Expert opinion on laparoscopic surgery for colorectal cancer parallels evidence from a cumulative meta-analysis of randomized controlled trials

Background

This study sought to synthesize survival outcomes from trials of laparoscopic and open colorectal cancer surgery, and to determine whether expert acceptance of this technology in the literature has parallel cumulative survival evidence.

Study Design

A systematic review of randomized trials was conducted. The primary outcome was survival, and meta-analysis of time-to-event data was conducted. Expert opinion in the literature (published reviews, guidelines, and textbook chapters) on the acceptability of laparoscopic colorectal cancer was graded using a 7-point scale. Pooled survival data were correlated in time with accumulating expert opinion scores.

Results

A total of 5,800 citations were screened. Of these, 39 publications pertaining to 23 individual trials were retained. As well, 414 reviews were included (28 guidelines, 30 textbook chapters, 20 systematic reviews, 336 narrative reviews). In total, 5,782 patients were randomized to laparoscopic (n = 3,031) and open (n = 2,751) colorectal surgery. Survival data were presented in 16 publications. Laparoscopic surgery was not inferior to open surgery in terms of overall survival (HR = 0.94, 95% CI 0.80, 1.09). Expert opinion in the literature pertaining to the oncologic acceptability of laparoscopic surgery for colon cancer correlated most closely with the publication of large RCTs in 2002–2004. Although increasingly accepted since 2006, laparoscopic surgery for rectal cancer remained controversial.

Conclusions

Laparoscopic surgery for colon cancer is non-inferior to open surgery in terms of overall survival, and has been so since 2004. The majority expert opinion in the literature has considered these two techniques to be equivalent since 2002–2004. Laparoscopic surgery for rectal cancer has been increasingly accepted since 2006, but remains controversial. Knowledge translation efforts in this field appear to have paralleled the accumulation of clinical trial evidence.     

Helicobacter pylori infection and colorectal cancer risk: a meta-analysis

BACKGROUND: Several studies suggested an association between Helicobacter pylori infection and colorectal carcinoma or adenoma risk. However, different authors reported quite varying estimates. We carried out a systematic review and meta-analysis of published studies investigating this association and paid special attention to the possibility of publication bias and sources of heterogeneity between studies. Materials and METHODS: An extensive literature search and cross-referencing were performed to identify all published studies. Summary estimates were obtained using random-effects models. The presence of possible publication bias was assessed using different statistical approaches. RESULTS: In a meta-analysis of the 11 identified human studies, published between 1991 and 2002, a summary odds ratio of 1.4 (95% CI, 1.1-1.8) was estimated for the association between H. pylori infection and colorectal cancer risk. The graphical funnel plot appeared asymmetrical, but the formal statistical evaluations did not provide strong evidence of publication bias. The proportion of variation of study results because of heterogeneity was small (36.5%). CONCLUSIONS: The results of our meta-analysis are consistent with a possible small increase in risk of colorectal cancer because of H. pylori infection. However, the possibility of some publication bias cannot be ruled out, although it could not be statistically confirmed. Larger, better designed and better controlled studies are needed to clarify the situation.     

Matrix metalloproteinase 2 overexpression and prognosis in colorectal cancer: a meta-analysis

Many studies investigated the relationship between matrix metalloproteinase 2 (MMP-2) overexpression and survival in patients with colorectal cancer (CRC), but yielded inconsistent results. To derive a more precise estimate of the prognostic significance of MMP-2 overexpression, we reviewed published studies and carried out a meta-analysis. Eligible articles were identified for the period up to March 2012 in electronic databases. To evaluate the correlation between MMP-2 overexpression and the prognosis in CRC, pooled hazard ratio (HR) and its 95?% confidence interval (95?% CI) for poorer overall and progression-free survival were appropriately derived from fixed-effects or random-effects models using standard meta-analysis techniques. Thirteen studies with a total of 1,919 CRC patients stratifying overall survival (OS) and/or progression-free survival in CRC patients by MMP-2 expression status were eligible for analysis. Ten studies investigated the OS in a total of 1,612 cases with CRC, and five studies investigated the progression-free survival in a total of 508 patients CRC. The combined HR estimate for OS and progression-free survival was 1.74 (95?% CI, 1.34?C2.26) and 1.35 (95?% CI, 1.07?C1.80), respectively. Both subgroup analyses and sensitivity analysis further identified the prognostic role of MMP-2 overexpression in patients with CRC. There was no evidence for publication bias. In conclusion, MMP-2 overexpression is associated with poorer overall and progression-free survival in patients with CRC.     

