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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 and aim: Hepatic decompensation is a severe on-treatment adverse event for chronic hepatitis C treated with paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD). Till now, few papers regarding on-treatment hepatic decompensation have been reported. The study aims to analyze the general feature and predictive factors of on-treatment hepatic decompensation in hepatitis C virus (HCV) genotype 1b-infected patients with advanced fibrosis and compensated cirrhosis who receive treatment with PrOD. Methods: A real-word cohort enrolled 189 HCV genotype 1b patients with advanced fibrosis and compensated cirrhosis treated with 12-week PrOD. Clinical and laboratory data were analyzed between patients with and without on-treatment hepatic decompensation. Results: The sustained virologic response rate at 12 weeks after treatment was 97.3% in HCV subtype 1b patients with advanced fibrosis and cirrhosis. On-treatment hyperbilirubinemia (total bilirubin >2 mg/dL) occurred in 27 (14.3%) patients, and the incidence of the increase of total and direct form bilirubin was significantly different during treatment between patients with Child-Turcotte-Pugh score 5 and score 6. Five (18.5%) hyperbilirubinemia patients progressed to hepatic decompensation. Older age (adjusted OR: 1.2, 95% CI: 1.0–1.4) and albumin ≤3.6 g/dL (adjusted OR: 10.4, 95% CI: 1.3–81.2) may be two predictors for on-treatment hepatic decompensation by multivariate analysis. Conclusions: PrOD is an effective direct-acting antiviral agent for antiviral therapy in HCV genotype 1b patients with advanced fibrosis and cirrhosis. Hyperbilirubinemia is possibly the early warning feature of on-treatment hepatic decompensation. This serious adverse event of on-treatment hepatic decompensation is not common. Older age and low baseline albumin level may be predictive factors. [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]

Purpose: Portal vein thrombosis (PVT) is generally recognized as a prognostic factor in HCC. Our purpose is to assess and compare the survival of patients with PVT and without PVT, after Y-90 Trans-Arterial Radio-Embolization (TARE) of unresectable HCC, unresponsive to other loco-regional treatments. Materials and methods: Between November 2005 and November 2012, Y-90 resin-based TARE was performed in an IRB-approved prospective protocol, on 89 patients with unresectable HCC. 33/89 patients had PVT, the remaining 56 were resistant-to-cTACE or underwent TARE as a downstaging therapy. All patients were studied with Multi-Detector Computed Tomography (MDCT), angiography, 99mTc-MAA-scintigraphy and liver biopsy. Gastro-duodenal artery was embolized in most cases. Proton-Pump Inhibitors were administered to prevent gastritis and ulcers. χ2 test with Yates correction and log rank test were used to compare the two proportions and Kaplan-Meier survival curves, respectively. Results: The average activity administered was 1.7 ± 0.4 GBq. After the treatment, CTCAE grade 2 adverse events occurred in 46% (41/89) patients: in particular, fever and abdominal pain were found in 25 and 16 patients, respectively. No major side-effect was observed. According to mRECIST criteria, partial response or complete response was found in 70% of patient three months after the treatment, and in 90.5% nine months after the treatment. No significant difference was found in survival of patients with PVT compared to those without PVT (p-value = 0.672). A complete regression of PVT was observed in almost half patients (13/27, 48.1%). Conclusions: Portal vein invasion does not affect survival in advanced stage HCC-patients undergoing TARE using Y-90 resin-based microspheres. Y90 procedure is associated with regression of portal vein tumor thrombus. [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]

