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Objective The benefit of adjuvant chemotherapy is still controversial for stage II gastric cancer patients. This study aims to identify prognostic factors to guide individualized treatment for stage II gastric cancer patients. Methods We retrospectively reviewed 1121 stage II gastric cancer patients who underwent D2 radical gastrectomy from 2007 to 2017 in the Sixth Affiliated Hospital of Sun Yat-sen University, FuJian Medical School Affiliated Union Hospital and Sun Yat-sen University Cancer Center. Propensity score matching was used to ensure that the baseline data were balanced between the adjuvant chemotherapy group and surgery-only group. Kaplan–Meier survival and multivariate Cox regression analyses were carried out to identify independent prognostic factors. Results In univariate analysis, after propensity score matching, age, tumor location, tumor size, CEA, T stage and N stage were associated with overall survival (OS). Multivariate analysis illustrated that age ≥ 60 years old, linitis plastica and T4 were independent risk factors for OS, but lower location and adjuvant chemotherapy were protective factors. Conclusion Stage II gastric cancer patients with adverse prognostic factors (age ≥ 60, linitis plastica and T4) have poor prognosis. Adjuvant chemotherapy may be more beneficial for these patients.

Purpose: Previous studies proposed that the multidisciplinary team (MDT) consultation could improve tumor staging accuracy and outcomes of patients with gastric malignancy. However, evidence-based reports remain limited. This study aimed to determine the effectiveness of MDT for tumor staging accuracy and outcomes of patients with resectable gastric cancer, and to explore the potential factors affecting its effectiveness. Methods: This retrospective study enrolled 719 gastric cancer patients who underwent gastrectomy in our hospital. After propensity score matching, 378 patients were selected, including 189 in the non-MDT group and 189 in the MDT group. Data regarding baseline characteristics, staging, treatments, and survival were analyzed. Results: The data showed that the staging accuracy in the MDT group and non-MDT group was comparable (53% vs 61% for T stage, 46.1% vs 35.3% for N stage, and 78.3% vs 78.7% for M stage). The MDT group had a higher proportion of preoperative chemotherapy (39.2% vs 28%, p=0.03) and laparoscopic surgery (82.5% vs 72%, p=0.02) than the non-MDT group. However, the achievement of R0 resection was similar in the two groups (93.7% vs 88.9%, p=0.73). There was no significant difference in the 1-year and 3-year overall survival rates between the two groups. Moreover, we observed poor patient compliance when the MDT recommended further examinations, radiotherapy, or chemotherapy before surgical interventions. Conclusion: MDT consultation has limited effects on improving the staging accuracy and treatment outcomes including survival of patients with resectable gastric cancer. Poor patient compliance may be a factor affecting the effectiveness of MDT consultation.

There is an urgent need for novel agents for colorectal cancer (CRC) due to the increasing number of cases and drug-resistance related to current treatments. In this study, we aim to uncover the potential of chaetocin, a natural product, as a chemotherapeutic for CRC treatment. We showed that, regardless of 5-FU-resistance, chaetocin induced proliferation inhibition by causing G2/M phase arrest and caspase-dependent apoptosis in CRC cells. Mechanically, our results indicated that chaetocin could induce reactive oxygen species (ROS) accumulation and activate c-Jun N-terminal kinase (JNK)/c-Jun pathway in CRC cells. This was confirmed by which the JNK inhibitor SP600125 partially rescued CRC cells from chaetocin induced apoptosis and the ROS scavenger N-acetyl-L-cysteine (NAC) reversed both the chaetocin induced apoptosis and the JNK/c-Jun pathway activation. Additionally, this study indicated that chaetocin could down-regulate the expression of CD47 at both mRNA and protein levels, and enhance macrophages phagocytosis of CRC cells. Chaetocin also inhibited tumor growth in CRC xenograft models. In all, our study reveals that chaetocin induces CRC cell apoptosis, irrelevant to 5-FU sensitivity, by causing ROS accumulation and activating JNK/c-Jun, and enhances macrophages phagocytosis, which suggests chaetocin as a candidate for CRC chemotherapy.

Objective Peritoneal dissemination is difficult to diagnose by conventional imaging technologies. We aimed to construct a nomogram to predict peritoneal dissemination in gastric cancer (GC) patients. Methods We retrospectively analyzed 1,112 GC patients in Sun Yat-sen University Cancer Center between 2001 and 2010 as the development set and 474 patients from The Sixth Affiliated Hospital, Sun Yat-sen University between 2010 and 2016 as the validation set. The clinicopathological variables associated with gastric cancer with peritoneal dissemination (GCPD) were analyzed. We used logistic regression analysis to identify independent risk factors for peritoneal dissemination. Then, we constructed a nomogram for the prediction of GCPD and defined its predictive value with a receiver operating characteristic (ROC) curve. External validation was performed to validate the applicability of the nomogram. Results In total, 250 patients were histologically identified as having peritoneal dissemination. Logistic regression analysis demonstrated that age, sex, tumor location, tumor size, signet-ring cell carcinoma (SRCC), T stage, N stage and Borrmann classification IV (Borrmann IV) were independent risk factors for peritoneal dissemination. We constructed a nomogram consisting of these eight factors to predict GCPD and found an optimistic predictive capability, with a C-index of 0.791, an area under the curve (AUC) of 0.791, and a 95% confidence interval (95% CI) of 0.762-0.820. The results found in the external validation set were also promising. Conclusions We constructed a highly sensitive nomogram that can assist clinicians in the early diagnosis of GCPD and serve as a reference for optimizing clinical management strategies.

Introduction Although neoadjuvant chemo-radiotherapy (CRT) achieves low local recurrence rates in locally advanced rectal cancer (LARC), it raises a lot of concerns about long-term anal and sexual functions. We explored the efficacy of preoperative chemotherapy with mFOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) in patients with LARC. Patients and Methods Patients with LARC evaluated by pelvic magnetic resonance imaging (MRI) were enrolled in this trial. All received 4 to 6 cycles of mFOLFOXIRI. MRI was performed to assess clinical response after chemotherapy. Patients with mesorectal fascia-positive or ycT4a/b after re-evaluation would receive radiation before surgery, whereas responders would have immediate total mesorectal excision (TME). Adjuvant chemotherapy with mFOLFOX6 (folinic acid, 5-fluorouracil, and oxaliplatin) was recommended. The primary endpoint was the proportion of tumor downstaging to ypT0-2N0M0. The secondary endpoints were pathologic complete response rate (pCR), 3-year disease-free survival rate, and safety. Results Overall, 106 patients were enrolled and received neoadjuvant mFOLFOXIRI chemotherapy. A total of 103 participants underwent TME surgery. Among 103 patients who completed at least 4 cycles of preoperative chemotherapy, 2 received short-term radiation before TME, and 12 underwent long-term CRT after MRI evaluation. The pCR rate was 20.4%, and the tumor downstaging rate was 42.7%. Among patients without preoperative long-term radiotherapy, the pCR rate and tumor downstaging rate were 17.4% and 41.3%, respectively. Among the per-protocol population, the tumor downstaging rate was 48.1%, and the pCR rate was 20.3%. The chemotherapy-related toxicity was well-tolerated. Conclusion Neoadjuvant chemotherapy with mFOLFOXIRI and selective radiation does not seem to compromise outcomes in LARC. It could be a reasonable alternative to CRT in previously untreated patients with LARC.

