Prognostic significance of neutrophil to lymphocyte ratio in pancreatic cancer: A meta-analysis

AIM: To conduct a meta-analysis evaluating the association between the peripheral blood neutrophil to lymphocyte ratio (NLR) and the outcome of patients with pancreatic cancer.METHODS: Studies evaluating the relationship between the peripheral blood NLR and outcome of patients with pancreatic cancer published up to May 2014 were searched using electronic databases, including PubMed, Web of Science, Embase and Ovid. A meta-analysis was performed to pool the hazard ratios (HRs) or odds ratios (ORs) and their 95% confidence intervals (CIs) using either a fixed-effects model or a random-effects model to quantitatively assess the prognostic value of NLR and its association with clinicopathological parameters.RESULTS: Eleven studies containing a total of 1804 patients were eligible according to our selection criteria, and combined hazard ratios indicated that high NLR was a poor prognostic marker for pancreatic cancer patients because it had an unfavorable impact on the overall survival (OS) (HR = 2.61, 95%CI: 1.68-4.06, P = 0.000) and cancer specific survival (HR = 1.66, 95%CI: 1.08-2.57, P = 0.021). Subgroup analysis revealed that high NLR was associated with poor OS in patients with mixed treatment (HR = 4.36, 95%CI: 2.50-7.61, P = 0.000), chemotherapy (HR = 2.08, 95%CI: 1.49-2.9, P = 0.000), or surgical resection (HR = 1.2, 95%CI: 1.00-1.44, P = 0.048). Additionally, high NLR was significantly correlated with tumor metastasis (OR = 1.69, 95%CI: 1.10-2.59, P = 0.016), poor tumor differentiation (OR = 2.75, 95%CI: 1.19-6.36, P = 0.016), poor performance status (OR = 2.56, 95%CI: 1.63-4.03, P = 0.000), high cancer antigen 199 (OR = 2.62, 95%CI: 1.49-4.60, P = 0.000), high C-reactive protein (OR = 4.32, 95%CI: 2.71-6.87, P = 0.000), and low albumin (OR = 3.56, 95%CI: 1.37-9.27, P = 0.009).CONCLUSION: High peripheral blood NLR suggested a poor prognosis for patients with pancreatic cancer, and it could be a novel marker of survival evaluation and could help clinicians develop therapeutic strategies for pancreatic cancer patients.     

Prognostic and clinicopathological significance of glypican-3 overexpression in hepatocellular carcinoma: A meta-analysis

AIM: To investigate the prognostic and clinicopathological significance of glypican-3 (GPC3) overexpression in hepatocellular carcinoma (HCC).METHODS: Publications were searched using PubMed, EMBASE, the Cochrane Library and the Chinese Biomedical Literature Database up to March 2013. Inclusion and exclusion criteria were established to screen eligible studies for meta-analysis. The hazard ratios (HRs) of the eligible studies were pooled using RevMan 5.2 software to evaluate the impact of GPC3 overexpression on overall survival (OS) and disease-free survival (DFS) in HCC patients. The correlation between GPC3 expression and clinicopathological parameters of HCC was also analyzed.RESULTS: A total of five studies with 493 patients were included in the meta-analysis. The combined HRs indicated that GPC3 overexpression can predict poor OS (n = 362 in 3 studies, HR = 2.18, 95%CI: 1.47-3.24, Z = 3.86, P = 0.0001) and DFS (n = 325 in 3 studies, HR = 2.05, 95%CI: 1.43-2.93, Z = 3.94, P < 0.0001) in HCC patients without heterogeneity. Egger’s and Begg’s tests were applied to detect publication bias, and the results showed that there was no evidence of publication bias detected in the OS studies (the P value for Egger’s test was 0.216) or DFS studies (the P value for Egger’s test was 0.488). The combined odds ratios (ORs) suggested that GPC3 expression tends to be associated with tumor vascular invasion (OR = 2.74, 95%CI: 1.15-6.52, P = 0.02), hepatic cirrhosis (OR = 2.10, 95%CI: 1.31-3.36, P = 0.002), poor tumor differentiation (OR = 0.22, 95%CI: 0.13-0.40, P < 0.00001) and advanced TNM stage (OR = 0.31, 95%CI: 0.18-0.51, P < 0.00001).CONCLUSION: From this study, we conclude that GPC3 overexpression tends to be associated with a poor prognosis (poor OS or DFS) in HCC.     

