溃疡性结肠炎癌变的回顾性分析

目的分析558例溃疡性结肠炎(UC)发生结直肠癌的风险以及危险因素,为溃疡性结肠炎相关癌(UC-CRC)的监测、筛查以及预防提供依据。方法 1997年1月至2007年12月南方医院共行结肠镜检查32926例,对其中558例UC患者以及UC-CRC患者的相关临床资料进行回顾性分析。结果在558例UC患者中,发现结直肠癌8例,均为进展期癌,总体风险为1.43%,2组病人在年龄、疾病病程、病变范围、诊断结直肠癌前活检是否有不典型增生、是否使用5-ASA类药物、激素治疗以及是否参加内镜随访等方面有显著性差别。危险因素分析提示,疾病病程、病变范围以及结肠镜检查发现不典型增生为UC-CRC的危险因素;定期内镜随访、5-ASA以及激素治疗可降低UC-RC发病的风险。结论 UC患者有较高癌变的风险,但总体风险较西方国家低;UC病程大于10年、全结肠炎以及活检发现有不典型增生是发生结肠癌的高危因素,定期内镜随访以及5-ASA和激素治疗是UC患者防止发生结直肠癌的保护因素。     

IL-6在溃疡性结肠炎大鼠结肠组织中的表达及意义

目的研究白介素-6(IL-6)在溃疡性结肠炎(ulcerative colitis,UC)大鼠模型结肠组织中的表达情况,探讨其在溃疡性结肠炎发病机制中的作用。 方法30只SD大鼠,随机抽取20只为模型组,另外10只为对照组。用"三硝基苯磺酸＋乙醇"法造模后,用Elisa法检测IL-6在模型组与对照组的结肠组织中的表达水平。 结果UC模型组表达水平明显高于对照组,差异有统计学意义。 结论UC大鼠结肠黏膜中IL-6的表达与UC的发生、发展密切相关。     

Met-RANTES干预实验性小鼠溃疡性结肠炎对MIP-3α及其受体CCR6的影响

目的:探讨MIP-3α及其受体CCR6在实验性小鼠溃疡性结肠炎(UC)发病中的作用,并分析Met-RANTES疗效机制.方法:用葡聚糖硫酸钠(DSS)诱导建立结肠炎小鼠模型,观察Met-RANTES对小鼠结肠炎病活动指数(DAI)、大体形态评分(GMS)、结肠组织学病理评分(HPS)的影响:并通过RT-PCR检测其对小鼠结肠组织MIP-3α、CCR6mRNA的表达变化及Western blot和免疫组织化学方法检测其小鼠结肠组织MIP-3α、CCR6的蛋白表达变化.结果:DAI、GMS和HPS在DSS模型组和生理盐水治疗组中高于空白对照组,MIP-3α和CCR6在小鼠溃疡性结肠炎中表达上调,在小鼠空白对照组中不表达或弱阳性表达,差异有统计学意义(P<0.01):与DSS模型组和生理盐水治疗组相比,Met-RANTES治疗组小鼠DAI、GMS和HPS降低,MIP-3α和CCR6表达下调(mRNA:0.21±0.08 vs 1.09±0.08.1.08±0.07;0.25±0.08 vs 1.11±0.07,1.05±0.08,P<0.01:蛋白:0.28±0.08 vs 0.98±0.07,1.05±0.06;0.25±0.07 vs 1.19±0.07.1.15±0.06.P<0.01):生理盐水治疗组小鼠DAI、GMS和HPS 以及MIP-3α和CCR6表达与DSS模型组相比表达无明显差异(P>0.05).结论:MIP-3α与CCR6参与了小鼠UC的发生、发展;Met-RANTES能下调MIP-3α及CCR6的表达,并能减轻炎症损伤;针对MIP-3α或CCR6的靶向治疗可能是UC一种有效的治疗方法.     

Pim-1、C-myc在溃疡性结肠炎病灶组织中的表达及其临床意义

[目的]观察Pim-1、C-myc在溃疡性结肠炎(UC)病灶组织中的表达,并探讨其临床意义.[方法]84例UC患者根据相关诊断标准分为缓解期组(32例)和活动期组(52例),活动期组根据Truelove-Witts标准分为轻度亚组(15例)、中度亚组(17例)和重度亚组(20例),同期选择30例单纯结肠息肉患者作为对照...     

缺血性结肠炎与溃疡性结肠炎临床表现及内镜特点的对比分析

目的 比较缺血性结肠炎(IC)与溃疡性结肠炎(UC)临床及内镜表现的差异,研究对两者的鉴别以利对其的诊断和治疗.方法 回顾分析2007年1月～2010年8月诊断为IC 30例和UC 40例患者的资料,重点分析两者在年龄分布、性别构成、病程、基础疾患、临床和内镜表现及病理诊断的异同点.结果 IC组和UC组在年龄分布、病...     