PURPOSE In the multicenter, open-label, phase III FOWARC trial, modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus radiotherapy resulted in a higher pathologic complete response rate than fluorouracil plus radiotherapy in Chinese patients with locally advanced rectal cancer. Here, we report the final results. METHODS Adults ages 18 to 75 years with stage II/III rectal cancer were randomly assigned (1:1:1) to five cycles of infusional fluorouracil (leucovorin 400 mg/m2, fluorouracil 400 mg/m2, and fluorouracil 2.4 g/m2 over 48 hours) plus radiotherapy (46.0 to 50.4 Gy delivered in 23 to 25 fractions during cycles 2 to 4) followed by surgery and seven cycles of infusional fluorouracil, the same treatment plus intravenous oxaliplatin 85 mg/m2 on day 1 of each cycle (mFOLFOX6), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. The primary end point was 3-year disease-free survival (DFS). RESULTS In total, 495 patients were randomly assigned to treatment. After a median follow-up of 45.2 months, DFS events were reported in 46, 39, and 46 patients in the fluorouracil plus radiotherapy, mFOLFOX6 plus radiotherapy, and mFOLFOX6 arms. In each arm, the probability of 3-year DFS was 72.9%, 77.2%, and 73.5% ( P = .709 by the log-rank test), the 3-year probability of local recurrence after R0/1 resection was 8.0%, 7.0%, and 8.3% ( P = .873 by the log-rank test), and the 3-year overall survival rate was 91.3%, 89.1%, and 90.7% ( P = .971 by log-rank test), respectively. CONCLUSION mFOLFOX6, with or without radiation, did not significantly improve 3-year DFS versus fluorouracil with radiation in patients with locally advanced rectal cancer. No significant difference in outcomes was found between mFOLFOX6 without radiotherapy and fluorouracil with radiotherapy, which requires additional investigation of the role of radiotherapy in these regimens.

AimsTo develop and validate a model for predicting major pathological response to neoadjuvant chemotherapy (NAC) in advanced gastric cancer (AGC) based on a machine learning algorithm.MethodA total of 221 patients who underwent NAC and radical gastrectomy between February 2013 and September 2020 were enrolled in this study. A total of 144 patients were assigned to the training cohort for model building, and 77 patients were assigned to the validation cohort. A major pathological response was defined as primary tumor regressing to ypT0 or T1. Radiomic features extracted from venous-phase computed tomography (CT) images were selected by machine learning algorithms to calculate a radscore. Together with other clinical variables selected by univariate analysis, the radscores were included in a binary logistic regression analysis to construct an integrated prediction model. The data obtained for the validation cohort were used to test the predictive accuracy of the model.ResultA total of 27.6% (61/221) patients achieved a major pathological response. Five features of 572 radiomic features were selected to calculate the radscores. The final established model incorporates adenocarcinoma differentiation and radscores. The model showed satisfactory predictive accuracy with a C-index of 0.763 and good fitting between the validation data and the model in the calibration curve.ConclusionA prediction model incorporating adenocarcinoma differentiation and radscores was developed and validated. The model helps stratify patients according to their potential sensitivity to NAC and could serve as an individualized treatment strategy-making tool for AGC patients.

OBJECTIVE To evaluate the effect of art therapy on cancer patients' quality of life and physical and psychological symptoms. METHODS The databases PubMed, Embase, Web of Science, The Cochrane Library, Clinical Trial.gov, the China National Knowledge Infrastructure (CNKI), Wanfang and the Chinese Biomedical Literature Database (CBM) were searched from their inception up to 20 August 2019. Trials examining the effects of art therapy on physical and psychological symptoms and quality of life versus a control group were included. The methodological quality of the included randomised controlled trials was assessed using the risk of bias tool of Cochrane Handbook. Meanwhile, the Newcastle-Ottawa Quality Assessment Scale (NOS) was used to evaluate the methodological quality of the non-randomised studies. RESULTS Twelve studies involving 587 cancer patients were included. The results revealed that art therapy significantly reduced anxiety symptoms (standard mean difference [SMD] = -0.46, 95% confidence interval [CI] [-0.90, 0.02], p = .04), depression symptoms (SMD = -0.47, 95% CI [-0.72, 0.21], p

Background: Billroth I, Billroth II, Roux-en-Y, and Un-cut Roux-en-Y are common reconstruction techniques of distal gastrectomy. Which of these techniques is better has yet to be established. We performed an indirect comparison to evaluate which technique was optimal for preventing reflux symptoms. Methods: The PubMed, Cochrane Collaboration, Embase, ClinicalTrials.gov and Web of Science databases were searched to identify clinical trials that compared at least two of the reconstruction skills among Billroth I, Billroth II, Roux-en-Y, and Un-cut Roux-en-Y. Data on reflux gastritis, intraoperative blood loss, bile reflux and postoperative hospital stays were extracted from the included clinical trials for meta-analysis using a random-effects model. Results: Twenty-four articles that included 5419 individuals were assessed as eligible for meta-analysis. The indirect comparison suggested that Roux-en-Y reconstruction significantly reduces reflux gastritis, and it tended to rank first and had the highest probability of preventing bile reflux. No significant differences were found in intraoperative blood loss and postoperative hospital stays. Conclusion: This indirect comparison suggested some superiority of Roux-en-Y reconstruction after distal gastrectomy. Further perspective clinical trials are required to provide evidence for the optimal reconstruction skill.

Background/Aims: Three extensively investigated polymorphisms (rs3810936, rs7848647, and rs6478108) in tumor necrosis factor super family member 15 (TNFSF15) gene have been implicated in risk for inflammatory bowel disease (IBD). We performed a quantitative synthesis of the evidence to clarify these associations of TNFSF15 polymorphisms with IBD. Materials and Methods: Data were extracted from PubMed and EMBASE, up to March 15, 2018. Meta-analysis was performed by critically reviewing five studies for rs3810936 polymorphism (2251 cases and 2442 controls), four studies for rs7848647 polymorphism (1503 cases and 1816 controls), and four studies for rs6478108 polymorphism (1502 cases and 1817 controls). Results: Our analysis suggested that rs3810936 polymorphism was significantly associated with decreased risk of Crohn's disease (CD) and ulcerative colitis (UC). For rs7848647 polymorphism, significantly protective association between this polymorphism and CD risk was also observed, but not in UC. For rs6478108 polymorphism, we also detected a significantly protective association with CD risk in all genetic model but not in UC. Conclusions: This meta-analysis suggests that TNFSF15 polymorphisms may contribute to genetic susceptibility of IBD.