Clinical outcome of small hepatocellular carcinoma after different treatments:A meta-analysis

AIM:To compare clinical outcomes between surgical resection(RES)and nonsurgical-RES(nRES)ablation therapies for small hepatocellular carcinoma(HCC).METHODS:MEDLINE,Embase and Cochrane Library databases were systematically searched for studies of RES and nRES treatments for small HCC between January 2003 and October 2013.The clinical outcome measures evaluated included overall survival rate,disease-free survival rate,adverse events,and local recurrence rate.Odds ratios(ORs)with 95%CIs were calculated using either the fixed effects model or random effects model.Theχ2 and I2 tests were calculated to assess the heterogeneity of the data.Funnel plots were used to assess the risk of publication bias.RESULTS:Our analysis included 12 studies that consisted of a total of 1952 patients(RES vs nRES),five studies that consisted of 701 patients[radiofrequency ablation(RFA)vs percutaneous ethanol injection(PEI)],and five additional studies[RFA vs RFA+transcatheter arterial chemoembolization(TACE)]that all addressed the treatment of small HCC.For cases of RES vs nRES,there was no significant difference in the 1-year(OR=0.99,95%CI:0.87-1.12,P=0.85)or 3-year(OR=0.97,95%CI:0.84-1.11,P=0.98)overall survival rate;however,there was a significant increase in the RES group in the 5-year overall survival rate(OR=0.81,95%CI:0.68-0.95,P=0.01).The 1-year(OR=0.94,95%CI:0.82-1.08,P=0.37)and 5-year(OR=0.99,95%CI:0.85-1.14,P=0.85)disease-free survival rates showed no significant differences between the two groups.The3-year disease-free survival rate(OR=0.81,95%CI:0.69-0.96;P=0.02)was higher in the RES group.For cases of RFA vs PEI,our data analysis indicated that RFA treatment was associated with significantly higher2-year(OR=0.76,95%CI:0.58-0.99,P=0.043)and3-year(OR=0.73,95%CI:0.54-0.98,P=0.039)overall survival rates;however,there were no significant differences in the 1-year(OR=0.92,95%CI:0.72-1.17,P=0.0502)overall survival rate or incidence of adverse events(OR=1.84,95%CI:0.76-4.45,P=0.173).For cases of RFA vs RFA+TACE,there were no significant differences in the 1-year(OR=1.17,95%CI:0.88-1.56,P=0.27)or 3-year(OR=1.25,95%CI:0.90-1.73,P=0.183)overall survival rate;however,the 5-year overall survival rate(OR=3.19,95%CI:1.51-6.74,P=0.002)in patients treated by RFA+TACE was higher than that treated by RFA alone.CONCLUSION:Surgical resection is superior to nonsurgical ablation for the treatment of small HCC.Among the studies analyzed,RFA is the most efficacious single nonsurgical ablation treatment.     

Association between hepatocellular carcinoma and tumor necrosis factor alpha polymorphisms in South Korea

AIM: To investigate associations between the tumor necrosis factor alpha(TNF-α)-1031 TC,-863 CA,-857 CT,-308 GA,and-238 GA polymorphisms and HCC in Korea.METHODS: Hepatocellular carcinoma(HCC) cases were diagnosed at CHA Bundang Medical Center from June 1996 to August 2008. The association between TNF-α polymorphisms and HCC was analyzed in 157HCC patients and 201 controls using a polymerase chain reaction-restriction fragment length polymorphism assay. We investigated five TNF-α polymorphisms,which are TNF-α-1031 TC,-863 CA,-857 CT,-308 GA,and-238 GA. The TNF-α genotype frequencies,genotype combinations and haplotypes were analyzed to disclose the association with HCC.RESULTS: None of the TNF-α polymorphisms was significantly associated with HCC. However,nine genotype combinations had associations with increased likelihood of HCC. Among them,TNF-α-1031/-857/-238 TT/CC/GA(AOR = 18.849,95%CI: 2.203-161.246,P = 0.007),TNF-α-1031/-308/-238 TT/GG/GA(AOR = 26.956,95%CI: 3.071-236.584,P = 0.003),and TNF-α-1031/-238 TT/GA(AOR = 21.576,95%CI: 2.581-180.394,P = 0.005) showed marked association with HCC. There were five haplotypes of TNF-α polymorphisms which were significantly associated with HCC. They are TNF-α-1031/-863/-857/-308/-238 T-C-C-G-A(OR = 25.824,95%CI: 1.491-447.223,P = 0.0005),TNF-α-1031/-857/-308/-238 T-C-G-A(OR = 12.059,95%CI: 2.747-52.950,P 0.0001),TNF-α-1031/-857/-238 T-C-A(OR = 10.696,95%CI: 2.428-47.110,P = 0.0001),TNF-α-1031/-308/-238 T-G-A(OR = 7.556,95%CI: 2.173-26.280,P = 0.0002) and TNF-α-1031/-238 T-A(OR = 10.865,95%CI: 2.473-47.740,P = 0.0001). Moreover,HCC Okuda stage Ⅲ cases with the TNF-α-1031 CC genotype had better survival than those with the TT genotype(AOR = 5.795,95%CI: 1.145-29.323). CONCLUSION: Although no single TNF-α polymorphism is associated with HCC in this study,some TNF-α genotype combinations and haplotypes are associated with HCC. In addition,HCC Okuda stage Ⅲ cases with the TNF-α-1031 TT genotype may have a better prognosis than those with the CC genotype.     

