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.     

Prognostic factors and long-term outcomes of hilar cholangiocarcinoma:A single-institution experience in China

AIM: To evaluate the prognostic factors of hilar cholangiocarcinoma in a large series of patients in a single institution.METHODS: Eight hundred and fourteen patients with a diagnosis of hilar cholangiocarcinoma that were evaluated and treated between 1990 and 2014, of which 381 patients underwent curative surgery, were included in this study. Potential factors associated with overall survival(OS) and disease-free survival(DFS) were evaluated by univariate and multivariate analyses.RESULTS: Curative surgery provided the best long-term survival with a median OS of 26.3 mo. The median DFS was 18.1 mo. Multivariate analysis showed that patients with tumor size > 3 cm [hazard ratio(HR) = 1.482, 95%CI: 1.127-1.949; P = 0.005], positive nodal disease(HR = 1.701, 95%CI: 1.346-2.149; P < 0.001), poor differentiation(HR = 2.535, 95%CI: 1.839-3.493; P < 0.001), vascular invasion(HR = 1.542, 95%CI: 1.082-2.197; P = 0.017), and positive margins(HR = 1.798, 95%CI: 1.314-2.461; P < 0.001) had poor OS outcome. The independent factors for DFS were positive nodal disease(HR = 3.383, 95%CI: 2.633-4.348; P < 0.001), poor differentiation(HR = 2.774, 95%CI: 2.012-3.823; P < 0.001), vascular invasion(HR = 2.136, 95%CI: 1.658-3.236; P < 0.001), and positive margins(HR = 1.835, 95%CI: 1.256-2.679; P < 0.001). Multiple logistic regression analysis showed that caudate lobectomy [odds ratio(OR) = 9.771, 95%CI: 4.672-20.433; P < 0.001], tumor diameter(OR = 3.772, 95%CI: 1.914-7.434; P < 0.001), surgical procedures(OR = 10.236, 95%CI: 4.738-22.116; P < 0.001), American Joint Committee On Cancer T stage(OR = 2.010, 95%CI: 1.043-3.870; P = 0.037), and vascular invasion(OR = 2.278, 95%CI: 0.997-5.207; P = 0.051) were independently associated with tumorfree margin, and surgical procedures could indirectly affect survival outcome by influencing the tumor resection margin. CONCLUSION: Tumor margin, tumor differentiation, vascular invasion, and lymph node status were independent factors for OS and DFS. Surgical procedures can indirectly affect survival outcome by influencing the tumor resection margin.     

Meta-analysis of subtotal stomach-preserving pancreaticoduodenectomy vs pylorus preserving pancreaticoduodenectomy

AIM: To investigate the differences in outcome following pylorus preserving pancreaticoduodenectomy (PPPD) and subtotal stomach-preserving pancreaticoduodenectomy (SSPPD).METHODS: Major databases including PubMed (Medline), EMBASE and Science Citation Index Expanded and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library were searched for comparative studies between patients with PPPD and SSPPD published between January 1978 and July 2014. Studies were selected based on specific inclusion and exclusion criteria. The primary outcome was delayed gastric emptying (DGE). Secondary outcomes included operation time, intraoperative blood loss, pancreatic fistula, postoperative hemorrhage, intraabdominal abscess, wound infection, time to starting liquid diet, time to starting solid diet, period of nasogastric intubation, reinsertion of nasogastric tube, mortality and hospital stay. The pooled odds ratios (OR) or weighted mean difference (WMD) with 95% confidence intervals (95%CI) were calculated using either a fixed-effects or random-effects model.RESULTS: Eight comparative studies recruiting 650 patients were analyzed, which include two RCTs, one non-randomized prospective and 5 retrospective trial designs. Patients undergoing SSPPD experienced significantly lower rates of DGE (OR = 2.75; 95%CI: 1.75-4.30, P < 0.00001) and a shorter period of nasogastric intubation (OR = 2.68; 95%CI: 0.77-4.58, P < 0.00001), with a tendency towards shorter time to liquid (WMD = 2.97, 95%CI: -0.46-7.83; P = 0.09) and solid diets (WMD = 3.69, 95%CI: -0.46-7.83; P = 0.08) as well as shorter inpatient stay (WMD = 3.92, 95%CI: -0.37-8.22; P = 0.07), although these latter three did not reach statistical significance. PPPD, however, was associated with less intraoperative blood loss than SSPPD [WMD = -217.70, 95%CI: -429.77-(-5.63); P = 0.04]. There were no differences in other parameters between the two approaches, including operative time (WMD = -5.30, 95%CI: -43.44-32.84; P = 0.79), pancreatic fistula (OR = 0.91; 95%CI: 0.56-1.49; P = 0.70), postoperative hemorrhage (OR = 0.51; 95%CI: 0.15-1.74; P = 0.29), intraabdominal abscess (OR = 1.05; 95%CI: 0.54-2.05; P = 0.89), wound infection (OR = 0.88; 95%CI: 0.39-1.97; P = 0.75), reinsertion of nasogastric tube (OR = 1.90; 95%CI: 0.91-3.97; P = 0.09) and mortality (OR = 0.31; 95%CI: 0.05-2.01; P = 0.22).CONCLUSION: SSPPD may improve intraoperative and short-term postoperative outcomes compared to PPPD, especially DGE. However, these findings need to be further ascertained by well-designed randomized controlled trials.     

