Early signet ring cell carcinoma arising from colonic adenoma: The molecular profiling supports the adenoma-carcinoma sequence

Among colorectal cancers, the prevalence of signet ring cell carcinoma (SRCC) is lower than 1%; to date, only 6 cases of early SRCCs arising in colonic adenoma have been reported. In spite of the well-established understanding of the phenotypic and genetic changes occurring in conventional colonic carcinogenesis, the molecular landscape of colon SRCC is still far to be elucidated. We describe the histologic and immunohistochemical phenotype and the molecular profile of a case of intramucosal SRCC developed within a 4.5-cm large sigmoid adenoma. The DNA sequencing of the 2 microdissected neoplastic components (adenomatous and SRCC) showed the same G12V KRAS mutation. Interestingly, although the adenomatous epithelium showed unequivocal p53 overexpression, no signet ring cancer cells featured p53 nuclear immunostain. This molecular pattern supports the unique histogenesis of the 2 coexisting neoplastic oncotypes, also suggesting that the signet ring cell component is derived from the molecular de-differentiation (p53 loss) of the preexisting adenomatous lesion

P1282 A COST\u2013CONSEQUENCE ANALYSIS OF SCREENING AND TREATMENT FOR CHRONIC HEPATITIS B (CHB) VIRUS INFECTION IN RESIDENT IMMIGRANTS OF AN ITALIAN NORTH-EAST REGION

Background and Aims: The epidemiology of hepatitis B in Europe is changing, with migration causing significant increases in prevalence rates. It is of paramount importance to identify the most effective ways to contain the disease. Systematic screening and treatment of migrants for CHB virus infection is likely to be cost-effective, but it is crucial to take into account the significant associated costs and the considerable net investment by governments. The objective of this study is to estimate the health and economic effects of screening for CHB screening among immigrants. Methods: We used the Markov model to examine the costconsequence of screening and treatment vs a no screening strategy in a cohort of 348,991 adult migrants resident in the Veneto Region. The rate of adherence to the HBV screening program was judged to be 40%. The prevalence of HBV infection and the chance of having active CHB was based on our recent screening campaign in Padua involving 465 migrants (table). Likelihood of HBV-related events were obtained from literature. Population 465,322 Age group >20 y 348,991 HBsAg+, n (%) 21,048 (6) Active CHB, n (%) 6,314 (30) Rate of adherence to screening program, n (%) 2,525 (40) Results: The screening-treatment strategy prevented 273 cases of cirrhosis, 18 decompensated cirrhosis, 28 HCC, and 54 CHB related deaths, over a period of 5 years. The incremental cost of the screening strategy totaled 51,597,980 \u20ac in five years (0.1% of the Veneto annual health budget). Conclusions: This study provides information useful mainly to policy makers, who need to establish whether the cost generated by a screening strategy are affordable when set against the better health outcomes for resident immigrants

Event generators for high-energy physics experiments

We provide an overview of the status of Monte-Carlo event generators for high-energy particle physics. Guided by the experimental needs and requirements, we highlight areas of active development, and opportunities for future improvements. Particular emphasis is given to physics models and algorithms that are employed across a variety of experiments. These common themes in event generator development lead to a more comprehensive understanding of physics at the highest energies and intensities, and allow models to be tested against a wealth of data that have been accumulated over the past decades. A cohesive approach to event generator development will allow these models to be further improved and systematic uncertainties to be reduced, directly contributing to future experimental success. Event generators are part of a much larger ecosystem of computational tools. They typically involve a number of unknown model parameters that must be tuned to experimental data, while maintaining the integrity of the underlying physics models. Making both these data, and the analyses with which they have been obtained accessible to future users is an essential aspect of open science and data preservation. It ensures the consistency of physics models across a variety of experiments.peerReviewe