3D conformal radiotherapy combined with transcatheter arterial chemoembolization for hepatocellular carcinoma

AIM:To compare transcatheter arterial chemoembolization(TACE)and 3D conformal radiotherapy(3D-CRT)with TACE monotherapy in hepatocellular carcinoma(HCC).METHODS:We searched all the eligible studies from the Cochrane Library,Pub Med,Medline,Embase,and CNKI.The meta-analysis was performed to assess the survival benefit,tumor response,and the decline inα-fetoprotein(AFP)level.According to the heterogeneity of the studies,pooled OR with 95%CI were calculated using the fixed-effects or random-effects model.An observed OR>1 indicated that the addition of 3D-CRT to TACE offered survival benefits to patients that could be considered statistically significant.Statistical analyses were performed using Review Manager Software.RESULTS:Ten studies met the criteria to perform a meta-analysis including 908 HCC participants,with 400patients in the TACE/3D-CRT combination group and508 in the TACE alone group.TACE combined with 3DCRT significantly improved 1-,2-and 3-year overall survival compared with TACE monotherapy(OR=1.87,95%CI:1.37-2.55,P<0.0001),(OR=2.38,95%CI:1.78-3.17,P<0.00001)and(OR=2.97,95%CI:2.10-4.21,P<0.00001).In addition,TACE plus 3DCRT was associated with a higher tumor response(complete remission and partial remission)(OR=3.81;95%CI:2.70-5.37;P<0.00001),and decline rates of AFP level(OR=3.24,95%CI:2.09-5.02,P<0.00001).CONCLUSION:This meta-analysis demonstrated that TACE combined with 3D-CRT was better than TACE monotherapy for patients with HCC,which needs to be confirmed by large multicenter trials.     

Association between Helicobacter pylori infection and migraine: A meta-analysis

AIM: To quantify the association between Helicobacter pylori (H. pylori) infection and migraine.METHODS: A systematic literature search of PubMed and EMBASE was conducted from inception to December 2013. Studies that provided data dealing with H. pylori infection in patients with migraine, as well as healthy controls, were selected. Meta-analysis was carried out using the odds ratio (OR) with a fixed or random effects model, and a 95%CI for the OR was calculated. An unconditional logistic regression model was used to analyze potential parameters related to H. pylori prevalence. Subgroup analyses were conducted as methods of detection and evidence grade.RESULTS: Five case-control studies published between 2000 and 2013 were finally identified, involving 903 patients, with a total H. pylori infection rate of 39.31%. The prevalence of H. pylori infection was significantly greater in migraineurs than in controls (44.97% vs 33.26%, OR = 1.92, 95%CI: 1.05-3.51, P = 0.001). A sensitivity test indicated that no single study dominated the combined results. Univariate regression analysis found that publication year, geographical distribution and evidence grade were relevant to the results and were the main reason for the heterogeneity. Subgroup analysis found a significantly greater infection rate of H. pylori in Asian patients with migraine, but no statistically significant infection rate in European patients. The ORs were 3.48 (95%CI: 2.09-5.81, P = 0.000) and 1.19 (95%CI: 0.86-1.65, P = 0.288), respectively.CONCLUSION: The pooled data suggest a trend of more frequent H. pylori infections in patients with migraine.     

Meta-analysis of laparoscopic vs open liver resection for hepatocellular carcinoma

AIM: To conduct a meta-analysis to determine the safety and efficacy of laparoscopic liver resection (LLR) and open liver resection (OLR) for hepatocellular carcinoma (HCC).METHODS: PubMed (Medline), EMBASE and Science Citation Index Expanded and Cochrane Central Register of Controlled Trials in the Cochrane Library were searched systematically to identify relevant comparative studies reporting outcomes for both LLR and OLR for HCC between January 1992 and February 2012. Two authors independently assessed the trials for inclusion and extracted the data. Meta-analysis was performed using Review Manager Version 5.0 software (The Cochrane Collaboration, Oxford, United Kingdom). Pooled odds ratios (OR) or weighted mean differences (WMD) with 95%CI were calculated using either fixed effects (Mantel-Haenszel method) or random effects models (DerSimonian and Laird method). Evaluated endpoints were operative outcomes (operation time, intraoperative blood loss, blood transfusion requirement), postoperative outcomes (liver failure, cirrhotic decompensation/ascites, bile leakage, postoperative bleeding, pulmonary complications, intraabdominal abscess, mortality, hospital stay and oncologic outcomes (positive resection margins and tumor recurrence).RESULTS: Fifteen eligible non-randomized studies were identified, out of which, 9 high-quality studies involving 550 patients were included, with 234 patients in the LLR group and 316 patients in the OLR group. LLR was associated with significantly lower intraoperative blood loss, based on six studies with 333 patients [WMD: -129.48 mL; 95%CI: -224.76-(-34.21) mL; P = 0.008]. Seven studies involving 416 patients were included to assess blood transfusion requirement between the two groups. The LLR group had lower blood transfusion requirement (OR: 0.49; 95%CI: 0.26-0.91; P = 0.02). While analyzing hospital stay, six studies with 333 patients were included. Patients in the LLR group were found to have shorter hospital stay [WMD: -3.19 d; 95%CI: -4.09-(-2.28) d; P < 0.00001] than their OLR counterpart. Seven studies including 416 patients were pooled together to estimate the odds of developing postoperative ascites in the patient groups. The LLR group appeared to have a lower incidence of postoperative ascites (OR: 0.32; 95%CI: 0.16-0.61; P = 0.0006) as compared with OLR patients. Similarly, fewer patients had liver failure in the LLR group than in the OLR group (OR: 0.15; 95%CI: 0.02-0.95; P = 0.04). However, no significant differences were found between the two approaches with regards to operation time [WMD: 4.69 min; 95%CI: -22.62-32 min; P = 0.74], bile leakage (OR: 0.55; 95%CI: 0.10-3.12; P = 0.50), postoperative bleeding (OR: 0.54; 95%CI: 0.20-1.45; P = 0.22), pulmonary complications (OR: 0.43; 95%CI: 0.18-1.04; P = 0.06), intra-abdominal abscesses (OR: 0.21; 95%CI: 0.01-4.53; P = 0.32), mortality (OR: 0.46; 95%CI: 0.14-1.51; P = 0.20), presence of positive resection margins (OR: 0.59; 95%CI: 0.21-1.62; P = 0.31) and tumor recurrence (OR: 0.95; 95%CI: 0.62-1.46; P = 0.81).CONCLUSION: LLR appears to be a safe and feasible option for resection of HCC in selected patients based on current evidence. However, further appropriately designed randomized controlled trials should be undertaken to ascertain these findings.     

