy improves the survival of patients with esophageal adenocarcinoma. We conducted a prospective, randomized trial comparing surgery alone with combined chemotherapy, radiotherapy, and surgery. Methods Patients assigned to multimodal therapy received two courses of chemotherapy in weeks 1 and 6 (fluorouracil, 15 mg per kilogram of body weight daily for five days, and cisplatin, 75 mg per square meter of body-surface area on day 7) and a course of radiotherapy (40 Gy, administered in 15 fractions over a three-week period, beginning concurrently with the first course of chemotherapy), followed by surgery. The patients assigned to surgery had no preoperative therapy. Results Of the 58 patients assigned to multimodal therapy and the 55 assigned to surgery, 10 and 1, respectively, were withdrawn for protocol violations. At the time of surgery, 23 of 55 patients (42 percent) treated with preoperative multimodal therapy who could be evaluated had positive nodes or metastases, as compared with 45 of the 55 patients (82 percent) who underwent surgery alone (P Ͻ 0.001). Thirteen of the 52 patients (25 percent) who underwent surgery after multimodal therapy had complete responses, as determined pathologically. The median survival of patients assigned to multimodal therapy was 16 months, as compared with 11 months for those assigned to surgery alone (P ϭ 0.01). At one, two, and three years, 52, 37, and 32 percent, respectively, of patients assigned to multimodal therapy were alive, as compared with 44, 26, and 6 percent of those assigned to surgery, with the survival advantage favoring multimodal therapy reaching significance at three years (P ϭ 0.01). Conclusions Multimodal treatment is superior to surgery alone for patients with resectable adenocarcinoma of the esophagus.

The role of cytotoxic T lymphocyte responses, restricted by human leukocyte antigen (HLA) class I alleles, is recognized as highly significant in the successful clearance of hepatitis C virus (HCV). The frequency of class I alleles in females inoculated with HCV genotype 1b from a single source was examined for an association with outcome. Class I typing was performed using polymerase chain reaction sequence-specific primers in 227 female subjects: 141 had chronic infection and 86 had viral clearance. Statistical analysis included 2 testing and multiple logistic regression analysis. A*03, B*27, and Cw*01 occurred more frequently in those with viral clearance (39.5%, 14%, and 9.3%, respectively) compared with those with chronic infection (19.1%, 2.1%, and 1.4%, respectively; P < .005). B*08 occurred more often in those with chronic infection compared with viral clearance (39.7% vs. H epatitis C virus (HCV) is a hepatotropic virus with a high rate of chronic infection. It is known that progression to cirrhosis and hepatocellular carcinoma may take up to 20 years in individuals who are chronically infected and thus represents a leading cause of hepatocellular morbidity and mortality. [1][2][3][4] To date, viral factors (e.g., genotype) and host factors (e.g., age of acquisition, male sex, and alcohol consumption) are known to alter both the natural history of the disease and treatment outcomes. 2,4-6 As yet, no in vivo models of infection are available in HCV infection, therefore the pathogenic mechanism of disease remains unclear. 19.8%; P ‫؍‬ .002). In combination with previously reported class II allele associations, overIn HCV infection, recognition and elimination of infected cells by cytotoxic T lymphocytes (CTLs) require the presentation of specific HCV antigens on the membrane of hepatocytes in the context of HLA-A, -B and -C antigens. In acute HCV infection, animal models suggest that viral clearance appears to be dependent on an intrahepatic CTL response directed against multiple HCV antigens restricted by several class I molecules. 7 Human studies on peripheral blood similarly report that viral clearance is associated with a strong initial HCV-specific

Objectives To compare exposure to secondhand smoke and respiratory health in bar staff in the Republic of Ireland and Northern Ireland before and after the introduction of legislation for smoke-free workplaces in the Republic. Design Comparisons before and after the legislation in intervention and control regions. Setting Public houses in three areas in the Republic (intervention) and one area in Northern Ireland (control). Participants 329 bar staff enrolled in baseline survey; 249 (76%) followed up one year later. Of these, 158 were non-smokers both at baseline and follow-up. Main outcome measures Salivary cotinine concentration, self reported exposure to secondhand smoke, and respiratory and sensory irritation symptoms. Results In bar staff in the Republic who did not themselves smoke, salivary cotinine concentrations dropped by 80% after the smoke-free law (from median 29.0 nmol/l (95% confidence interval 18.2 to 43.2 nmol/l)) to 5

BACKGROUND: As part of EUROCAT's surveillance of congenital anomalies in Europe, a statistical monitoring system has been developed to detect recent clusters or long-term (10 year) time trends. The purpose of this article is to describe the system for the identification and investigation of 10-year time trends, conceived as a ''screening'' tool ultimately leading to the identification of trends which may be due to changing teratogenic factors. METHODS: The EUROCAT database consists of all cases of congenital anomalies including livebirths, fetal deaths from 20 weeks gestational age, and terminations of pregnancy for fetal anomaly. Monitoring of 10-year trends is performed for each registry for each of 96 non-independent EUROCAT congenital anomaly subgroups, while Pan-Europe analysis combines data from all registries. The monitoring results are reviewed, prioritized according to a prioritization strategy, and communicated to registries for investigation. Twenty-one registries covering over 4 million births, from 1999 to 2008, were included in monitoring in 2010. CONCLUSIONS: Significant increasing trends were detected for abdominal wall anomalies, gastroschisis, hypospadias, Trisomy 18 and renal dysplasia in the Pan-Europe analysis while 68 increasing trends were identified in individual registries. A decreasing trend was detected in over one-third of anomaly subgroups in the Pan-Europe analysis, and 16.9% of individual registry tests. Registry preliminary investigations indicated that many trends are due to changes in data quality, ascertainment, screening, or diagnostic methods. Some trends are inevitably chance phenomena related to multiple testing, while others seem to represent real and continuing change needing further investigation and response by regional/national public health authorities. Birth Defects Research (Part A) 91:S31-S43,