Association between type 2 diabetes and depressive symptoms after a 1-year follow-up in an older adult Mediterranean population.

OBJECTIVES: To examine the cross-sectional association between baseline depressive symptoms and the presence of type 2 diabetes (T2D), and its association with glycated hemoglobin (HbA1c) and other metabolic variables, and the prospective association of depressive symptoms and HbA1c after 1 year of follow-up. METHODS: n = 6224 Mediterranean older adults with overweight/obesity and metabolic syndrome (48% females, mean age 64.9 ± 4.9 years) were evaluated in the framework of the PREDIMED-Plus study cohort. Depressive symptoms were assessed using the Beck Depression Inventory-II and HbA1c was used to measure metabolic control. RESULTS: The presence of T2D increased the likelihood of higher levels of depressive symptoms (χ2 = 15.84, p = 0.001). Polynomial contrast revealed a positive linear relationship (χ2 = 13.49, p = 0.001), the higher the depressive symptoms levels, the higher the prevalence of T2D. Longitudinal analyses showed that the higher baseline depressive symptoms levels, the higher the likelihood of being within the HbA1c ≥ 7% at 1-year level (Wald-χ2 = 24.06, df = 3, p < .001, for the full adjusted model). Additionally, depressive levels at baseline and duration of T2D predicted higher HbA1c and body mass index, and lower physical activity and adherence to Mediterranean Diet at 1 year of follow-up. CONCLUSIONS: This study supports an association between T2D and the severity of depressive symptoms, suggesting a worse metabolic control from mild severity levels in the short-medium term, influenced by lifestyle habits related to diabetes care. Screening for depressive symptoms and a multidisciplinary integrative therapeutic approach should be ensured in patients with T2D.

Determinants of adherence to recommendations on physical activity, red and processed meat intake, and body weight among lynch syndrome patients.

This study aimed to identify determinants of adherence to lifestyle and body weight recommendations for cancer prevention among Lynch Syndrome (LS) patients. Cross-sectional baseline data of LS patients participating in the Lifestyle & Lynch (LiLy) study was used to assess determinants of adherence to the World Cancer Research Fund cancer prevention recommendations on body weight, physical activity, and red and processed meat intake. Adherence and potential determinants of adherence were assessed using questionnaires. Multivariable logistic regression analyses were conducted to identify determinants of adherence. Of the 211 participants, 50.2% adhered to the body weight recommendation, 78.7% adhered to the physical activity recommendation, and 33.6% adhered to the red and processed meat recommendation. Being younger and having a higher level of education were associated with adherence to the recommendation on body weight. Having knowledge about the recommendation was associated with adherence to the recommendations on physical activity and red and processed meat. Results confirm that knowledge about recommendations for cancer prevention is an important determinant for adherence and suggest that strategies to increase knowledge should be included in lifestyle promotion targeted at LS patients, along with behavior change techniques influencing other modifiable determinants.

Support needs of couples with hereditary breast and ovarian cancer during reproductive decision making.

OBJECTIVE: Reproductive decision making for couples with hereditary breast and ovarian cancer (HBOC) is complex and can result in decisional conflict or regret. This study investigated couples' support needs and aimed to identify vulnerable couples. Ultimately, we should strive to develop a clear standard of care guideline regarding reproductive decision support. METHODS: Mixed methods were used for data collection. A focus group study was conducted among 18 couples (N = 35) with HBOC who had made a reproductive decision after reproductive counselling. Subsequently, 129 similar couples (N = 258) were invited to complete a cross-sectional survey based on the focus group study. RESULTS: Clinical and practical aspects of reproductive counselling were positively evaluated in the focus group study, although couples indicated a need for additional support with emotional and social concerns in which their relationship, social environment, and the way they picture their desired family were key elements. The survey was completed by 86 participants. Making a reproductive choice was experienced as (very) difficult by 43%, and 69% showed a need for additional support during decision making. Younger participants and those who opted for a natural pregnancy experienced more difficulty with reproductive decision making, and partners showed a higher need for psychological support than carriers. CONCLUSIONS: Couples with HBOC who need to make a reproductive decision have specific needs for guidance and support, of which the desired content and methods can vary. It is therefore important to identify vulnerable couples and to attune counselling to couples' needs.

Professionals' knowledge, attitude and referral behaviour of preimplantation genetic diagnosis for hereditary breast and ovarian cancer.

