Thromboprophylaxis for patients with cancer and central venous catheters: a systematic review and a meta-analysis

BACKGROUND.

Central venous catheter (CVC) placement increases the risk of thrombosis and subsequent death in patients with cancer. The objective of this systematic review was to determine the efficacy and safety of anticoagulation in reducing mortality and thromboembolic events in cancer patients with a CVC.

METHODS.

The authors searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and ISI the Web of Science databases. They included randomized controlled trials in patients with cancer comparing unfractionated heparin (UFH), low‐molecular‐weight heparin (LMWH), vitamin K antagonists, fondaparinux, or ximelagatran with no intervention, placebo, or each other. The standard methods of the Cochrane Collaboration were used for the analyses.

RESULTS.

Of 3986 identified citations we included 9 randomized clinical trials, none of which evaluated fondaparinux or ximelagatran. Heparin therapy (UFH or LMWH) was associated with a trend toward a reduction in symptomatic deep venous thrombosis (DVT) (relative risk (RR), 0.43; 95% confidence interval (95% CI), 0.18–1.06), but there was no statistically significant effect on mortality (RR, 0.74; 95% CI, 0.40–1.36), infection (RR, 0.91; 95% CI, 0.36–2.28), major bleeding (RR, 0.68; 95% CI, 0.10–4.78), or thrombocytopenia (RR, 0.85; 95% CI, 0.49–1.46). The effect of warfarin on symptomatic DVT also was not statistically significant (RR, 0.62; 95% CI, 0.30–1.27).

CONCLUSIONS.

The balance of benefits and downsides of thromboprophylaxis in cancer patients with CVC are uncertain. Clinicians together with their patients must weigh these factors carefully when making decisions regarding thromboprophylaxis. Cancer 2008. © 2008 American Cancer Society.     

Anticoagulation for the initial treatment of venous thromboembolism in patients with cancer: a systematic review

BACKGROUND.

The authors compared the relative efficacy and safety of low‐ molecular‐weight heparin (LMWH) and unfractionated heparin (UFH) for the initial treatment of venous thromboembolism (VTE) between patients with and without cancer.

METHODS.

By using Cochrane methodology for systematic reviews, separate meta‐analyses were conducted for subgroups of patients with and without cancer, and relative risks (RRs) were compared for statistical significance. The methodologic quality for each outcome was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach.

RESULTS.

LMWH reduced mortality significantly compared with UFH in patients with cancer (RR of 0.71; 95% confidence interval [95% CI], 0.52‐0.98 [moderate‐quality evidence]) but not in patients without cancer (RR of 0.97; 95% CI, 0.65‐1.46 [low‐quality evidence]). However, the difference in the RR for the 2 subgroups did not reach statistical significance (P = .113). The difference between LMWH and UFH in the effect on recurrent VTE was not statistically significant in the subgroup with cancer (RR of 0.78; 95% CI, 0.29‐2.08 [low‐quality evidence]), in the subgroup without cancer (RR of 0.94; 95% CI, 0.60‐1.46 [low‐quality evidence]), or between the 2 subgroups (P = .367). No data were available for bleeding outcomes, thrombocytopenia, or postphlebitic syndrome.

CONCLUSIONS.

The current results indicated that LMWH most likely is superior to UFH in reducing mortality in the initial treatment of VTE for patients with cancer. There is a need for more and better designed trials to confirm these findings. Cancer 2008. © 2008 American Cancer Society.     

