Hai-Ning Chen

Tumor-Infiltrating Immune Cells Are Associated With Prognosis of Gastric Cancer

AbstractImmune cells contribute to determining the prognosis of gastric cancer. However, their exact role is less clear.We determined the prognostic significance of different immune cells in intratumoral tissue (T), stromal tissue (S), and adjacent normal tissue (N) of 166 gastric cancer cases and their interactions, including CD3+, CD4+, CD8+, CD57+, CD68+, CD66b+, and Foxp3+ cells, and established an effective prognostic nomogram based on the immune reactions.We found high densities of TCD3+, TCD4+, TCD8+, SCD3+, SCD4+, SCD57+, SCD66b+, and NFoxp3+ cells, as well as high TCD8+/SCD8+ ratio, TCD68+/SCD68+ ratio, TCD3+/TFoxp3+ ratio, TCD4+/TFoxp3+ ratio, TCD8+/TFoxp3+ ratio, SCD3+/SFoxp3+ ratio, and SCD4+/SCD8+ ratio were associated with better survival, whereas high densities of TCD66b+, TFoxp3+, SFoxp3+ and NCD66b+ cells as well as high TCD57+/SCD57+ ratio, TCD66b+/SCD66b+ ratio, SCD8+/SFoxp3+ ratio, and TFoxp3+/NFoxp3+ ratio were associated with significantly worse outcome. Multivariate analysis indicated that tumor size, longitudinal tumor location, N stage, TCD68+/SCD68+ ratio, TCD8+/TFoxp3+ ratio, density of TFoxp3+ cells, and TCD66b+/SCD66b+ ratio were independent prognostic factors, which were all selected into the nomogram. The calibration curve for likelihood of survival demonstrated favorable consistency between predictive value of the nomogram and actual observation. The C-index (0.83, 95% CI: 0.78 to 0.87) of our nomogram for predicting prognosis was significantly higher than that of TNM staging system (0.70).Collectively, high TCD68+/SCD68+ ratio and TCD8+/TFoxp3+ ratio were associated with improved overall survival, whereas high density of TFoxp3+ cells and TCD66b+/SCD66b+ ratio demonstrated poor overall survival, which are promising independent predictors for overall survival in gastric cancer.

The Impact of Body Mass Index on the Surgical Outcomes of Patients With Gastric Cancer: A 10-Year, Single-Institution Cohort Study.

Abstract This study aimed to investigate the impact of body mass index (BMI) on the short-term and long-term results of a large cohort of gastric cancer (GC) patients undergoing gastrectomy. Recently, the “obesity paradox” has been proposed, referring to the paradoxically “better” outcomes of overweight and obese patients compared with nonoverweight patients. The associations between BMI and surgical outcomes among patients with GC remain controversial. A single-institution cohort of 1249 GC patients undergoing gastrectomy between 2000 and 2010 were categorized to low-BMI (<18.49 kg/m2), normal-BMI (18.50–24.99 kg/m2), and high-BMI (≥25.00 kg/m2) groups. The postoperative complications were classified according to the Clavien-Dindo system, and their severity was assessed by using the Comprehensive Complication Index (CCI). The impact of BMI on the postoperative complications and overall survival was analyzed. There were 908, 158, and 182 patients in the normal-BMI, low-BMI, and high-BMI groups, respectively. The overall morbidity in the high-BMI group (24.7%) was higher than that in either the low-BMI or the normal-BMI group (20.9% and 15.5%, respectively; P = 0.006), but the mean CCI in the low-BMI group was significantly higher (8.32 ± 19.97) than the mean CCI in the normal-BMI and high-BMI groups (3.76 ± 11.98 and 5.58 ± 13.07, respectively; P < 0.001). The Kaplan–Meier curve and the log-rank test demonstrated that the low-BMI group exhibited the worst survival outcomes compared with the normal-BMI group, whereas the high-BMI group exhibited the best survival outcomes (P < 0.001). In multivariate analysis, BMI was identified as an independent prognostic factor. In the stage-specific subgroup analysis, a low BMI was associated with poorer survival in the cases of stage III–IV diseases. Low BMI was associated with more severe postoperative complications and poorer prognosis. Despite a higher risk of mild postoperative complications, the high-BMI patients exhibited paradoxically “superior” survival outcomes compared with the normal-BMI patients. These findings confirm the “obesity paradox” in GC patients undergoing gastrectomy.

