Therapy Refractory Ulcerative Colitis Research Articles

Long-term outcomes after appendicectomy as experimental treatment for patients with therapy-refractory ulcerative colitis.

This study assessed 25 patients with severe ulcerative colitis undergoing appendicectomy. During a median postoperative follow-up of 7.5 years, the median duration of clinical response, as observed in 15 patients, was 80 months; the median duration of endoscopic improvement, as observed in 12 of patients, was 46 months.

P110 activation protein is strongly expressed in intestinal fibrosis in inflammatory bowel disease patients

Abstract Background Intestinal fibrosis is a common complication of inflammatory bowel disease (IBD) with limited diagnostic modalities to detect and determine the degree of fibrosis. Fibroblast activation protein alpha (FAP) is a protein with both dipeptidyl peptidase and endopeptidase properties which is virtually absent in healthy tissues and has increased expression in chronic inflammatory and fibrotic diseases. In this study, we investigated the presence of FAP in intestinal fibrosis caused by Crohn’s disease (CD) and ulcerative colitis (UC). Methods For this study, transmural surgical resection specimens were retrieved from the Tytgat institute IBD biobank located at Amsterdam University Medical Center. IBD patients undergoing an ileocecal resection for stricturing CD or a subtotal colectomy for therapy-refractory disease, and patients undergoing a right-sided hemicolectomy or ileocecal resection for dysplasia or non-metastasized colorectal cancer (CRC), were included. All patients had an established diagnosis of (CD, UC, dysplasia or CRC) by previous endoscopy and biopsies and had provided informed consent prior to surgery. FAP protein and gene expression levels were determined using immunohistochemistry staining and quantitative polymerase chain reaction (qPCR). Mass cytometry was used to identify FAP–expressing cells. Results In total, 59 ileal and 35 colonic samples were stained and quantified to asses FAP expression (figure 1). A 1.7-fold and 1.9-fold increase of FAP protein expression was seen in inflamed (mean 22.3, p=0.0069); and stenotic (mean 25.5 p=0.0002) CD ileum compared to healthy non-IBD tissue (mean 13.1). Inflamed UC colon (mean 26.8, p = 0.0406) showed a 1.4-fold increase compared to healthy colon (mean 19.2). For the gene expression, 66 ileal and 42 colonic samples were processed and used for qPCR analysis. A 5-fold and 6.4-fold increase of FAP was found in inflamed (mean 0.011, p=0.0475) and stenotic (mean 0.014, p=0.0042) CD ileum, and a 1.7-fold increase was seen in inflamed UC colon (mean 0.278, p=0.0195) compared to controls (means: ileum 0.002; colon 0.165). Conclusion This is the first study reporting the potential of FAP as a fibrotic biomarker not only in stricturing CD, but also in therapy-refractory UC. Significantly increased FAP protein and gene expression is found in inflamed and stenotic ileum in CD and inflamed colon in UC. Additionally, CD90+GP38+ cells have been identified as the most present FAP expressing cells.

P474 Postoperative disease course after appendectomy as experimental treatment for patients with therapy refractory moderate to severe ulcerative colitis

Abstract Background Increasing evidence suggests appendectomy as a potential experimental therapy for ulcerative colitis (UC). A prospective cohort study of laparoscopic appendectomy for treatment of therapy refractory UC showed a clinical response in nearly half of the patients with a substantial proportion of patients in endoscopic remission, after a postoperative follow-up of 3.7 years1. The current study aimed to explore disease course during long-term follow-up in patients undergoing appendectomy for therapy-refractory UC. Methods In this monocenter cohort series, all patients with therapy refractory UC referred for (procto)colectomy between 2012-2015 were counselled to undergo laparoscopic appendectomy instead. The primary endpoint was long-term clinical (≥3 points decrease in partial mayo score) and endoscopic response (Endoscopic Mayo score ≤1) displayed in individual time lines. Secondary endpoints included duration and loss of clinical and endoscopic response, de-escalation of medication, and failure (medical treatment switch or colectomy). Results A total of 25 patients (12 men; median age 41.0 years) underwent appendectomy. The median postoperative follow-up time was 7.5 [IQR 6.4-8.6] years. Clinical response was observed in 60% (15/25) after a median follow-up of 4.0 [IQR 3.0-7.0] months, and was 32% (8/25) at the end of follow-up. Endoscopic response was observed in 48% (12/25) after a median follow-up of 17.5 [IQR 3.3-38.8] months and was 24% (6/25) at the end of follow-up. The median duration of clinical and endoscopic response was 80.0 [20.0-93.0] an 45.5 [21.8-56.8] months, respectively. Six (24%) patients de-escalated medication during follow-up, five of which without subsequent failure. Seventeen (68%) patients failed during postoperative follow-up after appendectomy, of which nine patients (36%) required colectomy a median of 5.0 [IQR 2.0-13.5] months after appendectomy. Figure 1. Disease course after appendectomy per patient. Conclusion During the postoperative course following appendectomy for refractory UC, approximately half of the patients demonstrated long-lasting endoscopic response, more than half demonstrated long-lasting clinical response, and one third underwent colectomy. 1Stellingwerf ME, Sahami S, Winter DC, Martin ST, D'Haens GR, Cullen G, Doherty GA, Mulcahy H, Bemelman WA, Buskens CJ. Prospective cohort study of appendicectomy for treatment of therapy-refractory ulcerative colitis. Br J Surg. 2019 Nov;106(12):1697-1704.

