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Background: Our systematic review summarizes the evidence concerning the accuracy of serum diagnostic and prognostic tests for colorectal cancer (CRC). Methods: The databases MEDLINE and EMBASE were searched iteratively to identify the relevant literature for serum markers of CRC published from 1950 to August 2012. The articles that provided adequate information to meet the requirements of the meta-analysis of diagnostic and prognostic markers were included. A 2-by-2 table of each diagnostic marker and its hazard ratio (HR) and the confidence interval (CI) of each prognostic marker was directly or indirectly extracted from the included papers, and the pooled sensitivity and specificity of the diagnostic marker and the pooled HR and the CI of the prognostic marker were subsequently calculated using the extracted data. Results: In total, 104 papers related to the diagnostic markers and 49 papers related to the prognostic serum markers of CRC were collected, and only 19 of 92 diagnostic markers were investigated in more than two studies, whereas 21 out of 44 prognostic markers were included in two or more studies. All of the pooled sensitivities of the diagnostic markers with > = 3 repetitions were less than 50%, and the meta-analyses of the prognostic markers with more than 3 studies were performed, VEGF with highest (2.245, CI: 1.347–3.744) and MMP-7 with lowest (1.099, CI: 1.018–1.187)) pooled HRs are presented. Conclusions: The quality of studies addressing the diagnostic and prognostic accuracy of the tests was poor, and the results were highly heterogeneous. The poor characteristics indicate that these tests are of little value for clinical practice. [ABSTRACT FROM AUTHOR]

Background: Some authors have studied the relationship between the presence of polyps, adenomas and cancers of upper gastrointestinal tract (stomach and duodenum) and risk of colorectal polyps and neoplasms; however, the results are controversial, which may be due to study sample size, populations, design, clinical features, and so on. No meta-analysis, which can be generalized to a larger population and could provide a quantitative pooled risk estimate of the relationship, of this issue existed so far. Methods: We performed a meta-analysis to evaluate risk of colorectal polyps or neoplasms in patients with polyps, adenomas or cancers in upper gastrointestinal tract comparing with controls. A search was conducted through PubMed, EMBASE, reference lists of potentially relevant papers, and practice guidelines up to 27 November 2013 without languages restriction. Odd ratios (ORs) were pooled using random-effects models. Results: The search yielded 3 prospective and 21 retrospective case-control studies (n = 37152 participants). The principal findings included: (1) OR for colorectal polyps was 1.15 (95% CI, 1.04–1.26) in the gastric polyps group comparing with control groups; (2) Patients with gastric polyps and neoplasms have higher risk (OR, 1.31 [95% CI, 1.06–1.62], and 1.72 [95% CI, 1.42–2.09], respectively) of colorectal neoplasms comparing with their controls; and (3) Positive association was found between the presence of colorectal neoplasms and sporadic duodenal neoplasms (OR, 2.59; 95% CI, 1.64–4.11). Conclusions: Findings from present meta-analysis of 24 case-control studies suggest that the prevalence of colorectal polyps was higher in patients with gastric polyps than in those without gastric polyps, and the risk of colorectal neoplasms increases significantly in patients with gastric polyps, neoplasms, and duodenal neoplasms. Therefore, screening colonoscopy should be considered for patients with upper gastrointestinal polyps and neoplasms. [ABSTRACT FROM AUTHOR]

Background: Clinical prediction models are increasingly used to predict outcomes such as survival in cancer patients. The aim of this study was threefold. First, to perform a systematic review to identify available clinical prediction models for patients with esophageal and/or gastric cancer. Second, to evaluate sources of bias in the included studies. Third, to investigate the predictive performance of the prediction models using meta-analysis. Methods: MEDLINE, EMBASE, PsycINFO, CINAHL, and The Cochrane Library were searched for publications from the year 2000 onwards. Studies describing models predicting survival, adverse events and/or health-related quality of life (HRQoL) for esophageal or gastric cancer patients were included. Potential sources of bias were assessed and a meta-analysis, pooled per prediction model, was performed on the discriminative abilities (c-indices). Results: A total of 61 studies were included (45 development and 16 validation studies), describing 47 prediction models. Most models predicted survival after a curative resection. Nearly 75% of the studies exhibited bias in at least 3 areas and model calibration was rarely reported. The meta-analysis showed that the averaged c-index of the models is fair (0.75) and ranges from 0.65 to 0.85. Conclusion: Most available prediction models only focus on survival after a curative resection, which is only relevant to a limited patient population. Few models predicted adverse events after resection, and none focused on patient’s HRQoL, despite its relevance. Generally, the quality of reporting is poor and external model validation is limited. We conclude that there is a need for prediction models that better meet patients’ information needs, and provide information on both the benefits and harms of the various treatment options in terms of survival, adverse events and HRQoL. [ABSTRACT FROM AUTHOR]

Background: Image texture analysis is a noninvasive technique for quantifying intratumoral heterogeneity, with derived texture features reported to be closely related to the treatment outcome of tumors. Gastric cancer is one of the most common tumors and the third leading cause of cancer-related deaths worldwide. Although trastuzumab is associated with a survival gain among patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer, optimal patient selection is challenging. The purpose of this study was to determine whether CT texture features of HER2-positive gastric cancer were related to the survival rate after trastuzumab treatment. Methods and Findings: Patients diagnosed with HER2-positive advanced gastric cancer from February 2007 to August 2014 were retrospectively selected. Using in-house built software, histogram features (kurtosis and skewness) and gray-level co-occurrence matrices (GLCM) features (angular second moment [ASM], contrast, entropy, variance, and correlation) were derived from the CT images of HER2-positive advanced gastric cancer in 26 patients. All the patients were followed up for more than 6 months, with no confirmed deaths. The patients were dichotomized into a good and poor survival group based on cutoff points of overall survival of 12 months. A receiver-operating characteristics (ROC) analysis was performed to test the ability of each texture parameter to identify the good survival group. Kaplan–Meier curves for patients above and below each threshold were constructed. Using a threshold of >265.8480 for contrast, >488.3150 for variance, and ≤0.1319×10−3. for correlation, all of the area under the ROC curves showed fair accuracy (>0.7). Kaplan–Meier analysis showed statistically significant survival difference between two groups according to optimal cutoff values of contrast, variance, correlation and ASM. However, as this study had a small number of patients, a further study with a larger population will be needed to validate the results. Conclusions: Heterogeneous texture features on CT images were associated with better survival in patients with HER2-positive advanced gastric cancer who received trastuzumab-based treatment. Therefore, texture analysis shows potential to be a clinically useful imaging biomarker providing additional prognostic information for patient selection. [ABSTRACT FROM AUTHOR]