Efficacy of adjuvant Immunochemotherapy with polysaccharide K for patients with curatively resected colorectal cancer: a meta-analysis of centrally randomized controlled clinical trials

The benefits of immunochemotherapy employing the biological response modifier polysaccharide K (PSK) for patients with curatively resected colorectal cancer was reassessed by means of a meta-analysis of data with center randomization from 1,094 patients enrolled in three clinical trials. In all three trials, patients were followed up for at least 5 years after surgery and enrollment of the last patient and outcomes for standard chemotherapy were compared with those for chemotherapy plus PSK. The endpoints were overall survival and disease-free survival; and intent-to-treat analysis was performed without patient exclusion. Data were analyzed using the weighted average of the individual log hazard ratios. The overall survival risk ratio for all eligible patients was 0.71 (95% confidence interval (CI) : 0.55–0.90; P=0.006), and the disease-free survival risk ratio was 0.72 (95% CI: 0.58–0.90; P=0.003). The results of this meta-analysis suggest that adjuvant immunochemotherapy with PSK can improve both survival and disease-free survival of patients with curatively resected colorectal cancer.     

Impact on survival of intensive follow up after curative resection for colorectal cancer: systematic review and meta-analysis of randomised trials

ObjectiveTo review the evidence from clinical trials of follow up of patients after curative resection for colorectal cancer.DesignSystematic review and meta-analysis of randomised controlled trials of intensive compared with control follow up.ResultsFive trials, which included 1342 patients, met the inclusion criteria. Intensive follow up was associated with a reduction in all cause mortality (combined risk ratio 0.81, 95% confidence interval 0.70 to 0.94, P=0.007). The effect was most pronounced in the four extramural detection trials that used computed tomography and frequent measurements of serum carcinoembryonic antigen (risk ratio 0.73, 0.60 to 0.89, P=0.002). Intensive follow up was associated with significantly earlier detection of all recurrences (difference in means 8.5 months, 7.6 to 9.4 months, P<0.001) and an increased detection rate for isolated local recurrences (risk ratio 1.61, 1.12 to 2.32, P=0.011).ConclusionsIntensive follow up after curative resection for colorectal cancer improves survival. Large trials are required to identify which components of intensive follow up are most beneficial.

What is already known on this topic

There is a lack of direct evidence that intensive follow up after initial curative treatment for colorectal cancer leads to increased survivalGuidelines are inconclusive and clinical practice varies widely

What this study adds

The cumulative analysis of available data supports the view that intensive follow up after curative resection for colorectal cancer improves survivalIf computed tomography and frequent measurements of serum carcinoembryonic antigen are used during follow up mortality related to cancer is reduced by 9-13%This survival benefit is partly attributable to the earlier detection of all recurrences, particularly the increased detection of isolated recurrent disease     

Vascular endothelial growth factor gene polymorphisms and colorectal cancer risk: a meta-analysis

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen involved in a number of pathologic processes, including angiogenesis, tumor growth and metastasis. Polymorphisms of the VEGF gene have been associated with susceptibility to colorectal cancer (CRC). However, the specific association still remains controversial. We made a meta-analysis of the association between VEGF gene polymorphisms and CRC risk. Only eight case-control studies were retrieved, with a total of 2337 CRC patients and 2032 healthy controls. Six VEGF gene polymorphisms were addressed in all studies included, +936C>T (rs3025039), -2578C>A (rs699947), -1154G>A (rs1570360), -634G>C (rs2010963), -460C>T (rs833061), and +405C>G (rs2010963). There was a significant association between -2578C>A polymorphism and susceptibility to CRC in the comparison of C allele carriers (CC + CA) versus AA (odds ratio = 0.77, 95% confidence interval = 0.62-0.96, P = 0.02). No association was found between +936C>T, -1154G>A, -634G>C, -460C>T, and +405C>G with susceptibility to CRC. We conclude that the C allele carrier (CC + CA) of VEGF -2578C>A polymorphism appears to be a protective factor for CRC.     

