Yanbing Zhou

Fast-track Surgery Improves Postoperative Recovery in Patients with Gastric Cancer: A Randomized Comparison with Conventional Postoperative Care

BackgroundFast-track surgery is a new, promising comprehensive program for surgical patients and is beneficial to recovery. Prospective randomized, controlled clinical trials involving fast-track surgery for gastric cancer are lacking.Patient and methodsNinety-two patients with gastric cancer were randomly divided into a fast-track surgery group (n = 45) and conventional surgery group (n = 47). We compared outcomes (duration of postoperative stay in hospital, fever, and flatus, complications, and medical costs); postoperative serum levels of tumor necrosis factor-α, interleukin-6, and C-reactive protein; and resting energy expenditure between two groups.ResultsCompared with the conventional surgery group, the fast-track surgery group had no more complications (P > 0.05) with a significantly shorter duration of fever, flatus, and hospital stay, and less medical costs as well as a higher quality of life score on hospital discharge (all P < 0.05). With a significantly lower resting energy expenditure (days 1 and 3) postoperatively (P < 0.05), the fast-track surgery group showed a lower serum level of tumor necrosis factor-α (days 1 and 3), interleukin-6 (days 1 and 3), and C-reactive protein (days 1, 3, and 7) than the conventional surgery group (all P < 0.05).ConclusionsFast-track surgery can lessen postoperative stress reactions and accelerate rehabilitation for patients with gastric cancer.

A Comparison Between the Seventh and Sixth Editions of the American Joint Committee on Cancer/International Union Against Classification of Gastric Cancer.

Objective:To evaluate the prognostic significance of the seventh edition TNM staging classification for gastric cancer. Background:The seventh edition TNM staging system for gastric cancer was adopted by the American Joint Committee on Cancer/International Union Against Cancer on January 1, 2010, and included major revisions. Methods:The authors analyzed data retrospectively collected on patients with gastric cancer who underwent surgery at the Affiliated Hospital of Qingdao University Medical College between 2000 and 2008. A total of 964 patients with gastric cancer who underwent R0 surgical resection were included. Results:The relative risk (RR) for the seventh edition T classification was found to increase steadily and reasonably compared with the sixth edition. However, the RR for the sixth edition N classification was found to increase steadily and reasonably compared with the seventh edition classification. Cox regression multivariate analysis showed that the sixth edition N classification was superior to the seventh edition N classification as an independent prognostic factor. In survival analysis, the seventh edition TNM classification provided a more detailed classification; however, some subgroups of the seventh edition TNM classification did not demonstrate significantly different survival rates. The combination of the seventh edition T classification and the sixth edition N classification, with ideal RR results, showed significantly different survival rates except for IA and IB. Conclusions:The combination of the seventh edition T classification and the sixth edition N classification seems to provide the optimal prognosis.

Slug down-regulation by RNA interference inhibits invasion growth in human esophageal squamous cell carcinoma.

BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most aggressive carcinomas of the gastrointestinal tract. We assessed the relevance of Slug in measuring the invasive potential of ESCC cells in vitro and in vivo in immunodeficient mice.MethodsWe utilized RNA interference to knockdown Slug gene expression, and effects on survival and invasive carcinoma were evaluated using a Boyden chamber transwell assay in vitro. We evaluated the effect of Slug siRNA-transfection and Slug cDNA-transfection on E-cadherin and Bcl-2 expression in ESCC cells. A pseudometastatic model of ESCC in immunodeficient mice was used to assess the effects of Slug siRNA transfection on tumor metastasis development.ResultsThe EC109 cell line was transfected with Slug-siRNA to knockdown Slug expression. The TE13 cell line was transfected with Slug-cDNA to increase Slug expression. EC109 and TE13 cell lines were tested for the expression of apoptosis-related genes bcl-2 and metastasis-related gene E-cadherin identified previously as Slug targets. Bcl-2 expression was increased and E-cadherin was decreased in Slug siRNA-transfected EC109 cells. Bcl-2 expression was increased and E-cadherin was decreased in Slug cDNA-transfected TE13 cells. Invasion of Slug siRNA-transfected EC109 cells was reduced and apoptosis was increased whereas invasion was greater in Slug cDNA-transfected cells. Animals injected with Slug siRNA-transfected EC109 cells exhihited fewer seeded nodes and demonstrated more apoptosis.ConclusionsSlug down-regulation promotes cell apoptosis and decreases invasion capability in vitro and in vivo. Slug inhibition may represent a novel strategy for treatment of metastatic ESCC.

