Candidate gene association studies and risk of Hodgkin lymphoma: a systematic review and meta‐analysis

To evaluate the contribution of association studies of candidate polymorphisms to inherited predisposition to Hodgkin lymphoma (HL), we conducted a systematic review and meta‐analysis of published case‐control studies. Of the variants examined more than once in candidate gene association studies, we identified 21 studies that reported on 12 polymorphic variants in 10 genes. Data were also extracted from a published genome wide association study to allow analysis of an additional 47 variants in a further 30 genes. Promising associations were seen in nine of the variants (p < 0.05). Given that the estimated false positive report probabilities (FPRPs) for all associations are high (i.e. FPRP > 0.2), these findings should be interpreted with caution. While studies of candidate polymorphisms may be an attractive means of identifying risk factors for HL, future studies should employ sample sizes adequately powered to identify variants having only modest effects on HL risk. Furthermore, because of aetiological heterogeneity within HL, stratification of genotyping according to age, tumour Epstein‐Barr virus status and histology is essential. Copyright © 2015 John Wiley & Sons, Ltd.     

Efficacy and safety of amphotericin B lipid‐based formulations—A systematic review and meta‐analysis

Invasive fungal infections, an important cause of mortality, are primarily treated using amphotericin B, which is available in different formulations, both conventional and lipid‐based (liposomal, lipid complex, colloidal dispersion and Intralipid^® infusion). The aim of our study was to determine the efficacy and safety of conventional amphotericin B vs its lipid‐based formulations. A systematic review followed by pairwise meta‐analysis was performed, including randomised controlled trials (RCTs) that evaluated the use of lipid‐based amphotericin B in patients with any degree of immunosuppression and susceptibility to invasive fungal infection. An electronic search was conducted using PubMed, Scopus, Web of Science and Scielo databases. Extracted outcomes were related to efficacy (cure) and safety (incidence of adverse events). Results were evaluated and meta‐analyses were performed. Twenty‐three RCTs were identified (n=2677 participants) for meta‐analysis. No significant differences between conventional amphotericin B and any of the five formulations evaluated were observed, with regard to the efficacy analysis. With respect to the adverse events of nephrotoxicity, fever, chills and vomiting, all lipid formulations presented better profiles than the conventional formulation. The present systematic review and meta‐analysis showed that conventional amphotericin B presents the same efficacy profile as lipid‐based formulations, although the latter were associated with a safer profile.     

Consumption of omega‐3 fatty acids and the risk of skin cancers: A systematic review and meta‐analysis

Skin cancers have a higher incidence than all other cancers combined and are a major cause of morbidity worldwide. Laboratory data suggest certain dietary constituents, notably omega‐3 polyunsaturated fatty acids (n‐3 PUFAs), could potentially protect against skin malignancy, although no large‐scale review has been conducted in humans. The objective of this review and meta‐analysis was to determine the relationship between dietary n‐3 PUFAs and skin cancer incidence. It considered all published randomized controlled trials and observational studies up to March 2013. Five studies (two case–control and three cohort) were identified pertaining to oral n‐3 PUFA consumption and incidence of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), melanoma (or a combination) and were included in a random‐effects meta‐analysis. A further six studies considering nondietary n‐3 PUFA exposure (e.g. by tissue analysis) and/or recognized biological markers of skin cancer risk (e.g. p53 expression) were analyzed qualitatively. Dietary n‐3 PUFAs were not associated with BCC (pooled OR 1.05, 95% CIs 0.86–1.28). Consumption of high levels of n‐3 PUFAs were inversely associated with melanoma, although with only one estimate available (OR 0.52, 95% CI 0.34–0.78), and SCC, although nonsignificantly (pooled OR 0.86, 95% CIs 0.59–1.23). Available evidence is suggestive, but currently inadequate, to support the hypothesis that n‐3 PUFAs protect against skin malignancy.     

