Synergistic effect of vitamin E and selenium in human prostate cancer cell lines

Vitamin E and selenium are the two most popular dietary supplements used to prevent prostate cancer. The hypothesis that these antioxidants reduce prostate risk is being tested in the selenium and vitamin E chemoprevention trial (SELECT). We hypothesize that selenium potentiates vitamin E-induced inhibition of prostate cancer cell growth in vitro. Prostate cancer cell populations growing asynchronously were treated with a combination of vitamin E and selenium and processed for flow cytometric analysis. Prostate cancer cells treated with a combination of the antioxidants revealed that selenium potentiates vitamin E-induced inhibition of LNCaP cells in vitro. This was demonstrated by a reduction in the percentage of cells in the S phase. This crucial finding confirms our previous observations that antioxidant molecules act via distinct mechanistic pathways. These independent biological effects can be exploited in order to augment the anticancer properties of individual agents. These data also validate the two factorial design of the SELECT trial, permitting pairwise comparisons between agents in combination and alone.     

Diabetes mellitus and the incidence and mortality of colorectal cancer: a meta‐analysis of 24 cohort studies

Aim The incidence and mortality of colorectal cancer (CRC) were quantified in persons with and without diabetes mellitus (DM). Method Medline and Embase were searched for articles published before July 2010. Cohort studies that evaluated incidence and mortality of DM and CRC were included. The initial search identified 1887 titles, of which 24 articles met the inclusion criteria. We defined the relative risk (RR) as the metric of choice; 95% confidence intervals (CIs) were calculated with a random‐effects model. Results There was an increase in the RR of developing CRC in persons with DM compared with those without DM (RR 1.28; 95% CI 1.19–1.39), without heterogeneity between studies (P_{heterogeneity} = 0.13). The association between duration of DM and CRC incidence was stronger in the 11–15‐year group (RR 1.51; 95% CI 1.12–2.03) than in the <10‐year group (RR 1.05; 95% CI 0.90–1.22) and the >15‐year group (RR 1.25; 95% CI 0.80–1.94), and there was significant heterogeneity among subgroups (P_{heterogeneity} = 0.01). In studies reporting standardized incidence ratios (SIRs), there was an increased incidence of CRC with DM (RR 1.27; 95% CI 1.14–1.42; P_{heterogeneity} = 0.09), and the association was stronger among men (RR 1.47; 95% CI 1.15–1.86) than women (RR 1.08; 95% CI 1.00–1.17); there was significant heterogeneity among gender (P_{heterogeneity} = 0.01). Conclusion This meta‐analysis suggests that individuals with DM have a significant increase in risk of developing CRC.     

The survival effect of E‐cadherin and catenins in colorectal carcinomas

Aim The E‐cadherin/catenin complex plays an important role in epithelial tissue architecture. Decreased expression of cell adhesion molecules (E‐cadherin, α‐, β‐ and γ‐catenin) have been reported to correlate with invasive behaviour. The aim of this study was to investigate the relation between the expression of adhesion molecules and clinicopathological characteristics and survival in colorectal carcinoma. Method The expression of adhesion molecules were studied by immunohistochemistry in 138 colorectal carcinomas. Results The mean age of the patients was 65 years (range: 21–89 years). In primary carcinomas, a reduction in membranous expression of E‐cadherin, α‐catenin, β‐catenin, γ‐catenin was demonstrated (70%, 68%, 73%, 77%, respectively). Nuclear expression of β‐catenin was found in eight (5%) patients. Decreased membranous β‐ and γ‐catenin expression significantly correlated with tumour differentiation (P = 0.013, P = 0.03, respectively). There was a significant association between advanced stage of the tumour and decreased membranous α‐catenin expression (P = 0.012). Decreased E‐cadherin and β‐catenin membranous expression correlated with short survival following curative resection of the primary tumour (P = 0.04, P = 0.03, respectively). Conclusion The decreased membranous expression of E‐cadherin and β‐catenin and increased cytoplasmic expression of β‐catenin might be used as a prognostic marker to monitor patients with colorectal cancer.     

