Contributions of Interactions Between Lifestyle and Genetics on Coronary Artery Disease Risk.

PURPOSE OF THE REVIEW: To summarize current knowledge on interactions between genetic variants and lifestyle factors (G×L) associated with the development of coronary artery disease (CAD) and prioritize future research. RECENT FINDINGS: Genetic risk and combined lifestyle factors and behaviors have a log-additive effect on the risk of developing CAD. First, we describe genetic and lifestyle factors associated with CAD and then focus on G×L interactions. The majority of G×L interaction studies are small-scale candidate gene studies that lack replication and therefore provide spurious results. Only a few studies, of which most use genetic risk scores or genome-wide approaches to test interactions, are robust in number and analysis strategy. These studies provide evidence for the existence of G×L interactions in the development of CAD. Further G×L interactions studies are important as they contribute to our understanding of disease pathophysiology and possibly provide insights for improving interventions or personalized recommendations.

Quality of life in elderly patients with an ostomy - a study from the population-based PROFILES registry.

AIM: Ostomies are being placed frequently in surgically treated elderly patients with colorectal cancer (CRC). An insight into the (potential) impact of ostomies on quality of life (QoL) could be useful in patient counselling as well as in the challenging shared treatment decision-making. METHOD: Patients with CRC diagnosed between 2000 and 2009 and registered in the population-based Eindhoven Cancer Registry received a QoL questionnaire (EORTC QLQ-C30) in 2010. In addition, QoL was compared with an age- and sex-matched normative population. RESULTS: The study included 2299 CRC patients, of whom 494 had an ostomy. No differences were found in reported ostomy-related problems between patients aged ≤65, 66-75 and ≥76 years. Ostomy patients aged 66-75 and ≥76 years reported significantly lower physical functioning compared with those without an ostomy. In the elderly (those aged ≥76 years) ostomates reported a worse physical and social functioning compared with the normative population. All these differences were of small clinical relevance. The impact of an ostomy seems to be more prominent in younger (≤75 years old) ostomates, as they experience more functional limitations and a decrease in global health status compared with younger nonostomy patients and the normative population. CONCLUSION: Although elderly (≥76 years old) patients with an ostomy report significantly more limitations in functioning compared with a normative population and elderly CRC patients without an ostomy, the clinical relevance of this finding is limited. In contrast, the impact of an ostomy is more prominent in younger patients. Thus, age itself is not a reason for withholding an ostomy.

The effect of a geriatric evaluation on treatment decisions for older patients with colorectal cancer.

BACKGROUND: Treating elderly colorectal cancer patients can be challenging. It is very important to carefully weigh the risks and benefits of potential treatments in individual patients. This treatment decision making can be guided by geriatric consultation. Our aim was to assess the effect of a geriatric evaluation on treatment decisions for older patients with colorectal cancer. METHODS: Colorectal cancer patients who were referred for a geriatric consultation between 2013 and 2015 in three Dutch teaching hospitals were included in a prospective database. The outcome of geriatric assessment, non-oncological interventions and geriatricians' treatment recommendations were evaluated. RESULTS: The total number of included referrals was 168. The median age was 81 years (range 60-94). Most patients (71%) had colon cancer and 49% had tumour stage III disease. The reason for geriatric consultation was uncertainty regarding the optimal oncologic treatment in 139 patients (83%). Overall 93% of patients suffered from geriatric impairments; non-oncological interventions that followed after geriatric consultation was mostly aimed at malnutrition. The geriatrician recommended the 'more intensive treatment' option in 69% and the 'less intensive treatment' option in 31% of which 63% 'supportive care only'. CONCLUSION: Geriatric consultation can be useful in treatment decision making in elderly patients with colorectal cancer. It may lead to changes in the treatment plan for individual cases and may result in an additional optimisation of patient's health status prior to treatment.

The impact of an ostomy on older colorectal cancer patients: a cross-sectional survey.

BACKGROUND: Ostomies are being placed in 35 % of patients after colorectal cancer surgery. As decision-making regarding colorectal surgery is challenging in the older patients, it is important to have insight in the potential impact due to ostomies. METHODS: An internet-based survey was sent to all members with registered email addresses of the Dutch Ostomy Patient Association. RESULTS: The response rate was 49 %; 932 cases were included of whom 526 were aged <70 years old ("younger respondents"), 301 were aged between 70 and 79 years old ("the elderly"), and 105 were aged ≥80 years old ("oldest old"). Ostomy-related limitations were similar in the different age groups, just as uncertainty (8-10 %) and dependency (18-22 %) due to the ostomy. A reduced quality of life was experienced least in the oldest old group (24 % vs 37 % of the elderly and 46 % of the younger respondents, p < 0.001). Over time, a decrease of limitations and impact due to the ostomy was observed. CONCLUSION: Older ostomates do not experience more limitations or psychosocial impact due to the ostomy compared to their younger counterparts. Over the years, impact becomes less distinct. Treatment decision-making is challenging in the older colorectal cancer patients but ostomy placement should not be withheld based on age alone.

