Leukocytapheresis Therapy for Severe Ulcerative Colitis

Abstract: Severe attacks of ulcerative colitis are medical emergencies, and surgical treatment is indicated when glucocorticoid therapy is not effective. We have carried out an open clinical study of patients with severe attacks of ulcerative colitis to find out whether leukocytapheresis (LCAP) therapy can improve their outcomes. Nine patients were enrolled in this study. Seven of the nine patients had failed to respond to an intensive intravenous regimen before LCAP. LCAP was performed once a week for 4–5 weeks as intensive therapy using a leukocyte apheresis filter. Six of the 9 patients had an overall improvement after intensive therapy. Three patients reached the remission stage. The percentages of HLA-DR+, HLA-DR+ CD3+, HLA-DR+ CD4+, and HLA-DR+ CD8+ cells in the peripheral blood were higher in the responders than in the nonresponders, but there were no significant differences. In conclusion, LCAP therapy is useful for patients with severe attacks of ulcerative colitis, even those patients who failed to respond to glucocorticoid therapy.     

重症溃疡性结肠炎的内科治疗

参照1973年全国慢性非感染肠道疾病学术研讨会制定的溃疡性结肠炎的诊断标准,对北京协和医院1974年1月至1995年1月的溃疡性结肠炎住院病人共148例进行了分析,着重探讨了我院对重症溃疡性结肠炎的药物治疗经验。结果显示:21年间溃疡性结肠炎在内科消化病的年住院率呈上升趋势,重症患者占 72.3 ％。其临床治疗仍以激素,水杨酸偶氮磺胺吡啶和免疫抑制剂为主要治疗药物。本病在我院内科治疗的临床缓解率达95.9 ％,其中重症的临床缓解率达95,3 ％,死亡率为6.08 ％。我们提出对溃疡性结肠炎的内科治疗应遵循尽早控制症状、维持缓解、预防复发、防治并发症和掌握手术时机的原则;并根据病变的范围、疾病的活动性和严重程度、病程、病人的全身情况、以前用药情况和有无并发症等进行综合治疗。     

重症溃疡性结肠炎的药物治疗

本文参照1993年全国慢性非感染性肠道疾病学术研讨会制定的溃疡性结肠炎的诊断标准,对北京协和医院1974年1月至1995年1月的溃疡性结肠炎住院病人共148例进行了分析,着重探讨了我院对重症溃疡性结肠炎的药物治疗经验。结果显示,21年间溃疡性结肠炎在内科消化病的年住院率呈上升趋势,重症患者占72.3％。其临床治疗方法仍以激素、水杨酸偶氮磺胺吡啶和免疫抑制剂为主要治疗药物。本病在我院内科治疗的临床缓解率达95.9％,其中重症的临床缓解率达95.3％。死亡率为6.08％。我们提出对溃疡性结肠炎的内科治疗应遵循尽早控制症状、维持缓解、预防复发、防治并发症和掌握手术时机的原则:并根据病变的范围、疾病的活动性和严重程度、病程、病人的全身情况,以前用药情况和有无并发症等进行综合治疗。     

Leukocytapheresis with Leukocyte Removal Filter as New Therapy for Ulcerative Colitis

Abstract: Leukocytapheresis (LCAP) with a leukocyte removal filter column was administered for 45 patients with ulcerative colitis (UC). We evaluated changes in the leukocyte count and the differential percentages during LCAP. Cytokine production was assessed from each patient's peripheral mononuclear cells or monocytes. Flow cytometry was performed to assess the removal rates of activated cells and adhesion molecule positive cells by LCAP. Clinical improvement was recognized in 35 of 45 patients during intensive LCAP therapy, and it continued throughout maintenance therapy in 32 patients (71.1%). The leukocyte count was decreased to about 40% during the first 30 min, but it increased to approximately 170% at 20 min after the completion of LCAP. The concentration of tumor necrosis factor (TNF)α before LCAP in the effective group was higher than it was in either the ineffective group or the control group. Its level decreased to near normal range after LCAP. In the effective group, the concentrations of interleukin (1L)-1β, IL-2, interferon (IFN)γ, and IL-8 were near the normal upper limits before LCAP; however, they had decreased after LCAP. The concentration of IL-4 increased after LCAP. In the ineffective group, in contrast, the concentrations had been at or near normal before the initial LCAP treatment. Flow cytometry study revealed that LCAP could remove the activated cells and adhesion molecule positive cells more effectively. The clinical improvement and the changes observed before and after LCAP therapy suggest that LCAP is able to intervene in the causal mechanism(s) of UC.     

