Increased risk of colorectal neoplasia in inflammatory bowel disease patients with post-inflammatory polyps:A systematic review and meta-analysis

BACKGROUND Inflammatory bowel disease(IBD)patients with post-inflammatory polyps(PIPs)may carry an increased risk of colorectal neoplasia(CRN)including dysplasia and cancer.Current guidelines recommend active colonoscopy follow-up for these patients.However,the evidence for guidelines is still poor.In addition,some recent high-quality reports present a different view,which challenges the current guidelines.We hypothesize that IBD patients with PIPs are at increased risk of CRN.AIM To evaluate the risk of CRN in IBD patients with and without PIPs.METHODS A systematic search of PubMed,Embase,Cochrane Library,and Web of Science was performed to identify studies that compared the risk of CRN in IBD patients with and without PIPs.In addition,we screened the reference lists and citation indices of the included studies.Quality assessment was performed using the Newcastle–Ottawa Scale.Pooled odds ratio(OR)was calculated using the random-effects model to explore the final pooled effect size of the included studies and determine whether PIPs increase the risk of CRN.Sensitivity analysis,subgroup analysis,and assessment of publication bias were performed to examine the sources of heterogeneity.RESULTS Twelve studies with 5819 IBD patients,including 1281(22.01%)with PIPs,were considered eligible for this meta-analysis.We found that IBD patients with PIPs were at an increased risk of CRN as compared to those without PIPs[OR 2.01;95%confidence interval(CI):1.43–2.83].The results were similar when colorectal cancer was used as the study endpoint(OR 2.57;95%CI:1.69–3.91).Furthermore,the risk of CRN was still increased(OR 1.80;95%CI:1.12–2.91)when restricted to ulcerative colitis patients.Heterogeneity was high among the included studies(I^(2)=75%).Subgroup analysis revealed that the high heterogeneity was due to the study design.Sensitivity analysis showed that the main statistical outcomes did not essentially change after excluding any one of the included studies.No significant publication bias was found in the funnel plots.CONCLUSION IBD patients with PIPs have an increased risk of CRN as compared with those without PIPs,which support the current guidelines.However,a high-quality randomized controlled trial is warranted.

过表达CXCR4的骨髓间充质干细胞通过增强的肠道归巢能力抑制小鼠肠炎相关肿瘤的形成

背景:骨髓来源间充质干细胞(MSC)用于炎症性肠病(IBD)及IBD相关肠癌的治疗潜力已受到越来越多的关注。然而,MSC究竟是抵制还是促进肿瘤形成仍然存在争议。基质细胞衍生因子1(SDF-1)/C-X-C趋化因子受体4(CXCR4)在MSC归巢过程具有非常关键的作用。本研究旨在评估过表达CXCR4的MSC在IBD瘤变过程中的作用。方法:应用携带CXCR4或绿色荧光蛋白(GFP)的慢病毒载体转染MSC。通过细胞趋化实验和侵袭实验检测CXCR4表达情况。采用偶氮甲烷和葡聚糖硫酸钠(DSS)制作小鼠结肠炎成瘤模型。将实验小鼠分为3组,分别注射磷酸盐缓冲液(PBS)、MSC-GFP或MSC-CXCR4。结果:与MSC-GFP组小鼠相比,MSC-CXCR4小鼠体重下降程度减少,结肠相对更长,肿瘤数量更少,肿瘤负荷减轻;此外,结肠组织中促炎细胞因子表达和STAT3磷酸化水平均下调。结论:过表达CXCR4的MSC表现出抑瘤功能,其机制可能是CXCR4促进MSC向炎性肠组织的归巢。

男性直肠癌患者全直肠系膜切除术后吻合口漏风险增高

背景:患者性别对于直肠癌全直肠系膜切除术(TME)后吻合口漏形成的影响目前仍存在争议。本研究旨在评估性别与吻合口漏的相关性。方法:回顾性分析2010-2014年间在我院接受TME手术且行一期吻合的直肠癌患者的临床资料。比较男性与女性患者术后吻合口漏发生率。结果:入组的956例直肠癌患者中,男性587例(61.4%),女性369例(38.6%)。相较于女性患者,男性患者中吸烟和饮酒的比例更高,但有腹部手术史者较少;术前肠梗阻的比例更高,肿瘤本身也相对较大。全组病例中出现术后吻合口漏81例(8.5%),其中男性患者发生率高于女性患者(10.6%vs.5.1%,P¼0.003)。多因素逻辑回归分析证实,男性是术后吻合口漏发生的独立危险因素(OR¼2.41,95%CI:1.37-4.23,P¼0.002);对于腹腔镜TME手术的亚组分析也得到了相同的结果(OR¼2.11,95%CI:1.15-3.89,P¼0.016)。结论:男性直肠癌患者TME手术后吻合口漏的发生风险相对较高。保护性肠造口或可为吻合口提供保护,降低吻合口漏的发生风险,尤其是对于男性患者。