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.

Multivariate logistic regression analysis of postoperative complications and risk model establishment of gastrectomy for gastric cancer: A single-center cohort report

Abstract Background. Reporting of surgical complications is common, but few provide information about the severity and estimate risk factors of complications. If have, but lack of specificity. Methods. We retrospectively analyzed data on 2795 gastric cancer patients underwent surgical procedure at the Affiliated Hospital of Qingdao University between June 2007 and June 2012, established multivariate logistic regression model to predictive risk factors related to the postoperative complications according to the Clavien-Dindo classification system. Results. Twenty-four out of 86 variables were identified statistically significant in univariate logistic regression analysis, 11 significant variables entered multivariate analysis were employed to produce the risk model. Liver cirrhosis, diabetes mellitus, Child classification, invasion of neighboring organs, combined resection, introperative transfusion, Billroth II anastomosis of reconstruction, malnutrition, surgical volume of surgeons, operating time and age were independent risk factors for postoperative complications after gastrectomy. Based on logistic regression equation, p=Exp∑BiXi / (1+Exp∑BiXi), multivariate logistic regression predictive model that calculated the risk of postoperative morbidity was developed, p = 1/(1 + e(4.810–1.287X1–0.504X2–0.500X3–0.474X4–0.405X5–0.318X6–0.316X7–0.305X8–0.278X9–0.255X10–0.138X11)). The accuracy, sensitivity and specificity of the model to predict the postoperative complications were 86.7%, 76.2% and 88.6%, respectively. Conclusions. This risk model based on Clavien-Dindo grading severity of complications system and logistic regression analysis can predict severe morbidity specific to an individual patient’s risk factors, estimate patients’ risks and benefits of gastric surgery as an accurate decision-making tool and may serve as a template for the development of risk models for other surgical groups.

Genome-wide association study identifies two new susceptibility loci for colorectal cancer at 5q23.3 and 17q12 in Han Chinese

Genome-wide association studies (GWAS) have reported a number of loci harboring common variants that influence risk of colorectal cancer (CRC) in European descent. But all the SNPs identified explained a small fraction of total heritability. To identify more genetic factors that modify the risk of CRC, especially Chinese Han specific, we conducted a three-stage GWAS including a screening stage (932 CRC cases and 966 controls) and two independent validations (Stage 2: 1,759 CRC cases and 1,875 controls; Stage 3: 943 CRC cases and 1,838 controls). In the combined analyses, we discovered two novel loci associated with CRC: rs12522693 at 5q23.3 (CDC42SE2-CHSY3, OR = 1.31, P = 2.08 × 10−8) and rs17836917 at 17q12 (ASIC2-CCL2, OR = 0.75, P = 4.55 × 10−8). Additionally, we confirmed two previously reported risk loci, rs6983267 at 8q24.21 (OR = 1.17, P = 7.17 × 10−7) and rs10795668 at 10p14 (OR = 0.86, P = 2.96 × 10−6) in our cohorts. These results bring further insights into the CRC susceptibility and advance our understanding on etiology of CRC.

