Association of cigarette smoking with risk of colorectal cancer subtypes classified by gut microbiota.

INTRODUCTION: Both cigarette smoking and gut microbiota play important roles in colorectal carcinogenesis. We explored whether the association between smoking and colorectal cancer (CRC) risk varies by gut microbial enterotypes and how smoking-related enterotypes promote colorectal carcinogenesis. METHODS: A case-control study was conducted. Fecal microbiota was determined by 16S rDNA sequencing. The cases with CRC or adenoma were subclassified by gut microbiota enterotypes. Multivariate analyses were used to test associations between smoking and the odds of colorectal neoplasm subtypes. Mann-Whitney U tests were used to find differential genera, genes, and pathways between the subtypes. RESULTS: Included in the study were 130 CRC patients (type I: n=77; type II: n=53), 120 adenoma patients (type I: n=66; type II: n=54), and 130 healthy participants. Smoking increased the odds for type II tumors significantly (all p for trend <0.05) but not for type I tumors. The associations of smoking with increased odds of colorectal neoplasm significantly differed by gut microbiota enterotypes (p<0.05 for heterogeneity). An increase in carcinogenic bacteria (genus Escherichia shigella) and a decrease in probiotics (family Lachnospiraceae and Ruminococcaceae) in type II tumors may drive disease progression by upregulating oncogenic signaling pathways and inflammatory/oxidative stress response pathways, as well as protein phospholipase D1/2, cytochrome C, and prostaglandin-endoperoxide synthase 2 expression. CONCLUSIONS: Smoking was associated with a higher odds of type II colorectal neoplasms but not type I tumors, supporting a potential role for the gut microbiota in mediating the association between smoking and colorectal neoplasms.

Gut Microbiota Enterotypes Mediate the Effects of Dietary Patterns on Colorectal Neoplasm Risk in a Chinese Population.

Colorectal cancer (CRC) risk is influenced by dietary patterns and gut microbiota enterotypes. However, the interaction between these factors remains unclear. This study examines this relationship, hypothesizing that different diets may affect colorectal tumor risk in individuals with varied gut microbiota enterotypes. We conducted a case-control study involving 410 Han Chinese individuals, using exploratory structural equation modeling to identify two dietary patterns, and a Dirichlet multinomial mixture model to classify 250 colorectal neoplasm cases into three gut microbiota enterotypes. We assessed the association between dietary patterns and the risk of each tumor subtype using logistic regression analysis. We found that a healthy diet, rich in vegetables, fruits, milk, and yogurt, lowers CRC risk, particularly in individuals with type I (dominated by Bacteroides and Lachnoclostridium) and type II (dominated by Bacteroides and Faecalibacterium) gut microbiota enterotypes, with adjusted odds ratios (ORs) of 0.66 (95% confidence interval [CI] = 0.48-0.89) and 0.42 (95% CI = 0.29-0.62), respectively. Fruit consumption was the main contributor to this protective effect. No association was found between a healthy dietary pattern and colorectal adenoma risk or between a high-fat diet and colorectal neoplasm risk. Different CRC subtypes associated with gut microbiota enterotypes displayed unique microbial compositions and functions. Our study suggests that specific gut microbiota enterotypes can modulate the effects of diet on CRC risk, offering new perspectives on the relationship between diet, gut microbiota, and colorectal neoplasm risk.

Large-scale, national, family-based epidemiological study on Helicobacter pylori infection in China: the time to change practice for related disease prevention.