Hereditary breast and ovarian cancer caused by a BRCA1/2 mutation is the most frequent indication for preimplantation genetic diagnosis (PGD) in the Netherlands. The extent to which involved professionals are informed about this option, however, is unclear. The few available international studies mostly represent a limited range of professionals, and suggest that their knowledge about PGD for hereditary cancer syndromes is sparse and referral for PGD is based on limited understanding. A cross-sectional survey assessing awareness, knowledge, acceptability and PGD-referral for BRCA was completed by 188 professionals involved in the field of breast and ovarian cancer or reproduction. One-half of professionals were aware of PGD for BRCA, and most had a low to moderate level of knowledge. A total of 86% considered PGD for BRCA acceptable and 48% had referred patients with BRCA for PGD. Awareness and knowledge was higher among professionals who worked at a university hospital (compared with a general hospital). Knowledge of PGD was positively associated with discussing and referring for PGD, and PGD acceptability was associated with previous awareness. Although PGD counselling is the primary responsibility of the geneticist, other involved professionals may be gatekeepers as patients rely on them for raising awareness and referral.

Increasing awareness and knowledge of lifestyle recommendations for cancer prevention in Lynch syndrome carriers: Randomized controlled trial.

Lynch syndrome (LS) mutation carriers may reduce their cancer risk by adhering to lifestyle recommendations for cancer prevention. This study tested the effect of providing LS mutation carriers with World Cancer Research Fund-the Netherlands (WCRF-NL) health promotion materials on awareness and knowledge of and adherence to these recommendations. In this randomized controlled trial (n = 226), the intervention group (n = 114) received WCRF-NL health promotion materials. All LS mutation carriers were asked to fill out questionnaires at 2 weeks before (baseline, T0) and at 2 weeks (T1) and 6 months (T2) after the intervention. Linear mixed models were performed on awareness (0-7) and knowledge (0-7) of the recommendations, and on the secondary outcomes, that is adherence, distress, cancer worry, and risk perception. Compared with the control group, the intervention group became significantly more aware (overall mean difference = 1.24; 95%CI = 0.82-1.67) and obtained significantly improved knowledge of the recommendations (overall mean difference = 1.65; 95%CI = 1.27-2.03). Differences were significantly larger for T1 (Pinteraction = .003 and ≤.001, respectively) but remained significant for T2. No effect on secondary outcomes was found. In conclusion, provision of WCRF-NL health promotion materials increases awareness and knowledge of lifestyle recommendations for cancer prevention among LS mutation carriers without causing additional distress, but does not affect adherence.

Awareness and attitude regarding reproductive options of persons carrying a BRCA mutation and their partners.

STUDY QUESTION: To what extent are BRCA mutation carriers and their partners in the Netherlands aware about preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND) as reproductive options and what is their attitude towards these options? SUMMARY ANSWER: Awareness of PGD (66%) and PND (61%) among BRCA mutation carriers and their partners is relatively high and 80% and 26%, respectively, of BRCA carriers and their partners find offering PGD and PND for hereditary breast and ovarian cancer (HBOC) acceptable. WHAT IS KNOWN ALREADY: Internationally, awareness of PGD among persons with a genetic cancer predisposition appears to be relatively low (35%) and although acceptability is generally high (71%), only a small proportion of mutation carriers would consider using PGD (36%). However, for HBOC, there are no studies available that investigated the perspective of individuals with a confirmed BRCA1/2 mutation and their partners about PGD and PND including demographic and medical correlates of awareness and acceptability. STUDY DESIGN, SIZE, DURATION: A cross-sectional survey was completed by 191 participants between July 2012 and June 2013. Participants were recruited through patient organizations (88%) and the databases of two Clinical Genetics departments in the Netherlands (12%). PARTICIPANTS/MATERIALS, SETTING, METHODS: Male and female BRCA carriers and their partners completed an online survey, which assessed demographic and medical characteristics, and awareness, knowledge, acceptability and consideration of PGD and PND as main outcomes. Correlations between demographic and medical characteristics and the main outcomes were investigated. MAIN RESULTS AND ROLE OF CHANCE: The majority of respondents were female (87%), of reproductive age (86%) and about half reported a desire for a child in the future. About two-thirds (66%) were aware of PGD and 61% of PND for HBOC. PGD knowledge was moderate (5.5 on a 9-point scale) and acceptability of PGD and PND for HBOC was 80% and 26%, respectively. A minority would personally consider using PGD (39%) or PND (20%). Individuals with a higher educational level were more likely to be aware of PGD (P < 0.001) and PND (P < 0.001) and persons with a more immediate child wish were more often aware of PGD (P = 0.044) and had more knowledge about PGD (P = 0.001). PGD acceptability was positively associated with knowledge about PGD (P = 0.047), and PND acceptability was higher among partners in comparison to carriers (P = 0.001). Participants with a history of cancer and with a higher perceived seriousness of breast and ovarian cancer were more likely to consider using PGD (P = 0.003 and P < 0.001 respectively) or PND (P = 0.021 and P = 0.017 respectively). LIMITATIONS, REASONS FOR CAUTION: The response rate (23%) of participants invited by the clinical genetics departments was low, probably related to a simultaneous study that used a similar recruitment strategy within the same target group, which may have resulted in selection bias. Moreover, PGD knowledge was measured with an instrument that is not yet validated since to date such an instrument is not available in the literature. Finally, the cross-sectional design of this study limits us from drawing any causal conclusions. WIDER IMPLICATIONS OF THE FINDINGS: Improvement of information provision remains needed, in order to timely inform all couples with HBOC about the available reproductive options and enable them to make a balanced reproductive decision. This may limit the risk of negative psychological impact due to decisional conflict and possible regret. STUDY FUNDING/COMPETING INTEREST(S): The Dutch breast cancer foundation Stichting Pink Ribbon (grant number 2010.PS11.C74). None of the authors have competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Correlation between obesity and severity of distal radius fractures.