Increasing experience of modified two-stage transanal ileal pouch-anal anastomosis for therapy refractory ulcerative colitis. What have we learned? A retrospective analysis on 75 consecutive cases at a tertiary referral hospital.

Ileal pouch-anal anastomosis (IPAA) should be delayed to a second stage in patients with ulcerative colitis and prolonged exposure to medical therapy. However, there is still discussion about whether a modified two-stage approach is preferable to a three-stage approach. Recently, a transanal approach has been introduced to overcome the well-known difficulties of laparoscopic pelvic surgery. This paper presents short-term outcomes of transanal IPAA (Ta-IPAA) according to a modified two-stage approach. Data from all patients who underwent a modified two-stage Ta-IPAA for ulcerative colitis refractory to medical therapy were retrieved retrospectively from a prospective database. A comprehensive complication index was used for 90-day postoperative complications. Conversion, duration of surgery, hospital stay and reoperation were considered. A logistic regression model was used to assess risk factors for peri-pouch sepsis. Seventy-five (68.8%) patients were identified from 109 consecutive IPAAs. Median operation time was 159min. Conversion rate was 4%. Mean comprehensive complication index was 7. All anastomotic leaks (10.6%) were treated with diverting ileostomy. Additionally, active rescue with transanal drainage and early resuturing of the anastomotic gap was performed in six patients. Ileostomy closure occurred after a median period of 5.4months. At univariable analysis, factors associated with peri-pouch sepsis were male gender and age at IPAA construction. A modified two-stage Ta-IPAA is safe and feasible. Standardization and reproducibility of the technique are reflected in few conversions and intra-operative complications. Finally, morbidity and anastomotic leak do not differ from those reported in previous Ta-IPAA series with a variable proportion of multistage procedures.

Author response to: Comment on: Prospective cohort study of appendicectomy for treatment of therapy-refractory ulcerative colitis

Author response to: Comment on: Prospective cohort study of appendicectomy for treatment of therapy-refractory ulcerative colitis

Comment on: Prospective cohort study of appendicectomy for treatment of therapy-refractory ulcerative colitis

Comment on: Prospective cohort study of appendicectomy for treatment of therapy-refractory ulcerative colitis

Prospective cohort study of appendicectomy for treatment of therapy-refractory ulcerative colitis.

Appendicectomy may reduce relapses and need for medication in patients with ulcerative colitis, but long-term prospective data are lacking. This study aimed to analyse the effect of appendicectomy in patients with refractory ulcerative colitis. In this prospective multicentre cohort series, all consecutive patients with refractory ulcerative colitis referred for proctocolectomy between November 2012 and June 2015 were counselled to undergo laparoscopic appendicectomy instead. The primary endpoint was clinical response (reduction of at least 3 points in the partial Mayo score) at 12 months and long-term follow-up. Secondary endpoints included endoscopic remission (endoscopic Mayo score of 1 or less), failure (colectomy or start of experimental medication), and changes in Inflammatory Bowel Disease Questionnaire (IBDQ) (range 32-224), EQ-5D™ and EORTC-QLQ-C30-QL scores. A total of 28 patients (13 women; median age 40·5 years) underwent appendicectomy. The mean baseline IBDQ score was 127·0, the EQ-5D™ score was 0·65, and the EORTC-QLQ-C30-QL score was 41·1. At 12 months, 13 patients had a clinical response, five were in endoscopic remission, and nine required a colectomy (6 patients) or started new experimental medical therapy (3). IBDQ, EQ-5D™ and EORTC-QLQ-C30-QL scores improved to 167·1 (P < 0·001), 0·80 (P=0·003) and 61·0 (P < 0·001) respectively. After a median of 3·7 (range 2·3-5·2)years, a further four patients required a colectomy (2) or new experimental medical therapy (2). Thirteen patients had a clinical response and seven were in endoscopic remission. The improvement in IBDQ, EQ-5D™ and the EORTC-QLQ-C30-QL scores remained stable over time. Appendicectomy resulted in a clinical response in nearly half of patients with refractory ulcerative colitis and a substantial proportion were in endoscopic remission. Elective appendicectomy should be considered before proctocolectomy in patients with therapy-refractory ulcerative colitis.