Colorectal Cancer Resections in the Oldest Old Between 2011 and 2012 in The Netherlands.

INTRODUCTION: Adequate decision-making in elderly colorectal cancer patients requires accurate information regarding risks of treatment. We analysed the outcome and survival of colorectal resections in the oldest old (≥85 years). METHODS: An analysis of the 2011-2012 data from two large nationwide registries: the Dutch Surgical Colorectal Audit (DSCA), containing all colorectal cancer resections, and the Netherlands Cancer Registry (NCR), containing survival data for all newly diagnosed malignancies. RESULTS: The study included more than 1200 patients aged ≥85 years (DSCA n = 1232, NCR n = 1206). The postoperative complication rate was 41 % in the oldest old. The frequency of cardiopulmonary complications rose rapidly with age, from 11 % in those <70 years to 38 % for the oldest old (p < 0.001). Postoperative 30-day mortality rate was 10 % in the oldest old. Three-month mortality was 14 % (compared with 3 % of patients <85 years; p < 0.001). One-year mortality was 24 % and 2-year mortality 36 %. After correction for expected mortality in the general population, excess mortality for the oldest old was 12 % in the first year and 3 % in the second year. CONCLUSIONS: In this study of more than 1200 colorectal cancer patients aged ≥85 years undergoing surgical resection, we found high rates of cardiopulmonary complications and excess mortality, particularly in the first year after surgery. We propose that these data could be incorporated into individualized treatment algorithms, which also include detailed information regarding the patients' health status.

Improved survival for older patients undergoing surgery for colorectal cancer between 2008 and 2011.

INTRODUCTION: Older colorectal cancer patients have a higher risk of postoperative complications, and the impact of adverse events on survival is also significantly higher. Innovations like laparoscopic surgery which improve short-term outcome for older patients can also benefit their overall prognosis. We set out to analyse the impact of an increased utilisation of laparoscopic surgery for colorectal cancer in the Netherlands on overall survival. METHODS: All patients diagnosed with stages I-III colorectal cancer in the Netherlands between 2008 and 2011 were selected from the Netherlands Cancer Registry. Changes in perioperative mortality, 3-month mortality and 1-year mortality rates were analysed using year of diagnosis as an instrumental variable. RESULTS: Over 33,000 patients were included in the analyses. Data on surgical approach were not precisely known for 2008 and 2009; in 2010, 36.6 % of definitive surgical procedures were performed laparoscopically and 45.9 % in 2011. A laparoscopic approach was used less frequently in the patients aged ≥75 years (in 2011, 40.3 versus 49.2 % of younger patients; p < 0.001). Between 2008 and 2011, perioperative mortality decreased from 2.0 to 1.5 % (p = 0.02), 3-month mortality from 4.8 to 3.9 % (p = 0.01) and 1-year mortality from 9.6 to 8.3 % (p < 0.001). The absolute risk reduction was greatest for patients aged ≥75 years, reaching 2.1 % for 1-year mortality. CONCLUSION: Between 2008 and 2011, the utilisation of a laparoscopic approach increases significantly, resulting in reduced mortality rates, particularly for the elderly. Therefore, a laparoscopic approach should be used whenever possible, which may allow for further improvement of outcomes.

Imaging disease activity of rheumatoid arthritis by macrophage targeting using second generation translocator protein positron emission tomography tracers.

BACKGROUND: Positron emission tomography (PET) imaging of macrophages using the translocator protein (TSPO) tracer (R)-[11C]PK11195 has shown the promise to image rheumatoid arthritis (RA). To further improve TSPO PET for RA imaging, second generation TSPO tracers [11C]DPA-713 and [18F]DPA-714 have recently been evaluated pre-clinically showing better imaging characteristics. OBJECTIVE: A clinical proof of concept study to evaluate [11C]DPA-713 and [18F]DPA-714 to visualize arthritis in RA patients. METHODS: RA patients (n = 13) with at least two active hand joints were included. PET/CT scans of the hands were obtained after injection of [18F]DPA-714, [11C]DPA-713 and/or (R)-[11C]PK11195 (max. 2 tracers pp). Standardized uptake values (SUVs) and target-to-background (T/B) ratios were determined. Imaging data of the 3 different tracers were compared by pooled post-hoc testing, and by a head to head comparison. RESULTS: Clinically active arthritis was present in 110 hand joints (2-17 pp). Arthritic joints were visualized with both [11C]DPA-713 and [18F]DPA-714. Visual tracer uptake corresponded with clinical signs of arthritis in 80% of the joints. Mean absolute uptake in PET-positive joints was significantly higher for [11C]DPA-713 than for [18F]DPA-714, the latter being not significantly different from (R)-[11C]PK11195 uptake. Background uptake was lower for both DPA tracers compared with that of (R)-[11C]PK11195. Higher absolute uptake and lower background resulted in two-fold higher T/B ratios for [11C]DPA-713. CONCLUSIONS: [11C]DPA-713 and [18F]DPA-714 visualize arthritic joints in active RA patients and most optimal arthritis imaging results were obtained for [11C]DPA-713. Second generation TSPO macrophage PET provides new opportunities for both early diagnosis and therapy monitoring of RA.