The association of polymorphisms on TGFBR1 and colorectal cancer risk: a meta-analysis

Epidemiological studies found inconsistent results on the association of two variants on TGFBR1 (TGFBR1*6A and Int7G24A) with colorectal cancer (CRC) risk. The present study was aimed to evaluate the association of these two variants with CRC susceptibility via the meta-analysis methods. For variant TGFBR1*6A, nine reports including 6,765 CRC patients and 8,496 unrelated controls were identified. The heterozygotes *6A/*9A showed a significant increased risk of CRC with the pooled OR was 1.12 (95% CI = 1.02–1.23), and the pooled OR for the homozygotes *6A/*6A was 1.13 (95% CI = 0.80–1.58) compared to the homozygotes *9A/*9A. However, under the dominant effect model, the TGFBR1*6A carriers showed a significantly increased CRC risk (pooled OR = 1.12, 95% CI = 1.03–1.23, *6A/*6A and *6A/*9A vs. *9A/*9A). For variant Int7G24A, three case–control studies with 1,074 cases and 1,945 controls were found. Although no significant association was found for heterozygosity Int7G24A carriers with CRC risk (pooled OR = 0.97, 95% CI = 0.67–1.42), the homozygosity A/A carriers showed a significant elevated risk of CRC (pooled OR = 1.68, 95% CI = 1.14–2.47) compared to G/G homozygotes. Under the recessive effect model, homozygotes A/A showed a 71% increase of CRC risk compared to the A/G and G/G genotype carriers (pooled OR = 1.71, 95% CI = 1.17–2.51). These data strongly suggested that the two polymorphisms of TGFBR1 may confer low-penetrance susceptibility of CRC risk.     

IL6 gene polymorphisms and susceptibility to colorectal cancer: a meta-analysis and review

A number of case-control studies were conducted to investigate the association of IL6 gene polymorphisms with colorectal cancer (CRC). However, the results were not always consistent. We performed a systematic review and meta-analysis to examine the association between the IL6 gene polymorphisms and CRC. Data were collected from the following electronic databases: PubMed, EMBASE, Web of Science, BIOSIS Previews, HuGENet, and Chinese Biomedical Literature Database, with the last report up to July 2011. A total of 17 studies involving 4 SNPs were included (16 for rs1800795, 2 for rs1800796, 2 for rs1800797, and 1 for rs13306435). Overall, no significant association of these polymorphisms with CRC was found in heterozygote comparisons as well as homozygote comparison, dominant genetic model and recessive model. In subgroup analysis, among studies using population-based controls, fulfilling Hardy-Weinberg equilibrium, or using Taqman genotyping method, we did not find any significant association. However, the rs1800795 C allele was significantly associated with reduced risk for CRC among persons who regularly or currently took NSAIDs (four studies, OR = 0.750; 95 % CI, 0.64-0.88; P = 0.474 for heterogeneity test), and with increased risk for CRC among persons who drank (one study, OR = 1.97; 95 % CI, 1.32-2.94). Individuals with the rs1800795 C allele in the IL6 gene have a significantly lower risk of CRC, but in the setting of NSAIDs use. Further studies are merited to assess the association between the IL6 gene polymorphisms and CRC risk among persons who take NSAIDs, drink or smoke, etc.     

Association between CYP1A1 polymorphism and colorectal cancer risk: a meta-analysis