The role of RecQ-like helicase 5 (RECQL5) in gastric cancer (GC) is unclear. This study investigated the expression, clinicopathological association and prognosis of RECQL5 protein in human GC. Firstly, the Oncomine database was used to determine the mRNA expression levels of RECQL5 in GC samples. GC samples and adjacent normal gastric tissue samples were subsequently assessed to determine RECQL5 protein expression levels using immunohistochemistry. The clinicopathological association with RECQL5 expression was analyzed. Multivariate Cox analysis was performed to determine the relationship between RECQL5 expression and survival outcomes. Data from the Oncomine database revealed that RECQL5 mRNA was significantly downregulated in GC tissues compared with that in normal gastric tissues (P

The role of RecQ protein-like 5 (RECQL5) in gastric carcinoma (GC) is still unclear. Here, we investigated the role of RECQL5 in human GC and its potential regulatory network via bioinformatics analysis.Bioinformatic analysis was performed using data in the Oncomine database, Kaplan- Meier Plotter online software, MethHC database, catalogue of somatic mutations in cancer (COSMIC), cbioportal database and String database. Then, we verified the association between RECQL5 expression and GC prognosis by immunohistochemistry (IHC). The independent prognostic factors were determined by Cox multivariate analysis.It was found that both the mRNA and protein expression levels of RECQL5 were downregulated in GC samples (P .05). Low RECQL5 expression indicated a poor prognosis in GC patients and is the independent prognostic factors for GC. No correlation between RECQL5 mRNA and DNA methylation was found using the MethHC database. The analysis of the COSMIC database showed a high proportion of missense mutation in GC. The functional enrichment analysis predicted that RECQL5 plays a role in DNA repair and cellular responses to DNA damage stimulus. RECQL5 might be enriched in homologous recombination pathways and Fanconi anemia pathway. Bioinformatics analysis identified 5 genes, namely POLR2D, POLR2G, DXO, KIN, and EIF2D, that were significantly correlated with RECQL5.The low expression of RECQL5 predicts poor overall survival in GC. RECQL5 may be a novel tumor suppressor for patients with GC.

Background and aims Mucosal healing is regarded as a clinical endpoint of Crohn’s disease (CD), and transmural healing is correlated to the concept of deep remission. Current therapies to induce mucosal and transmural healing in CD are not satisfactory. Exclusive enteral nutrition (EEN) is underestimated therapy and its value has not been fully evaluated. Our aim was to investigate the efficacy of oral EEN for inducing mucosal and transmural healing in CD patients. Methods This was a prospective, single-center, open-label study including diagnosed CD children and adults conducted between January 2015 and December 2016 in the Sixth Affiliated Hospital of Sun Yat-sen University. All patients were treated with oral EEN and underwent paired assessment at baseline and completion using C-reaction protein, erythrocyte sedimentation rate, platelets, hemoglobin, body mass index, CD activity index, simple endoscopic score for CD and bowel sonography. Azathioprine was combined to prevent relapse. Results In this prospective observational study, 29 CD patients with an average age of 28.9 years were identified. After oral EEN treatment, 23 patients (79%) achieved complete mucosal healing, and the mean time to reach mucosal healing was 123 days (ranged from 50 to 212 days). Although only five patients (17%) achieved transmural healing, a significant reduction was observed in bowel-wall thickness (9.41 ± 3.06 vs 4.97 ± 1.76 mm, P

Objective To identify independent prognostic factors to be included in a nomogram to predict the prognosis of gastric cancer patients with peritoneal dissemination. Methods This is a retrospective study on 684 patients with a histological diagnosis of gastric cancer with peritoneal dissemination from the Sun Yat-sen University Cancer Center as the development set, and 62 gastric cancer patients from the Sixth Affiliated Hospital of Sun Yat-sen University as the validation group. Chi-square test and Cox regression analysis were used to compare the clinicopathological variables and the prognosis of gastric cancer patients with peritoneal dissemination. The Harrell's concordance index (C-index) and calibration curve were determined for comparisons of predictive ability of the nomogram. Results Univariate and multivariate analyses showed that serum carcinoembryonic antigen (CEA) level (P=0.032), ascites grading (P=0.008), presence of extraperitoneal metastasis (P

Although many advances have been made in the treatment of gastric cancer (GC), numerous difficulties, such as the emergence of chemo-drug resistance, continue to lead to disappointing GC prognoses. Thus, novel alternative strategies are urgently needed. The use of natural products could be a viable option to treat GC. Toosendanin (TSN) is a triterpenoid derived from the bark of Melia toosendanin Sieb. et Zucc that has been shown to be highly cytotoxic to multiple cancer cells. As the underlying impact of TSN on GC and its molecular mechanism remain poorly understood, in this study, we performed a series of experiments involving the use of TSN to treat GC cells. In the present study, we showed that TSN suppressed cell viability, inhibited cell proliferation by causing G1/S arrest and induced caspase-dependent apoptosis in AGS and HGC-27 cells. The possible mechanism of TSN-induced apoptosis may be associated with the activation of the p38 MAPK pathway. These results demonstrated the potential of TSN as a promising therapeutic compound to treat gastric cancer.

The present study aimed to investigate the expression, clinical association, and prognosis of RecQ protein-like 4 (RECQL4) protein in human gastric cancers (GCs). The expression levels and prognostic value of RECQL4 were initially predicted by using bioinformatics. GC specimens and matched normal gastric tissues were evaluated by immunohistochemistry (IHC), and patient clinicopathological parameters and survival times were analyzed. Multivariate Cox analysis was used to determine the prognostic role of RECQL4 expression. The Oncomine database predicted that RECQL4 mRNA expression levels were significantly increased in GCs as compared with those in normal gastric tissues (P

The aim of the present study was to compare the tumor volume reduction rate (TVRR), as determined by three-dimensional region-of-interest magnetic resonance volumetry, and Response Evaluation Criteria in Solid Tumors (RECIST) data for predicting the pathological tumor response (PTR) of locally advanced rectal cancer (LARC) following treatment with neoadjuvant chemoradiation (CRT). The current cohort consisted of 105 patients with LARC [clinical tumor stage (cT)3–4 or clinical lymph node stage (cN)+] from a prospective randomized trial who had undergone pre-operative CRT and radical proctectomy. Tumor volumes were measured prior to and following CRT to determine TVRR. Furthermore, receiver operating characteristic (ROC) curves of TVRR and RECIST were constructed to predict the PTR in terms of tumor regression grade (TRG) and downstaging. Values for the area under the ROC curve (AUC) were compared and TVRR cut-off levels were determined. RECIST was used to identify 5 (4.8%) cases of complete response, 44 (41.9%) of partial response, 55 (52.4%) of stable disease and 1 (0.9%) of progressive disease. The mean TVRR was 58.6±24.4%, and a good TRG (0–1) and downstaging occurred in 54 (51.4%) and 59 (56.2%) patients, respectively. In addition, TVRR and RECIST were significantly correlated with TRG and downstaging (P