Esophageal cancer represents the 6th cause of cancer mortality in the World. New treatments led to outcome improvements, but patient selection and prognostic stratification is a critical aspect to gain maximum benefit from therapies. Today, patients are stratified into 9 prognostic groups, according to a staging system developed by the American Joint Committee on Cancer. Recently, trying to better select patients with curing possibilities several authors are reconsidering tumor length as a valuable prognostic parameter. Specifically, endoscopic tumor length can be easily measured with an esophageal endoscopy and, if its utility in esophageal cancer staging is demonstrated, it may represent a simple method to identify high risk patients and an easy-to-obtain variable in prognostic stratification. In this study we retrospectively analyzed 662 patients treated for esophageal cancer, stratified according to cancer histology and current staging system, to assess the possible role of endoscopic tumor length. We found a significant correlation between endoscopic tumor length, current staging parameters and 5-year survival, proving that endoscopic tumor length may be used as a simple risk stratification tool. Our results suggest a possible indication for preoperative therapy in early stage squamocellular carcinoma patients without lymph nodes involvement, who are currently treated with surgery alone. [ABSTRACT FROM AUTHOR]

Purpose: In the developed countries, the incidence of esophageal adenocarcinoma (EAC) is increasing over recent decades. The purpose of this meta-analysis was to arrive at quantitative conclusions about the contribution of alcohol intakes and the progression of Barrett's esophagus. Methods: A comprehensive, systematic bibliographic search of medical literature published up to Oct 2013 was conducted to identify relevant studies. A meta-analysis was conducted for alcohol consumption on the Barrett's esophagus progression. Results: A total of 882 cases in 6,867 individuals from 14 observational studies were indemnified in this meta-analysis. The result of this current meta-analysis, including 10 case-control and 4 cohort studies, indicated that alcohol consumption was not associated with the neoplastic progression in Barrett's esophagus (RR, 1.17; 95% CI, 0.93–1.48). When stratified by the study designs, no significant association was detected in either high vs low group or ever vs never group. Conclusions: Alcohol drinking is not associated with risk of neoplastic progression in Barrett's esophagus. Further well designed studies are needed in this area. [ABSTRACT FROM AUTHOR]

Background: Growing evidence from recent studies has revealed the association of microRNA-21 (mir-21) with outcomes in multiple cancers, but inconsistent findings have been reported, which rationalized a summary and analysis of available data to investigate the prognostic role of mir-21. Materials and Methods: Eligible studies were identified through several search strategies and assessed for quality. Data was extracted from studies in terms of baseline characteristics and key statistics such as hazard ratio (HR), 95% confidence interval (CI) and P value, which were utilized to calculate pooled effect size. Results: 25 studies were included in the meta-analysis to evaluate the prognostic role of mir-21 in malignant tumors. Elevated mir-21 level was demonstrated to moderately predict poor overall survival (OS) (HR = 1.903, 95% CI: 1.713–2.113, P = 0.000) and disease-free survival (DFS) (HR = 1.574, 95% CI: 1.139–2.175, P = 0.006) by the fixed and random effect model respectively. Importantly, subgroup analysis disclosed significant association between increased mir-21 level in cancerous tissue and worse survival status. Furthermore, over-expression of mir-21 was an independent prognostic factor for non-small cell lung cancer (NSCLC) and pancreatic cancer patients, with the pooled HR being 2.153 (95% CI: 1.693–2.739, P = 0.000) and 1.976 (95% CI: 1.639–2.384, P = 0.000). Conclusions: Over-expression of mir-21, especially in cancerous tissue, was effectively predictive of worse prognosis in various carcinomas. Non-invasive circulating mir-21, however, exhibited modest ability to discriminate outcomes. Major concerns about mir-21 assay standardization and selection of specimen need to be fully addressed before its practical implementation in management of cancer. [ABSTRACT FROM AUTHOR]

Background: Drug eluting beads (DEB) are relatively new embolic agents that allow sustained release of chemotherapeutic agents in a localized fashion to the tumor. This technique is associated with reduced systemic side effects relative to systemic chemotherapy and an increase in the dose of antineoplastic agent delivered to the lesion. The meta-analysis was undertaken to assess the effectiveness of DEB-transcatheter arterial chemoembolization (TACE) in the management of hepatocellular cancer. Methods: We searched the Web of Science, PubMed, EBSCO, EMBASE, the Wiley Library and Google Scholar for studies on DEB-TACE in the management of hepatocellular cancer from 1979 to April 2013. The risk of bias was assessed using RevMan 5·1. Random and fixed-effects meta-analytical models were used where indicated, and between-study heterogeneity was assessed. Disease control, complications and severe complications were recorded. Results: Five studies met the selection criteria, three RCTs and two case-control studies, published from 2010 to 2012, included 217 patients in the DEB-TACE group and 237 in the conventional-TACE group. There was no significance over disease control (OR 2.27, 95% CI 0.78–6.63) with moderate between-study heterogeneity (χ2 = 6.83, degrees of freedom [df] = 3; p<0.08; I2 = 56%). Complications in both groups were assessed and no significant difference was observed (χ2 = 6.34, degrees of freedom [df] = 4; p<0.18; I2 = 37%). Severe complications were also assessed and no significant difference was observed (χ2 = 6.47, degrees of freedom [df] = 4; p<0.17; I2 = 38%). No publication bias relating to the above outcomes was detected by funnel plot. DEB-TACE benefited disease control without an increase in complications and severe complications. [ABSTRACT FROM AUTHOR]

Background: The previous published data on the association between CYP1A2*F (rs762551), CYP1B1 Leu432Val (rs1056836), Asn453Ser (rs180040), and Arg48Gly (rs10012) polymorphisms and colorectal cancer risk remained controversial. Methodology/Principal Findings: The purpose of this study is to evaluate the role of CYP1A2*F, CYP1B1 Leu432Val, Asn453Ser, and Arg48Gly genotypes in colorectal cancer susceptibility. We performed a meta-analysis on all the eligible studies that provided 5,817 cases and 6,544 controls for CYP1A2*F (from 13 studies), 9219 cases and 10406 controls for CYP1B1 Leu432Val (from 12 studies), 6840 cases and 7761 controls for CYP1B1 Asn453Ser (from 8 studies), and 4302 cases and 4791 controls for CYP1B1Arg48Gly (from 6 studies). Overall, no significant association was found between CYP1A2*F, CYP1B1 Leu432Val, Asn453Ser, and Arg48Gly and colorectal cancer risk when all the eligible studies were pooled into the meta-analysis. And in the subgroup by ethnicity and source of controls, no evidence of significant association was observed in any subgroup analysis. Conclusions/Significance: In summary, this meta-analysis indicates that CYP1A2*F, CYP1B1 Leu432Val, Asn453Ser, and Arg48Gly polymorphisms do not support an association with colorectal cancer, and further studies are needed to investigate the association. In addition, our work also points out the importance of new studies for CYP1A2*F polymorphism in Asians, because high heterogeneity was found (dominant model: I2 = 81.3%; heterozygote model: I2 = 79.0). [ABSTRACT FROM AUTHOR]