The Effects of Calcium Supplementation on Verified Coronary Heart Disease Hospitalization and Death in Postmenopausal Women: A Collaborative Meta‐Analysis of Randomized Controlled Trials

Calcium supplementation, particularly with vitamin D, has been an approved public health intervention to reduce fracture risk. Enthusiasm for this intervention has been mitigated by meta‐analyses suggesting that calcium supplementation with or without vitamin D increases myocardial infarction (MI) risk; however, concern has been raised over the design of these meta‐analyses. We, therefore, undertook a meta‐analysis of randomized controlled trials with placebo or no‐treatment control groups to determine if these supplements increase all‐cause mortality and coronary heart disease (CHD) risk including MI, angina pectoris and acute coronary syndrome, and chronic CHD verified by clinical review, hospital record, or death certificate in elderly women. The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases were searched from January 1, 1966, to May 24, 2013, for potentially eligible studies, reference lists were checked, and trial investigators were contacted where additional unpublished data were required. The search yielded 661 potentially eligible reports of which 18 met the inclusion criteria and contributed information on 63,563 participants with 3390 CHD events and 4157 deaths. Two authors extracted the data independently with trial data combined using random‐effects meta‐analysis to calculate the relative risk (RR). Five trials contributed CHD events with pooled relative RR of 1.02 (95% confidence interval [CI], 0.96–1.09; p = 0.51). Seventeen trials contributed all‐cause mortality data with pooled RR of 0.96 (95% CI, 0.91–1.02; p = 0.18). Heterogeneity among the trials was low for both primary outcomes (I² = 0%). For secondary outcomes, the RR for MI was 1.08 (95% CI, 0.92–1.26; p = 0.32), angina pectoris and acute coronary syndrome 1.09 (95% CI, 0.95–1.24; p = 0.22) and chronic CHD 0.92 (95% CI, 0.73–1.15; p = 0.46). In conclusion, current evidence does not support the hypothesis that calcium supplementation with or without vitamin D increases coronary heart disease or all‐cause mortality risk in elderly women. © 2014 American Society for Bone and Mineral Research.     

Evolving strategies for prostate cancer chemoprevention trials

Prostate cancer chemoprevention (CP) can be defined as the use of natural and synthetic agents that inhibit, reverse or regress precancer and delay progression to invasive cancer. During the past two decades several CP strategies have evolved. The first generation of CP trials tested the efficacy of antioxidants and vitamins including B-carotene, vitamin A, retinol, 13 cis retinoic acid, vitamins E, C and selenium. Although these trials were disappointing, provocative hypotheses were generated for selenium and vitamin E that set the stage for future prostate trials. In the 1990s, the NCI launched a second generation of large CP trials aimed at breast and prostate cancer. One of these trials is the PCPT, testing the efficacy of a 5 alpha-reductase inhibitor-finasteride to prevent prostate cancer in 18,000 men. Although PCPT is still in progress, the NCI recently launched a second large primary prostate CP trial called SELECT, testing the efficacy of selenium and vitamin E in 32,400 men. The Prostate Cancer Progress Report to the Director of NCI in 1998 challenged the research community to design more efficient CP trials for prostate cancer. In response, the NCI has evolved a third generation of CP trials. This involves pharmacologically driven translational science research including agents and their targets, biomarker endpoints, suitable clinical models for testing agents and efficient trial designs employing high risk cohorts and surrogate endpoints. In summary, a dual strategy for CP is being developed which includes public health measures and a medical intervention approach.     

Effects of avoidance or use of neuromuscular blocking agents on outcomes in tracheal intubation: a Cochrane systematic review

Cohort studies have indicated that avoidance of neuromuscular blocking agents (NMBA) is a risk factor for difficult tracheal intubation. However, the impact of avoiding NMBA on tracheal intubation, possible adverse effects, and postoperative discomfort has not been evaluated in a systematic review of randomised trials. We searched several databases for trials published until January 2017. We included randomised controlled trials comparing the effect of avoiding vs using NMBA. Two independent authors assessed risk of bias and extracted data. The risk of random errors was assessed by trial sequential analysis (TSA). We included 34 trials (3565 participants). In the four trials judged to have low risk of bias, there was an increased risk of difficult tracheal intubation with no use of NMBA [random-effects model, risk ratio (RR) 13.27, 95% confidence interval (CI) 8.19–21.49, P<0.00001, TSA-adjusted CI 1.85–95.04]. The result was confirmed when including all trials, (RR 5.00, 95% CI 3.49–7.15, P<0.00001, TSA-adjusted CI 1.20–20.77). There was a significant risk of upper airway discomfort or injury by avoiding NMBA (RR=1.37, 95% CI 1.09–1.74, P=0.008, TSA-adjusted CI 1.00–1.86). None of the trials reported mortality. Avoiding NMBA was significantly associated with difficult laryngoscopy, (RR 2.54, 95% CI 1.53–4.21, P=0.0003, TSA-adjusted CI 0.27–21.75). In a clinical context, one must balance arguments for using NMBA when performing tracheal intubation.     