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.     

Comparison of selected inflammation-based prognostic markers in relapsed or refractory metastatic colorectal cancer patients

AIM: To investigate the impact of systemic inflammationbased prognostic markers on overall survival in relapsed/refractory metastatic colorectal cancer(m CRC) patients. METHODS: To investigate prognostic markers in m CRC patients,this study was performed with patients who have experienced relapsed/refractory m CRC with standard chemotherapy or were inapplicable to conventional treatment modality because of poor performance status,age,or comorbidity. We reviewed the medical records of 177 m CRC patients managed with Korean Medicine(KM) treatment modality using an anticancer agent of Rhus verniciflua Stokes extract from June 2006 to April 2013. The clinicopathologic characteristics,laboratory test,the systemic inflammation markers including the modified Glasgow prognostic score(m GPS),neutrophil lymphocyte ratio(NLR),platelet lymphocyte ratio(PLR),lymphocyte monocyte ratio(LMR),and prognostic nutritional index(PNI) were analyzed. The overall survival of patients was calculated with the Kaplan-Meier method and the statistical significance was compared using with the log-rank test. To compare the impact of systemic inflammation based markers,the hazard ratio(HR) of m GPS,NLR,PLR,LMR,and PNI for overall survival were evaluated with the Cox proportional hazards regression.RESULTS: The majority of m CRC patients had relapsed/refractory to standard chemotherapy; 128 patients(72.3%) had undergone more than second line chemotherapy,and the median time from diagnosis of m CRC to initiation of KM was 9.4 mo. The median overall survival of enrolled patients was 8.3 mo. On univariate analyses,the inflammation markers of higher m GPS(P 0.001),NLR ≥ 5(P 0.001),PLR 300(P = 0.004),LMR ≤ 3.4(P 0.001),and PNI ≤ 45.3(P = 0.001) were significantly associated with decreased survival time. On stepwise multivariate proportional hazards model,m GPS at 2 vs 0(HR = 3.212,95%CI: 1.437-7.716,P = 0.004),and LMR ≤ 3.4(HR = 1.658,95%CI: 1.092-2.518,P = 0.018) as independent predictors associated with poor overall survival along with carbohydrate antigen 19-9(HR = 1.482,95%CI: 1.007-2.182,P = 0.046),AST ≥ 40(HR = 2.377,95%CI: 1.359-4.155,P = 0.002),and the treatment duration for KM less than 2.9 mo(HR = 1.718,95%CI: 1.160-2.543,P = 0.007).CONCLUSION: These results indicate that the inflammatory markers,m GPS and LMR are independent prognostic factors for predicting overall survival in relapsed/refractory m CRC patients.     

Lower serum folate is associated with development and invasiveness of gastric cancer

