Risk factors for recurrence after bowel resection for Crohn’s disease

BACKGROUND Complications of Crohn’s disease such as intestinal obstruction,fistula or perforation often need surgical treatment.Nearly 70%-80%patients with Crohn’s disease would receive surgical treatment during the lifetime.However,surgical treatment is incurable for Crohn’s disease.The challenge of recurrence postoperatively troubles both doctors and patients.Over 50%patients would suffer recurrence postoperatively.Some certain risk factors are associated with recurrence of Crohn’s disease.AIM To evaluate the risk factors for endoscopic recurrence and clinical recurrence after bowel resection in Crohn’s disease.METHODS Patients diagnosed Crohn’s disease and received intestinal resection between April 2007 and December 2013 were included in this study.Data on the general demographic information,preoperative clinical characteristics,surgical information,postoperative clinical characteristics were collected.Continuous data are expressed as median(inter quartile range),and categorical data as frequencies and percentages.Kaplan-Meier method was applied to estimate the impact of the clinical variables above on the cumulative rate of postoperative endoscopic recurrence and clinical recurrence,then log-rank test was applied to test the homogeneity of those clinical variables.Multivariate Cox proportional hazard regression analysis was performed to identify the risk factors of postoperative endoscopic recurrence and clinical recurrence.RESULTS A total of 64 patients were included in this study.The median follow-up time for the patients was 17(9.25-25.75)mo.In this period,41 patients(64.1%)had endoscopic recurrence or clinical recurrence.Endoscopic recurrence occurred in 34(59.6%)patients while clinical recurrence occurred in 28(43.8%)patients,with the interval between the operation and recurrence of 13.0(8.0-24.5)months and 17.0(8.0-27.8)mo,respectively.In univariate analysis,diagnosis at younger age(P<0.001),disease behavior of penetrating(P=0.044)and preoperative use of anti-tumor necrosis factor(TNF)(P=0.020)were significantly correlated with endoscopic recurrence,while complication with perianal lesions(P=0.032)and preoperative use of immunomodulatory(P=0.031)were significantly correlated with clinical recurrence.As to multivariate analysis,diagnostic age(P=0.004),disease behavior(P=0.041)and preoperative use of anti-TNF(P=0.010)were independent prognostic factors for endoscopic recurrence,while complication with perianal lesions(P=0.023)was an independent prognostic factor for clinical recurrence.CONCLUSION Diagnostic age,disease behavior,preoperative use of anti-TNF and complication with perianal lesions were independent risk factors for postoperative recurrence in Crohn’s disease.

Overexpression of G protein-coupled receptor 31 as a poor prognosticator in human colorectal cancer

AIM To investigate the expression of G protein-coupled receptor 31 (GPR31) and its clinical significance in human colorectal cancer (CRC).METHODS To determine the association between the GPR31 expression and the prognosis of patients, we obtained paraffin-embedded pathological specimens from 466 CRC patients who underwent initial resection. A total of 321 patients from the First Affiliated Hospital of Sun Yat-sen University from January 1996 to December 2008 were included as a training cohort, whereas 145 patients from the Sixth Affiliated Hospital of Sun Yat-sen University from January 2007 to November 2008 were included as a validation cohort. We examined GPR31 expression levels in CRC tissues from two independent cohorts via immunohistochemical staining. All patients were categorized into either a GPR31 low expression group or a GPR31 high expression group. The clinicopathological factors and the prognosis of patients in the GPR31 low expression group and GPR31 high expression group were compared.RESULTS We compared the clinicopathological factors and the prognosis of patients in the GPR31 low expression group and GPR31 high expression group. Significant differences were observed in the number of patients in pM classification between patients in the GPR31 low expression group and GPR31 high expression group (P = 0.007). The five-year survival and tumor-free survival rates of patients were 84.3% and 82.2% in the GPR31 low expression group, respectively, and both rates were 59.7% in the GPR31 high expression group (P < 0.05). Results of the Cox proportional hazard regression model revealed that GPR31 upregulation was associated with shorter overall survival and tumor-free survival of patients with CRC (P < 0.05). Multivariate analysis identified GPR31 expression in colorectal cancer as an independent predictive factor of CRC patient survival (P < 0.05).CONCLUSION High GPR31 expression levels were found to be correlated with pM classification of CRC and to serve as an independent predictive factor of poor survival of CRC patients.

Incidentally discovered asymptomatic splenic hamartoma misdiagnosed as an aneurysm:A case report

BACKGROUND Splenic hamartoma(SH)is a rare,benign vascular proliferation that is often found incidentally.It may be misdiagnosed as a splenic aneurysm or splenic malignancy.CASE SUMMARY A 21-year-old male patient was admitted to our hospital with a complaint of an incidentally discovered asymptomatic splenic space-occupying lesion for 2 wk.Abdominal computed tomography(CT)scan showed a circular low-density shadow in the hilum of the spleen.Contrast-enhanced CT revealed an aneurysm located in the hilum of the spleen before operation.Laparoscopic splenectomy was performed and postoperative pathology revealed the presence of SH.CONCLUSION Imaging studies are insufficient for the differential diagnosis of SH from other diseases,and laparoscopic splenectomy is a less invasive procedure and useful for the diagnostic purpose as well.