Meta-analysis of Temporary Ileostomy Versus Colostomy for Colorectal Anastomoses

Background/Aims : Defunctioning stoma is a common surgical procedure, it is now generally acknowledged that defunctioning stoma significantly reduce the rates of complications in colorectal surgery, but the choice of temporary ileostomy or temporary colostomy for defunctioning colorectal anastomoses remains controversial. This meta-analysis evaluated two types of defunctioning stoma to determine whether one is superior to the other.

Methodology : Studies and relevant literatures comparing temporary ileostomy with temporary colostomy for defunctioning colorectal anastomoses were searched though PubMed, Embase and The Cochrane Library. The rates of complications were pooled and compared using a meta-analysis. The risk ratios were calculated with 95% confidence intervals to evaluate the safety and efficacy of each technique.

Results : Five randomized controlled trials and seven non-randomized studies were included, with 1687 patients in total. The meta-analysis of the RCTs demonstrated a lower risk of stoma prolapse (RR 0.15; 95% CI: 0.04–0.48, p = 0.001) in the temporary ileostomy group. Meta-analysis of the non-randomized studies showed a lower risk of stoma prolapse (RR 0.26; 95% CI 0.10–0.67, p = 0.005) and wound infection after stoma closure (RR 0.28; 95% CI 0.15–0.52, p < 0.0001) in the temporary ileostomy group. No other statistically significant difference was observed for complications. Conclusions : Each type of defunctioning stoma has its advantages and disadvantages, and there is not a strong evidence for the superiority of one temporary stoma over another for colorectal anastomoses. According to this, large scale RCTs and high quality studies are needed to conduct.     

The Relationship Between Vitamin A and Risk of Fracture: Meta‐Analysis of Prospective Studies

Osteoporotic fracture is a significant cause of morbidity and mortality and is a challenging global health problem. Previous reports of the relation between vitamin A intake or blood retinol and risk of fracture were inconsistent. We searched Medline and Embase to assess the effects of vitamin A (or retinol or beta‐carotene but not vitamin A metabolites) on risk of hip and total fracture. Only prospective studies were included. We pooled data with a random effects meta‐analysis with adjusted relative risk (adj.RR) and 95% confidence interval (CI). We used Q statistic and I² statistic to assess heterogeneity and Egger's test to assess publication bias. Eight vitamin A (or retinol or beta‐carotene) intake studies (283,930 participants) and four blood retinol level prospective studies (8725 participants) were included. High intake of vitamin A and retinol were shown to increase risk of hip fracture (adj.RR [95% CI] = 1.29 [1.07, 1.57] and 1.40 [1.03, 1.91], respectively), whereas beta‐carotene intake was not found to increase the risk of hip fracture (adj.RR [95% CI] = 0.82 [0.59, 1.14]). Both high or low level of blood retinol was shown to increase the risk of hip fracture (adj.RR [95% CI] = 1.87 [1.31, 2.65] and 1.56 [1.09, 2.22], respectively). The risk of total fracture does not differ significantly by level of vitamin A (or retinol) intake or by blood retinol level. Dose‐response meta‐analysis shows a U‐shaped relationship between serum retinol level and hip fracture risk. Our meta‐analysis suggests that blood retinol level is a double‐edged sword for risk of hip fracture. To avoid the risk of hip fracture caused by too low or too high a level of retinol concentration, we suggest that intake of beta‐carotene (a provitamin A), which should be converted to retinol in blood, may be better than intake of retinol from meat, which is directly absorbed into blood after intake. © 2014 American Society for Bone and Mineral Research.     