Association of metabolic health phenotypes,obesity, and hepatocellular carcinoma risk

BackgroundThe obesity and hepatocellular carcinoma (HCC) risk association may differ by individuals’ metabolic health status.AimTo investigate the association between obesity categories and HCC risk among individuals with different metabolic health phenotypes.MethodsA case-control study among 518 HCC cases and 1,036 frequency-matched controls was conducted. Body mass index (BMI) was assessed before diagnosis. Pre-diagnosis data on dyslipidemia, hypertension, and diabetes were used to categorize participants as metabolically healthy or metabolically unhealthy. Participants were further categorized into metabolically healthy normal weight (MHNW), metabolically healthy overweight (MHOW), metabolically healthy obese (MHO), metabolically unhealthy normal weight (MUNW), metabolically unhealthy overweight (MUOW), and metabolically unhealthy obese (MHO). We used logistic regression to calculate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs).ResultsBeing overweight (OR=1.68, 95%CI=1.21–2.34) or obese (OR=1.49, 95%CI=1.11–1.89) was associated with higher HCC risk. Among metabolically healthy participants, no association was found between being overweight or obese and HCC risk. However, among the metabolically unhealthy participants, being overweight (OR=1.89, 95%CI=1.31–2.72) or obese (OR=1.50, 95%CI=1.07–2.09) was associated with higher HCC risk. Compared to the MHNW phenotype, no association was found between the MHOW and MHO phenotypes and HCC risk, but the MUNW (OR=1.94, 95%CI=1.09–3.43), MUOW (OR=3.78, 95%CI=2.15–6.65), and MUO (OR=2.93, 95%CI=1.70–5.05) phenotypes were associated with higher HCC risk.ConclusionThe association between BMI and HCC appears to be restricted to individuals with underlying metabolic abnormalities.     

S-1-based combination therapy vs S-1 monotherapy in advanced gastric cancer:A meta-analysis

AIM:To assess the efficacy and safety of combination therapy based on S-1,a novel oral fluoropyrimidine,vs S-1 monotherapy in advanced gastric cancer(AGC).METHODS:We searched PubMed,EMBASE and the Cochrane Library for eligible studies published before March 2013.Our analysis identified four randomized controlled trials involving 790 participants with AGC.The outcome measures were overall survival(OS),progression-free survival(PFS),overall response rate(ORR)and grade 3-4 adverse events.RESULTS:Meta-analysis showed that S-1-based combination therapy significantly improved OS(HR=0.77,95%CI:0.66-0.91,P=0.002),PFS(HR=0.58,95%CI:0.46-0.72,P=0.000)and ORR(OR=2.23,95%CI:1.54-3.21,P=0.000).Sensitivity analysis further confirmed this association.Lower incidence of grade 3-4 leucopenia(OR=4.06,95%CI:2.11-7.81),neutropenia(OR=3.94,95%CI:2.1-7.81)and diarrhea(OR=2.41,95%CI:1.31-4.44)was observed in patients with S-1 monotherapy.CONCLUSION:S-1-based combination therapy is superior to S-1 monotherapy in terms of OS,PFS and ORR.S-1 monotherapy is associated with less toxicity.     