Objectives: To compare surgical efficacy and postoperative recovery of ultrasonic scalpel (USS) with conventional techniques for the resection of gastric carcinoma. Methods: A systematic search of major medical databases (PubMed, Embase, CCRT and CNKI) was conducted. Both randomized and non-randomized controlled trials (RCTs and nRCTs) were considered eligible. Operation time (OT), intraoperative blood loss (BL) and postoperative complications (POC) rates as well as postoperative hospitalization days, number of dissected lymph nodes, abdominal drainage volume and time for recovery of gastrointestinal functions were synthesized and compared. Results: Nineteen studies were included (7 RCTs and 12 nRCTs), in which 1930 patients were enrolled totally (946 in the USS group and 984 in the conventional group). Monopolar electrocautery and ligation were used as the conventional methods. Comparative meta-analysis showed perioperative outcomes were significantly improved using USS compared with conventional surgical instrumentation. OT was reduced from a weighted mean of 185.3 min in the conventional group to 151.0 min in the USS group (MD = −33.30, 95% CI [−41.75, −24.86], p<0.001) and intraoperative BL was decreased from a weighted mean of 217.9 ml in the conventional group to 111.6 ml in the USS group (MD = −113.42, 95% CI [−142.05, −84.79], p<0.001). Results from RCTs subgroup were consistent with those from nRCTs subgroup. The weighted cumulative risk of POC accounted for 8.9% (0%–25%) and 12.9% (5.5%–45%) in the USS and conventional groups, respectively. Pooled estimated results from nRCTs (OR = 0.54, 95% CI [0.27, 1.06], p = 0.07) and RCTs (RR = 0.75, 95% CI [0.44, 1.26], p = 0.27) showed no significant difference between the USS and control groups. Analysis of secondary outcomes showed the improvements of the USS group over control group regarding the number of dissected lymph nodes, postoperative hospitalization days, abdominal drainage volume and time for recovery of gastrointestinal functions. Conclusion: Compared with conventional electrosurgery, the USS is a safe and effective technique with more short-term advantages in open surgery for gastric cancer. [ABSTRACT FROM AUTHOR]

Objective: The prognostic significance of circulating tumor cells (CTCs) is controversial in gastric cancer (GC). We performed a meta-analysis of available studies to assess its prognostic value detected by RT-PCR for patients diagnosed with GC. Methods: EMBase, PubMed, Ovid, Web of Science, Cochrane library and Google Scholar database search was conducted on all studies reporting the outcomes of interest. The studies were set up according to the inclusion/exclusion criteria. Meta-analysis was performed by using a random-effects model; hazard ratio (HR), risk ratio (RR) and their 95% confidence intervals (95% CIs) were set as effect measures. The information about trial design, results from the data was independently extracted. Heterogeneity of the studies was tested for each pooled analysis. Results: Nineteen studies published matched the selection criteria and were included in this meta-analysis. CTCs positivity was significantly associated with poor relapse free survival (RFS) (HR 2.42, 95% CI: [1.94–3.02]; P<0.001) and poor overall survival (OS) (HR 2.42, 95% CI: [1.94–3.02]; P<0.001). CTCs positivity were also significantly associated with regional lymph nodes (RLNs) metastasis (RR 1.42, 95% CI: [1.20–1.68]; p<0.0001), depth of infiltration (RR 1.51, 95% CI: [1.27–1.79]; p<0.0001), vascular invasion (RR  = 1.43, 95% CI: [1.18–1.74], p = 0.0002) and TNM stage(I,II versus III) (RR 0.63, 95% CI [0.48–0.84]; p = 0.001). Conclusion: Preoperative CTCs positivity indicates poor prognosis in patients with gastric cancer, and associated with poor clinicopathological prognostic factors. [ABSTRACT FROM AUTHOR]

Background: The Xeroderma pigmento-sum group D gene (XPD) plays a key role in nucleotide excision repair. Single nucleotide polymorphisms (SNP) located in its functional region may alter DNA repair capacity phenotype and cancer risk. Many studies have demonstrated that XPD polymorphisms are significantly associated with digestive tract cancers risk, but the results are inconsistent. We conducted a comprehensive meta-analysis to assess the association between XPD Lys751Gln polymorphism and digestive tract cancers risk. The digestive tract cancers that our study referred to, includes oral cancer, esophageal cancer, gastric cancer and colorectal cancer. Methods: We searched PubMed and EmBase up to December 31, 2012 to identify eligible studies. A total of 37 case-control studies including 9027 cases and 16072 controls were involved in this meta-analysis. Statistical analyses were performed with Stata software (version 11.0, USA). Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Results: The results showed that XPD Lys751Gln polymorphism was associated with the increased risk of digestive tract cancers (homozygote comparison (GlnGln vs. LysLys): OR = 1.12, 95% CI = 1.01–1.24, P = 0.029, Pheterogeneity = 0.133). We found no statistical evidence for a significantly increased digestive tract cancers risk in the other genetic models. In the subgroup analysis, we also found the homozygote comparison increased the susceptibility of Asian population (OR = 1.28, 95% CI = 1.01–1.63, P = 0.045, Pheterogeneity = 0.287). Stratified by cancer type and source of control, no significantly increased cancer risk was found in these subgroups. Additionally, risk estimates from hospital-based studies and esophageal studies were heterogeneous. Conclusions: Our meta-analysis suggested that the XPD 751Gln/Gln genotype was a low-penetrate risk factor for developing digestive tract cancers, especially in Asian populations. [ABSTRACT FROM AUTHOR]

Background: Previous studies suggested that diabetes mellitus was associated with cancer risk and prognosis, but studies investigating the relationship between diabetes mellitus and survival in patients with hepatocellular carcinoma (HCC) reported inconsistent findings. To derive a more precise estimate of the prognostic role of diabetes mellitus in HCC, we systematically reviewed published studies and carried out a meta-analysis. Methods: Eligible articles were identified in electronic databases from their inception through September 16, 2013. To evaluate the correlation between diabetes mellitus and prognosis in HCC, the pooled hazard ratios (HR) and their 95% confidence intervals (95% CI) for poorer overall and disease-free survivals were calculated by standard meta-analysis techniques with fixed-effects or random-effects models. Results: 21 studies with a total of 9,767 HCC patients stratifying overall survival and/or disease-free survival in HCC patients by diabetes mellitus status were eligible for meta-analysis. 20 studies with a total of 9,727 HCC cases investigated the overall survival, and 10 studies with a total of 2,412 HCC patients investigated the disease-free survival. The pooled HRs for overall survival and disease-free survival were 1.46 (95% CI, 1.29 to 1.66; P<0.001) and 1.57 (95% CI, 1.21 to 2.05; P = 0.001), respectively. The adjusted HRs for overall survival and disease-free survival were 1.55 (95% CI, 1.27 to 1.91; P<0.001) and 2.15 (95% CI, 1.75 to 2.63; P<0.001), respectively. In addition, for patients receiving hepatic resection, diabetes mellitus was associated with both poorer overall survival and poorer disease-free survival, and for patients receiving non-surgical treatment or patients receiving radiofrequency ablation, diabetes mellitus was associated with poorer overall survival. There was no evidence for publication bias. Conclusion: Diabetes mellitus is independently associated with both poorer overall survival and poorer disease-free survival in HCC patients. [ABSTRACT FROM AUTHOR]

