Efficacy of the Short-Term versus Long-Term Administration of Antimicrobial Prophylaxis in Gastric Cancer Surgery: A Meta-Analysis of Randomized Controlled Trials.

Background: We performed a meta-analysis to confirm the efficacy of short-term compared with long-term administration of antimicrobial prophylaxis in gastric cancer surgery. Methods: Randomized controlled trials of the efficacy of short-term versus long-term administration of antimicrobial prophylaxis in gastric cancer surgery were searched using the MEDLINE, EMBASE, and the Cochrane Controlled Trials Register databases. The data were evaluated and statistically analyzed using RevMan version 5.3.0. Five studies including 2,053 participants who received short-term versus long-term administration of antimicrobial prophylaxis in gastric cancer surgery were considered. Results: There was no significant difference in the surgical site infection (SSI) rate between the short-term group and the long-term group (8.1% vs. 9.2%; odds ratio [OR], 0.87; 95% confidence interval [CI], 0.64-1.09; p = 0.39). Hierarchical analysis also showed no significant differences in incisional-site incisions, organ/space incisions, or leakage. Multivariable analysis showed no significant differences in gender, age (>65 years), body mass index (>25 kg/m2), D2, operation time (>3 hours), pathologic stage 3, blood loss, combined resection, diabetes mellitus, total gastrectomy, or blood transfusion between the two groups. Conclusions: Short-term administration of antimicrobial prophylaxis did not increase the incidence of SSIs after gastrectomy.

Dehydrocostus lactone inhibits in vitro gastrinoma cancer cell growth through apoptosis induction, sub-G1 cell cycle arrest, DNA damage and loss of mitochondrial membrane potential.

INTRODUCTION: The purpose of the present study was to evaluate the antiproliferative activity of dehydrocostus lactone against human BON-1 cancer cell lines and to explore the possible underlying mechanism. MATERIAL AND METHODS: MTT cell viability assay was used to determine cytotoxic effects of dehydrocostus lactone in BON-1 cells. Fluorescence and transmission electron microscopic (TEM) techniques were used to study the effect of the compound on cellular morphology and apoptosis. Flow cytometry was used to assess the effect on cell cycle phase distribution. Effects of the drug on cell apoptosis and mitochondrial membrane potential were analyzed by flow cytometry using annexin v and rhodamine-123 as fluorescent probes. RESULTS: The results of the present study indicated that dehydrocostus lactone significantly (p < 0.01) inhibited the growth of BON-1 cancer cells. These growth inhibitory effects of dehydrocostus lactone on BON-1 were found to be time and concentration-dependent. The IC50 of dehydrocostus lactone were found to be 71.9 µM and 52.3 µM at 24 and 48 h time intervals respectively. The growth inhibitory effects of dehydrocostus lactone were found to be due to loss of mitochondrial membrane potential, the induction of apoptosis and sub-G1 cell cycle arrest. CONCLUSIONS: Dehydrocostus inhibits in vitro gastrinoma cancer cell growth and therefore may prove beneficial in the management of gastrinoma cancer.

A pilot study on clinicopathological features and intestinal microflora changes in colorectal cancer patients born over a nine-year period encompassing three years before and after the Great Chinese famine.

BACKGROUND: Exposure to energy restriction during childhood is associated with a lower risk of developing colorectal cancer (CRC). To date, the association between this critical period of growth and prognosis of CRC has rarely been investigated. Changes in microbiota and epigenetic dysregulation may be key underlying mechanisms. METHODOLOGY: Tissues collected from patients born between 1956 and 1964 were grouped based on time-period. The differences in overall survival among patients from the three time-periods were examined via univariate analysis. The 16S rRNA gene sequencing approach was to determine differences in microbiota among the groups. Samples were randomly selected to detect BRAF mutations, microsatellite instability (MSI) and promoter CpG island methylator phenotype (CIMP) status. The chi-square test was to assess the relationship between alterations in these molecules and microbiota differences. RESULTS: Patients from the three groups differed in terms of location of CRC (P = 0.034) and carcinoembryonic antigen (CEA) level (P = 0.036). A survival advantage was observed in the famine group compared with the other two groups. Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli were more abundant in the two comparing groups. Abundance of B. fragilis was associated with BRAF mutations, microsatellite instability (MSI) and abundance of E. coli. Moreover, the incidence of CIMP and MSI was higher in patients with greater abundance of F. nucleatum. CONCLUSIONS: Limitation of energy intake during childhood may affect the composition of gut microbiota, resulting in persistent epigenetic changes that subsequently influence the prognosis of patients with CRC.

Effect of long non-coding RNA AOC4P on gastrointestinal stromal tumor cells.