Efficacy of interventions for prevention of chemotherapy‐induced alopecia: A systematic review and meta‐analysis

Chemotherapy‐induced alopecia (CIA) is a highly distressing event for cancer patients, and hence, we here aimed to assess the efficacy of various interventions in the prevention of CIA. We searched PubMed, EMBASE and the Cochrane Library, from June 20, 2013 through August 31, 2013. Two of the authors independently reviewed and selected clinical trials that reported the efficacy of any intervention for prevention of CIA compared with that of controls. Two authors extracted data independently on dichotomized outcome in terms of CIA occurrence. Relative risks (RRs) and 95% confidential intervals (CIs) were calculated for efficacy of CIA prevention by using random‐effect or fixed‐effect models. Out of 691 articles retrieved, a total of eight randomized controlled trials and nine controlled clinical trials involving 1,098 participants (616 interventions and 482 controls), were included in the final analyses. Scalp cooling, scalp compression, a combination of cooling and compression, topical minoxidil and Panicum miliaceum were used as interventions. The participants were mainly breast cancer patients receiving doxorubicin‐ or epirubicin‐containing chemotherapy. Scalp cooling, which is the most popular preventive method, significantly reduced the risk of CIA (RR = 0.38, 95% CI = 0.32–0.45), whereas topical 2% minoxidil and other interventions did not significantly reduce the risk of CIA. No serious adverse effects associated with scalp cooling were reported. Our results suggest that scalp cooling can prevent CIA in patients receiving chemotherapy. However, the long‐term safety of scalp cooling should be confirmed in further studies.     

调强适形放疗在乳腺癌保乳术后应用的系统评价

目的评价早期乳腺癌保乳术后调强适形放疗（IMRT）的疗效。方法计算机检索中文科技期刊全文数据库、中国期刊全文数据库、数字化期刊全文数据库、中国生物医学文献数据库、PubMed、Cochrane Library、SCI及EMBASE数据库,并辅手工检索和其他检索。纳入比较早期乳腺癌保乳术后调强适形放疗与传统放疗（RT）的随机对照试验,根据Cochrane系统评价手册5.0.0质量评价标准进行质量评价,使用RevMan5.0软件进行Meta分析。结果共纳入4个研究（1 440例）。Meta分析显示,与RT相比,IMRT可降低急性湿性皮炎、乳房浮肿和色素沉着的发生。结论IMRT可明显降低急性湿性皮炎的发生,减轻患者痛苦,提高生活质量。     

Deep vein thrombosis in cancer: the scale of the problem and approaches to management.

Patients with cancer have long been recognised to be at high risk of venous thromboembolism (VTE), although the condition remains under diagnosed and under treated in these patients. As a consequence, the morbidity and mortality due to deep venous thrombosis and pulmonary embolism remains unacceptably high in this group. Furthermore, the management of VTE in the presence of malignancy is complex, due both to the effects of the cancer itself and its treatments. Conventional long-term management of VTE involves the use of vitamin K antagonists (VKAs), such as warfarin, to reduce the risk of recurrence. However, this approach is associated with a range of practical difficulties including the need for regular laboratory monitoring, the potential for drug interactions, in addition to the risk of treatment resistance and bleeding in patients with cancer. Recent research indicates that the use of low molecular weight heparin (LMWH) therapy instead of VKAs may be beneficial in these patients. In particular, evidence from a large clinical trial of the LMWH dalteparin indicates that this agent offers an effective alternative to VKAs in the long-term management of VTE, that is free from the practical problems associated with the use of VKAs and without increasing the risk of bleeding.     

西妥昔单抗联合化疗治疗晚期结直肠癌疗效的meta分析

目的:评价西妥昔单抗联合化疗治疗晚期结直肠癌的临床疗效和不良反应。方法:在PubMed、EMBASE、CENTRAL(Cochrane central register of controlled trials)、中国生物医学文献数据库(Chinese biomedical abstract database,CBM)和中国期刊全文数据库(China national knowledge infrastructure database,CNKI)中检索从建库以来至2011年12月关于西妥昔单抗联合化疗治疗晚期结直肠癌的随机对照试验,然后对这些文献进行筛选和质量评价,并对符合标准的文献进行meta分析。结果:纳入5项研究,共3 479例晚期结直肠癌患者。西妥昔单抗联合化疗组(联合组)和化疗组的合并缓解率分别为28.85%和18.63%,合并后的相对危险度(relative risk,RR)(95%可信区间)为2.18(1.24～3.85,P=0.007)。联合组和化疗组3～4级乏力发生率分别为10.91%和7.37%,合并RR值(95%可信区间)为1.46(1.19～1.79,P<0.01);3～4级腹泻发生率分别为20.41%和12.53%,合并RR值(95%可信区间)为1.62(1.37～1.92,P<0.01)。结论:西妥昔单抗联合化疗可以明显提高晚期结直肠癌患者的缓解率,但也增加了3～4级乏力和腹泻的发生率。     

