Bisphosphonate use and risk of colorectal cancer: a systematic review and meta-analysis

Aim

A growing body of evidence suggests that bisphosphonates may have chemopreventive potential against colorectal cancer. Our aim was to examine this association through a meta-analysis of observational studies.

Methods

A comprehensive search for relevant articles published up to October 2012 was performed, reviews of each study were conducted and data were abstracted. Prior to meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using the random effects and the fixed effects models. Subgroup and sensitivity analyses were also performed.

Results

Eight large population-based epidemiological studies (one case-control, two nested case-control analyses within a cohort and five cohort studies), involving more than 630 000 participants, contributed to the analysis. We found no evidence of publication bias. However, significant heterogeneity was detected among the cohort studies. The analysis revealed a significant protective association between bisphosphonate use and colorectal cancer risk (fixed RR = 0.85, 95% CI 0.80, 0.90, random RR = 0.85, 95% CI 0.75, 0.96). When the analysis was stratified into subgroups according to study design, the association was inverse in both case-control and cohort studies, but only in the former was it statistically significant. The sensitivity analysis confirmed the stability of our results. Furthermore, we found evidence for a dose effect; Long term bisphosphonate use was associated with a 27% decrease in the risk of developing colorectal cancer as compared with non-use (RR = 0.73, 95% CI 0.57, 0.93).

Conclusion

Our findings support a protective effect of bisphosphonates against colorectal cancer. However, further evidence is warranted.     

Statin use and risk of kidney cancer: a meta-analysis of observational studies and randomized trials

Aim

Clinical studies have shown that statin use may modify the risk of kidney cancer. However, these studies yielded different results. To quantify the association between statin use and risk of kidney cancer, we performed a detailed meta-analysis of published studies regarding this subject.

Methods

A literature search was carried out using MEDLINE, EMBASE and the Cochrane database between January 1966 and October 2012. Prior to performing a meta-analysis, the studies were evaluated for publication bias and heterogeneity. Fixed effect and random effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Subgroup analyses and sensitivity analysis were also performed.

Results

A total of 12 (two randomized controlled trials, five cohort, and five case–control) studies contributed to the analysis. There was heterogeneity among the studies but no evidence of publication bias. Pooled results indicated a non-significant decrease of total kidney cancer risk among all statin users (RR = 0.92, 95% CI 0.71, 1.19). Long term statin use did not significantly affect the risk of total kidney cancer (RR = 1.01, 95% CI 0.83, 1.22). In our subgroup analyses, the results were not substantially affected by study design, confounder adjustment and gender. Furthermore, sensitivity analysis confirmed the stability of the results.

Conclusion

The findings of this meta-analysis suggested that there was no association between statin use and risk of kidney cancer. More studies, especially randomized controlled trials and high quality cohort studies with larger sample size and well controlled confounding factors, are needed to confirm this association in the future.     

Paracetamol use and risk of ovarian cancer: a meta-analysis

AIM: Ovarian cancer remains the most fatal gynaecological malignancy. Several observational studies have examined paracetamol as a potential chemopreventive agent. The nonconclusive nature of the epidemiological evidence prompted us to conduct a detailed meta-analysis of the studies published on the subject in peer-reviewed literature. METHODS: A comprehensive search for articles published up to 2004 was performed, reviews of each study were conducted and data were abstracted. Prior to meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk estimates (RR) and 95% confidence intervals (CIs) were calculated using the random and the fixed-effects models. RESULTS: Eight studies (four case-control and four cohort studies), published between 1998 and 2004, were included. We found no evidence of publication bias or heterogeneity among the studies. The analysis revealed an inverse association between paracetamol use and ovarian cancer risk. This association was marginally significant assuming a random-effects model (RR=0.84, 95% CI 0.70, 1.00), but not statistically significant assuming a fixed-effects model (RR=0.90, 95% CI 0.80, 1.01). When the analysis was stratified into subgroups according to study design, the association was inverse in both case-control and cohort studies, but only in the former was it statistically significant. The sensitivity analysis strengthened our confidence in the validity of this association. Furthermore, our results provided evidence for a dose effect; 'regular use' was associated with a statistically significant 30% reduction in the risk of developing ovarian cancer compared with non-use (RR=0.70, 95% CI 0.51, 0.95). CONCLUSIONS: Our meta-analysis supports a protective association between paracetamol use and ovarian cancer, and provides evidence for a dose effect. However, the question of paracetamol's potential association with ovarian cancer deserves further verification, since proof of chemoprevention would represent a major public health advance.     

