MSCT对结肠Crohn病的诊断价值

目的:探讨MSCT对结肠Crohn病的诊断价值。方法:回顾性分析经内镜、手术及病理证实的39例结肠Crohn病患者的MSCT影像学表现。结果:39例中多节段病变30例(76.9%),单独大肠受累4例(10.3%)、大肠伴小肠受累35例(89.7%)。大肠病变累及盲肠31例(79.5%)、升结肠26例(66.7%)、横结肠17例(43.6%)、降结肠10例(25.6%)、乙状结肠16例(41.0%)、直肠6例(15.4%)。MSCT征象:肠壁增厚、强化增加、肠壁分层、肠腔狭窄、肠壁脓肿、肠系膜血管增多("梳征")、病变肠管周围纤维脂肪增多、蜂窝织炎、腹腔脓肿和炎性肿块、肛周病变、瘘管/窦道、系膜淋巴结肿等。肠管增厚、肠壁分层、强化增加、肠壁内脓肿、病变肠管周围蜂窝织炎、"梳征"等可提示病变处在活动期。结论:结肠Crohn病易累及盲、升结肠,MSCT表现有一定特征性,MSCT在显示肠壁病变及肠腔外并发症以及判断病变是否在活动期具有优势。

Crohn’s病的肠外表现特征及其临床意义

目的探讨Crohn’s病(CD)患者肠外表现的特点和临床意义。方法回顾性收集有肠外并发症表现的51例CD患者的临床资料,分析患者出现肠外并发症的特征表现,结合文献报道对比复习这些肠外并发症在Crohn’s的诊断和治疗中的意义。结果51例患者肠外表现依次为骨关节病变、口腔溃疡、肝胆病变、皮肤病变、眼部、代谢性骨病、血管闭塞等。出现一种肠外病变的29例,两种肠外病变的为13例,三种或以上病变的为9例。原发CD病灶的受累范围越广,其肠外表现的种类越多。结论肠外表现与Crohn’s病的累及部位与严重度有一定关系,肠外并发症对其原发Crohn’s病诊断和治疗均有一定的影响。

肠外Crohn’s病:病例报道和文献回顾

Crohn’s病传统地称为慢性肉芽肿性炎症性肠病。病理学表现包括非接触性慢性炎症和非干酪化肉芽肿。疾病可累及胃肠道的任何一段,但很少见该病扩展到上呼吸消化道。本文报告1例肠外Crohn’s病,在胃肠道隐匿性受累,而鼻腔、喉和皮肤活动性受累为特征。

Systematic review: Safety of balloon assisted enteroscopy in Crohn's disease

AIM To determine the overall and comparative risk of procedure related perforation of balloon assisted enteroscopy(BAE) in Crohn's disease(CD). METHODS Systematic review(PROSPERO #CRD42015016381) of studies reporting on CD patients undergoing BAE. Seventy-three studies reporting on 1812 patients undergoing 2340 BAEs were included. Primary outcome of interest was the overall and comparative risk of procedure related perforation of diagnostic BAE in CD. Secondary outcomes of interest were risk of procedure related perforation of diagnostic double balloon enteroscopy(DBE), risk of procedure related perforation of therapeutic BAE, efficacy of stricture dilation, and clinical utility of endoscopically assessing small bowel disease activity.RESULTS Per procedure perforation rate of diagnostic BAE in CD was 0.15%(95%CI: 0.05-0.45), which was similar to diagnostic BAE for all indications(0.11%; IRR = 1.41, 95%CI: 0.28-4.50). Per procedure perforation rate of diagnostic DBE in CD was 0.12%(95%CI: 0.03-0.44), which was similar to diagnostic DBE for all indications(0.22%; IRR = 0.54, 95%CI: 0.06-0.24). Per procedure perforation rate of therapeutic BAE in CD was 1.74%(95%CI: 0.85-3.55). Eighty-six percentof therapeutic perforations were secondary to stricture dilation. Dilation was attempted in 207 patients and 30% required surgery during median follow-up of 18 months. When diagnostic BAE assessed small bowel disease activity, changes in medical therapy resulted in endoscopic improvement in 77% of patients. CONCLUSION Diagnostic BAE in CD has a similar rate of perforation as diagnostic BAE for all indications and can be safely performed in assessment of mucosal healing.