[Colorectal cancer surgery in the oldest Dutch patients: retrospective analysis of two national databases covering 2011 and 2012]. / Darmkankerchirurgie bij de oudste Nederlanders.

OBJECTIVE: Adequate decision-making concerning elderly patients with colorectal cancer requires accurate information regarding the risks of treatment. We analysed the post-operative outcomes and survival following colorectal resections in the oldest old patients (≥ 85 years old). DESIGN: Retrospective study. METHOD: We analysed the data from 2011 and 2012 of all patients with colorectal carcinoma, stage I-III, from two national databases, namely the Dutch Surgical Colorectal Audit registry (DSCA) and the Netherlands Cancer Registry (NKR). RESULTS: The study included over 1200 elderly patients. The postoperative complication rate was 41%. The frequency of cardiopulmonary complications rose rapidly with age, from 11% in those < 70 years to 38% in those aged > 85 years. The postoperative 30-day mortality rate was 10% for the oldest old patients, whereas it was 14% after three months, 24% after one year and 36% after two years. After correction for expected mortality in the general population, excess mortality for the oldest old was 12% in the first year and 3% in the second year. CONCLUSION: For patients aged ≥ 85 years who undergo surgical resection for colorectal carcinoma, high rates of cardiopulmonary complications and excess mortality in the first year after surgery are observed. We propose that these data could be analysed together with information regarding individual patients' health status, to enable optimisation of future decision-making regarding potential surgical intervention in elderly patients.

Non-surgical complications after laparoscopic and open surgery for colorectal cancer - A systematic review of randomised controlled trials.

BACKGROUND: Cardiac and pulmonary complications account for a large part of postoperative mortality, especially in the growing number of elderly patients. This review studies the effect of laparoscopic surgery for colorectal cancer on short term non-surgical morbidity. METHODS: A literature search was conducted to identify randomised trials on laparoscopic compared to open surgery for colorectal cancer with reported cardiac or pulmonary complications. RESULTS: The search retrieved 3302 articles; 18 studies were included with a total of 6153 patients. Reported median or mean age varied from 56 years to 72 years. The percentage of included patients with ASA-scores ≥ 3 ranged from 7% to 38%. Morbidity was poorly defined. Overall reported incidence of postoperative cardiac complications was low for both laparoscopic and open colorectal resection (median 2%). There was a trend towards fewer cardiac complications following laparoscopic surgery (OR 0.66, 95% CI 0.41-1.06, p = 0.08), and this effect was most marked for laparoscopic colectomy (OR 0.28, 95% CI 0.11-0.71, p = 0.007). Incidence of pulmonary complications ranged from 0 to 11% and no benefit was found for laparoscopic surgery, although a possible trend was seen in favour of laparoscopic colectomy (OR 0.78, 95% CI 0.53-1.13, p = 0.19). Overall morbidity rates varied from 11% to 69% with a median of 33%. CONCLUSION: Although morbidity was poorly defined, for laparoscopic colectomies, significantly less cardiac complications occurred compared with open surgery and a trend towards less pulmonary complications was observed. Subgroup analysis from two RCTs suggests that elderly patients benefit most from a laparoscopic approach based on overall morbidity rates.

Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults.

Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 longitudinal studies including 169,551 adult Caucasians among whom 27,100 died during follow-up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI (n = 169,551; 0.32 kg m(-2) ; 95% CI 0.28-0.32, P < 1 × 10(-32) ), WC (n = 152,631; 0.76 cm; 0.68-0.84, P < 1 × 10(-32) ) and FMI (n = 48,192; 0.17 kg m(-2) ; 0.13-0.22, P = 1.0 × 10(-13) ). Cox proportional hazard regression analyses for mortality showed that the hazards ratio (HR) for the minor allele of the FTO SNPs was 1.02 (1.00-1.04, P = 0.097), but the apparent excess risk was eliminated after adjustment for BMI and WC (HR: 1.00; 0.98-1.03, P = 0.662) and for FMI (HR: 1.00; 0.96-1.04, P = 0.932). In conclusion, this study does not support that the FTO SNP is associated with all-cause mortality independently of the adiposity phenotypes.