Pouchitis: a practical guide
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.
Sa1316 Granulocyte and Monocyte Adsorptive Apheresis (GMA) Might Be Useful for Patients With Ulcerative Colitis by Inhibition of S100A12-S100a12 Correlates With Acute and Chronic Inflammation by Induction of CCL and CXCL Chemokines
Shingo Kato, Kazuhito Kani, Hidehiko Takabayashi, Ryuichi Yamamoto, Koji Yakabi Gastroenterology 2011 140(5) Suppl. S-279–S-280
Backgrounds&Aims; Granulocyte and monocyte adsorptive apheresis (GMA) adsorbs mainly granulocyte and monocytes, as well as Leukocyteapheresis (LMA) filters many cells such as granulocyte, monocytes, lymphocytes and platelets. However, there was no significant difference in clinical effectiveness between GMA and LMA (Eur J Gastroenterol Hepatol 2008;20:629). We hypothesized effectiveness of GMA and LMA might be dependent on depletion of granulocyte and monocytes. S100A12 was reported to be exclusively expressed in neutrophils and up-regulated by TNF α. The aim of this study was to investigate the changes of serum S100 A12 concentration in the GMA treatments and whether S100A12 increases the expression of adhesion molecules, CXCL and CCL chemokines. Methods; 24 patients with ulcerative colitis were treated with GMA. Serum S100A12 was estimated by ELISAmethods.Clinicalactivityindex(CAI)andserumCRPconcentrationwerealsochecked. Immunohistochemical staining of S100A12 and receptor for advanced glication end products (RAGE) were performed in the operated specimens of patients with ulcerative colitis and with colonic carcinoma (control). HUVEC were seeded into 12 well plates and confluent plates were used to experiments. Each experiment was performed in triplicate. HUVEC were treated with human recombinant S100A12 protein. RNA was extracted by RNeasy Mini Kit. 1.5μg RNA was reverse-transcriptated into cDNA. ICAM-1, VCAM-1, IL-8, CCL-2 (MCP1), CCL5 (RANTES), CXCL9 (IP-10) and CXCL10 (Mig) mRNA was quantitated by realtime PCR. Results; S100A12 staining was faintly recognized in the mucosal layer of normal control. S100A12 staining was increased in infiltrating cells in inflamed colon in patients with ulcerative colitis. Strong staining was also recognized in crypt abscess. RAGE staining was also faintly recognized in the epithelial cells in nornmal control. However, RAGE staining was increased in the inflamed epithelial cells. Significantly serum S100A12 concentration was positively correlated with CAI (n=34, p=0.02, rs=0.404). 16 patients were able to estimate S100A12 concentration in the points of pre-and post-GMA treatment. 13 patients wereGMA-respondersand3patientswere nonGMA-responders.SerumS100A12concentration was significantly decreased in GMA responders (pre-vs post-GMA, 1.34±1.08 vs 0.60±0.50, p<0.05). However, Serum S100A12 concentration of non GMA-responders was gradually increased with GMA treatments. ICAM-1, VCAM-1, IL-8, IP-10, Mig, MCP-1 and RANTES mRNA expressions were increased by S100A12 in HUVEC cell lines in time and dose-dependent manners. Conclusion; one of the mechanisms of GMA effect might be correlated with depletion of S100A12 by adsorption of activated neutrophils. S100A12 might aggravate acute and chronic inflammation by up-regulation of adhesion molecules, CXCL and CCL chemokines.
Emerging drugs for the treatment of ulcerative colitis
Background: Ulcerative colitis (UC) is a chronic, relapsing inflammatory disorder of the colon for which the etiology is currently unknown. At present, strategies to treat UC are primarily targeted to control inflammation during active phases of disease as well as maintain remission during quiescence. As such, several unmet needs in the treatment of UC still remain. In recent years, basic research has led to the recognition of several key factors in the pathogenesis of UC, translating into the development of several novel therapeutic agents. Objective: The aim of this study is to review emerging therapies that may advance the treatment and improve the overall care of UC patients. Methods: An extensive literature search on published manuscripts and meeting proceedings has been performed to provide a comprehensive review of future drug therapies to treat UC. Results/conclusion: The translational application of new discoveries in the basic understanding of UC pathogenesis is continuing and critical for the development of novel treatment strategies. Design of novel biologic therapies to treat UC has the challenge of addressing potential safety issues, while more traditional drugs should be further developed to facilitate patient compliance to treat this chronic, debilitating disease.
Adsorptive monocyte and granulocyte apheresis in the chronic inflammatory illness: ulcerous colitis, Crohn’s disease, rheumatoid arthritis and Behcet syndrome
J. Muñoz, M. Clavo, O. Garcia, D. Reina, A. Vidaller, R. Lafuente & L. I. Massuet
ISBT Science Series (2007) 2, 96–101
There is a strong basis to support the modulators properties of innate immunity of GCAP, although there is a lack of data that explains deeply the interactions between the mechanisms involved. GMA may represent a new therapy that offers not a single pathway effect but a global modulation of the most important pathways involved in innate immune response. Future investigations should elucidate the intimate mechanism of action.
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