Folic acid supplementation and cancer risk: A meta‐analysis of randomized controlled trials

There are growing data and a continuing controversy over the effect of folic acid supplementation on cancer risk. We conducted a meta‐analysis based on up‐to‐date published relevant randomized trials to further examine this issue. Relative risk (RR) was used to measure the effect of folic acid supplementation on risk of cancer using a random‐effects model. Overall, folic acid supplementation had no significant effect on total cancer incidence (13 trials, n = 49,406, RR = 1.05; 95% CI: 0.99–1.11, p = 0.13), colorectal cancer (seven trials, n = 33,824, 1.01; 0.82–1.23, p = 0.95), other gastrointestinal cancer (two trials, n = 20,228, 1.00; 0.75–1.33, p = 0.99), prostate cancer (five trials, n = 27,065, 1.17; 0.84–1.62, p = 0.35), other genitourinary cancer (two trials, n = 20,228, 0.97; 0.75–1.27, p = 0.84), lung cancer (five trials, n = 31,864, 1.00; 0.84–1.21, p = 0.97), breast cancer (four trials, n = 19,800, 0.82; 0.63–1.07, p = 0.15), hematological malignancy (three trials, n = 25,670, 0.87; 0.64–1.17, p = 0.35) and total cancer mortality (six trials, n = 31,930, 1.02; 0.90–1.15, p = 0.81). However, a significantly reduced risk was observed for melanoma (three trials, n = 19,128, 0.47; 0.23–0.94, p = 0.03). Furthermore, higher total cancer incidence risk was observed among those trials with a higher percent use of lipid‐lowering drugs (>60%, 1.10; 1.00–1.20, p = 0.04), or with lower percent baseline hypertension (≤70%, 1.08; 1.00–1.16, p = 0.057).Consistently, meta‐regression analyses suggested that the similar trend between percent use of lipid‐lowering drugs (p = 0.084) or percent baseline hypertension (p = 0.056) and log‐RR for total cancer incidence associated with folic acid supplementation. Our findings indicate that folic acid supplementation has no significant effect on total cancer incidence, colorectal cancer, prostate cancer, lung cancer, breast cancer or hematological malignancy, but reduces the risk of melanoma.     

Investigating Black-White differences in prostate cancer prognosis: A systematic review and meta-analysis

The case-fatality rate following a diagnosis of prostate cancer is higher for Black men compared to White men. How this elevated rate arises is uncertain, with differences in disease biology, presentation, treatment and comorbidity having been suggested. A systematic search was conducted for articles that reported ethnic differences in overall-survival, prostate cancer specific survival (PSS) or biochemical recurrence. 48 articles met the inclusion criteria. Black men had worse overall survival (risk ratio 1.35, 95% CI 1.23-1.48) but this was not due to comorbidity alone as PSS and risk of biochemical recurrence were also elevated (1.29, 95% CI 1.13-1.47 and 1.34, 95% CI 1.23-1.46, respectively). Studies adjusting for clinical predictors and socioeconomic variables no longer supported a difference in overall survival (1.01, 95% CI 0.88-1.16), but continued to find an increased risk amongst Black men for PSS (1.13, 95% CI 1.00-1.27) and biochemical recurrence (1.25, 95% CI 1.11-1.41). Similar results were seen for studies from the pre-PSA era and free-health care settings. In contrast to others, studies of metastatic cancer did not find evidence of Black-White differences (p for interaction = 0.01). In conclusion, Black men had a poorer prognosis which was not fully explained by comorbidity, PSA screening, or access to free health care, although few studies measure these factors well. Either management differences for local disease and/or biological differences may be behind Black-White differences in prostate cancer prognosis.     

