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The mutational spectrum of the MMR genes is highly heterogeneous, but specific mutations are observed at high frequencies in well-defined populations or ethnic groups, due to founder effects. The MSH2 mutation c.2152C>T, p.(Gln718*), has occasionally been described in Lynch families worldwide, including in Portuguese Lynch syndrome families. During genetic testing for Lynch syndrome at the Portuguese Oncology Institutes of Porto and Lisbon, this mutation was identified in 28 seemingly unrelated families. In order to evaluate if this alteration is a founder mutation, haplotype analysis using microsatellite and SNP markers flanking the MSH2 gene was performed in the 28 probands and 87 family members. Additionally, the geographic origin of these families was evaluated and the age of the mutation estimated. Twelve different haplotypes were phased for 13 out of the 28 families and shared a conserved region of ∼3.6 Mb. Based on the mutation and recombination events observed in the microsatellite haplotypes and assuming a generation time of 25 years, the age estimate for the MSH2 mutation was 273 ± 64 years. The geographic origins of these families were mostly from the Northern region of Portugal. Concluding, these results suggest that the MSH2 c.2152C>T alteration is a founder mutation in Portugal with a relatively recent origin. Furthermore, its high proportion indicates that screening for this mutation as a first step, together with the previously reported Portuguese founder mutations, may be cost-effective in genetic testing of Lynch syndrome suspects of Portuguese ancestry., (© 2019 Wiley Periodicals, Inc.)

Background and Aims: A recent review of economic studies relating to gastric cancer revealed that authors use different tests to estimate utilities in patients with and without gastric cancer. Our aim was to determine the utilities of gastric premalignant conditions and adenocarcinoma with a single standardized health measure instrument., Methods: Cross-sectional nationwide study of patients undergoing upper endoscopy (n=1,434) using the EQ-5D-5L quality of life (QoL) questionnaire., Results: According to EQ-5D-5L, utilities in individuals without gastric lesions were 0.78 (95% confidence interval: 0.76-0.80), with gastric premalignant conditions 0.79 (0.77-0.81), previously treated for gastric cancer 0.77 (0.73-0.81) and with present cancer 0.68 (0.55-0.81). Self-reported QoL according to the visual analogue scale (VAS) for the same groups were 0.67 (0.66-0.69), 0.67 (0.66-0.69), 0.62 (0.59-0.65) and 0.62 (0.54-0.70) respectively. Utilities were consistently lower in women versus men (no lesions 0.71 vs. 0.78; premalignant conditions 0.70 vs. 0.82; treated for cancer 0.72 vs. 0.78 and present cancer 0.66 vs. 0.70)., Conclusion: The health-related QoL utilities of patients with premalignant conditions are similar to those without gastric diseases whereas patients with present cancer show decreased utilities. Moreover, women had consistently lower utilities than men. These results confirm that the use of a single standardized instrument such as the EQ-5D-5L for all stages of the gastric carcinogenesis cascade is feasible and that it captures differences between conditions and gender dissimilarities, being relevant information for authors pretending to conduct further cost-utility analysis.

The article describes the recent Portuguese Act of 16 July 2012 on Living wills and Health care proxy, in a comparative perspective. After six years of parliamentary debate, the law was approved by unanimity and provides binding advance declaration of will, as long as it respects strict procedural control (Notary control, non-compulsory medical information and a (declarative) National Registry of Advance Declarations). The Author considers the Law a step forward in the right direction for the promotion of health care planning and ageing, especially for people suffering from dementia, and the autonomy of the patient in the end-of-life.

Introduction: Hospital readmissions are associated with increased healthcare expenses and with higher hospital fatality rates. We aim to characterize unplanned hospital readmissions occurred within 30 days after discharge, according to its Major Diagnosis Category, hospital type and location, and patients' demographic attributes. We also intend to estimate the hospital fatality rates associated to those readmissions, as well as to study the evolution of hospital readmissions rates in the last decade (2000-2008). Moreover, we aim to characterize heart failure readmissions., Material and Methods: We analysed a database (provided by Autoridade Central do Sistema de Saúde) containing all hospital admissions occurred in Portuguese public hospitals. In order to compare readmissions rates, we performed chi-square tests and linear-by-linear association tests., Results: Between 2000 and 2008, there were 5 514 331 unplanned admissions, of which 4.1% corresponded to hospital readmissions, classified with the same Major Diagnosis Category of the first admission. Between 2000 and 2008, hospital readmissions rate increased continuously from 3.0% to 4.7%. Hospital fatality rate was significantly higher among readmitted cases (9.5 versus 5.6%, p < 0.001). Readmissions rates were also significantly higher among episodes involving older patients (2.6% in children versus 5.3% in the elderly) and males (4.5% versus 3.9% in females, p < 0.001), being lower in Lisbon region (2.7%) and in central hospitals (3.0%, p < 0.001). For episodes of heart failure, we found a readmissions rate of 6.7%., Discussion and Conclusion: Most of the differences found are consistent with those described in other Western countries. Readmission episodes, whose rates have been increasing in Portugal, are associated with higher hospital fatality rates.

In a fraction of families fulfilling the Amsterdam criteria for hereditary non-polyposis colorectal cancer, colorectal cancers are microsatellite stable and DNA mismatch repair gene (MMR) mutations are not found. These families were designated as familial colorectal cancer type X (FCCTX). We aimed to characterise a group of FCCTX families defined by the Amsterdam criteria and MSS tumours at clinical and molecular level. Twenty-four tumours from 15 FCCTX families were analysed for loss of known tumour suppressor gene (TSG) loci (APC, TP53, SMAD4 and DCC), MGMT and MMR genes promoter methylation, and also APC and KRAS somatic mutations. FCCTX families presented specific clinical features: absence of endometrial tumours, high adenoma/carcinoma ratio (1.91) and prevalence of rectal cancers (13/27, 48%). New molecular features were found: the majority of FCCTX tumours (13/18; 72%) presented TSG loss. TSG loss positive tumours presented frequent APC and KRAS somatic mutations and MGMT methylation [10/13 (77%), 7/13 (54%) and 6/11 (54%), respectively]. In TSG loss negative tumours (5/18; 28%), the same molecular events were found in 2/5 (40%), 2/5 (40%) and 1/3 (33%) tumours, respectively. Transition mutations in KRAS were more frequent among MGMT methylated tumours than in unmethylated [5/8 (63%) vs. 1/10 (10%), P = 0.03]. Although sharing similar clinical features, at least two different molecular entities should exist among FCCTX families, one whose tumours present frequent TSG loss, APC and KRAS somatic mutations, and MGMT promoter methylation, and a second, lesser predominant, with no evidence of TSG loss and rarely presenting promoter methylation.