炎症因子TNF-α、IL-6和IL-4在溃疡性结肠炎中的表达及临床意义

目的探讨炎症因子肿瘤坏死因子-α(tumor necrosis factors-α,TNF-α)、白介素-6(IL-6)和白介素-4(IL-4)在溃疡性结肠炎(ulcerative colitis,UC)中的表达水平及临床意义。方法利用葡聚糖硫酸钠盐(dextran sodium sulfate,DSS)诱导C57BL/6小鼠,构建UC小鼠模型,病理学鉴定结肠炎症组织及正常组织,并采用实时荧光定量PCR(RT-PCR)方法检测不同炎症组织中TNF-α、IL-6和IL-4的mRNA水平。临床上,采用酶联免疫吸附试验(ELISA)方法检测62例UC患者及26名正常对照者血清中TNF-α、IL-6和IL-4的水平,分析炎症因子与结肠炎病变的相关性。结果 UC动物模型中,结肠炎症组织TNF-α、IL-6的mRNA表达水平明显高于正常组织(P0.05),而IL-4 mRNA表达水平明显低于正常组织(P0.01)。UC活动期患者血清TNF-α、IL-6水平明显高于正常对照组和UC缓解组(P0.05),且与结肠炎严重程度呈正相关;而IL-4水平明显低于对照组和UC缓解组(P0.05),且与UC严重程度呈负相关。结论促炎因子TNF-α、IL-6和抑炎因子IL-4的表达失衡与UC的病情进展相关,对UC的诊断和临床评估具有重要意义。     

CD44v3和CD44v6在溃疡性结肠炎与其他类型结肠炎中的表达

目的比较CD44v3和CD44v6在溃疡性结肠炎(UC)与对照组(包括感染性结肠炎、阿米巴痢疾、血吸虫性结肠炎及克罗恩病等其他类型结肠炎)中表达的差异.方法免疫组化SP法检测两组患者结肠粘膜CD44v3和CD44v6的表达.结果 UC组患者CD44v3和CD44v6表达阳性率分别为68.8%和56.3%,与对照组比较有显著性增高(P<0.05).UC组与感染性结肠炎、阿米巴痢疾、血吸虫性结肠炎病及克罗恩病分别比较差异仍有显著性(P<0.05).结论 CD44v3和CD44v6的检测有助于鉴别UC和感染性结肠炎等其他类型结肠炎.     

TNF-α、IL-13在溃疡性结肠炎中的表达及临床意义

目的检测溃疡性结肠炎患者血清中TNF-α、IL-13表达情况,探讨其在溃疡性结肠炎发病过程中所发挥的作用及临床意义。 方法收集来源为溃疡性结肠炎患者(UC组)30例及正常人(对照组)30例的外周静脉血,采用ELISA法检测两组血清TNF-α、IL-13的表达情况。 结果UC组血清水平明显高于对照组,差异有统计学意义(P<0.05);UC组患者IL-13的水平低于对照组,差异有统计学意义(P<0.05)。 结论UC组患者血清TNF-α、IL-13水平变化,作为反映溃疡性结肠炎患者结肠炎病症损害程度的灵敏的指标,对于判断溃疡性结肠炎病情变化具有临床意义。     

SSTR亚型在活动性溃疡性结肠炎中的表达及临床意义

目的 探讨生长抑素受体(SSTR)2、5亚型在溃疡性结肠炎(UC)活动期中的表达,为临床应用生长抑素(SS)及其类似物诊断治疗UC提供依据.方法 采用免疫组化法检测30例活动期UC患者(结肠炎组)结肠黏膜标本及26例体检者(对照组)结肠黏膜标本的SSTR2、SSTR5亚型蛋白的表达.结果 SSTR2、SSTR5亚型表达主要定位于结肠黏膜的上皮细胞、纤维细胞、淋巴细胞和小血管内皮细胞的细胞质中,二者在结肠炎组表达阳性率分别为93%、90%,对照组分别为69.2%、61.3%.便血明显组SSTR2、SSTR5表达阳性率均为100%,便血不明显组表达阳性率均为83.3%.活动期UC患者结肠黏膜SSTR2、SSTR5表达均上调.结论 结肠黏膜SSTR改变提示SS在UC发生发展中可能起重要作用.     