Background/Aims: Limited treatment options are available for patients with hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT). Transarterial radioembolization using Yttrium-90 microspheres is a new treatment modality for HCC with PVT. For this analysis, we compared responses to treatment with radioembolization and with sorafenib. Methods: We evaluated 32 patients who were part of a multicenter retrospective cohort. All patients had PVT without extrahepatic metastasis and were treated with radioembolization in one of six tertiary referral hospitals in Korea. We retrospectively enrolled another 31 consecutive PVT patients without extrahepatic metastasis from a single center who received sorafenib treatment to serve as the control group. We used inverse probability weighting (IPW) using propensity scores to adjust for the between-group differences in baseline characteristics. Results: At 3 months, the response rate and disease control rate were 32.1% (9/32) and 57.1% (16/32), respectively, in the radioembolization group and 3.2% (1/31) and 41.9% (13/31) in the sorafenib group. Median overall survival (OS) and time to progression (TTP) were not significantly different between the radioembolization group and the sorafenib group (13.8 months and 10.0 months, P = 0.22; and 6.0 months and 6.0 months, P = 0.08; respectively). No differences in OS (P = 0.97) or TTP (P = 0.34) were observed after IPW was applied to balance the population characteristics. The sorafenib group showed significantly more grade 3/4 adverse effects than the radioembolization group (P < 0.01). Conclusion: HCC patients with PVT who underwent radioembolization achieved comparable survival to patients who received sorafenib, even after application of IPW. The radioembolization group also experienced fewer severe adverse effects. Radioembolization can be considered a new treatment option for patients with HCC with PVT. [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]

Objective: Recent evidence indicates a crucial role of the immunoinhibitory receptor programmed death-1 (PD-1) in enforcing T-cell dysfunction during chronic viral infection and cancer. We assessed the impact of circulating soluble PD-1 (sPD-1) levels on long-term dynamics of hepatitis B virus (HBV) load and hepatocellular carcinoma (HCC) risk. Methods: In a case-cohort study on longitudinal analysis of viral load within a cohort of 2903 men chronically infected with HBV, followed up from baseline (1989–1992) through 2010, we determined sPD-1 levels in baseline plasma with enzyme-linked immunosorbent assay from 126 men who subsequently developed HCC and 1155 men who did not develop HCC. To evaluate whether patients' characteristics involved the use of sPD-1 as a biomarker, sPD-1 was also tested in 614 newly-diagnosed patients with HBV-related HCC recruited from a multicenter study for comparison with the 1155 noncases in the case-cohort study. Results: Plasma quartile levels of sPD-1 were positively associated with HCC risk for men in the case-cohort analysis (vs. quartile 1: adjusted odds ratios [95% confidence intervals] for quartile 2-quartile 4 were 1.51 [0.75–3.03], 2.15 [1.12–4.13], and 2.29 [1.20–4.38], respectively), and in the case-control study regardless of age-of-onset and clinical stage. Furthermore, we found longitudinal effect of elevated sPD-1 levels to maintain higher viral load for 4 or more years, with greater and more prolonged effect among HBV genotype C- vs. non-C-infected participants. High levels of viral load and sPD-1 (vs. absence of both) was associated with a 6.29-fold increase in risk of HCC, and combining both conditions with HBV genotype C yielded an odds ratio of 30.47 with significant additive interaction (relative excess risk due to interaction: 27.08 [95% confidence interval = 8.76–45.41]). Conclusions: Our data suggest plasma sPD-1 as an important immune-related marker for assessment of HBV activity and HCC risk. [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: Previous epidemiologic studies have reported that a history of allergy is associated with reduced risk of colorectal cancer and other malignancies. However, no information is available for the association between allergy and the risk of lymph node metastasis. Our study was designed to determine this association in rectal cancer. Methods: Patients who were treated at our hospital in the period from January 2003 to June 2011, and with a pathologically hospital discharge diagnosis of rectal adencarcinoma, were included. The clinical, laboratory, and pathologic parameters were analyzed. A multivariate logistic regression model was used to determine the association. Moreover, for type of allergic drug, sub-group analysis was performed. Results: 469 patients were included, including 231 with pathological lymph node metastasis (pLNM) (49.3%) and 238 without pLNM. Univariate analysis showed, compared with patients without pLNM, patients with pLNM had a younger age (60.6±12.8 yr vs. 63.6±12.2 yr, P = 0.012), a lower percentage of drug allergy (8.7% vs. 16.0%, P = 0.016), an increased CEA (median/interquartile-range 5.40/2.40–13.95 vs. 3.50/2.08–8.67, P = 0.009), and a lower serum sodium (141±3.1 mmol/L vs. 142±2.9 mmol/L, P = 0.028). Multivariate analysis showed that drug allergy was associated with a reduced risk of pLNM (OR = 0.553; 95% CI, 0.308–0.994; P = 0.048). In addition, our results showed that: (1) for tumor classification, patients with drug allergy had a higher percentage of group patients with pT1/pT2; and (2) for type of allergic drug, this inverse association was found for penicillins, not for other allergic drugs. Conclusion: Drug allergy is associated with a reduced risk of pLNM in rectal cancer. [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: 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]