BACKGROUND AND AIMS: Current practice on Helicobacter pylori infection mostly focuses on individual-based care in the community, but family-based H. pylori management has recently been suggested as a better strategy for infection control. However, the family-based H. pylori infection status, risk factors and transmission pattern remain to be elucidated. METHODS: From September 2021 to December 2021, 10 735 families (31 098 individuals) were enrolled from 29 of 31 provinces in mainland China to examine family-based H. pylori infection, related factors and transmission pattern. All family members were required to answer questionnaires and test for H. pylori infection. RESULTS: Among all participants, the average individual-based H. pylori infection rate was 40.66%, with 43.45% for adults and 20.55% for children and adolescents. Family-based infection rates ranged from 50.27% to 85.06% among the 29 provinces, with an average rate of 71.21%. In 28.87% (3099/10 735) of enrolled families, there were no infections; the remaining 71.13% (7636/10 735) of families had 1-7 infected members, and in 19.70% (1504/7636), all members were infected. Among 7961 enrolled couples, 33.21% had no infection, but in 22.99%, both were infected. Childhood infection was significantly associated with parental infection. Independent risk factors for household infection were infected family members (eg, five infected members: OR 2.72, 95% CI 1.86 to 4.00), living in highly infected areas (eg, northwest China: OR 1.83, 95% CI 1.57 to 2.13), and large families in a household (eg, family of three: OR 1.97, 95% CI 1.76 to 2.21). However, family members with higher education and income levels (OR 0.85, 95% CI 0.79 to 0.91), using serving spoons or chopsticks, more generations in a household (eg, three generations: OR 0.79, 95% CI 0.68 to 0.92), and who were younger (OR 0.57, 95% CI 0.46 to 0.70) had lower infection rates (p<0.05). CONCLUSION: Familial H. pylori infection rate is high in general household in China. Exposure to infected family members is likely the major source of its spread. These results provide supporting evidence for the strategic changes from H. pylori individual-based treatment to family-based management, and the notion has important clinical and public health implications for infection control and related disease prevention.

FIT-based risk-stratification model effectively screens colorectal neoplasia and early-onset colorectal cancer in Chinese population: a nationwide multicenter prospective study.

No fully validated risk-stratification strategies have been established in China where colonoscopies resources are limited. We aimed to develop and validate a fecal immunochemical test (FIT)-based risk-stratification model for colorectal neoplasia (CN); 10,164 individuals were recruited from 175 centers nationwide and were randomly allocated to the derivation (n = 6776) or validation cohort (n = 3388). Multivariate logistic analyses were performed to develop the National Colorectal Polyp Care (NCPC) score, which formed the risk-stratification model along with FIT. The NCPC score was developed from eight independent predicting factors and divided into three levels: low risk (LR 0-14), intermediate risk (IR 15-17), and high risk (HR 18-28). Individuals with IR or HR of NCPC score or FIT+ were classified as increased-risk individuals in the risk-stratification model and were recommended for colonoscopy. The IR/HR of NCPC score showed a higher prevalence of CNs (21.8%/32.8% vs. 11.0%, P < 0.001) and ACNs (4.3%/9.2% vs. 2.0%, P < 0.001) than LR, which was also confirmed in the validation cohort. Similar relative risks and predictive performances were demonstrated between non-specific gastrointestinal symptoms (NSGS) and asymptomatic cohort. The risk-stratification model identified 73.5% CN, 82.6% ACN, and 93.6% CRC when guiding 52.7% individuals to receive colonoscopy and identified 55.8% early-onset ACNs and 72.7% early-onset CRCs with only 25.6% young individuals receiving colonoscopy. The risk-stratification model showed a good risk-stratification ability for CN and early-onset CRCs in Chinese population, including individuals with NSGS and young age.

Helicobacter pylori Infection and Serum Pepsinogen Level With the Risk of Gastric Precancerous Conditions: A Cross-sectional Study of High-risk Gastric Cancer Population in China.

