Introduction: A variety of factors have been identified in the literature which influence survival following resection of colorectal liver metastases (CRLM). Much of this literature is historical, and its relevance to contemporary practice is not known. The aim of this study was to identify those factors which influence survival during the era of preoperative chemotherapy in patients undergoing resection of CRLM in a UK centre. Methods: All patients having liver resection for CRLM during an 11-year period up to 2011 were identified from a prospectively maintained database. Prognostic factors analysed included tumour size (≥5 or <5 cm), lymph node status of the primary tumour, margin positivity (R1; <1 mm), neo-adjuvant chemotherapy (for liver), tumour differentiation, number of liver metastases (≥4), preoperative carcinoembryonic antigen (CEA; ≥200 ng/ml) and whether metastases were synchronous (i.e. diagnosed within 12 months of colorectal resection) or metachronous to the primary tumour. Overall survival (OS) was compared using Kaplan-Meier plots and a log rank test for significance. Multivariate analysis was performed using a Cox regression model. Statistical analysis was performed in SPSS v19, and p < 0.05 was considered to be significant. Results: 432 patients underwent resection of CRLM during this period (67% male; mean age 64.5 years), and of these, 54 (13.5%) had re-resections. The overall 5-year survival in this series was 43% with an actuarial 10-year survival of 40%. A preoperative CEA ≥200 ng/ml was present in 10% of patients and was associated with a poorer 5-year OS (24 vs. 45%; p < 0.001). A positive resection margin <1 mm was present in 16% of patients, and this had a negative impact on 5-year OS (15 vs. 47%; p < 0.001). Tumour differentiation, number, biliary or vascular invasion, size, relationship to primary disease, nodal status of the primary disease or the use of neo-adjuvant chemotherapy had no impact on OS. Multivariate analysis identified only the presence of a positive resection margin (OR 1.75; p < 0.05) and a preoperative CEA ≥200 ng/ml (OR 1.88; p < 0.01) as independent predictors of poor OS. Conclusion: Despite the wide variety of prognostic factors reported in the literature, this study was only able to identify a preoperative CEA ≥200 ng/ml and the presence of tumour within 1 mm of the resection margin as being of value in predicting survival. These variables are likely to identify patients who may benefit from intensive follow-up to enable early aggressive treatment of recurrent disease.
BackgroundThe prevalence of hyperuricemia and gout has increased in recent decades. The role of dietary fructose in the development of these conditions remains unclear.ObjectiveTo conduct a systematic review and meta-analysis of prospective cohort studies investigating the association fructose consumption with incident gout and hyperuricemia.DesignMEDLINE, EMBASE and the Cochrane Library were searched (through September 2015). We included prospective cohort studies that assessed fructose consumption and incident gout or hyperuricemia. 2 independent reviewers extracted relevant data and assessed study quality using the Newcastle-Ottawa Scale. We pooled natural-log transformed risk ratios (RRs) using the generic inverse variance method. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). The overall quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.Results2 studies involving 125 299 participants and 1533 cases of incident gout assessed the association between fructose consumption and incident gout over an average of 17 years of follow-up. No eligible studies assessed incident hyperuricemia as an outcome. Fructose consumption was associated with an increase in the risk of gout (RR=1.62, 95% CI 1.28 to 2.03, p<0.0001) with no evidence of interstudy heterogeneity (I2=0%, p=0.33) when comparing the highest (>11.8% to >11.9% total energy) and lowest (<6.9% to <7.5% total energy) quantiles of consumption.LimitationsDespite a dose–response gradient, the overall quality of evidence as assessed by GRADE was low, due to indirectness. There were only two prospective cohort studies involving predominantly white health professionals that assessed incident gout, and none assessed hyperuricemia.ConclusionsFructose consumption was associated with an increased risk of developing gout in predominantly white health professionals. More prospective studies are necessary to understand better the role of fructose and its food sources in the development of gout and hyperuricemia.Protocol registration numberNCT01608620.
More than 250 million South and South East Asians use SLT in some form. As cigarettes prices climb up all over the world, more people could potentially take up SLT, particularly in the absence of epidemiological evidence regarding the harmful effects of these products, and SLT being advocated as a means of tobacco harm reduction. Our findings are thus relevant and timely in highlighting the harmful effects of SLT use, with a potential of influencing tobacco control policies in South Asia and beyond.
Targeted therapy plays a pivotal role in cancer therapeutics by countering the drawbacks of conventional treatment like adverse events and drug resistance. Over the last decade, heterocyclic derivatives have received considerable attention as cytotoxic agents by modulating various signaling pathways. Benzothiazole is an important heterocyclic scaffold that has been explored for its therapeutic potential.Benzothiazole-based derivatives have emerged as potent inhibitors of enzymes such as EGFR, VEGFR, PI3K, topoisomerases, and thymidylate kinases. Several researchers have designed, synthesized, and evaluated benzothiazole scaffold-based enzyme inhibitors. Of these, several inhibitors have entered various phases of clinical trials. This review describes the recent advances and developments of benzothiazole architecture-based derivatives as potent anticancer agents.
IntroductionOral potentially malignant disorders (OPMDs) are chronic lesions or conditions characterized by a potential for malignant transformation. Apart from being possible pre-cursors to oral cancer, OPMDs themselves are usually painful and debilitating conditions having an influence on the quality of life, both in terms of pain and social disability. Smokeless tobacco (SLT) use is considered a major risk factor for OPMDs. SLT use is a culturally and socially acceptable habit in South Asia. According to a recent report, 90 % of the SLT burden of the whole world lies in the South Asian countries of Pakistan, India, Sri Lanka, Bangladesh, Bhutan, Nepal, Afghanistan, and Maldives. This review aims to assess the association between the use of various SLT products in South Asia and risk of OPMDs.MethodsThis review will focus on epidemiological studies on the use of SLT and risk modification for OPMDs, which have been carried out in the human population of South Asian countries. Articles reporting estimates of relative risk, e.g., odds ratio (OR) or relative risk (RR) with their 95 % confidence intervals (CI) for SLT users versus non-users. Articles reporting data from which these effect estimates can be computed will be included in the review. We will search MEDLINE, the Science Citation Index (SCI), Scopus, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases for relevant literature using a combination of keywords and MeSH terms, where applicable. Appropriate sources of gray literature will also be included in the search. The electronic searches will be supplemented by a hand search of the bibliographies of the included articles. The included studies will be assessed for their quality using an established quality assessment tool. All relevant data from the included articles will be recorded in an MS Excel spread sheet and then transferred to Rev Man 5.3 to carry out a meta-analysis. Heterogeneity among the estimates will be assessed through the I2 statistic. Sensitivity and subgroup analysis will be carried out to see the effects of individual or group of studies on the pooled effect estimate. Results of the review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.DiscussionThis review may have a potential limitation with regard to the designs of the studies included as we expect that most of the included studies will be of the observational types. We will however try to address this issue by conducting sensitivity and subgroup analysis of similar quality studies.Systematic review registrationPROSPERO CRD42015029705.Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-016-0320-7) contains supplementary material, which is available to authorized users.
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