SELECT: the next prostate cancer prevention trial. Selenum and Vitamin E Cancer Prevention Trial

PURPOSE: Growing evidence implies that selenium and vitamin E may decrease the risk of prostate cancer. The Selenium and Vitamin E Cancer Prevention Trial (SELECT) is a randomized prospective double-blind study designed to determine whether selenium and vitamin E decrease the risk of prostate cancer in healthy men. MATERIALS AND METHODS: The preclinical and epidemiological evidence regarding chemoprevention with selenium and vitamin E were reviewed. Secondary analyses from randomized trials of the 2 agents were included in the current analysis. Data from these analyses as well as evidence from the Prostate Cancer Prevention Trial were used to develop the SELECT schema. RESULTS: Preclinical, epidemiological and phase III data imply that selenium and vitamin E have potential efficacy for prostate cancer prevention. The experience of the Prostate Cancer Prevention Trial shows the interest and dedication of healthy men to long-term studies of cancer prevention. A total of 32,400 men are planned to be randomized in SELECT. CONCLUSIONS: SELECT is the second large-scale study of chemoprevention for prostate cancer. Enrollment in the study is planned to begin in 2001 with final results anticipated in 2013.     

Capecitabine/oxaliplatin as first‐line treatment for metastatic colorectal cancer: a meta‐analysis

Objective A meta‐analysis of randomized controlled trials (RCT) was carried out to determine the efficacy and safety of capecitabine plus oxaliplatin (CAPOX) or fluorouracil plus oxaliplatin (FUOX) as first‐line treatment for metastatic colorectal cancer (MCRC). Method A literature search was conducted of the Cochrane Controlled Trials Register Databases, Medline, Embase, ISI databases and Chinese Biomedical Literature Database without exclusion of material published in any language. RCTs conducted between 1998 and 2008 of CAPOX compared with FUOX regimens were considered for inclusion. Statistical analyses were carried out using RevMan software. Results Ten RCTs were included, involving 3208 patients. The meta‐analysis showed that there were no statistically significant differences in tumour response rate (RR, 0.93; 95% CI, 0.87–1.01; P = 0.09), progression‐free survival (PFS) (RR, 0.98; 95% CI, 0.94–1.01; P = 0.19), and overall survival (OS) (RR, 1.02; 95% CI, 0.97–1.07; P = 0.47) between CAPOX and FUOX regimen. However, symptoms of thrombocytopenia and hand‐foot syndrome (HFS) were increased in the CAPOX regimen (RR, 1.89; 95% CI, 1.33–2.69; P = 0.0004 and RR, 3.40; 95% CI, 2.25–5.15; P < 0.00001 respectively), while neutropenia and leucopenia occurred more frequently in the FUOX regimen (RR, 0.29; 95% CI, 0.15–0.55; P = 0.0002 and RR, 0.41; 95% CI, 0.18–0.95; P = 0.04respectively). Conclusion CAPOX was equivalent to FUOX in terms of tumour response rate, progression‐free survival (PFS), and OS in first‐line treatment for patients with MCRC, which may be considered as standard first‐line treatment in patients with MCRC.     

Reoperation as a quality indicator in colorectal surgery: a population-based analysis

OBJECTIVE: To describe unplanned procedures following colorectal cancer surgery that might be used as intermediate outcome measures, and to determine their association with mortality and length of stay. SUMMARY BACKGROUND: Variation in the quality of surgical care, especially for common illnesses like colorectal cancer, has received increasing attention. Nonfatal complications resulting in procedural interventions are likely to play a role in poor outcomes but have not been well explored. METHODS: Cohort analysis of 26,638 stage I to III colorectal cancer patients in the 1992 to 1996 SEER-Medicare database. Independent variables: sociodemographics, tumor characteristics, comorbidity, and acuity. Primary outcome: postoperative procedural intervention. Analysis: Logistic regression identified patient characteristics predicting postoperative procedures and the adjusted risk of 30-day mortality and prolonged hospitalization among patients with postoperative procedures. RESULTS: A total of 5.8% of patients required postoperative intervention. Patient characteristics had little impact on the frequency of postoperative procedures, except for acute medical conditions, including bowel perforation (relative risk [RR] = 3.0, 95% confidence interval [CI] = 2.5-3.6), obstruction (RR = 1.6; 95% CI = 1.4-1.8), and emergent admission (RR = 1.3; 95% CI = 1.1-1.4). After a postoperative procedure, patients were more likely to experience early mortality (RR = 2.4; 95% CI = 2.1-2.9) and prolonged hospitalization (RR = 2.2; 95% CI = 2.1-2.4). The most common interventions were performed for abdominal infection (31.7%; RR mortality = 2.9; 95% CI = 2.3-3.7), wound complications (21.1%; RR mortality = 0.7; 95% CI = 0.4-1.3), and organ injury (18.7%; RR mortality = 1.6; 95% CI = 1.1-2.3). CONCLUSIONS: Postoperative complications requiring additional procedures among colorectal cancer patients correlate with established measures of surgical quality. Prospective tracking of postoperative procedures as complication markers may facilitate outcome studies and quality improvement programs.     