P594 Predictors of non-response to repeated faecal microbiota transplantation in patients with therapy refractory ulcerative colitis

P594 Predictors of non-response to repeated faecal microbiota transplantation in patients with therapy refractory ulcerative colitis

Appendectomy for Therapy-refractory Ulcerative Colitis Results in Pathological Improvement of Colonic Inflammation

Appendectomy for Therapy-refractory Ulcerative Colitis Results in Pathological Improvement of Colonic Inflammation

675 - Therapy Refractory Ulcerative Colitis Patients may Benefit from Appendectomy; Long-Term Clinical Results from a Multicenter Prospective Cohort Series

675 - Therapy Refractory Ulcerative Colitis Patients may Benefit from Appendectomy; Long-Term Clinical Results from a Multicenter Prospective Cohort Series

P578 Therapy refractory ulcerative colitis patients may benefit from appendectomy: long-term clinical results from a multicentre prospective cohort series

P578 Therapy refractory ulcerative colitis patients may benefit from appendectomy: long-term clinical results from a multicentre prospective cohort series

The taxonomic composition of the donor intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in therapy refractory ulcerative colitis

SummaryBackgroundFaecal microbiota transplantation is an experimental approach for the treatment of patients with ulcerative colitis. Although there is growing evidence that faecal microbiota transplantation is effective in this disease, factors affecting its response are unknown.AimsTo establish a faecal microbiota transplantation treatment protocol in ulcerative colitis patients, and to investigate which patient or donor factors are responsible for the treatment success.MethodsThis is an open controlled trial of repeated faecal microbiota transplantation after antibiotic pre‐treatment (FMT‐group, n = 17) vs antibiotic pre‐treatment only (AB‐group, n = 10) in 27 therapy refractory ulcerative colitis patients over 90 days. Faecal samples of donors and patients were analysed by 16SrRNA gene‐based microbiota analysis.ResultsIn the FMT‐group, 10/17 (59%) of patients showed a response and 4/17 (24%) a remission to faecal microbiota transplantation. Response to faecal microbiota transplantation was mainly influenced by the taxonomic composition of the donor's microbiota. Stool of donors with a high bacterial richness (observed species remission 946 ± 93 vs no response 797 ± 181 at 15367 rps) and a high relative abundance of Akkermansia muciniphila (3.3 ± 3.1% vs 0.1 ± 0.2%), unclassified Ruminococcaceae (13.8 ± 5.0% vs 7.5 ± 3.7%), and Ruminococcus spp. (4.9 ± 3.5% vs 1.0 ± 0.7%) were more likely to induce remission. In contrast antibiotic treatment alone (AB‐group) was poorly tolerated, probably because of a sustained decrease of intestinal microbial richness.ConclusionsThe taxonomic composition of the donor's intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in ulcerative colitis patients. The design of specific microbial preparation might lead to new treatments for ulcerative colitis.

Long-term Combination Therapy with Anti-TNF plus Vedolizumab Induces and Maintains Remission in Therapy-refractory Ulcerative Colitis.