BACKGROUND AND AIM: Gastric precancerous conditions are generally considered to play an essential role in the gastric carcinogenesis cascade. This study identified risk factors of gastric precancerous conditions in a nationwide multicenter cross-sectional study. METHODS: Individuals who made their visit to 115 hospitals in China for gastric cancer screening were recruited. Lifestyle habits and personal information were collected through a series of questionnaires. Serum biomarker test (pepsinogen I, pepsinogen II, gastrin-17, and anti-Helicobacter pylori immunoglobulin G antibody) and endoscopy were then performed. Risk factors for gastric precancerous conditions were identified by univariate and multivariate analyses. RESULTS: Of 14,929 subjects eligible for analysis, 4477 (30.0%) developed gastric precancerous conditions and 405 (2.71%) developed gastric cancer. In multiple logistic regression, precancerous conditions were associated with advanced age [odds ratio (OR)=1.027; 95% confidence interval (Cl), 1.023-1.032; P<0.001], male gender (OR=1.303; 95% Cl, 1.188-1.429; P<0.001), H. pylori infection (OR=1.377; 95% Cl, 1.272-1.490, P<0.001), and smoking (OR=1.142; 95% Cl, 1.005-1.298, P=0.004), whereas they were inversely correlated with white meat intake (OR=0.731; 95% Cl, 0.673-0.794; P<0.001) and pepsinogen I level (30 to 70 subgroup OR=1.536; 95% Cl, 1.163-2.028; P=0.002; <30 subgroup OR=1.354; 95% Cl, 1.206-1.520; P<0.001). Also, the authors observed a statistically lower prevalence of reflux esophagitis (2.8% vs. 4.7%) and of gastric polyps (11.0% vs. 13.7%) in H. pylori-infected population. CONCLUSIONS: Patients with H. pylori have a 1.4-fold higher risk of having gastric precancerous conditions. Besides, precancerous conditions were associated with advanced age, male gender, H. pylori infection, and smoking in a large population. However, regular white meat intake and higher pepsinogen I level were associated with reduced risk of having precancerous lesions.

Development and validation of a prediction rule for estimating gastric cancer risk in the Chinese high-risk population: a nationwide multicentre study.

OBJECTIVE: To develop a gastric cancer (GC) risk prediction rule as an initial prescreening tool to identify individuals with a high risk prior to gastroscopy. DESIGN: This was a nationwide multicentre cross-sectional study. Individuals aged 40-80 years who went to hospitals for a GC screening gastroscopy were recruited. Serum pepsinogen (PG) I, PG II, gastrin-17 (G-17) and anti-Helicobacter pylori IgG antibody concentrations were tested prior to endoscopy. Eligible participants (n=14 929) were randomly assigned into the derivation and validation cohorts, with a ratio of 2:1. Risk factors for GC were identified by univariate and multivariate analyses and an optimal prediction rule was then settled. RESULTS: The novel GC risk prediction rule comprised seven variables (age, sex, PG I/II ratio, G-17 level, H. pylori infection, pickled food and fried food), with scores ranging from 0 to 25. The observed prevalence rates of GC in the derivation cohort at low-risk (≤11), medium-risk (12-16) or high-risk (17-25) group were 1.2%, 4.4% and 12.3%, respectively (p<0.001).When gastroscopy was used for individuals with medium risk and high risk, 70.8% of total GC cases and 70.3% of early GC cases were detected. While endoscopy requirements could be reduced by 66.7% according to the low-risk proportion. The prediction rule owns a good discrimination, with an area under curve of 0.76, or calibration (p<0.001). CONCLUSIONS: The developed and validated prediction rule showed good performance on identifying individuals at a higher risk in a Chinese high-risk population. Future studies are needed to validate its efficacy in a larger population.

Changes in gut microbiota and plasma inflammatory factors across the stages of colorectal tumorigenesis: a case-control study.

BACKGROUND: Colorectal cancer (CRC) is a common malignant gastrointestinal tumor. In China, CRC is the 5th most commonly diagnosed cancer. The vast majority of CRC cases are sporadic and evolve with the adenoma-carcinoma sequence. There is mounting evidence indicating that gut microbiota and inflammation play important roles in the development of CRC although study results are not entirely consistent. In the current study, we investigated the changes in the CRC-associated bacteria and plasma inflammatory factors and their relationships based on data from a case-control study of Han Chinese. We included 130 initially diagnosed CRC patients, 88 advanced colorectal adenoma patients (A-CRA), 62 patients with benign intestinal polyps and 130 controls. RESULTS: Fecal microbiota composition was obtained using 16S ribosomal DNA (16S rDNA) sequencing. PCOA analysis showed structural differences in microbiota among the four study groups (P = 0.001, Unweighted Unifrac). Twenty-four CRC-associated bacteria were selected by a two-step statistical method and significant correlations were observed within these microbes. CRC-associated bacteria were found to change with the degree of malignancy. Plasma C-reactive protein (CRP) and soluble tumor necrosis factor II (sTNFR-II) displayed significant differences among the four study groups and increased with adenoma-carcinoma sequence. The correlations of CRP and sTNFR-II with several CRC-associated microbes were also explored. CONCLUSIONS: CRC-associated species and plasma inflammatory factors tended to change along the adenoma-carcinoma sequence. Several CRC-associated bacteria were correlated with CRP and sTNFR-II. It is likely that gut microbiome and inflammation gradually form a microenvironment that is associated with CRC development.