Purpose: Tumor-infiltrating FoxP3+ T cells have been reported in various human tumors, which impaired cell-mediated immunity and promoted disease progression. However, its prognostic value for survival in patients with different gastrointestinal cancers [hepatocellular carcinoma (HCC), colorectal cancer (CRC), gastric cancer (GC)] remains controversial. Methods: Relevant literature was searched using PubMed, Embase, Cochrane, Ovid Medline and Chinese wanfang databases. A meta-analysis was conducted to estimate pooled survival and recurrence ratios. The odds ratio (OR) and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. Results: For HCC and GC, the overall survival at 1, 3 and 5-year of high FoxP3+ T cells infiltration patients were lower than low FoxP3+ T cells infiltration patients (P<0.05). The recurrences at 1, 3 and 5-year of high FoxP3+ T cells infiltration patients were higher than low FoxP3+ T cells infiltration patients (P<0.001). But for CRC, the overall survival at 1, 3 and 5-year of high FoxP3+ T cells infiltration patients were higher than low FoxP3+ T cells infiltration patients (P<0.001). There were no differences in 1, 3 and 5-year recurrences between high and low FoxP3+ T cells infiltration patients (P>0.05). Conclusions: Our findings suggested that tumor-infiltrating FoxP3+ T cells were a factor for a poor prognosis for HCC and GC, but a good prognosis for CRC. [ABSTRACT FROM AUTHOR]

Background and Aim: The optimal treatment for huge unresectable hepatocellular carcinoma (HCC) remains controversial. The outcome of transcatheter arterial chemoembolization (TACE) for patients huge unresectable HCC is generally poor and the survival benefit of TACE in these patients is unclear. The aim of the study is to compare the effect of hepatic arterial infusion chemotherapy (HAIC) versus symptomatic treatment in patients with huge unresectable HCC. Methods: Since 2000 to 2005, patients with huge (size >8cm) unresectable HCC were enrolled. Fifty-eight patients received HAIC and 44 patients received symptomatic treatment. In the HAIC group, each patient received 2.4+1.4 (range: 1–6) courses of HAIC. Baseline characteristics and survival were compared between the HAIC and symptomatic treatment groups. Results: The HAIC group and the symptomatic treatment group were similar in baseline characteristics and tumor stages. The overall survival rates at one and two years were 29% and 14% in the HAIC group and 7% and 5% in the symptomatic treatment group, respectively. The patients in the HAIC group had significantly better overall survival than the symptomatic treatment group (P<0.001). Multivariate analysis revealed that HAIC was the significant factor associated with the overall survival (relative risk: 0.321, 95% confidence interval: 0.200–0.515, P<0.001). None of the patients died due to immediate complications of HAIC. Conclusions: HAIC is a safe procedure and provides better survival than symptomatic treatment in patients with huge unresectable HCC. [ABSTRACT FROM AUTHOR]

Background: Previous studies have yielded conflicting results regarding the relationship between p53 status and response to chemotherapy in patients with gastric cancer. We therefore performed a meta-analysis to expound the relationship between p53 status and response to chemotherapy. Methods/Findings: Thirteen previously published eligible studies, including 564 cases, were identified and included in this meta-analysis. p53 positive status (high expression of p53 protein and/or a mutant p53 gene) was associated with improved response in gastric cancer patients who received chemotherapy (good response: risk ratio [RR]  = 0.704; 95% confidence intervals [CI]  = 0.550–0.903; P = 0.006). In further stratified analyses, association with a good response remained in the East Asian population (RR = 0.657; 95% CI = 0.488–0.884; P = 0.005), while in the European subgroup, patients with p53 positive status tended to have a good response to chemotherapy, although this did not reach statistical significance (RR = 0.828, 95% CI = 0.525–1.305; P = 0.417). As five studies used neoadjuvant chemotherapy (NCT) and one used neoadjuvant chemoradiotherapy (NCRT), we also analyzed these data, and found that p53 positive status was associated with a good response in gastric cancer patients who received chemotherapy-based neoadjuvant treatment (RR = 0.675, 95% CI = 0.463–0.985; P = 0.042). Conclusion: This meta-analysis indicated that p53 status may be a useful predictive biomarker for response to chemotherapy in gastric cancer. Further prospective studies with larger sample sizes and better study designs are required to confirm our findings. [ABSTRACT FROM AUTHOR]

Background: Distinguishing early gastric cancer is challenging with current imaging techniques. Narrow band imaging (NBI) is effective for characterizing gastric lesions. Objectives: The aim of this meta-analysis was to estimate the diagnostic accuracy of NBI in the gastric intestinal metaplasia (GIM). Methods: We performed data analysis using Meta-DiSc (version 1.4) and STATA (version 11.0) software. To assess study quality and potential for bias, we used the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Results: Six studies involving 347 patients were included. On a per-patient basis, the sensitivity of NBI for diagnosis of GIM was 0.65 (95% CI  =  0.56–0.74), and the specificity was 0.93 (95% CI  =  0.88–0.97). The area under the summary receiver operating characteristic (SROC) curve was 0.8731. However, on a per-lesion basis, the sensitivity and specificity of NBI were 0.69 (95% CI  =  0.63–0.74) and 0.91 (95% CI  =  0.87–0.94), respectively. The SROC was 0.9009. The pooled sensitivity and specificity of magnification endoscopy (NBI-ME) were 0.76 (95% CI  =  0.61–0.87) and 0.89 (95% CI  =  0.80–0.94), respectively, on per-patient analysis. On a per-lesion basis, the pooled sensitivity and specificity of NBI-ME were 0.84 (95% CI  =  0.76–0.89) and 0.93 (95% CI  =  0.89–0.96), respectively. Heterogeneity was observed with an I2 for diagnostic odds ratio (DOR) of 0.01% and 85.8%, respectively. There was no statistical significance for the evaluation of publication bias. Conclusions: Our meta-analysis shows that NBI is a useful tool for differential diagnosis of GIM with relatively low sensitivity and high specificity. [ABSTRACT FROM AUTHOR]

Objective: Cyclooxygenase-2 (COX-2) is an inducible enzyme converting arachidonic acid to prostaglandins and playing important roles in inflammatory diseases as well as tumor development. Previous studies investigating the association between COX-2 polymorphisms and colorectal cancer (CRC) risk reported conflicting results. We performed a meta-analysis of all available studies to explore this association. Methods: All studies published up to October 2013 on the association between COX-2 polymorphisms and CRC risk were identified by searching electronic databases PubMed, EMBASE, and Cochrane library. The association between COX-2 polymorphisms and CRC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). Results: Ten studies with 6,774 cases and 9,772 controls were included for −1195A>G polymorphism, 13 studies including 6,807 cases and 10,052 controls were available for −765G>C polymorphism, and 8 studies containing 5,121 cases and 7,487 controls were included for 8473T>C polymorphism. With respect to −765G>C polymorphism, we did not find a significant association with CRC risk when all eligible studies were pooled into the meta-analysis. However, in subgroup analyses by ethnicity and cancer location, with a Bonferroni corrected alpha of 0.05/2, statistical significant increased CRC risk was found in the Asian populations (dominant model CC+CG vs. GG: OR = 1.399, 95%CI: 1.113–1.760, P = 0.004) and rectum cancer patients (CC vs. GG: OR = 2.270, 95%CI: 1.295–3.980, P = 0.004; Recessive model CC vs. CG+GG: OR = 2.269, 95%CI: 1.297–3.970, P = 0.004). In subgroup analysis according to source of control, no significant association was detected. With respect to −1195A>G and 8473T>C polymorphisms, no significant association with CRC risk was demonstrated in the overall and subgroup analyses. Conclusions: The present meta-analysis suggests that the COX-2 −765G>C polymorphism may be a risk factor for CRC in Asians and rectum cancer patients. Further large and well-designed studies are needed to confirm this association. [ABSTRACT FROM AUTHOR]