低剂量环磷酰胺的抗肿瘤免疫:结肠癌肝转移治疗后T细胞、转移生长因子β及白介素10的改变

背景:肿瘤免疫微环境是结直肠癌肝转移最重要的预后因素之一。低剂量环磷酰胺(CTX)被认为可以调节免疫系统,然而,其调节机制尚不明了。本研究旨在研究低剂量CTX治疗结直肠癌肝转移时的抗肿瘤免疫特性。方法:将30只小鼠随机分为5组。在结肠癌肝转移模型建立后,治疗组在不同时间点注射低剂量CTX(20 mg/kg)。取肝脏和脾脏组织,通过流式细胞方法检测T细胞标志物;通过免疫组化方法分析肝脏组织中白介素(IL)10和转化生长因子(TGF)β1表达水平。采用酶联免疫吸附实验检测血清干扰素(IFN)γ和IL-10水平。另取20只小鼠随机分为治疗组和对照组,记录其存活情况。结果:结直肠癌肝转移组小鼠CD4^(+)T细胞、CD8^(+)T细胞及IFN-γ表达水平均下调,但IL-10和TGF-β1表达上调。而且,肝转移小鼠肝脏的局部及系统免疫微环境均发生了变化,导致抗肿瘤免疫反应减弱,从而出现肝转移。然而,低剂量CTX治疗可以逆转上述情况。低剂量CTX组小鼠的生存时间显著延长。结论:低剂量CTX可以通过改变系统及局部的免疫微环境、增强免疫调控而发挥抗肿瘤作用。CTX或可用于结肠癌肝转移的预防和治疗。

Nomogram for predicting overall survival time of patients with stageⅣcolorectal cancer

Background Prognosis varies among stageⅣcolorectal cancer(CRC).Our study aimed to build a robust prognostic nomogram for predicting overall survival(OS)of patients with stageⅣCRC in order to provide evidence for individualized treatment.Method We collected the information of 16,283 patients with stageⅣCRC in the Surveillance,Epidemiology,and End Results(SEER)database and then randomized these patients in a ratio of 7:3 into a training cohort and an internal validation cohort.In addition,501 patients in the Sixth Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)database were selected and used as an external validation cohort.Univariate and multivariate Cox analyses were used to screen out significant variables for nomogram establishment.The nomogram model was assessed using time-dependent receiveroperating characteristic curve(time-dependent ROC),concordance index(C-index),calibration curve,and decision curve analysis.Survival curves were plotted using the Kaplan–Meier method.Result The C-index of the nomogram for OS in the training,internal validation,and external validation cohorts were 0.737,0.727,and 0.655,respectively.ROC analysis and calibration curves pronounced robust discriminative ability of the model.Further,we divided the patients into a high-risk group and a low-risk group according to the nomogram.Corresponding Kaplan–Meier curves showed that the prediction of the nomogramwas consistent with the actual practice.Additionally,model comparisons and decision curve analysis proved that the nomogram for predicting prognosis was significantly superior to the tumor-node-metastasis(TNM)staging system.Conclusions We constructed a nomogram to predict OS of the stageⅣCRC and externally validate its generalization,which was superior to the TNM staging system.

疫情期间胃肠外科的应对策略与诊疗推荐:中国外科医师的经验分享

由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的COVID-19正在全球暴发。尽管SARS-CoV-2被认为主要是通过呼吸道飞沫传播,但最新研究发现其也可以通过粪/口途径传播,这也引起了大家对胃肠道病毒传播的担忧。因此,作为抗疫一线的中国胃肠外科医师,我们愿意分享一些抗疫期间的经验和教训。在疫情期间建立一个科学、合理的应对策略是非常必要的。本文中,我们就如何在继续提供胃肠外科医疗服务的同时尽可能从各个方面减少病毒传播,取得了中国多家机构的共识,包括胃肠外科门诊防护、胃肠外科病房防护、胃肠内镜中心防护以及围手术期管理模式的优化。我们的经验分享和诊治推荐或有助于全球仍处于疫区的胃肠外科建立自己的病毒防控策略。