布地奈得和氢化可的松灌肠治疗溃疡性结肠炎的对比研究

目的:本实验对比观察布地奈得(BUD)和氢化可的松(HD)灌肠治疗轻中度远段溃疡性结肠炎(UC)的疗效 及副反应:建立高效液相色谱仪(HPLC)检测血和结肠粘膜中HD浓度的方法 方法:随机对照单(?)观察BUD组12例 HD组19例UC患者 治疗两周,比较两组在临床症状,结肠镜下,组织学及William疾病活动指数(DAI)几方面的变化同时观察副反应,并通过检测清晨皮质醇浓度来客观评价HD对肾上腺皮质的抑制作用 采用HPLC测定HD灌肠后不同时间血及肠粘膜活检组织中的该药浓度 结果:两组在临床症状,结肠镜下,组织学及DAI进步方面(?)L显著性差异(P>0.05)HD组2例出现颜面及双下肢水肿.而BUD组无此副反应:清晨皮质醇浓度变化两组有显著性差异(P<0.05)测出两例UC患者使用HD灌肠后粘膜及血中的药代学参数 结论:BUD和HD灌肠治疗(?)段UC临床疗效相当,前者副反应小 HD局部灌肠可能有部分全身作用     

Meta-Analysis of the Placebo Response in Ulcerative Colitis

Purpose The placebo response rate in randomized controlled trials (RCTs) in ulcerative colitis (UC) varies from 0 to 76%. The aims of this study were to quantify the pooled placebo response rate and identify the factors affecting it. Methods We performed a meta-analysis of 110 RCTs carried out between 1955 and 2005 and published in English. Regression analysis was used to identify factors significantly modifying placebo response. Results The pooled placebo remission rate was 23% (95%CI: 18.4–28%) and the pooled placebo improvement rate was 32.1% (95%CI: 28.1–36.3%). Multivariate analysis showed that the country where the study was performed (P = 0.025 for placebo remission and P = 0.0083 for placebo response rates) significantly influenced the placebo remission and response rates. Conclusion Placebo remission and response rates in RCTs of UC are highly variable and are significantly influenced by the country in which the RCT is performed.     

Predictive Factors of Response to Leukocytapheresis Therapy for Ulcerative Colitis

Abstract. Leukocytapheresis (LCAP) using a leukocyte removal filter was performed for 8 patients with moderate to severe ulcerative colitis (UC). Significant clinical improvement was attained in 5 of 8 patients (62.5%). All of them had been suffering from moderately active colitis and Received corticosteroid therapy. On the other hand, 3 patients with severely active disease and treated with little or no corticosteroid were resistant to LCAP. This result indicates that LCAP is an effective treatment for steroid-resistant cases of UC when combined with steroid therapy. LCAP alone, however, seems to have little efficacy for severely active UC.     

溃疡性结肠炎的并发症

溃疡性结肠炎是慢性复发性疾病,其并发症直接影响该病的预后。本文以1993年全国慢性非感染肠道疾病学术研讨对本病会制定的诊断标准,对北京协和医院1974年1月至1995年1月溃疡性结肠炎住院和门诊病人483例进行了分析,着重探讨并发症的种类与疾病严重程度的关系以及对预后的影响。本组病人并发症的发生率为6.2％(30/483)。重症患者并发症的发生率为24.3％。并发症的种类,按其发生频率的多少依次排列如下:严重电解质紊乱(9.01％)、肠梗阻(8.11％)、人出血、菌群失调,肠穿孔(各3.60％)、败血症(2.70％)、肠瘘、癌变(各1.80％).中毒性肠扩张(0.90％)。本组溃疡性结肠炎早期并发症,除电解质紊乱外尚有大出血、中毒性肠扩张、败血症多见,随病程迁延则以肠梗阻、肠瘘、肠穿孔和癌变为主。并发症多发生于重度活动期(24.3％);其中病变累及全结肠为82％,左半结肠仅为18％。住院病人中该病病死率为6.08％,并发症组为23.08％,高于无并发症组(2％)。因此,对溃疡性结肠炎的并发症,要提请广大临床医师注意:需早期诊断,积极治疗,以减少病死率。     

溃疡性结肠炎的并发症

目的:探讨溃疡性结肠炎并发症的种类与疾病严重程度的关系以及对预后的影响.方法:以1993年全国慢性非感染肠道疾病学术研讨会制定的对本病的诊断标准,分析了北京协和医院1974年1月至1995年1月溃疡性结肠炎住院和门诊病人483例.结果:本组病人并发症的发生率为6.2%(30/483).重症患者并发症的发生率为24.3%.并发症的种类按其发生频率的多少依次为:严重的电解质紊乱(9.01%)、肠梗阻(8.11%)、大出血、菌群失调、肠穿孔(各3.6%)、败血症(2.70%)、肠瘘、癌变(各1.80%)、中毒性肠扩张(0.90%).本组溃疡性结肠炎早期并发症,除电解质紊乱外尚有大出血、中毒性肠扩张、败血症多见,随病程迁延则以肠梗阻、肠瘘、肠穿孔和癌变为主.并发症多发生于重度活动期(24.3%);其中病变累及全结肠为82%,左半结肠仅为18%.住院病人中该病病死率为6.08%,并发症组为23.08%,高于无并发症组(2%).结论:溃疡性结肠炎的并发症需早期诊断,积极治疗以减少病死率.     