The nerve growth factor receptor (NGFR/p75) is a potential tumor suppressor, but its role in colorectal cancer is unknown. Here, the hypermethylation status, biologic function, and clinical relevance were determined for p75NGFR in colorectal cancer. The methylation status and expression of p75NGFR were assessed in colorectal cancer cell lines and clinical tissues by bisulfite genomic sequencing (BGS), qRT-PCR, and immunoblot assay. Methylation of p75NGFR was frequently found in colorectal cancer, leading to its silencing or downregulation, and it was effectively restored by a demethylation agent. The overexpression of p75NGFR in multiple colorectal cancer cell model systems significantly inhibited cell proliferation (concomitant with G1-phase arrest), invasion, and colony formation and induced cell apoptosis. In contrast, p75NGFR knockdown significantly promoted proliferative and invasive phenotypes. Importantly, p75NGFR methylation was observed in the majority of primary colorectal cancer specimens and was associated with histologic grade and preoperative serum CA19-9 levels. Multivariate analysis indicated that patients who lack p75NGFR have reduced overall survival (64% vs. 75%, P = 0.028) and disease-free survival (61% vs. 72%, P = 0.034) compared with p75NGFR-positive patients. In conclusion, p75NGFR is predominantly silenced or downregulated in colorectal cancer, and its biologic activities are consistent with it being a relevant tumor suppressor. Implications: p75NGFR is a candidate tumor suppressor and has independent prognostic potential in colorectal cancer. Mol Cancer Res; 13(1); 107–19. ©2014 AACR.

Lin28 plays important roles in the development, maintenance of pluripotency and progression of various types of cancers. Lin28 represses the biogenesis of let-7 microRNAs and is implicated in both development and tumorigenesis. Oncogenic regulation of let-7 microRNAs has been demonstrated in several human malignancies, yet their correlation with Lin28 has not yet been studied in gastric cancer. Therefore, in the present study, we explored the possible mechanisms involved in the effects by Lin28 on the proliferation, migration, cell cycle arrest and apoptosis in gastric cancer cells via alteration of let-7 miRNA. The expression levels of Lin28 and let-7 were detected by real-time PCR in gastric cancer cell lines in vitro. Lin28 was overexpressed in the BGC-823 cells via lentiviral transfection, and let-7 expression was assessed. Cell proliferation and migration capabilities were investigated by MTT and Transwell assays, while cell cycle distribution and the apoptosis rate were detected using flow cytometry. The expression of Lin28 was moderately expressed in the GES cells while underexpressed in the BGC-823, SGC-7901 and HGC-27 cells. Let-7a miRNA was highly expressed in the GES, BGC-823, SGC-7901 and HGC-27 cells. Overexpression of Lin28 was inversely correlated with the downregulated expression of let-7a, and markedly suppressed the proliferation, migration, cell cycle progression and induced apoptosis in the BGC-823 cells. These findings demonstrated that overexpression of Lin28 can suppress the biological behavior of gastric cancer in vitro, and let-7 miRNA may play an important role in the process. We suggest that Lin28 may be a candidate predictor or an anticancer therapeutic target for gastric cancer patients.

Integrin subunit alpha V (ITGAV), a member of integrin family of extracellular matrix receptors, is involved in many types of cancer. In this study, the expression levels, clinical features and prognosis of ITGAV in gastric cancer (GC) patients were investigated, and the functional roles of ITGAV were also investigated. Cell Counting Kit-8 (CCK-8) assay was performed to examine the proliferation of GC cells. Transwell assays and wound-healing assays were conducted to explore the effect of ITGAV expression on GC cell migration and invasion. We found that ITGAV was overexpressed in both GC tissues and GC cells. ITGAV expression was positively correlated with lymph node metastasis and TNM stage of GC. High expression of ITGAV was associated with shorter overall survival (OS) and disease-free survival (DFS). Interestingly, the downregulation of ITGAV resulted in suppression of proliferation, migration, and invasion in GC cells. In conclusion, ITGAV is overexpressed in gastric cancer and is associated with poorer prognostic outcomes. ITGAV may serve as an important prognostic marker for GC staging and progression.

In the past, vascular prostheses have been developed for mesocaval shunt surgeries in the treatment of portal hypertension. Penetration of prosthesis into the duodenum is a rare complication. We report the case of a 65-year-old man who presented with duodenal erosion and obstruction caused by the prosthesis, 22 years after its insertion. This is the ninth reported case of such events, but it demonstrates the longest interval to date between insertion and complication.

Background and Aim Although the effect of neoadjuvant chemotherapy in gastric cancer has been extensively studied, the data of survival benefit are still controversial. The purpose of this work was to assess the effectiveness of neoadjuvant chemotherapy followed by surgery in patients with gastric cancer. Methods We searched systematically electronic through the databases of PUBMED, EMBASE, China Biological Medicine, and China National Knowledge Infrastructure Whole Article for studies published from 1975. Two reviewers independently evaluated the relevant reports and searched manually reference from these reports for additional trials. Outcomes assessed by meta-analysis included overall survival rate, progression-free survival rate, R0 resection rate, downstaging effect, postoperative complications, and perioperative mortality. Results Six randomized, controlled trials with 781 patients were included in the meta-analysis. Odds ratio (95% confidence interval; P-value), expressed as neoadjuvant chemotherapy and surgery versus surgery alone, was 1.16 (0.85–1.58; P = 0.36) for overall survival, 1.24 (0.78–1.96; P = 0.36) for R0 resection, 1.25 (0.75–2.09; P = 0.39) for postoperative complications, and 3.60 (0.59–22.45; P = 0.17) for perioperative mortality. Conclusions Compared with surgery alone, neoadjuvant chemotherapy followed by surgery was not associated with a higher rate of overall survival or complete resection (R0 resection). It does not increase treatment-related morbidity and mortality. This meta-analysis did not demonstrate a survival benefit for the combination of neoadjuvant chemotherapy and surgery.

BACKGROUND Gastric cancer is one of the most common malignancies, and has a high mortality rate. miR-495 acts as a suppressor in some cancers and HMGA2 (high mobility group AT-hook 2) is a facilitator for cell growth and epithelial-mesenchymal transition (EMT), but little is known about their effect in gastric cancer. This study aimed to investigate the role and mechanism of miR-495 in gastric cancer. MATERIAL AND METHODS miR-495 levels were quantitatively analyzed in gastric cancer tissue and GES-1, SGC-7901, BGC-823, and HGC-27 cell lines by qRT-PCR. Levels of miR-495 and HMGA2 were altered by cell transfection, after which cell migration and invasion were examined by Transwell and E-cadherin (CDH1); vimentin (VIM), and alpha smooth muscle actin (ACTA2) were detected by qRT-PCR and Western blotting. The interaction between miR-495 and HMGA2 was verified by dual-luciferase reporter assay. RESULTS miR-495 was significantly downregulated in cancer tissue and cell lines (p

Background The aim of this study is to investigate whether body mass index (BMI) is a prognostic factor in gastric cancer patients with peritoneal dissemination. Methods This is a retrospective study consisting of 518 patients with a histological diagnosis of gastric cancer with peritoneal dissemination seen at the Sixth Affiliated Hospital of Sun Yat-Sen University and Sun Yat-sen University Cancer Center between January 2010 and April 2014. Patients were followed until December 2015. Chi-square test and Kaplan-Meier survival analysis were used to compare the clinicopathological variables and prognosis. Results Univariate analyses showed that significant prognostic factors included palliative gastrectomy (p

