间充质干细胞治疗克罗恩病肛瘘研究进展

克罗恩病(Crohn’s disease, CD)是一种累及全消化道的跳跃性全层炎症性肠病,肛瘘是CD常见的临床表现之一,临床发病率可达28%～43%。CD肛瘘的治疗需要结合患者的实际情况选择个体化的治疗方案,包括合适的药物种类和手术方法,目前并没有高成功率的金标准治疗方案,临床复发率较高。间充质干细胞(mesenchymal stem cell, MSC)是一种多能干细胞,具有自我更新和分化为多种类型细胞的能力,被广泛应用于再生医学领域,MSC疗法对于CD患者是一种富有前景的新选择。与传统治疗手段相比,MSC在诱导和维持瘘管闭合方面表现出更高的效率,具有很强的免疫调节作用和微创性,特别是对于瘘管复杂、常规治疗不耐受的患者。本文结合国内外最新研究报道,就MSC治疗CD肛瘘的研究进展进行综述。     

克罗恩病诊断和治疗要点

近年来克罗恩病（CD）的发病率在我国似有增高的趋势，其诊断和治疗均有一定难度，需临床医师有足够的认识。     

克罗恩病的诊断与鉴别诊断

本文简介了克罗恩病的诊断技术和方法,介绍了鉴别诊断的主要疾病和辨析要点,对于提高对本病的认识和诊断思维能力有很大帮助。     

肛周手术治疗克罗恩病肛瘘的有效性：一项网状Meta分析

目的 探讨在药物治疗基础上,FGI、AFP、MSC、MSC+FGI治疗克罗恩病肛瘘患者的疗效。方法 检索常用的中英文数据库筛选并纳入随机对照研究,采用ADDIS 1.16.6软件进行贝叶斯网状Meta分析比较各干预措施。结果 共纳入8篇随机对照研究,涉及510例克罗恩病肛瘘患者。结果显示：随访时间≤3个月时,MSC+FGI治疗组的肛瘘闭合率显著优于临床观察组(OR=0.02,95%CI:0.00～0.88)。在随访6个月、12个月亚组中,MSC、安慰剂、FGI、AFP、临床观察组组间在肛瘘闭合率方面均未见明显差异。Rank等级分析显示,MSC可能是各干预措施中的最佳干预手段。在肛周脓肿发生率中,各干预措施未见明显差异,Rank等级分析提示MSC+FGI发生肛周脓肿的可能性最小,其次是安慰剂、MSC。结论 FGI、 AFP、 MSC、MSC+FGI治疗克罗恩病肛瘘,肛瘘闭合率、肛周脓肿发生率均未见显著差异,但由于纳入文献及病例数量较少,结论有待验证。     

克罗恩病肛瘘研究进展

肛瘘是克罗恩病患者长期不良预后的预测因素,克罗恩病肛瘘（pfCD）严重影响患者的生命质量。pfCD的治疗提倡手术与药物治疗相结合,生物制剂尤其是TNF-α抑制剂的出现,极大地改善了pfCD患者的预后。近年发现一些新型生物制剂、间充质干细胞等治疗方式有助于缓解病情,对于复杂性肛瘘,保留括约肌等术式可极大减少尿失禁等术后并发症,给pfCD患者带来新的希望。本文就pfCD的诊治进展作一综述。     

肠结核与克罗恩病的鉴别诊断

在诸多肠道炎症性病变中,肠结核和克罗恩病是两大重要的疾病,近年来两者的发病率均呈上升趋势。肠结核与克罗恩病的临床、影像学、内镜和病理学表现均十分相似。肺结核的存在和结核杆菌的发现有利于肠结核的诊断,但克罗恩病误诊为肠结核的概率仍很高。本文就这两种疾病的诊断和鉴别诊断作一综述。 一、诊断标准 1.肠结核:符合以下任何一项标准即可确诊:①肠壁或肠系膜淋巴结找到干酪样坏死性肉芽肿;②病变组织病理检查找到结核杆菌;③病变处取材培养结核杆菌阳性;④病变处取材动物接种有结核改变。一般病例根据临床症状、体征以及X线检查有典型结核改变、肠外找到结核灶和抗痨试验治疗6周病情有改善,便可作出临床诊断。     