Colorectal cancer is one of the most common forms of cancer and is the third leading cause of cancer-related death worldwide. Published data on the association between CYP1A1 (MspI and Ile ⁴⁶² Val) polymorphisms and colorectal cancer risk are inconclusive. To address these issues, we carried out a meta-analysis of available case–control study. Online electronic searches of PubMed were performed. We identified 17 studies (6,673 colorectal cancer patients and 8,102 control subjects) that examined the association between CYP1A1 (MspI and Ile ⁴⁶² Val) polymorphisms and risk of colorectal cancer. For CYP1A1 MspI polymorphism, we performed a meta-analysis from 13 studies including 5,468 cases and 6,492 controls. Overall, there was no statistically significant association between CYP1A1 MspI polymorphism and colorectal cancer susceptibility. In the subgroup analyses based on ethnicities, no statistically significant associations were observed in all genetic models. With respect to CYP1A1 Ile ⁴⁶² Val polymorphism, a total of 14 studies including 6,654 cases and 7,859 controls were involved in this meta-analysis. The CYP1A1 Ile ⁴⁶² Val polymorphism was associated with risk of colorectal cancer. Ethnic subgroup analyses revealed that significant associations were found in Asians and Caucasians. In summary, this meta-analysis suggests that CYP1A1 Ile ⁴⁶² Val polymorphism was a low-penetrance susceptibility gene in colorectal cancer development. On the contrary, CYP1A1 MspI polymorphism does not seem capable of modifying colorectal cancer risk.     

Attempted tests of the surrogacy value of the ED environmental diversity measures highlight the need for corroboration assessment of surrogacy hypotheses

A recent paper in this journal (Hortal et al., 2009) claimed to have evaluated the ED biodiversity surrogates methods of Faith and Walker, 1994, Faith and Walker, 1996, and to have provided evidence for poor performance of the continuous ED method. In fact, their study neither used nor evaluated the continuous ED method. Here, I document their misrepresentation. I then discuss some constructive lessons emerging from their study and other recent studies that have attempted tests of ED surrogacy value. The need to consider the actual degree of support that observed evidence provides for a hypothesis about surrogacy raises general issues for evaluations of indicators’ performance, and suggests a greater role for corroboration assessments. Guidelines for achieving this cover three aspects of surrogates testing: experimental design of tests, ongoing corroboration assessment of evidence produced by tests, and accumulation of lessons learned from multiple test studies over time.     

Survival pattern of colorectal cancer in Sub-Saharan Africa: A systematic review and meta-analysis

Cancer incidence is relatively low in sub-Saharan Africa (SSA), however, prognosis is expected to be poor in comparison with high-income countries. Comprehensive evidence is limited on the survival pattern of colorectal cancer patients in the region. We conducted a systematic review and meta-analysis to investigate the pattern of colorectal cancer survival in the region and to identify variation across countries and over time. We searched international databases MEDLINE, Scopus, Embase, Web of Science, ProQuest, CINAHL, and Google Scholar to retrieve studies that estimated survival from colorectal cancer in SSA countries from inception to December 31, 2021 without language restriction. Due to between-study heterogeneity, we performed a random-effects meta-analysis to pool survival rates. To identify study-level sources of variation, we performed subgroup analysis and meta-regression. Results are reported in line with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2020 guideline and the protocol was registered in PROSPERO database (CRD42021246935). 23 studies involving 10,031 patients were included in the review, of which, 20 were included in the meta-analysis. The meta-analysis results showed that the pooled 1-, 2-, 3-, 4-, and 5-year survival rates in SSA were 0.74 (95% CI, 0.66–0.81), 0.50 (95% CI, 0.41–0.58), 0.36 (95% CI, 0.27–0.47), 0.31 (95% CI, 0.22–0.42), and 0.28 (95% CI, 0.19–0.38) respectively. Subgroup analyses indicated that the survival rate varied according to year of study, in which those conducted in recent decades showed relatively better survival. The 5-year survival was higher in middle-income SSA countries (0.31; 95%CI: 0.17–0.49) than low-income countries (0.20; 95%CI: 0.11–0.35), however, the difference was not statistically significant. In conclusion, survival from colorectal cancer is low in sub-Saharan Africa compared to other regions. Thus, intervention strategies to improve screening, early diagnosis and treatment of colorectal cancer should be developed and implemented to improve survival in the region.     