The aim of this study was to determine the clinicopathological characteristics and outcomes of Chinese colorectal cancer (CRC) patients aged 75 years and older undergoing potentially curative surgery.A total of 2,482 CRC patients at TNM stage I-III undergoing surgical treatment between 1995 and 2005 were evaluated, and patients were divided into a younger (75 years old) and an elderly (≥75 years) group.There were 2,482 CRC patients in this study, of which 2,194 (88.4 %) patients were in the younger group (mean age 57 years) and 288 (11.6 %) were in the elderly group (mean age 79 years). Significant differences were observed between the two groups with regard to the American Society of Anesthesiologists' score, tumor location, co-morbidities, emergency procedures, use of chemotherapy, proportion admitted to the ICU, length of ICU stay, causes of death, T/N stage and postoperative recurrence. The postoperative mortality increased from 4.8 % in the younger group to 8.3 % in the older group (p = 0.011). Although significant differences were found in the overall 5-year survival (73 vs. 56 %, p 0.0001) and disease-free 5-year survival (68 vs. 54 %, p 0.0001) between the two groups, the cancer-specific 5-year survival was similar (88 vs. 85 %, p = 0.089) in both groups.Although elderly CRC patients have unique clinicopathological features, a higher postoperative mortality and a worse overall and disease-free survival compared with younger patients, the cancer-specific survival at five years is similar between elderly and younger patients. Elderly patients benefit from radical surgery and have a good postoperative oncological outcome, irrespective of their age.

Background: Zonulin is a newly discovered protein that has an important role in the regulation of intestinal permeability. Our previous study showed that probiotics can decrease the rate of infectious complications in patients undergoing colectomy for colorectal cancer.Objective: The objective was to determine the effects of the perioperative administration of probiotics on serum zonulin concentrations and the subsequent effect on postoperative infectious complications in patients undergoing colorectal surgery.Design: A total of 150 patients with colorectal carcinoma were randomly assigned to the control group (n = 75), which received placebo, or the probiotics group (n = 75). Both the probiotics and placebo were given orally for 6 d preoperatively and 10 d postoperatively. Outcomes were measured by assessing bacterial translocation, postoperative intestinal permeability, serum zonulin concentrations, duration of postoperative pyrexia, and cumulative duration of antibiotic therapy. The postoperative infection rate, the positive rate of blood microbial DNA, and the incidence of postoperative infectious complications—including septicemia, central line infection, pneumonia, urinary tract infection, and diarrhea—were also assessed.Results: The infection rate was lower in the probiotics group than in the control group (P < 0.05). Probiotics decreased the serum zonulin concentration (P < 0.001), duration of postoperative pyrexia, duration of antibiotic therapy, and rate of postoperative infectious complications (all P < 0.05). The p38 mitogen-activated protein kinase signaling pathway was inhibited by probiotics.Conclusions: Perioperative probiotic treatment can reduce the rate of postoperative septicemia and is associated with reduced serum zonulin concentrations in patients undergoing colectomy. We propose a clinical regulatory model that might explain this association. This trial was registered at http://www.chictr.org/en/ as ChiCTR-TRC-00000423.

Current neoadjuvant chemoradiotherapy had limited impact on distal metastasis and survival in locally advanced rectal cancer. Here, we investigated a new sandwich-like neoadjuvant regimen with bevacizumab. This was a single-arm, open-labeled, phase II trial. Patients with locally advanced rectal cancer received sandwich-like neoadjuvant therapy with bevacizumab (induction therapy with bevacizumab and FOLFOX, concurrent chemoradiotherapy with bevacizumab and consolidation chemotherapy with FOLFOX). Surgery was performed 4–6 weeks later. The primary endpoint of this study was pathologic complete response. Twenty-five eligible patients were included. All completed the neoadjuvant therapy protocol. During the course of neoadjuvant therapy, 3 patients (12 %) had grade 4 hematological toxicity events and 12 (48 %) had grade 3 non-hematological toxicity events. According to RECIST criteria, 18 patients (72 %) achieved partial response and the rest seven patients (28 %) remained stable disease. Two patients (8 %) refused the subsequent surgical therapy for personal reasons, and 23 patients (92 %) underwent operations finally. Nine (39.1 %, 95 % CI 18.0–57.5 %) of them achieved pathologic complete response. Five of them (21.7 %) had postoperative complications. After a median follow-up period of 25.3 (14.4–40.9) months, four patients developed disease progression and two died of cancer. The 3-year overall survival rate was 95 % (95 % CI 69.5–99.3 %), and the 3-year disease-free survival rate was 72.5 % (95 % CI 33.7–90.9 %). Sandwich-like neoadjuvant therapy with bevacizumab is safe and effective for locally advanced rectal cancer.

Background Colorectal liver metastases (CLM) occur frequently and postoperative intestinal infection is a common complication. Our previous study showed that probiotics could decrease the rate of infectious complications after colectomy for colorectal cancer. To determine the effects of the perioperative administration of probiotics on serum zonulin levels which is a marker of intestinal permeability and the subsequent impact on postoperative infectious complications in patients with CLM. Methods 150 patients with CLM were randomly divided into control group (n = 68) and probiotics group (n = 66). Probiotics and placebo were given orally for 6 days preoperatively and 10 days postoperatively to control group and probiotics group respectively. We used the local resection for metastatic tumor ,while for large tumor, the segmental hepatectomy. Postoperative outcome were recorded. Furthermore, complications in patients with normal intestinal barrier function and the relation with serum zonulin were analyzed to evaluate the impact on the liver barrier dysfunction. Results The incidence of infectious complications in the probiotics group was lower than control group. Analysis of CLM patients with normal postoperative intestinal barrier function paralleled with the serum zonulin level. And probiotics could also reduce the concentration of serum zonulin (P = 0.004) and plasma endotoxin (P

This study evaluated the efficacy, safety and impact on quality of life (QoL) of a dose-dense biweekly regimen of docetaxel and 5-fluorouracil in first-line treatment of advanced gastric cancer (AGC). Eligible patients received docetaxel 60 mg/m(2) and 5-fluorouracil (400 mg/m(2) bolus followed by 2,400 mg/m(2) 46-h infusion), fortnightly. Prophylactic use of G-CSF was adopted in all patients. The primary end point was response rate (RR). Secondary end points were progression-free survival (PFS), overall survival (OS), toxicity and QoL. Thirty-nine patients with a median age of 55 (28-80) were included. The RR was 51.3 %. Median PFS and OS were 6.7 and 14.0 months, respectively. The most common adverse events (all grades) were anemia (34, 87.2 %), fatigue (29, 74.4 %), neutropenia (26, 66.7 %), nail change (19, 48.7 %) and liver dysfunction (15, 38.5 %). In QoL analysis, improvements were obtained in seven scales, whereas drops were seen in three scales. Common Grade 3/4 toxicities included anemia (28.2 %), liver dysfunction (7.7 %) and fatigue (7.7 %). This novel regimen is a promising option for AGC, showing high RR, improvement on QoL and acceptable toxicity.