克罗恩病临床特征以及诊断和治疗选择

目的 分析克罗恩病的临床表现、误诊原因和诊疗方法,以促进与提高对本病的认识及诊治效果。方法 对近期诊治31例患者的发病情况、临床表现、内镜及实验室检查结果,结合文献报道,分析本病的临床特征与诊治方案。结果 患者以表中年为主,女略多于男。病变侵犯胃肠道任一部位,呈节段性分布,常同时侵犯多个部位,以结肠及小肠为主;腹痛与腹泻为主要的肠道症状;但尚有低热、消瘦、贫血及皮肤、关节与肛周疾病等多系统症状。内镜可见跳跃式分布的黏膜充血、水肿、溃疡、息肉、狭窄或铺路石征等破坏与增殖病变并存的特点,诊断正确率为62.9%。活检肉芽肿检出率为30.8%。B超可探查出肠道并发症。误衣原因：对本病认识不足;肠道病变多部位性,致使临床症状多样化;过于强调病理学检查及肉芽肿的诊断意义。口服泼尼松对轻－中型患者诱导缓解较氨基水杨酸盐类更迅速;免疫制剂为二线药物,个体间疗效不一;20例接受强化性营养支持治疗,具有辅助治疗作用。16例手术治疗收到较好疗效。结论 本病发病数明显增多,临床表现缺乏特异性;内镜联合活检,加强临床与病理医师沟通是及时和正确诊断的关键。治疗宜个体化选择方案,手术具有积极意义。     

克罗恩病的诊治进展

本文简介了克罗恩病的流行病学、发病因素和临床表现,评析了各种诊断方法和方法的选择,重点介绍了各种药物治疗的进展,对克罗恩病的临床诊治很有帮助。     

克罗恩病诊断状况的调查研究

目的 以世界卫生组织(WHO)及中国克罗恩病诊断治疗共识意见为标准,调查分析上海交通大学医学院附属瑞金医院克罗恩病的诊断情况.方法 采用回顾性调查研究方式,分析1998年至2007年就诊的268例克罗恩病患者.根据WHO的克罗恩病诊断标准及我国2007年制定的克罗恩病共识意见.重新评价这些克罗恩病患者临床、内镜检查、影像学检查、病理检查的诊断符合情况;并分析临床医师对克罗恩病诊断能力是否有所提高.结果 符合我国拟诊标准的有236例,符合WHO疑诊标准的有20例.完全符合两种诊断规范的分别只有5例和10例.近年来内镜诊断水平较前有所提高.确诊必需的病理诊断能力较低,与最近几年相比.2004年之前的病理确诊率更高.结论 克罗恩病典型病变的病理学诊断率偏低.临床诊断克罗恩病的水平距离诊断共识意见的要求还有较大差距.     

克罗恩病20例临床分析

目的探讨克罗恩病的临床特点、诊断及治疗。方法对20例克罗恩病进行回顾性分析。结果多以腹痛、腹泻、消化道出血、长期发热、消瘦、腹块为临床表现，有的合并肠外表现，病变以回肠末端最多见，表现为肠管狭窄、僵硬，局部粘膜粗糙、充血水肿、糜烂，病变呈节段性改变，中间粘膜正常。病理有非干酪样肉芽肿形成或炎细胞浸润，累及肠壁全层，局部形成溃疡，有时可见裂隙。治疗缓解9例，好转5例，无效2例，手术复发3例。结论临床表现缺乏特异性，内镜、影像联合活检，加强临床与病理医师沟通是及时和正确诊断的关键。治疗宜个体化选择方案，以皮质类固醇及水杨酸为一线药物，手术具有积极意义，但容易复发。     

Diagnosis and treatment of perianal fistulas in Crohn disease.

Perianal fistulas occur in up to 43% of patients with Crohn disease. Diagnostic evaluation to determine the location and type of fistulas and the presence or absence of rectal inflammation is required. A combined medical and surgical approach to the management of such patients is the optimal treatment plan. Perianal abscesses must be drained. Superficial, low transsphincteric, and low intersphincteric fistulas are usually treated with fistulotomy and antibiotics. High transsphincteric, suprasphincteric, and extrasphincteric fistulas are usually treated with noncutting setons, antibiotics, and azathioprine or 6-mercaptopurine and, in many cases, infliximab.     

Clinical course of perianal fistulas in Crohn's disease.