Statin therapy on glycaemic control in type 2 diabetes: a meta-analysis

Objective: Randomised controlled trials (RCTs) indicate that statin therapy has cardiovascular benefit among patients with type 2 diabetes. Recently, statins were reported to increase risk of diabetes by 9%. The aim was to investigate by a meta-analysis whether statins deteriorate glycaemic control in type 2 diabetes.

Methods: Medline, EMBASE and Cochrane Central Register of Controlled Trials from 1966 to 2012 were searched for RCTs of statins. Included were only trials with type 2 diabetes.

Main outcome measures: The I² statistic was used to measure heterogeneity between trials and calculated mean differences for glycaemic parameters with random-effect meta-analysis.

Results: 26 eligible studies were identified with 3232 participants. Statin therapy had no remarkable influence on HbA1c (WMD 0.04%, 95% CI -0.08 to 0.16, I² = 45.7%, n = 3070), FPG (2.25 mg/dl, 95% CI -3.50 to 7.99, I² = 46%, n = 1176), BMI, fasting insulin or HOMA-IR. However, subgroup analysis showed significant, detrimental effect of atorvastatin on HbA1c, whereas simvastatin presented an ameliorative effect. Meta-regression presented that neither baseline age nor relative reduction in LDL-cholesterol concentrations accounted for residual heterogeneity.

Conclusion: Statin therapy showed non-significant effect on glycaemic control in type 2 diabetes. Statin therapy need not change among them with moderate or high cardiovascular risk or existing cardiovascular disease.     

Incidence and risk of hypertension associated with cabozantinib in cancer patients: a systematic review and meta-analysis

Introduction: Cabozantinib (XL184) is an oral inhibitor of multiplereceptor tyrosine kinases including mesenchymal-epithelial transition factor (MET) and vascular endothelial growth factor receptor 2 (VEGFR2). Hypertension is one of its major side effects, but the incidence rate and overall risk has not been systematically studied. We thus conducted this meta-analysis to investigate the overall incidence and risk of developing hypertension in cancer patients treated with cabozantinib.

Areas covered: Pubmed, Embase and oncology conference proceedings were searched for relevant studies. Eligible studies were phase II and III prospective clinical trials of cabozantinib in cancer patients with data on hypertension available. A total of 1,514 patients (cabozantinib, 1083; control, 431) with a variety of solid tumors from 8 prospective clinical trials were included for the meta-analysis. The use of cabozantinib was associated with significantly increased risk of developing all grade (RR 5.48; 95%CI, 3.76–7.99; p < 0.001) and high grade (5.09; 95% CI: 2.71–9.54, p < 0.001) hypertension in comparison with controls. Additionally, the risk of high grade hypertension with cabozantinib was substantially higher than other four approved VEGFR-TKIs (sorafenib, sunitinib, vandetanib and pazopanib).

Expert commentary: Cancer patients receiving cabozantinib have an increased risk of developing hypertension. Close monitoring and management of hypertension are recommended.     