Aim: To investigate the risk factors of gastric remnant cancer. Methods: A search on PubMed, Embase, ISI Web of SCIENCE, Cochrane Library, CNKI, and Wanfang was performed to identify relevant literature published from January 1990 to May 2014. The effect of gastric remnant cancer was estimated by risk ratio (RRs) with 95% confidence intervals (CIs) for each study using a fixed effects or random effects model. Results: 28 studies with a total of 1132 patients met the inclusion criteria in our study. The risk for gastric remnant cancer was positively associated with a male gender, an initial ulcerative disease, a previous Billroth II anastomosis. Gastric remnant cancer was also more likely to be located at the site of initial anastomosis and was associated with a poorly differentiated and/or undifferentiated histology. However no significance was observed between the TNM stage and the gastric remnant cancer. Conclusion: Meta-analysis found that gastric remnant cancer is associated with gender, reason for initial surgery, type of initial surgery performed, location, histology.

Background Human replication factor C4 (RFC4) is involved in DNA replication as a clamp loader and is aberrantly regulated across a range of cancers. The current study aimed to investigate the function of RFC4 in colorectal cancer (CRC). Methods The mRNA levels of RFC4 were assessed in 30 paired primary CRC tissues and matched normal colonic tissues by quantitative PCR. The protein expression levels of RFC4 were evaluated by western blotting (n = 16) and immunohistochemistry (IHC; n = 49), respectively. Clinicopathological features and survival data were correlated with the expression of RFC4 by IHC analysis in a tissue microarray comprising 331 surgically resected CRC. The impact of RFC4 on cell proliferation and the cell cycle was assessed using CRC cell lines. Results RFC4 expression was significantly increased in CRC specimens as compared to adjacent normal colonic tissues (P

Background: Beta-defensin-2 (BD-2), an endogenous antimicrobial peptide, plays a key role in immune response against microbial invasion. This study aimed to observe the effect of Alanyl–Glutamine (Ala–Gln) on BD-2 protein expression in pulmonary tissues after intestinal ischemia reperfusion (IIR) in rats and to investigate its correlations to pulmonary inflammatory and oxidative injury. Methods: Rats in IIR and the two treatment groups were subjected to intestine ischemia for 60 min and those in the treatment groups were administered orally with Ala–Gln or alanine (Ala) respectively. Lung tissues were harvested to detect the BD-2 protein expression. Concentrations of Tumor necrosis factor (TNF)-α and malondialdehyde (MDA) as well as superoxide dismutase (SOD) activity in lung tissues were determined simultaneously. Results: Ala–Gln attenuated the up-regulation of BD-2 expression (p

Subarachnoid hemorrhage (SAH) is a devastating disease with high mortality. The mechanisms underlying its pathological complications have not been fully identified. Here, we investigate the potential involvement of the glymphatic system in the neuropathology of SAH. We demonstrate that blood components rapidly enter the paravascular space following SAH and penetrate into the perivascular parenchyma throughout the brain, causing disastrous events such as cerebral vasospasm, delayed cerebral ischemia, microcirculation dysfunction and widespread perivascular neuroinflammation. Clearance of the paravascular pathway with tissue-type plasminogen activator ameliorates the behavioral deficits and alleviates histological injury of SAH. Interestingly, AQP4−/− mice showed no improvements in neurological deficits and neuroinflammation at day 7 after SAH compared with WT control mice. In conclusion, our study proves that the paravascular pathway dynamically mediates the pathological complications following acute SAH independently of glymphatic control.

Research on molecular mechanisms of carcinogenesis plays an important role in diagnosing and treating gastric cancer. Metabolic profiling may offer the opportunity to understand the molecular mechanism of carcinogenesis and help to non-invasively identify the potential biomarkers for the early diagnosis of human gastric cancer. The aims of this study were to explore the underlying metabolic mechanisms of gastric cancer and to identify biomarkers associated with morbidity. Gas chromatography/mass spectrometry (GC/MS) was used to analyze the serum metabolites of 30 Chinese gastric cancer patients and 30 healthy controls. Diagnostic models for gastric cancer were constructed using orthogonal partial least squares discriminant analysis (OPLS-DA). Acquired metabolomic data were analyzed by the nonparametric Wilcoxon test to find serum metabolic biomarkers for gastric cancer. The OPLS-DA model showed adequate discrimination between cancer and non-cancer cohorts while the model failed to discriminate different pathological stages (I-IV) of gastric cancer patients. A total of 44 endogenous metabolites such as amino acids, organic acids, carbohydrates, fatty acids, and steroids were detected, of which 18 differential metabolites were identified with significant differences. A total of 13 variables were obtained for their greatest contribution in the discriminating OPLS-DA model [variable importance in the projection (VIP) value >1.0], among which 11 metabolites were identified using both VIP values (VIP >1) and the Wilcoxon test. These metabolites potentially revealed perturbations of glycolysis and of amino acid, fatty acid, cholesterol, and nucleotide metabolism of gastric cancer patients. These results suggest that gastric cancer serum metabolic profiling has great potential in detecting this disease and helping to understand its metabolic mechanisms.

BACKGROUND/AIMS This study aimed to determine the overall survival time and clinical characteristics affecting the outcomes in patients with resectable colorectal cancer (CRC). METHODOLOGY Clinical data from CRC patients who underwent surgical resections from 1994 to 2004 was analyzed retrospectively using the documented records and gastrointestinal tumor databases at the gastrointestinal institute. Univariate and multivariate analyses were conducted to investigate the association between clinical variables and overall survival time. RESULTS A consecutive series of 1.294 CRC patients were enrolled for the final analyses. The five-year survival rates were 94.1%, 80.2%, 61.7% and 23.2% of patients with stage from I to IV CRC, respectively. One hundred and seven patients (8.3%) had disease recurrence during the follow-up with a median of 50.3 months. After radical surgical resections, patients with recurrence could still expect a five-year survival rate of 44.3%. Multivariate analysis showed that patient age >60 years, infiltrative tumor type, intestinal obstruction, poor tumor differentiation, disease recurrence and late TNM stage were associated with poor survival (all p

This study was to investigate the clinicopathologic characteristics and prognosis of colorectal cancer (CRC) patients aged 44 years and younger. Patients were identified from a prospectively maintained CRC database and divided into two groups by age: younger and older group (≤44 and >44 years). Clinicopathologic characteristics and postoperative outcomes were compared. There were 530 patients aged ≤44 years at diagnosis. More patients in the younger group had a family history of CRC compared with older patients. Younger patients were more likely than older patients to have larger tumours, infiltrative growth type tumours, poorly differentiated tumours, mucinous and signet-ring cell adenocarcinoma, and advanced TNM stages. Compared to older patients, more younger patients received chemotherapy and died of cancer-related causes. Overall survival, disease-free survival and cancer-specific survival of younger patients were comparable to older patients. Blood transfusion, TNM stage, histological grade and disease recurrence were independently associated with survival in the younger group. Despite younger patients having unfavourable clinicopathologic features, younger age at diagnosis of CRC appears to be associated with similar oncologic outcomes as compared to older patients.