X-ray repair cross-complementing group 1 polymorphisms and hepatocellular carcinoma: a meta-analysis

AIM: To perform a systematic meta-analysis to investigate the association between X-ray repair cross-complementing group 1 (XRCC1) polymorphisms and hepatocellular carcinoma (HCC) risk.METHODS: Relevant studies extracted from PubMed, Embase, Wanfang, VIP and the Chinese National Knowledge Infrastructure databases up to March 2012 were included in the study. Stata software, version 11.0, was used for the statistical analysis. The odds ratios (ORs) and 95% confidence interval (CI) of the XRCC1 polymorphisms in HCC patients were analyzed and compared with healthy controls. The meta-analysis was performed using fixed-effect or random-effect methods, depending on the absence or presence of significant heterogeneity.RESULTS: Eleven studies with 2075 HCC cases and 2604 controls met our eligibility criteria (four studies, 888 cases and 938 controls for Arg194Trp, four studies, 858 cases and 880 controls for Arg280His, and nine studies, 1845 cases and 2401 controls for Arg399Gln). The meta-analysis revealed no associations between the Arg194Trp and Arg399Gln polymorphisms of the XRCC1 gene and HCC risk under all contrast models (codominant, dominant and recessive models) in the overall analysis and sensitivity analysis (the studies with controls not in the Hardy-Weinberg equilibrium were excluded). For XRCC1 Arg280His polymorphism, the overall analysis revealed the significant association between the His/His genotype and the increased risk of HCC (His/His vs Arg/Arg model, OR: 1.96, 95% CI: 1.03-3.75, P = 0.04). However, sensitivity analysis showed an altered pattern of result and non-significant association (OR: 2.06, 95% CI: 0.67-6.25, P = 0.20). The heterogeneity hypothesis test did not reveal any heterogeneity, and Begg’s and Egger’s tests did not find any obvious publication bias.CONCLUSION: The XRCC1 Arg194Trp and Arg399Gln polymorphisms are not associated with HCC risk. More rigorous association studies are needed to verify the involvement of XRCC1 Arg280His polymorphism in HCC susceptibility.     

Association between obesity-related adipokines and colorectal cancer:A case-control study and meta-analysis

AIM:To examine the association between obesityrelated adipokines(adiponectin,leptin,resistin,interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)and colorectal cancer(CRC)risk.METHODS:Serum levels of adipokines were measured in 100 CRC patients and age-and sex-matched controls for the data analysis.Unconditional logistic regression models were used for estimating ORs and95%CIs related to each adipokine.For the metaanalysis,studies published before July 2013 available on Medline/PubMed and EMBASE were retrieved.The analysis included a total of 17 relevant studies(including the present case-control study):nine studies on adiponectin and eight on leptin.The effect sizes of ORs and 95%CIs were estimated using RevMan 5.1.Heterogeneity was evaluated using Cochran’s Q-test and I2 statistics.RESULTS:Among the five adipokines,only resistin levels were significantly higher in cases than in controls(P<0.001).The case-control study results showed no association between adiponectin and CRC and a negative association between leptin and CRC.However,the results of the meta-analysis showed a significant inverse association between adiponectin and CRC(OR=0.91,95%CI:0.83-1.00,P=0.04)and no association between CRC and leptin.After stratification by study design,an inverse association between adiponectin and CRC was observed in prospective studies only(OR=0.90,95%CI:0.82-0.99,P=0.03),whereas the association between leptin and CRC was inconsistent(prospective studies:OR=1.14,95%CI:1.02-1.27,P=0.02 and retrospective studies:OR=0.47,95%CI:0.29-0.74,P=0.001).The associations of resistin and TNF-αwith CRC risk were positive,but no association was observed for IL-6.CONCLUSION:Our results suggest a negative association of leptin,positive associations of resistin and TNF-α,and null associations of adiponectin and IL-6with CRC.However,further studies with larger number of prospective approaches are needed.     

MiR-146a rs2910164 polymorphism increases risk of gastric cancer: A meta-analysis

AIM: To systematically evaluate the association between the miR-146a rs2910164 polymorphism and susceptibility to gastric cancer.METHODS: A comprehensive electronic search was conducted for articles published up until January 27, 2014 in Medline (PubMed), Excerpta Medica Database (Embase), the Cochrane Library and Google Scholar. Only case-control studies published in English that evaluated the association between the miR-146a rs2910164 polymorphism and susceptibility to gastric cancer were included. Furthermore, only studies with sufficient data allowing for calculation of odds ratio (OR) and corresponding 95% confidence interval (CI) were included. These values were used in the quantitative synthesis to assess the strength of the association between the miR-146a rs2910164 polymorphism and risk of gastric cancer.RESULTS: The database search identified 1002 eligible studies, of which seven (comprising 4112 cases and 5811 controls) were included for the meta-analysis. The results indicate that miR-146a rs2910164 polymorphism is more likely to be associated with gastric cancer risk. In the overall analysis, a significantly increased cancer risk was found in the heterozygote (GG vs GC) comparison (OR = 1.14, 95%CI: 1.03-1.27; P = 0.01 for pooled OR). In the ethnicity subgroup analysis, a similar result was found among Caucasians (OR = 1.36, 95%CI: 1.01-1.85; P = 0.04 for pooled OR). In the stratified analysis by quality of studies, a significantly increased cancer risk was found in the heterozygote comparison among high quality studies (OR = 1.12, 95%CI: 1.01-1.26; P = 0.04 for pooled OR). When stratified on the basis of sample size, a significantly increased cancer risk was found among small sample size subgroups for the allelic (G vs C: OR = 1.16, 95%CI: 1.03-1.30; P = 0.01), homozygote (GG vs CC: OR = 1.33, 95%CI: 1.03-1.73; P = 0.03) and recessive model (GG vs GC + CC: OR = 0.05, 95%CI: 0.00-0.10; P = 0.03) comparisons.CONCLUSION: The miR-146a rs2910164 polymorphism is associated with increased gastric cancer risk, particularly evident in high quality studies with small sample sized Caucasian populations.     

