Xianrui Wu

High expression of CD73 as a poor prognostic biomarker in human colorectal cancer

To investigate the expression dynamics of CD73 and its prognostic significance in human colorectal cancer (CRC).

Extraperitoneal vs. intraperitoneal route for permanent colostomy: a meta-analysis of 1,071 patients

BackgroundParastomal hernia is a common complication after colostomy construction. Whether an extraperitoneal route for colostomy creation can reduce the risk of parastomal hernia remains controversial.ObjectiveA meta-analysis was performed to evaluate the value of extraperitoneal route in the prevention of parastomal hernia and other postoperative complications related to colostomy.Data sourcesA literature search of Medline, Embase, Ovid, and Cochrane databases from the years 1966 to 2010 was performed.Study selectionStudies comparing extraperitoneal colostomy with intraperitoneal colostomy were identified.InterventionExtraperitoneal colostomy was performed to prevent colostomy-related complications.Main outcome measuresData on the following outcomes were sought: incidence of postoperative colostomy complications including parastomal hernia, prolapse, and bowel obstruction.ResultsSeven retrospective studies with a combined total of 1,071 patients (250 extraperitoneal colostomy and 821 intraperitoneal colostomy) were identified. There was a significantly lower rate of parastomal hernia (odds ratio, 0.41; 95% confidence interval, 0.23–0.73, p = 0.002) in the extraperitoneal colostomy group. However, the occurrences of bowel obstruction and prolapse were not significantly different between the two groups.LimitationsA limitation of the study lies on the meta-analysis of observational studies.ConclusionExtraperitoneal colostomy is associated with a lower rate of postoperative parastomal hernia as compared to intraperitoneal colostomy. Prospective randomized controlled trial is warranted to further determine the role of extraperitoneal route in the prevention of parastomal hernia.

Significance of mTOR Signaling and Its Inhibitor Against Cancer Stem-Like Cells in Colorectal Cancer

PurposeTo determine the role of the mammalian target of rapamycin (mTOR) signaling in sustaining cancer stem-like cells and its clinical values in colorectal cancer (CRC).MethodsmTOR expression in CRC patients was analyzed by immunohistochemistry and survival analysis was used to confirm the clinical value of mTOR. Colorectal cell lines were treated by mTOR inhibitors rapamycin and PP242, and sphere formation assay and aldehyde dehydrogenase (ALDH) assay were utilized to determine the impact of mTOR inhibition in CRC stem-like cells, combined or not combined with chemotherapeutic drug (fluorouracil and oxaliplatin).ResultsmTOR expression was associated with outcomes of CRC patients and predicted poor prognosis in stage II CRC patients. mTOR signaling was activated in stem-like colorectal cancer cells, and mTOR inhibitors (rapamycin and PP242) decreased the capacity of sphere formation as well as ALDH activity. Furthermore, mTOR inhibitors also were demonstrated to suppress the stimulation of stem-like cells by chemotherapy.ConclusionsmTOR shared predictive significance in stage II CRC patients’ outcomes and played a vital role in the maintenance of colorectal cancer stem-like cells. mTOR inhibitors might hold the potential to become a therapeutic target against CRC stem cells.

Tumor-Infiltrating Mast Cells in Colorectal Cancer as a Poor Prognostic Factor

The purpose of this study is to investigate the clinical/prognostic significance of tumor-infiltrating mast cells (TIMs) in patients with colorectal cancer (CRC). TIM infiltration in 325 stage I to III CRC specimens was detected by immunohistochemistry. The optimal cutpoint of TIM density was assessed by the X-tile program. TIM infiltration in CRC was significantly higher than in normal colorectal tissues. According to the X-tile program, the cutpoint for high TIM infiltration in CRC was determined when TIM density was more than 8.0 per high-power field. Correlation analysis between TIM density and clinicopathological variables demonstrated that TIM infiltration was significantly associated with gender, nodal status, and American Joint Committee on Cancer stage. Multivariate Cox regression analysis showed that high TIM infiltration was a risk factor for both overall survival and disease-free survival. Taken together, high TIM infiltration can be an independent and useful biomarker for predicting the poor survival of patients with CRC.