罗格列酮治疗2型糖尿病患者发生非致命性心力衰竭风险的meta分析

目的:系统评价罗格列酮治疗2型糖尿病患者发生非致命性心力衰竭的风险。方法:以"rosiglitazone"、"randomizedclinical trial"和"human"为关键词,分别检索Medline数据库、ClinicalTrials.gov网站和葛兰素史克公司(GSK)网站,检索时间均从最早至2010年8月31日。收集比较罗格列酮与其他降糖药物治疗2型糖尿病患者发生非致命性心力衰竭风险的随机对照试验(RCT)进行meta分析;同时按照疗程、病程、治疗模式、对照类型将收集的RCT分成不同的亚组进行meta分析,并进行累积meta分析和敏感性分析。结果:共检索到相关文献678篇,根据纳入和排除标准共得到170项研究,其中Medline数据库和ClinicalTrials.gov网站公开发表的研究为99项,GSK网站发表者为71项。meta分析结果显示,与对照组相比,罗格列酮组发生非致命性心力衰竭的比值比(OR)为1.24[95%可信区间(CI)为0.99～1.55,P=0.065]。亚组分析结果显示,在公开发表的99项和GSK网站发表的71项研究中,罗格列酮组发生非致命性心力衰竭的OR值分别为1.42(95%CI:1.06～1.90,P=0.019)和1.01(95%CI:0.71～1.44,P=0.958);在疗程≥52周的30项研究中,罗格列酮组发生非致命性心力衰竭的OR值为1.62(95%CI:1.17～2.23,P=0.004)。公开发表的疗程≥52周的21项研究和病程≥5且<10年的33项研究显示,罗格列酮组发生非致命性心力衰竭的OR值分别为1.79(95%CI:1.22～2.64,P=0.003)和1.55(95%CI:1.06～2.26,P=0.025)。累积meta分析结果显示,OR值受2009年大型随机对照试验RECORD的影响,在2009年出现阳性拐点。对JADAD质量评分中≥3分的43项研究的meta分析结果显示,罗格列酮组发生非致命性心力衰竭的OR值为1.62(95%CI:1.17～2.23,P=0.004);其中疗程≥52周的16项研究、病程≥5且<10年的13项研究和复合用药的19项研究的OR值分别为1.79(95%CI:1.24～2.57,P=0.002)、1.76(95%CI:1.15～2.71,P=0.010)和1.68(95%CI:1.11～2.53,P=0.014)。结论:罗格列酮可能增加2型糖尿病患者发生非致命性心力衰竭的风险,且患病时间长、用药时间久、联合用药者发病风险更高。     

钠-葡萄糖转运蛋白2抑制剂与2型糖尿病患者恶性肿瘤发生风险的Meta分析

目的： 系统评价钠-葡萄糖转运蛋白2（sodium-glucose transporter 2 inhibitors,SGLT2）抑制剂的使用与2型糖尿病患者肿瘤发病的关系,为明确二者之间关系提供循证医学依据。方法： 以"钠-葡萄糖转运蛋白2（SGLT2）抑制剂、达格列净（dapagliflozin）、坎格列净（canagliflozin）、恩格列净（empagliflozin）、2型糖尿病、肿瘤"等为关键词,通过PubMed、Embase、Web of Science、Cochrane Library及万方、中国知网（CNKI）、维普中文期刊（VIP）等数据库检索2021年2月以前发表的中英文文献,确定符合条件的随机对照试验（randomized controlled trials,RCTs）。运用RevMan 5.3和Stata 15.0软件进行统计学处理。结果： 最终纳入17篇文献,共35 299例患者,其中1 072例2型糖尿病患者罹患恶性肿瘤。Meta分析结果表明,与对照组相比,SGLT2抑制剂与总体肿瘤风险增加无显著相关性（RR=0.98,95% CI：0.96~1.36）。不同SGLT2抑制剂对肿瘤发生的风险无显著相关性（RR=0.92,95% CI：0.81~1.04）。结论： 目前来自短期随机对照试验的证据并未表明使用SGLT2抑制剂的2型糖尿病患者有增加发生恶性肿瘤的风险。     

Insulin initiation in elderly patients with type 2 diabetes in France: a subpopulation of the LIGHT study

Abstract

Objective:

To examine the management of basal insulin analogue initiation in combination with oral antidiabetic drug (OAD) therapy in elderly patients with type 2 diabetes (aged ≥70 years) by physicians via comparison to the same treatment strategy in younger individuals (<70 years).     

Insulin analogues: how observational studies provide key insights into management of patients with type 2 diabetes mellitus

Abstract

Objective:

The aim of this commentary was to evaluate the current evidence regarding the use of synthetic insulin analogues in the ‘real-world’ clinic setting for the treatment of type 2 diabetes mellitus (T2DM).     