Overexpression of YKL-40 Predicts Poor Prognosis in Patients Undergoing Curative Resection of Pancreatic Cancer.

OBJECTIVES: The aim of this study was to determine the prognostic value of YKL-40 expression in patients undergoing curative resection of pancreatic cancer. METHODS: This cohort study included 234 consecutive patients with pancreatic ductal adenocarcinoma who underwent curative resection. Surgical specimens were immunohistochemically assessed for YKL-40 expression. Kaplan-Meier method and Cox regression were used to evaluate the prognostic impact of YKL-40 expression. A multivariate logistic regression model was performed to examine the correlation between YKL-40 expression and tumor stage. RESULTS: Of the 234 patients, YKL-40 overexpression was detected in 149 (63.7%) patients. Survival curves showed that patients with YKL-40 overexpression had significantly shorter survival time than those with low YKL-40 expression (P < 0.001). Cox regression analysis indicated that YKL-40 expression was an independent prognostic factor for both overall survival (hazard ratio, 3.82; 95% confidence interval [CI], 2.38-6.13) and progression-free survival (hazard ratio, 3.73; 95% CI, 2.33-5.99). Multivariate logistic regression analysis demonstrated that YKL-40 overexpression was an independent predictor for advanced tumor stage (odds ratio 4.15; 95% CI, 1.35-12.71). CONCLUSIONS: YKL-40 overexpression predicts poor prognosis and advanced tumor stage in patients undergoing curative resection of pancreatic cancer. Application of adjuvant treatment targeting the YKL-40 pathway may improve prognosis.

Low-dose ticagrelor yields an antiplatelet efficacy similar to that of standard-dose ticagrelor in healthy subjects: an open-label randomized controlled trial.

Ticagrelor has a greater antiplatelet efficacy than clopidogrel but may be accompanied by an increased risk of bleeding. This study evaluated the antiplatelet effect and pharmacokinetic profile of low-dose ticagrelor in healthy Chinese volunteers. Thirty healthy subjects were randomized to receive standard-dose ticagrelor (180-mg loading dose, 90-mg twice daily [bid] [n = 10]), low-dose ticagrelor (90-mg loading dose, 45-mg bid [n = 10]), or clopidogrel (600-mg loading dose, 75-mg once daily [n = 10]). Platelet reactivity was assessed by using the VerifyNow P2Y12 assay at baseline and 0.5, 1, 2, 4, 8, 24, 48, and 72 hours post-dosing. The ticagrelor and AR-C124910XX concentrations were measured for pharmacokinetic analysis. The percentage inhibition of P2Y12 reaction units was higher in the low-dose and standard-dose ticagrelor group than in the clopidogrel group at 0.5, 1, 2, 4, 8, and 48 hours post-dosing (P < 0.05 for all), but did not differ significantly between the two ticagrelor doses at any time-point (P > 0.05). The plasma ticagrelor and ARC124910XX concentrations were approximately 2-fold higher with standard-dose versus low-dose ticagrelor. No serious adverse events were reported. In conclusion, low-dose ticagrelor achieved faster and higher inhibition of platelet functions in healthy Chinese subjects than did clopidogrel, with an antiplatelet efficacy similar to that of standard-dose ticagrelor.

A new computational model for human thyroid cancer enhances the preoperative diagnostic efficacy.

