Qiwen Ben

Increased risk of hepatocellular carcinoma in patients with diabetes mellitus: a systematic review and meta-analysis of cohort studies.

In recent years, increasing evidence has suggested a strong association between diabetes mellitus (DM) and hepatocellular carcinoma (HCC). To provide a quantitative assessment of this association, we performed a systematic review and meta‐analysis of cohort studies. We collected studies through a literature search of Medline from January 1, 1966 and EMBASE from January 1, 1974, through July 31, 2010. Summary relative risks (SRRs) with their corresponding 95% confidence intervals (CIs) were calculated using a random‐effects model. A total of 25 cohort studies that met our inclusion and exclusion criteria were included in our analysis. Among these, 18 studies showed that DM was associated with an increased incidence of HCC (SRRs = 2.01, 95% CI: 1.61–2.51), compared with individuals without DM. There was a statistically significant heterogeneity among these studies (Q = 136.68, p < 0.001, I2 = 87.6%). Analyses subgrouped by controlling confounders revealed that the increased incidence of HCC was independent of geographic location, alcohol consumption, history of cirrhosis, or infections with hepatitis B (HBV) or hepatitis C virus (HCV). In addition, DM was also positively associated with HCC mortality (SRR = 1.56; 95% CI: 1.30–1.87), with no significant evidence of heterogeneity among studies (Q = 1.16, p = 0.56, I2 =0%). There were no significant publication bias (p = 0.79 for Eggers regression asymmetry test). These findings strongly support a positive association between DM and increased risk of HCC in both males and females.

Assessment of morbidity and mortality associated with EUS-guided FNA: a systematic review

BACKGROUND EUS-guided FNA (EUS-FNA) permits both morphologic and cytologic analysis of lesions within or adjacent to the GI tract. Although previous studies have evaluated the accuracy of EUS-FNA, little is known about the complications of EUS-FNA. Moreover, the frequency and severity of complications may vary from center to center and may be related to differences in individual experience. OBJECTIVE To systematically review the morbidity and mortality associated with EUS-FNA. DESIGN MEDLINE and EMBASE were searched to identify relevant English-language articles. MAIN OUTCOME MEASUREMENTS EUS-FNA-specific morbidity and mortality rates. RESULTS We identified 51 articles with a total of 10,941 patients who met our inclusion and exclusion criteria; the overall rate of EUS-FNA-specific morbidity was 0.98% (107/10,941). In the small proportion of patients with complications of any kind, the rates of pancreatitis (36/8246; 0.44%) and postprocedure pain (37/10,941; 0.34%) were 33.64% (36/107) and 34.58% (37/107), respectively. The mortality rate attributable to EUS-FNA-specific morbidity was 0.02% (2/10,941). Subgroup analysis showed that the morbidity rate was 2.44% in prospective studies compared with 0.35% in retrospective studies for pancreatic mass lesions (P=.000), whereas it was 2.33% versus 5.07% for pancreatic cysts (P=.036). LIMITATIONS Few articles reported well-designed, prospective studies and few focused on overall complications after EUS-FNA. CONCLUSIONS EUS-FNA-related morbidity and mortality rates are relatively low, and most associated events are mild to moderate in severity.

Body Mass Index Increases Risk for Colorectal Adenomas Based on Meta-analysis

BACKGROUND & AIMS There have been inconsistent results published about the relationship between excess body weight, expressed as increased body mass index (BMI), and risk of colorectal adenoma (CRA). We conducted a meta-analysis to explore this relationship. We focused on whether the relationship varied based on the sex of the study subjects, study design, features of the polyps, or potential confounders, including alcohol use, nonsteroidal anti-inflammatory drug use, smoking, and exercise. METHODS We identified studies by performing a literature search of Medline, EMBASE, and ISI Web of Science through July 31, 2011, and by searching the reference lists of pertinent articles. We analyzed 36 independent studies, which included 29,860 incident cases of CRA. Summary relative risks with their 95% confidence intervals (CIs) were calculated with a random-effects model. Between-study heterogeneity was assessed using Cochrans Q statistic and I(2) analyses. RESULTS Overall, a 5-unit increase in BMI (calculated as kg/m(2)) increased the risk for CRA (summary relative risk = 1.19; 95% CI: 1.13-1.26), although there was a high level of heterogeneity among studies (P(heterogeneity) < .001; I(2) = 76.8%). Subgroup analyses revealed that the increased risk of CRA in obese individuals was independent of race, geographic location, study design, sex, adenoma progression, and confounders. The association between increased BMI and risk for CRA was stronger for colon than rectal adenoma. CONCLUSIONS Based on a meta-analysis, increased BMI increases the risk for colon but not rectal adenoma. Unlike colorectal cancer, there is no sex difference in the relationship between increased BMI and risk of CRA.