AIM: To evaluate the associations of serum folate level with development, invasiveness and patient survival of gastric cancer.METHODS: In this nested case-control study, patients with newly diagnosed gastric cancer undergoing gastrectomy were enrolled, and patients receiving chemotherapy prior to surgery, with other concurrent malignancy, or of the aboriginal and alien populations were excluded. In total, 155 gastric cancer patients and 149 healthy controls were enrolled for determination of serum folate levels and their correlation with gastric cancer. Using the median value of serum folate computed among the overall population as the cutoff value, the associations between serum folate and gastric cancer in all cases and different age and gender subgroups were analyzed by multivariate logistic regression analysis. In the patient cohort of gastric cancer, receiver-operating characteristic analyses were performed to calculate the best cutoff values of serum folate, and the associations between serum folate levels and clinicopathological features were further analyzed by multivariate regression analysis. Survival analyses were conducted using the Cox proportional hazards model.RESULTS: The mean serum folate level was significantly lower in gastric cancer patients than that in controls (3.71 ± 0.30 ng/mL vs 8.00 ± 0.54 ng/mL, P < 0.01), and folate levels were consistently lower in gastric cancer patients regardless of age and gender (all P < 0.01). Using the median serum folate value as the cutoff value, low serum folate was significantly associated with gastric cancer risk in the whole population (OR = 19.77, 95%CI: 10.54-37.06, P < 0.001) and all strata (age < 60 years OR = 17.39, 95%CI: 7.28-41.54, age ≥ 60 years (OR = 21.67, 95%CI: 8.27-56.80), males (OR = 17.95, 95%CI: 7.93-40.62), and females (OR = 20.95, 95%CI: 7.66-57.31); all P < 0.001. In the patient cohort of gastric cancer, the respective cutoff values showed that low serum folate levels were significantly associated with serosal invasion (OR = 2.54, 95%CI: 1.23-5.23), lymphatic invasion (OR = 2.23, 95%CI: 1.17-4.26), and liver metastasis (OR = 6.67, 95%CI: 1.28-34.91) of gastric cancer (all P < 0.05). Serum folate level below 1.90 ng/mL was associated with poor patient survival (HR = 1.84, 95%CI: 1.04-3.27, P < 0.05) in univariate analysis.CONCLUSION: Lower serum folate levels were significantly associated with gastric cancer development and invasive phenotypes. The role of folate depletion in gastric cancer invasion warrants further study.     

Association between cadherin-17 expression and pathological characteristics of gastric cancer:A meta-analysis

AIM: To construct a meta-analysis in order to examine the relationship between cadherin-17(CDH17) andgastric cancer(GC). METHODS: Related articles were selected by searching the following English or Chinese electronic databases: CINAHL, MEDLINE, Science Citation Index, the Chinese Journal Full-Text, and the Weipu Journal. NewcastleOttawa Scale(NOS) criteria were used to ensure consistency in reviewing and reporting results. Statistical analyses were conducted with Version 12.0 STATA statistical software.RESULTS: Ultimately, 11 articles, with a total of 2,120 GC patients, were found to be eligible for study inclusion. In comparisons of GC patients by TNM stage(Ⅲ-Ⅳ vs ?Ⅰ-Ⅱ: OR = 2.35, 95%CI: 1.15-4.825, P = 0.019), histologic grade(3-4 vs 1-2: OR = 3.48, 95%CI: 1.36-8.92, P = 0.009), invasion grade(T3-4 vs T1-2: OR = 2.86; 95%CI: 1.69-4.83; P = 0.000), and lymph node metastasis(positive vs negative: OR = 2.64; 95%CI: 1.33-5.27; P = 0.006), it was found that CDH17 showed more positive expressions in each of the more severe cases. Country-stratified analyses from all four experimental subgroups showed that high CDH17 expression levels may be related to GC among Chinese and Korean populations(all P < 0.05), with the exception of the invasion grade T3-4 vs T1-2 comparison, where the relation only held among the Chinese population(OR = 2.86, 95%CI: 1.69-4.83, P = 0.000). CONCLUSION: Collectively, the data reflects the capacity of CDH17 in tumor proliferation and metastasis among GC patients.     

Prognostic value of c-Met in colorectal cancer:A metaanalysis

AIM: To assess the prognostic value of c-Met status in colorectal cancer. METHODS: We conducted a search in Pub Med, Web of Science, and the Cochrane Library covering all published papers up to July 2014. Only studies assessing survival in colorectal cancer by c-Met status were included. This meta-analysis was performed by using STATA11.0.RESULTS: Ultimately, 11 studies were included in this analysis. Meta-analysis of the hazard ratios(HR)indicated that patients with high c-Met expression have a significantly poorer overall survival(OR)(HR = 1.33, 95%CI: 1.06-1.59) and progression-free survival(PFS)(HR = 1.47, 95%CI: 1.03-1.91). Subgroup analysis showed a significant association between high c-Met expression and poorer overall survival in the hazard ratio reported(HR = 1.41, 95%CI: 1.08-1.74).CONCLUSION: The present meta-analysis indicated that high c-Met expression was associated with poor prognosis in patients with colorectal cancer.     