INTRODUCTION: The incidence of obesity has increased significantly worldwide. Our hypothesis was that patients with obesity have a more severe distal radius fracture and we realized a study to evaluate this correlation between obesity and severity of distal radius fractures caused by low-energy injuries. MATERIALS AND METHODS: A total of 114 patients with distal radius fracture were examined in a cross-sectional, observational study. Fractures were classified according to the international AO-Müller/Orthopedic Trauma Association (AO/OTA) classification in order to determine the severity. The patient's Body Mass Index (BMI) was calculated and a Pearson correlation was performed. RESULTS: The patients were predominantly female, and left side was more frequently affected. Most of the fractures were AO/OTA type A (71 patients). The majority of the involved patients in our study were overweighed or obese. We do not observe a direct correlation between grade of obesity and distal radius fracture severity. CONCLUSIONS: Based on the results of this study obesity and severity of distal radius fractures do not correlate. LEVEL OF EVIDENCE: Prognostic. Level IV.

Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup (GCIG): clinical trial design for rare ovarian tumours.

This manuscript reports the consensus statements on designing clinical trials in rare ovarian tumours reached at the fifth Ovarian Cancer Consensus Conference (OCCC) held in Tokyo, November 2015. Three important questions were identified concerning rare ovarian tumours (rare epithelial ovarian cancers (eOC), sex-cord stromal tumours (SCST) and germ cell tumours (GCT)): (i) What are the research and trial issues that are unique to rare ovarian tumours? There is a lack of randomised phase III data defining standards of care which makes it difficult to define control arms, but identifies unmet needs that merit investigation. Internationally agreed upon diagnostic criteria, expert pathological review and translational research are crucial. (ii) What should be investigated in rare eOC, GCT and SCST? Trials dedicated to each rare ovarian tumour should be encouraged. Nonetheless, where the question is relevant, rare eOC can be included in eOC trials but with rigorous stratification. Although there is emerging evidence suggesting that rare eOC have different molecular profiles, trials are needed to define new type-specific standards for each rare eOC (clear cell, low grade serous and mucinous). For GCTs, a priority is reducing toxicities from treatment while maintaining cure rates. Both a robust prognostic scoring system and more effective treatments for de novo poor prognosis and relapsed GCTs are needed. For SCSTs, validated prognostic markers as well as alternatives to the current standard of bleomycin/etoposide/cisplatin (BEP) should be identified. (iii) Are randomised trials feasible? Randomised controlled trials (RCT) should be feasible in any of the rare tumours through international collaboration. Ongoing trials have already demonstrated the feasibility of RCT in rare eOC and SCST. Mucinous OC may be considered for inclusion, stratified, into RCTs of non-gynaecological mucinous tumours, while RCTs in high risk or relapsed GCT may be carried out as a subset of male and/or paediatric germ cell studies.