Pancreatic cancer incidence and outcome in relation to ABO blood groups among Han Chinese patients: a case-control study

The aim of the current study was to determine the association between ABO blood group and the risk and progression of pancreatic ductal adenocarcinoma (PDAC) in the Han Chinese ethnic group. During the period of 2000–2009, 1,431 patients with PDAC and 1,449 age‐ and sex‐matched controls were recruited in two university‐affiliated hospitals. An unconditional multivariable logistic regression analysis was used to estimate adjusted odds ratios (ORs). The relationship between patient ABO blood group and clinicopathologic features was also analyzed. Compared with subjects having blood group O, a modestly higher risk was observed among cases with blood group A or AB with adjusted ORs (95% confidence interval) of 1.368 (1.127–1.661) and 1.391 (1.053–1.838), respectively. The TNM stages of tumors in patients with non‐O blood groups (A, B or AB) were more highly advanced than in patients with blood group O (p < 0.001). Among patients who underwent a potentially curative operation, the median survival time of patients with blood group O was significantly longer than that of patients with non‐O blood groups (16.0 months vs. 11.0 months, p = 0.001, log‐rank test). This study shows evidence of an association between blood group type and risk for development and progression of PDAC. These findings merit further confirmation in a large population‐based prospective study in patients of the Han Chinese ethnic group.

The relationship between new-onset diabetes mellitus and pancreatic cancer risk: a case-control study.

Diabetes mellitus (DM) is widely considered to be associated with pancreatic cancer, however, whether DM is a cause or consequence of pancreatic cancer is controversial. In the present study, 1458 patients with pancreatic ductal adenocarcinoma (PDAC) and 1528 age-, sex- and sociodemographic variables-matched controls were recruited in two university-affiliated hospitals from 1st January 2000 to 31st December 2009. DM was defined as fasting blood glucose (FBG) level of 7.0 mmol/L or greater. An unconditional multivariable logistic regression analysis was used to estimate adjusted odds ratios (AORs) and 95% confidence interval (CI). Compared with controls, a moderate increased risk of PDAC was observed among cases with long-standing diabetes (≥ 2-year duration), with an AOR (95% CI) of 2.11 (1.51-2.94). Interestingly, a significant higher risk was observed among cases with new-onset DM (<2-year duration), with an AOR of 4.43 (3.44-5.72) compared to controls without DM. In addition, we found a synergistic interaction between cigarette smoking and DM on modifying the risk of pancreatic cancer development (AOR=6.17, 95% CI 3.82-9.94). Similarly, a synergistic interaction between new-onset DM and family history of pancreatic cancer was found for pancreatic cancer risk, with an AOR (95% CI) of 11.04 (2.51-48.53). This study suggested that DM could be both an early manifestation of pancreatic cancer and an aetiologic factor. Possible effect modification on DM by family history of pancreatic cancer and smoking status should be further explored in future aetiologic studies.

Adiponectin levels in patients with colorectal cancer and adenoma: a meta-analysis.

Inconsistent results with regard to adiponectin levels in patients with colorectal cancer (CRC) and adenoma have been reported. To evaluate adiponectin levels in patients with CRC and adenoma, a meta-analysis on studies which compared adiponectin levels in patients with CRC or adenoma with healthy controls was carried out. A literature search was performed through Pubmed, EMBASE, and Science Citation Index Expanded database. Pooled-weighted mean differences and 95% confidence intervals (95%CI) were calculated by using random-effects models. Heterogeneity between studies was assessed using the Cochran’s Q and I2 statistics. A total of 13 studies were identified, which included 2632 cases of CRC or adenoma and 2753 healthy controls. Adiponectin levels were significantly lower in patients with CRC or adenoma compared with healthy controls, with significant heterogeneity [weighted mean differences of −1.51 (95% CI: −2.42 to −0.59; Pheterogeneity<0.001) for CRC and −1.29 (95% CI: −2.01to −0.58; Pheterogeneity<0.001) for colorectal adenoma, respectively]. On stratified analysis of CRC, significant difference in adiponectin levels between patients with CRC and healthy controls was reported only in case–control studies or small sample size studies (n<100), but not in nested case–control studies or large sample size studies (n≥100). In addition, metaregression analysis indicated that study design and sample size partly contributed to the significant heterogeneity (P=0.022 for study design and P=0.018 for sample size, respectively). For colorectal adenoma studies, stratified analysis indicated that sample size was one of the heterogeneous factors. Sensitivity analysis showed that there were no changes in the direction of effect when any one study was excluded. No publication bias was detected. Adiponectin levels are lower in patients with CRC or colorectal adenoma compared with those in healthy controls. Future studies are warranted to clarify the association of adiponectin levels and carcinogenesis of the colorectum.

