溃疡性结肠炎患者手术治疗预测因素分析

手术是溃疡性结肠炎（UC）内科治疗无效或发生严重并发症者的治疗选择.目的：分析UC患者行手术治疗的可能预测因素.方法：纳入1998年8月～2009年9月北京协和医院住院UC患者312例,其中34例接受手术治疗,278例接受非手术治疗,回顾性分析、比较两组患者的各类临床资料.结果：住院UC患者手术率为10.9%,手术死亡率为5.9%,重度UC患者手术率为23.9%.手术组13例患者为激素抵抗,8例为激素依赖,9例发生严重并发症,4例激素治疗有效者主动要求手术治疗.手术组平均住院次数显著多于非手术组（P〈0.05）,术前Hb、白蛋白显著低于非手术组（P〈0.05）,CRP显著高于非手术组（P〈0.05）,重度结肠炎、全结肠炎患者比例显著高于非手术组（P〈0.05）.结论：疾病严重程度高、病变范围广、对激素抵抗的UC患者,手术需求增加.     

溃疡性结肠炎患者P-选择素和血小板参数分析

背景：研究发现凝血机制活化在炎症性肠病（IBD）的进展过程中起重要作用。P-选择素（CD62P）参与介导凝血和炎症反应时中性粒细胞和单核细胞与活化的血小板或内皮细胞的黏附。目的：探讨血小板活化标记物P．选择素以及血小板计数（PLT）、平均血小板体积（MPV）用于溃疡性结肠炎（UC）疾病活动度评估的价值。方法：纳入65例活动期UC患者、31例缓解期UC患者和60例健康对照者。流式细胞术测定外周血P-选择素阳性率,血细胞分析仪测定PLT、MPV,分析三者与UC活动度的相关性。结果：UC患者外周血CD62P阳性率、PLT显著高于对照组（P〈0．01）,MPV显著低于对照组（P〈0．01）;活动期UC患者三项指标的变化均较缓解期UC患者更为显著,组间差异有统计学意义（P〈0．05）。外周血CD62P、PLT与UC活动度呈正相关（P〈0．05）,MPV与UC活动度呈负相关（P〈0．05）。结论：UC患者的机体处于高凝状态。P-选择素、PLT、MPV能反映UC疾病活动度,对病情评估和治疗方案的制定有一定参考价值。     

核周型抗中性粒细胞胞质抗体在溃疡性结肠炎患者中的意义

背景:核周型抗中性粒细胞胞质抗体(pANCA)阳性是诊断溃疡性结肠炎(UC)的特异性指标,但与疾病严重程度和疾病分期的相关性有待进一步研究。目的:探讨pANCA在UC患者中的意义。方法:选取2008年1月~2012年9月北京军区总医院125例UC患者,采用间接免疫荧光法检测血清pANCA,回顾性分析其与临床特征的相关性。结果:UC患者血清pANCA阳性率显著高于健康对照组(51.2%对0,P0.05)。活动期UC血清pANCA阳性率显著高于缓解期(57.9%对11.1%,P0.05),而不同临床类型、严重程度、病变范围之间无明显差异(P0.05)。结论:UC患者血清pANCA阳性率可能与疾病分期有关,与临床类型、严重程度、病变范围等无关。     

钙卫蛋白、乳铁蛋白在溃疡性结肠炎患者中表达的临床研究

背景:溃疡性结肠炎(UC)是慢性反复发作的肠道炎性疾病,评估疾病活动度对其疗效判断非常重要,实验室标记物尤其是粪便标记物可很好地反映疾病活动度。目的:探讨钙卫蛋白(Cal)、乳铁蛋白(Lf)在UC患者结肠黏膜和粪便中表达的临床意义。方法:选取1998年1月～2008年1月安徽医科大学第一附属医院收治的具备完整结肠镜或手术病理检查结果的UC患者120例。以临床活动度指数(CAI)评分进行疾病分期,以免疫组化SP法检测结肠黏膜Cal、Lf表达,以ELISA法检测粪便Cal、Lf含量。结果:活动期UC患者结肠黏膜中均表达Cal、Lf,缓解期无或仅弱表达。活动期UC患者粪便Cal、Lf含量显著高于缓解期(P0.01)。UC患者结肠黏膜Cal和Lf表达以及粪便Cal和Lf含量均与CAI评分呈正相关(P=0.000)。粪便Cal和Lf含量与结肠黏膜Cal和Lf表达亦呈正相关(r=0.588,P=0.000;r=0.519,P=0.000),且判断UC活动性的敏感性和特异性均较高。结论:UC患者结肠黏膜Cal、Lf表达可反映临床严重度,粪便Cal、Lf含量与UC活动性显著相关。     