Background and Aims: The prevention of esophageal strictures following circumferential mucosal resection remains a major clinical challenge. Human amniotic membrane (AM) is an easily available material, which is widely used in ophthalmology due to its wound healing, anti-inflammatory and anti-fibrotic properties. We studied the effect of AM grafts in the prevention of esophageal stricture after endoscopic submucosal dissection (ESD) in a swine model. Animals and Methods: In this prospective, randomized controlled trial, 20 swine underwent a 5 cm-long circumferential ESD of the lower esophagus. In the AM Group (n = 10), amniotic membrane grafts were placed on esophageal stents; a subgroup of 5 swine (AM 1 group) was sacrificed on day 14, whereas the other 5 animals (AM 2 group) were kept alive. The esophageal stent (ES) group (n = 5) had ES placement alone after ESD. Another 5 animals served as a control group with only ESD. Results: The prevalence of symptomatic strictures at day 14 was significantly reduced in the AM group and ES groups vs. the control group (33%, 40% and 100%, respectively, p = 0.03); mean esophageal diameter was 5.8±3.6 mm, 6.8±3.3 mm, and 2.6±1.7 mm for AM, ES, and control groups, respectively. Median (range) esophageal fibrosis thickness was 0.87 mm (0.78–1.72), 1.19 mm (0.28–1.95), and 1.65 mm (0.7–1.79) for AM 1, ES, and control groups, respectively. All animals had developed esophageal strictures by day 35. Conclusions: The anti-fibrotic effect of AM on esophageal wound healing after ESD delayed the development of esophageal stricture in our model. However, this benefit was of limited duration in the conditions of our study. [ABSTRACT FROM AUTHOR]

At present, carcinogenic models imply that all individuals in a population are susceptible to cancer. These models either ignore a fall of the cancer incidence rate at old ages, or use some poorly identifiable parameters for its accounting. In this work, a new heuristic model is proposed. The model assumes that, in a population, only a small fraction (pool) of individuals is susceptible to cancer and decomposes the problem of the carcinogenic modeling on two sequentially solvable problems: (i) determination of the age-specific hazard rate in individuals susceptible to cancer (individual hazard rate) from the observed hazard rate in the population (population hazard rate); and (ii) modelling of the individual hazard rate by a chosen “up” of the theoretical hazard function describing cancer occurrence in individuals in time (age). The model considers carcinogenesis as a failure of individuals susceptible to cancer to resist cancer occurrence in aging and uses, as the theoretical hazard function, the three-parameter Weibull hazard function, often utilized in a failure analysis. The parameters of this function, providing the best fit of the modeled and observed individual hazard rates (determined from the population hazard rates), are the outcomes of the modeling. The model was applied to the pancreatic cancer data. It was shown that, in the populations stratified by gender, race and the geographic area of living, the modeled and observed population hazard rates of pancreatic cancer occurrence have similar turnovers at old ages. The sizes of the pools of individuals susceptible to this cancer: (i) depend on gender, race and the geographic area of living; (ii) proportionally influence the corresponding population hazard rates; and (iii) do not influence the individual hazard rates. The model should be further tested using data on other types of cancer and for the populations stratified by different categorical variables. [ABSTRACT FROM AUTHOR]