The principal way to improve the outcome of gastric cancer (GC) is to predict carcinogenesis and metastasis at an early stage. The aims of the present study were to test the hypothesis that distinct metabolic profiles are reflected in GC tissues and to further explore potential biomarkers for GC diagnosis. Gas chromatography/mass spectrometry (GC/MS) was utilized to analyze tissue metabolites from 30 GC patients. A diagnostic model for GC was constructed using orthogonal partial least squares discriminant analysis (OPLS-DA), and the metabolomic data were analyzed using the non-parametric Wilcoxon rank sum test to identify the metabolic tissue biomarkers for GC. Over 100 signals were routinely detected in one single total ion current (TIC) chromatogram, and the OPLS-DA model generated from the metabolic profile of the tissues adequately discriminated the GC tissues from the normal mucosae. Among the low-molecular-weight endogenous metabolites, a total of 41 compounds, such as amino acids, organic acids, carbohydrates, fatty acids and steroids, were detected, and 15 differential metabolites were identified with significant difference (p0.05). A total of 20 variables were noted which contributed to a great extent in the discriminating OPLS-DA model (VIP value1.0), among which 12 metabolites were identified using both VIP values (VIP1) and the Wilcoxon test (p0.05). In conclusion, the identification of the metabolites associated with GC morbidity potentially revealed perturbations of glycolysis, fatty acid β-oxidation, cholesterol and amino acid metabolism. These results suggest that tissue metabolic profiles have great potential in detecting GC and may aid in understanding its underlying mechanisms.

The aim of this retrospective study was to analyze the clinicopathologic characteristics and short-term and long-term outcomes of colorectal cancer patients with obstruction compared to those of non-obstructive colorectal cancer patients.Between January 1998 and December 2005, 1,672 colorectal cancer patients undergoing operation were enrolled in this study. Patients were classified into two groups according to the presentation: patients with complete obstructive colorectal cancer (COC, n = 215) receiving emergency procedures and patients with non-obstructive colorectal cancer (NOC, n = 1,457) receiving elective procedures. The data on the clinicopathologic characteristics and short-term and long-term outcomes of patients were analyzed retrospectively.Among 1,672 colorectal cancer patients, 215 cases presented with complete obstruction. The distribution of tumor location and size, macroscopic type, depth of invasion, liver metastasis, peritoneal carcinomatosis, and TNM stage were found to be different between the COC and NOC groups. Logistic regression analysis showed that tumor location, depth of invasion, and peritoneal carcinomatosis were independent factors associated with obstruction. Patients with obstruction had an increased risk of death by a factor of 2.251 compared to patients without obstruction. Peritoneal carcinomatosis and TNM stage were independent factors for the survival of the COC group. Obstruction, peritoneal carcinomatosis, tumor macroscopic type, and TNM stage were independent indicators for postoperative recurrence. Postoperative mortality was significantly higher in the COC group than the NOC group. The overall 5- and 10-year survival rates in the COC group were 47.8% and 42.8%, respectively, compared to 67.2% and 59.8% in the NOC group, respectively (p 0.05). The postoperative recurrence rates were 43.1% in the COC group and 32.8% in the NOC group (p 0.05).Obstruction is an independent indicator for the survival and postoperative recurrence for patients with colorectal cancer. Patients in the COC group have worse overall survival with high postoperative recurrence rate compared to those in the NOC group.

Hepatic resection (HR) is the only option offering a potential cure for patients with synchronous colorectal cancer liver metastases (SCRLM). The optimal timing of HR for SCRLM is still controversial. This study aimed to determine whether simultaneous HR is similar to staged resection regarding the morbidity and mortality rates in patients with SCRLM. Four hundred and five consecutive patients with SCRLM were treated with either simultaneous (n = 129) or staged (n = 276) HR. The postoperative complications were analyzed retrospectively according to the documented records and hepatectomy databases at the Gastrointestinal Institute. Perioperative morbidity and mortality did not differ between simultaneous resections and staged resections for selected patients with SCRLM (morbidity, 47.3% versus 54.3%; mortality, 1.5% versus 2.0%, respectively; both p > 0.05). Simultaneous liver resections of three or more segments would not increase the rate of complications compared to staged resections (56.8% and 42.4%, respectively; p = 0.119). Meanwhile, patients with simultaneous resections experienced shorter duration of surgery and postoperative hospitalization time as well as less blood loss during surgery (all p

Background The development and progression of liver cancer may involve abnormal changes in DNA methylation, which lead to the activation of certain proto-oncogenes, such as c-myc, as well as the inactivation of certain tumor suppressors, such as p16. Betaine, as an active methyl-donor, maintains normal DNA methylation patterns. However, there are few investigations on the protective effect of betaine in hepatocarcinogenesis. Methods Four groups of rats were given diethylinitrosamine (DEN) and fed with AIN-93G diets supplemented with 0, 10, 20 or 40 g betaine/kg (model, 1%, 2%, and 4% betaine, respectively), while the control group, received no DEN, fed with AIN-93G diet. Eight or 15 weeks later, the expression of p16 and c-myc mRNA was examined by Real-time PCR (Q-PCR). The DNA methylation status within the p16 and c-myc promoter was analyzed using methylation-specific PCR. Results Compared with the model group, numbers and areas of glutathione S-transferase placental form (GST-p)-positive foci were decreased in the livers of the rats treated with betaine (P < 0.05). Although the frequency of p16 promoter methylation in livers of the four DEN-fed groups appeared to increase, there is no difference among these groups after 8 or 15 weeks (P > 0.05). Betaine supplementation attenuated the down-regulation of p16 and inhibited the up-regulation of c-myc induced by DEN in a dose-dependent manner (P < 0.01). Meanwhile, increases in levels of malondialdehyde (MDA) and glutathione S-transferase (GST) in model, 2% and 4% betaine groups were observed (P < 0.05). Finally, enhanced antioxidative capacity (T-AOC) was observed in both the 2% and 4% betaine groups. Conclusion Our data suggest that betaine attenuates DEN-induced damage in rat liver and reverses DEN-induced changes in mRNA levels.

Elucidating the molecular mechanism underlying the development of adenoma, the major precursor lesion of colorectal cancer (CRC), would provide a basis for early detection, prevention as well as treatment of CRC. Using the highly sensitive 2-D DIGE method coupled with MS, we identified 24 differentially expressed proteins in adenoma tissues compared with matched normal colonic mucosa and CRC tissues. Fifteen proteins were downregulated and three proteins were upregulated in adenoma tissues when compared with individual-matched normal colonic mucosa. Five proteins were downregulated, while one protein was upregulated in adenoma tissues when compared with matched CRC tissues. A protein, β-tropomyosin (TM-β), recently suggested to be a biomarker of esophageal squamous carcinoma, was downregulated in both adenoma and CRC tissues. Additionally, the reduction in the level of TM-β in adenoma and CRC tissues was further validated by Western blotting (p