OBJECTIVE: In this research, we explored the effect of long non-coding RNA (lncRNA) AOC4P on gastrointestinal stromal tumor (GIST) cells. MATERIALS AND METHODS: The expression of lncRNA AOC4P in tissues was detected by real-time PCR (RT-PCR). The epithelial-mesenchymal transition (EMT)-related proteins in tissues were analyzed by Western blot. The experiment included negative control group (CN), silence AOC4P group (si AOC4P), and silence negative control group (si CT). RT-PCR, MTT, Scratch, Transwell, and Annexin V-FITC methods were used to detect the expression of lncRNA AOC4P, cell proliferation, cell migration ability, cell invasion ability, and apoptosis, respectively. The EMT-related proteins including TGF-ß, ZEB1, Vimentin, Snail, and E-cadherin were analyzed by Western blot. RESULTS: The expression of lncRNA AOC4P and the expression of EMT-related proteins in high-risk GISTs were higher than that in low- and intermediate-risk GISTs (P<0.05). It was revealed that cell proliferative migration and invasive ability in si AOC4P group was decreased than that in CN and si CT groups (P<0.05), and cell apoptosis in si AOC4P group was higher than that in si CT group. The results of Western blot demonstrated that the expression of TGF-ß1, ZEB1, Vimentin, and Snail in si AOC4P group were lower than that in si CT and CN group (P<0.05), and the expression of E-cadherin in si AOC4P group was higher than that in si CT and CN group (P<0.05).

The influence of neoadjuvant chemotherapy on gastric cancer patients' postoperative infectious complications: What is the negative role played by the intestinal barrier dysfunction?

Evidence has shown that neoadjuvant chemotherapy (NACT) is correlated with patients' overall postoperative complications. But investigations on relationship between NACT and postoperative infectious complications, which is closely linked to intestinal barrier damage, were scanty. Accordingly, 90 patients with advanced gastric cancer were included in this study. The differences in postoperative infectious complications were determined between NACT group in which patients received NACT before surgery and SURG group in which received surgical treatment immediately after diagnosis. The damage of mechanical structure of intestinal barrier was assessed by hematoxylin and eosin staining, transmission electron microscopy, and immunohistochemistry. Mucosal microbiota changes were determined by using a 16S rRNA gene sequencing approach. Results showed that the incidence of postoperative infectious complications were significantly higher in the NACT group. Tight junctions were disrupted, and claudin-1, ZO-1 and occludin were down-regulated in patients with infectious complications in overall compared with those without. And similarly, the patients in the NACT group also showed damaged intestinal barrier compared with those in SURG group. Besides, the total diversity of mucosal related bacteria was decreased and relative abundance of some probiotics, such as Bifidobacterium, Faecalibacterium and Ruminococcus, was reduced in the NACT group as well. In conclusion, our study identifies a higher incidence of postoperative infection in gastric cancer patients who underwent NACT treatment, and these changes might be caused by a significant damage in the intestinal barrier as well as reduced probiotics.

Evolutionary biologic changes of gut microbiota in an 'adenoma-carcinoma sequence' mouse colorectal cancer model induced by 1, 2-Dimethylhydrazine.

The molecular biological mechanisms underlying the evolutionary biologic changes leading to carcinogenesis remain unclear. The main objective of our study was to explore the evolution of the microbiota community and molecules related with CRC in the dynamic transition from normal colon epithelium to premalignant adenoma with the aid of an 'adenoma-carcinoma sequence' mouse CRC model induced by DMH. We generated a modified mouse CRC model induced by DMH for DNA sequences, and characterized the molecular networks. Data from 454 pyrosequencing of the V3- V5 region of the 16S rDNA gene and immunohistochemical detection of APC, P53, K-RAS and BRAF genes were assessed with Principal coordinates, UniFrac, and Kruskal-Wallis rank sum test. The inflammatory group showed enrichment of Bacteroidetes and Porphyromonadaceae (P < 0.01). OTUs affiliated with Firmicutes were enriched in the hyperproliferative group (P < 0.01). Rikenellaceae and Ruminococcaceae showed an increasing trend during the CRC process while the opposite pattern was observed for Prevotellaceaeand Enterobacteriaceae. OTUs related to Alistipes finegoldii were significantly increased during CRC development, P53, K-RAS and BRAF, were gradually increased (P < 0.05). Conversely, expression of APC was decreased during the course of development of CRC. Our results demonstrate that the biological evolutionary shift of gut microbiota, characterized by a gradual decrease in 'driver' bacteria and an increase in DNA damage-causing bacteria, is accompanied by tumor development in the CRC model. The synergistic actions of microbiota dysbiosis and effects of bacterial metabolites on related molecular events are proposed to contribute to the progression of CRC tumorigenesis.