Application of textural features analysis to 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) images has been used to characterize intra-tumor uptake heterogeneity and has been shown to reflect disease outcome. A current hypothesis is that 18F-FDG uptake heterogeneity may reflect the physiological tracer uptake related to tumor perfusion. The purpose of our study was to investigate the correlations between intra-tumor uptake heterogeneity and vascular parameters derived from dynamic contrast enhanced (DCE) computed tomography (CT) obtained from an integrated 18F-FDG PET/perfusion CT examination. Methods: Thirty patients with proven colorectal cancer prospectively underwent integrated 18F-FDG PET/DCE-CT to assess the metabolic-flow phenotype. Both CT blood flow parametric maps and PET images were analyzed. Correlations between PET heterogeneity and perfusion CT were assessed by Spearman's rank correlation analysis. Results: Blood flow visualization provided by DCE-CT images was significantly correlated with 18F-FDG PET metabolically active tumor volume as well as with uptake heterogeneity for patients with stage III/IV tumors (|ρ|:0.66 to 0.78; p-value<0.02). Conclusion: The positive correlation found with tumor blood flow indicates that intra-tumor heterogeneity of 18F-FDG PET accumulation reflects to some extent tracer distribution and consequently indicates that 18F-FDG PET intra-tumor heterogeneity may be associated with physiological processes such as tumor vascularization. [ABSTRACT FROM AUTHOR]

Objective and Background: Although many studies on evaluating the safety of liver resection in obese patients have been conducted, the results remain contradictory. The aim of our study was to investigate the safety of overweight and obese patients undergoing liver resection for hepatitis B-related hepatocellular carcinoma in a large sample. Methods: In a retrospective cohort with 1543 hepatitis B-related hepatocellular carcinoma patients, the subjects were stratified into four groups according to their body mass index(BMI): obesity(BMI≥28), overweight(BMI:24.0–27.9), normal weight(BMI:18.5–23.9) and underweight(BMI<18.5). The Dindo–Clavien classification system was used for grading complications. Clinical characteristics and operative outcomes were compared among the four groups. Risk factors for postoperative complications were evaluated by multivariate analysis. Results: According to the category criteria of the Working Group on Obesity in China (WGOC) criteria, 73(4.7%) obese, 412(26.7%) overweight, 982(63.6%) normal weight and 76(4.9%) underweight patients were included in our cohort. Overweight and obese patients had more preoperative comorbidities such as hypertension(P<0.001). Mortality, total complications and complications classified by Clavien system were similar among the four groups except that the underweight patients had fewer total complications. However, postoperative wound complication was more common in overweight and obese patients(6.3% vs 2.5%,P<0.001,11.0% vs 2.5%,P = 0.001). Multivariate analysis revealed that BMI was not an independently significant factor for postoperative complications. Conclusions: Liver resection for obese and overweight patients is safe and BMI itself is not a risk factor for mortality and morbidity. [ABSTRACT FROM AUTHOR]

Background: Serum carcinoembryonic antigen (sCEA) level might be an indicator of disease. Indeed, an elevated sCEA level is a prognostic factor in colorectal cancer (CRC) patients. However, the genetic determinants of sCEA level in healthy and CRC population remains unclear. Thus we investigated the genetic markers associated with elevated serum sCEA level in these two populations and its clinical implications. Methods and Findings: Genome-wide association study (GWAS) was conducted in a cohort study with 4,346 healthy male adults using the Illumina Omni 1 M chip. Candidate SNPs associated with elevated sCEA levels were validated in 194 CRC patients on ABI Taqman platform. Eight candidate SNPs were validated in CRC patients. The rs1047781 (chr19- FUT2) (A/T) was associated with elevated sCEA levels, and rs8176746 (chr9- ABO) was associated with the regional lymph metastasis in the CRC patients. The preoperative sCEA level was a risk factor for tumor recurrence in 5 years after operation (OR = 1.427, 95% CI: 1.005∼1.843, P = 0.006). It was also one of the risk factors for regional lymph node metastasis (OR = 2.266, 95% CI: 1.196∼4.293, P = 0.012). The sCEA level in rs1047781-T carriers was higher than that in the A carriers in CRC patients without lymph node metastasis (P = 0.006). The regional lymph node metastasis in patients with homozygote AA of rs8176746 was more common than that in the heterozygote AG carriers (P = 0.022). In addition, rs1047781-AT and TT CRC patients exhibited a worse disease-free survival than AA genotype carriers (P = 0.023). Conclusions: We found candidate SNPs associated with elevated sCEA levels in both healthy males and CRC population. Rs1047781 (chr19- FUT2) may be the susceptible locus for recurrence of CRC in a population from Southern China. [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]

