European guidelines from the EHTG and ESCP for Lynch syndrome: an updated third edition of the Mallorca guidelines based on gene and gender.

BACKGROUND: Lynch syndrome is the most common genetic predisposition for hereditary cancer but remains underdiagnosed. Large prospective observational studies have recently increased understanding of the effectiveness of colonoscopic surveillance and the heterogeneity of cancer risk between genotypes. The need for gene- and gender-specific guidelines has been acknowledged. METHODS: The European Hereditary Tumour Group (EHTG) and European Society of Coloproctology (ESCP) developed a multidisciplinary working group consisting of surgeons, clinical and molecular geneticists, pathologists, epidemiologists, gastroenterologists, and patient representation to conduct a graded evidence review. The previous Mallorca guideline format was used to revise the clinical guidance. Consensus for the guidance statements was acquired by three Delphi voting rounds. RESULTS: Recommendations for clinical and molecular identification of Lynch syndrome, surgical and endoscopic management of Lynch syndrome-associated colorectal cancer, and preventive measures for cancer were produced. The emphasis was on surgical and gastroenterological aspects of the cancer spectrum. Manchester consensus guidelines for gynaecological management were endorsed. Executive and layperson summaries were provided. CONCLUSION: The recommendations from the EHTG and ESCP for identification of patients with Lynch syndrome, colorectal surveillance, surgical management of colorectal cancer, lifestyle and chemoprevention in Lynch syndrome that reached a consensus (at least 80 per cent) are presented.

Factors associated with decision-making on prophylactic hysterectomy and attitudes towards gynecological surveillance among women with Lynch syndrome (LS): a descriptive study.

To prevent endometrial carcinoma in Lynch syndrome (LS), regular gynecological surveillance visits and prophylactic surgery are recommended. Previous data have shown that prophylactic hysterectomy is an effective means of cancer prevention, while the advantages and disadvantages of surveillance are somewhat unclear. We aimed to evaluate female LS carriers' attitudes towards regular gynecological surveillance and factors influencing their decision-making on prophylactic surgery that have not been well documented. Pain experienced during endometrial biopsies was also evaluated. Postal questionnaires were sent to LS carriers undergoing regular gynecological surveillance. Questionnaires were sent to 112 women with LS, of whom 76 responded (68%). Forty-two (55%) had undergone prophylactic hysterectomy by the time of the study. The majority of responders (64/76; 84.2%) considered surveillance appointments beneficial. Pain level during endometrial biopsy was not associated with the decision to undergo prophylactic surgery. The level of satisfaction the women had with the information and advice provided during surveillance was significantly associated with the history of prophylactic hysterectomy (satisfaction rate of 73.2% versus 31.8% of nonoperated women, p = 0.003). The women who had undergone prophylactic surgery were older than the nonoperated women both at mutation testing (median of 42.3 years versus 31.6 years, p < 0.001) and at the time of the study (median of 56.9 years versus 46.0 years, respectively, p < 0.001). Women with LS pathogenic variants have positive experiences with gynecological surveillance visits, and their perception of the quality of the information and advice obtained plays an important role in their decision-making concerning prophylactic surgery.

Treatment provided in the Public Dental Service in Finland in 2009.

OBJECTIVES: To analyse treatment measures provided in the Public Dental Service (PDS) and to discuss the therapy given against treatment needs as expressed in the national clinical epidemiological studies. METHODS: In 2009, the Chief Dentists of the PDS units collected data from their local registers on patients and treatment provided. Data were obtained from 166 PDS units (86%). Treatment patterns were compared between age groups, provider groups and geographical areas using chi-square tests. RESULTS: Altogether 8.9 million treatments were provided for 1.7 million patients. Examinations, restorative treatment and anaesthesia accounted for 61.3% of all treatments. Preventive measures (8.4%) and periodontal treatment (6.3%) were small proportions of the total. Prosthetic treatment was uncommon (0.5%). Working age adults received half of all treatments (53.2%), the young a third (36.4%) and the elderly 10.4%. Dental hygienists or dental assistants provided 29.7% of all treatment for children and adolescents, 11.1% for adults and 14.1% for the elderly. CONCLUSION: Relatively healthy children had plenty of examinations and preventive measures, and adults had mostly restorative care when their needs were more periodontal and prosthetic care, indicating that treatment given was not fully in line with needs.

Combination of microsatellite instability and BRAF mutation status for subtyping colorectal cancer.