Trefoil factor-3 is not a useful marker of mucosal healing in Crohn's disease treated with anti-TNF-α antibodies

AIMTo evaluate whether repeated serum measurements of trefoil factor-3 (TFF-3) can reliably reflect mucosal healing (MH) in Crohn’s disease (CD) patients treated with anti-tumor necrosis factor-α (anti-TNF-α) antibodies.METHODSSerum TFF-3 was measured before and after anti-TNF-α induction therapy in 30 CD patients. The results were related to clinical, biochemical and endoscopic parameters. MH was defined as a ≥ 50% decrease in Simple Endoscopic Score for Crohn’s disease (SES-CD).RESULTSSES-CD correlated significantly with CD clinical activity and several standard biochemical parameters (albumin, leukocyte and platelet counts, C-reactive protein, erythrocyte sedimentation rate, fibrinogen). In contrast, SES-CD did not correlate with TFF-3 (P = 0.54). Moreover, TFF-3 levels did not change significantly after therapy irrespectively of whether the patients achieved MH or not. Likewise, TFF-3 did not correlate with changes in fecal calprotectin, which has been proposed as another biochemical marker of mucosal damage in CD.CONCLUSIONSerum TFF-3 is not a convenient and reliable surrogate marker of MH during therapy with TNF-α antagonists in CD.

Indications and surgical options for small bowel, large bowel and perianal Crohn's disease

Despite advancements in medical therapy of Crohn's disease(CD), majority of patients with CD will eventually require surgical intervention, with at least a third of patients requiring multiple surgeries. It is important to understand the role and timing of surgery, with the goals of therapy to reduce the need for surgery without increasing the odds of emergency surgery and its associated morbidity, as well as to limit surgical recurrence and avoid intestinal failure. The profile of CD patients requiring surgical intervention has changed over the decades with improvements in medical therapy with immunomodulators and biological agents. The most common indication for surgery is obstruction from stricturing disease, followed by abscesses and fistulae. The risk of gastrointestinal bleeding in CD is high but the likelihood of needing surgery for bleeding is low. Most major gastrointestinal bleeding episodes resolve spontaneously, albeit the risk of re-bleeding is high. The risk of colorectal cancer associated with CD is low. While current surgical guidelines recommend a total proctocolectomy for colorectal cancer associated with CD, subtotal colectomy or segmental colectomy with endoscopic surveillance may be a reasonable option. Approximately 20%-40% of CD patients will need perianal surgery during their lifetime. This review assesses the practice parameters and guidelines in the surgical management of CD, with a focus on the indications for surgery in CD(and when not to operate), and a critical evaluation of the timing and surgical options available to improve outcomes and reduce recurrence rates.

Potential model for differential diagnosis between Crohn's disease and primary intestinal lymphoma

AIM To evaluate the usefulness of different parameters to differentiate Crohn's disease(CD) from primary intestinal lymphoma(PIL).METHODS The medical records of 85 patients with CD and 56 patients with PIL were reviewed retrospectively. Demographic, clinical, laboratory, endoscopic, and computed tomographic enterography(CTE) parameters were collected. The univariate value of each parameter was analyzed. A differentiation model was established by pooling all the valuable parameters. Diagnostic efficacy was analyzed, and a receiver operating characteristic(ROC) curve was plotted.RESULTS The demographic and clinical parameters that showed significant values for differentiating CD from PIL included age of onset, symptom duration, presence of diarrhea, abdominal mass, and perianal lesions(P < 0.05). Elevated lactate dehydrogenase and serum β2-microglobulin levels suggested a PIL diagnosis(P < 0.05). The endoscopic parameters that showed significant values for differentiating CD from PIL included multiple-site lesions, longitudinal ulcer, irregular ulcer,and intraluminal proliferative mass(P < 0.05). The CTE parameters that were useful in the identification of the two conditions included involvement of ≤ 3 segments, circular thickening of the bowel wall, wall thickness > 8 mm, aneurysmal dilation, stricture with proximal dilation, "comb sign", mass showing the "sandwich sign", and intussusceptions(P < 0.05). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the differentiation model were 91.8%, 96.4%, 93.6%, 97.5%, and 88.5%, respectively. The cutoff value was 0.5. The area under the ROC curve was 0.989.CONCLUSION The differentiation model that integrated the various parameters together may yield a high diagnostic efficacy in the differential diagnosis between CD and PIL.