Changes of T Cells and Cytokines TGF-β1 and IL-10 in Mice During Liver Metastasis of Colon Carcinoma: Implications for Liver Anti-tumor Immunity

BackgroundThe local and systemic regulation of the immune system may play important roles in the process of liver metastasis of colorectal carcinoma. The aim of this study was to establish a reproducible experimental liver metastasis model, to identify changes in T cells and cytokines TGF-β1 and IL-10, and to explore a possible mechanism of liver metastasis of colon carcinoma.MethodsWe used a colon carcinoma liver metastasis model, in which different numbers of CT-26 murine colon carcinoma cells (1 × 103, 5 × 103, 1 × 104, 5 × 104, and 1 × 105) were injected into the spleen. The liver and spleen tissues were examined for T cell markers using flow cytometry. Liver tissues were analyzed for IL-10 and transforming growth factor beta 1 (TGF-β1) expression using immunohistochemistry.ResultsSpleen injection of colon carcinoma cells is a reproducible animal model for liver metastases, which resulted in quantity-dependent metastatic growth. We provided a snapshot of the hepatic immune microenvironment in the mouse liver metastasis model. Injection of A large number of tumor cells (5 × 104 and 1 × 105) decreased anti-tumor cell counts, such as CD4+ and CD8+ T cells, and increased immune-suppressive cell counts (CD4+CD25+ Treg cells). In addition, the expression levels of immunosuppressive cytokines IL-10 and TGF-β1 were also increased with the number of tumor cells.ConclusionsChanges in the systemic and local immunological environment contribute to immunological escape mechanisms during liver metastasis of colon carcinoma, and therapies aiming at immune microenvironment may prove a useful strategy in the treatment of metastatic disease in the future.

CCL21 as an independent favorable prognostic factor for stage III/IV colorectal cancer

The aim of the present study was to investigate the expression dynamics of CCL21 and its prognostic significance in human stage III/IV colorectal cancer (CRC). CCL21 expression dynamics were detected with western blotting. The expression of CCL21 in CRC tissue microarrays was examined by immunohistochemistry. The optimal cut-point of CCL21 expression was assessed by the X-tile program. The prognostic significance was analyzed using both Kaplan-Meier curves and Cox regression analysis. Western blot analysis demonstrated that CCL21 expression was comparable in the CRC and normal colorectal tissues. According to the X-tile program, the cut-point for high expression of CCL21 in CRC was determined when the CCL21 expression index was >56.1. Overexpression of CCL21 was significantly correlated with larger tumor diameter, more mucinous carcinoma or signet ring cell carcinoma and poor tumor differentiation. Patients with high expression of CCL21 had a higher overall survival rate in comparison to patients with low expression. In the multivariate Cox regression analysis, CCL21 expression was found to be an independent prognostic biomarker for CRC. ROC curves showed that CCL21 expression could improve the prognostic capability of TNM stage in stage III/IV CRC patients. High expression of CCL21 is an independent and useful biomarker for predicting longer survival of stage III/IV CRC patients.

Safety and Efficacy of Sodium Hyaluronate Gel and Chitosan in Preventing Postoperative Peristomal Adhesions After Defunctioning Enterostomy: A Prospective Randomized Controlled Trials

AbstractPeristomal adhesions complicate closure of defunctioning enterostomy. The efficacy and safety of sodium hyaluronate gel and chitosan in preventing postoperative adhesion have not been extensively studied. This study aims to evaluate the safety and efficacy of sodium hyaluronate gel and chitosan in the prevention of postoperative peristomal adhesions.This was a prospective randomized controlled study. One hundred and fourteen patients undergoing defunctioning enterostomy were enrolled. Patients were randomly assigned to receive sodium hyaluronate gel (SHG group) or chitosan (CH group) or no antiadhesion treatment (CON group) during defunctioning enterostomy. The safety outcomes included toxicities, stoma-related complications, and short-term and long-term postoperative complications. Eighty-seven (76.3%) of the 114 patients received closure of enterostomy, during which occurrence and severity of intra-abdominal adhesions were visually assessed by a blinded assessor.Incidence of adhesion appears to be lower in patients received sodium hyaluronate gel or chitosan but differences did not reach a significant level (SHG group vs CH group vs CON group: 62.1% vs 62.1% vs 82.8%, P = 0.15). Compared with the CON group, severity of postoperative adhesion was significantly decreased in the SHG and CH group (SHG group vs CH group vs CON group: 31.0% vs 27.6% vs 62.1%; P = 0.01). There was no significant difference in the occurrence of postoperative complications and other safety outcomes among the 3 groups.Sodium hyaluronate gel or chitosan smeared around the limbs of a defunctioning enterostomy was safe and effective in the prevention of postoperative peristomal adhesions.