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: 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]

Background and Aims: Laterally spreading tumor (LST) is a colorectal pre-cancerous lesion. Previous studies have demonstrated distinct LST clinicopathological characteristics in different populations. This study evaluated clinicopathological characteristics of LST in a Chinese population. Methods: A total of 259 Chinese LST patients with 289 lesions were recruited for endoscopic and clinicopathological analyses. Results: Among these 289 lesions, 185 were granular type (LST-G), whereas 104 were non-granular type (LST-NG). LST-G lesions were further classified into homogeneous G-type and nodular mixed G-type, while LST-NG lesions were further classified into flat elevated NG-type and pseudo-depressed NG-type. Clinically, these four LST subtypes showed distinct clinicopathological characteristics, e.g., lesion size, location, or histopathological features (high-grade intraepithelial neoplasia and submucosal carcinoma). The nodular mixed G-type showed larger tumor size and higher incidence of high-grade intraepithelial neoplasia compared to the other three subtypes, while pseudo-depressed NG-type lesions showed the highest incidence of submucosal carcinoma. Noticeably, no diffidence was detected between the lesions of homogeneous G-type and flat elevated NG-type with regard to the histopathological features. Histology of the malignancy potential was associated with nodular mixed G-type [OR = 2.41, 95% CI (1.09–5.29); P = 0.029], flat elevated NG-type [OR = 3.49, 95% CI (1.41–8.22); P = 0.007], Diameter ≥30 mm [OR = 2.56, 95% CI (1.20–5.20); P = 0.009], Villous adenoma [OR = 2.76, 95% CI (1.01–7.58); P = 0.048] and serrated adenoma [OR = 6.99, 95% CI (1.81–26.98); P = 0.005]. Conclusion: Chinese LSTs can be divided into four different subtypes, which show distinct clinicopathological characteristics. Morphology, size and pathological characteristics are all independent predictors of advanced histology. [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]

Gastric and colorectal cancers (GC and CRC) have poor prognosis and are resistant to chemo- and/or radiotherapy. In the present study, the prophylactic effects of dendritic cell (DC) vaccination are evaluated on disease progression and clinical benefits in a group of 54 GC and CRC patients treated with DC immunotherapy combined with cytokine-induced killer (CIK) cells after surgery with or without chemo-radiotherapy. DCs were prepared from the mononuclear cells isolated from patients using IL-2/GM-CSF and loaded with tumor antigens; CIK cells were prepared by incubating peripheral blood lymphocytes with IL-2, IFN-γ, and CD3 antibodies. The DC/CIK therapy started 3 days after low-dose chemotherapy and was repeated 3–5 times in 2 weeks as one cycle with a total of 188.3±79.8×106 DCs and 58.8±22.3×108 CIK cells. Cytokine levels in patients' sera before and after treatments were measured and the follow-up was conducted for 98 months to determine disease-free survival (DFS) and overall survival (OS). The results demonstrate that all cytokines tested were elevated with significantly higher levels of IFN-γ and IL-12 in both GC and CRC cohorts of DC/CIK treated patients. By Cox regression analysis, DC/CIK therapy reduced the risk of post-operative disease progression (p<0.01) with an increased OS (<0.01). These results demonstrate that in addition to chemo- and/or radiotherapy, DC/CIK immunotherapy is a potential effective approach in the control of tumor growth for post-operative GC and CRC patients. [ABSTRACT FROM AUTHOR]