Clinicopathological features and survival analysis of gastroenteropancreatic neuroendocrine neoplasms: a retrospective study in a single center of China

OBJECTIVE To investigate the clinicopathological features, survival and prognostic factors for gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) in a Chinese population. METHODS We investigated 154 consecutive patients (88 males, 66 females; median age 56 years, age range 9-86 years) diagnosed with GEP-NENs between 2001 and 2013 at The Affiliated Hospital of Qingdao University. Demographic, clinical and pathological variables and survival data were retrieved. RESULTS The pancreas was the most common site of involvement (63/154, 40.9%). Tumor size varied from 0.3 to 16.0 cm (median, 1.2 cm). The patients were followed up for a median period of 22 months (range, 1-157 months). The estimated 3- and 5-year overall survival (OS) rates for all patients were 84.0% and 81.9%, respectively. Multivariate analysis showed that larger tumor size, lymphatic metastases and distant metastases were significant predictors for poor survival outcome. CONCLUSIONS Our data provide further information on the clinicopathological features of GEP-NENs in China. Additionally, we identified tumor size, lymphatic metastases and distant metastases as independent prognostic factors for long-term survival.

Total parathyroidectomy versus total parathyroidectomy with autotransplantation for secondary hyperparathyroidism: systematic review and meta-analysis

Abstract Background: Total parathyroidectomy (tPTX) and total parathyroidectomy with autotransplantation (tPTX + AT) are effective and inexpensive treatments for secondary hyperparathyroidism (sHPT), but we do not know which one is the optimal approach. Therefore, we undertook a meta-analysis to compare the safety and efficacy of these two surgical procedures. Methodology: Studies published in English on PubMed, Embase and the Cochrane Library from inception to 27 September 2016 were searched systematically. Eligible studies comparing tPTX with tPTX + AT for sHPT were included and Review Manager v5.3 was used. Results: Eleven studies were included in this meta-analysis. Ten cohort studies and one randomized controlled trial (RCT) involving 1108 patients with sHPT were identified. There was no significant difference in the prevalence of surgical complications (relative risk [RR], 1.71; 95% confidence interval [CI], 0.77–3.79; p = .19), all-cause mortality (RR, 0.68; 95% CI, 0.33–1.39; p = .29), sHPT persistence (RR, 3.81; 95% CI, 0.56–25.95; p = .17) or symptomatic improvement (RR, 1.02; 95% CI, 0.91–1.13; p = .79). tPTX could reduce the risk of sHPT recurrence (RR, 0.19; 95% CI, 0.09–0.41; p < .0001) and reoperation because of recurrence or persistence of sHPT (RR, 0.46; 95% CI 0.24–0.86; p = .01) compared with tPTX + AT. Simultaneously, tPTX increased the risk of hypoparathyroidism (RR, 2.63; 95% CI, 1.06–6.51; p = .04). Conclusions: We found tPTX and tPTX + AT to be useful methods for sHPT treatment. tPTX was superior for reducing the risk of sHPT recurrence and reoperation than tPTX + AT but, due to a lack of high statistical-power RCTs, comparative studies will be needed in the future.

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.

Pancreatic stellate cells increase pancreatic cancer cells invasion through the hepatocyte growth factor /c-Met/survivin regulated by P53/P21

ABSTRACT Pancreatic stellate cells (PSCs) are a key cellular component of the pancreatic tumor microenvironment and are considered to contribute to tumor invasion and metastasis. Multiple cytokines and growth factors derived from PSCs are involved in malignant cancer progression, including hepatocyte growth factor (HGF). However, the molecular mechanisms by which HGF regulates cancer invasion and metastasis have not been completely elucidated. Here, we report that two pancreatic cancer (PC) cell lines, Panc‐1 and SW1990, displayed different invasive and migratory abilities after treatment with HGF secreted by PSCs. We found that HGF enhanced the invasive and migratory capacity of Panc‐1 cells because of P53 deficiency, leading to overexpression of c‐Met, which was regulated through P21. Additionally, our data showed that HGF/c‐Met‐mediated invasion and migration required the upregulation of survivin expression. In conclusion, PSCs promote PC cells invasion and migration via the HGF/c‐Met/survivin pathway, which is negatively regulated by P53/P21.