Racial/ethnic disparities in hepatocellular carcinoma treatment and survival in California, 1988-2012

AIMTo describe racial/ethnic differences in treatment and survival among liver cancer patients in a population-based cancer registry.METHODSInvasive cases of primary hepatocellular carcinoma, n = 33270, diagnosed between January 1, 1988-December 31, 2012 and reported to the California Cancer Registry were analyzed by race/ethnicity, age, gender, geographical region, socio-economic status, time period of diagnosis, stage, surgical treatment, and survival. Patients were classified into 15 racial/ethnic groups: non-Hispanic White (White, n = 12710), Hispanic (n = 8500), Chinese (n = 2723), non-Hispanic Black (Black, n = 2609), Vietnamese (n = 2063), Filipino (n = 1479), Korean (n = 1099), Japanese (n = 658), American Indian/Alaskan Native (AIAN, n = 281), Laotian/Hmong (n = 244), Cambodian (n = 233), South Asian (n = 190), Hawai`ian/Pacific Islander (n = 172), Thai (n = 95), and Other Asian (n = 214). The main outcome measures were receipt of surgical treatment, and cause-specific and all-cause mortality.RESULTSAfter adjustment for socio-demographic characteristics, time period, and stage of disease, compared to Whites, Laotian/Hmong [odds ratio (OR) = 0.30, 95%CI: 0.17-0.53], Cambodian (OR = 0.65, 95%CI: 0.45-0.96), AIAN (OR = 0.66, 95%CI: 0.46-0.93), Black (OR = 0.76, 95%CI: 0.67-0.86), and Hispanic (OR = 0.78, 95%CI: 0.72-0.84) patients were less likely, whereas Chinese (OR = 1.58, 95%CI: 1.42-1.77), Koreans (OR = 1.45, 95%CI: 1.24-1.70), Japanese (OR = 1.41, 95%CI: 1.15-1.72), and Vietnamese (OR = 1.26, 95%CI: 1.12-1.42) were more likely to receive surgical treatment. After adjustment for the same covariates and treatment, cause-specific mortality was higher for Laotian/Hmong [(hazard ratio (HR) = 1.50, 95%CI: 1.29-1.73)], Cambodians (HR = 1.35, 95%CI: 1.16-1.58), and Blacks (HR = 1.07, 95%CI: 1.01-1.13), and lower for Chinese (HR = 0.82, 95%CI: 0.77-0.86), Filipinos (HR = 0.84, 95%CI: 0.78-0.90), Vietnamese (HR = 0.85, 95%CI: 0.80-0.90), Koreans (HR = 0.90, 95%CI: 0.83-0.97), and Hispanics (HR = 0.91, 95%CI: 0.88-0.94); results were similar for all-cause mortality.CONCLUSIONDisaggregated data revealed substantial racial/ethnic differences in liver cancer treatment and survival, demonstrating the need for development of targeted interventions to mitigate disparities.     

Abnormal β-catenin immunohistochemical expression as a prognostic factor in gastric cancer: A meta-analysis

AIM: To evaluate the effect of β-catenin immunohistochemical expression on the prognosis of gastric cancer (GC).METHODS: We searched Pubmed and Embase to identify eligible studies. The search ended on November 10, 2013, with no lower date limit. The citation lists associated with the studies were used to identify additional eligible studies. We included studies reporting sufficient information to estimate the HR and 95%CI, and information to estimate the OR in the analysis of clinicopathological features. The qualities of these studies were assessed using the Newcastle-Ottawa Quality Assessment Scale. HRs and ORs and their variance were calculated and pooled using Review Manager Version 5.2.RESULTS: A total of 24 studies were identified and comprised 3404 cases. β-catenin expression was significantly correlated with poor overall survival (OS) in GC patients (HR = 1.85, 95%CI: 1.39-2.46), but showed a significant degree of heterogeneity (I² = 71%, P < 0.0001). Subgroup analysis indicated that an abnormal pattern of β-catenin expression had an unfavorable effect on OS (HR = 1.79, 95%CI: 1.39-2.32). However, accumulation in the nucleus or loss of membrane did not influence the survival of GC patients independently. Moreover, the combined OR of β-catenin indicated that β-catenin expression was associated with Lauren classification (OR = 1.98, 95%CI: 1.19-3.29), lymph node metastasis (OR = 2.00, 95%CI: 1.44-2.77), distant metastasis (OR = 2.69, 95%CI: 1.35-5.38) and grade of differentiation (OR = 2.68, 95%CI: 1.66-4.34). β-catenin expression did not correlate with TNM stage (OR = 1.34 95%CI: 0.96-1.86), the depth of invasion (OR = 1.48, 95%CI: 0.94-2.33) or vascular invasion (OR = 1.11, 95%CI: 0.70-1.76).CONCLUSION: Abnormal β-catenin immunohistochemical expression may be associated with tumor progression and could be a predictive factor of poor prognosis in patients with GC.     