Prognosis of patients with colorectal cancer (CRC) is generally poor because of the lack of simple, convenient, and noninvasive tools for CRC detection at the early stage. The discovery of microRNAs (miRNAs) and their different expression profiles among different kinds of diseases has opened a new avenue for tumor diagnosis. We built a serum microRNA expression profile signature and tested its specificity and sensitivity as a biomarker in the diagnosis of CRC. We also studied its possible role in monitoring the progression of CRC. We conducted a two phase case-control test to identify serum miRNAs as biomarkers for CRC diagnosis. Using quantitative reverse transcription polymerase chain reactions, we tested ten candidate miRNAs in a training set (30 CRCs vs 30 controls). Risk score analysis was used to evaluate the diagnostic value of the serum miRNA profiling system. Other independent samples, including 83 CRCs and 59 controls, were used to validate the diagnostic model. In the training set, six serum miRNAs (miR-21, let-7g, miR-31, miR-92a, miR-181b, and miR-203) had significantly different expression levels between the CRCs and healthy controls. Risk score analysis demonstrated that the six-miRNA-based biomarker signature had high sensitivity and specificity for distinguishing the CRC samples from cancer-free controls. The areas under the receiver operating characteristic (ROC) curve of the six-miRNA signature profiles were 0.900 and 0.923 for the two sets of serum samples, respectively. However, for the same serum samples, the areas under the ROC curve used by the tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were only 0.649 and 0.598, respectively. The expression levels of the six serum miRNAs were also correlated with CRC progression. Thus, the identified six-miRNA signature can be used as a noninvasive biomarker for the diagnosis of CRC, with relatively high sensitivity and specificity. [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]

Background and Aim: Circulating microRNAs (miRNAs) are potential biomarkers for cancer detection; however, little is known about their prognostic impact on oesophageal squamous cell carcinoma (ESCC). The current study aims to uncover novel miRNAs for prognostic biomarkers in ESCC patients. Patients and Methods: We initially screened the expression of 754 serum miRNAs using TaqMan Low Density Array in two pooled samples respectively from 28 ESCC and 28 normal controls. Markedly upregulated miRNAs in ESCC and some miRNAs reported to be differently expressed in ESCC tissue were then validated individually by RT-qPCR in another 83 patients and 83 controls arranged in two phases. The changes of the selected miRNAs during the esophagectomy and their prognostic value were examined. Results: Seven serum miRNAs were found to be significantly higher in ESCC than in controls; namely, miR-25, miR-100, miR-193-3p, miR-194, miR-223, miR-337-5p and miR-483-5p (P<0.0001), and the area under the receiver-operating-characteristic (ROC) curve (AUC) for the seven-miRNA panel was 0.83 (95% CI 0.75–0.90). Most of these miRNAs declined markedly in postoperative samples versus preoperative samples (P<0.05). Moreover, high level of miR-25 was significantly correlated with shorter overall survival in patients (P = 0.027). Cox regression analysis identified lymph node metastasis, miR-25 and miR-100 as the independent risk factors for overall survival (hazard ratio (HR) 2.98 [1.36–6.55], P = 0.006; HR 3.84 [1.02–14.41], P = 0.029; HR 4.18 [1.21–14.50], P = 0.024, respectively). Conclusion: The seven serum miRNAs could potentially serve as novel biomarkers for ESCC; moreover, specific miRNAs such as miR-25 and miR-100 can predict poor survival in ESCC. [ABSTRACT FROM AUTHOR]