SELECT: the selenium and vitamin E cancer prevention trial

PURPOSE: Growing evidence suggests that both selenium and vitamin E may reduce the risk of prostate cancer. SELECT is a randomized, prospective, double-blind study designed to determine if selenium and vitamin E can reduce the risk of prostate cancer among healthy men. MATERIALS AND METHODS: The preclinical and epidemiologic evidence regarding chemoprevention with selenium and vitamin E were reviewed. Secondary analyses from randomized trials of both agents were included in the analysis. Data from these analyses as well as evidence from the Prostate Cancer Prevention Trial were used to develop the schema of SELECT. RESULTS: Preclinical, epidemiologic, and Phase III data suggest that both selenium and vitamin E have potential efficacy in prostate cancer prevention. The experience of the Prostate Cancer Prevention Trial and the rapid accrual of SELECT during its first year demonstrate the interest and dedication of healthy men to long-term studies of cancer prevention. A total of 32,400 men are planned to be randomized in SELECT. CONCLUSIONS: SELECT is the second large-scale study of chemoprevention for prostate cancer. Enrollment began in 2001 with final results anticipated in 2013.     

Cinacalcet versus standard treatment for chronic kidney disease: a systematic review and meta-analysis

Background: Chronic kidney disease-mineral and bone disorders (CKD-MBD) have been associated with poor health outcomes, including diminished quality and length of life. Standard management for CKD-MBD includes phosphate restricted diet, vitamin D and phosphate binders. Persistently elevated parathyroid hormone levels may require the addition of cinacalcet hydrochloride (cinacalcet), which sensitizes calcium receptors in the parathyroid gland.

Purpose: The objective of this systematic review is to compare, in patients with CKD-MBD the effect of cinacalcet versus standard treatment on patient-important outcomes, including parathyroidectomy, fractures, hospitalizations due to cardiovascular events, cardiovascular mortality, all-cause mortality, and intermediate outcomes, in particular Kidney Disease Outcome Quality Initiative targets.

Methods: Data sources included MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and Web of Science from 1996 to June 2015. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstracted data and assessed risk of bias in eligible trials. We calculated the effect estimates (risk ratios or mean differences) and 95% confidence intervals, as well as statistical measures of variability in results across studies using random effect models. We used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate quality of evidence about estimates of effect on an outcome-by-outcome basis for all outcomes. We presented our results with a GRADE summary table.

Results: Twenty-four trials including 8311 CKD patients proved eligible. The results left considerable uncertainty regarding the impact of cinacalcet on reducing fractures (relative risk [RR] 0.59, 95% confidence interval [CI] 0.13–2.60; heterogeneity: p?=?0.03, I²=?78%; very low quality evidence), and indicated that cinacalcet did not reduce hospitalizations due to cardiovascular events (RR 0.93, 95% CI 0.85–1.02, moderate quality of evidence), cardiovascular mortality (RR 0.95, 95% CI 0.84–1.07; heterogeneity p=?0.61, high quality evidence) or all-cause mortality (RR 0.96, 95% CI 0.89–1.04; heterogeneity: p=?0.98, I²=?0%; moderate quality evidence). Cinacalcet reduced the need for parathyroidectomy (RR 0.30, 95% CI 0.22–0.42; heterogeneity: p=?0.70, I²=?0%; absolute effect 55 fewer per 1000 [95% CI 61 fewer to 45 fewer], high quality of evidence). The most common adverse event associated with cinacalcet therapy was gastrointestinal side effects. Cinacalcet increased nausea (RR 2.16, 95% CI 1.46–3.21, absolute effect 158 more per 1000 [95% CI 82 more to 302 more]) and vomiting (RR 2.15, 95% CI 1.66–2.80, absolute effect 63 more per 1000 [95% CI 109 more to 171 more]). Cinacalcet treatment increased the rate of hypocalcemia (RR 6.0, 95% CI 3.65–9.87; heterogeneity: p=?0.71, I²=?0%, absolute effect 20 more per 1000 [95% CI 11 more to 36 more], high quality of evidence).

Conclusions: In the hands of clinicians participating in these studies, cinacalcet decreased the rate of parathyroidectomy but had no influence on mortality. Patients and clinicians can trade of the benefit of fewer parathyroidectomies against the adverse effects.     