Current and Emerging Biologics for Ulcerative Colitis

Conventional medical treatment for ulcerative colitis can have limited efficacy or severe adverse reactions requiring additional treatment or colectomy. Hence, different biological agents that target specific immunological pathways are being investigated for treating ulcerative colitis. Anti-tumor necrosis factor (TNF) agents were the first biologics to be used for treating inflammatory bowel disease. For example, infliximab and adalimumab, which are anti-TNF agents, are being used for treating ulcerative colitis. Recently, golimumab, another anti-TNF agent, and vedolizumab, an anti-adhesion therapy, have been approved for ulcerative colitis by the U.S. Food and Drug Administration. In addition, new medications such as tofacitinib, a Janus kinase inhibitor, and etrolizumab, another anti-adhesion therapy, are emerging as therapeutic agents. Therefore, there is a need for further studies to select appropriate patient groups for these biologics and to improve the outcomes of ulcerative colitis treatment through appropriate medical usage.     

溃疡性结肠炎60例临床分析

目的探讨溃疡性结肠炎(Ulcerativecolitis,UC)的临床特点。方法回顾性分析我院5年来确诊的UC住院病人60例。结果60例UC患者中,男多于女(1.07∶1),各年龄段均有发病,60%～87%UC患者有腹痛、腹泻、血便和粘液便;UC病变范围分型为直肠炎3例(5%),直肠乙状结肠炎24例(40%),左半结肠炎7例(12%),全结肠炎24例(40%),区域性结肠炎2例(3%);病情轻、中、重度分别为32例(53%)、16例(27%)、12例(20%);临床类型为暴发型3例(5%),初发型25例(42%),慢性持续型10例(17%),慢性复发型22例(35%)。结论腹痛、腹泻、粘液脓血便为UC主要表现。     

Predictors of Clinical Response to Systemic Steroids in Active Ulcerative Colitis

Although systemic steroids remain as the gold standard for the treatment of acute moderate to severe active ulcerative colitis (UC), 15–57% of patients do not achieve clinical remission. We sought to identify clinical, biological, or radiologic predictive factors of response to steroid treatment in acute UC attacks. The medical records of 39 consecutive patients admitted for an acute attack of UC and treated with systemic steroids, were reviewed. Epidemiologic, demographic, and clinical data at baseline and clinical data 3 days after starting steroid treatment were registered. Treatment failure was defined as the need of IV cyclosporine or colectomy before hospital discharge. Twenty-four patients (62%) responded to systemic steroids. Thirteen out of the 15 nonresponders, were treated with IV cyclosporine, avoiding colectomy in 7 cases (54%). More than six bowel movements per day at the third day of treatment, blood in stools in the third day of therapy, extensive UC, and the presence of malnutrition were associated with steroid treatment failure, but only blood in stools (P=.04), and more than six movements per day (P=.012) after 3 days of treatment, were found to be independent predictive factors of steroid refractoriness. In conclusion, clinical evaluation 3 days after starting systemic steroids seems to be the best tool to assess short-term prognosis.     

Off‐Line Leukapheresis Using Leukofiltration for Active Ulcerative Colitis: A Case Report

Abstract: The method of leukocytapheresis for ulcerative colitis (UC) by using extracorporeal circulation (on‐line system) has been reported. To perform leukocytapheresis, we have applied leukocyte elimination filters for blood transfusion to leukocytapheresis without using extracorporeal circulation (off‐line leukocytapheresis system). Four hundred milliliters of peripheral blood was collected and reinfused through a leukocyte elimination filter. This procedure was repeated 5 times, and up to 2,000 ml of peripheral blood was treated. This method has been applied once a week for 5 weeks. We applied the off‐line leukapheresis system to a 31‐year‐old male ulcerative colitis patient. As a result, the frequency of defecation and the dose of medicine were effectively decreased, and endoscopic finding was also improved. Because of the absence of complications observed with the on‐line system, the off‐line leukocytapheresis system that we have applied to the clinical patient is simple, safe, and useful.     