溃疡性结肠炎患者血浆和肠黏膜组织中神经降压素的含量及其临床意义

背景:在新疆自治区,溃疡性结肠炎(UC)是一种常见病、多发病,其病因和发病机制至今尚不清楚,临床治疗效果亦不令人满意。目的:测定UC患者和对照者血浆和肠黏膜组织中神经降压素(NT)的含量,探讨NT含量与UC病因之间的关系。方法:采用放射免疫法测定31例UC患者(其中17例为少数民族)和38例对照者治疗前后血浆和肠黏膜组织中NT的含量。结果:UC患者血浆和肠黏膜组织中的NT含量较对照者显著降低(P<0.01);UC患者治疗后的血浆NT含量与治疗前相比无显著差异;少数民族UC患者的血浆NT含量与汉族患者相比无显著差异。结论:血浆和肠黏膜组织中NT含量降低可能与UC的发病有关。NT含量降低不是少数民族UC高发的直接原因。     

活动期溃疡性结肠炎患者血清vaspin水平及其临床意义

脂肪细胞因子与机体内能量稳定相关,并介导多种免疫应答和炎症反应。内脏脂肪特异性丝氨酸蛋白酶抑制剂vaspin是近年发现的一种与炎症反应有关的脂肪细胞因子。目的:检测活动期溃疡性结肠炎(UC)患者的血清vaspin水平并探讨其临床意义。方法:选取2008年1月~2013年4月苏州市立医院收治的150例活动期UC患者,以150名健康体检者作为正常对照组。采用ELISA法检测血清vaspin水平,并分析其与UC临床特征的相关性。结果:UC患者血清vaspin水平显著高于正常对照者[(1.86±0.38)μg/L对(0.96±0.43)μg/L,P0.01],并与血清CRP水平和疾病活动指数呈显著正相关(r=0.628,P0.01;r=0.514,P0.05),与血清ESR水平和病变部位无关(r=0.098,P0.05;r=0.124,P0.0)5)。结论:Vaspin可能在UC发生、发展的病理生理机制中发挥重要作用。     

Detection of Ki-ras Mutations by PCR and Differential Hybridization and of p53 Mutations by SSCP Analysis in Endoscopically Obtained Lavage Solution from Patients with Long-Standing Ulcerative Colitis

Objectives : The goal of this study was the early detection of malignant transformation in patients with longstanding ulcerative colitis; therefore, mutations of the Ki-ras and p53 gene were analyzed in lavage solution and biopsies obtained at surveillance colonoscopy. Methods : DNA was isolated from 14 patients (nine female, five male) with a history of pancolitis for more than 10 yr. Exon 1 of the Ki-ras gene and exons 5–8 of the p53 gene were amplified via polymerase chain reaction. Mutations of the p53 gene were detected via single-strand conformation polymorphism analysis; point mutations of the Ki-ras gene were hybridized on dot blots with oligonucleotides marked with digoxigenin. Results : Wild-type Ki-ras and wild-type p53 were detected in all cases of ulcerative colitis and in four of seven control patients. In two ulcerative colitis patients, a mutation was found in the Ki-ras gene (Gly → Asp 12 and Gly → Val 12), and in one patient, a mutation in exon 5 of the p53 gene. Mutations were found only in the lavage fluid, whereas random biopsies were negative. Conclusions : From colonic lavage fluid, it is possible to extract DNA of sufficient quantity and quality for polymerase chain reaction-based amplification and subsequent analysis via single-strand conformation polymorphism or hybridization. Mutations were found in three of 14 patients with long-standing ulcerative colitis but were not found in controls. The method may he useful for the screening of such patients.     