Objective: Cyclin D1 plays a vital role in cancer cell cycle progression and is overexpressed in many human cancers, including colorectal cancer (CRC). However, the prognostic value of cyclin D1 overexpression in colorectal cancer is conflicting and heterogeneous. We conducted a meta-analysis to more precisely evaluate its prognostic significance. Methods: A comprehensive literature search for relevant studies published up to January 2014 was performed using PubMed, EMBASE, and ISI Web of Science. The pooled hazard ratio (HR) with 95% confidence intervals (CI) was used to estimate the effects. Results: 22 studies with 4150 CRC patients were selected to evaluate the association between cyclin D1 and overall survival (OS), disease-free survival (DFS) and clinicopathological parameters. In a random-effects model, the results showed that cyclin D1 overexpression in CRC was significantly associated with both poor OS (HR = 0.73, 95% CI: 0.63–0.85, P<0.001) and DFS (HR = 0.60, 95% CI: 0.44–0.82, P = 0.001). Additionally, cyclin D1 overexpression was significantly associated with more relative older patients (≥60 years) (OR 0.62, 95% CI 0.44–0.89, P = 0.009), T3,4 tumor invasion (OR 0.70, 95% CI 0.57–0.85, P<0.001), N positive (OR 0.75, 95% CI 0.60–0.95, P = 0.016) and distant metastasis (OR 0.60, 95% CI 0.36–0.99, P = 0.047) of CRC. Conclusion: The meta-analysis results indicated that cyclin D1 is an unfavorable prognostic factor for CRC. Cyclin D1 overexpression might be associated with poor clinical outcome and some clinicopathological factors such as age, T category, N category and distant metastasis in CRC patients. [ABSTRACT FROM AUTHOR]

Escalation with overdose control (EWOC) is a Bayesian adaptive phase I clinical trial design that produces consistent sequences of doses while controlling the probability that patients are overdosed. However, this design does not take explicitly into account the time it takes for a patient to exhibit dose limiting toxicity (DLT) since the occurrence of DLT is ascertained within a predetermined window of time. Models to estimate the Maximum Tolerated Dose (MTD) that use the exact time when the DLT occurs are expected to be more precise than those where the variable of interest is categorized as presence or absence of DLT, given that information is lost in the process of categorization of the variable. We develop a class of parametric models for time to toxicity data in order to estimate the MTD efficiently, and present extensive simulations showing that the method has good design operating characteristics relative to the original EWOC and a version of time to event EWOC (TITE-EWOC) which allocates weights to account for the time it takes for a patient to exhibit DLT. The methodology is exemplified by a cancer phase I clinical trial we designed in order to estimate the MTD of Veliparib (ABT-888) in combination with fixed doses of gemcitabine and intensity modulated radiation therapy in patients with locally advanced, un-resectable pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background: The diagnostic yield of light blue crest(LBC) sign, which was observed by narrow band imaging with magnification endoscopy(NBI-ME), in detecting gastric intestinal metaplasia(IM) has shown variable results. Objective: We aimed to assess the diagnostic value of LBC under NBI-ME for detecting gastric IM. Methods: We performed a literature search of the Medline/PubMed, Embase, Web of Science, Science Direct and the Cochrane Library Databases; and a meta-analysis of pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and SROC area under the curve, using fixed- and random-effects models, for the accuracy of LBC-based IM diagnosis. Results: We initially included 4 articles, but excluded 1 article to counter significant heterogeneity. When pooled, the remaining 3 articles, which included 247 patients with 721 lesions, showed the following patterns in IM diagnosis: sensitivity: 0.90 (95% confidence interval [CI] 0.86–0.92); specificity: 0.90 (95% CI 0.86–0.93), positive likelihood ratio: 8.98 (95% CI 6.42–12.58), negative likelihood ratio: 0.12 (95% CI 0.09–0.16), and SROC area under the curve: 0.9560. Limitations: As the studies varied by their definitions for positive LBC, endoscopy types, biopsy protocols, race of patient cohort, and physicians' proficiency, some sample sizes were limited so that subgroup analyses could not be performed. Conclusion: We concluded that observing LBC under NBI-ME is an accurate and precise means of diagnosing gastric IM. [ABSTRACT FROM AUTHOR]