Impact of family history of gastric cancer on colorectal neoplasias in young Japanese

Aim The aim of this study was to elucidate risk factors for the development of colorectal neoplasia in the young population. In particular, we focused on the family history of gastric cancer. Method Young Japanese subjects aged 30–49 years old who underwent colonoscopy for the first time from August 2007 to August 2008 were included in this study. A total of 300 unselected consecutive patients (mean age 40.5 years) were eligible for analysis, and family history of colorectal cancer and gastric cancer, sex, age, body mass index, positivity of faecal occult blood test and the presence of symptoms were evaluated. Risk factors for developing colorectal adenoma and/or carcinoma were assessed. Results Colorectal neoplasias were detected in 83 (27.7%) cases. Two were found to have invasive carcinoma. Univariate and multivariate analyses revealed that family history of gastric cancer (OR 2.09, 95% CI 1.12–3.92, P = 0.02) was an independent risk factor for the development of colorectal neoplasia, as well as male sex (OR 1.89, 95% CI 1.10–3.27, P = 0.02), older age (OR 2.05, 95% CI 1.18–3.55, P = 0.01) and positive faecal occult blood test (OR 1.99, 95% CI 1.14–3.48, P = 0.02). Conclusion In the young population under 50 years of age, a family history of gastric cancer is an independent risk factor for the development of colorectal neoplasia.     

Can we prevent prostate cancer? Rationale and current status of prostate cancer chemoprevention

Prostate cancer has been one of the most frequent cancers among men in Western countries for the past decade. Investigation of prostate cancer prevention is very attractive, because prostate cancer has a high incidence, long-term natural history, regional difference in incidence, and is effected by sex steroids. Chemoprevention is defined as the use of specific agents to suppress or reverse carcinogenesis and to prevent the development of cancer. The development of chemoprevention strategies against prostate cancer would be of medical and economic importance. Basic and clinical research of chemoprevention of prostate cancer are under active investigation. This article aims to summarize and review the basic evidence and clinical trials on prostate cancer chemoprevention. Recent research has demonstrated that many agents, such as agents altering sex steroid signaling, drugs inducing antiproliferation/differentiation, retinoids, anti-inflammatory drugs, and antioxidants, could be potential preventatives for prostate cancer. Large-scale clinical trials have suggested that 5alpha-reductase inhibitor finasteride, selenium, and vitamin E can function as a chemopreventive agent. Although no definitely effective strategies of prostate cancer prevention have been identified yet, increasing evidence will provide effective and safe strategies that bring clinical benefits.     

The Selenium and Vitamin E Cancer Prevention Trial

BACKGROUND: Evidence suggests that both selenium and vitamin E reduce the risk of prostate cancer. The Selenium and Vitamin E Cancer Prevention Trial (SELECT) is a randomized, prospective, double-blind study designed to determine whether selenium and vitamin E alone and in combination can reduce the risk of prostate cancer among healthy men. MATERIALS AND METHODS: The preclinical and epidemiological evidence supporting a role for selenium and vitamin E as chemopreventive agents in prostate cancer are reviewed, and details of the trial design are presented. RESULTS. Preclinical, epidemiological, and phase III data from randomized, placebo-controlled clinical trials suggest that both selenium and vitamin E have potential efficacy in prostate cancer prevention. SELECT is a 2x2 factorial study with an accrual goal of 32,400 men with nonsuspicious DRE and serum PSA of 4 ng/ml or lower. CONCLUSIONS: SELECT is the second large-scale study of chemoprevention for prostate cancer. Enrollment began in 2001 with final results anticipated in 2013.     