Assessing biases of information contained in pedigrees for the classification of BRCA-genetic variants: a study arising from the ENIGMA analytical working group.

PURPOSE: One way of evaluating family history (FH) for classifying BRCA1/2 variants of uncertain clinical significance (VUS) is to assess the "BRCA-ness" of a pedigree by comparing it to reference populations. The aim of this study was to assess if prediction of BRCA pathogenic variant (mutation) status based on pedigree information differed due to changes in FH since intake, both in families with a pathogenic variant (BRCAm) and in families with wild-type (BRCAwt). PATIENTS AND METHODS: We compared the BRCA1/2 pathogenic variant detection probabilities between intake and most recent pedigree for BRCAm families (n = 64) and BRCAwt (n = 118) using the BRCAPRO software program. RESULTS: Follow-up time between intake and most recent pedigree was significantly longer (p < 0.001) in the BRCAm compared to the BRCAwt families. Among BRCAwt families, the probability to detect a pathogenic variant did not change over time. Conversely, among the BRCAm, this probability was significantly higher for most recent vs. intake pedigree (p = 0.006). CONCLUSION: Clinical scores change significantly over time for BRCAm families. This may be due to differences in follow-up, but also to differences in cancer risks from carrying a pathogenic variant in a highly penetrant gene. To reduce bias, models for VUS classification should incorporate FH collected at intake.

Yogurt consumption and abdominal obesity reversion in the PREDIMED study.

BACKGROUND AND AIMS: Evidence on the association yogurt consumption and obesity is not conclusive. The aim of this study was to prospectively evaluate the association between yogurt consumption, reversion of abdominal obesity status and waist circumference change in elderly. METHODS AND RESULTS: 4545 individuals at high cardiovascular risk were prospectively followed. Total, whole-fat and low-fat yogurt consumption were assessed using food frequency questionnaires. Generalized estimating equations were used to analyze the association between yogurt consumption and waist circumference change (measured at baseline and yearly during the follow-up). Logistic regression models were used to evaluate the odds ratios (ORs) and 95% CIs of the reversion rate of abdominal obesity for each quintile of yogurt consumption compared with the lowest quintile. After multivariable adjustment, the average yearly waist circumference change in the quintiles of whole-fat yogurt consumption was: Q1: 0.00, Q2: 0.00 (-0.23 to 0.23), Q3: -0.15 (-0.42 to 0.13), Q4: 0.10 (-0.21 to 0.42), and Q5: -0.23 (-0.46 to -0.00) cm; p for trend = 0.05. The ORs for the reversion of abdominal obesity for whole-fat yogurt consumption were Q1: 1.00, Q2: 1.40 (1.04-1.90), Q3: 1.33 (0.94-1.89), Q4: 1.21 (0.83-1.77), and Q5: 1.43 (1.06-1.93); p for trend = 0.26. CONCLUSION: Total yogurt consumption was not significantly associated with reversion of abdominal obesity status and a lower waist circumference. However, consumption of whole-fat yogurt was associated with changes in waist circumference and higher probability for reversion of abdominal obesity. Therefore, it seems that whole-fat yogurt has more beneficial effects in management of abdominal obesity in elderly population at high cardiovascular risk.

Colorectal cancer risk variants at 8q23.3 and 11q23.1 are associated with disease phenotype in APC mutation carriers.

Familial adenomatous polyposis (FAP) is a dominantly inherited syndrome caused by germline mutations in the APC gene and characterized by the development of multiple colorectal adenomas and a high risk of developing colorectal cancer (CRC). The severity of polyposis is correlated with the site of the APC mutation. However, there is also phenotypic variability within families with the same underlying APC mutation, suggesting that additional factors influence the severity of polyposis. Genome-wide association studies identified several single nucleotide polymorphisms (SNPs) that are associated with CRC. We assessed whether these SNPs are associated with polyp multiplicity in proven APC mutation carriers. Sixteen CRC-associated SNPs were analysed in a cohort of 419 APC germline mutation carriers from 182 families. Clinical data were retrieved from the Dutch Polyposis Registry. Allele frequencies of the SNPs were compared for patients with <100 colorectal adenomas versus patients with ≥100 adenomas, using generalized estimating equations with the APC genotype as a covariate. We found a trend of association of two of the tested SNPs with the ≥100 adenoma phenotype: the C alleles of rs16892766 at 8q23.3 (OR 1.71, 95 % CI 1.05-2.76, p = 0.03, dominant model) and rs3802842 at 11q23.1 (OR 1.51, 95 % CI 1.03-2.22, p = 0.04, dominant model). We identified two risk variants that are associated with a more severe phenotype in APC mutation carriers. These risk variants may partly explain the phenotypic variability in families with the same APC gene defect. Further studies with a larger sample size are recommended to evaluate and confirm the phenotypic effect of these SNPs in FAP.