Purpose: This study was to quantitatively summarize published data for evaluating the clinical and prognostic significance of four proteins involved in hypoxia-inducible factor-1 (HIF-1α) regulation of the metastasis cascade. Methods: Searches were performed using the MEDLINE, EMBASE, Cochrane Library, and Chinese Biomedicine databases without any language restrictions. Studies were pooled and either the summary risk ratio (RR) or odds ratio (OR) was calculated. Potential sources of heterogeneity were sought out via subgroup and sensitivity analyses, and publication bias was also performed. Results: Seventeen studies evaluated HIF-1α, 20 studies evaluated phosphatase and tensin homolog (PTEN), 20 studies evaluated Survivin, and 16 studies evaluated CD44v6. Our results showed that increased HIF-1α expression was linked to a poor 5-year overall survival (RR = 1.508; 95% confidence interval (CI) 1.318–1.725; P<0.001). Decreased survival was heavily influenced by advanced tumor invasion (OR = 3.050; 95% CI 2.067–4.501; P<0.001), lymph node metastasis (1415 patients; OR = 3.486, 95% CI 2.737–4.440; P<0.001), distant metastasis (OR = 6.635; 95% CI 1.855–23.738; P = 0.004), vascular invasion (OR = 2.368; 95% CI 1.725–3.252; P<0.001), dedifferentiation (OR = 2.112; 95% CI 1.410–3.163; P<0.001), tumor size (OR = 1.921; 95% CI 1.395–2.647; P<0.001), and a higher TNM stage (OR =  2.762; 95% CI 1.941–3.942; P<0.001). Similarly, aberrant expression of PTEN, CD44v6, and Survivin were also observed in tumors that correlated with poor OS. The higher ORs of death at 5 years were 1.637 (95% CI = 1.452–1.845; P<0.001), 1.901 (95% CI = 1.432–2.525; P<0.001), and 1.627 (95% CI = 1.384–1.913; P<0.001), respectively, with an OR>2 for the main stratified meta-analyses of clinical factors. Conclusions: Our findings indicate that HIF-1α/PTEN/CD44v6/Survivin, as measured by immunohistochemistry, can be used to predict the prognosis and potential for invasion and metastasis in Asian patients with gastric cancer. The development of strategies against this subset of proteins could lead to new therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background & Aims: IL28B polymorphisms were shown to be strongly associated with the response to interferon therapy in chronic hepatitis C (CHC) and spontaneous viral clearance. However, little is known about how these polymorphisms affect the natural course of the disease. Thus, we conducted the present meta-analysis to assess the impact of IL28B polymorphisms on disease progression. Methods: A literature search was conducted using MEDLINE, EMBASE, and the Cochrane Library. Integrated odds ratios (OR) were calculated with a fixed-effects or random-effects model based on heterogeneity analyses. Results: We identified 28 studies that included 10,024 patients. The pooled results indicated that the rs12979860 genotype CC was significantly associated (vs. genotype CT/TT; OR, 1.122; 95%CI, 1.003–1.254; P = 0.044), and that the rs8099917 genotype TT tended to be (vs. genotype TG/GG; OR, 1.126; 95%CI, 0.988–1.284; P = 0.076) associated, with an increased possibility of severe fibrosis. Both rs12979860 CC (vs. CT/TT; OR, 1.288; 95%CI, 1.050–1.581; P = 0.015) and rs8099917 TT (vs. TG/GG; OR, 1.324; 95%CI, 1.110–1.579; P = 0.002) were significantly associated with a higher possibility of severe inflammation activity. Rs8099917 TT was also significantly associated with a lower possibility of severe steatosis (vs. TG/GG; OR, 0.580; 95%CI, 0.351–0.959; P = 0.034), whereas rs12979860 CC was not associated with hepatic steatosis (vs. CT/TT; OR, 1.062; 95%CI, 0.415–2.717; P = 0.901). Conclusions: IL28B polymorphisms appeared to modify the natural course of disease in patients with CHC. Disease progression seems to be promoted in patients with the rs12979860 CC and rs8099917 TT genotypes. [ABSTRACT FROM AUTHOR]

Background: Several studies suggest that metformin has the potential effect of reducing cancer risk. However, its survival benefit in patients with colorectal cancer (CRC) and diabetes is unknown. The aim of our study is to address the effect of metformin on outcomes for CRC based on a systematic review and meta-analysis. Methods and Findings: We searched EMBASE and MEDLINE databases from inception through August, 2013, using search terms related to metformin, diabetes, colorectal cancer, and prognostic outcome. The outcome measures were hazard ratios (HRs) with 95% CIs comparing CRC survival in diabetic patients using metformin and without using metformin. The primary end points were overall survival (OS) and CRC specific survival (CS). A total of six cohort studies including 2,461 patients met full eligibility criteria. The pooled HR favoring metformin users was 0.56 for OS (95% CI, 0.41 to 0.77) and 0.66 for CRC-specific survival (95% CI, 0.50 to 0.87). Thus metformin therapy reduced the risk of all cause of death by 44% and the risk of CRC specific death by 34% in CRC patients compared to those in non-users. However, evidence of heterogeneity and possible publication bias was noted for OS. Conclusions: Patients with CRC and diabetes treated with metformin appear to have an improved survival outcome. Prospective study should be warranted to examine the association between metformin exposure intensity as well as some other confounding variables and survival outcome in diabetic CRC patients. [ABSTRACT FROM AUTHOR]

Background and Aim: A large number of studies have tried to combine sorafenib with TACE for patients with unresectable hepatocellular carcinoma (HCC) and the results were controversial. We conducted this systematic review and meta-analysis to evaluate the safety and efficacy of combination therapy of sorafenib and TACE in the management of unresectable HCC. Methods: MEDLINE, PsycINFO, Scopus, EMBASE, and the Cochrane Library were searched from January 1990 to October 2013 and these databases were searched for appropriate studies combining TACE and sorafenib in treatment of HCC. Two authors independently reviewed the databases and extracted the data and disagreements were resolved by discussion. Effective value and safety were analyzed. Effective value included disease control rate (DCR), time to progression (TTP) and overall survival (OS). Results: 17 studies were included in the study. In the 10 noncomparative studies, DCR ranged from 18.4 to 91.2%. Median TTP ranged from 7.1 to 9.0 months, and median OS ranged from 12 to 27 months. In the 7 comparative studies, the hazard ratio (HR) for TTP was found to be 0.76 (95% CI 0.66–0.89; P<0.001) with low heterogeneity among studies (P = 0.243; I2 = 25.5%). However, the HR for OS was found to be 0.81 (95% CI 0.65–1.01; P = 0.061) with low heterogeneity among studies (P = 0.259; I2 = 25.4%). The common toxicities included fatigue, diarrhea, nausea, hand foot skin reaction (HFSR), hematological events, hepatotoxicity, alopecia, hepatotoxicity, hypertension and rash/desquamation. AEs are generally manageable with dose reductions. Conclusions: Combination therapy may bring benefits for unresectable HCC patients in terms of TTP but not OS. Further well-designed randomized controlled studies are needed to confirm the efficacy of combination therapy. [ABSTRACT FROM AUTHOR]

Objective: To expand the current knowledge on the feasibility and safety of laparoscopic total gastrectomy (LTG) for gastric cancer in comparison with open total gastrectomy (OTG). Background: Additional studies comparing laparoscopic versus open total gastric resection have been published, and it is necessary to update the meta-analysis of this subject. Methods: Original articles compared LTG and OTG for gastric cancer, which published in English from January 1990 to July 2013 were searched in PubMed, Embase, and Web of Knowledge by two reviewers independently. Operative time, blood loss, harvested lymph nodes, proximal resection margin, analgesic medication, first flatus day, first oral intake, postoperative hospital stay, postoperative complications, hospital mortality, 5-year overall survival (OS) and disease-free survival (DFS) were compared using STATA version 10.1. Results: 17 studies were selected in this analysis, which included a total of 2313 patients (955 in LTG and 1358 in OTG). LTG showed longer operative time, less blood loss, fewer analgesic uses, earlier passage of flatus, quicker resumption of oral intake, earlier hospital discharge, and reduced postoperative morbidity. The number of harvested lymph nodes, proximal resection margin, hospital mortality, 5-year OS and DFS were similar. Conclusion: LTG had the benefits of less blood loss, less postoperative pain, quicker bowel function recovery, shorter hospital stay and lower postoperative morbidity, at the price of longer operative time. There were no statistical differences in lymph node dissection, resection margin, hospital mortality, and long-term outcomes, which indicated the similar oncological safety with OTG. A positive trend was indicated towards LTG. So LTG can be performed as an alternative to OTG by the experienced surgeons in high-volume centers. Whereas, due to the relative small sample size of long-term outcomes and lack of randomized control trials, more studies are required. [ABSTRACT FROM AUTHOR]

