Clinical relevance of thymidylate syntetase expression in the signet ring cell histotype component of colorectal carcinoma

Thymidylate Synthase (TS) is the key enzyme for DNA synthesis pathways and is inhibited by 5-fluorouracil (5FU). The aim of this work was to study TS expression and the proliferation rate in the different histological types of colorectal carcinoma (CRC). 50 patients with CRC were included in this study and evaluated immunohistochemically using the monoclonal antibodies, TS106 and Ki67. 20 tumours were of the intestinal type, 15 cases were signet ring cell carcinoma (SRCCs) and 15 cases were "mixed-type", with at least two different histological components. Intestinal and mucinous histotypes were positive for TS and Ki67, while "signet ring cell" samples were negative or showed only weak and focal positivity for both the TS and Ki67 antibodies. Our results show that signet ring cells (that are also often present in intestinal and mucinous carcinomas), are in the post-mitotic phase of the cell cycle and show a low proliferation index and TS expression. As TS is the key enzyme for DNA synthesis pathways and is inhibited by 5-fluorouracil (5FU), we can hypothesise that TS expression levels in the different histotypes of CRC could affect the potential responsiveness of these tumours to fluoropyrimidine chemotherapy, with a low efficacy being expected in signet ring cell areas

TP53 mutations and S-phase fraction but not DNA-ploidy are independent prognostic indicators in laryngeal squamous cell carcinoma

To prospectively evaluate the prognostic significance of TP53, H-, K-, and N-Ras mutations, DNA-ploidy and S-phase fraction (SPF) in patients affected by locally advanced laryngeal squamous cell carcinoma (LSCC). Eight-one patients (median follow-up was 71 months) who underwent resective surgery for primary operable locally advanced LSCC were analyzed. Tumor DNA was screened for mutational analysis by PCR/SSCP and sequencing. DNA-ploidy and SPF were performed by flow cytometric analyses. Thirty-six patients (44%) had, at least, a mutation in the TP53 gene. Of them, 22% (8/36) had double mutations and 3% (1/36) had triple mutations. In total, 46 TP53 mutations were observed. The majority (41%) of these occur in exon 5 (19/46), while the mutations in exons 6, 7, and 8 were represented in 14, 7, and 6 patients, respectively (31% 15%, and 16%). Five LSCC patients (6%) showed a mutation in H-Ras gene. Sixty-three percent of the cases (51/81) were DNA aneuploidy, 14% of these (7/51) were multiclonal. Thirty-nine patients (48%) had an high SPF value. At Univariate analysis, the DNA aneuploidy, high SPF (> 15.1%), TP53 mutations and, in particular, the mutations that occur in exons 5 and 8 were significantly related to quicker disease relapse and short OS. At Multivariate analysis, the major significant predictors for both disease relapse and death were high SPF and any TP53 mutations. While histological grade G3 was an independent factor only for relapse. In conclusions, any TP53 mutations and high SPF are important biological indicators to predict the outcome of LSCC patients

Obstetric near-miss cases among women admitted to intensive care units in Italy

Objective. Maternal near-miss defines a narrow category of morbidity encompassing potentially life-threatening episodes. The purpose of this study was to detect near-miss instances among women admitted to intensive care units or coronary units, analyze associated causes, and compute absolute and specific maternal morbidity rates in six Italian regions. Design. Observational retrospective study. Setting. Six Italian regions representing 49% of all resident Italian women aged 15-49 years. Population. The study population included all pregnant women aged 15-49 years admitted to intensive care units or coronary care units in the participating regions. Cases were defined as women aged 15-49 years resident in the participating regions, with one or more hospitalizations in intensive care for pregnancy or any pregnancy outcome between 2004 and 2005. Methods. Cases were identified through the Hospital Discharge Database. Enrolled cases were diagnosed according to the 9th International Classification of Diseases. Main outcome measure. Maternal near-miss rate (number of women experiencing an admission to intensive care units/all women with live or stillborn babies). Results. A total of 1259 near-miss cases were identified and the total maternal near-miss rate was 2.0/1000 deliveries. Seventy percent of the women were admitted to intensive care units or coronary units after a cesarean section. The leading associated risk factors were obstetric hemorrhage/disseminated intravascular coagulation (40%) and hypertensive disorders of pregnancy (29%). Conclusions. Monitoring of near-miss morbidity in conjunction with mortality surveillance could help to identify effective preventive measures for potentially life-threatening episodes

Epidemiological patterns of asbestos exposure and spatial clusters of incident cases of malignant mesothelioma from the Italian national registry

Abstract BACKGROUND: Previous ecological spatial studies of malignant mesothelioma cases, mostly based on mortality data, lack reliable data on individual exposure to asbestos, thus failing to assess the contribution of different occupational and environmental sources in the determination of risk excess in specific areas. This study aims to identify territorial clusters of malignant mesothelioma through a Bayesian spatial analysis and to characterize them by the integrated use of asbestos exposure information retrieved from the Italian national mesothelioma registry (ReNaM). METHODS: In the period 1993 to 2008, 15,322 incident cases of all-site malignant mesothelioma were recorded and 11,852 occupational, residential and familial histories were obtained by individual interviews. Observed cases were assigned to the municipality of residence at the time of diagnosis and compared to those expected based on the age-specific rates of the respective geographical area. A spatial cluster analysis was performed for each area applying a Bayesian hierarchical model. Information about modalities and economic sectors of asbestos exposure was analyzed for each cluster. RESULTS: Thirty-two clusters of malignant mesothelioma were identified and characterized using the exposure data. Asbestos cement manufacturing industries and shipbuilding and repair facilities represented the main sources of asbestos exposure, but a major contribution to asbestos exposure was also provided by sectors with no direct use of asbestos, such as non-asbestos textile industries, metal engineering and construction. A high proportion of cases with environmental exposure was found in clusters where asbestos cement plants were located or a natural source of asbestos (or asbestos-like) fibers was identifiable. Differences in type and sources of exposure can also explain the varying percentage of cases occurring in women among clusters. CONCLUSIONS: Our study demonstrates shared exposure patterns in territorial clusters of malignant mesothelioma due to single or multiple industrial sources, with major implications for public health policies, health surveillance, compensation procedures and site remediation programs

Childhood health and educational investment under risk

En: IZA Journal of Labor & Development, 6:2. doi: 10.1186/s40175-016-0068-4A huge literature shows that childhood health and educational attainment are highly correlated. However, estimates for the effect of childhood health on educational attainment under risk generally confound the effect of liquidity constraints and of lack of insurance against risk. It is unclear whether the correlation between health and education under uninsured risk would remain if the capital markets were perfect and household faced no liquidity constraints. This paper fills in this lacuna in the literature. We develop a two period model of investment in education when future labor earnings are stochastically dependent on current investments in schooling and health. It is found that when there is uninsured risk, then parental investment in a child’s education will be inefficient even in the presence of perfect capital markets. Under certain assumptions, there will be a positive correlation between childhood health and educational investment. Health inequalities will translate into educational inequalities in an environment of uninsured risk. We are able to show that when perfect insurance markets are present, investments in child health and schooling will be optimal. From the policy perspective, this argues for the development of insurance markets. The results also suggest that policy interventions that target higher levels of educational investment among the population need to account for the effect of childhood differences in health