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.

Canmei Formula Reduces Colitis-Associated Colorectal Carcinogenesis in Mice by Modulating the Composition of Gut Microbiota.

The gut microbiota, including pathogenic microorganisms and probiotics, has been involved in tumor initiation and progression by regulating the components of intestinal flora. Canmei formula (CMF), a traditional Chinese medicine, chronicled in the Chuang Yang Jing Yan Quan Shu, has been clinically used as an adjuvant therapy to treat patients with colorectal carcinoma (CRC) in China. In this study, we investigate the treatment effect of CMF in the azoxymethane (AOM) and dextran sodium sulfate (DSS) induced and high-fat diet augmented colitis-associated colorectal cancer in vivo, and explore its mechanism of action. We found that CMF treatment relieved the inflammation and alteration of the gut microbiota and significantly inhibited the development of intestinal adenoma. Linear discriminant analysis showed that the flora diversity in the normal mice, model mice and CMF treatment mice was different. At the family level, the relative abundance of Desulfovibrionaceae decreased in CMF groups. The relative abundance of Desulfovibrionaceae were lower in the CMF groups than in model group, whereas Rikenellaceae and Alistipes were increased. Altogether our results indicate that CMF treatment ameliorate colitis-associated colorectal carcinogenesis by modulating the composition of the gut microbiota in vivo.

Carbon dioxide insufflation improves the intubation depth and total enteroscopy rate in single-balloon enteroscopy: a randomised, controlled, double-blind trial.

OBJECTIVE: The total enteroscopy rate of single-balloon enteroscopy (SBE) using air insufflation is not satisfactory, and whether carbon dioxide (CO2) insufflation increases the total enteroscopy rate of SBE is unknown. This randomised controlled trial aimed to determine whether CO2 insufflation facilitates the intubation depth and total enteroscopy rate of SBE. DESIGN: A total of 214 eligible patients referred for SBE were randomised to receive either air or CO2 insufflation, and included in the intention-to-test (ITT) analysis. In addition, 199 patients in whom enteroscopy was completed were included in the per-protocol (PP) analysis. Both the patients and endoscopists were blinded, and the intubation depth and total enteroscopy rate were defined as the primary outcomes. RESULTS: The CO2 group showed a superiority of intubation in the ITT analysis (oral route: 323.8±64.2 vs 238.3±68.6 cm; anal route: 261.6±74.2 vs 174.7±62.1 cm, both p<0.001), and the total enteroscopy rate (34.9% vs 17.6%, p=0.006). Similar results were obtained in a PP analysis for both outcomes. In addition, in the PP analysis, the addition of circumference after the procedure was less in the CO2 group (0.8±0.6 vs 3.3±1.8 cm, p=0.005) for the oral route. No serious complications were reported. The overall percentage of procedures with significant pathological findings was 52.8%; the rates were 58.5% and 47.2% (p=0.100, ITT analysis) in the CO2 and air groups, respectively. CONCLUSIONS: CO2 insufflation improves the intubation depth and total enteroscopy rate in SBE with a good safety profile and acceptability compared with that of air, and thus is recommended for clinical utilisation. TRIAL REGISTRATION NUMBER: ClinicalTrial.gov identifier: NCT01758900.

Downregulation of apurinic/apyrimidinic endonuclease 1/redox factor-1 enhances the sensitivity of human pancreatic cancer cells to radiotherapy in vitro.

UNLABELLED: Abstract Background: Radiotherapy is an important treatment for the patients with advanced pancreatic cancer. Emerging studies determined apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) might associate with the resistance of human pancreatic cancer cells to radiotherapy. AIMS: To investigate whether downregulation of APE1/Ref-1 expression by ribonucleic acid interference would increase the sensitivity of chromic-P32 phosphate to pancreatic cancer cells. METHODS: The plasmids containing APE-specific and unspecific short hairpin were transfected into Patu-8898 cells. Stable cell clones were selected by G418. The mRNA expression of APE1/Ref-1 was detected by semiquantitative reverse transcription-polymerase chain reaction and the protein expression of APE1/Ref-1 was detected by Western blot analysis; cell proliferation was studied by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and colony formation assay; apoptosis was detected by flow cytometry. RESULTS: After 24 hours irradiation, APE1/Ref-1 mRNA and protein expression were upregulated, in a concentration-dependent manner. Suppression of APE1/Ref-1 by siRNA increased the pancreatic cancer cells hypersensitive to (32)P-CP. In the combination of (32)P-CP and siRNA group, MTT assay showed that the cell inhibition increased to (74.33%±9.02%), the surviving fraction in the colony formation assay was only 25.00%, and the apoptosis rate was up to (16.77%±0.98%). CONCLUSIONS: Knockdown APE1/Ref-1 gene expression may significantly sensitize the Patu-8988 cells to radiotherapy, which may be a useful target for modifying radiation resistance of pancreatic cancer cells to irradiation.

Effects of thalidomide in experimental models of post-endoscopic retrograde cholangiopancreatography pancreatitis.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) plays a central role in the pathogenesis of acute pancreatitis and related systemic complications. The authors hypothesized that it may also play an important role in the development of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). The aim of the study was to evaluate the effectiveness of thalidomide, an immunomodulator that exerts an inhibitory action on TNF-alpha by enhancing mRNA degradation, in reducing post-ERCP pancreatitis in a rat model. METHODS: A total of 200 mg/kg thalidomide was given intragastric once a day (total 8 days) before the experimental models of post-ERCP pancreatitis were established. After 24 h, histology and edema of pancreas, serum amylase, and TNF-alpha mRNA in the pancreatic tissue were evaluated. RESULTS: Intraductal contrast infusion caused increases in serum amylase, edema, histological grade, and TNF-alpha mRNA of pancreas. The prophylactic use of thalidomide significantly reduced serum amylase, pancreatic edema and the histologic grade of pancreatitis accompanied by a decrease in mRNA expression of TNF-alpha in the pancreatic tissue. CONCLUSIONS: Prophylactic intragastric administration of thalidomide provides a protective effect in post-ERCP pancreatitis. The mechanism of the protective effects of thalidomide seems to be the reduction of expression of TNF-alpha mRNA in pancreatic tissue.

Role of prophylactic antibiotic administration in severe acute pancreatitis: a meta-analysis.

OBJECTIVE: To carry out a meta-analysis of published studies in order to evaluate the clinical efficacy of prophylactic antibiotics in severe acute pancreatitis (SAP). MATERIAL AND METHODS: MEDLINE, China Biological Medicine, Embase and Cochrane Data Base for Systematic Reviews were searched for randomized controlled trials on the efficacy of prophylactic antibiotics in patients with SAP from 1966 to 2004. Six studies met our inclusion criteria. Two authors (G.S.X. and Z.H.W.) independently extracted the following data from these studies: trial design, characteristics of participants and outcomes. Data were analyzed by Revman 4.2 software. RESULTS: In patients with SAP, prophylactic antibiotics, including broad-spectrum antibiotics that usually achieve therapeutic pancreatic tissue levels, did not reduce pancreatic infection (relative risk, RR, 0.77, 95% confidence interval 0.48-1.24, p = 0.28), surgical intervention (RR 0.84, 95% confidence interval 0.40-1.74, p = 0.64) and mortality rate (RR 0.54, 95% confidence interval 0.28-1.04, p = 0.07). CONCLUSIONS: Prophylactic antibiotic administration is not an appropriate treatment strategy in patients with SAP, it should be limited in patients with pancreatic necrosis, as demonstrated by computerized tomography.