2型糖尿病患者结直肠腺瘤发病的多因素风险预测模型构建

目的 分析2型糖尿病患者结直肠腺瘤（CRA）发生的独立影响因素并构建风险预测模型。方法 将行结直肠镜检查的2型糖尿病患者分为腺瘤组（145例,病理诊断为CRA）和对照组（174例,结直肠黏膜无异常）。比较2组年龄、性别、体质量指数（BMI）、糖尿病病程、高血压史、糖尿病周围神经病变、脂肪肝、胃肠道症状、近5年二甲双胍与胰岛素应用情况、幽门螺杆菌（Hp）感染情况、吸烟史、饮酒史、大便隐血情况。实验室资料：肿瘤异常蛋白（TAP）、糖化血红蛋白（HbA1c）、胰岛素抵抗指数（HOMA-IR）、血清总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）、尿酸（UA）、维生素D₃水平。应用多因素Logistic回归分析T2DM患者发生CRA的独立影响因素,并构建产生新的联合预测因子（L_联合）。应用受试者工作特征（ROC）曲线评估L_联合预测价值,采用Hosmer-Lemeshow检验评价拟合度。结果 腺瘤组年龄、男性、BMI、高血压史、Hp阳性、吸烟史、饮酒史、大便隐血阳性比例,HbA1c、TG、TAP凝聚物面积、HOMA-IR高于对照组,应用二甲双胍比例、维生素D₃水平低于对照组（P<0.05）。多因素Logistic回归显示年龄、BMI、TG升高,TAP凝聚物面积增大、吸烟史、Hp阳性、大便隐血阳性是T2DM患者发生CRA的独立危险因素,而应用二甲双胍为独立保护因素（P<0.05）。ROC曲线显示L_联合的AUC为0.815（95%CI：0.768~0.862,P<0.01）,Hosmer-Lemeshow检验该风险模型拟合度较好（χ² =10.249,P=0.248）。结论 由年龄、BMI、TAP、TG、吸烟史、Hp感染、大便隐血和应用二甲双胍构成的联合预测因子对2型糖尿病患者结直肠腺瘤发病风险的预测效能较好。     

Exposure to bisphosphonates and risk of colorectal cancer

Animal and in vitro studies suggest that the use of bisphosphonates (BPs) may be associated with reduced risk for colorectal cancer (CRC). However, results from these studies have been inconsistent. The aim of our study was to review and summarize the evidence provided by longitudinal studies on the association between BP use and CRC risk A comprehensive literature search for articles published up to October 2012 was performed. Prior to performing a meta-analysis, the studies were evaluated for publication bias and heterogeneity. Relative risks (RRs) or odds ratios were calculated. Six reports (four case–control studies and two cohort studies) published between 2010 and 2012 were identified. There was evidence of an association between any use of BPs and CRC risk using a fixed-effects model (RR = 0.80, 95% confidence interval = 0.74, 0.85) and a random-effects model (RR = 0.80, 95% confidence interval = 0.71, 0.90). However, we did not observe any evidence of a trend with increasing duration of use. Our findings indicate that there is evidence of an association between any use of BP and reduced CRC risk. However, this subject deserves further investigation.     

2003－2012年殷行社区大肠癌发病分析

目的：分析殷行社区居民大肠癌发病特征。方法：统计分析2003－2012年居民大肠癌粗发病率、性别和年龄段等指标。结果：大肠癌粗发病率为59.99/10万,标化发病率为25.24/10万,发病为全部肿瘤的前二位;随年龄增长发病率逐渐增加。结论：大肠癌的发病率高,男性高于女性,中老年人群是大肠癌的高危发病人群。     

Treatment of patients with colorectal cancer: emphasis on liver metastases

The treatment of colorectal liver metastases has progressed considerably in recent years. Coordinated multidisciplinary management of patients on clinical trials has resulted in 5-year survival rates exceeding 50%, and for certain patients cure is now a realistic goal. For all patients, the approval of six new drugs has contributed to an increase in median survival from 6 months to over 20 months. Recent molecular discoveries promise an era of tailored therapy in which only patients known to benefit will be treated, an approach that will enable more efficient use of the already stretched resources. Clinical trials continue to investigate different combinations and methods of administering approved therapies, but if the progress of the past decade is to be replicated it is imperative that we embrace innovative treatment strategies and novel trial designs. In this review, we highlight the developments that have improved survival for patients with colorectal liver metastases and discuss the many issues that challenge further progress.     

2型糖尿病患者合并心脑血管疾病时的胰岛素治疗

对于糖尿病患者，心脑血管疾病已经成为致残和致死率最高、危害最大的合并症，65％～75％的糖尿病患者死于心脑血管疾病。胰岛素治疗2型糖尿病伴心脑血管疾病的益处已得到广泛证实，本文总结胰岛素对心脑血管疾病的有利影响，以及心脑血管疾病患者高血糖的处理原则。     

Antidepressant use and risk of coronary heart disease: meta-analysis of observational studies

Aims

Our goal was to evaluate the association between antidepressant use and the risk of coronary heart disease (CHD) among subjects with no history of coronary heart disease.