Considering the high rate of missed diagnosis and delayed treatments for thyroid cancer, an effective systematic model for the differential diagnosis is highly needed. Thus we analyzed the data on the clinicopathological characteristics, routine laboratory tests and imaging examinations in a cohort of 13,980 patients with thyroid cancer to establish a new diagnostic model for differentiating thyroid cancer in clinical practice. Here, we randomly selected two-thirds of the population to develop the thyroid malignancy risk scoring system (TMRS) for preoperative differentiation between thyroid cancer and benignant thyroid diseases, and then validated its differential diagnostic power in the rest one-third population. The 18 predictors finally enrolled in the TMRS included male gender, clinical manifestations (fever, neck sore, neck lump, palpitations or sweating), laboratory findings (TSH>1.56mIU/L, FT3>5.85pmol/L, TPOAb>14.97IU/ml, TgAb>48.00IU/ml, Tg>34.59µg/L, Ct>64.00ng/L, and CEA>0.41µg/L), and ultrasound features (tumor number≤ 23mm, site, size, echo texture, margins, and shape of neck lymphnodes). The TMRS is validated to be well-calibrated (P = 0.437) and excellently discriminated (AUC = 0.93, 95% CI [0.92, 0.94]), with an accuracy of 83.2%, a sensitivity of 89.3%, a specificity of 81.5%, positive and negative predictive values of 56.8% and 96.6%, positive and negative likelihood ratios of 4.83 and 0.13 in the development cohort, respectively. The TMRS highlights that this differential diagnostic system could help provide accurate preoperative risk stratification for thyroid cancer, and avoid unnecessary over- and under-treatment for such patients.

Questionnaire survey about use of an online appointment booking system in one large tertiary public hospital outpatient service center in China.

BACKGROUND: As a part of nationwide healthcare reforms, the Chinese government launched web-based appointment systems (WAS) to provide a solution to problems around outpatient appointments and services. These have been in place in all Chinese public tertiary hospitals since 2009. METHODS: Questionnaires were collected from both patients and doctors in one large tertiary public hospital in Shanghai, China.Data were analyzed to measure their satisfaction and views about the WAS. RESULTS: The 1000 outpatients randomly selected for the survey were least satisfied about the waiting time to see a doctor. Even though the WAS provided a much more convenient booking method, only 17% of patients used it. Of the 197 doctors surveyed, over 90% thought it was necessary to provide alternative forms of appointment booking systems for outpatients. However, about 80% of those doctors who were not associated professors would like to provide an 'on-the-spot' appointment option, which would lead to longer waits for patients. CONCLUSIONS: Patients were least satisfied about the waiting times. To effectively reduce appointment-waiting times is therefore an urgent issue. Despite the benefits of using the WAS, most patients still registered via the usual method of queuing, suggesting that hospitals and health service providers should promote and encourage the use of the WAS. Furthermore, Chinese health providers need to help doctors to take others' opinions or feedback into consideration when treating patients to minimize the gap between patients' and doctors' opinions. These findings may provide useful information for both practitioners and regulators, and improve recognition of this efficient and useful booking system, which may have far-reaching and positive implications for China's ongoing reforms.

[The derivation and validation of a prediction rule for differential diagnosis of thyroid nodules].

OBJECTIVE: To set up a prediction rule for the pro-operative differential diagnosis of thyroid nodules and evaluate its clinical value. METHODS: All patients of thyroid nodules underwent thyroid operations in Changzheng hospital from June, 1997 to July, 2012 were included in this study. They were randomly divided into the derivation cohort (2/3) and the validation cohort (1/3). A prediction rule was developed based on the logistic regression model and the scoring system was established in accordance with assigning of the value of each variable ß in the model. The prediction consistency, discriminatory power and diagnostic accuracy were conducted to evaluate the clinical value of the scoring system. RESULTS: A total of 13 980 patients were enrolled in the study with 9195 in the derivation cohort and 4785 in the validation cohort. The prediction rule consisted of 18 variables, which were gender, clinical manifestations including fever, neck sore, neck mass, palpitation and sweating, serum level of thyroid stimulating hormone (TSH) , free triiodothyronine (FT3) , thyroid peroxidase antibody (TPOAb) , thyroglobulin antibody (TgAb) , thyroglobulin (Tg) , calcitonin and carcinoembryonic antigen (CEA) , ultrasonography features including nodules number, location, size, boundaries and ethological patterns and the presence and patterns of lymph nodes. The model showed good calibration consistency (P = 0.437) and discrimination power (area under the receiver operating characteristic curve was 0.928) in the derivation cohort. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio of the model were 89.3%, 81.5%, 83.2%, 56.8%, 96.6%, 4.83 and 0.13, respectively. CONCLUSION: The prediction rule and its scoring system established in the study are efficacious for the calibration and discrimination of thyroid nodules in Chinese population, which could be a useful tool for the pro-operative risk stratification.

