S Ihara 1, Y Yamaji 2, H Kinoshita 1, A Yamada 1, Y Hirata 1, K Hasegawa 3, Y Sugawara 3, N Kokudo 3, K Koike 1
Tag: ulcerative colitis
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First Case Report of De Novo Ulcerative Colitis Developing After Orthotopic Liver Transplantation Successfully Treated by Granulocyte and Monocyte Apheresis.
Background: Immunosuppressants such as tacrolimus and cyclosporine are prescribed long-term after orthotopic liver transplantation (OLT) to prevent allograft rejection. Although these immunosuppressants are known to effectively control ulcerative colitis (UC), some post-OLT patients develop exacerbation of preexisting UC or de novo UC. Although aminosalicylates and corticosteroid courses are usually effective to treat such UC, several patients have developed uncontrollable disease and required colectomies. Case report: We have reported a patient who developed de novo UC after OLT to treat liver cirrhosis and hepatocellular carcinoma associated with hepatitis B virus (HBV) infection. Existence of the HBV infection made us avoid to increase the corticosteroid dose or to use other immunosuppressants such as azathioprine or infliximab. Conclusions: In this patient, granulocyte and monocyte apheresis was highly effective in terms of inducing remission of de novo UC. No adverse event was noted.
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Treating Inflammatory Bowel Disease by Adsorptive Leucocytapheresis: A Desire to Treat without Drugs
Abbi R Saniabadi 1, Tomotaka Tanaka 1, Toshihide Ohmori 1, Koji Sawada 1, Takayuki Yamamoto 1, Hiroyuki Hanai World J gastroenterol. 2014 Aug 7;20(29):9699-715
Ulcerative colitis and Crohn’s disease are the major phenotypes of the idiopathic inflammatory bowel disease (IBD), which afflicts millions of individuals throughout the world with debilitating symptoms, impairing function and quality of life. Current medications are aimed at reducing the symptoms or suppressing exacerbations. However, patients require life-long medications, and this can lead to drug dependency, loss of response together with adverse side effects. Indeed, drug side effects become additional morbidity factor in many patients on long-term medications. Nonetheless, the efficacy of anti-tumour necrosis factors (TNF)-α biologics has validated the role of inflammatory cytokines notably TNF-α in the exacerbation of IBD. However, inflammatory cytokines are released by patients’ own cellular elements including myeloid lineage leucocytes, which in patients with IBD are elevated with activation behaviour and prolonged survival. Accordingly, these leucocytes appear logical targets of therapy and can be depleted by adsorptive granulocyte/monocyte apheresis (GMA) with an Adacolumn. Based on this background, recently GMA has been applied to treat patients with IBD in Japan and in the European Union countries. Efficacy rates have been impressive as well as disappointing. In fact the clinical response to GMA seems to define the patients’ disease course, response to medications, duration of active disease, and severity at entry. The best responders have been first episode cases (up to 100%) followed by steroid naïve and patients with a short duration of active disease prior to GMA. Patients with deep ulcers together with extensive loss of the mucosal tissue and cases with a long duration of IBD refractory to existing medications are not likely to benefit from GMA. It is clinically interesting that patients who respond to GMA have a good long-term disease course by avoiding drugs including corticosteroids in the early stage of their IBD. Additionally, GMA is very much favoured by patients for its good safety profile. GMA in 21st century reminds us of phlebotomy as a major medical practice at the time of Hippocrates. However, in patients with IBD, there is a scope for removing from the body the sources of pro-inflammatory cytokines and achieve disease remission. The bottom line is that by introducing GMA at an early stage following the onset of IBD or before patients develop extensive mucosal damage and become refractory to medications, many patients should respond to GMA and avoid pharmacologics. This should fulfill the desire to treat without drugs.