Efficacy and safety of intraoperative radiotherapy in rectal cancer: A systematic review and meta-analysis

BACKGROUNDIn recent years, intraoperative radiotherapy (IORT) has been increasingly used for the treatment of rectal cancer. However, the efficacy and safety of IORT for the treatment of rectal cancer are still controversial.AIMTo evaluate the value of IORT for patients with rectal cancer.METHODSWe searched PubMed, Embase, Cochrane Library, Web of Science databases, and conference abstracts and included randomized controlled trials and observational studies on IORT vs non-IORT for rectal cancer. Dichotomous variables were evaluated by odds ratio (OR) and 95% confidence interval (CI), hazard ratio (HR) and 95%CI was used as a summary statistic of survival outcomes. Statistical analyses were performed using Stata V.15.0 and Review Manager 5.3 software.RESULTSIn this study, 3 randomized controlled studies and 12 observational studies were included with a total of 1460 patients, who are mainly residents of Europe, the United States, and Asia. Our results did not show significant differences in 5-year overall survival (HR = 0.80, 95%CI = 0.60-1.06; P = 0.126); 5-year disease-free survival (HR = 0.94, 95%CI = 0.73-1.22; P = 0.650); abscess (OR = 1.10, 95%CI = 0.67-1.80; P = 0.713), fistulae (OR = 0.79, 95%CI = 0.33-1.89; P = 0.600); wound complication (OR = 1.21, 95%CI = 0.62-2.36; P = 0.575); anastomotic leakage (OR = 1.09, 95%CI = 0.59-2.02; P = 0.775); and neurogenic bladder dysfunction (OR = 0.69, 95%CI = 0.31-1.55; P = 0.369). However, the meta-analysis of 5-year local control was significantly different (OR = 3.07, 95%CI = 1.66-5.66; P = 0.000).CONCLUSIONThe advantage of IORT is mainly reflected in 5-year local control, but it is not statistically significant for 5-year overall survival, 5-year disease-free survival, and complications.     

The Finnish prostate cancer screening trial: Analyses on the screening failures

Prostate cancer (PC) screening with prostate‐specific antigen (PSA) has been shown to decrease PC mortality in the European Randomized Study of Screening for Prostate Cancer (ERSPC). However, in the Finnish trial, which is the largest component of the ERSPC, no statistically significant mortality reduction was observed. We investigated which had the largest impact on PC deaths in the screening arm: non‐participation, interval cancers or PSA threshold. The screening (SA) and control (CA) arms comprised altogether 80,144 men. Men in the SA were screened at four‐year intervals and referred to biopsy if the PSA concentration was ≥4.0 ng/ml, or 3.0–3.99 ng/ml with a free/total PSA ratio ≤16%. The median follow‐up was 15.0 years. A counterfactual exclusion method was applied to estimate the effect of three subgroups in the SA: the non‐participants, the screen‐negative men with PSA ≥3.0 ng/ml and a subsequent PC diagnosis, and the men with interval PCs. The absolute risk of PC death was 0.76% in the SA and 0.85% in the CA; the observed hazard ratio (HR) was 0.89 (95% confidence interval (CI) 0.76–1.04). After correcting for non‐attendance, the HR was 0.78 (0.64–0.96); predicted effect for a hypothetical PSA threshold of 3.0 ng/ml the HR was 0.88 (0.74–1.04) and after eliminating the effect of interval cancers the HR was 0.88 (0.74–1.04). Non‐participating men in the SA had a high risk of PC death and a large impact on PC mortality. A hypothetical lower PSA threshold and elimination of interval cancers would have had a less pronounced effect on the screening impact.     