The clinical course of perianal fistulas and associated abscesses was evaluated prospectively in 90 patients with Crohn's disease. Fistula type, rectal disease, faecal diversion, and immunosuppression were examined as prognostic indicators for fistula healing and recurrence. Median follow up was 22 months. The outcome was evaluated with life table analysis. Prognostic factors were analysed by multiple regression. Inactivation was achieved in all patients. The risks of recurrent fistula activity were 48% at one year and 59% at two years. Fistulas were healed in 51% after two years but reopened in 44% within 18 months of healing. Faecal diversion and absence of rectal disease decreased recurrence rates (p = 0.019/0.04) and increased healing rates (p = 0.005/0.017). The outcome in patients with trans-sphincteric fistulas was better than that in those with ischiorectal fistulas but worse than in patients with subcutaneous fistulas (p = 0.015 for healing; p = 0.007 for recurrent fistula activity). After initial treatment about 20% of the patients were symptomatic and about 10% had painful events per six month period. Incontinence was rare and did not increase during the study period. Perianal fistulas and associated abscesses can be controlled safely by simple drainage of pus collections. Frequent reinfection and re-opening after healing of fistulas are characteristic. Fistula type, rectal disease, and stool contamination influence the clinical course. Only a few patients, however, have continuous symptoms from perianal fistulas.     

Management of perianal fistulas in Crohn’s disease:An upto-date review

Perianal disease is one of the most disabling manifestations of Crohn’s disease.A multidisciplinary approach of gastroenterologist,colorectal surgeon and radiologist is necessary for its management.A correct diagnosis,based on endoscopy,magnetic resonance imaging,endoanal ultrasound and examination under anesthesia,is crucial for perianal fistula treatment.Available medical and surgical therapies are discussedin this review,including new local treatment modalities that are under investigation.     

Evaluation of surgery for perianal Crohn's fistulas

PURPOSE: This study was designed to evaluate the operative treatments performed on patients with perianal Crohn's disease at a tertiary referral colorectal university hospital and to determine the efficacy of management by assessing patient satisfaction. METHODS: A retrospective survey included 59 patients with perianal Crohn's disease who had undergone surgery during the period of 1991 to 1993, inclusive. RESULTS: Twenty-seven patients were treated by laying the fistula open (81 percent successful), and another 27 cases were treated with a loose seton (85 percent successful). Five cases were complicated fistulas and underwent diversionary stomas as part of a primary procedure. Overall success rate, as judged by patient satisfaction, was 83 percent. CONCLUSION: Conservative surgery has a role in management of perianal Crohn's disease. Patient satisfaction can be achieved without complete healing. Better preoperative assessment may improve results further.     

Burden and outcomes for complex perianal fistulas in Crohn's disease:Systematic review

AIM To systematically review the literature on epidemiology,disease burden, and treatment outcomes for Crohn's disease(CD) patients with complex perianal fistulas.METHODS PubMed, Embase, and Cochrane were searched for relevant articles(published 2000-November 2016) and congress abstracts(published 2011-November 2016).RESULTS Of 535 records reviewed, 62 relevant sources were identified(mostly small observational studies). The cumulative incidence of complex perianal fistulas in CD from two referral-centre studies was 12%-14%(follow-up time, 12 years in one study; not reported in the second study). Complex perianal fistulas result in greatly diminished quality of life; up to 59% of patients are at risk of faecal incontinence. Treatments include combinations of medical and surgical interventions and expanded allogeneic adipose-derived stem cells. High proportions of patients experience lack of or inadequate response to treatment(failure and relapse rates,respectively: medical, 12%-73% and 0%-41%; surgical:0%-100% and 11%.20%; combined medical/surgical:0%-80% and 0%-50%; stem cells: 29%-47% and not reported). Few studies(1 of infliximab; 3 of surgical interventions)have been conducted in treatment-refractory patients, a population with high unmet needs. Limited data exist on the clinical value of anti-tumour necrosis factor-α dose escalation in patients with complex perianal fistulas in CD.CONCLUSION Complex perianal fistulas in CD pose substantial clinical and humanistic burden. There is a need for effective treatments, especially for patients refractory to antitumour necrosis factor-α agents, as evidenced by high failure and relapse rates.     