A systematic review and meta‐analysis of exercise interventions for colorectal cancer patients

The aim of this systematic review and meta‐analysis was to investigate the effectiveness of exercise for colorectal cancer patients. Pubmed/Medline, Scopus and the Cochrane Library were searched through December 2012 without language restrictions. Randomised controlled trials (RCTs) comparing exercise interventions to control conditions were analysed when they assessed health‐related quality of life, fatigue, physical fitness, survival and/or tumour‐associated biomarkers in colorectal cancer patients. Risk of bias was assessed using the risk of bias tool recommended by the Cochrane Back Review Group. Literature search identified 342 non‐duplicate records of which five RCTs with a total of 238 patients were included; three RCTs had low risk of bias. No evidence was found for short‐term effects on quality of life [standardised mean difference (SMD) = 0.18; 95% confidence interval (CI) ?0.39, 0.76; P = 0.53] or fatigue (SMD = 0.18; 95% CI ?0.22, 0.59; P = 0.38). There was strong evidence for short‐term improvements of physical fitness after aerobic exercise compared with controls (SMD = 0.59; 95% CI 0.25, 0.93; P < 0.01). One RCT each assessed immune parameters and oxidative DNA damage. No study reported survival rates or safety data. Given this insufficient evidence and the lack of safety data, no recommendation can be made regarding exercise interventions as a routine intervention for colorectal cancer patients.     

The effect of psychological interventions on quality of life in patients with head and neck cancer: A systematic review and meta‐analysis

This systematic review and meta‐analysis aimed to evaluate the effectiveness of psychological interventions in improving quality of life for head and neck cancer patients. Five databases were systematically searched in July 2016. Studies were included if they reported original empirical data from intervention studies utilising psychological approaches (excluding psychoeducational‐only interventions) and provided data on quality of life outcomes. Six studies, involving 185 participants, fulfilled eligibility criteria. Study designs included a case study, single‐group designs, non‐randomised controlled trials and one randomised controlled trial. Meta‐analysis of two studies did not provide support for the effectiveness of psychological intervention improving total quality of life scores (or subscales) compared to control groups at end of intervention. Intervention studies evaluating psychological interventions for patients with head and neck cancer have produced insufficient data to support their effectiveness for improving quality of life. This review further highlights the limited evidence base within this area. Existing studies are based on small samples and are inconsistent regarding: intervention type, duration and intensity; follow‐up measurement periods; and methodological quality. Further research, addressing these limitations, is required for more definitive conclusions to be drawn about the effectiveness of psychological interventions with this population.     

Adherence to Mediterranean diet and risk of cancer: A systematic review and meta‐analysis of observational studies

The aim of this research study was to meta‐analyze the effects of adherence to Mediterranean diet (MD) on overall cancer risk, and different cancer types. Literature search was performed using the electronic databases MEDLINE, SCOPUS and EMBASE until January 10, 2014. Inclusion criteria were cohort or case–control studies. Study specific risk ratios (RRs) were pooled using a random effect model by the Cochrane software package Review Manager 5.2. Twenty‐one cohort studies including 1,368,736 subjects and 12 case–control studies with 62,725 subjects met the objectives and were enclosed for meta‐analyses. The highest adherence to MD category resulted in a significantly risk reduction for overall cancer mortality/incidence (cohort; RR: 0.90, 95% CI 0.86–0.95, p < 0.0001; I² = 55%), colorectal (cohort/case–control; RR: 0.86, 95% CI 0.80–0.93, p < 0.0001; I² = 62%], prostate (cohort/case–control; RR: 0.96, 95% CI 0.92–0.99, p = 0.03; I² = 0%) and aerodigestive cancer (cohort/case–control; RR: 0.44, 95% CI 0.26–0.77, p = 0.003; I² = 83%). Nonsignificant changes could be observed for breast cancer, gastric cancer and pancreatic cancer. The Egger regression tests provided limited evidence of substantial publication bias. High adherence to a MD is associated with a significant reduction in the risk of overall cancer mortality (10%), colorectal cancer (14%), prostate cancer (4%) and aerodigestive cancer (56%).     