Comparative efficacy and tolerability of antiemetic prophylaxis for adult highly emetogenic chemotherapy: A network meta‐analysis of 143 randomized controlled trials

Chemotherapy‐induced nausea and vomiting (CINV) is one of the commonest side‐effects among cancer patients. However, there is lacking of hierarchical evidences comparing different antiemetics against highly emetogenic chemotherapy. Therefore, we conducted a network meta‐analysis to investigate their comparative efficacy and tolerability. Randomized controlled trials that compared different antiemetic categories for adult highly emetogenic chemotherapy were included after searching PubMed, Web of Science, Embase and Cochrane Central. Acute‐phase no emesis and no nausea were identified as primary endpoints. We made pairwise and hierarchical calculations by random‐effects model. Effect sizes were presented by odds ratio and 95% confidential interval. Subgroup analysis was additionally performed. 143 randomized trials were included into pooled analysis, containing 22,776 patients and 18 antiemetic categories. 5‐HT₃ RA plus corticosteroid plus NK‐1 RA plus other (5CNO) displayed best protection against both acute emesis (SUCRA: 99.7%) and nausea (95.6%). 5CNO (99.7%) and 5‐HT₃ RA plus corticosteroid plus other (5CO, 85.3%) topped subgroup hierarchies for no‐naivety and anthracycline plus cyclophosphamide (AC)‐based studies. On the other hand, 5‐HT₃ RA plus dopamine RA plus other (5DO) may be best fit for delayed emesis (92.0%) and nausea (92.7%). Subgroups featuring no‐naivety and AC‐based trials preferred 5DO (91.9%) and 5CN (88.6%), respectively. In addition, dopamine RA plus other (DO) had the lowest incidence of TRAE in most circumstances, except for AC‐based subgroup where corticosteroid plus dopamine RA plus other (CDO) preponderated (69.2%). 5CNO and 5DO should be considered as first‐line regimens against highly emetogenic chemotherapy induced acute and delayed CINV, respectively.     

Infectious complications of monoclonal antibodies used in cancer therapy: a systematic review of the evidence from randomized controlled trials

The introduction of monoclonal antibodies (MoAbs) into the treatment of cancer has led to improvements in patient survival. However, to the authors' knowledge, little attention has been paid to the infectious complications associated with their use. The authors performed a systematic review of the literature to identify randomized controlled trials (RCTs) that included in their outcomes a comparison of the infectious complications of a MoAb plus chemotherapy or radiotherapy versus the therapy regimen given without the addition of a MoAb. Twenty RCTs with relevant data regarding the use of MoAbs in patients with hematologic malignancies (10 RCTs) and solid tumors (10 RCTs) were retrieved. Six RCTs compared rituximab in conjunction with the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) versus CHOP alone for the treatment of B-cell non-Hodgkin lymphoma (NHL). No significant increase in the incidence of infections was observed with the addition of rituximab to chemotherapy (based on data from 5 RCTs). However, in patients who were seropositive for the human immunodeficiency virus (HIV), a 12% increase in infection-related deaths and a rate of higher opportunistic infections was associated with the rituximab-containing regimen (data taken from 1 RCT). Five RCTs either compared trastuzumab plus chemotherapy versus chemotherapy alone or trastuzumab monotherapy versus observation in patients with breast cancer. The addition of trastuzumab to the various chemotherapy regimens was found to cause a slight increase in the frequency of high-grade infections while bevacizumab caused a negligible increase in Grade III/IV infections compared with the same regimens given of chemotherapy alone. Based on a single trial, a higher comparable increase in the rate of high-grade infections was noted with the use of cetuximab in addition to chemotherapy compared with chemotherapy alone. MoAbs added to chemotherapy appear to have infectious complications that are comparable to the chemotherapy-alone regimen when administered for the treatment of NHL, with the exception of HIV-seropositive patients. Trastuzumab, which is reported to have a clear benefit in the prognosis of breast cancer patients, was found to cause a small increase in Grade III/IV infectious complications; however, there was no apparent difference in the rate of infection-related death.     