AIM: To examine the expression of E-cadherin in the primary tumor and to evaluate its relationship with lymph node micrometastasis (LNM). METHODS: The authors studied 850 lymph nodes resected from 30 patients with gastric carcinoma who underwent gastrectomy with lymphadenectomy using reverse transcription polymerase chain reaction (RT-PCR) assay in addition to H&E staining. Cytokeratin-20 (CK-20) gene marker was used in this assay. The level of E-cadherin expression in the primary tumor was examined by immunochemical technique (EliVisionTM plus). RESULTS: LNM was detected in 77 (12.5%) lymph nodes of 14 patients (46.7%) with gastric carcinoma. The incidence of LNM was significantly higher in the diffuse type (12 of 19 cases, 63.2%) than in the intestinal type of gastric carcinoma (2 of 11 cases, 18.2%, P = 0.026). The incidence of LNM also increased in accordance with the depth of tumor invasion. The loss of expression of E-cadherin in primary tumors was found in 14 (46.7) of 30 tumors. The absence of E-cadherin expression was significantly associated with the Lauren classification (P = 0.026), lymph node metastasis (P = 0.011), the grade of differentiation (P = 0.004) and the lymphatic invasion (P = 0.001). Expression of E-cadherin was negative in 10 (71.4%) of the 14 patients with LNM, and in 4 (25%) of the 16 patients without LNM (P = 0.026). CONCLUSION: The current results indicate that the RT-PCR assay is useful for the detection of LNM and can significantly increase the detection rate of lymph node metastasis in patients with gastric carcinoma. The Lauren classification and depth of tumor invasion are significantly associated with lymph node micrometastases. Our findings also indicate that E-cadherin may play an important role in determining the growth type and differentiation of gastric carcinoma. The loss of E-cadherin expression may contribute to LNM.

AIM:To study the telomerase expression in gastric carcinoma and its clinical implications.METHODS:Telomerase activity was examined in gastric cancer and corresponding normal tissues using a modified TRAP (telomeric repeat amplify-cation protocol) assay (TRAP-eze) in tissue samples from 94 gastric carcinomas and 58 normal tissues, 12 gastric adenomas and 9 gastric ulcer lesions.RESULTS:Telomerase activity was present in 81 of the 94 (86.2%) gastric cancer tissues, whereas no telomerase activity was detected in any normal tissues.The incidence of telomerase activity in gastric cancer tissues was unrelated to the tumor diameter, histological grade, tumor invasion in depth, lymph node metastasis and TNM stage.CONCLUSION:Telomerase plays an important role in carcinogenesis and progression of gastric cancer, and it is suggested to be a useful tumor marker.

AIM: To investigate gut barrier damage and intestinal bacteria translocation in severe acute pancreatitis (SAP), a simple rat model of SAP was induced and studied. METHODS: Pancreatitis was induced by uniformly distributed injection of 3.8% Na taurocholate (1 mL/kg) beneath the pancreatic capsule. Rats in the control group were injected with normal saline in the identical location. RESULTS: Serum amylase, plasma endotoxin, intestinal permeability, and pancreatitis pathology scores were all markedly higher in the pancreatitis group than in the control group (P < 0.01). The bacterial infection rate was significantly higher in the SAP group than in the control group (P < 0.01), observed in parallel by both bacterial culture and real-time polymerase chain reaction. Acute damage of the pancreas was observed histologically in SAP rats, showing interstitial edema, leukocyte infiltration, acinar cell necrosis and hemorrhage. The microstructure of the intestinal mucosa of SAP rats appeared to be destroyed with loose, shortened microvilli and rupture of the intercellular junction, as shown by electron microscopy. CONCLUSION: Significant gut barrier damage and intestinal bacterial translocation were definitely observed with few potential study confounders in this SAP rat model, suggesting that it may be an appropriate animal model for study of gut barrier damage and bacterial translocation in SAP.

To explore the expression of heparanase gene, CD44v6, MMP-7 and nm23 proteins in human gastric carcinoma as well as their relationship with the clinicopathological factors.Reverse transcription polymerase chain reaction (RT-PCR) was used to measure the expressions of heparanase mRNA in 43 human gastric carcinomas and 10 adjacent normal gastric tissues. Streptavidin-peroxidase (S-P) two step method was used to measure the immunohistochemical expression of CD44v6, MMP-7 and nm23 protein in 43 human gastric carcinomas.The expression of heparanase gene was positive in 29 cases of gastric cancer with a positive rate of 67.4%, which was significantly higher than those in adjacent normal gastric tissues (P0.05). The heparanase mRNA expression was significantly related to advanced stage of disease, serosal infiltration, lymph node metastasis and size of tumors (P0.05), but not related to tumor location, gross and histological types of the cancer, peritoneal dissemination and liver metastasis (P0.05). The positive rate of CD44v6, nm23 and MMP-7 proteins was 76.7%, 37.2% and 60.5%, respectively. The CD44v6 protein expression was significantly related to serosal infiltration, lymph node metastasis and TNM stage of disease (P0.05). The nm23 protein expression was significantly related to the tumor gross appearance, lymph node and peritoneal metastasis (P0.05). The MMP-7 protein expression was significantly related to serosal infiltration and TNM stage of disease (P0.05). In an attempt to measure the association between these agents, we found that the expression of heparanase mRNA had significantly negative correlation with the expression of CD44v6 and MMP-7 protein (P0.05), the expression of MMP-7 protein had significantly positive correlation with the expression of CD44v6 protein (r=0.568, P0.05), the expression of MMP-7 protein had no correlation with the expression of nm23 protein (P0.05), and the expression of nm23 protein had no correlation with the expression of CD44v6 protein (P0.05).Despite their different mechanisms of action, heparanase, CD44v6 and nm23 may play important roles in the invasive infiltration and lymph node metastasis in gastric carcinomas. Instead of metastatic spreading, MMP-7 may be just related to the invasion of gastric carcinomas. However, co-detection of these factors may be important to predict metastatic spreading in such patients.

Background Mitogen/extracellular signal-regulated kinase kinase-5 (MEK5) has been confirmed to play a pivotal role in tumor carcinogenesis and progression. However, few studies have investigated the role of MEK5 in colorectal cancer (CRC). Methods MEK5 expression was determined by immunohistochemistry (IHC) in tissue microarrays (TMAs) containing 2 groups of tissues, and western blotting was used to confirm MEK5 expression in 8 cases of primary CRC tissues and paired normal mucosa. RNA interference was used to verify the biological function of MEK5 gene in the development of CRC. Results IHC revealed the expression of MEK5 was higher in tumor tissues (38.1 %), compared with adjacent normal tissue (8.3 %). Western blot showed that, MEK5 expression was upregulated in CRC tumor tissues compared with normal tissue. Analysis of clinical pathology parameters indicated MEK5 overexpression was significantly correlated with the depth of invasion, lymph node metastasis, distant metastasis and histological grade. Survival analysis revealed that MEK5 overexpression negatively correlated with cancer-free survival (hazard ratio 1.64, P = 0.017). RNA interference-mediated knockdown of MEK5 in SW480 colon cancer cells decreased their proliferation, division, migration and invasiveness in vitro and slowed down tumors growth in mice engrafted with the cells. Conclusion MEK5 plays an important role in CRC progression and may be a potential molecular target for the treatment of CRC.