CT小肠造影评估Crohn's病活动度的临床价值

目的探讨计算机断层扫描(CT)小肠造影评估Crohn's病活动度的临床价值。方法 42例活动期Crohn's病患者作为观察组,33例缓解期Crohn's病患者作为对照组。所有患者均接受CT小肠造影检查,对比检查结果。结果两组患者的病变强化方式比较,差异有统计学意义(P<0.05)。观察组肠腔狭窄或梗阻例数多于对照组,游离缘假性憩室例数少于对照组,差异均具有统计学意义(P<0.05)。观察组肠系膜密度增高、腹腔淋巴结肿大、梳状征、蜂窝织炎例数均多于对照组,差异均具有统计学意义(P<0.05)。观察组肠壁厚度为(10.6±2.5)mm,厚于对照组的(4.9±2.0)mm,观察组病变肠壁动脉期CT值为(97.1±13.5)Hu、病变肠壁门脉期CT值为(109.8±14.6)Hu,均高于对照组的(74.2±6.4)、(81.6±5.7)Hu,差异均具有统计学意义(P<0.05)。结论 CT小肠造影可以准确地鉴别Crohn's病活动期与缓解期,在评估Crohn's病活动度方面有重要的临床实用价值。

Factors associated with surgery in patients with intra-abdominal fistulizing Crohn's disease

AIM To characterize radiological and clinical factors associated with subsequent surgical intervention in Crohn's disease(CD) patients with intra-abdominal fistulae.METHODS From a cohort of 1244 CD patients seen over an eight year period(2006 to 2014), 126 patients were identified as having intra-abdominal fistulae, and included in the study. Baseline patient information was collected from the medical records. Imaging studies were assessed for: anatomic type and number of fistulae; diameter of the inflammatory conglomerate; length of diseased bowel; presence of a stricture with pre-stenotic dilatation; presence of an abscess; lymphadenopathy; and the degree of bowel enhancement. Multivariate analysis for the prediction of abdominal surgery was calculated via Generalized Linear Models.RESULTS In total, there were 193 fistulae in 132 patients, the majority(52%) being entero-enteric. Fifty-nine(47%) patients underwent surgery within one year of the imaging study, of which 36(29%) underwent surgery within one month. Radiologic features that were associated with subsequent surgery included: multiple fistulae(P = 0.009), presence of stricture(P = 0.02), and an entero-vesical fistula(P = 0.01). Evidence of an abscess, lymphadenopathy, or intense bowel enhancement as well as C-reactive protein levels was not associated with an increased rate of surgery. Patients who were treated after the imaging study with combination immunomodulatory and anti-TNF therapy had significantly lower rates of surgery(P = 0.01). In the multivariate analysis, presence of a stricture [RR 4.5(1.23-16.3), P = 0.02] was the only factor that increased surgery rate.CONCLUSION A bowel stricture is the only factor predicting an increased rate of surgery. Radiological parameters may guide in selecting treatment options in patients with fistulizing CD.

Cystic fibrosis and Crohn’s disease:Successful treatment and long term remission with infliximab

The association of cystic fibrosis and Crohn's disease (CD) is well known, but to date, there are very few cas-es in the literature of patients suffering from mucovisci-dosis who have required treatment with infliximab. We report the case of a 23-year-old patient suffering from cystic fibrosis and severe CD treated successfully with infliximab without any infective complications or wors-ening of the pulmonary disease and with a long term (2 years) complete remission.

An unusual presentation of fistulating Crohn's disease:Ascites

Whilst ascites is a common presenting complaint in patients with decompensated chronic liver disease and disseminated malignancy,in Crohn's disease however,it is exceptionally rare.We describe a patient with no prior history of inflammatory bowel or liver disease,presenting with rapid onset gross ascites and scrotal swelling.Further investigations revealed severe hypoalbuminemia and transudative ascitic fluid with normal other liver function tests and a negative liver screen.Computed tomography revealed widespread ascites and pleural effusions with no features of malignancy or portal hypertension,and a small bowel barium series showed features of fistulating small bowel Crohn's disease.An ileo-colonoscopy confirmed the presence of terminal ileal inflammatory stricture.The patient's clinical condition and serum albumin improved with a combination of diuretics,elemental diet,antibiotics and oral 5-aminosalicylic acid therapy.

JAK-STAT通路相关的克罗恩病治疗药物研究

克罗恩病(Crohn’s disease,CD)为炎症性肠病(inflamatory bowel disease,IBD)的一种,其内科治疗包括传统治疗和生物治疗,生物治疗越来越成为CD的主流治疗方法。而生物治疗涉及炎症因子及其介导的炎性信号通路,这些通路在CD的发病、进展、预后、结局中均有着重要作用。本文总结了与CD有关的JAK-STAT信号通路及阻断该通路相关的药物进展,以期提高人们对CD发病机制的进一步认识。