Risk of treatment-related mortality in cancer patients treated with ipilimumab: A systematic review and meta-analysis

BackgroundFatal adverse events (FAEs) have been reported in cancer patients receiving ipilimumab—a monoclonal antibody against cytotoxic T-lymphocyte antigen-4, but the risk of treatment-related mortality is unknown. We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) of ipilimumab to determine the overall risk of FAEs associated with ipilimumab.MethodsWe systematically searched MEDLINE, EMBASE, Cochrane CENTRAL, ClinicalTrial.gov and conference proceedings from inception to December 2016, for prospective trials that randomly assigned patients to ipilimumab treatment (with or without concurrent therapy) or controls with available data regarding incidence of FAEs. Two reviewers extracted data independently. Incidence of FAEs was pooled using a random effects model, and the risk of FAEs associated with ipilimumab was estimated using Peto odds ratios (ORs).ResultsA total of 5775 patients with solid tumours included in 12 RCTs (10 from journal reports and 2 from ClinicalTrials.gov) were included in the meta-analysis. The pooled incidence of FAEs for patients treated with ipilimumab was 1.13% (95% confidence interval [CI], 0.56–1.86), compared with 0.22% in the control arms. Ipilimumab was associated with statistically significantly increased risk of FAEs, with a pooled Peto OR of 2.3 (95% CI, 1.4–3.6; P < 0.001). Analyses according to cancer type (melanoma versus other cancers); treatment mode (combination therapy or monotherapy); control type (active control versus placebo/best supportive care only); ipilimumab dose (high versus low dose [10 versus 3 mg/kg every 3 weeks]) found no statistically significantly differential effect by subgroups. Among the specific causes of FAEs, ipilimumab was associated with an increased risk of fatal gastrointestinal toxicity, with an OR of 4.5 (95% CI, 1.5–13.6).ConclusionThe use of ipilimumab, compared with controls, was associated with increased risk of treatment-related mortality.     

The volume-outcome relation in the surgical treatment of esophageal cancer: a systematic review and meta-analysis

This study was undertaken to conduct a systematic review and meta-analysis of the literature on the relation between procedural volume and outcome of esophagectomies. A systematic search was carried out to identify articles investigating effects of hospital or surgeon volume on short-term and long-term outcomes published between 1995 and 2010. Articles were scrutinized for methodological quality, and after inclusion of only high-quality studies, a meta-analysis assuming a random effects model was done to estimate the effect of higher volume on patient outcome. Heterogeneity in study results was evaluated with an I(2) -test and risk of publication bias with an Egger regression intercept. Forty-three studies were found. Sixteen studies met the strict inclusion criteria for the meta-analysis on hospital volume and postoperative mortality and 4 studies on hospital volume and survival. The pooled estimated effect size was significant for high-volume providers in the analysis of postoperative mortality (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.89-2.80) and in the survival analysis (OR, 1.17; 95% CI, 1.05-1.30). The meta-analysis of surgical volume and outcome showed no significant results. Studies in which the results were adjusted not only for patient characteristics but also for tumor characteristics and urgency of the operation showed a stronger correlation between hospital volume and mortality. Also, studies performed on data from the United States showed higher effect sizes. The evidence for hospital volume as an important determinant of outcome in esophageal cancer surgery is strong. Concentration of procedures in high-volume hospitals with a dedicated setting for the treatment of esophageal cancer might lead to an overall improvement in patient outcome.     