Comparison of lymph node number and prognosis in gastric cancer patients with perigastric lymph nodes retrieved by surgeons and pathologists.

OBJECTIVE: To compare the numbers of positive and total lymph nodes and prognosis in gastric cancer patients whose perigastric lymph node retrieval was performed by surgeons and pathologists. METHODS: We conducted a retrospective analysis of clinical and follow-up data from 1, 056 patients who underwent gastric cancer D2 radical lymph node resection between January 2008 and December 2010 in the Gastrointestinal Surgery Department of Yantai Yuhuangding Hospital. The follow-up ended in December 2015. Patients were divided into two groups according to the specialty of physicians who performed the postoperative perigastric lymph node retrieval: the surgeon group (475 cases) and the pathologist group (581 cases). The numbers of positive and total perigastric lymph nodes and the 3- and 5-year survival were compared between gastric cancer patients in the two groups overall and stratified by TNM stage (the 7th Edition of the American Joint Committee on Cancer). RESULTS: Overall, the numbers of positive and total lymph nodes were significantly higher in the surgeon group than in the pathologist group (6.53±4.07 vs. 4.09±3.70, P=0.021; 29.64±11.50 vs. 20.71±8.56, P<0.001). Further analysis showed that the total number of lymph nodes in stage I patients (19.40±9.62 vs. 15.45±8.59, P=0.011) and the numbers of positive and total lymph nodes in stage II (1.38±1.08 vs. 0.87±1.55, P=0.031; 25.35±10.80 vs. 16.75±8.56, P<0.001) and stage III patients (8.11±6.91 vs. 6.66±5.12, P=0.026; 32.34±12.55 vs. 25.45±8.31, P<0.001) were significantly higher in the surgeon group than in the pathologist group. The survival analysis showed that the 3- and 5-year survival of stage II and III patients was significantly higher in the surgeon group than in the pathologist group (82.0% vs. 73.1%, 69.5% vs. 61.2%, P=0.038; 49.2% vs. 38.9%, 36.3% vs. 28.0%; P=0.045). CONCLUSIONS: Compared with retrieval performed by pathologists, postoperative perigastric lymph node retrieval performed by surgeons was associated with significant increase in the total lymph node number of stage I patients, the numbers of positive and total lymph nodes of stage II and III patients, and the survival of stage II and stage III gastric cancer patients.

Could gut microbiota serve as prognostic biomarker associated with colorectal cancer patients' survival? A pilot study on relevant mechanism.

Evidences have shown that dysbiosis could promote the progression of colorectal cancer (CRC). However, the association of dysbiosis and prognosis of CRC is barely investigated. Therefore, we used 16S rRNA gene sequencing approach to determine differences in microbiota among tumor tissues of different prognosis and found that Fusobacterium nucleatum and Bacteroides fragilis were more abundant in worse prognosis groups, while Faecalibacterium prausnitzii displayed higher abundance in survival group. To further explore the prognostic value of the found bacteria, Kaplan-Meier and Cox proportional regression analyses were used and the results exhibited that high abundance of F. nucleatum and B. fragilis were independent indicators of poor patient's survival. Besides, the expression of major inflammatory mediator were analyzed using PCR and western blot methods, and it turned out that high abundance of F. nucleatum was associated with increased expression of TNF-α, ß-catenin and NF-κB, while COX-2, MMP-9 and NF-κB were positively related with high B. fragilis level, and high level of F. prausnitzii showed lower expression of ß-catenin, MMP-9 and NF-κB. Moreover, immunohistochemical analysis indicated that KRAS and BRAF expression were prominent in F. nucleatum and B. fragilis high abundance group, while MLH1 showed lower expression. In conclusion, F. nucleatum, B. fragilis and F. prausnitzii can be identified as useful prognostic biomarkers for CRC, and dysbiosis might worsen the patients' prognosis by up-regulating gut inflammation level.

[Progress of research in the relationship between microorganisms and colorectal cancer].

Colorectal cancer is a common carcinoma of gastrointestinal tract, and its incidence is associated with genetic mutations, environment as well as inflammation. Recent studies have shown that many microorganisms may have played an important role in pathogenesis of colorectal cancer. The common bacteria involved in colorectal cancer are Streptococcus bovis, Helicobacter pylori, Escherichia coli, Bacteroides, and Fusobacterium, etc. The common viruses are Polyomavirus, Epstein Barr virus, Cytomegalovirus and Human papillomavirus, etc. The detailed mechanism of these microorganisms in the pathogenesis of colorectal cancer is unclear, and there are no reports on specific pathogenic microorganisms which cause the disease directly. The direction of future researches will focus on metagenome, metatranscriptome, and metaproteome of microorganisms associated with the incidence of colorectal cancer.