Gastro-protecting effect of gefarnate on chronic erosive gastritis with dyspeptic symptoms.

BACKGROUND: The role of gastro-protecting agents on symptomatic chronic gastritis is unclear. This multicenter, open, randomized trial was designed to compare the comprehensive effects of gefarnate with sucralfate on erosive gastritis with dyspeptic symptoms. METHODS: Totally 253 dyspepsia patients confirmed with erosive gastritis were enrolled from six centers in China. They randomly received either daily 300 mg gefarnate or 3 g sucralfate for six weeks. The primary endpoint was the effective rate of both treatments on endoscopic erosion at week six. RESULTS: Gefarnate showed an effective rate of 72% and 67% on endoscopic score and dyspeptic symptom release, which is statistically higher than sucralfate (40.1% and 39.3%, P < 0.001, intension-to-treat). For histological improvement, gefarnate showed both effective in decreasing mucosal chronic inflammation (57.7% vs. 24.8%, P < 0.001, intension-to-treat) and active inflammation (36.4% vs. 23.1%, P < 0.05, intension-to-treat) than the control. A significant increase of prostaglandins and decrease of myeloperoxidase in mucosa were observed in gefarnate group. Severity of erosion is non-relevant to symptoms but Helicobacter pylori (H. pylori) status does affect the outcome of therapy. CONCLUSIONS: Gefarnate demonstrates an effective outcome on the mucosal inflammation in patients with chronic erosive gastritis. Endoscopic and inflammation score should be the major indexes used in gastritis-related trials.

Knowledge of, attitudes toward, and barriers to participation of colorectal cancer screening tests in the Asia-Pacific region: a multicenter study.

BACKGROUND: The rapid increase in the incidence of colorectal cancer (CRC) in the Asia-Pacific region in the past decade has resulted in recommendations to implement mass CRC screening programs. However, the knowledge of screening and population screening behaviors between countries is largely lacking. OBJECTIVE: This multicenter, international study investigated the association of screening test participation with knowledge of, attitudes toward, and barriers to CRC and screening tests in different cultural and sociopolitical contexts. METHODS: Person-to-person interviews by using a standardized survey instrument were conducted with subjects from 14 Asia-Pacific countries/regions to assess the prevailing screening participation rates, knowledge of and attitudes toward and barriers to CRC and screening tests, intent to participate, and cues to action. Independent predictors of the primary endpoint, screening participation was determined from subanalyses performed for high-, medium-, and low-participation countries. RESULTS: A total of 7915 subjects (49% male, 37.8% aged 50 years and older) were recruited. Of the respondents aged 50 years and older, 809 (27%) had undergone previous CRC testing; the Philippines (69%), Australia (48%), and Japan (38%) had the highest participation rates, whereas India (1.5%), Malaysia (3%), Indonesia (3%), Pakistan (7.5%), and Brunei (13.7%) had the lowest rates. Physician recommendation and knowledge of screening tests were significant predictors of CRC test uptake. In countries with low-test participation, lower perceived access barriers and higher perceived severity were independent predictors of participation. Respondents from low-participation countries had the least knowledge of symptoms, risk factors, and tests and reported the lowest physician recommendation rates. "Intent to undergo screening" and "perceived need for screening" was positively correlated in most countries; however, this was offset by financial and access barriers. LIMITATIONS: Ethnic heterogeneity may exist in each country that was not addressed. In addition, the participation tests and physician recommendation recalls were self-reported. CONCLUSIONS: In the Asia-Pacific region, considerable differences were evident in the participation of CRC tests, physician recommendations, and knowledge of, attitudes toward, and barriers to CRC screening. Physician recommendation was the uniform predictor of screening behavior in all countries. Before implementing mass screening programs, improving awareness of CRC and promoting the physicians' role are necessary to increase the screening participation rates.