Valoración de una Encuesta sobrde Atención Farmacéutica a Farmacéuticos de Alicante / Survey’s Assessment of the Pharmaceutical Care Services Carried out by Alicante’s Pharmacists

Introducción: Hay descritas barreras y facilitadores para implantar la AF. Algunos facilitadores podrían ser proporcionados desde los colegios profesionales. Objetivo: Conocer el interés de los farmacéuticos comunitarios alicantinos por los servicios de AF, y sus preferencias para implantar/mejorar éstos. Método: Estudio transversal realizado marzo-mayo de 2012, mediante un cuestionario anónimo a todos los colegiados ejercientes en OF, consensuado por la comisión de AF del COFA, disponible en la web colegial 70 días. Con preguntas referentes a su implantación, protocolización, registros, evaluación y ayudas sugeridas para su implantación/mejora. Resultados: Respondieron 19,9% de los colegiados ejercientes en FC, afirmando la mayoría querer mejorar su trabajo. Siguen protocolos para IF el 58%, automedicación un 60% y 33% para dispensación con receta. Realizan SFT un 23% y SPD 15%. La mayoría no registra las actuaciones, siendo 77% en IF, 70% en automedicación, 78% dispensación con receta, excepto SFT con 25%. Como formato de registro, se prefiere papel, excepto en SFT que son aplicaciones informáticas. La mayoría evalúa el resultado en ocasiones, solo un 8% lo hace siempre. En SFT lo evalúan siempre un 29%. Se prefiere un servicio de información frente a dudas, seguido de uno de apoyo a la implantación. Conclusiones: Existe interés entre los farmacéuticos alicantinos por la AF. Sería deseable un mayor grado de implantación de estos servicios, existiendo gran recorrido de mejora en la protocolización, el registro y la evaluación de los resultados. Como herramientas para ello, destaca la solicitud al colegio de un servicio de información frente a dudas

There are described both, barriers and facilitators in the implementation of Pharmaceutical Care. Some facilitators might be provided from the professional associations. Objective: To find the interest of Alicante’s community pharmacists in the Pharmaceutical Care services and their preferences when implementing / improving these services. Method: It was conducted a cross-sectional study from March to May 2012 by using an anonymous questionnaire that was taken to all practicing members in OF. The questionnaire has been agreed by the Pharmaceutical Care Commission of the COFA (Colegio Oficial de Farmacéuticos de Alicante) and was available in the College web for 70 days. It included questions concerning Pharmaceutical Care implementation, its records and evaluation and some suggested aids to be implemented or to improve the Pharmaceutical Care. Results: 19.9% of the collegiate members that are community pharmacists answered the questionnaire. Most of them want to improve their work. Among them, 58% follow protocols for IF, 60% for self-medication and 33% for prescription-only products. Besides, 23% carry out SFT and 15%, SPD. The vast majority of them do not record their performances, among which 77% are in IF, 70% in self-medication, 78% in prescription-only products and the exception of SFT with only 25%. The preferred record format is paper except in SFT in which case they are computer applications. Most of the participants in the questionnaire evaluate the result occasionally; only 8% do so always. In SFT 29% evaluate it always. They prefer an information service against doubts, followed by one of support to the implementation. Conclusions: There is an interest among Alicante’s pharmacists in Pharmaceutical Care. A greater degree of implementation of these services would be desirable: there is a long room for improvement concerning the Pharmaceutical Care records and results evaluation. In order to go on and to improve information against doubts service has been required to the College

BRCA1 and BRCA2 genetic testing-pitfalls and recommendations for managing variants of uncertain clinical significance.