A High Degree of Aneuploidy,Loss of p53 Gene,and Low Soluble p53 Protein Serum Levels Are Detected in Ulcerative Colitis Patients

PURPOSE The causes for the increased risk of colorectal cancer associated with ulcerative colitis have not been fully defined. Colonic tissue of ulcerative colitis patients was examined for changes in chromosome-17-centromere copy number, loss of the p53 gene, and alterations in serum levels of the 53-kDa protein. This study was performed under the assumption that these molecular events correlate with ulcerative colitis status and duration.METHODS Ulcerative colitis patients (n = 42) and healthy controls (n = 37) participated in the study. All participants were histopathologically and medically diagnosed. The stage of ulcerative colitis patients was stratified according to increasing risk factors for the development of colorectal cancer: left-sided colitis, pancolitis, sclerosing cholangitis, and dysplasia-associated lesions or masses. Changes in centromere number of chromosome 17 alone or in association with changes in copy number of the p53 gene were analyzed in colon tissue biopsies by fluorescence in situ hybridization. Serum p53 level was determined in blood samples by immunoprecipitation followed by separation using high-pressure liquid chromatography.RESULTS Changes in chromosome 17 and p53 copy number and lower levels of serum p53 protein in ulcerative colitis patients directly correlated with colorectal cancer risk factors. All values significantly differed from controls. Significant direct correlations were obtained for ulcerative colitis disease duration, levels of p53 in the serum, and extent of aneuploidy.CONCLUSIONS We demonstrate that in the colonic mucosa of ulcerative colitis patients, high levels of genomic instability, changes in p53 gene copy number, and lower levels of p53 in the serum directly correlate with the extent of disease duration and increased risk factors for colorectal cancer. Any of the measurements described herein can provide an acceptable prognostic tool in the assessment of colorectal cancer risk in ulcerative colitis patients.     

Acute CMV-Colitis in a Patient with a History of Ulcerative Colitis

A symptomatic cytomegalovirus (CMV) infection usually occurs in patients with debilitating diseases, immunosuppression, transplantations and acquired immunodeficiency syndrome (AIDS). Gastrointestinal infections with CMV, especially colitis, are usually found in immunocompromised patients and rarely affect immunocompetent subjects. Here we report the case of a young female patient with a history of ulcerative colitis (UC) who presented with an acute attack of colitis caused by CMV infection. This was documented by the presence of CMV early antigen, antibodies and evidence of CMV in the colonic mucosa. After combined anti-inflammatory and antiviral treatment the patient recovered completely. As most attention is given to CMV-pathogeneity in immunocompromised patients, here we discuss the relationship to inflammatory bowel diseases.     

Twenty Years' Colonoscopic Surveillance of Patients with Ulcerative Colitis Detection of Dysplastic and Malignant Transformation

Background: Endoscopic cancer surveillance in patients with ulcerative colitis has been performed for almost 3 decades. There is still no consensus on its clinical value. Methods: This study evaluates a 20-year prospective study of 143 patients with extensive ulcerative colitis and a disease duration exceeding 10 years. Colonoscopy with double biopsy specimens from nine locations of the colon was performed every 2nd year. Biopsy specimens showing dysplasia were reviewed at the end of the study. Results: Through the surveillance dysplasia/cancer was detected in 55 patients; 7 of these patients had carcinomas, and 2 were in a possibly curable stage (Dukes A). The predictive value of low-grade dysplasia for either high-grade dysplasia or cancer was 41%. Conclusions: Although impaired by limiting factors, colonoscopic surveillance of chronic extensive colitis may identify patients with dysplasia and thereby prevent malignant transformation.     

溃疡性结肠炎患者炎症黏膜中IL-6、L-23的表达及其临床意义

研究显示促炎细胞因子在溃疡性结肠炎（UC）的发病机制中起重要作用。目的：探讨UC患者炎症黏膜中白细胞介素．6（IL-6）、IL．23的表达情况及其临床意义。方法：选取42例UC患者（轻、中、重度活动期分别为9例、10例和13例．缓解期10例）于内镜下取结直肠炎症黏膜活检标本．另取18名健康志愿者的结肠黏膜作为正常对照。以免疫组化方法检测黏膜细胞因子IL-6、IL-23表达。结果：轻、中、重度活动期UC患者IL-6、IL-23表达量依次增高,组间两两比较差异均有统计学意义（P〈O．05）,且均显著高于缓解期患者和正常对照组（P〈0．05）;缓解期患者仅IL-23表达量显著高于正常对照组（P〈O．05）,IL-6表达量与正常对照组无明显差异。结论：IL-6和IL-23在UC的发生、发展中起重要作用．两者的黏膜表达水平可反映UC疾病活动度。     