Cardiac glycosides and breast cancer risk: A systematic review and meta‐analysis of observational studies

Cardiac glycosides are phytoestrogens and have been linked to the risk of estrogen sensitive cancers such as uterus cancer. However, the association between use of cardiac glycosides and risk of breast cancer remains unclear. We investigated the association between cardiac glycosides use and the risk of breast cancer by systematically reviewing the published literature and performing meta‐analyses. A comprehensive literature search was performed using MEDLINE, EMBASE, Web of Science and SCOPUS to identify all relevant articles published up to November 2015. Risk estimates, and accompanying standard errors, for the association between cardiac glycoside use and breast cancer were extracted from identified studies. Meta‐analysis models were used to calculate a combined hazard ratio (HR), and 95% confidence interval (CI), and to investigate heterogeneity between studies. In total, nine studies were identified investigating cardiac glycosides use and risk of developing breast cancer. Overall, there was evidence to suggest an association between cardiac glycosides use and breast cancer risk (HR = 1.34; 95% CI 1.25, 1.44; p < 0.001) with little variation in the association between studies (I² = 16%, p for heterogeneity = 0.30). Results were little altered when analysis was restricted to studies with high quality scores or cohort studies. Overall, there was a 34% increase in breast risk with use of cardiac glycosides but it is unclear whether this association reflects confounding or is causal. Further observational studies are required to examine this association particularly for estrogen receptor positive breast cancer and to explore the role of potential confounding variables.     

Risk of venous thromboembolic events associated with VEGFR‐TKIs: A systematic review and meta‐analysis

Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) have been widely used in advanced cancers. Concerns have arisen regarding the risk of venous thromboembolism with the use of these drugs. Currently, the contribution of VEGFR‐TKIs to venous thromboembolism is still unknown. We performed a meta‐analysis to determine the incidence and relative risk (RR) of venous thromboembolism events (VTEs) associated with these agents. Eligible studies included phase II and III prospective trials evaluating US Food and Drug Administration approved VEGFR‐TKIs (pazopanib, sunitinib, sorafenib and vandetanib), and data on VTEs were available. Overall incidence rates, RR and 95% confidence intervals (CI) were calculated employing fixed‐ or random‐effects models depending on the heterogeneity of included trials. A total of 14 studies (4,430 patients) were selected for this meta‐analysis. The incidence of VTEs related to VEGFR‐TKIs was 3% (95%CI: 1.7–5.1%), and there was no statistically significant increase in the risk of VTEs for VEGFR‐TKIs versus controls in overall population (RR0.912, 95%CI: 0.617–1.348, p = 0.643). On subgroup analysis, no significant increase in the risk of VTEs was found among different VEGFR‐TKIs or tumor types. No evidence of publication bias was observed. The use of VEGFR‐TKIs does not significantly increase the risk of VTEs, the risk of VTEs in patients with cancer is driven predominantly by tumor types, host factors and concomitant usage of anticancer agents. These results would provide important information for clinicians who use VEGFR‐TKIs to treat patients with solid cancer.     

Dietary supplement use and colorectal cancer risk: A systematic review and meta‐analyses of prospective cohort studies

Use of dietary supplements is rising in countries where colorectal cancer is prevalent. We conducted a systematic literature review and meta‐analyses of prospective cohort studies on dietary supplement use and colorectal cancer risk. We identified relevant studies in Medline, Embase and Cochrane up to January 2013. Original and peer‐reviewed papers on dietary supplement use and colorectal cancer, colon cancer, or rectal cancer incidence were included. “Use‐no use”(U‐NU), “highest‐lowest”(H‐L) and “dose‐response”(DR) meta‐analyses were performed. Random‐effects models were used to estimate summary estimates. In total, 24 papers were included in the meta‐analyses. We observed inverse associations for colorectal cancer risk and multivitamin (U‐NU: RR = 0.92; 95% CI: 0.87,0.97) and calcium supplements (U‐NU: RR = 0.86; 95% CI: 0.79,0.95; H‐L: RR = 0.80; 95% CI: 0.70,0.92; DR: for an increase of 100 mg/day, RR = 0.96; 95% CI: 0.94,0.99). Inconsistent associations were found for colon cancer risk and supplemental vitamin A and vitamin C, and for colorectal cancer risk and supplemental vitamin D, vitamin E, garlic and folic acid. Meta‐analyses of observational studies suggest a beneficial role for multivitamins and calcium supplements on colorectal cancer risk, while the association with other supplements and colorectal cancer risk is inconsistent. Residual confounding of lifestyle factors might be present. Before recommendations can be made, an extensive assessment of dietary supplement use and a better understanding of underlying mechanisms is needed.     