Objective: To identify, on the basis of past performance, those hospitals that demonstrate good outcomes in sufficient numbers to make it likely that they will provide adequate quality of care in the future, using a combined measure of volume and outcome (CM-V&O). To compare this CM-V&O with measures using outcome-only (O-O) or volume-only (V-O), and verify 2010-quality of care assessment on 2011 data. Design: Secondary analysis of clinical audit data. Setting: The Dutch Surgical Colorectal Audit database of 2010 and 2011, the Netherlands. Participants: 8911 patients (test population, treated in 2010) and 9212 patients (verification population, treated in 2011) who underwent a resection of primary colorectal cancer in 89 Dutch hospitals. Main Outcome Measures: Outcome was measured by Observed/Expected (O/E) postoperative mortality and morbidity. CM-V&O states 2 criteria; 1) outcome is not significantly worse than average, and 2) outcome is significantly better than substandard, with ‘substandard care’ being defined as an unacceptably high O/E threshold for mortality and/or morbidity (which we set at 2 and 1.5 respectively). Results: Average mortality and morbidity in 2010 were 4.1 and 24.3% respectively. 84 (94%) hospitals performed ‘not worse than average’ for mortality, but only 21 (24%) of those were able to prove they were also ‘better than substandard’ (O/E<2). For morbidity, 42 hospitals (47%) met the CM-V&O. Morbidity in 2011 was significantly lower in these hospitals (19.8 vs. 22.8% p<0.01). No relationship was found between hospitals' 2010 performance on O-O en V-O, and the quality of their care in 2011. Conclusion: CM-V&O for morbidity can be used to identify hospitals that provide adequate quality and is associated with better outcomes in the subsequent year. [ABSTRACT FROM AUTHOR]

Background: The incidence of esophageal and gastric cancer has been increasing rapidly worldwide in recent years, although the reason for this increase is unclear. Here, a statistical synthesis of studies that evaluated the association between physical activity, a well-known protecting factor against death and other chronic diseases, and the risk of esophageal and gastric cancer was performed. Methods: Potentially suitable studies were identified using Medline and Embase. The reference lists of all included articles and those of several recent reviews were searched manually. Studies were included if they (1) were published as case-control or cohort studies evaluating the association between physical activity and risk of esophageal or gastric cancer; and (2) reported point estimates (i.e., risk ratios, odds ratios) and measures of variability (i.e., 95% confidence intervals [CIs]) for physical activity and risk of esophageal or gastric cancer. Results: Fifteen studies were identified (7 cohorts, 8 case-controls; 984 esophageal and 7,087 gastric cancers). Collectively, they indicated that the risk of gastric cancer was 13% lower among the most physically active people than among the least active people (RR = 0.87, 95% confidence interval [CI] = 0.78 to 0.97) and that of esophageal cancer was 27% lower (RR = 0.73, 95% CI = 0.56 to 0.97). Conclusions: Pooled results from observational studies support a protective effect of physical activity against both esophageal and gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Salvage liver transplantation (SLT) has recently been proposed for recurrent hepatocellular carcinoma after liver resection; however, criteria for candidate assessment in SLT have not been thoroughly evaluated. Methods and Findings: We retrospectively analyzed outcomes and factors affecting survival of 53 recipients who received SLT in the Liver Transplantation Center, The First Affiliated Hospital of Zhejiang University between 2004 and 2012. Thirty recipients fulfilled the Hangzhou criteria, of which 16 also fulfilled the Milan criteria, while the remaining 23 exceeded both criteria. The 1-year, 3-year and 5-year overall survival rates and tumor-free survival rates were both superior in patients fulfilling Milan or Hangzhou criteria compared with those exceeding the criteria. For recipients outside Milan criteria but within Hangzhou criteria, the 1-year, 3-year overall survival rates were 70.1%, 70.1%, similar to recipients within Milan criteria, with the 1-year, 3-year and 5-year overall survival of 93.8%%, 62.1% and 62.1% (P = 0.586). The tumor-free survival rates were also similar between these two subgroups, with 51.9% and 51.9% vs. 85.6%, 85.6% and 64.2% during the same time interval, respectively (P = 0.054). Cox regression analysis identified Hangzhou criteria (within vs. outside, hazard ratio (HR) 0.376) and diameter of the largest tumor (HR 3.523) to be independent predictors for overall survival. The only predictor for tumor-free survival was diameter of the largest tumor (HR 22.289). Conclusions: Hangzhou criteria safely expanded the candidate pool and are feasible in assessment of candidates for SLT. This is helpful in donor liver allocation in transplant practice. [ABSTRACT FROM AUTHOR]

Purpose: Oral fluoropyrimidine (S-1, capecitabine) has been considered as an important part of various regimens. We aimed to evaluate the efficacy and safety of S-1-based therapy versus capecitabine -based therapy in gastrointestinal cancers. Methods: Eligible studies were identified from Pubmed, EMBASE. Additionally, abstracts presented at American Society of Clinical Oncology (ASCO) conferences held between 2000 and 2013 were searched to identify relevant clinical trials. The outcome included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR) and advent events. Results: A total of 6 studies (4 RCTs and 2 retrospective analysis studies) containing 790 participants were included in this meta-analysis, including 401 patients in the S-1-based group and 389 patients in the capecitabine-based group. Results of our meta-analysis indicated that S-1-based and capecitabine-based regimens showed very similar efficacy in terms of PFS (HR 0.92, 95% CI 0.78–1.09, P = 0.360), OS (HR 1.01, 95% CI 0.84–1.21, P = 0.949), ORR (HR 1.04, 95% CI 0.87–1.25, P = 0.683) and DCR (HR 1.02, 95% CI 0.94–1.10, P = 0.639). There was also no significant difference in toxicity between regimens other than mild more hand–foot syndrome in capecitabine-based regimens. Conclusion: Both the S-1-based and capecitabine-based regimens are equally active and well tolerated, and have the potential of backbone chemotherapy regimen in further studies of gastrointestinal cancers. [ABSTRACT FROM AUTHOR]

Background: The effect of interferon(IFN) in the management of hepatocellular carcinoma (HCC) remains controversial, and no clear recommendations have been proposed. Objectives: To evaluate the effect and safety of IFN for HCC. Methods: PubMed, OvidSP, and Cochrane Library were searched from their establishment date until August 30, 2012. Studies that met the inclusion criteria were systematically evaluated and then subjected to meta-analysis. Results: Thirteen randomized control trials (RCTs) involving 1344 patients were eligible for this study. When IFN was used as an adjuvant therapy for HCC patients after curative therapy, the meta-analysis showed that IFN reduced the 1-, 2-, 3-, 4-, and 5-year recurrence rates. Subgroup analysis showed that IFN reduced the 2-, 3-, 4-, and 5-year recurrence rates of hepatitis C viral (HCV)-related HCC. The effect of IFN for on hepatitis B virus(HBV)-related HCC patients could not be determined because of isufficient data. After surgical resection, adjuvant IFN therapy reduced the 4- and 5- recurrence rates. All studies reported that IFN could not improve the overall survival of HCV-realated HCC patients after curative therapies. Only one study showed that IFN was associated with better overall survival in HCC patients after curative therapy and subgroup of HCC patients after surgical resection. Thus, meta-analysis was not performed. Different treatment options were used as control to study the effect of IFN for intermediate and advanced HCC patients, thus meta-analysis was not appropriate. All included studies, except for one, reported that IFN treatment was well tolerated. Conclusions: After curative therapies, adjuvant IFN reduced the recurrence of HCC. IFN did not improve the survival of HCV-related HCC patients after curative therapy. Whether IFN is effective for intermediate and advanced HCC patients could not be determined because of insufficient data. The toxicity of IFN was acceptable. [ABSTRACT FROM AUTHOR]