血浆细胞因子表达紊乱与儿童克罗恩(Crohn′s)病的关系研究

目的探讨血浆细胞因子表达紊乱与儿童克罗恩病发病的关系。方法选取2014年6月~2016年9月间于我院收治的CD患儿35例及体检健康正常儿童30例为研究对象,按照CD活动程度差异分为轻度活动组和中重度活动组;检测CD组和对照组血浆IL-2、IL-4、IL-6、IL-12、IL-17A、IL-23、TNF-α、TGF-β、IL-10、IFN-γ蛋白表达水平及转录因子T-bet、GATA-3、RORγt m RNA表达水平差异。结果 CD组患者血浆IL-2、IL-4、IL-6、IL-12、IL-17A、IL-23、TNF-α、TGF-β、IFN-γ表达水平均较对照组显著升高,IL-10表达水平均较对照组显著降低(P<0.05);中、重度期活动组患者血浆IL-2、IL-12、IL-17A、IL-23、TNF-α、TGF-β表达水平均较轻度活动组显著升高(P<0.05)。CD组患者T-bet、RORγt表达水平较对照组显著升高(P<0.05);中、重度期活动组患者T-bet、RORγt表达水平均较轻度活动组显著升高(P<0.05)。CD组患者T-bet/GATA-3、RORγt/GATA-3、RORγt/T-bet比值较对照组显著升高(P<0.05);中、重度期活动组患者T-bet/GATA-3、RORγt/GATA-3、RORγt/T-bet比值均较轻度活动组显著升高(P<0.05)。结论 Th1、Th2、Th17型细胞失衡导致的血清细胞因子表达紊乱与儿童型CD的发生有关,Th17型细胞数量增加在CD发病机制中起主导作用。

Hepatosplenic T-cell lymphoma in a 47-year-old Crohn's disease patient on thiopurine monotherapy

Hepatosplenic T-cell lymphoma(HSTCL) is a rare nonHodgkin lymphoma with a high mortality rate. Higher incidence is reported in patients with inflammatory bowel disease, specifically in male patients that are younger than 35 years, and have been treated with thiopurine and tumor necrosis factor(TNF)-α inhibitor combination therapy for over 2 years. In this case report we describe a 47-year-old patient with Crohn's disease(CD) who developed HSTCL after having been treated with thiopurine monotherapy for 14 years. To our best knowledge, only eleven cases exist of patients with CD who developed HSTCL while on thiopurine monotherapy. We report the first patient with CD, older than 35 years, who developed HSTCL while on thiopurine monotherapy. This emphasizes that HSTCL risk is not limited to young men receiving both thiopurines and TNF-α inhibitors.

Altered pattern of tumor necrosis factor-alpha production in peripheral blood monocytes from Crohn's disease

AIM To evaluate the inflammatory state in Crohn's disease(CD) patients and correlate it with genetic background and microbial spreading.METHODS By means of flow cytometry, production of tumor necrosis factor-alpha(TNF-α) was measured in peripheral blood monocytes from patients suffering from CD, ulcerative colitis(UC) and in healthy subjects after stimulation of the NOD2 and TLR pathways. CD patients were genotyped for the three most common NOD2 variants(R702W, G908 R and L1007Pfs*2) and basal production of TNF-α was correlated to NOD2 genotype. Also, production of TNF-α was correlated to plasmatic levels of LPS Binding Protein(LBP), soluble(s) CD14 and to the activity state of the disease.RESULTS The patients with CD were characterized by a significantly higher monocyte basal expression of TNF-αcompared with healthy subjects and UC patients, and after stimulation with Pam3CSK4(ligand of TLR2/1) and MDP-L18(ligand of NOD2) this difference was maintained, while other microbial stimuli(LPS, ligand of TLR4 and Poly I:C, ligand of TLR3) induced massive activation in CD monocytes as well as in UC and in healthy control cells. There was no significant difference in the production of TNF- α between patients who carried CD-associated heterozygous or homozygous variants in NOD2 and patients with wild type NOD2 genotype. Although serum LBP levels have been shown to correlate positively with the state of activity of the disease, TNF-α production did not show a clear correlation with either LBP or s CD14 levels in plasma. Moreover, no clear correlation was seen between TNF-α production and activity indices in either CD or UC.CONCLUSION Peripheral monocytes from CD express higher basal and stimulated TNF-α than controls, regardless of NOD2 genotype and without a clear correlation with disease activity.