Anti-EGFR therapy appears to be a potential treatment option for squamous cell anal carcinoma (SCAC). KRAS mutation is a rare event in SCAC, indicating the absence of the principal mechanism of resistance to this type of therapy. However, no information is available from the literature regarding the status of BRAF or PIK3CA in this cancer type. We analysed KRAS, BRAF and PIK3CA status in SCAC patients in relation to the clinical-pathological characteristics of patients and to the presence of the human papilloma virus (HPV). One hundred and three patients were treated with the Nigro scheme for anal cancer from March 2001 to August 2012. Fifty patients were considered for the study as there was insufficient paraffin-embedded tumour tissue to perform molecular analysis the remaining 53. DNA was extracted from paraffin-embedded sections. KRAS, BRAF and PIK3CA gene status and HPV genotype were evaluated by pyrosequencing. KRAS and BRAF genes were wild-type in all cases. Conversely, PIK3CA gene was found to be mutated in 11 (22%) cases. In particular, 8 mutations occurred in exon 9 and 3 in exon 20 of the PIK3CA gene. These findings suggest that SCAC could potentially respond to an anti-EGFR drug. PIK3CA mutation may be involved in the process of carcinogenesis in some cases of SCAC. [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: Evidence suggests that many types of cancers are composed of different cell types, including cancer stem cells (CSCs). We have previously shown that the chemotherapeutic agent oxaliplatin induced epithelial-mesenchymal transition, which is thought to be an important mechanism for generating CSCs. In the present study, we investigate whether oxaliplatin-treated cancer tissues possess characteristics of CSCs, and explore oxaliplatin resistance in these tissues. Methods: Hepatocellular carcinoma cells (MHCC97H cells) were subcutaneously injected into mice to form tumors, and the mice were intravenously treated with either oxaliplatin or glucose. Five weeks later, the tumors were orthotopically xenografted into livers of other mice, and these mice were treated with either oxaliplatin or glucose. Metastatic potential, sensitivity to oxaliplatin, and expression of CSC-related markers in the xenografted tumor tissues were evaluated. DNA microarrays were used to measure changes in gene expression as a result of oxaliplatin treatment. Additionally, an oxaliplatin-resistant cell line (MHCC97H-OXA) was established to assess insulin-like growth factor 1 secretion, cell invasion, cell colony formation, oxaliplatin sensitivity, and expression of CSC-related markers. The effects of an insulin-like growth factor 1 receptor inhibitor were also assessed. Results: Oxaliplatin treatment inhibited subcutaneous tumor growth. Tumors from oxaliplatin-treated mice that were subsequently xenografted into livers of other mice exhibited that decreasing sensitivity to oxaliplatin and increasing pulmonary metastatic potential. Among the expression of CSC-related proteins, the gene for insulin-like growth factor 1, was up-regulated expecially in these tumor tissues. Additionally, MHCC97H-OXA cells demonstrated that increasing cell invasion, colony formation, and expression of insulin-like growth factor 1 and CSC-related markers, whereas treatment with an inhibitor of the insulin-like growth factor 1 receptor suppressed these effects. Conclusion: Maintenance of stemness in oxaliplatin-resistant hepatocellular carcinoma cells is associated with increased autocrine of IGF1. [ABSTRACT FROM AUTHOR]

Background: McKeown-type esophagectomy combined with retrosternal reconstruction is a common surgical treatment for esophageal cancer. Various enteral feeding options are available post-esophagectomy, but no definitive preference exists. Method: “Retrosternal Route Gastrostomy Feeding (RGF)” was developed as an alternative enteral feeding approach that requires few additional surgical interventions. RGF is based on McKeown-type esophagectomy. We retrospectively compared RGF (n = 121) to jejunostomy feeding (JF) (n = 153) in 274 patients at the Department of Cardiothoracic Surgery in Changzheng Hospital (Shanghai, China) between June 2008 and Sept. 2012. Data pertaining to efficacy and procedural complications were compared among patients. Results: RGF had a significantly shorter postoperative hospital stay (11 vs. 15 days, p<0.001) and time to removal of the feeding tube (9 vs. 14 days, p<0.001) compared to JF. Bowel obstruction (0.0% vs. 7.2% p = 0.003), abdominal distension (9.1% vs. 19% p = 0.022), and the occurrence of pneumonia (11.6% vs. 26.1% p = 0.003) were significantly lower in the RGF group. Feeding tube related complications and the associated morbidity rate were reduced in the RGF group. The two groups had similar tolerance to surgery. Conclusion: Our data suggests that RGF is a safe post-esophagectomy enteral feeding alternative to JF. [ABSTRACT FROM AUTHOR]