Can physical activity modulate pancreatic cancer risk? a systematic review and meta‐analysis

Numerous epidemiological studies have examined the association between physical activity and pancreatic cancer; however, findings from individual cohorts have largely not corroborated a protective effect. Among other plausible mechanisms, physical activity may reduce abdominal fat depots inducing metabolic improvements in glucose tolerance and insulin sensitivity, thereby potentially attenuating pancreatic cancer risk. We performed a systematic review to examine associations between physical activity and pancreatic cancer. Six electronic databases were searched from their inception through July 2009, including MEDLINE and EMBASE, seeking observational studies examining any physical activity measure with pancreatic cancer incidence/mortality as an outcome. A random effects model was used to pool individual effect estimates evaluating highest vs. lowest categories of activity. Twenty‐eight studies were included. Pooled estimates indicated a reduction in pancreatic cancer risk with higher levels of total (five prospective studies, RR: 0.72, 95% CI: 0.52–0.99) and occupational activity (four prospective studies, RR: 0.75, 95% CI: 0.59–0.96). Nonsignificant inverse associations were seen between risks and recreational and transport physical activity. When examining exercise intensity, moderate activity appeared more protective (RR: 0.79, 95% CI: 0.52–1.20) than vigorous activity (RR: 0.97, 95% CI: 0.85–1.11), but results were not statistically significant and the former activity variable incorporated marked heterogeneity. Despite indications of an inverse relationship with higher levels of work and total activity, there was little evidence of such associations with recreational and other activity exposures.     

CT enterography in obscure gastrointestinal bleeding: A systematic review and meta‐analysis

The objective of this article is to provide a comprehensive and update overview of clinical application of CT enterography (CTE) in the evaluation of obscure gastrointestinal bleeding (OGIB). We performed a systematic review of relevant literatures in PubMed, EMBASE and The Cochrane Library and pooled the yield of CTE and the incremental yield (IY) of CTE over an alternate modality. A total of 18 studies (n = 660) reported the yield of CTE in evaluating OGIB and the pooled yield was 40% (95% confidence interval (CI): 33–49%). Seven studies (n = 279) compared the yield of CTE with capsule endoscopy (CE). The yield for CTE and CE for all findings was 34% and 53%, respectively (IY = ?19%, 95% CI = ?34% to ?4%). When considering the types of identified lesions, the yield was significantly different for vascular and inflammatory lesions but not significantly different for neoplastic or other lesions. Two studies (n = 63) compared the yield of CTE with double‐balloon enteroscopy (DBE). The yield for CTE and DBE was 38% and 78%, respectively (IY = ?40%, 95% CI = ?55% to ?25%). Three studies (n = 49) compared the yield of CTE with digital subtraction angiography. The yield for CTE and digital subtraction angiography was 64% and 60%, respectively (IY = 4%, 95% CI = ?40% to 47%). CTE is an excellent diagnostic tool in patients with OGIB. It may play a complementary role to CE and can be used as a triage tool prior to DBE in evaluating OGIB.     

Listening to the voice of patients with head and neck cancer: A systematic review and meta‐synthesis

The aim was to conduct a systematic review and a meta‐synthesis of primary qualitative studies exploring experiences of head and neck cancer patients (HNC) undergoing radio and/or chemotherapy, in order to provide a better understanding of this phenomenon and supply new directions for care and clinical practice. Six databases were systematically searched, and 13 studies were included. The meta‐synthesis methodology was adopted to conceptualise the way in which patients lived their cancer journey and the impact of treatments on their daily life. Four themes embracing various aspects of HNC patients’ experiences were identified: (a) self‐body image and perceived quality of life; (b) experiences and treatment of symptoms; (c) cancer journey; and (d) the relationship with health professionals. The finding demonstrates the importance of acknowledging that treatment sequelae and patients’ daily issues do not appear, develop and affect people's lives in isolation and should be considered and analysed as a whole within the social and cultural context of patients’ lives. Further research is needed to explore the treatment experience of HNC patients throughout their cancer journey with a more holistic approach that involves health professionals, caregivers and other family members and peers in the community.