
		Ulcerative colitis (UC) is a chronic inflammatory bowel disease
(IBD) associated with multiple colonic and extraintestinal
complications, the most severe being the development of colorectal
cancer (CRC). Compared to the general population, there is an
increased risk of CRC associated with UC. Although the
pathogenesis of CRC in UC is unknown, most studies have linked it
to long-standing inflammation as well as other risk factors such
as duration of disease, extent of inflammation, family history of
CRC, and coexisting conditions such as primary sclerosing
cholangitis (PSC). UC is a life-long disease for which patients
enter a vigilant screening program which includes surveillance
colonoscopy to promote early detection of CRC yet some
controversies exist regarding the cost effectiveness of
surveillance colonoscopy and improving survival. Newer modalities
such as chromoendoscopy, narrow band imaging, high definition
colonoscopy, and confocal microscopy have aided in developing a
more targeted approach for early detection of dysplasia in
surveillance colonoscopy. This review focuses on the role of
chronic colonic inflammation and dysplasia in development of
UC-associated CRC and current methods of screening, detection,
chemoprevention, and treatment of UC-associated CRC.

Sai Sunkara

Garth Swanson

Christopher B. Forsyth

Ali Keshavarzian

Chronic Inflammation and Malignancy in Ulcerative Colitis

Ulcerative colitis (UC) is a relapsing inflammatory bowel disease whose pathogenesis has yet to be defined completely. A genetic predisposition is needed to develop the colitis, but environmental factors are necessary to trigger an exaggerated and aberrant immune response, which stands at the basis of the mucosal healing. Cytokines, small cell-signaling protein molecules secreted by various types of cells including immune and glia cells, are the main mediators of the mucosal healing in IBD; ulcerative colitis is characterized by a Th2 atypical immune response, since, beside the classical proinflammatory cytokines, such as IL-1, IL-6, and TNF-α, in the pathogenesis of UC, we find a complex network in which the Th2 cytokines, IL-10 and IL-13, play a key role, but little IL-4 was found. Our aim was to review the literature to point out the state of the art in terms of cytokines because the knowledge of cytokine network in UC could lead to the discovery of  new therapeutical targets.

Giulia Roda

Margherita Marocchi

Alessandro Sartini

Enrico Roda

Cytokine Networks in Ulcerative Colitis

The aim was to characterize short- and long-term clinical outcomes of infliximab in fulminant ulcerative colitis. Patients with severe ulcerative colitis meeting the criteria of fulminant colitis after 3 days of glucocorticosteroid treatment were randomized to control or additional induction therapy of infliximab followed by an on demand/maintenance therapy of infliximab. Twenty six patients with fulminant colitis were equally randomized. At Day 7, ten patients in the control group and none in the infliximab group were in the need of colectomy (<svg style="vertical-align:-0.27pt;width:50.349998px;" id="M1" height="9.9375" version="1.1" viewBox="0 0 50.349998 9.9375" width="50.349998"  xmlns="http://www.w3.org/2000/svg"    >
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</svg>). Due to superior effect of infliximab, patients in the control group were of ethical reasons transformed to infliximab treatment instead of performing colectomy. The probability to avoid colectomy was 0.66 with a median observation time of 52 months and a maximal of 91 months. The addition of azathioprine reduced the risk of late colectomy. We conclude that infliximab is effective in preventing early and late colectomy in fulminant colitis. 


J. Florholmen

G. &#xD8;verland

T. Olsen

R. Rismo

G. Cui

I. Christiansen

E. J. Paulssen

R. Goll

Short-and Long-Term Clinical Outcomes of Infliximab in Fulminant Ulcerative Colitis

Ulcerative colitis (UC) patients are believed to have an increased risk for the colonic reactivation of cytomegalovirus (CMV) infection due to both inherent and iatrogenic factors. Numerous studies and case reports have described CMV infection as complicating the disease course of ulcerative colitis patients; the existing evidence suggests an association between the presence of CMV infection and increased colectomy and mortality rates in UC patients. Whether CMV is nonpathogenic with a tropism towards areas of dysplasia and inflammation in the colon of UC or plays an active role in pathogenesis is still debated. In this paper, we examine the existing evidence for the diagnosis and management of CMV infection in UC patients.