BACKGROUND: The objective of the study was to examine the role of microsatellite instability (MSI) and BRAF(V600E)mutation in colorectal cancer (CRC) by categorising patients into more detailed subtypes based on tumour characteristics. METHODS: Tumour samples from 762 population-based patients with sporadic CRC were analysed for MSI and BRAF(V600E) by immunohistochemistry. Patient survival was followed-up for a median of 5.2 years. RESULTS: Compared with microsatellite stable (MSS) CRC, MSI was prognostic for better disease-free survival (DFS; 5 years: 85.8% vs 75.3%, 10 years: 85.8% vs 72.9%, P=0.027; HR 0.49, CI 0.30-0.80, P=0.005) and disease-specific survival (DSS; 5 years: 83.2% vs 70.5%; 10 years: 83.2 vs 65.0%, P=0.004). Compared with BRAF wild type, BRAF(V600E) was a risk for poor survival (overall survival; 5 years: 62.3% vs 51.6%, P=0.014; HR 1.43, CI 1.07-1.90, P=0.009), especially in rectal cancer (for DSS, HR: 10.60, CI: 3.04-36.92, P<0.001). The MSS/BRAF(V600E) subtype was a risk for poor DSS (HR: 1.88, CI: 1.06-3.31, P=0.030), but MSI/BRAF(V600E) was a prognostic factor for DFS (HR: 0.42, CI: 0.18-0.96, P=0.039). Among stage I-II patients, the MSS/BRAF(V600E) subtype was independently associated with poor DSS (HR: 5.32, CI: 1.74-16.31, P=0.003). CONCLUSIONS: Microsatellite instable tumours were associated with better prognosis compared with MSS. BRAF(V600E) was associated with poor prognosis unless it occurred together with MSI. The MSI/BRAF(V600E) subtype was a favourable prognostic factor compared with the MSS/BRAF wild-type subtype. BRAF(V600E) rectal tumours showed particularly poor prognosis. The MSS/BRAF(V600E) subtype was associated with increased disease-specific mortality even in stage I-II CRC.

CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings.

OBJECTIVE: To assess the relationship between Alzheimer disease (AD)-related pathologic changes in frontal cortical brain biopsy and AD biomarkers in ventricular vs lumbar CSF, and to evaluate the relationships of AD biomarkers in CSF and cortical biopsy with the final clinical diagnosis of AD. METHODS: In 182 patients with presumed normal pressure hydrocephalus (152 with known APOE carrier status), Aß plaques and tau in the cortical brain biopsies were correlated with the ventricular and lumbar CSF Aß42, total tau, and p-tau levels measured by ELISA. In a median follow-up of 2.0 years, 51 patients developed AD dementia. RESULTS: The patients with Aß plaques in the cortical biopsy had lower (p = 0.009) CSF Aß42 levels than those with no Aß plaques. The patients with tau in the cortical biopsy had lower (p = 0.014) Aß42 but higher (p = 0.015) p-tau 181 in CSF as compared to those with no tau in the cortical biopsy. The patients with amyloid + tau + biopsies had the lowest Aß42 and highest tau and p-tau 181 levels in CSF. The Aß42 levels were lower and the tau and p-tau 181 higher in the ventricular vs corresponding lumbar CSF samples. In multivariate analysis, the presence of cortical Aß was independently predicted by the APOE ε4 carrier status and age but not by CSF Aß42 or tau levels. CONCLUSIONS: Amyloid plaques and hyperphosphorylated tau in cortical brain biopsies are reflected by low CSF Aß42 and high CSF tau and p-tau levels, respectively.

Plasma Abeta42 and Abeta40 as markers of cognitive change in follow-up: a prospective, longitudinal, population-based cohort study.

BACKGROUND: Single measurements of plasma Aß are not useful in the diagnostics of Alzheimer's disease (AD). However, changes in plasma Aß levels during repeated testing may be helpful in the prediction and evaluation of progression of the incipient AD or mild cognitive impairment. OBJECTIVE: To examine the relation of baseline and serial plasma Aß levels to cognitive change in follow-up. METHODS: 269 subjects (52 cognitively impaired and 217 controls) from a population-based cohort were clinically followed up from 3 to 6 years. Serial plasma samples were available from 70 subjects who were followed up for 3 years and 43 subjects followed for 6 years. The plasma Aß levels were measured using ELISA. RESULTS: Subjects who declined cognitively during the follow-up had lower levels of plasma Aß42 at the baseline. Plasma Aß42 and the Aß42/Aß40 ratio decreased (-2.4 pg/ml for Aß42 in 6 years) in those who declined in follow-up, whereas Aß42 and the Aß42/Aß40 ratio increased in the subjects who remained cognitively stable or improved in follow-up. Subjects using acetylsalicylic acid, dipyridamole, antidiabetic or anticoagulant drugs as well as subjects with coronary heart disease had higher levels of Aß40. CONCLUSIONS: Low or decreasing plasma Aß42 during the follow-up is associated with cognitive decline. Serial measurement of plasma Aß42 may be useful in the detection of the subjects who are at risk for cognitive decline.