Is CD133 a biomarker for cancer stem cells of colorectal cancer and brain tumors? A meta-analysis

Background CD133 has been used to identify normal and cancer stem cells from several different tissues. Nowadays some researchers have reported that CD133 expression was not restricted to cancer stem cells (CSCs) of colorectal cancer and brain tumors, and CD133-negative subsets could also initiate tumors. We therefore performed a meta-analysis to assess the value of CD133 as a biomarker of CSCs for colorectal cancer and brain tumors. Methods A Medline search was performed to identify relevant studies for the analysis. The meta-analysis was done using RevMan 5.0 software. Outcome measures were colony formation rate and xenotransplanted tumor formation rate. Results Fifteen identified studies were available for analysis. For in vitro tests, there were no significant differences in the colony formation rates between CD133-positive and CD133-negative cells for colorectal cancer and brain tumors. For in vivo tests, the xenotransplanted tumor formation rate showed a significant difference between CD133-positive cells and CD133-negative cells in colorectal cancer only, corresponding to a risk difference of 0.40 (95%CI: 0.07, 0.73). Samples (cell lines versus tissues), applied biomarkers (combined versus single), and injection site were included as factors in sensitivity analyses, but the results were very inconsistent. Conclusions CD133 may not be suitable as a universe biomarker in identifying CSCs of colorectal cancer and brain tumors. Additional studies are necessary to further delineate its role.

Prognostic significance of the combination of preoperative hemoglobin, albumin, lymphocyte and platelet in patients with gastric carcinoma: a retrospective cohort study

Nutritional and immune status is important to the prognosis of patients with gastric carcinoma (GC). Here, we evaluated the prognostic significance of the combination of preoperative hemoglobin, albumin, lymphocyte and platelet (HALP) in patients with GC. From January 2005 to December 2011, 1332 patients with GC who underwent gastrectomy were randomly divided into the training (n = 888) and the validation sets (n = 444) by X-tile according to the sample size ratio 2:1. The cut-point of HALP was 56.8 and the patients were subsequently subdivided into HALP < 56.8 and HALP ≥ 56.8 groups in both two sets. Multivariate analysis revealed that gender (p < 0.001, p < 0.001), tumor size (p = 0.003, p = 0.035) and T stage (p < 0.001, p = 0.044) were independently related to HALP both in the training and the validation sets. Kaplan-Meier (p < 0.001, p = 0.003) and Cox regression (p = 0.043, p = 0.042) showed that the prognosis of HALP ≥ 56.8 group was significantly better than that of HALP < 56.8 group both in two sets (p < 0.001, p < 0.001). Nomograms of these two sets based on HALP was more accurate in prognostic prediction than TNM stage alone. Our findings suggested that HALP was closely associated with clinicopathological features and was an independent prognostic factor in GC patients. Nomogram based on HALP could accurately predict the prognosis of GC patients.

Transthoracic Resection versus Non-Transthoracic Resection for Gastroesophageal Junction Cancer: A Meta-Analysis

Background The aim of this meta-analysis is to evaluate the impact of transthoracic resection on long-term survival of patients with GEJ cancer and to compare the postoperative morbidity and mortality of patients undergoing transthoracic resection with those of patients who were not undergoing transthoracic resection. Method Searches of electronic databases identifying studies from Medline, Cochrane Library trials register, and WHO Trial Registration etc were performed. Outcome measures were survival, postoperative morbidity and mortality, and operation related events. Results Twelve studies (including 5 RCTs and 7 non-RCTs) comprising 1105 patients were included in this meta-analysis, with 591 patients assigned treatment with transthoracic resection. Transthoracic resection did not increase the 5-y overall survival rate for RCTs and non-RCTs (HR = 1.01, 95% CI 0.80- 1.29 and HR = 0.89, 95% CI 0.70- 1.14, respectively). Stratified by the Siewert classification, our result showed no obvious differences were observed between the group with transthoracic resection and group without transthoracic resection (P>0.05). The postoperative morbidity (RR = 0.69, 95% CI 0.48- 1.00 and OR = 0.55, 95% CI 0.25- 1.22) and mortality (RD =  −0.03, 95% CI −0.06- 0.00 and RD = 0.00, 95% CI −0.05- 0.05) of RCTs and non-RCTs did not suggest any significant differences between the two groups. Hospital stay was long with thransthoracic resection (WMD =  −5.80, 95% CI −10.38- −1.23) but did not seem to differ in number of harvested lymph nodes, operation time, blood loss, numbers of patients needing transfusion, and reoperation rate. The results of sensitivity analyses were similar to the primary analyses. Conclusions There were no significant differences of survival rate and postoperative morbidity and mortality between transthoracic resection group and non-transthoracic resection group. Both surgical approaches are acceptable, and that one offers no clear advantage over the other. However, the results should be interpreted cautiously since the qualities of included studies were suboptimal.