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OC.11.4 LONG TERM EFFICACY OF GRANULOCYTE-MONOCYTE-APHERESIS IN ULCERATIVE COLITIS. THE ITALIAN REGISTRY OF THERAPEUTIC APHERESIS
R. Sacco, V. D’Ovidio, +18 authors G. Bresci Abstracts of the 20th National Congress of Digestive Diseases / Digestive and Liver Disease 46S (2014) S1–S144
Background and aim: Granulocyte-monocyte-apheresis (GMA) is effective in the treatment of ulcerative colitis (UC). However, all published studies evaluated a low number of patients, with an overall limited follow-up. This observational study investigates the long-term efficacy of GMA in a large number of patients included in the Italian Registry of Therapeutic Apheresis. Material and methods: Data of patients with mild/moderate UC treated with a standard protocol of GMA (5 sessions in 5 weeks) were evaluated. All patients had failed to respond to mesalamine or sulphasalazine, and were under steroid treatment. Clinical evaluations were performed at 3, 12 and 24 months since the end of GMA session. The following parameters were assessed: incidence of clinical remission (CAI [Colits Active Index] <4); CAI; erythrocyte sedimentation rate (ESR); c-reactive protein (CRP); white cells blood count (WBC). Endoscopical evaluations were performed at a 3- month follow-up: the incidence of endoscopical remission (EAI [endoscopical activity index] 0/1) was assessed. Results: Data for 347 patients (214 males, age 46.3 years; CAI 7.47) were available; 288 patients were either steroid-resistant or steroid-dependent. The proportion of patients with remission of disease was 66% at 3 months, 77% at 12 months and 78% at 24 months. At 24 months, all other efficacy parameters had improved from baseline: CAI (7.47 vs 3.47), ESR (35.87 vs 24.1 mm/h), CRP (4.31 vs 2.75 mg/dl) and WBC (8.61 vs 7.19) (p<0.001 for all comparisons). Endoscopic data were available for 107 patients. The incidence of mucosal healing was 47% and all patients with mucosal healing presented a clinical remission over the entire follow-up period. No major adverse events were reported during GMA sessions. Conclusions: Data collected on a large sample of steroid-resistant or steroidrefractory patients included in the Italian Registry of Therapeutic Apheresis show that GMA is a safe and effective procedure over a long-term follow-up. Mucosal healing appears strongly associated with clinical remission.
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Effects of Preoperative Leukocytapheresis on Inflammatory Cytokines Following Surgery for Ulcerative Colitis: A Prospective Randomized Study
Takuya Bamba 1, Takayuki Yamamoto, Satoru Umegae, Koichi Matsumoto, J Clin Apher. 2014 Apr;29(2):107-12.
Targeted extracorporeal granulocyte and monocyte apheresis (GMA) has produced clinical efficacy together with down modulation of specific inflammatory cytokines in patients with ulcerative colitis (UC). This study was to investigate if preoperative GMA produces immunological effect on dysregulated immune activity after restorative proctocolectomy (RPC) in patients with UC. Forty patients requiring RPC were included. Twenty randomly selected patients received five GMA sessions with the Adacolumn over two consecutive weeks before RPC (GMA group). RPC was performed within 2 weeks following the last GMA session. The other 20 patients did not receive GMA before RPC (non-GMA group). Blood samples were obtained immediately before surgery, at 1 h after surgery, and on postoperative Days 1, 3, and 7 from all patients. Abdominal exudate was obtained from the drainage tube at 1 h after surgery, and on postoperative Days 1, 3, and 7. Concentrations of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in plasma and peritoneal fluid from a drainage tube were measured by enzyme linked immunosorbent assay. Between the two groups, patients were matched with respect to age, sex, UC duration, severity, extent and the dose of prednisolone at surgery. IL-1β, IL-6, and TNF-α levels in plasma and peritoneal fluid were not significantly different between the two groups during the entire study period. Based on the assays of IL-1β, IL-6, and TNF-α levels in the plasma and the peritoneal fluid, this study did not find any effect on these inflammatory cytokines by preoperative GMA in patients with UC who underwent RPC.
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Granulo-monocyto apheresis is more effective in mild ulcerative colitis than in moderate to severe disease.
Chiara De Cassan 1, Edoardo Savarino 1, Piero Marson 1, Tiziana Tison 1, Giorgia Hatem 1, Giacomo Carlo Sturniolo 1, Renata D’Incà 1 , World J Gastroenterol. 2014 Dec 7;20(45):17155-62.