Best Practicable Aggregation of Species: a step forward for species surrogacy in environmental assessment and monitoring

The available taxonomic expertise and knowledge of species is still inadequate to cope with the urgent need for cost‐effective methods to quantifying community response to natural and anthropogenic drivers of change. So far, the mainstream approach to overcome these impediments has focused on using higher taxa as surrogates for species. However, the use of such taxonomic surrogates often limits inferences about the causality of community patterns, which in turn is essential for effective environmental management strategies. Here, we propose an alternative approach to species surrogacy, the “Best Practicable Aggregation of Species” (BestAgg), in which surrogates exulate from fixed taxonomic schemes. The approach uses null models from random aggregations of species to minimizing the number of surrogates without causing significant losses of information on community patterns. Surrogate types are then selected in order to maximize ecological information. We applied the approach to real case studies on natural and human‐driven gradients from marine benthic communities. Outcomes from BestAgg were also compared with those obtained using classic taxonomic surrogates. Results showed that BestAgg surrogates are effective in detecting community changes. In contrast to classic taxonomic surrogates, BestAgg surrogates allow retaining significantly higher information on species‐level community patterns than what is expected to occur by chance and a potential time saving during sample processing up to 25% higher. Our findings showed that BestAgg surrogates from a pilot study could be used successfully in similar environmental investigations in the same area, or for subsequent long‐term monitoring programs. BestAgg is virtually applicable to any environmental context, allowing exploiting multiple surrogacy schemes beyond stagnant perspectives strictly relying on taxonomic relatedness among species. This prerogative is crucial to extend the concept of species surrogacy to ecological traits of species, thus leading to ecologically meaningful surrogates that, while cost effective in reflecting community patterns, may also contribute to unveil underlying processes. A specific R code for BestAgg is provided.     

Cardiac resynchronization therapy: a meta-analysis of randomized controlled trials

Background

Studies of cardiac resynchronization therapy in addition to an implantable cardioverter defibrillator in patients with mild to moderate congestive heart failure had not been shown to reduce mortality until the recent RAFT trial (Resynchronization/Defibrillation for Ambulatory Heart Failure Trial). We performed a meta-analysis including the RAFT trial to determine the effect of cardiac resynchronization therapy with or without an implantable defibrillator on mortality.

Methods

We searched electronic databases and other sources for reports of randomized trials using a parallel or crossover design. We included studies involving patients with heart failure receiving optimal medical therapy that compared cardiac resynchronization therapy with optimal medical therapy alone, or cardiac resynchronization therapy plus an implantable defibrillator with a standard implantable defibrillator. The primary outcome was mortality. The optimum information size was considered to assess the minimum amount of information required in the literature to reach reliable conclusions about cardiac resynchronization therapy.

Results

Of 3071 reports identified, 12 studies (n = 7538) were included in our meta-analysis. Compared with optimal medical therapy alone, cardiac resynchronization therapy plus optimal medical therapy significantly reduced mortality (relative risk [RR] 0.73, 95% confidence interval [CI] 0.62–0.85). Compared with an implantable defibrillator alone, cardiac resynchronization therapy plus an implantable defibrillator significantly reduced mortality (RR 0.83, 95% CI 0.72–0.96). This last finding remained significant among patients with New York Heart Association (NYHA) class I or II disease (RR 0.80, 95% CI 0.67–0.96) but not among those with class III or IV disease (RR 0.84, 95% CI 0.69–1.07). Analysis of the optimum information size showed that the sequential monitoring boundary was crossed, which suggests no need for further clinical trials.

Interpretation

The cumulative evidence is now conclusive that the addition of cardiac resynchronization to optimal medical therapy or defibrillator therapy significantly reduces mortality among patients with heart failure.Congestive heart failure is currently reaching epidemic proportions in Canada, with 500 000 Canadians affected and 50 000 new patients identified each year.¹ It accounts for more than 100 000 hospital admissions per year and has a one-year mortality ranging from 15% to 50%, depending on the severity of heart failure.² By 2050, the number of patients with heart failure is projected to increase threefold.²Advances in medical therapies have resulted in substantial reductions in mortality associated with congestive heart failure.^3–7 The use of devices has recently become an important adjuvant therapy.⁸ Cardiac resynchronization therapy involves pacing from both the right and left ventricles simultaneously to improve myocardial efficiency (see radiographs in Appendix 1, at www.cmaj.ca/cgi/content/full/cmaj.101685/DC1). Cardiac resynchronization therapy has been shown to reduce morbidity and, when compared with medical therapy alone, to reduce mortality.^9–13 Until recently, it was not shown to reduce mortality among patients who also received an implantable cardioverter defibrillator. Among patients receiving optimal medical therapy, the Resynchronization/Defibrillation for Ambulatory Heart Failure Trial (RAFT) showed the superiority of cardiac resynchronization therapy in addition to an implantable defibrillator over a standard implantable defibrillator in reducing mortality and the combined outcome of death from any cause or hospital admission related to heart failure.¹⁴We performed a meta-analysis to further assess the effect on mortality of cardiac resynchronization therapy with and without an implantable defibrillator among patients with mildly symptomatic and advanced heart failure.     