BACKGROUND: Increasing use of BRCA1/2 testing for tailoring cancer treatment and extension of testing to tumour tissue for somatic mutation is moving BRCA1/2 mutation screening from a primarily prevention arena delivered by specialist genetic services into mainstream oncology practice. A considerable number of gene tests will identify rare variants where clinical significance cannot be inferred from sequence information alone. The proportion of variants of uncertain clinical significance (VUS) is likely to grow with lower thresholds for testing and laboratory providers with less experience of BRCA. Most VUS will not be associated with a high risk of cancer but a misinterpreted VUS has the potential to lead to mismanagement of both the patient and their relatives. DESIGN: Members of the Clinical Working Group of ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) global consortium (www.enigmaconsortium.org) observed wide variation in practices in reporting, disclosure and clinical management of patients with a VUS. Examples from current clinical practice are presented and discussed to illustrate potential pitfalls, explore factors contributing to misinterpretation, and propose approaches to improving clarity. RESULTS AND CONCLUSION: Clinicians, patients and their relatives would all benefit from an improved level of genetic literacy. Genetic laboratories working with clinical geneticists need to agree on a clinically clear and uniform format for reporting BRCA test results to non-geneticists. An international consortium of experts, collecting and integrating all available lines of evidence and classifying variants according to an internationally recognized system, will facilitate reclassification of variants for clinical use.

A white raven detected by imaging.

The purpose of this case report is to describe a rare case of a patient with a phaeochromocytoma with several cardiovascular complications, which can be attributed to the tumour. Detection of a phaeochromocytoma sometimes needs a 'Sherlock Holmes spirit' or simply time.

Breast cancer risk after salpingo-oophorectomy in healthy BRCA1/2 mutation carriers: revisiting the evidence for risk reduction.

BACKGROUND: Previous studies have reported a breast cancer (BC) risk reduction of approximately 50% after risk-reducing salpingo-oophorectomy (RRSO) in BRCA1/2 mutation carriers, but may have been subject to several types of bias. The purpose of this nationwide cohort study was to assess potential bias in the estimated BC risk reduction after RRSO. METHODS: We selected BRCA1/2 mutation carriers from an ongoing nationwide cohort study on Hereditary Breast and Ovarian Cancer in the Netherlands (HEBON). First, we replicated the analytical methods as previously applied in four major studies on BC risk after RRSO. Cox proportional hazards models were used to calculate hazard ratios and conditional logistic regression to calculate odds ratios. Secondly, we analyzed the data in a revised design in order to further minimize bias using an extended Cox model with RRSO as a time-dependent variable to calculate the hazard ratio. The most important differences between our approach and those of previous studies were the requirement of no history of cancer at the date of DNA diagnosis and the inclusion of person-time preceding RRSO. RESULTS: Applying the four previously described analytical methods and the data of 551 to 934 BRCA1/2 mutation carriers with a median follow-up of 2.7 to 4.6 years, the odds ratio was 0.61 (95% confidence interval [CI] = 0.35 to 1.08), and the hazard ratios were 0.36 (95% CI = 0.25 to 0.53), 0.62 (95% CI = 0.39 to 0.99), and 0.49 (95% CI = 0.33 to 0.71), being similar to earlier findings. For the revised analysis, we included 822 BRCA1/2 mutation carriers. After a median follow-up period of 3.2 years, we obtained a hazard ratio of 1.09 (95% CI = 0.67 to 1.77). CONCLUSION: In previous studies, BC risk reduction after RRSO in BRCA1/2 mutation carriers may have been overestimated because of bias. Using a design that maximally eliminated bias, we found no evidence for a protective effect.

Decision-making on preimplantation genetic diagnosis and prenatal diagnosis: a challenge for couples with hereditary breast and ovarian cancer.