活动期溃疡性结肠炎患者尿单核细胞趋化因子-1临床分析

背景：单核细胞趋化因子（MCP）-1在溃疡性结肠炎（UC）发病中起重要作用。目的：探讨活动期UC患者尿MCP-1的变化及其临床意义。方法：纳入50例活动期UC患者和25例正常对照者,以ELISA法检测所有入选者的尿MCP-1水平,并与UC患者的主要临床病理特征行相关性分析。结果：活动期UC患者尿MCP-1水平显著高于正常对照组[（33．24±16．84）pg／ml对（16．47±7．73）pg／ml,P〈0．05]。UC患者尿MCP-1水平与疾病严重程度、病变范围、营养风险相关（P〈0．05）,但与疾病临床类型、内镜分级不相关（P〉0．05）。结论：活动期UC患者尿MCP-1水平增高．且与UC疾病严重程度、病变范围和营养风险相关。     

Use of Infliximab as rescue therapy in acute severe Ulcerative Colitis with recent norovirus infection

Background and aimsNorovirus infection is a common cause of acute diarrhoeal illness and may occur in the setting of inflammatory bowel disease.MethodsA patient with an acute severe first presentation of Ulcerative Colitis failed to settle with intravenous steroids and rescue therapy was considered. The isolation of norovirus in his stool caused concern about aggravating the infection if immunosuppression ensued. Following a brief period of watchful waiting and a full discussion between physician, surgeon and patient, Infliximab was administered (5 mg/kg).ResultsThe patient responded well both clinically and biochemically.ConclusionsIn this case, Infliximab was a safe and efficacious intervention in a patient with acute Ulcerative Colitis and recent norovirus infection.     

溃疡性结肠炎中防御素、一氧化氮和丙二醛的表达

背景：溃疡性结肠炎（UC）是一种慢性非特异性肠道炎症性疾病，其病因尚不明确。近年来，防御素家族在先天免疫中的作用受到广泛关注。目的：研究UC患者结肠组织中中性粒细胞防御素人中性粒细胞肽（HNP）1-3与一氧化氮（NO）、丙二醛（MDA）的相关性，了解三者在UC发病中的作用。方法：以逆转录聚合酶链反应（RT—PCR）检测16例活动期UC患者结肠组织和10例正常结肠组织中HNP1-3mRNA的表达，分别以硝酸还原酶法和硫代巴比妥酸（TBA）显色法检测结肠组织NO和MDA水平。结果：UC患者结肠组织HNP1-3mRNA和NO、MDA的表达水平显著高于正常对照组（P〈0．01），其中UC受累黏膜又显著高于未受累黏膜（P〈0．01）。UC受累黏膜中HNP1-3mRNA与NO、MDA的表达具有显著相关性（rs^1=0．643，P〈0．01；rs^1=0．831，P〈0．01）。结论：HNP1-3可能参与了UC结肠组织的炎症损伤过程，NO和MDA可能与HNP1-3协同发挥作用。     

Oral Microemulsion Cyclosporine in the Treatment of Steroid-Refractory Attacks of Ulcerative and Indeterminate Colitis

Background: To assess the efficacy of oral microemulsion cyclosporine (CyA Neoral®) in the treatment of steroid-refractory attacks of ulcerative and indeterminate colitis. Methods: In this non-randomized study on the use of oral microemulsion cyclosporine in steroid refractory ulcerative colitis, we used CyA Neoral in 10 patients suffering from ulcerative colitis and in 1 patient suffering from indeterminate colitis with a steroid-refractory attack. The initial dose was 7-7.5 mg kg^-1 day^-1 adjusted to maintain whole blood cyclosporine levels between 250 and 350 ng/mL, as measured by RIA using monoclonal antibodies. Results: Nine patients presented a favourable response in a mean time of 3.6 days, that is, 81.8% of cases. One initial responder developed megacolon on the 11th day and another did not respond; surgical treatment was performed in both cases. The remaining nine patients, followed for a mean period of 14.6 months (2-36 months). Nine patients presented side effects, the most frequent being slight hand tremor with hypomagnesaemia, followed by hypertension, slight increase in creatinine and hirsutism. No one needed to withdraw from treatment, but the dose was lowered in three cases. Conclusions: Oral microemulsion cyclosporine is an effective drug in the initial management of patients suffering from a steroid-refractory attack of ulcerative and indeterminate colitis. Additional controlled studies with the new oral formulation are required to confirm these results.     