Patients with mild UC benefit from GMA more than patients with moderate to severe disease in the short-term period. GMA should be considered a valid therapeutic option in cases of contraindications to immunosuppressants, corticosteroids and/or biologics.
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Pouchitis: a practical guide
A Hillary Steinhart , Ofer Ben-Bassat Frontline Gastroenterol 2013 Jul;4(3):198-204. doi: 10.1136/flgastro-2012-100171. Epub 2013 Nov 12.
Up to 30% of patients with ulcerative colitis (UC) will require surgical management. The established surgical procedure of choice is colectomy with ileal pouch-anal anastomosis (IPAA) for most patients. Patients with UC who have undergone IPAA are prone to develop inflammatory and non-inflammatory complications. Up to 50% of patients can be expected to experience at least one episode of pouchitis, and most of these patients will experience at least one additional acute episode within 2 years. In other cases, pouchitis might follow a relapsing-remitting course or a chronically active course. The specific aetiology of pouchitis is unknown and the optimal means of diagnosis and classification of pouchitis is not completely agreed upon. Diagnosis of pouchitis based on symptoms alone has been shown to be non-specific due to the fact that symptoms can originate from a myriad of aetiologies, not necessarily inflammatory in nature. As a result, the diagnosis of pouchitis should generally be based on the appropriate constellation of symptoms, combined with endoscopic and histological assessment. Due to the frequently relapsing course of pouchitis, and the fact that the aetiology and pathogenesis are not entirely clear, the long-term management can sometimes be challenging. This review outlines the features suggestive of deviation from ‘normal’ pouch function and provides an approach to the optimal use of diagnostic modalities and medical therapies to treat pouchitis in its various forms.
active / antibiotic dependent / antibiotic refractory / chronic / gma / GUIDELINES / pouchitis / relapse / ulcerative colitis /
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Factors affecting short- and long-term effects of leukocyte removal therapy in active ulcerative colitis.
Ryo Nakano 1, Ryuichi Iwakiri, Yuji Ikeda, Tomoya Kishi, Nanae Tsuruoka, Ryo Shimoda, Yasuhisa Sakata, Kanako Yamaguchi, Kazuma Fujimoto, J Gastroenterol Hepatol. 2013 Feb;28(2):303-8.
Both GMA and LCAP were effective to treat active UC. However, long duration of UC, multiple UC attacks, and past history of LRT reduce the efficacy.
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Long-term prognosis of patients with ulcerative colitis treated with cytapheresis therapy
Tetsuro Takayama 1, Takanaori Kanai, Katsuyoshi Matsuoka, Susumu Okamoto, Tomohisa Sujino, Yohei Mikami, Tadakazu Hisamatsu, Tomoharu Yajima, Yasushi Iwao, Haruhiko Ogata, Toshifumi Hibi, J Crohns Colitis. 2013 Mar;7(2):e49-54.
Background: Although accumulating studies in Japan show that cytapheresis (CAP) therapy is safe and effective for the induction of remission of moderate or severe ulcerative colitis (UC), the long-term prognosis of UC patients treated with CAP is unknown. The aim of this study was to determine the long-term prognosis of UC patients treated with CAP. Methods: Ninety patients treated previously with CAP and followed for more than 3 years were evaluated. The rates of operation, readmission, and use or dose-up of corticosteroid were analyzed as long-term prognosis. Results: Following the first course of CAP treatment, 64% of patients showed clinical improvement (> 4-point decrease in the clinical activity index (CAI)), and 49% of patients achieved clinical remission (CAI ≤ 4). Longer disease duration and lower age at the first CAP treatment correlated significantly with the therapeutic effects of CAP (p = 0.003 and 0.035, respectively). The rates of operation and readmission were significantly lower in patients who showed previous clinical effects of CAP than in those who did not respond to CAP. The rates of operation and readmission were also significantly lower in patients whose treatment was combined with immunomodulators after the initiation of CAP than in patients who did not use immunomodulators. Importantly, the second course of CAP was also effective in most of the patients who showed a clinical response to the first CAP. Conclusions: Patients who achieve remission after the first CAP therapy may have a good long-term prognosis and a good response to a second CAP therapy even after relapse.