缺血性结肠炎与溃疡性结肠炎的对比分析

目的:研究缺血性结肠炎(ischemic colitis,IC)与溃疡性结肠炎(ulcerative colitis,UC)临床及组织病理学的差异,有助两者的鉴别诊断,利于临床治疗.方法:收集20例IC和30例UC患者,对其临床及组织病理学等资料进行对比分析.结果:IC组发病时间[(5±7)d]明显较UC组发病时间[(953±1354)d]短.IC组中65%的患者伴有高血压、冠状动脉性心脏病、心房颤动、房性早搏、腹部手术史等疾病史中的一项或几项,明显高于UC组的20%;IC组以急性发病、腹痛(85%)、血便(60%)及腹泻(50%)多见,而UC且以腹痛(83%)、腹泻(63%)、黏液脓血便(57%)及里急后重(20%)为主要临床表现;在内镜表现方面,IC多以沿肠系膜侧分布的纵形溃疡为主(60%),且病变多仅累及肠腔的1/4～1/2周(80%),呈节段性分布(60%),与邻近正常黏膜分界清楚(75%),而UC则以弥漫性地图状溃疡为主(43%),病变多累及肠腔全周(90%),炎性息肉明显多见(37%).在组织病理学方面,血管扩张充血(90%)、间质严重水肿(95%)在IC中多见,血管壁增厚(50%)是其特征性表现,隐窝脓肿(47%)则在UC中多见.两组以上差异均有统计学意义(P<0.05).结论:组织病理学特点、肠镜下表现以及患者临床特征的差异,为IC和UC的鉴别提供了有力依据.     

溃疡性结肠炎相关结直肠癌临床特点及癌变相关蛋白的表达

目的 探讨溃疡性结肠炎(UC)相关结直肠癌的临床特点及其癌变的可能机制.方法 收集北京协和医院1984年至2008年6例UC相关性结直肠癌,分析其发病情况、临床表现、病理类型、治疗及预后特点,免疫组化检测组织标本中结肠腺瘤性息肉蛋白(APC蛋白)、β-连环蛋白、p53蛋白和Wnt1蛋白表达的情况.结果 UC的癌变率为1.1%(6/534),女性多见(5/6),平均病程14.3年.临床均呈现典型的UC表现,病变常累及全结肠(5/6),均无原发性硬化性胆管炎.其中直肠癌4例、降结肠癌2例,病理类型以腺癌为主,预后较差.APC蛋白、β-连环蛋白、p53蛋白和wnt1蛋白表达的阳性率分别为6/6、6/6、5/6和6/6.结论 临床对病变累及全结肠、病程长的UC患者,应注意防止结直肠癌的发生,其癌变过程可能有多途径参与.     

不同月龄大鼠大脑中低密度脂蛋白受体相关蛋白的表达

目的　探讨不同月龄大鼠大脑额叶、海马、纹状体低密度脂蛋白受体相关蛋白 (LRP 1)表达的变化。方法　雄性SD大鼠 15只 ,流式细胞技术检测并计算 1,3,10月龄大鼠大脑额叶、海马、纹状体匀浆单细胞悬液LRP 1表达的平均荧光指数 ;免疫组织化学技术测定大脑海马CA1区神经细胞、微血管LRP 1表达 ,并应用MIAS图像分析系统进行平均吸光度测定。结果　流式细胞研究显示 ,大鼠海马 1、3月龄LRP 1表达强度均显著高于 10月龄大鼠 ;而额叶及纹状体各月龄组间差异无显著性意义。 1、3月龄大鼠海马区LRP 1表达强度均显著高于额叶及纹状体。免疫组织化学结果显示 ,LRP 1在海马CA1区微血管、神经细胞均有表达。随着月龄的增加 ,LRP 1在微血管的表达显著下降 ,而在海马CA1区神经细胞的表达各月龄组差异无显著性意义。结论　随着月龄的增加 ,海马区LRP 1的表达有下降趋势 ,尤其是海马CA1区微血管LRP 1的表达显著下降。     