Cost-Effectiveness Analysis on Endoscopic Surveillance Among Western Patients With Barrett's Esophagus for Esophageal Adenocarcinoma Screening.

AbstractPerirenal fat (PRF) is associated with cardiovascular risk factors. Gender differences in the correlations of cardiovascular disease risk factors and PRF in the Brazilian population are lacking.Cross-sectional study with 101 (50.49% men; mean age 56.5 ± 18, range 19–74 years) drawn from the Uberlândia Heart Study underwent ultrasonography assessment of abdominal adipose. For the PRF, a 3.5 MHz transducer was measured in the middle third of the right kidney, with the transducer positioned at the axillary midline. The examinations were always performed by the same examiner. The PRF thickness was examined in relation to waist circumference, blood pressure, and metabolic risk factors. The PRF was significantly associated with the levels of gamma-glutamyl transferase (P < 0.05, r = 0.08), fasting plasma glucose (P < 0.05, r = 0.07), waist circumference (P < 0.05, r = 0.10), and metabolic syndrome (P < 0.001, r = 0.38) in men, and with the levels of fasting plasma glucose (P < 0.05) in women.The PRF was correlated with most cardiovascular risk factors in men and only in glucose at the women.Abstract Incidence of esophageal adenocarcinoma (EAC) has risen rapidly over the past decades in Western countries. As a premalignant lesion, Barretts esophagus (BE) is an established risk factor of EAC. This study estimated the impact of surveillance endoscopy for BE on populations survival upon EAC by a whole-population cost-effectiveness analysis among modeled Western population. Possibilities and survival payoffs were retrieved through literature searching based on PubMed database. Patients with BE were classified as adequate surveillance (AS), inadequate surveillance (IAS), and no surveillance groups. Direct cost of endoscopy per person-year was estimated from diagnosis of BE to before diagnosis of EAC in the whole-population model, whereas the payoff was 2-year disease-specific survival rate of EAC. AS for patients with BE had lower cost-effectiveness ratio (CER) than that of IAS group, as well as lower incremental cost-effectiveness ratio (6116 €/% vs 118,347 €/%). Prolonging the surveillance years could decrease the yearly cost in whole population and also relevant CERs, despite increased total cost. Increasing the proportion of participants in AS group could improve the survival benefit. The maximal payoff was up to 2-year mortality reduction of 2.7 per 100,000 persons by spending extra €1,658,913 per 100,000 person-years. A longer endoscopic surveillance among BE subpopulation plan can reduce yearly budget. Attempt to increase the proportion of AS participants can induce decline in population mortality of EAC, despite extra but acceptable expenditure. However, regarding optimal cost-effectiveness, further studies are still required to identify a high-risk subpopulation out of BE patients for endoscopic surveillance.

Necessity of harvesting at least 25 lymph nodes in patients with stage N2-N3 resectable gastric cancer: a 10-year, single-institution cohort study.

AbstractA minimum of 15 lymph nodes (LNs) has been recommended as an adequate number for radical gastrectomy for gastric cancer (GC). This study aimed to investigate whether the harvesting of at least 25 LNs was a better criterion for stage N2–3 GC based on the 10-year experience of a high-volume hospital.A total of 1363 patients who underwent radical gastrectomy for gastric cancer between 2000 and 2010 were included in this study. The relationship between the number of lymph nodes examined during gastrectomy and overall survival (OS) was analyzed.In multivariate analysis, the numbers of LNs examined (P = 0.001) and N stage were confirmed as 2 of the independent prognostic factors. A larger proportion of N2/N3a/N3b patients was observed in the group with ≥20 LNs examined. The cutoff of ≥25 LNs examined exhibited a significantly lower hazard ratio (HR) than other LN cutoffs among N2–N3 diseases, but the cutoff was not significantly superior to other cutoffs in patients with N0 and N1 disease (HR, 0.64, 0.62, and 0.53 for N2, N3a, and N3b, respectively). The 5-year OS rates were 58.59% and 32.77% for N2 and N3 diseases, respectively, with ≥25 LNs examined, which represents a significant improvement over 15–24 LNs examined (52.48% and 21.67% for N2 and N3 stages, respectively).Among patients with stage N2–N3 GC, harvesting at least 25 LNs may represent a superior cutoff for radical gastrectomy and could yield better survival outcomes.