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Treatment of children and adolescents with ulcerative colitis by adsorptive depletion of myeloid lineage leucocytes as monotherapy or in combination with low dose prednisolone after failure of first-line medications.
Tomotaka Tanaka 1, Shinichiro Sugiyama, Hirokazu Goishi, Tsuyoshi Kajihara, Morihisa Akagi, Toshio Miura, BMC Gastroenterol. 2013 Aug 20;13:130.
Background: Currently available drugs for the treatment of ulcerative colitis (UC) include salicylates, thiopurines, corticosteroids and new anti-tumour necrosis factor (TNF)-α biologics. Among these medications, corticosteroids in children and adolescents may adversely affect the patients’ growth and development. Further, UC patients have elevated and activated myeloid lineage leucocytes including the CD14 + CD16+ monocytes, which release TNF-α as a significant exacerbating factor. Accordingly, depletion of these cells by granulocyte/monocyte adsorption (GMA) should alleviate inflammation and promote UC remission. The objective of this study was to evaluate the efficacy of GMA in children and adolescents in whom conventional first-line medications had failed to induce remission. Methods: In a single centre setting, between 2007 and 2012, a total of 24 consecutive children and adolescents, age 11-19 years were given mesalazine or sulphasalazine as a first-line medication. Seventeen patients relapsed or did not respond to the first-line medications, and received GMA with the Adacolumn, 2 sessions in the first week, and then weekly, up to 11 sessions. Patients who achieved a decrease of ≥5 in the clinical activity index (CAI) were to continue with GMA, while non-responders were to receive 0.5 to 1.0 mg/kg/day prednisolone (PSL) plus additional GMA sessions similar to GMA responder cases. At entry and week 12, patients were clinically and endoscopically evaluated, allowing each patient to serve as her/his own control. Results: Seven patients achieved remission with the first-line medications and did not receive GMA. Five patients did not respond to the first 5 GMA sessions and received PSL plus GMA, while 12 patients responded to the first 5 GMA sessions and received additional sessions. At entry, the average CAI was 12.7 ± 2.5, range 8-17, and the average endoscopic index was 8.5 ± 1.5, range 7-11. The corresponding values at week 12 were 2.1 ± 0.2, range 1-4 (P < 0.001) and 2.4 ± 0.2, range 1-4 (P < 0.001). PSL was tapered to 0 mg within 3 months. Conclusions: With the strategy we applied in this study, all 24 consecutive patients achieved remission. In growing patients with active UC refractory to first-line medications, GMA was associated with clinical remission and mucosal healing, while in non-responders to GMA monotherapy, addition of a low dose PSL enhanced the efficacy of GMA and tapering of the PSL dose soon after remission was not associated with UC relapse. Therefore, the majority of young corticosteroid naive UC patients in whom first-line salicylates have failed may respond to GMA and be spared from additional drug therapy. Avoiding corticosteroids at an early stage of UC should ensure better long-term clinical course.
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Therapeutic landscape for ulcerative colitis: where is the Adacolumn(®) system and where should it be?
Maurizio Vecchi 1, Piero Vernia, Gabriele Riegler, Renata D’Incà, Vito Annese, Siro Bagnoli, Clin Exp Gastroenterol. 2013;6:1-7.
Granulocyte-monocyte apheresis is a relatively new therapy that has been proposed, sometimes with controversial results, for the treatment of inflammatory bowel disease, particularly ulcerative colitis. The aim of the present study was to perform a thorough review of the literature on the application of this type of treatment in ulcerative colitis and discuss the results, in order to provide an opinion on its use which is shared by the involved experts. The review of the literature was performed by searching PubMed with appropriate key words. The results obtained suggest that the major role for this treatment at this moment is for those patients with steroid dependency or with major contraindications to use of steroids. However, promising, albeit very preliminary, results have also been observed in steroid-naïve subjects, and this is of particular interest in consideration of the safety profile of this therapeutic method. As such, the Adacolumn may prove useful in specific subgroups of patients. Future phenotypic, genotypic, and molecular characterization of patients with inflammatory bowel disease might prove useful in defining better those subjects who might benefit most from this treatment modality.
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