溃疡性结肠炎患者结肠黏膜转化生长因子-β1及其受体表达与临床病理因素的相关性

背景：转化生长因子（TGF）-β1是溃疡性结肠炎（UC）的一种重要抗炎因子,目前TGF-β1及其Ⅰ型受体（TGFβRⅠ）在UC中表达状况的研究仍较少。目的：探讨TGF-β1、TGFβRⅠ在UC结肠黏膜中的表达及其与临床病理因素的关系。方法：以免疫组化SABC法检测60例UC患者结肠黏膜中TGF-β1、TGFβRⅠ的表达,设16例正常结肠组织作为对照。分析TGF-β1、TGFβRⅠ的表达与病变范围和组织病理学分级的关系。结果：TGF-β1、TGFβRⅠ在UC中的表达显著强于正常对照组（P〈0.05）,且活动期显著强于缓解期（P〈0.05）。TGF-β1、TGFβRⅠ与组织病理学分级均呈正相关（rs分别为0.421和0.553,P〈0.05）,与病变范围均不相关（rs分别为-0.031和-0.037,P〉0.05）。结论：UC结肠黏膜中TGF-β1和TGFβRⅠ表达增强,与UC的发病机制密切相关,有可能成为反映UC疾病活动度的生物学指标。     

选择性白细胞分离法联合药物治疗对溃疡性结肠炎诱导缓解和维持治疗的荟萃分析

不同研究显示选择性白细胞分离法对溃疡性结肠炎（UC）的疗效差异很大.目的：系统性评价选择性白细胞分离法联合药物治疗对UC诱导缓解和维持治疗的作用.方法：检索PubMed、EMBASE、Cochrane Central Register of Controlled Trials、Science Citation Index和中文科技期刊数据库.纳入所有比较选择性白细胞分离法联合药物治疗与传统药物治疗对UC诱导缓解和维持治疗疗效的随机对照试验（RCTs）.采用RevMan 5.0软件分析两者的诱导缓解率、维持缓解率和不良反应发生率.结果：共9项RCTs、685例患者符合人选标准,7项评估诱导缓解率,2项评估维持缓解率.选择性白细胞分离法联合药物治疗组的诱导缓解率显著高于传统药物治疗组（40.7%对29.1%,OR值为2.19,P〈0.0001）,维持缓解率亦显著高于传统药物治疗组（70.4%对25.0%,OR值为8.14,P=0.002）.选择性白细胞分离法联合药物治疗组的轻中度不良反应发生率明显低于传统药物治疗组（44.7%对65.3%,OR值为0.16,P=0.003）.结论：与传统药物治疗相比,选择性白细胞分离法联合药物治疗能明显提高UC患者的诱导缓解率和维持缓解率,并能降低不良反应发生率.     

单核样髓源性抑制细胞在炎症性肠病中的表达及其临床意义

背景：近年来炎症性肠病（IBD）发病率呈上升趋势,其病理生理学机制复杂且仍未明确。目的：研究单核样髓源性抑制细胞（MDSCs）在IBD患者外周血单核细胞中的比例,分析单核样MDSCs与IBD活动性的关系,从而初步探讨单核样MDSCs在IBD中的作用机制。方法：纳入IBD患者60例,分为克罗恩病（CD）组（n=33）和溃疡性结肠炎（UC）组（n=27）,选取30名同期健康体检者作为正常对照组,采用流式细胞仪检测CD组、UC组、正常对照组患者外周血单核样MDSCs／单核细胞比例,分析单核样MDSCs与IBD患者WBC、PLT、ESR、CRP的相关性。结果：CD组和UC组外周血单核样MDSCs／单核细胞比例较正常对照组相比显著升高[（43．7±23．0）％、（49．1±27．2）％对（10．7±7．4）％]（P〈0．01）,CD组与UC组相比差异无统计学意义（P〉0．05）。活动期CD和UC组外周血单核样MDSCs／单核细胞比例均较缓解期组显著升高[（60．3±16．8）％、（66．3±17．6）％对（28．1±16．2）％、（19．9±9．0）％]（P〈0．01）。IBD患者外周血单核样MDSCs／单核细胞比例与WBC计数、PLT计数呈正相关（r=0．44,P=0．02;r=0．43,P=0．02）,与ESR、CRP不相关（r=0．33,P=0．08;r=0．30,P=0．12）。结论：IBD患者外周血单核样MDSCs比例明显升高,与IBD活动性密切相关。单核样MDSCs在IBD发病中具有重要作用。