Hepatitis B virus status and risk of pancreatic ductal adenocarcinoma: a case-control study from China.

OBJECTIVES: This study was to assess the role of hepatitis B virus (HBV) infection in pancreatic ductal adenocarcinoma (PDAC) risk using a hospital-based case-control design. METHODS: Patients with pathologically confirmed PDAC (943) and 1128 matched controls were recruited from 2 hospitals. We evaluated the associations between risk of PDAC and age, sex, history of diabetes mellitus (DM), etc. In addition, we examined the interactive effects of HBV status and known risk factors for pancreatic cancer. RESULTS: Chronic hepatitis B and inactive hepatitis B surface antigen (HBsAg) carrier state (HBsAg positive) had a significantly increased risk of pancreatic cancer, with an adjusted odds ratio of 1.60 (95% confidence interval [CI], 1.15-2.24). Furthermore, significant interactions were detected between a history of DM and chronic hepatitis B and inactive HBsAg positive, but not with antibodies to hepatitis B core antigen (anti-HBc) positive/antibodies to HBsAg (anti-HBs) negative, with an adjusted odds ratio of 5.42 (95% CI, 2.76-10.64), compared with those who were HBsAg negative/anti-HBc negative without a history of DM. CONCLUSIONS: These results suggest that HBsAg-positive or anti-HBc-positive/anti-HBs-negative patients have an increased risk for PDAC independent of other risk factors. Significant interactions were found between a history of DM and chronic HBV infection for PDAC risk.

Abdominal obesity and the risk of colorectal adenoma: a meta-analysis of observational studies.

Inconsistent results regarding the association between abdominal obesity and the risk of colorectal adenoma (CRA), the precursor of colorectal cancer (CRC), have been reported. To provide a quantitative assessment of this relationship, we summarized the evidence from observational studies in categorical, linear dose-response meta-analyses. We searched MEDLINE and EMBASE for studies of waist circumference (WC) and/or waist-hip ratio (WHR) and CRA risk published until the end of October 2011. Summary relative risks (SRRs) with 95% confidence intervals (CIs) were summarized using a random-effects model. Between-study heterogeneity was assessed using the Cochran's Q and I statistics. A total of 21 studies (four case-control studies, 12 cross-sectional studies, and five cohort studies) were included in this meta-analysis. Overall, the SRRs of CRA were 1.39 (95% CI: 1.24-1.56) for the highest versus the lowest level of WC and 1.22 (95% CI: 1.10-1.35) for WHR (P-value for heterogeneity 0.013 and 0.458, respectively). In linear dose-response analysis, a 10-cm increase in WC was related to an increased risk of CRA (SRR, 1.19; 95% CI, 1.13-1.26) and a 0.1-unit increment in WHR gave 1.16 (95% CI: 1.06-1.26). Subgroup analyses revealed that the increased risk of CRA in abdominally obese individuals was independent of geographic location, design, sex, and confounders: alcohol use, smoking status, and family history of colorectal cancer. However, BMI may be a confounder for the association between WC and CRA risk. These results suggest that abdominally obese individuals, both men and women, may have an increased risk of CRA.

Derivation and validation of a prediction rule for estimating advanced colorectal neoplasm risk in average-risk Chinese.