Treatment of complex perianal fistulas with seton and infliximab in adolescents with Crohn's disease

Background and aimsTreatment of complex perianal fistulas associated with Crohn's disease is challenging. In adults, seton drainage combined with infliximab therapy has proven to be more effective than either one alone. Results following such treatment among pediatric patients have not been reported previously. The aim of this study was to describe outcomes after combined seton and infliximab treatment for complex perianal fistulas in adolescents with Crohn's disease.MethodsWe performed a retrospective medical record review of all consecutive Crohn's disease patients treated for perianal fistulas with seton drainage and infliximab between 2007 and 2013 (n = 13). A follow-up interview was conducted at median of two years.ResultsMedian age at fistula diagnosis was 14 years. Following seton placement in fistula tracks, infliximab induction was administered at weeks 0, 2, and 6 and maintenance therapy at 8-week intervals. Over 90% responded to seton drainage and infliximab induction. Final fistula response was obtained at median of 8 weeks, being complete in 77% and partial in 15%. Setons were kept in place for median of 8 months. Fistulas recurred in 23% over a year after the final response. At last follow-up, 85% still had a response and 70% were free from perianal symptoms. Most were still on anti-TNF-α therapy, but one third had switched to adalimumab. Patients' anorectal function was well preserved and overall satisfaction with the treatment was high.ConclusionsThe results suggest that combining seton drainage with infliximab therapy improves the perianal fistula response rates in pediatric patients.     

Surgical treatment of enterovesical fistulas in Crohn's disease

A review of the surgical treatment of enterovesical fistula in Crohn's disease was undertaken to evaluate its effectiveness and long-term results. Sixty-three patients, 39 men and 24 women, with a mean age of 34.4 years were identified with enterovesical fistula. They had documented Crohn's disease for a mean period of 7.0 years. Distribution of anatomic pattern was 34.9 percent ileal, 7.9 percent colonic, and 57.2 percent ileocolic. Nineteen (30.1 percent) had previous abdominal surgery for Crohn's disease. Presenting symptoms included frequency and dysuria in 93.6 percent, pneumaturia in 79.3 percent, and fecaluria in 63.4 percent; 60.3 percent of patients had all three features. Enterovesical fistula was confirmed preoperatively in 43 patients, suspected clinically in 15 patients, and diagnosed intraoperatively in 5 patients. Sixty-one of 63 patients underwent surgery with resection of the phlegmon or abscess with the diseased bowel and curettage or resection of the fistula. After curettage of the bladder defect, pelvic and bladder drainage was instituted. Coexistent fistulas, most commonly ileosigmoid, occurred in 31 patients. Intra-abdominal abscesses were found in 21 patients, of whom 15 required two-stage procedures. One patient died (mortality 1.6 percent), urine leak occurred in 3.2 percent, and wound infection occurred in 1.6 percent. Follow-up (mean, 106 months) has identified one recurrence of enterovesical fistula due to Crohn's disease, and a further recurrence from concomitant sigmoid diverticulitis. Enterocutaneous fistulas developed in 6.4 percent and 11 patients (17.4 percent) have required further resections for Crohn's disease. Surgical treatment of enterovesical fistula in Crohn's disease is a safe and effective treatment.Study performed at The Cleveland Clinic Foundation.Read at the meeting of The American Society of Colon and Rectal Surgeons, Toronto, Canada, June 11 to 16, 1989.     

克罗恩病合并肛门周围疾病的诊治

在克罗恩病的并发症中,肛门周围疾病较为常见,其诊断除用儿童常规体格检查和麻醉下肛瘘探查术外,盆腔磁共振显像无创伤且准确性较好。评估肛瘘活动性采用肛周疾病活动指数,肛瘘分类临床上以单纯性和复杂性分类应用最多。治疗上单纯肛瘘以内科治疗为主,常用甲硝唑/环丙沙星、硫唑嘌呤/6-巯基嘌呤、infliximab,或上述两种药物联合应用;复杂肛瘘应内外科联合治疗,肛周脓肿应及时切开引流。     

Diagnostic and treatment recommendations on perianal Crohn's disease.

Treatment of perianal fistulas in Crohn's disease should be defined on an individual basis. A combined medical and surgical approach is the optimal treatment. Adequate management of perianal fistula disease is based on the presence or absence of active proctitis, anatomic location, and fistula type. Furthermore, the presence of perianal abscesses must be ruled out. This evaluation includes digital rectal examination, endoscopy, and examination under anesthesia combined with pelvic magnetic resonance imaging or anorectal endoscopy ultrasonography findings.