Prognostic factors for survival after transarterial chemoembolization combined with microwave ablation for hepatocellular carcinoma

AIM: To analyze prognostic factors for survival after transarterial chemoembolization (TACE) combined with microwave ablation (MWA) for hepatocellular carcinoma (HCC).METHODS: Clinical data of 86 patients who underwent TACE combined with MWA between January 2006 and December 2013 were retrospectively analyzed in this study. Survival curves were detected using log-rank test. Univariate analysis was performed using log-rank test with respect to 13 prognostic factors affecting survival. All statistically significant prognostic factors identified by univariate analysis were entered into a Cox proportion hazards regression model to identify independent predictors of survival. P values were two-sided and P < 0.05 was considered statistically significant.RESULTS: Median follow-up time was 47.6 mo, and median survival time of enrolled patients was 21.5 mo. The 1-, 2-, 3- and 5-year overall survival rates were 72.1%, 44.1%, 31.4% and 13.9%, respectively. Tumor size(χ² = 14.999, P = 0.000), Barcelona Clinic Liver Cancer (BCLC) stage (χ² = 29.765, P = 0.000), Child-Pugh class (χ² = 51.820, P = 0.000), portal vein tumor thrombus (PVTT) (χ² = 43.086, P = 0.000), arterio-venous fistula (χ² = 29.791, P = 0.000), MWA therapy times (χ² = 12.920, P = 0.002), Eastern Cooperative Oncology Group (ECOG) score (χ² = 28.660, P = 0.000) and targeted drug usage (χ² = 10.901, P = 0.001) were found to be significantly associated with overall survival by univariate analysis. Multivariate analysis identified that tumor size (95%CI: 1.608-4.962, P = 0.000), BCLC stage (95%CI: 1.016-2.208, P = 0.020), PVTT (95%CI: 2.062-9.068, P = 0.000), MWA therapy times (95%CI: 0.402-0.745, P = 0.000), ECOG score (95%CI: 1.012-3.053, P = 0.045) and targeted drug usage (95%CI: 1.335-3.143, P = 0.001) were independent prognostic factors associated with overall survival.CONCLUSION: Superior performance status, MWA treatment and targeted drug were favorable factors, and large HCC, PVTT and advanced BCLC stage were risk factors for survival after TACE-MWA for HCC.     

Association between polymorphisms of the APOBEC3G gene and chronic hepatitis B viral infection and hepatitis B virusrelated hepatocellular carcinoma

AIM to determine the relationship between five A3 G gene single nucleotide polymorphisms and the incidence of hepatitis B virus(HBV) infection and hepatocellular carcinoma(HCC). METHODS this association study was designed as a retrospective study, including 657 patients with chronic HBV infection(CHB) and 299 healthy controls. All subjects were ethnic Han Chinese. Chronic HBV-infected patients recruited between 2012 and 2015 at the First Hospital of Jilin University(Changchun) were further classified into HBV-related HCC patients(n = 287) and non-HCC patients(n = 370). Frequency matching by age and sex was performed for each group. Human genomic DNAwas extracted from whole blood. Gene polymorphisms were identified using a mass spectroscopic method.RESULTS there were no significant differences between the genotype and allele frequencies of the rs7291971, rs5757465 and rs5757463 A3 G gene polymorphisms, and risk of CHB and HBV-related HCC. the AG genotype and G allele for rs8177832 were significantly related to a decreased risk of CHB(OR = 0.67, 95%CI: 0.47-0.96; OR = 0.69, 95%CI: 0.50-0.95, respectively) and HCC(OR = 0.53, 95%CI: 0.34-0.84; OR = 0.58, 95%CI: 0.39-0.87, respectively). A significant relationship was found between rs2011861 computed tomography, tt genotypes and increased risk of HCC(OR = 1.69, 95%CI: 1.02-2.80; OR = 1.82, 95%CI: 1.08-3.06, respectively). Haplotype analyses showed three protective and four risk haplotypes for HCC. Also, one protective haplotype was found against CHB.CONCLUSION this study indicates that the A3 G rs8177832 polymorphism is associated with a decreased risk of CHB infection and HCC, while the rs2011861 polymorphism is associated with an increased risk of HCC.     