Oral microbiome and pancreatic cancer

BACKGROUNDMicrobiota profiles differ between patients with pancreatic cancer and healthy people, and understanding these differences may help in early detection of pancreatic cancer. Saliva sampling is an easy and cost-effective way to determine microbiota profiles compared to fecal and tissue sample collection.AIMTo investigate the saliva microbiome distribution in patients with pancreatic adenocarcinoma (PDAC) and the role of oral microbiota profiles in detection and risk prediction of pancreatic cancer.METHODSWe conducted a prospective study of patients with pancreatic cancer (n = 41) and healthy individuals (n = 69). Bacterial taxa were identified by 16S ribosomal ribonucleic acid gene sequencing, and a linear discriminant analysis effect size algorithm was used to identify differences in taxa. Operational taxonomic unit values of all selected taxa were converted into a normalized Z-score, and logistic regressions were used to calculate risk prediction of pancreatic cancer.RESULTSCompared with the healthy control group, carriage of Streptococcus and Leptotrichina (z-score) was associated with a higher risk of PDAC [odds ratio (OR) = 5.344, 95% confidence interval (CI): 1.282-22.282, P = 0.021 and OR = 6.886, 95%CI: 1.423-33.337, P = 0.016, respectively]. Veillonella and Neisseria (z-score) were considered a protective microbe that decreased the risk of PDAC (OR = 0.187, 95%CI: 0.055-0.631, P = 0.007 and OR = 0.309, 95%CI: 0.100-0.952, P = 0.041, respectively). Among the patients with PDAC, patients reporting bloating have a higher abundance of Porphyromonas (P = 0.039), Fusobacterium (P = 0.024), and Alloprevotella (P = 0.041); while patients reporting jaundice had a higher amount of Prevotella (P = 0.008); patients reporting dark brown urine had a higher amount of Veillonella (P = 0.035). Patients reporting diarrhea had a lower amount of Neisseria and Campylobacter (P = 0.024 and P = 0.034), and patients reporting vomiting had decreased Alloprevotella (P = 0.036).CONCLUSIONSaliva microbiome was able to distinguish patients with pancreatic cancer and healthy individuals. Leptotrichia may be specific for patients living in Sichuan Province, southwest China. Symptomatic patients had different bacteria profiles than asymptomatic patients. Combined symptom and microbiome evaluation may help in the early detection of pancreatic cancer.     

Placement of prophylactic pancreatic stents to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis in high-risk patients: A meta-analysis

AIM:To assess the effectiveness of pancreatic stents for preventing pancreatitis in high-risk patients after endoscopic retrograde cholangiopancreatography(ERCP).METHODS:PubMed,Embase,Science Citation Index,and Cochrane Controlled Trials Register were searched to identify relevant trials published in English.Inclu-sion and exclusion criteria were used to screen for suitable studies.Two reviewers independently judged the study eligibility while screening the citations.The methodological quality of the included trials was assessed using the Jadad scoring system.All results were expressed as OR and 95%CI.Data were analyzed using Stata12.0 software.RESULTS:Ten eligible randomized controlled trials were selected,including 1176 patients.A fixed-effects model in meta-analysis supported that pancreatic duct stents significantly decreased the incidence of postERCP pancreatitis(PEP)in high-risk patients(OR=0.25;95%CI:0.17-0.38;P<0.001).Pancreatic stents also alleviated the severity of PEP(mild pancreatitis after ERCP:OR=0.33;95%CI:0.21-0.54;P<0.001;moderate pancreatitis after ERCP:OR=0.30;95%CI:0.13-0.67;P=0.004).The result of severe pancreatitis after ERCP was handled more rigorously(OR=0.24;95%CI:0.05-1.16;P=0.077).Serum amylase levels were not different between patients with pancreatic stents and control patients(OR=1.08;95%CI:0.82-1.41;P=0.586).CONCLUSION:Placement of prophylactic pancreatic stents may lower the incidence of post-ERCP pancreatitis in high-risk patients and alleviate the severity of this condition.     