溃疡性结肠炎相关性大肠癌P53、K-ras及hMSH2蛋白表达的研究

目的 探讨溃疡性结肠炎相关性大肠癌组织中P53、K-ras及hMSH2蛋白表达。方法 以溃疡性结肠炎伴不典型增生(UD)和溃疡性结肠炎相关性大肠癌(UCACRC)组织为实验组，溃疡性结肠炎(UC)和散发性大肠癌(SCRC)组织为对照组，应用免疫组化法检测组织中P53、K-ras、hMSH2蛋白的表达状况；聚合酶链式反应一单链构象多态性分析法(PCR-SSCP)检测组织中的微卫星不稳定性(MSI)状态(6个位点)，并进行统计学分析。结果 P53蛋白过表达的阳性率在UC(1／25例)与UD(3／7例)组间，UC与UCACRC(4／8例)组间差异均有统计学意义(P＜0．05，P＜0．01)，UCACRC与SCRC(17／30例)组间差异无统计学意义(P＞0．05)；突变型K-ras表达的阳性率在UC(4／25例)与UD(4／7例)组间，UC与UCACRC(7／8例)组间差异均有统计学意义(P＜0．05，P＜0．01)，UCACRC与SCRC(24／30例)组间差异无统计学意义(P＞0．05)；hMSH2蛋白缺失率在UC(2／25例)与UD(0／7例)组间、UD与UCACRC(4／8例)组间、UCACRC与SCRC(13／30例)组间差异均无统计学意义(P＞0．05)。MSI阳性率在UC(0／25例)与UD(3／7例)组间差异有统计学意义(P＜0．01)，在UD与UCACRC(2／8例)组间、UCACRC与SCRC(7／30例)组间差异无统计学意义(P＞0．05)。结论 P53、K-ras基因突变、MSI在UCACRC的发生发展过程中可能是一早期事件。UCACRC中MSI与hMSH2蛋白的缺失可能无关。     

Significance of glucocorticoid receptor expression in colonic mucosal cells of patients with ulcerative colitis

AIM: Glucocorticoid (GC) resistant ulcerative colitis (UC) remains a serious disease and is difficult to manage. Although the molecular basis of GC insensitivity is still unknown, GC receptors (GRAAA and GRp) may play an important role in it. This study was aimed to investigate the relationship between the expression of GRa and GRp in colonic mucosal cells of patients with UC, the efficacy of GC therapy and the intensity of inflammation. METHODS: Twenty-five cases of UC were classified into: GC sensitive (n = 16) and GC resistant (n - 9) cases. Patients consisted of mild (n = 6), moderate (n = 8) and severe (n = 11) cases. GRa and GRp expression in colonic mucosal specimens were investigated by immunohistochemistry, and compared between GC resistant and sensitive groups, and also among various degrees of inflammation. RESULTS: All cases were positive for GRa and GRp expression. Both positive association between GRa expression and the response of UC to GC and strong negative association between GRp expression and the response of UC to GC were identified. There was no significant association between GRa/GRp expression and the degree of inflammation of UC. CONCLUSION: These findings suggest that both GRa and GRp may play an important role in the action of GC, and that GRp functions as a dominant negative inhibitor of GRa. Expression of GRa and GRp in colonic mucosal cells of patients with UC may serve as predictors of glucocorticoid response, but can not function as markers of inflammatory intensity.     

Up-regulation of mitochondrial chaperone TRAP1 in ulcerative colitis associated colorectal cancer

AIM:To characterize tumor necrosis factor receptorassociated protein 1(TRAP1)expression in the progression of ulcerative colitis(UC)-associated colorectal cancer.METHODS:Chronic UC is an inflammatory bowel disease that predisposes to colorectal cancer.Immunohistochemical analysis was used to evaluate TRAP1expression on tissue microarrays containing colonic tissues from 42 UC progressors(patients with cancer or dysplasia)and 38 non-progressors(dysplasia/cancer free patients).Statistical analyses of the TRAP1immunohistochemistry staining were performed using Graph Pad Prism.Differences in the TRAP1 level between non-progressors and progressors were tested for statistical significance using the Mann-Whitney test.Receiver operating characteristic curve method was used to quantify marker performance in distinguishing diseased cases from controls.RESULTS:TRAP1 was up-regulated in the colon tissues from UC progressors,but not in the colon tissues from UC non-progressors.Moreover,up-regulation of TRAP1 preceded the neoplastic changes:it was present in both the dysplastic and non-dysplastic tissues of UC progressors.When TRAP1 staining in rectal tissue was used as a diagnostic marker,it could distinguish progressors from non-progressors with 59%sensitivity and 80%specificity.Our study further showed that the increase of TRAP1 expression positively correlated with the degree of inflammation in the colorectal cancer tissues,which could be related to the increased oxidation present in the colonic mucosa from UC progressors.We then investigated the cellular proteome changes underlying oxidative stress,and found that oxidative stress could induce up-regulation of TRAP1 along with several other negative modulators of apoptosis.CONCLUSION:These results suggest that oxidative stress in long standing UC could lead to the increase of cytoprotective protein TRAP1,which in turn could promote cancer progression by preventing or protecting the oxidative damaged epithelial cells from undergoing apoptosis.TRAP1 could be a potential diagnostic marker for UC associated colorectal cancer.     