紫菀酮通过抑制肠上皮细胞凋亡改善TNBS诱导的克罗恩病样结肠炎

目的研究紫菀酮(SHI)对2,4,6-三硝基苯磺酸(TNBS)诱导的小鼠克罗恩病(CD)样结肠炎的作用及潜在机制。方法18只野生型小鼠随机分为3组:对照组(WT组)、模型组(TNBS组)和SHI干预组(SHI组),每组6只。TNBS组小鼠肛门推注5%TNBS诱导CD样结肠炎;SHI组在TNBS造模的同时给予SHI灌胃干预[40 mg/(kg·d)],WT组和TNBS组每日给予等量的生理盐水灌胃。1周后处死小鼠,采用疾病活动度(DAI)评分、体质量改变、结肠长度、组织学炎症评分和小鼠结肠黏膜肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)水平评估肠炎程度。采用荧光素异硫氰酸酯-右旋糖酐(FITC)渗透性测定、肠型脂肪酸结合蛋白(I-FABP)测定、细菌移位率评估肠屏障功能。通过TUNEL染色检测小鼠肠上皮细胞凋亡情况;通过Western blot检测小鼠凋亡相关蛋白(Bcl-2和Bax)的表达量。采用网络药理学以及生信富集分析预测SHI干预对小鼠CD样结肠炎保护作用的可能途径。结果与WT组比较,TNBS组DAI评分、体质量降低幅度、组织学炎症评分和结肠黏膜TNF-α、IL-6、IL-1β水平显著升高(P<0.05);与TNBS组比较,SHI组DAI评分、体质量降低幅度、组织学炎症评分和结肠黏膜TNF-α、IL-6、IL-1β水平显著降低(P<0.05)。与WT组比较,TNBS组小鼠结肠长度缩短(P<0.05);与TNBS组比较,SHI组小鼠结肠长度增加(P<0.05)。网络药理学以及生信富集分析发现SHI可能通过拮抗肠上皮细胞凋亡治疗CD。与TNBS组比较,SHI组小鼠外周血FITC-dextran、I-FABP水平和肝脏、肠系膜淋巴结的细菌移位率较低(P<0.05)。TUNEL染色结果显示,与TNBS组比较,SHI组小鼠结肠组织中肠上皮细胞凋亡数量显著减少(P<0.05),Bax的表达下调,Bcl-2的表达上调(均P<0.05)。结论SHI可能通过抑制肠上皮细胞凋亡进而缓解TNBS诱导的小鼠CD样结肠炎。

T-spot.TB在克罗恩病和肠结核鉴别诊断中的价值

目的探讨结核杆菌T细胞斑点试验(T-spot.TB)在克罗恩病和肠结核鉴别诊断中的价值。方法对北京大学深圳医院2010年1月至2012年8月收治的35例克罗恩病和37例肠结核患者进行T-spot.TB、糖类抗原125(CA125)测定,比较两种检测方法检测克罗恩病和肠结核的阳性率,并比较T-spot.TB和血CA125对克罗恩病和肠结核的鉴别诊断价值。结果肠结核组T-spot.TB、血CA125检测阳性率分别为91.9%(34/37)和78.4%(29/38),均显著高于克罗恩病组的8.6%(3/37)和21.6%(9/38)(P<0.05),T-spot.TB鉴别克罗恩病和肠结核的灵敏度、特异度、准确度、阳性预测值、阴性预测值分别为9.19%、91.4%、91.7%、91.9%和91.4%,均高于血CA125检测。结论 T-spot.TB方便快捷,敏感性和特异性高,在克罗恩病和肠结核的鉴别诊断中具有重要价值。

Inflammatory bowel disease in Hubei Province of China

AIM To investigate the inpatients with inflammatory bowel disease admitted to The Second Hospital, Hubei Medical University from 1986 to 1995 and analyze clinical features and follow up results of the patient in Hubei region. METHODS Data was collected retrospectively from 74 patients with inflammatory bowel disease (66 patients with ulcerative colitis and 8 patients with Crohn′s disease) hospitalized in The Second Hospital, Hubei Medical University from 1986 to 1995. RESULTS Abdominal pain, diarrhea, bloody and mucus stool and constipation are commonest symptoms of inflammatory bowel disease. Extraintestinal diseases were not common. The disease was mainly located in sigmoid and left colon in ulcerative colitis and located in ileum and colon in Crohn′s disease. Sulphasalazine and corticosteroid were effective (95%) in the treatment of ulcerative colitis, but about 42% patients had recurrence during the follow up of 1 11 years. Of 8 patients with Crohn′s disease, 5 had partial intestinal removal, and 3 treated with medicine of anti tuberculosis or metronidazole. Of 4 patients followed up for 1～8 years, 1 patient died of severe complications after surgery, 2 had recurrence with the medicine and 1 maintained remission with the treatment of sulphasalazine after operation. CONCLUSION From our data, family history of inflammatory bowel disease was seen in 5%. About 34% patients were smoking and 32% patients were alcoholic. Epidemiological investigation is urgently needed in Hubei of China to judge the strength of genetics and environmental factors in the pathogenesis of inflammatory bowel diseases.