S-1-based vs non-S-1-based chemotherapy in advanced gastric cancer: A meta-analysis

AIM: To assess the efficacy and tolerability of S-1-based vs non-S-1-based chemotherapy in advanced gastric cancer (AGC).METHODS: We extracted reported endpoints, including overall survival (OS), progression-free survival (PFS), time-to-treatment failure (TTF), objective response rate (ORR) and adverse effects, from randomized controlled trials identified in PubMed, the Cochrane library, Science Direct, EMBASE and American Society of Clinical Oncology meetings. Stata software was used to calculate the pooled values.RESULTS: Seven randomized controlled trials involving 2176 patients were included in this meta-analysis. Compared to non-S-1-based regimens, the use of S-1-based regimens were associated with an increase in ORR (RR = 1.300; 95%CI: 1.028-1.645); OS (HR = 0.89; 95%CI: 0.81-0.99; P = 0.025), TTF (HR = 0.83; 95%CI: 0.75-0.92; P = 0.000), and a lower risk of febrile neutropenia (RR = 0.225; P = 0.000) and stomatitis (RR = 0.230; P = 0.032). OS, PFS and TTF were prolonged, especially in the Asian population. In subgroup analysis, statistically significant increases in ORR (RR = 1.454; P = 0.029), OS (HR = 0.895; P = 0.041) and TTF (HR = 0.832; P = 0.000) were found when S-1-based chemotherapy was compared to 5-fluorouracil (5-FU)-based chemotherapy. The incidence of leukopenia (RR = 0.584; P = 0.002) and stomatitis (RR = 0.230; P = 0.032) was higher in the 5-FU-based arm. S-1-based regimens had no advantage in ORR, OS, PFS, TTF and grade 3 or 4 adverse events over capecitabine-based regimens.CONCLUSION: S-1-based chemotherapy may be a good choice for AGC because of longer survival times, better tolerance and more convenient use.     

IFOBT与肿瘤标志物、炎症指标联合检测对结直肠进展期腺瘤发生的预测价值

背景目前临床缺乏对结直肠癌前病变有效的无创筛查手段,识别高危人群和多指标联合检测已成为癌及癌前病变筛查的趋势.多种炎症指标已广泛用于各种肿瘤的诊断及预后,而对癌前病变诊断价值的研究较少.目的探讨粪便免疫潜血实验(immunochemical fecal occult blood testing,IFOBT),肿瘤标志物(CEA、CA199),炎症指标包括中性粒细胞/淋巴细胞比值(neutrophil/lymphocyte ratio,NLR)、血小板/淋巴细胞比值(platelet/lymphocyte ratio,PLR)及一般临床特征对结直肠进展期腺瘤息肉发生的预测价值.方法回顾性分析我院2014-2018年行电子结肠镜检查并经病理学证实的295例结直肠进展期腺瘤病例作为观察组,选择同期448例非进展期腺瘤病例作为对照组,收集患者的一般临床资料包括基本特征(性别、年龄)、生活习惯(吸烟史、饮酒史)、既往史(高血压史、冠心病史、糖尿病史),手术史(胆囊或阑尾切除史);实验室检查(NLR、PLR、CEA、CA199、IFOBT);进行单因素差异分析,将有意义的结果纳入二元logistic回归分析,绘制ROC曲线,评估相关指标对结直肠进展期腺瘤发生的预测价值.结果Logistic回归分析显示:年龄(OR=1.047,95%CI:1.028-1.066,P=0.000)、吸烟(OR=1.880,95%CI:1.250-2.826,P=0.002)、糖尿病(OR=2.073,95CI%:1.216-3.535,P=0.007)、既往胆囊切除(OR=9.206,95CI%:2.904-29.181,P=0.000)、IFOBT(OR=7.681,95%CI:4.585-12.869,P=0.000)、CA199(OR=1.039,95%CI:1.018-1.059,P=0.000)、NLR(OR=1.706,95%CI:1.388-2.097,P=0.000)与进展期腺瘤的发生独立相关.对于预测进展期腺瘤的发生,IFOBT的灵敏度为34.6%,特异度为94.2%,AUC为0.644,95%CI:0.602-0.686,CA199的最佳截断点为7.87 U/mL,灵敏度为53.9%,特异度为66.1%,AUC为0.639,95%CI:0.598-0.679,NLR的最佳截断点为2.04,灵敏度为50.2%.特异度为71.8%,AUC为0.645,95%CI:0.605-0.685,当三者联合检测时其灵敏度为52.9%,特异度为82.8%,AUC 95%CI为0.752(0.716-0.788),进展期腺瘤亚组分析中,IFOBT(-)和IFOBT(+)亚组之间的腺瘤位置(P=0.048)、腺瘤直径(P=0.000)、分化级别(P=0.000)差异有统计学意义,低NLR(<2.04)和高NLR(≥2.04)亚组之间的性别(P=0.004)、腺瘤直径(P=0.028)、分化级别(P=0.000)差异有统计学意义.结论高龄、吸烟、糖尿病、既往胆囊切除人群更易发生结直肠进展期腺瘤,临床需对此类人群提高重视,IFOBT、NLR、CA199对进展期腺瘤的发生具有诊断意义,三者联合检测时其诊断效能最佳.     