Methods

A search of Medline, EMBASE, PsycINFO and the Cochrane Library was performed in January 2013. Two authors independently reviewed and selected eligible observational studies, based on predetermined selection criteria. Pooled relative risks (RRs) with confidence intervals (CIs) were calculated using random-effects or fixed-effects models.

Results

Sixteen observational studies (seven case–control studies and nine cohort studies) were included in the final analysis. There was no association between selective serotonin reuptake inhibitor use and the risk of CHD overall [odds ratio (OR), 0.93; 95% CI, 0.65–1.33] or in subgroup meta-analysis of case–control studies (OR, 0.91; 95% CI, 0.60–1.37) and cohort studies (RR, 0.96; 95% CI, 0.59–1.55). The use of tricyclic antidepressant was associated with an increased risk of CHD overall (OR, 1.51; 95% CI, 1.07–2.12), but it was observed only in case–control studies (OR, 1.56; 95% CI, 1.24–1.96) and low-quality studies (OR, 1.49; 95% CI, 1.20–1.85) in the subgroup meta-analyses.

Conclusions

This meta-analysis of observational studies in subjects with no history of CHD suggests that neither selective serotonin reuptake inhibitor nor tricyclic antidepressant use is associated with an increased risk of CHD.     

Insulin therapy in type 2 diabetes: insulin analogue mix 50, a potential role in reducing postprandial hyperglycaemia and cardiovascular disease

Importance of the field: Postprandial hyperglycaemia is becoming topical, with studies suggesting a link to cardiovascular disease. Recently, a number of new therapies for the treatment of type 2 diabetes have become available.

Areas covered in this review: This review looks at the evidence for the potential role of insulin analogue mix 50 to reduce postprandial hyperglycaemia and cardiovascular disease. Search Strategy: Medline and Embase databases were searched using the MeSH terms to identify relevant studies from 1980 to 2009. Both original articles and reviews were extracted. Published reference lists were also examined. MeSH terms used for literature searching: human insulins, insulin analogues, insulin analogue mix 50, glycaemia, postprandial glucose, fasting glucose, type 2 diabetes, type 1 diabetes, cardiovascular disease.

What the reader will gain: The reader is presented with evidence discussing the importance of postprandial hyperglycaemia and studies comparing different insulin regimes and in particular insulin analogue mix 50 and its potential to reduce postprandial glucose surges and reduce cardiovascular disease.

Take-home message: Insulin analogue mix 50 is a viable therapeutic option in a sub-group of patients with type 2 diabetes.     

Reduced colorectal cancer incidence in type 2 diabetic patients treated with metformin: a meta-analysis

Context: Diabetic patients have a higher risk of colorectal cancer (CRC). The role of metformin in CRC incidence among type 2 diabetes mellitus (T2DM) remains controversial.

Objective: A meta-analysis was performed to evaluate the role of metformin treatment in the occurrence of CRC among T2DM patients.

Methods: Search was performed throughout PubMed, Embase, Springer databases up to November 2014. The search terms were (biguanides or metformin) and (bowel or colon or rectal or colorectal) and (cancer or neoplasm or neoplasia). Relative risk (RR) and 95% confidence interval (CI) was pooled using random-effects model or fixed-effect model basing on heterogeneity, which was calculated basing on Q statistics and χ² test. In addition, subgroup analyses were performed according to region, study design and control treatment. Finally, publication bias was evaluated using Egger’s regression test and trim and fill analysis.

Results: A total of 11 studies, including eight cohort studies and three case-control studies, were enrolled in the meta-analysis. Obvious heterogeneity was noted, and a 25% lower CRC incidence was found among diabetic patients treated with metformin (pooled RR=0.75, 95% CI: 0.66-0.86), using the random-effects model. Subgroup analyses showed that CRC incidence significantly reduced among T2DM in different regions, non-metformin treatment and cohort studies. Evidence supported significant publication for studies investigating from Egger’s regression test. Conversely, no missing data were found using trim and fill analysis.

Conclusion: In conclusion, the meta-analysis suggests metformin may reduce CRC incidence among diabetics, which is useful medical information for clinicians.