STUDY QUESTION: How do couples with a BRCA1/2 mutation decide on preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND) for hereditary breast and ovarian cancer syndrome (HBOC)? SUMMARY ANSWER: BRCA couples primarily classify PGD and/or PND as reproductive options based on the perceived severity of HBOC and moral considerations, and consequently weigh the few important advantages of PGD against numerous smaller disadvantages. WHAT IS KNOWN ALREADY: Awareness of PGD is generally low among persons at high risk for hereditary cancers. Most persons with HBOC are in favour of offering PGD for BRCA1/2 mutations, although only a minority would consider this option for themselves. Studies exploring the motivations for using or refraining from PGD among well-informed BRCA carriers of reproductive age are lacking. We studied the reproductive decision-making process by interviewing a group of well-informed, reproductive aged couples carrying a BRCA1/2 mutation, regarding their decisional motives and considerations. STUDY DESIGN, SIZE, DURATION: This exploratory, qualitative study investigated the motives and considerations taken into account by couples with a BRCA1/2 mutation and who have received extensive counselling on PGD and PND and have made a well-informed decision regarding this option. Eighteen couples took part in focus group and dyadic interviews between January and September 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: Semi-structured focus groups were conducted containing two to four couples, assembled based on the reproductive method the couple had chosen: PGD (n = 6 couples) or conception without testing (n = 8 couples). Couples who had chosen PND for BRCA (n = 4) were interviewed dyadically. Two of the women, of whom one had chosen PND and the other had chosen no testing, had a history of breast cancer. MAIN RESULTS AND THE ROLE OF CHANCE: None of the couples who opted for PGD or conception without testing found the use of PND, with possible pregnancy termination, acceptable. PND users chose this method because of decisive, mainly practical reasons (natural conception, high chance of favourable outcome). Motives and considerations regarding PGD largely overlapped between PGD users, PND users and non-users, all mentioning some significant advantages (e.g. protecting the child and family from the mutation) and many smaller disadvantages (e.g. the necessity of in vitro fertilization (IVF), low chance of pregnancy by IVF/PGD). For female carriers, the safety of hormonal stimulation and the time required for PGD before undergoing preventive surgeries were important factors in the decision. Non-users expressed doubts about the moral justness of their decision afterwards and emphasized the impact the decision still had on their lives. LIMITATIONS, REASON FOR CAUTION: The interviewed couples were at different stages in their chosen trajectory, up to 3 years after completion. This may have led to recall bias of original motives and considerations. Couples who did not actively seek information about PGD were excluded. Therefore the results may not be readily generalizable to all BRCA couples. WIDER IMPLICATIONS OF THE FINDINGS: The perceived severity of HBOC and, for female carriers, the safety of hormonal stimulation and the time frames for PGD planning before preventive surgeries are essential items BRCA couples consider in reproductive decision-making. The emotional impact of this decision should not be underestimated; especially non-users may experience feelings of doubt or guilt up to several years afterwards. PGD counselling with tailored information addressing these items and decisional support in order to guarantee well-informed decision-making is needed. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Dutch breast cancer foundation Stichting Pink Ribbon, grant number 2010.PS11.C74. None of the authors have competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Nonpolypoid colorectal neoplasms: a challenge in endoscopic surveillance of patients with Lynch syndrome.

BACKGROUND AND STUDY AIMS: Patients with Lynch syndrome may develop colorectal cancer (CRC), despite intensive colonoscopic surveillance. Nonpolypoid colorectal neoplasms might be a major contributor to the occurrence of these cancers. The aim of this case - control study was to compare the endoscopic appearance of colorectal neoplasms between patients with Lynch syndrome and control individuals at average risk for CRC. PATIENTS AND METHODS: The endoscopists at the Maastricht University Medical Center were first given training to ensure familiarity with the appearance and classification of nonpolypoid lesions. Patients with Lynch syndrome and patients at average risk for CRC who underwent elective colonoscopy at the Center were prospectively included. Nonpolypoid lesions were defined as lesions with a height of less than half the diameter, and advanced histology was defined as the presence of high grade dysplasia or early cancer. RESULTS: A total of 59 patients with Lynch syndrome (mean age 48.7 years, 47.5 % men) and 590 matched controls (mean age 50.2 years, 47.5 % men) were included. In patients with Lynch syndrome, adenomas were significantly more likely to be nonpolypoid than they were in controls: 43.3 % vs. 16.9 % (OR 3.60, 95 %CI 1.90 - 6.83; P < 0.001). This was particularly true for proximal adenomas: 58.1 % vs. 16.3 % (OR 6.93, 95 %CI 2.92 - 16.40; P < 0.001). Adenomas containing advanced histology were more often nonpolypoid in patients with Lynch syndrome than in controls (4/5, 80.0 % vs. 5/17, 29.4 %; P = 0.19). Serrated polyps were also more often nonpolypoid in patients with Lynch syndrome than in controls: 49.2 % vs. 20.4 % (OR 3.57, 95 %CI 1.91 - 6.68; P < 0.001). CONCLUSIONS: In patients with Lynch syndrome, colorectal neoplasms are more likely to have a nonpolypoid shape than those from average risk patients, especially in the proximal colon. These findings suggest that proficiency in recognition and endoscopic resection of nonpolypoid colorectal lesions are needed to ensure colonoscopic prevention against CRC in this high risk population.