Relationships between cell cycle pathway gene polymorphisms and risk of hepatocellular carcinoma

AIM: To investigate the associiations between the polymorphisms of cell cycle pathway genes and the risk of hepatocellular carcinoma (HCC).METHODS: We enrolled 1127 cases newly diagnosed with HCC from the Tumor Hospital of Guangxi Medical University and 1200 non-tumor patients from the First Affiliated Hospital of Guangxi Medical University. General demographic characteristics, behavioral information, and hematological indices were collected by unified questionnaires. Genomic DNA was isolated from peripheral venous blood using Phenol-Chloroform. The genotyping was performed using the Sequenom MassARRAY iPLEX genotyping method. The association between genetic polymorphisms and risk of HCC was shown by P-value and the odd ratio (OR) with 95% confidence interval (CI) using the unconditional logistic regression after adjusting for age, sex, nationality, smoking, drinking, family history of HCC, and hepatitis B virus (HBV) infection. Moreover, stratified analysis was conducted on the basis of the status of HBV infection, smoking, and alcohol drinking.RESULTS: The HCC risk was lower in patients with the MCM4 rs2305952 CC (OR = 0.22, 95%CI: 0.08-0.63, P = 0.01) and with the CHEK1 rs515255 TC, TT, TC/TT (OR = 0.73, 95%CI: 0.56-0.96, P = 0.02; OR = 0.67, 95%CI: 0.46-0.97, P = 0.04; OR = 0.72, 95%CI: 0.56-0.92, P = 0.01, respectively). Conversely, the HCC risk was higher in patients with the KAT2B rs17006625 GG (OR = 1.64, 95%CI: 1.01-2.64, P = 0.04). In addition, the risk was markedly lower for those who were carriers of MCM4 rs2305952 CC and were also HBsAg-positive and non-drinking and non-smoking (P < 0.05, respectively) and for those who were carriers of CHEK1 rs515255 TC, TT, TC/TT and were also HBsAg-negative and non-drinking (P < 0.05, respectively). Moreover, the risk was higher for those who were carriers of KAT2B rs17006625 GG and were also HBsAg-negative (P < 0.05).CONCLUSION: Of 12 cell cycle pathway genes, MCM4, CHEK1 and KAT2B polymorphisms may be associated with the risk of HCC.     

-449 C>G polymorphism of NFKB1 gene,coding nuclear factor-kappa-B,is associated with the susceptibility to ulcerative colitis

AIM: To clarify the association between a polymorphism -449 C>G (rs72696119) in 5’-UTR of NFKB1 with ulcerative colitis (UC).METHODS: The studied population comprised 639 subjects, including patients with UC (UC cases, n = 174) and subjects without UC (controls, n = 465). We employed polymerase chain reaction-single strand conformation polymorphism to detect the gene polymorphism.RESULTS: The rs72696119 G allele frequencies in controls and UC cases were 33.4% and 38.5%, respectively (P = 0.10). Genotype frequency of the GG homozygote in UC cases was significantly higher than that in controls (P = 0.017), and the GG homozygote was significantly associated with susceptibility to UC [odds ratio (OR), 1.88; 95%CI, 1.13-3.14]. In male subjects, the GG homozygote was associated with an increased risk for UC (OR, 3.10; 95%CI, 1.47-6.54; P = 0.0053), whereas this association was not found in female subjects. In addition, the GG homozygote was significantly associated with the risk of non-continuous disease (OR, 2.06; 95%CI, 1.12-3.79; P = 0.029), not having total colitis (OR, 2.40; 95%CI, 1.09-3.80, P = 0.040), disease which developed before 20 years of age (OR, 2.80; 95%CI, 1.07-7.32, P = 0.041), no hospitalization (OR, 2.28; 95%CI, 1.29-4.05; P = 0.0090) and with a maximum of 8 or less on the UCDAI score (OR, 2.45; 95%CI, 1.23-4.93; P = 0.022).CONCLUSION: Our results provide evidence that NFKB1 polymorphism rs72696119 was significantly associated with the development of UC. This polymorphism influences the susceptibility to and pathophysiological features of UC.     

XPC Lys939Gln polymorphism,smoking and risk of sporadic colorectal cancer among Malaysians

AIM: To investigate the risk association of xeroderma pigmentosum group C (XPC ) Lys939Gln polymorphism alone and in combination with cigarette smoking on colorectal cancer (CRC) predisposition. METHODS: Peripheral blood samples of 510 study subjects (255 CRC patients, 255 controls)were collected. DNA was extracted and genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism. The association between polymorphic genotype and CRC predisposition was determined using the OR and 95%CI. RESULTS: The frequency of the homozygous variant (Gln/Gln) genotype was significantly higher in cases compared with controls (16.0% vs 10.2%, P = 0.049). The Gln/Gln genotype of XPC showed a significantly higher association with the risk of CRC (OR = 1.884; 95%CI: 1.082-3.277; P = 0.025). In the case of allele frequencies, variant allele C was associated with a significantly increased risk of CRC (OR = 1.375; 95%CI: 1.050-1.802; P = 0.020). Moreover, the risk was markedly higher for those who were carriers of the Gln/Gln variant genotype and were also cigarette smokers (OR = 3.409; 95%CI: 1.061-10.949; P = 0.032). CONCLUSION: The XPC Gln/Gln genotype alone and in combination with smoking increases the risk of CRC among Malaysians.     