No prediction rule is currently available for advanced colorectal neoplasms, defined as invasive cancer, an adenoma of 10 mm or more, a villous adenoma, or an adenoma with high-grade dysplasia, in average-risk Chinese. In this study between 2006 and 2008, a total of 7,541 average-risk Chinese persons aged 40 years or older who had complete colonoscopy were included. The derivation and validation cohorts consisted of 5,229 and 2,312 persons, respectively. A prediction rule was developed from a logistic regression model and then internally and externally validated. The prediction rule comprised 8 variables (age, sex, smoking, diabetes mellitus, green vegetables, pickled food, fried food, and white meat), with scores ranging from 0 to 14. Among the participants with low-risk (≤3) or high-risk (>3) scores in the validation cohort, the risks of advanced neoplasms were 2.6% and 10.0% (P < 0.001), respectively. If colonoscopy was used only for persons with high risk, 80.3% of persons with advanced neoplasms would be detected while the number of colonoscopies would be reduced by 49.2%. The prediction rule had good discrimination (area under the receiver operating characteristic curve = 0.74, 95% confidence interval: 0.70, 0.78) and calibration (P = 0.77) and, thus, provides accurate risk stratification for advanced neoplasms in average-risk Chinese.

Risk of esophageal cancer in diabetes mellitus: a meta-analysis of observational studies.

OBJECTIVE: Inconsistent findings from observational studies have prolonged the controversy over the effects of history of diabetes mellitus (DM) on the risk of esophageal cancer (EC). We conducted a meta-analysis of epidemiologic studies to evaluate the association of a history of DM with the risk of EC. METHODS: We identified studies by a literature search of MEDLINE (from 1 January 1966) and EMBASE (from 1 January 1974), through 28 Feburary 2011, and by searching the reference lists of pertinent articles. Summary relative risks (SRRs) with 95% confidence intervals (CIs) were calculated with a random-effects model. All statistical tests were two-sided. RESULTS: A total of 17 studies (6 case-control studies and 11 cohort studies) fulfilled the inclusion and exclusion criteria. Compared with non-diabetic individuals, diabetic individuals had a modestly increased risk of EC (SRRs 1.30, 95% CI: 1.12-1.50), with significant heterogeneity among studies (p = 0.042). In stratified analysis, the SRRs of EC were 1.28 (1.10-1.49) for diabetic men and 1.07 (95% CI, 0.71-1.62) for diabetic women, respectively. In addition, DM was associated with an increased risk of esophageal adenocarcinoma (SRR 2.12, 95% CI 1.01-4.46). There was no significant publication bias (p = 0.127 for Begg's adjusted rank correlation test and p = 0.629 for Egger's regression test). CONCLUSION: These findings support the hypothesis that men with diabetes may have a modestly increased risk of EC, while diabetic women were not the case.

High expression of delta-like ligand 4 predicts poor prognosis after curative resection for pancreatic cancer.

BACKGROUND: Delta-like ligand 4 (DLL4)-Notch signaling plays a key role in tumor angiogenesis, but its prognostic value in patients with pancreatic ductal adenocarcinoma (PDAC) remains unclear. Our aim was to determine whether high DLL4 expression is correlated with poor prognosis after curative resection for PDAC. METHODS: Surgical specimens obtained from 89 patients with PDAC were immunohistochemically assessed for DLL4 and vascular endothelial growth factor receptor 2 (VEGFR-2) expression. Prognostic significance of DLL4 expression was evaluated by Kaplan-Meier method and Cox regression. The correlations of DLL4 expression with VEGFR-2 expression, tumor stage, and lymph node metastasis were examined by chi-square test and multivariate logistic regression. RESULTS: There were 38 (42.7%) and 51 patients who showed high and low DLL4 expression, respectively. Survival curves showed that patients with low DLL4 expression had a significantly better survival than those with high DLL4 expression (P < .001). Multivariate survival analysis demonstrated that high DLL4 expression was independently associated with both reduced overall survival (hazard ratio [HR] 2.24; 95% confidence interval [95% CI] 1.14-4.38) and reduced progression-free survival (HR 2.37; 95% CI 1.22-4.60). Multivariate logistic regression analyses showed that high DLL4 expression was independently associated with both advanced tumor stage (odds ratio [OR] 6.84; 95% CI 2.42-9.36) and lymph node metastasis (OR 3.27; 95% CI 1.04-10.34). We also found a positive correlation between DLL4 and VEGFR-2 expression (P < .001). CONCLUSIONS: High DLL4 expression is significantly associated with poor prognosis for surgically resected PDAC, advanced tumor stage, and lymph node metastasis. Application of adjuvant therapy targeting DLL4-Notch signaling may improve prognosis.