Male gender is associated with an increased risk of anastomotic leak in rectal cancer patients after total mesorectal excision

Abstract Background The impact of a patient’s gender on the development of anastomotic leak (AL) in rectal cancer patients following total mesorectal excision (TME) remains controversial. The aim of this study was to evaluate the association between patients’ gender and the risk of AL. Methods All rectal cancer patients following TME with a primary anastomosis during the study period from 2010 to 2014 were examined. Comparisons of the post-operative AL incidence rate between male and female patients were performed. Results Of all patients examined (n = 956), 587 (61.4%) were males and 369 (38.6%) were females. Male patients were more likely to have a history of smoking and drinking alcohol, but less likely to have a history of abdominal surgery compared to female patients. A higher incidence rate of pre-operative bowel obstruction and larger tumor volume in male patients was observed in our study. Of all the patients, 81 (8.5%) developed post-operative AL. More male patients (n = 62, 10.6%) suffered from AL than females (n = 19, 5.1%) (P = 0.003). Multivariate logistic regression analyses confirmed the association between male gender and AL [odds ratio (OR): 2.41, 95% confidence interval (CI): 1.37–4.23, P = 0.002]. Similar results were also obtained in patients who underwent laparoscopic TME (OR: 2.11, 95% CI: 1.15–3.89, P = 0.016). Conclusions Male patents were found to have an increased risk for AL following TME with a primary anastomosis. A temporary protecting stoma may help to protect the anastomosis and lessen the risk for AL especially in male patients.

Enteral nutrition is associated with a decreased risk of surgical intervention in Crohn's disease patients with spontaneous intra-abdominal abscess

BACKGROUND The impact of enteral nutrition (EN) on surgical risk in Crohns disease (CD) patients suffering from spontaneous intra-abdominal abscess (IAA) was evaluated. METHODS CD patients diagnosed with spontaneous IAA from 2008 to 2015 were included in the study. The impact of EN on surgical risk was evaluated using both univariate and multivariate analyses. RESULTS A total of 87 patients were enrolled, 66 (75.9%) were male. The mean age at the development of an abscess was 30.2 ± 10.1 years and the median duration of illness from CD diagnosis until the development of an abscess was three (2-6) years. After a median follow-up of 1.9 (1.1-2.9) years, surgical intervention was performed in 42 patients (48.3%). Patients treated with EN were less likely to require surgical intervention (26.1% vs 56.3%, p = 0.01). Multivariate analysis showed that EN was an independent protective factor for the risk of surgery with a hazard ratio of 0.27 (95% confidence interval: 0.11-0.65, p = 0.004) after adjusting for abdominal pain, history of abdominal surgery, concomitant intestinal stenosis and prior use of antibiotics within three months. CONCLUSIONS Surgical intervention is common for CD patients with IAA. Appropriate application of EN may help obviate the need for surgical treatment.

Preoperative hypoalbuminemia is associated with an increased risk for intra-abdominal septic complications after primary anastomosis for Crohn’s disease

Abstract Objective The aim of this study was to evaluate the impact of preoperative hypoalbuminemia on the development of intra-abdominal septic complications (IASCs) after primary anastomosis for patients with Crohn’s disease (CD). Methods All CD patients undergoing bowel resection with a primary anastomosis during the study period from 2007 to 2015 were enrolled. The association of preoperative hypoalbuminemia (<30 g/L) with the risk for IASCs were assessed using both univariate and multivariate analyses. Results A total of 124 eligible patients were included, 117 (94.4%) of whom had available preoperative albumin level. Preoperative hypoalbuminemia occurred in 13 (11.7%) patients. The duration from diagnosis to surgery was longer for patients with preoperative hypoalbuminemia than those without (p = 0.012). Patients with preoperative hypoalbuminemia were more likely to have a history of preoperative use of 5-aminosalicylic acid (p = 0.013) and have an intraoperative finding of small bowel obstruction (p = 0.015). Of all patients, 24 (19.4%) developed postoperative IASCs. Univariate analysis showed that patients with preoperative hypoalbuminemia had an increased risk for IASCs (p = 0.012). Multivariate analysis confirmed the association between preoperative hypoalbuminemia and IASCs (odds ratio 4.67, 95% confidence interval: 1.28–17.04, p = 0.02). Similar findings were also obtained when preoperative albumin level was analysed as a continuous variable (p = 0.019). Conclusions Preoperative hypoalbuminemia is a significant predictor for the development of postoperative IASCs in CD patients after bowel resection with a primary anastomosis. Favorable preoperative nutrition status might lessen the risk for IASCs.