Alanine aminotransferase normalization at week 8 predicts viral response during hepatitis C treatment

AIM:To investigate alanine aminotransferase(ALT)and sustained virological response(SVR)in chronic hepatitis C(CHC)during peginterferon-ribavirin treatment.METHODS:One hundred and fifty-one genotype 1CHC patients underwent treatment for 48 wk with peginterferon and ribavirin,and were retrospectively divided into two groups as having a rapid virological response(RVR)(Group 1,n=52)and not having an RVR(Group 2,n=99).We also subdivided each group into two according to the initial ALT level being high(Group1h and Group 2h)or normal(Group 1n and Group 2n).HCV RNA and ALT levels were measured at baseline;at 4,12,24 and 48 wk during the treatment period;and at 24 wk follow-up.ALT levels were also obtained at 8 wk.According to the results of ALT,patients were enrolled in either the follow-up abnormal or follow-up normalized ALT groups at each interval.Patients with high and normal ALT levels were compared for each interval in terms of SVR.RESULTS:The SVR rates were 83%vs 40%(P=0.000),82%vs 84%(P=0.830),and 37%vs 44%(P=0.466)when comparing Group 1 with 2,1h with1n,and 2h with 2n,respectively.In Group 2h,the SVR rates were 34%vs 40%(P=0.701),11%vs 52%(P=0.004),12%vs 50%(P=0.007),7%vs 50%(P=0.003),6%vs 53%(P=0.001),and 0%vs 64%(P=0.000)when comparing patients with high and normalized ALT levels at week 4,8,12,24,48 and 72,respectively.The multiple logistic regression analysis revealed that RVR(OR=7.05;95%CI:3.1-16.05,P=0.000),complete early virological response(cEVR)(OR=17.55;95%CI:6.32-48.76,P=0.000),normalization of ALT at8 wk(OR=3.04;95%CI:1.31-7.06,P=0.008),and at 12 wk(OR=4.21;95%CI:1.65-10.76,P=0.002)were identified as independent significant predictive factors for SVR.CONCLUSION:Normalization of ALT at 8 wk may predict viral response during peginterferon-ribavirin treatment in genotype-1 CHC patients especially without RVR.     

TIPS improves liver transplantation-free survival in cirrhotic patients with refractory ascites:An updated meta-analysis