Synchronous global assessment of gene and protein expression in colorectal cancer progression

Well-established models of colorectal cancer progression are based on the idea that the disease evolves through a multistep process involving sequential genetic mutations, suggesting that progression through clinically defined stages should correlate with well-defined patterns of gene expression. The majority of studies to date, however, have assessed these processes one gene and one protein at a time. We report the first comprehensive assessment of both gene and protein expression performed in parallel across progressive stages of human colorectal neoplasia. Remarkably, despite the global nature of the gene expression assessment, very few genes could be linked with certainty to specific proteins through currently available annotations. Furthermore, the correlation of expression between identified genes and proteins was poor. Nevertheless, both produced expression signatures that differentiated normal mucosa and nonmalignant adenomas from each other and from the malignant carcinomas and both produced fairly consistent subclasses of the malignancies, suggesting that a molecular staging might be more appropriate provided that these profiles can be tied to clinical outcome. This is potentially important as clinical staging is widely used as a prognostic indicator and used in the decision to pursue adjuvant therapies.     

Strengths and weaknesses of immunotherapy for advanced non-small-cell lung cancer: a meta-analysis of 12 randomized controlled trials

Background

Lung cancer is one of the leading causes of cancer death worldwide. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Immunotherapy has yielded no consistent benefit to date for those patients. Assessing the objective efficacy and safety of immunotherapy for advanced NSCLC patients will help to instruct the future development of immunotherapeutic drugs.

Methodology and Principal Findings

We performed a meta-analysis of 12 randomized controlled trials including 3134 patients (1570 patients in the immunotherapy group and 1564 patients in the control group) with histologically confirmed stage IIIA, IIIB, or IV NSCLC. The analysis was executed with efficacy end points regarding overall survival (OS), progression-free survival (PFS), complete response (CR), partial response (PR), and total effective rate. Overall unstratified OS, PFS, PR, and total effective rate were significantly improved in advanced NSCLC patients in the immunotherapy group (P = 0.0007, 0.0004, 0.002, 0.003, respectively), whereas CR was not improved (P = 0.97). Subgroup analysis showed that monoclonal antibody (mAb) immunotherapy significantly improved the PFS, PR, and total effective rate and showed a trend of improving OS of advanced NSCLC patients compared with the control group, with one kind of adverse event being significantly dominant. Compared with the control group, the vaccine subgroup showed no significant difference with regard to serious adverse events, whereas cytokine immunotherapy significantly induced three kinds of serious adverse events.

Conclusions

Immunotherapy works efficiently on advanced NSCLC patients. Of several immunotherapies, mAb therapy may be a potential immunotherapy for advanced NSCLC patients, and become a standard complementary therapeutic approach in the future if the issues concerning toxicity and allergenicity of mAbs have been overcome.     

Red and processed meat and colorectal cancer incidence: meta-analysis of prospective studies

Background

The evidence that red and processed meat influences colorectal carcinogenesis was judged convincing in the 2007 World Cancer Research Fund/American Institute of Cancer Research report. Since then, ten prospective studies have published new results. Here we update the evidence from prospective studies and explore whether there is a non-linear association of red and processed meats with colorectal cancer risk.