Fischer, Sarah MD1; Rath, Timo MD1; Geppert, Carol-Immanuel MD2; Manger, Bernhard MD3; Schett, Georg MD3; Neurath, Markus F MD1; Atreya, Raja MD1 Author Information

P317 Postoperative complications, outcome, quality of life and self-image after ileal pouch-anal anastomosis in patients operated due to acute, severe or chronic, therapy refractory ulcerative colitis

P317 Postoperative complications, outcome, quality of life and self-image after ileal pouch-anal anastomosis in patients operated due to acute, severe or chronic, therapy refractory ulcerative colitis

992 Therapy Refractory Ulcerative Colitis Patients May Benefit From Appendectomy; Early Result From the Passion Study

992 Therapy Refractory Ulcerative Colitis Patients May Benefit From Appendectomy; Early Result From the Passion Study

P376. Therapy refractory ulcerative colitis patients may benefit from appendectomy: early result from the PASSION study

P376. Therapy refractory ulcerative colitis patients may benefit from appendectomy: early result from the PASSION study

Dose-intensified granulocyte-monocyte apheresis in therapy refractory ulcerative colitis.

Granulocyte-monocyte apheresis (GMA) is an emerging therapeutic option in active course of ulcerative colitis (UC). Appropriate GMA dose, including total number, frequency, and duration of the individual GMA session, is a matter of debate. It was the aim of the present study to evaluate the efficacy of a dose-intensified GMA regimen in patients with moderately to severely active UC. A prospective open-label, single-center study was performed in 10 patients with active UC (Rachmilewitz Clinical Activity Index [CAI] ≥ 8 points; Rachmilewitz Endoscopic Index ≥ 7 points). Patients had failed to improve after treatment with steroids and/or immunomodulators. GMA was performed twice weekly for 2 h to a maximum of 10 sessions. In each GMA session, the adsorber was changed after 1 h of treatment time. Four patients achieved remission with a CAI ≤ 4 points. Three patients had a response with an improvement of CAI of ≥3 points. Three patients showed no benefit from GMA. The quality of life score determined by the inflammatory bowel disease questionnaire-Deutschland increased by 26 points in median. First and second filters had similar efficiency in granulocyte and monocyte adsorption. No major adverse effects were observed. Dose-intensified GMA as reported in this study provided an encouraging short-term response rate of 70% in patients with moderately to severely active UC not responding to standard steroid or immunomodulator therapy. Although all patients relapsed not later than 16 weeks, GMA might be useful to reduce steroid and immunomodulator usage, or to delay surgery in this patient group.

Initial diagnosis of Wegener’s granulomatosis mimicking severe ulcerative colitis: a case report

IntroductionWe describe the case of a woman with an unusual presentation of Wegener’s granulomatosis.Case presentationA 20-year old Caucasian woman presented with the principal feature of a pancolonic, superficial microulceration mimicking severe ulcerative colitis. Our patient was refractory to therapy and had persisting signs of septic shock as well as being at risk of perforation, so we performed a subtotal colectomy and a cholecystectomy due to the incipient necrosis of her gallbladder. Histologic analysis of her colon showed multiple superficial microulcera of the mucosa, lamina propria mucosae and, to a lesser extent, the lamina submucosa. The medium-sized arteries and arterioles of her entire colon, appendix and gallbladder showed acute vasculitic changes with fibrinoid necrosis of the walls and diffuse infiltration with neutrophil granulocytes, accompanied by a strong perivascular histiocyte-rich and partially granulomatous reaction. These findings strongly suggested an autoimmune multisystem disease like Wegener’s granulomatosis or microscopic polyangiitis. A diagnosis of Wegener’s granulomatosis was confirmed by the results of serologic antibody tests: her cytoplasmic antineutrophil cytoplasmic antibody titer was considerably elevated at 1:2560 specific for subclass proteinase 3 (>200kU/L). After the histopathological diagnosis and serological tests, immunosuppression with high doses of corticosteroids and plasmapheresis was started.ConclusionIn critically ill patients with severe, therapy-refractory ulcerative colitis, Wegener´s granulomatosis should be considered and serologic antibody testing should be performed.

Su1196 Prediction of Clinical Responders to Treatment With Dims0150 a Toll -Like Receptor 9 Agonist in Therapy Refractory Ulcerative Colitis Patients

Su1196 Prediction of Clinical Responders to Treatment With Dims0150 a Toll -Like Receptor 9 Agonist in Therapy Refractory Ulcerative Colitis Patients

P408 Prediction of clinical responders to treatment with DIMS0150 a Toll-Like Receptor 9 agonist in therapy refractory ulcerative colitis patients

P408 Prediction of clinical responders to treatment with DIMS0150 a Toll-Like Receptor 9 agonist in therapy refractory ulcerative colitis patients