AIM:To compare the liver transplantation-free(LTF)survival rates between patients who underwent transjugular intrahepatic portosystemic shunts(TIPS)and those who underwent paracentesis by an updated meta-analysis that pools the effects of both number of deaths and time to death.METHODS:MEDLINE,EMBASE,and the Cochrane Library were searched from the inception to October2012.LTF survival,liver transplantation,liver diseaserelated death,non-liver disease-related death,recurrent ascites,hepatic encephalopathy(HE)and severe HE,and hepatorenal syndrome were assessed as outcomes.LTF survival was estimated using a HR with a95%CI.Other outcomes were estimated using OR with95%CIs.Sensitivity analyses were performed to assess the effects of potential outliers in the studies according to the risk of bias and the study characteristics.RESULTS:Six randomized controlled trials with 390patients were included.In comparison to paracentesis,TIPS significantly improved LTF survival(HR=0.61,95%CI:0.46-0.82,P<0.001).TIPS also significantly decreased liver disease-related death(OR=0.62,95%CI:0.39-0.98,P=0.04),recurrent ascites(OR=0.15,95%CI:0.09-0.24,P<0.001)and hepatorenal syndrome(OR=0.32,95%CI:0.12-0.86,P=0.02).However,TIPS increased the risk of HE(OR=2.95,95%CI:1.87-4.66,P=0.02)and severe HE(OR=2.18,95%CI:1.27-3.76,P=0.005).CONCLUSION:TIPS significantly improved the LTF survival of cirrhotic patients with refractory ascites and decreased the risk of recurrent ascites and hepatorenal syndrome with the cost of increased risk of HE compared with paracentesis.Further studies are warranted to validate the survival benefit of TIPS in clinical practice settings.     

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.     

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.     

Feasible endoscopic therapy for early gastric cancer

AIM: To analyze the relationship between lymph node metastasis and clinical pathology of early gastric cancer(EGC) in order to provide criteria for a feasible endoscopic therapy.METHODS: Clinical data of the 525 EGC patients who underwent surgical operations between January 2009 and March 2014 in the West China Hospital of Sichuan University were analyzed retrospectively. Clinical pathological features were compared between different EGC patients with or without lymph node metastasis, and investigated by univariate and multivariate analyses for possible relationships with lymph node metastasis.RESULTS: Of the 2913 patients who underwent gastrectomy with lymph node dissection, 529 cases were pathologically proven to be EGC and 525 cases were enrolled in this study, excluding 4 cases of gastric stump carcinoma. Among 233 patients with mucosal carcinoma, 43(18.5%) had lymph node metastasis. Among 292 patients with submucosal carcinoma, 118(40.4%) had lymph nodemetastasis. Univariate analysis showed that gender, tumor size, invasion depth, differentiation type and lymphatic involvement correlated with a high risk of lymph node metastasis. Multivariate analysis revealed that gender(OR = 1.649, 95%CI: 1.091-2.492, P = 0.018), tumor size(OR = 1.803, 95%CI: 1.201-2.706, P = 0.004), invasion depth(OR = 2.566, 95%CI: 1.671-3.941, P = 0.000), histological differentiation(OR = 2.621, 95%CI: 1.624-4.230, P = 0.000) and lymphatic involvement(OR = 3.505, 95%CI: 1.590-7.725, P = 0.002) wereindependent risk factors for lymph node metastasis. Comprehensive analysis showed that lymph node metastasis was absent in patients with tumor that was limited to the mucosa, size ≤ 2 cm, differentiated and without lymphatic involvement.CONCLUSION: We propose an endoscopic therapy for EGC that is limited to the mucosa, size ≤ 2 cm, differentiated and without lymphatic involvement.     

Factors associated with incomplete colonoscopy at a Japanese academic hospital

AIM:To evaluate significant risk factors for incomplete colonoscopy at a Japanese academic hospital.METHODS:A total of 11812 consecutive Japanese people were identified who underwent a colonoscopy at an academic hospital.A multiple logistic regression model was used to evaluate retrospectively the significant risk factors for incomplete colonoscopy.RESULTS:The cecal intubation rate was 95.0%.By univariate analysis,age,female sex,poor bowel cleansing,and a history of abdominal or pelvic surgery were significant risk factors for incomplete colonoscopy(P<0.001).Moreover,age-and sex-adjusted analysis showed that significant risk factors for incomplete colonoscopy were female sex(OR=1.38,95%CI:1.17-1.64,P=0.0002),age≥60 years old(OR=1.44,95%CI:1.22-1.71,P<0.0001),a history of prior abdominal or pelvic surgery(OR=1.55,95%CI:1.28-1.86,P<0.0001),poor bowel cleansing(OR=4.64,95%CI:3.69-5.84,P<0.0001),and inflammatory bowel disease(IBD)(OR=1.48,95%CI:1.13-1.95,P=0.0048).In Japanese men,by age-adjusted analysis,IBD(OR=1.69,95%CI:1.18-2.43,P=0.005)was an independent risk factor for incomplete colonoscopy.CONCLUSION:Several characteristics in the Japanese population were identified that could predict technical difficulty with colonoscopy.