Can K-ras Gene Mutation Be Utilized as Prognostic Biomarker for Colorectal Cancer Patients Receiving Chemotherapy? A Meta-Analysis and Systematic Review

Introduction K-ras gene mutations were common in colorectal patients, but their relationship with prognosis was unclear. Objective Verify prognostic differences between patient with and without mutant K-ras genes by reviewing the published evidence. Method Systematic reviews and data bases were searched for cohort/case-control studies of prognosis of colorectal cancer patients with detected K-ras mutations versus those without mutant K-ras genes, both of whom received chemotherapy. Number of patients, regimens of chemotherapy, and short-term or long-term survival rate (disease-free or overall) were extracted. Quality of studies was also evaluated. Principal Findings 7 studies of comparisons with a control group were identified. No association between K-ras gene status with neither short-term disease free-survival (OR=1.01, 95% CI, 0.73-1.38, P=0.97) nor overall survival (OR=1.06, 95% CI, 0.82-1.36, P=0.66) in CRC patients who received chemotherapy was indicated. Comparison of long-term survival between two groups also indicated no significant difference after heterogeneity was eliminated (OR=1.09, 95% CI, 0.85-1.40, P=0.49). Conclusions K-ras gene mutations may not be a prognostic index for colorectal cancer patients who received chemotherapy.

Cytotoxin-Associated Gene A-Negative Strains of Helicobacter pylori as a Potential Risk Factor of Pancreatic Cancer: A Meta-Analysis Based on Nested Case-Control Studies.

Objectives Risk of pancreatic cancer between Helicobacter pylori infected and noninfected persons is controversial, and therefore a meta-analysis was performed. Methods PubMed was searched up to September 2014. Only population-based nested case-control studies comparing the serological prevalence of Helicobacter pylori between pancreatic cancer cases and cancer-free controls were eligible. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for pancreatic cancer risk between Helicobacter pylori infected and noninfected persons were estimated. Results Five eligible nested case-control studies were included, with 1446 pancreatic cancer cases and 2235 cancer-free controls. On the whole, the proportion of pancreatic cancer cases among those infected with Helicobacter pylori was not significant different from those noninfected (OR, 0.99; 95% CI, 0.65–1.50; P = 0.96). Likewise, seropositivity of cytotoxin-associated gene A (CagA) showed nonsignificant association with pancreatic cancer (OR, 0.92; 95% CI, 0.65–1.30; P = 0.63). The CagA-positive virulent strains of Helicobacter pylori did not increase the risk of pancreatic cancer (OR, 0.97; 95% CI, 0.50–1.89; P = 0.93). However, CagA-negative nonvirulent strains of Helicobacter pylori had a significant increased risk for pancreatic cancer (OR, 1.47; 95% CI, 1.11–1.96; P = 0.008). Conclusions The CagA-negative non-virulent strains of Helicobacter pylori may be a potential risk factor of pancreatic cancer. High-quality prospective large-scaled studies are required for more conclusive results.

Expression and clinicopathological significance of CD9 in gastrointestinal stromal tumor.

This study investigated the expression and clinicopathological significance of CD9 in gastrointestinal stromal tumor (GIST). Immunohistochemistry staining for CD9 was performed on tumor tissues from 74 GIST patients. The correlation with clinicopathological features, risk classification and prognosis was analyzed. CD9-positive staining comprised 59.5% (44/74) of the GIST patients. The CD9-positive expression rate of the sample was significantly associated with diameter (P = 0.028), mitotic counts (P = 0.035), risk classification (P = 0.018) and three-year recurrence-free survival (RFS) (P < 0.001). Cox proportional hazards regression (HR = 0.352; P = 0.015) showed that CD9 is an independent factor for post-operative RFS. The subgroup analysis showed that CD9 expression in gastric stromal tumor (GST) is significantly associated with diameter (P = 0.031), risk classification (P = 0.023) and three-year RFS (P = 0.001). The Cox proportional hazards regression (HR = 0.104; P = 0.006) also showed that CD9 is an independent factor for RFS of GST. However, CD9 expression does not have a statistically significant correlation with clinicopathological features, risk classification, and prognosis in non-GST. In conclusion, CD9 expression in GIST appears to be associated with the recurrence and/or metastasis of GIST patients, especially in GST, which may indicate the important role of CD9 in the malignant biological behavior and prognosis of GST.