Yifeng Zou

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.

Bone marrow mesenchymal stem cells ameliorate colitis-associated tumorigenesis in mice.

BACKGROUND AND AIMS Bone marrow-derived mesenchymal stem cell (MSC) is widely studied in inflammatory bowel disease (IBD) in basic and clinical research. However, patients with IBD have higher risk of developing colorectal cancer and MSC has dual effect on tumorigenesis. This study aims to evaluate the role of MSC on tumorigenesis of IBD. METHODS MSCs were isolated from the bone marrow of allogenic mice and identified by flow cytometry. Mice in the model of colitis-associated tumorigenesis induced by azoxymethane and dextran sulfate sodium were injected with MSCs. Colon length, spleen size and tumors formation were assessed macroscopically. Pro-inflammatory cytokines and STAT3 phosphorylation in colon tissues were analyzed. RESULTS MSCs ameliorated the severity of colitis associated tumorigenesis compared with PBS control, with attenuated weight loss, longer colons and smaller spleens. Tumor number and tumor load were significantly less in the MSC group while tumor size remained comparable. Histological assessment indicated MSCs could reduce histological damage of the colon tissue. Decreased expression of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), and down-regulation of STAT3 phosphorylation in colon tissue were found after MSC treatment. CONCLUSION MSCs might ameliorate the tumorigenesis of inflammatory bowel disease by suppression of expression of pro-inflammatory cytokines and STAT3 activation.

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.

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.

MicroRNA 26b promotes colorectal cancer metastasis by downregulating phosphatase and tensin homolog and wingless-type MMTV integration site family member 5A

Invasion and metastasis are crucially important factors in the survival of malignant tumors. Epithelial‐mesenchymal transition (EMT) is an early step in metastatic progression and the presence of cancer stem cells is closely related to tumor survival, proliferation, metastasis, and recurrence. Herein we report that ectopic overexpression of microRNA 26b (miR‐26b) in colorectal cancer (CRC) cell lines promoted EMT and stem cell‐like phenotypes in vitro. Furthermore, miR‐26b directly targeted and suppressed multiple tumor suppressors, including phosphatase and tensin homolog (PTEN) and wingless‐type MMTV integration site family member 5A (WNT5A). Notably, miR‐26b is markedly upregulated in tumor samples from patients with lymphatic metastases. These results indicate that miR‐26b promotes CRC metastasis by downregulating PTEN and WNT5A, and may represent a therapeutic target for metastatic CRC.

Conversion is a risk factor for postoperative anastomotic leak in rectal cancer patients - A retrospective cohort study

AIM The impact of conversion from laparoscopic surgery to laparotomy on the development of anastomotic leak (AL) in rectal cancer patients following laparoscopic low anterior resection (LAR) with total mesorectal excision (TME) has not been evaluated. The aim of this study was to evaluate the impact of conversion on the risk of AL and develop a prediction nomogram for postoperative AL. METHODS All rectal cancer patients following laparoscopic LAR with TME from January 2010 to October 2014 were enrolled in the primary cohort. Comparisons of the postoperative anastomotic leak incidence rate between converted patients and non-converted patients were performed using both univariate and multivariate logistic regression analyses. The result of multivariable analysis was used to develop the predicting model and the performance of nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. An independent validation cohort containing 200 patients from November 2014 to October 2015 was assessed. RESULTS Of all patients enrolled (n=646), 592 (91.6%) patients underwent totally laparoscopic surgery, and 54 (8.4%) were converted from laparoscopic surgery to laparotomy. Converted group patients were more likely to have a higher body mass index (BMI), prolonged length of stay (LOS), increased overall postoperative complication rates and advanced clinical T stage (T3 or T4), pathological N stage (N1 or N2) and pathological TNM stage (III or IV). The percentage of patients who had preoperative radiotherapy for rectal cancer was higher in non-converted patients. Patients who underwent conversion to laparotomy (n=10, 18.5%) were more likely to suffer from postoperative AL than those undergoing totally laparoscopic surgery (n=38, 6.4%) (P=0.004). Multivariate logistic regression analyses confirmed the association between conversion and postoperative AL (Odds ratio [OR], 95% confidence interval [CI]: 2.71 [1.31-5.63], P=0.007). Conversion, gender, and clinical N stage incorporated in the individualized prediction nomogram showed good discrimination, with a C-index of 0.697 (C-index, 0.621 and 0.772 through internal validation), and good calibration. In the validation cohort, the main results were consistent with the findings of the primary cohort, with a C-index of 0.670 (C-index, 0.562 and 0.777 through internal validation). Decision curve analysis demonstrated that the prediction nomogram was clinically useful. CONCLUSION Conversion during laparoscopic LAR was found to be associated with an increased risk for the postoperative AL in RC patients. A nomogram model incorporating conversion, gender and patients clinical N stage seems to offers a useful tool for predicting postoperative AL in these patients.

Accessing new prognostic significance of preoperative carcinoembryonic antigen in colorectal cancer receiving tumor resection: More than positive and negative.

OBJECTIVE Evaluating the prognostic significance of carcinoembryonic antigen (CEA) for colorectal cancer (CRC) patients in new cutoffs. PATIENTS Three hundred and seventy cases and 1164 cases of CRC patients receiving tumor resection from hospitals of Sun Yat-sen University were retrospectively investigated as training cohort and validation cohort respectively. CEA was categorized into quintiles for Kaplan-Meier analysis and Cox proportional hazards regression analysis. RESULTS CEA was categorized into quintiles with the cutoff points of (0-1.5) ng/ml, (1.5-2.3) ng/ml, (2.3-3.98) ng/ml, (3.98-8.02) ng/ml, (8.02-Maximum) ng/ml. In CRC patients from training cohort, progressively worse outcomes were observed in each increasing quintile of CEA in term of overall survival (Log-rank Test: P< 0.0001, Log-rank Test for Trend: P< 0.0001) and progression free survival (Log-rank Test: P= 0.0002, Log-rank Test for Trend: P< 0.0001). CEA quintile was associated with overall survival (HR: 1.209, 95%CI: 1.033-1.416, P= 0.018) and progression free survival (HR: 1.195, 95%CI: 1.024-1.394, P= 0.024). Validation analysis also showed that patients with increasing CEA quintile suffered unfavorable overall survival (Log-rank Test: P= 0.0001, Log-rank Test for Trend: P= 0.0001) and progression free survival (Log-rank Test: P= 0.0001, Log-rank Test for Trend: P= 0.0001). CEA quintile was associated with overall survival (HR: 1.330, 95%CI: 1.123-1.576, P< 0.001) and progression free survival (HR: 1.218, 95%CI: 1.089-1.362, P= 0.001). CONCLUSIONS Preoperative CEA quintile was an independent predictor of unfavorable prognosis in CRC patients. Even within normal range, CEA quintile might still impact prognosis outcomes of CRC.