A Comparison of Adverse Events and Functional Outcomes After Restorative Proctocolectomy for Familial Adenomatous Polyposis and Ulcerative Colitis

Purpose Restorative proctocolectomy is the procedure of choice for patients undergoing proctocolectomy for familial adenomatous polyposis or ulcerative colitis. This meta-analysis was designed to identify differences in adverse events and functional outcomes between these two groups. Methods Studies published between 1986 and 2003 that compared outcomes between patients with familial adenomatous polyposis and ulcerative colitis were included. Meta-analytical techniques using random effect models were used to compare short-term and long-term adverse events as well as functional outcomes between the groups. Results Nineteen studies comprising 5,199 patients (familial adenomatous polyposis, 782; ulcerative colitis, 4,417) were analyzed. There were no significant differences in immediate postoperative adverse events between the two groups. Pouch-related fistulation was significantly increased in the ulcerative colitis group (10.5 percent vs. familial adenomatous polyposis 4.8 percent; odds ratio 2.31; P < 0.001). There was no significant difference in pouch failure between the two groups (ulcerative colitis 5.8 percent vs. familial adenomatous polyposis 4.5 percent; odds ratio 1.22; P = 0.43). The incidence of pouchitis was significantly greater in the ulcerative colitis group (30.1 vs. 5.5 percent; odds ratio 6.44; P < 0.001). Patients with familial adenomatous polyposis had a significant advantage in stool frequency with one less motion per 24 hours (95 percent confidence interval, 0.21–1.76; P = 0.01). Conclusions In contrast to studies reporting similar outcomes for patients undergoing restorative proctocolectomy for familial adenomatous polyposis or ulcerative colitis, the present meta-analysis suggested that patients with ulcerative colitis are at greater risk of pouch-related fistulation and pouchitis. Although there was an increase in the 24-hour stool frequency in the ulcerative colitis group, this may be accounted for by the younger age at surgery in the familial adenomatous polyposis group. Henry S. Tilney is sponsored by a research grant from The Royal College of Surgeons of England. Read at the meeting of the Association of Surgeons of Great Britain and Ireland, Edinburgh, Scotland, May 3 to 5, 2006.     

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...     

Real-World Incidence of Suboptimal Response to Anti-Tumor Necrosis Factor Therapy for Ulcerative Colitis: A Nationwide Population-Based Study

Background/AimsAlthough anti-tumor necrosis factor (TNF) agents have been widely used to treat ulcerative colitis (UC), the real-world incidence of suboptimal response to anti-TNF agents has not been thoroughly investigated, especially among Asians.MethodsUsing the Korean National Health Insurance database, we collected data on UC patients who initiated anti-TNF agents between July 1, 2014, and June 30, 2017. We assessed suboptimal responses, including anti-TNF discontinuation or dose escalation, switching to other biologics, augmentation with a non-biologic therapy, and the requirement for colectomy.ResultsA total of 1,268 patients were included as new anti-TNF users (infliximab 713, adalimumab 433, golimumab 122). The proportion of patients who experienced at least one suboptimal response within 1 year among all patients was 63.5%, including 59.1%, 69.5%, and 68.0% of patients treated with infliximab, adalimumab, and golimumab, respectively. The cumulative incidences of at least one suboptimal response over time were 41.5%, 63.7%, 80.5%, and 87.1% at 6, 12, 24, and 36 months, respectively. Cox proportional hazards modeling revealed that adalimumab was associated with a higher risk of at least one suboptimal response (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.13 to 1.48), dose escalation (HR, 4.35; 95% CI, 2.97 to 6.38) and discontinuation (HR, 1.25; 95% CI, 1.03 to 1.52) than infliximab. Golimumab was associated with a higher risk of switching to other biologics than infliximab (HR, 1.78; 95% CI, 1.21 to 2.60).ConclusionsMore than half of Korean UC patients had suboptimal responses to anti-TNF agents within 1 year. UC patients treated with infliximab might be less prone to suboptimal responses than those treated with adalimumab or golimumab.     

昆明市379例溃疡性结肠炎患者治疗分析

目的 回顾性调查昆明市近10年来溃疡性结肠炎(UC)住院病例的资料,以进一步了解昆明市UC患者的治疗状况.方法 选取昆明市1998年1月～2007年3月期间7家大型综合医院379例住院的炎症性肠病患者作为调查对象.诊断均符合2007年中华医学会消化病学分会的UC诊治标准,分析UC患者的治疗状况.结果 379例UC患者有...     

Refractory Ulcerative Colitis Improved by Scheduled Combination Therapy of Vedolizumab and Granulocyte and Monocyte Adsorptive Apheresis

Granulocyte and monocyte adsorptive apheresis (GMA) is occasionally introduced as an alternative combination therapy after loss of response to biologics in ulcerative colitis (UC) patients. However, there have been no reports of the concomitant use of vedolizumab (VDZ) and GMA for the initial induction of UC. A 20-year-old man with refractory UC was admitted for recrudescence. VDZ monotherapy had previously been introduced but was ineffective. Therefore, he received scheduled combination of VDZ and GMA and achieved clinical remission. The combination of two different approaches to inhibit the migration of leukocytes into the inflamed tissue led to satisfactory clinical outcomes.