3100例溃疡性结肠炎住院病例回顾分析

目的 回顾性调查住院溃疡性结肠炎（UC）患者,探讨近年住院病例UC的特点.方法全国选取11个地区23家医院,调查1990-2003年期间住院符合UC诊断的3100例患者的诊断、治疗、逐年住院情况和同期内镜检出率,并粗略估计患病率.结果 近14年UC住院例数和内镜检出例数均有逐年增加的趋势.UC粗略患病率为11.62/105.住院UC患者以轻度（35.4%）和中度（42.9%）为主.临床类型以慢性复发型（46%）和初发型（34.6%）为主,暴发型仅占2.4%.主要症状有腹泻（75.8%）、腹痛（67.3%）、血便（63.3%）等.肠外表现（14.0%）和并发症（9.6%）少见.辅助确诊手段主要为结肠镜（95.0%）及病理（62.3%）.UC治疗上以氨基水杨酸类（66.8%）和类固醇激素（42.8%）为主.仅2.1%患者应用免疫抑制剂.单纯内科治疗总有效率达93.6%,手术率3%,死亡19例（0.6%）.结论 UC近年有逐渐增加的趋势,以轻中度为主,疾病类型以慢性复发型和初发型为主,暴发型少见.肠外表现及并发症较少.国内轻中度患者治疗以柳氮磺胺吡啶及类固醇激素为主,手术率、死亡率及癌变率均较国外低.     

Diagnostic accuracy of confocal laser endomicroscopy in diagnosing dysplasia in patients affected by long-standing ulcerative colitis

AIM:To evaluate the diagnostic accuracy of confocal laser endomicroscopy(CLE) for the detection of dysplasia in long-standing ulcerative colitis(UC).METHODS:We prospectively performed a surveillance colonoscopy in 51 patients affected by long-standing UC.Also,in the presence of macroscopic areas with suspected dysplasia,both targeted contrasted indigo carmine endoscopic assessment and probe-based CLE were performed.Colic mucosal biopsies and histology,utilised as the gold standard,were assessed randomly and on visible lesions,in accordance with current guidelines.RESULTS:Fourteen of the 51 patients(27%) showed macroscopic mucosal alterations with the suspected presence of dysplasia,needing chromoendoscopic and CLE evaluation.In 5 macroscopically suspected cases,the presence of dysplasia was confirmed by histology(3 flat dysplasia;2 DALMs).No dysplasia/cancer was found on any of the outstanding random biopsies.The diagnostic accuracy of CLE for the detection of dysplasia compared to standard histology was sensitivity 100%,specificity 90%,positive predictive value 83% and negative predictive value 100%.CONCLUSION:CLE is an accurate tool for the detection of dysplasia in long-standing UC and shows optimal values of sensitivity and negative predictivity.The scheduled combined application of chromoendoscopy and CLE could maximize the endoscopic diagnostic accuracy for diagnosis of dysplasia in UC patients,thus limiting the need for biopsies.     

Ileal lesions in patients with ulcerative colitis after ileo-rectal anastomosis：Relationship with colonic metaplasia

AIM：To assess whether in ulcerative colitis （UC） patients with ileo-rectal anastomosis （IRA）, ileal lesions may develop in the neo-terminal-ileum and their possible relation with phenotypic changes towards colonic epithelium. METHODS： A total of 19 patients with IRA under regular follow up were enrolled, including 11 UC and 8 controls （6 Crohn’s disease, CD; 1 familial adenomatous polyposis, FAP; 1 colon cancer, colon K）. Ileal lesions were identifi ed by ileoscopy with biopsies taken from the ileum （involved and uninvolved） and from the rectal stump. Staining included HE and immunohistochemistry using monoclonal antibodies against colonic epithelial protein CEP （Das-1） and human tropomyosin isoform 5, hTM5 （CG3）. Possible relation between development of colonic metaplasia and ileal lesions was investigated.RESULTS： Stenosing adenocarcinoma of the rectal stump was detected in 1 UC patient. The neo-terminal ileum was therefore investigated in 10/11 UC patients. Ileal ulcers were detected in 7/10 UC, associated with colonic metaplasia in 4/7 （57.1%） and Das-1 and CG3 reactivity in 3/4 UC. In controls, recurrence occurred in 4/6 CD, associated with colonic metaplasia in 3/4 and reactivity with Das-1 and CG3 in 2/3. CONCLUSION： Present fi ndings suggest that in UC, ileal lesions associated with changes towards colonic epithelium may develop also after IRA. Changes of the ileal content after colectomy may contribute to the development of colonic metaplasia, leading to ileal lesions both in the pouch and in the neo-terminal ileum after IRA.