Minh Nguyen

Kara Bradford

Xiaolan Zhang

David Q. Shih

Cytomegalovirus Reactivation in Ulcerative Colitis Patients

Lactic acid bacteria (LAB) represent a heterogeneous group of microorganisms that are naturally present in many foods and possess a wide range of therapeutic properties. The aim of this paper is to present an overview of the current expanding knowledge of the mechanisms by which LAB and other probiotic microorganisms participate in the prevention and treatment of inflammatory bowel diseases. These include changes in the gut microbiota, stimulation of the host immune responses, and reduction of the oxidative stress due to their antioxidant properties. A brief overview of the uses of genetically engineered LAB that produce either antioxidant enzymes (such as catalase and superoxide dismutase) or anti-inflammatory cytokines (such as IL-10) will also be discussed. This paper will show that probiotics should be considered in treatment protocols of IBD since they provide many beneficial effects and can enhance the effectiveness of traditional used medicines.

Silvina del Carmen

Alejandra de Moreno de LeBlanc

Anderson Miyoshi

Clarissa Santos Rocha

Vasco Azevedo

Jean Guy LeBlanc

Potential Application of Probiotics in the Prevention and Treatment of Inflammatory Bowel Diseases


		Inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease, is reported to be associated with impaired health-related quality of life (QOL). Although decreased QOL in these subjects has been reported to be associated with various factors, the effect of nutritional therapy, especially nutrients intake on QOL has received less attention. In this study, we evaluated the various factors including nutrients intake on QOL using SF-8 in 64 patients with IBD. Patients with IBD seem to have decreased QOL especially in the mental aspects. The percentage energy intake from fat of total energy fat intake (&#x25; energy) of the whole subjects, was lower than those of the annual National Nutrition Survey in Japan. Multiple regression analyses revealed that fat intake (&#x25; energy) was a significant predictor for mental component summary. In conclusion, fat restriction contributes to impaired QOL especially in the mental aspects in IBD patients.

A. Kuwabara

H. Nakase

H. Tsuji

K. Shide

T. Chiba

N. Inagaki

K. Tanaka

Fat Restriction Is Associated with Impaired Quality of Life in Patients with Ulcerative Colitis and Crohn&#39;s Disease

In ulcerative colitis (UC), the duration and severity of inflammation are responsible for the development of colorectal cancer. Reactive oxygen species (ROS), reactive nitric metabolites (RNMs) and interleukin (IL)-8, released by epithelial and immune cells, are involved in the pathogenesis of colitis-associated cancer. Nitric oxide and peroxynitrite activate epidermal growth factor receptor (EGFR), and therapeutic agents targeted towards EGFR are currently used to treat advanced colorectal cancer. IL-8 (a G-protein coupled receptor (GPCR) agonist), which is involved in neutrophil recruitment and activation in persistent active colitis, also promotes cleavage of the proheparin-binding epidermal growth factor-like growth factor (proHB-EGF) through a disintegrin and metalloproteinase (ADAM). The cleaved HB-EGF and C-terminal fragments (intracellular CTF) regulate proliferation via EGFR activation and nuclear export of promyelocytic leukemia zinc finger, transcription repressor, respectively. Here, we focus on the mechanisms by which RNM- and IL-8-induced EGF signaling regulate cell proliferation during the development of colitis-associated cancer.

Satoshi Tanida

Tsutomu Mizoshita

Takashi Mizushima

Takaya Shimura

Takeshi Kamiya

Hiromi Kataoka

Takashi Joh

Involvement of Cell Proliferation Induced by Dual Intracellular Signaling of HB-EGF in the Development of Colitis-Associated Cancer during Ulcerative Colitis

Recurrent Aphthous Ulceration (RAU) is a chronic oral inflammatory disease that affects approximately 25% of the general population. The etiology of the disease is unknown; however, factors that favor the onset of RAU have been correlated with a Th1 immune polarization, while factors that reduce RAU episodes have been associated with down regulation of immune reaction or stimulation of the peripheral tolerance. In this context, the integrity of the epithelial barrier is also fundamental for the prevention of the disease and conditions that augment its permeability or produce disruption are considered potential triggers. The key factor responsible for increased susceptibility is unclear, though a deficiency of Toll-like receptor (TLR) activity seems to be a good candidate. TLRs are a group of membrane proteins that recognize conserved molecules derived from bacterial, virus, fungal, or host tissues. Particularly, the TLR2 is involved in both immune regulation and control of epithelial barrier integrity. Thus, based on literature review, we showed evidences that correlate the TLR2 dysfunction and the diverse predisposing factors with the elements considered critical for disease pathogenesis: the Th1 immune reaction and the increased epithelial permeability.

Fabiana M. Barros

Mônica A. Lotufo

Priscila M. Andrade

Cristiane M. França

Ricardo C. Borra

Possible Association between Th1 Immune Polarization and Epithelial Permeability with Toll-Like Receptors 2 Dysfunction in the Pathogenesis of the Recurrent Aphthous Ulceration

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