Association between Ras association domain family 1A promoter methylation and hepatocellular carcinoma: A meta-analysis

AIM:To assess diagnostic accuracy of Ras association domain family 1A(RASSF1A)promoter methylation in body fluids(serum,plasma and whole blood)for hepatocellular carcinoma(HCC).METHODS:Relative information about study characteristics and incidence of RASSF1A methylation was collected.Quality of all included studies was evaluated by Quality Assessment of Diagnostic Accuracy Studies-2.Sensitivity and specificity were pooled using a randomeffect model,and a summary receiver operating characteristic curve was used to demonstrate the overall diagnostic performance.Positive likelihood ratio(PLR),negative likelihood ratio(NLR),and diagnostic odds ratio(DOR)with 95%CI were also calculated.Meta-regression was applied to analyze observed heterogeneity,and Deeks’test was performed to detect publication bias.RESULTS:After a systematic literature review,seven studies with a total of 302 cases of HCC and 250 cases of chronic liver diseases were included in the analysis.The pooled sensitivity and specificity were 0.70(95%CI:0.49-0.85)and 0.72(95%CI:0.54-0.85),respectively.The PLR was 2.51(95%CI:1.64-3.86),NLR was 0.41(95%CI:0.25-0.68),and DOR was 6.13(95%CI:3.17-11.84).Theχ2values of sensitivity,specificity,PLR,NLR and DOR were 59.41(P<0.001),50.50(P<0.001),17.40(P=0.010),31.24(P<0.001)and80.51(P<0.001),respectively.The area under the curve was 0.77(95%CI:0.73-0.81).Three factors were analyzed by univariate meta-regression and none was significant to interpret the observed heterogeneity(P>0.05).No significant publication bias was detected by Deeks’test(P=0.346).CONCLUSION:We showed the potential diagnostic value of RASSF1A methylation in body fluids in HCC patients and it may improve diagnostic accuracy combined with theα-fetoprotein test.     

白细胞介素-8基因251 A/T位点的多态性与亚洲人群胃癌易感性的Meta分析

[目的]用Meta分析的方法评价IL-8基因251 A/T位点的多态性与亚洲人群胃癌易感性的关系。[方法]检索Web of science、PubMed、EMBASE、万方数据库、中国生物医学文献数据库、中文科技期刊数据库、中国期刊全文数据库,日期均从各数据库开始建库至2018年1月。全面检索IL-8基因251 A/T位点的多态性与胃癌易感性的病例对照研究文献,采用STATA统计软件进行Meta分析。[结果]最终纳入15篇病例对照研究进行Meta分析,共计3738例胃癌患者、4497例健康对照者。分析结果显示,IL-8基因251 A/T位点在等位基因模型(A vs T:OR=1.12;95%CI为1.04~1.21;P=0.002)、共显性模型(AA vs AT:OR=1.15;95%CI为1.00~1.32;P=0.050)、相加模型(AA vs TT:OR=1.36;95%CI为1.18~1.57;P=0.000)、相加模型(AT vs TT:OR=1.23;95%CI为1.11~1.36;P=0.000)、显性模型(AA vs AT+TT:OR=1.23;95%CI为1.08~1.40;P=0.002)、隐性模型(TT vs AA+AT:OR=1.26;95%CI为1.15~1.39)下均与亚洲人群胃癌易感性有关。[结论]IL-8基因251 A/T位点多态性与亚洲人群胃癌的易感性相关。     

Association between diabetes mellitus and gastroesophageal reflux disease:A meta-analysis

AIM:To investigate whether there is a link between diabetes mellitus(DM) and gastroesophageal reflux disease(GERD).METHODS:We conducted a systematic search of Pub Med and Web of Science databases,from their respective inceptions until December 31,2013,for articles evaluating the relationship between DM andGERD.Studies were selected for analysis based on certain inclusion and exclusion criteria.Data were extracted from each study on the basis of predefined items.A meta-analysis was performed to compare the odds ratio(OR)in DM between individuals with and without GERD using a fixed effect or random effect model,depending on the absence or presence of significant heterogeneity.Subgroup analyses were used to identify sources of heterogeneity.Publication bias was assessed by Begg’s test.To evaluate the results,we also performed a sensitivity analysis.RESULTS:When the electronic database and hand searches were combined,a total of nine eligible articles involving 9067 cases and 81 968 controls were included in our meta-analysis.Based on the randomeffects model,these studies identified a significant association between DM and the risk of GERD(overall OR=1.61;95%CI:1.36-1.91;P=0.003).Subgroup analyses indicated that this result persisted in studies on populations from Eastern countries(OR=1.71;9 5%C I:1.3 8-2.1 2;P=0.0 0 3)a n d i n y o u n g e r patients(mean age50 years)(OR=1.70;95%CI:1.22-2.37;P=0.001).No significant publication bias was observed in this meta-analysis using Begg’s test(P=0.175).The sensitivity analysis also confirmed the stability of our results.CONCLUSION:This meta-analysis suggests that patients with DM are at greater risk of GERD than those who do not have DM.