Therapeutic strategies targeting cancer stem cells

Increasing studies have demonstrated a small proportion of cancer stem cells (CSCs) exist in the cancer cell population. CSCs have powerful self-renewal capacity and tumor-initiating ability and are resistant to chemotherapy and radiation. Conventional anticancer therapies kill the rapidly proliferating bulk cancer cells but spare the relatively quiescent CSCs, which cause cancer recurrence. So it is necessary to develop therapeutic strategies acting specifically on CSCs. In recent years, studies have shown that therapeutic agents such as metformin, salinomycin, DECA-14, rapamycin, oncostatin M (OSM), some natural compounds, oncolytic viruses, microRNAs, cell signaling pathway inhibitors, TNF-related apoptosis inducing ligand (TRAIL), interferon (IFN), telomerase inhibitors, all-trans retinoic acid (ATRA) and monoclonal antibodies can suppress the self-renewal of CSCs in vitro and in vivo. A combination of these agents and conventional chemotherapy drugs can significantly inhibit tumor growth, metastasis and recurrence. These strategies targeting CSCs may bring new hopes to cancer therapy.

High neuropilin 1 expression was associated with angiogenesis and poor overall survival in resected pancreatic ductal adenocarcinoma.

Objectives Neuropilin 1 (NRP-1) appears to promote angiogenesis by acting as a coreceptor with vascular endothelial growth factor receptor. We correlated NRP-1 expression with microvessel density (MVD) and overall survival (OS) in human pancreatic ductal adenocarcinomas (PDACs). Methods Neuropilin 1 expression was graded semiquantitatively using immunohistochemistry in patients with resected PDAC. Moreover, MVD was determined with an anti-CD31 antibody staining. Expression of NRP-1 was correlated with MVD and clinicopathologic features in patients with PDAC. Overall survival effects of NRP-1 expression were evaluated by multivariate Cox regression and Kaplan-Meier analyses. Results High NRP-1 expression was associated with advanced Union for International Cancer Control stage (P = 0.046), T stage (P = 0.031), and lymph node invasion (P = 0.045). Microvessel density was significantly higher in the tumors with high NRP-1 expression than that in the tumors with low NRP-1 expression (mean, 13.9 [SD, 9.1] vs 10.2 [SD, 7.2] per high-power field; P = 0.001). The multivariate Cox regression analysis demonstrated that high NRP-1 expression was independently associated with reduced OS (hazard ratio, 2.10; 95% confidence interval, 1.19–3.70). Conclusions Neuropilin 1 is highly expressed in PDACs, and high expression of NRP-1 is significantly correlated with angiogenesis, advanced tumor-node-metastasis stage, p T stage, node invasion, and poor postoperative OS.

Clinical profiles and long‐term outcomes of patients with pancreatic ductal adenocarcinoma and diabetes mellitus

Diabetes mellitus (DM) is considered to be a possible risk factor and/or a manifestation of pancreatic ductal adenocarcinoma (PDAC). This study is aimed at analysing the potential association of diabetes mellitus with the development and pathogenic degrees of PDAC and post‐surgical survival of Chinese Han PDAC patients.

Bulk pancreatic cancer cells can convert into cancer stem cells(CSCs) in vitro and 2 compounds can target these CSCs

ABSTRACT Increasing evidence has confirmed the existence of cancer stem cells (CSCs) in both hematological malignancies and solid tumors. However, the origin of CSCs is still uncertain, and few agents have been capable of eliminating CSCs till now. The aim of this study was to investigate whether bulk pancreatic cancer cells could convert into CSCs under certain conditions and explore whether metformin and curcumin can kill pancreatic CSCs. Aspc1, Bxpc3 and Panc1 pancreatic cancer cells were cultured in stem cell culture medium (serum-free Dulbeccos modified Eagle medium/Nutrient Mixture F-12 containing basic fibroblast growth factor, epidermal growth factor, B27 and insulin) for 5 days and it was found that all the pancreatic cancer cells aggregated into spheres and expressed pancreatic cancer stem cell surface markers. Then characteristics of Panc1 sphere cells were analyzed and cytotoxicity assays were performed. The results show that Panc1 sphere cells exhibited CSC characteristics and were more resistant to conventional chemotherapy and more sensitive to metformin and curcumin than their parent cells. These findings suggested that bulk pancreatic cancer cells could acquire CSC characteristics under certain conditions, which may support the “yin-yang” model of CSCs (interconversion between bulk cancer cells and CSCs). These results also showed that metformin and curcumin could be candidate drugs for targeting pancreatic CSCs.