Bone marrow-derived CXCR4-overexpressing MSCs display increased homing to intestine and ameliorate colitis-associated tumorigenesis in mice

Background and Objective:Increasing interest has developed in the therapeutic potential of bone marrow-derived mesenchymal stem cells(MSCs)for the treatment of inflammatory bowel disease(IBD)and IBD-induced cancer.However,whether MSCs have the ability to suppress or promote tumor development remains controversial.The stromal cell-derived factor 1(SDF-1)/C-X-C chemokine receptor type 4(CXCR4)axis is well known to play a critical role in the homing of MSCs.In this study,we aimed to evaluate the role of CXCR4-overexpressing MSCs on the tumorigenesis of IBD.Methods:MSCs were transduced with lentiviral vector carrying either CXCR4 or green fluorescent protein(GFP).Chemotaxis and invasion assays were used to detect CXCR4 expression.A mouse model of colitis-associated tumorigenesis was established using azoxymethane and dextran sulfate sodium(DSS).The mice were divided into three groups and then injected with phosphate buffer saline(PBS),MSC-GFP or MSC-CXCR4.Results:Compared with the mice injected with MSC-GFP,the mice injected with MSC-CXCR4 showed relieved weight loss,longer colons,lower tumor numbers and decreased tumor load;expression of pro-inflammatory cytokines decreased,and signal transducer and activator of transcription 3(STAT3)phosphorylation level in colon tissue was down-regulated.Conclusion:CXCR4-overexpressing MSCs exhibited effective anti-tumor function,which may be associated with enhanced homing to inflamed intestinal tissues.

Antitumor immunity of low-dose cyclophosphamide:changes in T cells and cytokines TGF-beta and IL-10 in mice with colon-cancer liver metastasis

Background:The tumor immune microenvironment is one of the most important prognostic factors in liver metastasis from colorectal cancer.Low-dose cyclophosphamide(CTX)is widely believed to be involved in the modulation of the immune system.However,the underlying mechanism of low-dose CTX remains unknown.This study aimed to investigate the antitumor immunity of low-dose CTX in the treatment of colon-cancer liver metastasis.Methods:Thirty mice were randomly divided into five groups.After liver metastasis was established in colon-cancer models,mice in the treatment groups were injected with low-dose CTX(20 mg/kg)at different time points.Liver and spleen tissues were examined for T-cell markers via flow cytometry.Interleukin(IL)-10 and transforming growth factor(TGF)-b1 expression levels in liver tissues were analysed by immunohistochemistry.Serum interferon(IFN)-c and IL-10 levels were detected by enzyme-linked immunosorbent assay.An additional 20 mice were randomly allocated into two groups and the survival times were recorded.Results:The expression levels of CD4^(+)T cells,CD8^(+)T cells,and IFN-c were down-regulated,whereas those of IL-10 and TGF-b1 were up-regulated in liver metastasis from colon cancer in mice.Furthermore,the local and systemic microenvironments of the liver were altered,which led to reduced antitumor immune responses and subsequently liver metastasis.However,treatment with low-dose CTX reversed these effects.The survival times of mice treated with low-dose CTX were significantly longer than those of the other groups.Conclusions:Low-dose CTX exerts its antitumor activity by changing the systemic and local immune microenvironments and enhancing immune regulation inmice.CTX could be used as a drug to prevent and treat livermetastasis from colon cancer.

An 11-gene signature for the prediction of systemic recurrences in colon adenocarcinoma

Background Prognosis varies among patients within the same colon adenocarcinoma(COAD)stage,indicating the need for reliable molecular markers to enable individualized treatment.This study aimed to investigate gene signatures that can be used for better prognostic prediction of COAD.Methods Gene-expression profiles of COAD patients were obtained from the Gene Expression Omnibus database(n=332)and The Cancer Genome Atlas database(n=431).The relationship between gene signature and relapse-free survival was analysed in the training set(n=93)and validated in the internal validation set(n=94)and external validation sets(n=145 and 431).Results Overall,11 genes(N-myc downstream regulated gene 1[NDRG1],fms-like tyrosine kinase 1[FLT1],lipopolysaccharide binding protein[LBP],fatty acid binding protein 4[FABP4],adiponectin gene[ADIPOQ],angiotensinogen gene[AGT],activin A receptor,type II-like kinase 1[ACVRL1],CC chemokine ligand 11[CCL11],cell division cycle 42[CDC42],T-cell receptor alpha variable 9_2[TRAV9_2],and proopiomelanocortin[POMC])were identified by univariable and least absolute shrinkage and selection operator(LASSO)Cox regression analyses.Based on the risk-score model,the patients were grouped into the high-risk or low-risk groups using the median risk score as the cut-off.The area under the curve(AUC)values for 1-,3-,and 5-year recurrence were 0.970,0.849,and 0.859,respectively.Patients in the high-risk group had significantly poorer relapsefree survival than did those in the low-risk group.The predictive accuracy of the 11-gene signature was proven in the validation sets.Our gene signature showed better predictive performance for 1-,3-,and 5-year recurrence than did the other four models.Conclusions The 11-gene signature showed good performance in predicting recurrence in COAD.The accuracy of the signature for prognostic classification requires further confirmation.

Percutaneous ultrasound-guided drainage of pneumomediastinum through the retropharyngeal space:a case report

Introduction Esophageal perforation(EP)is a rare but potentially lethal clinical condition with a mortality rate as high as 20%[1].The most common causes of EP are iatrogenic,spontaneous,and foreign body ingestion[2].EP is often accompanied by serious complications such as hemorrhagic pericardial effusion,mediastinal abscesses,and sepsis[3].Management is multidisciplinary and involves emergency physicians,thoracic surgeons,otaorhinolaryngologists,gastroenterologists,anesthesiologists,and radiologists[1].We herein report a case of pneumomediastinum caused by EP and discuss the effect of percutaneous ultrasound(US)-guided drainage through the retropharyngeal space.