Race in ovarian cancer treatment and survival: a systematic review with meta-analysis

Objective  There has long been recognition of racial disparities in cancer treatment and survival. In order to investigate the etiology of racial disparities in ovarian cancer, we undertook a systematic review of the published literature. Methods  Focusing on North America, our search of MEDLINE, PsychInfo, and EMBASE databases recovered 513 abstracts of which 98 underwent full text screening resulting in 24 studies included in the final review. After assessing heterogeneity, results were pooled where possible in a meta-analysis using a random effects model. Results  Eight articles reported treatment outcomes, nine survival, and seven both. Overall African Americans were less likely to receive any form of surgical treatment for ovarian cancer [pooled relative risk (RR) 1.17 (95% confidence interval (CI): 1.10, 1.23)] compared with white women. Although the majority of the included articles reporting survival outcomes did not control for known covariates such as medical co-morbidities or treatment, we were able to pool the unadjusted results from eight articles. Taken together the meta-analysis of 106,704 women did not find a difference in five-year survival between whites and African Americans, RR 1.07 (95% CI: 0.97, 1.18). When the results were stratified by year of cancer diagnosis, studies which captured patients prior to 1985 yielded a five-year RR of survival for whites compared to African Americans of 0.93 (95% CI: 0.89, 0.97) compared with 1.17 (95% CI: 1.05, 1.31) after 1985. Conclusion  These results suggest that racial disparities in ovarian cancer are not due to underlying biological differences rather to the unequal application of existing treatments. Previous presentation of results  The results from this study were presented at the XVIII IEA World Congress of Epidemiology, September 20–24, 2008 in Porto Alegre, Rio Grande do Sul, Brazil.     

C-reactive protein and colorectal cancer risk: a systematic review of prospective studies

C-reactive protein is a sensitive but nonspecific systemic marker of inflammation. Several prospective studies have investigated the association of prediagnostic circulating C-reactive protein concentrations with the development of colorectal cancer, but the results have been inconsistent. We performed a systematic review of prospective studies of the association between prediagnostic measurements of circulating high-sensitivity C-reactive protein and development of invasive colorectal cancer. Authors of original studies were contacted to acquire uniform data. We combined relative risks (RR) for colorectal cancer associated with a one unit change in natural logarithm-transformed high-sensitivity C-reactive protein using inverse variance weighted random effects models. We identified eight eligible studies, which included 1,159 colorectal cancer cases and 37,986 controls. The summary RR per one unit change in natural log-transformed high-sensitivity C-reactive protein was 1.12 (95% confidence intervals [CI], 1.01-1.25) for colorectal cancer, 1.13 (95% CI, 1.00-1.27) for colon cancer, and 1.06 (95% CI, 0.86-1.30) for rectal cancer. The association was stronger in men (RR, 1.18; 95% CI, 1.04-1.34) compared to women (RR, 1.09; 95% CI, 0.93-1.27) but this difference was sensitive to the findings from a single study. Prediagnostic high-sensitivity C-reactive protein concentrations were weakly associated with an increased risk for colorectal cancer. More work is needed to understand the extent to which circulating high-sensitivity C-reactive protein or other blood inflammatory markers are related to colonic inflammation.     

Bias-corrected estimates of effects of PSA screening decisions on the risk of prostate cancer diagnosis and death: Analysis of the Finnish randomized study of screening for prostate cancer

More information is needed about effects of prostate-specific antigen (PSA) screening for informed decision making. The objective of our study is to evaluate the effects of an implemented screening decision on the risk of prostate cancer (PC) diagnosis and PC death. In a randomized trial, 31,867 Finnish men aged 55–67 years were allocated to the screening arm and 48,282 to the control arm during 1996–1999. Two to three screening rounds were offered to the screening arm with a PSA cut-off of 4.0 ng/ml. A counterfactual exclusion method was used to adjust for the effects of screening noncompliance and PSA contamination on risk of PC death and PC incidence by prognostic group at 15 years of follow up. After correcting for noncompliance and contamination, PSA screening led to 32.4 (95% CI 26.4, 38.6) more PC diagnoses per 1,000 men after 15 years and 1.4 (95% CI 0.0, 2.8) fewer PC deaths compared to the control arm. The corresponding results of an intention-to-screen analysis were 16.5 (95% CI 12.3, 20.7) and 0.8 (95% CI 0.5, 2.0), respectively. These results can be used for patient counseling in informed decision making about PC screening. A limitation of the study was the lack of comprehensive data on contamination.     

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.