Methods and Findings

Relevant prospective studies were identified in PubMed until March 2011. For each study, relative risks and 95% confidence intervals (CI) were extracted and pooled with a random-effects model, weighting for the inverse of the variance, in highest versus lowest intake comparison, and dose-response meta-analyses. Red and processed meats intake was associated with increased colorectal cancer risk. The summary relative risk (RR) of colorectal cancer for the highest versus the lowest intake was 1.22 (95% CI  = 1.11−1.34) and the RR for every 100 g/day increase was 1.14 (95% CI  = 1.04−1.24). Non-linear dose-response meta-analyses revealed that colorectal cancer risk increases approximately linearly with increasing intake of red and processed meats up to approximately 140 g/day, where the curve approaches its plateau. The associations were similar for colon and rectal cancer risk. When analyzed separately, colorectal cancer risk was related to intake of fresh red meat (RR _{for 100 g/day increase}  = 1.17, 95% CI  = 1.05−1.31) and processed meat (RR _{for 50 g/day increase}  = 1.18, 95% CI  = 1.10−1.28). Similar results were observed for colon cancer, but for rectal cancer, no significant associations were observed.

Conclusions

High intake of red and processed meat is associated with significant increased risk of colorectal, colon and rectal cancers. The overall evidence of prospective studies supports limiting red and processed meat consumption as one of the dietary recommendations for the prevention of colorectal cancer.     

Ants as indicators for vertebrate fauna at a local scale: an assessment of cross-taxa surrogacy in a disturbed matrix

We examined the spatial fidelity in the pattern in species richness, abundance and composition of ants, birds, mammals and reptiles in a Eucalyptus vegetation type in Australian tropical savanna woodland. We sampled 32 sites representing intact (uncleared) vegetation, and three treatments of different clearing age (2, 12 and 18 years). We investigated whether each fauna taxon could act a surrogate for pattern in the other, and whether they responded in parallel to time since clearing. Reptiles and mammals were combined into a single group. The correlation between taxa was low for abundance (the best being between rept/mamm and ant abundance R = 0.34) and moderate for species richness (varied from 0.36 to 0.44). Mantel tests identified a moderately strong relationship between bird and rept/mamm composition (R = 0.48). Recent clearing (2–12 years) depleted both abundance and species richness of the vertebrate fauna, whereas ant abundance spiked. Ant species richness was consistent over time since clearing. ANOSIM revealed that clearing age was a strong a priori predictor of birds and rept/mamm composition (Global R = 0.48, 0.65, respectively), whereas it was not for ants (Global R = 0.20). Pair-wise comparisons suggested that for birds, rept/mamm, there was consistent changes in composition from intact woodlands to different aged clearing. This was not the case for ants; most distinct variation in composition occurred between treatments of increasing in clearing age (2–18 years R = 0.69, 12–18 years R = 0.65). The results of this study do not support the use of ants as a surrogate of vertebrates at a local scale in a cleared and intact vegetation mosaic. We acknowledge that identification of universal surrogates and indicators are difficult to find, but funding and political expediency that demand rapid solutions to conservation planning necessitate continued investigation of the merits of using surrogate species.     

Toremifene and tamoxifen have similar efficacy in the treatment of patients with breast cancer: a meta-analysis of randomized trials

A meta-analysis of randomized trials was performed to compare the efficacy of toremifene (TOR) with tamoxifen (TAM) in patients with breast cancer. A total of 4,768 intention-to-treat patients from nine randomized trials were identified, with 2,587 patients in TOR group and 2,181 patients in TAM group. The primary outcomes were objective response rate (ORR), time to progression (TTP), and overall survival (OS). The ORR for TOR group was 26.2 % (303/1,156), whereas the ORR for TAM group was 25.2 % (284/1,128). The pooled RR suggested that the ORR were not statistically different between the two therapeutic groups (RR 1.04, 95 % CI 0.91–1.20, P = 0.57). The median TTP was 6.7 months for the TOR group and 9.7 months for the TAM group. The median OS was 30.1 months for the TOR group and 31.7 months for the TAM group. There were no significant difference in TTP and OS between two therapeutic groups (for TTP: HR 0.91, 95 % CI 0.82–1.00; for OS: HR 1.02, 95 % CI 0.91–1.15). Adverse events were generally similar in two therapeutic groups, but TOR may cause fewer vaginal bleeding (4.0 vs. 6.7 %, P < 0.01), headache (0.2 vs. 3.1 %, P = 0.02) and thromboembolic events (4.7 vs. 7.0 %, P = 0.04). Sensitivity analyses were performed by deleting a single study each time; all the results were not materially altered. In summary, the results of this meta-analysis suggest that TOR and TAM have similar efficacy in the treatment of patients with breast cancer.