腹腔镜结直肠癌手术疗效及安全性的系统评价

目的 系统评价腹腔镜与开腹手术切除治疗结直肠癌的疗效及安全性.方法 采用Cochrane系统评价方法,检索Embase、PubMed、Cochrane图书馆、Sciencedirect、Springer、VIP、CNKI、CBMdisc等数据库中2000年1月至2010年10月公开发表的腹腔镜与开腹手术切除治疗结直肠癌的随机对照试验(RCT),对符合纳入标准的研究进行质量评价和资料提取,并采用RevMan 5.0对腹腔镜与开腹手术切除治疗结直肠癌的疗效及安全性进行meta分析.结果 共纳入13项RCT,共计4603例患者.其中6项为多中心RCT.meta分析结果显示:腹腔镜组手术时间长于开腹组(加权均数差值WMD=38.91,95% CI:33.89～43.93,P＜0.001),术中失血量少于开腹组(WMD=-138.14,95% CI:-195.79～-80.50,P＜0.001),总住院时间少于开腹组(WMD=2.91,95%CI:-4.65～-1.17,P=0.001);两组淋巴结清扫数量、术后并发症(30 d)发生率、3年总生存率、5年总生存率、5年总复发率的差异均无统计学意义(均为P＞0.05).结论 腹腔镜辅助下行结直肠癌根治术的短期和长期结果均表明其有效并且安全,有望成为结直肠癌治疗的新选择.

Abstract：

Objective To evaluate and compare the efficiency and safety of laparoscopic surgery (LS) and open surgery (OS) in the treatment of colorectal carcinoma. Methods Randomized controlled trials on laparoscopic surgery and open surgery for colorectal carcinoma from January 2000 to October 2010were searched in the databases of EMbase, PubMed, Cochrane Library, Sciencedirect, Springer, VIP,CNKI, CBMdisc. The methodological quality was assessed according to the standard of Cochrane systematic review. For homogeneous studies, RevMan5.0 software was used for meta-analysis. Results A total of 13 RCTs involving 4603 patients were included in this study, and among those 6 were multi-center randomized controlled trials. The meta-analysis showed that: the operation time of the LS group was longer than that of the OS group ( WMD = 38. 91, 95% CI: 33.89-43.93, P ＜ 0. 001 ), the blood loss ( WMD =- 138. 14, 95% CI:-195. 79-80. 50, P ＜ 0. 001 ) and the length of hospital stay ( WMD = 2. 91, 95%CI: -4. 65-1.17, P =0. 001 ) of the LS group was less than those in OS group. There was no significant differences between the two groups in the number of dissected lymph nodes( WMD = -0. 62, 95% CI:- 1.47-0. 23, P = 0.150). There was no significant differences between the two groups in terms of the postoperative complications(30 days) (RR =0.78,95% CI:0. 59-1.01, P = 0. 06 ). There was no significant differences between the two groups in 3-year overall survival ( RR = 1.00, 95% CI :0. 96-1.04, P = 0. 970).There was no significant differences between the two groups in 5-year overall survival (RR = 1.03, 95% CI:0. 99-1.08, P = 0. 140 ). There was no significant differences between the two groups in 5-year overall recurrence ( RR = 0. 89,95% CI:0. 74-1.07, P = 0. 200). Conclusions Laparoscopic surgery for colorectal carcinoma is a safe and effective therapy as open surgery in the short term or long term outcomes. It could be an acceptable alternative to open surgery for colorectal carcinoma.     

The incidence and outcome of brain metastases after liver resection for colorectal cancer metastases

Aim Brain metastases from colorectal cancer are rare, with an incidence of 0.6–4%. The risk and outcome of brain metastases after hepatic and pulmonary metastasectomy have not been previously described. This study aimed to determine the incidence, predictive factors, treatment and survival of patients developing colorectal brain metastases, who had previously undergone resection of hepatic metastases. Method A retrospective review was carried out of a prospectively maintained database of patients undergoing liver resection for colorectal metastases. Results Fifty‐two (4.0%) of 1304 patients were diagnosed with brain metastases. The annual incidence rate was 1.03% per person‐year. In the majority of cases brain metastases were found as part of multifocal disease. Median survival was 3.2 months (95% CI: 2.3–4.1), but was best for six patients treated with potentially curative resection [median survival = 13.2 (range, 4.9–32.1) months]. Multivariate analysis showed that a lymph node‐positive primary tumour [hazard ratio (HR) = 2.7, 95% CI: 1.8–6.19; P = 0.019], large liver metastases (> 6 cm) [HR = 2.23, 95% CI: 1.19–2.33; P = 0.012] and recurrent intrahepatic and extrahepatic disease [HR = 2.11, 95% CI: 1.2–4.62; P = 0.013] were independent predictors for the development of brain metastases. Conclusion The annual risk of developing brain metastases following liver resection for colorectal metastases is low, but highest for patients presenting with a Dukes’ C primary tumour, large liver metastases or who subsequently develop disseminated disease. The overall survival from colorectal brain metastases is poor, but resection with curative intent offers patients their best chance of medium‐term survival.