Background and Objective: The impact of perioperative allogenenic blood transfusion (ABT) on clinical outcomes for hepatocellular carcinoma (HCC) is conflicting and unclear. The aim of this meta-analysis is to evaluate the association between ABT and HCC clinical outcomes. Outcomes evaluated were all-cause death, tumor recurrence and postoperative complications. Methods: Relevant articles were identified through MEDLINE search (up to November 2012). Meta-analyses were performed by using the fixed or random effect models. Study heterogeneity was assessed by Q-test and I2 test. Publication bias was evaluated by funnel plots, Egger′s and Begg’s test. Results: A total of 5635 cases from 22 studies finally met our inclusion criteria. Meta-analysis indicated HCC patients with ABT had an increased risk of all-cause death at 3 and 5 years after surgery (respectively: OR = 1.92, 95% CI, 1.61–2.29,P<0.001; OR = 1.60, 95% CI, 1.47–1.73,P<0.001 ) compared with those without ABT. The risk of tumor recurrence was significantly higher for ABT cases at 1, 3 and 5 years (respectively: OR = 1.70, 95% CI, 1.38–2.10, P<0.001; OR = 1.22, 95% CI, 1.08–1.38, P<0.001; OR = 1.16, 95% CI, 1.08–1.24, P<0.001). The HCC cases with ABT significantly increased postoperative complications occurrence compared with non-ABT cases (OR = 1.78,95% CI, 1.34–2.37, P<0.001). Conclusions: The findings from the current meta-analysis demonstrated that ABT was associated with adverse clinical outcomes for HCC patients undergoing surgery, including increased death, recurrence and complications. Therefore, ABT should not be performed if possible. [ABSTRACT FROM AUTHOR]

Background: To report the feasibility, efficacy, and toxicity of stereotactic body radiotherapy (SBRT) for the treatment of portal vein tumor thrombosis (PVTT) and/or inferior vena cava tumor thrombosis (IVCTT) in patients with advanced hepatocellular carcinoma (HCC). Materials and methods: Forty-one patients treated with SBRT using volumetric modulated arc therapy (VMAT) for HCC with PVTT/IVCTT between July 2010 and May 2012 were analyzed. Of these, 33 had PVTT and 8 had IVCTT. SBRT was designed to target the tumor thrombosis and deliver a median total dose of 36 Gy (range, 30–48 Gy) in six fractions during two weeks. Results: The median follow-up was 10.0 months. At the time of analysis, 15 (36.6%) achieved complete response, 16 (39.0%) achieved partial response, 7 (17.1%) patients were stable, and three (7.3%) patients showed progressive disease. No treatment-related Grade 4/5 toxicity was seen within three months after SBRT. One patient had Grade 3 elevation of bilirubin. The one-year overall survival rate was 50.3%, with a median survival of 13.0 months. The only independent predictive factor associated with better survival was response to radiotherapy. Conclusions: VMAT-based SBRT is a safe and effective treatment option for PVTT/IVCTT in HCC. Prospective randomized controlled trials are warranted to validate the role of SBRT in these patients. [ABSTRACT FROM AUTHOR]

Objective: CD133 has recently been reported as a marker of cancer stem-like cells in colorectal cancer (CRC). However, its predictive value in CRC still remains controversial. In this study, we aimed to evaluate the association between the expression of CD133 and clinicopathological features and the outcome of CRC patients by performing a meta-analysis. Methods: A comprehensive literature search for relevant studies published up to December 2012 was performed using PubMed, MEDLINE and ISI Web of Science. Only articles in which CD133 antigen was detected in situ localisation by immunohistochemical staining were included. This meta-analysis was done using RevMan 4.2 software. Results: We found that a total of 15 studies involving 810 CD133-high and 1487 CD133-low patients met the inclusion criteria for the analysis of 5-year overall survival (OS) rate. In a random-effects model, the results showed that CD133-high expression in colorectal cancer was an independent prognostic marker correlating with both OS rate (RR = 0.67, 95%CI 0.54–0.82, P<0.01) and disease free survival (DFS) rate (RR = 0.71, 95%CI 0.52–0.96, P = 0.03). CD133-high expression was also associated with more T3,4 tumor invasion, N positive and vascular invasion cases, corresponding to a risk difference of 1.12 (95%CI 1.01–1.23, P = 0.03), 1.31 (95%CI 1.06–1.63, P = 0.01) and 1.24 (95%CI 1.08–1.41, P<0.01), respectively. However, when types of histology, lymphatic invasion and distant metastasis were considered, CD133 overexpression was not significantly related with these clinicopathological parameters. Conclusion: Our meta-analysis results suggest that CD133 is an efficient prognostic factor in CRC. Higher CD133 expression is significantly associated with poorer clinical outcome and some clinicopathological factors such as T category, N category and vascular invasion in CRC patients. [ABSTRACT FROM AUTHOR]

Background: The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and hepatocellular carcinoma (HCC) risk was inconsistent and underpowered. To clarify the effects of MTHFR gene polymorphisms on the risk of HCC, a meta-analysis of all available studies relating C677T and/or A1298C polymorphisms of MTHFR gene to the risk of HCC was conducted. Methods: The authors searched PubMed, EMBASE, Cochrane Library, Web of Science, and Chinese Biomedical Literature database (CBM) for the period up to July 2012. Data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Metaregression and subgroup analyses were performed to identify the source of heterogeneity. Results: Finally, 12 studies with 2,351 cases and 4,091 controls were included for C677T polymorphism and 6 studies with 1,333 cases and 1,878 controls were included for A1298C polymorphism. With respect to A1298C polymorphism, significantly decreased HCC risk was found in the overall population (CC vs. AA: OR = 0.660, 95%CI 0.460–0.946, P = 0.024; recessive model: OR = 0.667, 95%CI = 0.470–0.948, P = 0.024). In subgroup analyses, significantly decreased HCC risk was found in Asian population (CC vs. AA: OR = 0.647, 95%CI = 0.435–0.963; P = 0.032) and population-based studies (CC vs. AA: OR = 0.519, 95%CI = 0.327–0.823; P = 0.005). With respect to C677T polymorphism, no significant association with HCC risk was demonstrated in overall and stratified analyses. Conclusions: We concluded that MTHFR A1298C polymorphism may play a protective role in the carcinogenesis of HCC. Further large and well-designed studies are needed to confirm this association. [ABSTRACT FROM AUTHOR]