**Meet the editor**

Dr Sami Karoui was born in Tunis in 1968. He studied at the Faculty of Medicine of Tunis and attended Gastroenterology and Hepatology courses at University Hospitals in Tunis. He received the diploma of Gastroenterologist in 1998, and has been working at the Department of Gastroenterology, A. La Rabta Hospital – Tunis, and at the Faculty of Medicine of Tunis since 2000. Dr Karoui

also works as a Professor of Gastroenterology and Hepatology since 2008.

Contents

**Preface IX** 

Chapter 2 **Intestinal Barrier Dysfunction:** 

Chapter 4 **Role of Dipeptidyl Peptidase** 

Chapter 5 **The Roles of Interleukin-17 and** 

Yutao Yan

Chapter 7 **The Role of Imaging in** 

**Part 1 Pathogenesis of Inflammatory Bowel Disease 1** 

Sender J. Miszputen and Marcello Franco

**The Primary Driver of IBD? 23**  Pieter Hindryckx and Debby Laukens

Mladen Peršić and Jadranka Varljen

Rahul A. Sheth and Michael S. Gee

Chapter 1 **The Role of COX-2 Inhibitors on Experimental Colitis 3** 

Chapter 3 **Adenosine Receptors: New Targets to Protect Against** 

**IV/CD26 in Inflammatory Bowel Disease 59**  Dijana Detel, Lara Batičić Pučar, Ester Pernjak Pugel, Natalia Kučić, Sunčica Buljević, Brankica Mijandrušić Sinčić,

**T Helper 17 Cells in Intestinal Barrier Function 89**  Elizabeth Trusevych, Leanne Mortimer and Kris Chadee

**Part 2 Advances in Diagnosis of Inflammatory Bowel Disease 135** 

**Inflammatory Bowel Disease Evaluation 137** 

Chapter 6 **Pathogenesis of Inflammatory Bowel Diseases 111** 

Ana Paula R. Paiotti, Ricardo Artigiani-Neto, Daniel A. Ribeiro,

**Tissue Damage in Inflammatory Bowel Symptoms 41**  Sebastian Michael, H.-W. Rauwald, Haba Abdel-Aziz,

Dieter Weiser, Christa E. Müller, Olaf Kelber and Karen Nieber

## Contents

#### **Preface XI**

	- **Part 2 Advances in Diagnosis of Inflammatory Bowel Disease 135**
	- **Part 3 Management of Inflammatory Bowel Disease 247**

## Preface

Inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn's disease, are chronic and relapsing conditions, characterized by abdominal pain, diarrhea, bleeding and malabsorption. IBD is considered to be a hyper-inflammatory state due to disturbed interactions between the immune system and the commensal bacterial flora of the gut. In recent years, many studies have focused on etiopathogeny of IBD, as well as on advances in diagnosis tools. A better comprehension of mechanisms of the new drugs used for treatment of IBD has enabled new approach strategies in the management of Crohn's disease and ulcerative colitis.

There is accumulating evidence on the importance of microbes in the development and maintenance of both the intestinal and immune systems. No evidence that inflammatory bowel disease is caused by a single agent has been found, whereas a number of microbes have been strongly associated with the presence of disease. The majority of recent studies support a role for the ability of intestinal pathogens to promote chronic inflammation in individuals with genetic susceptibility and/or other environmental factors, which remain to be identified.

The lower gastrointestinal tract houses trillions of microbial cells, representing a large diversity of species in relatively well-defined phylogenetic ratios that are associated with maintenance of key aspects of host physiology and immune homeostasis. It is therefore not surprising that many GI inflammatory diseases, including inflammatory bowel disease, are associated with substantial changes in the composition of these microbial assemblages, either as a cause or consequence of host inflammatory response.

Inflammatory bowel diseases are the consequence of a dysregulated mucosal immune system. The mucosal immune system consists of two arms, innate and adaptive immunity, that have been studied separately for a long time. In the last several years, there has been a huge increase in the discovery of inflammatory bowel disease susceptibility genes. However, similar advances in identifying and defining environmental risk factors associated with IBD have lagged behind.

Treatment of inflammatory bowel disease has changed in recent years. Potential future treatment goals in Crohn's disease include reduction in bowel damage, prevention of complications and maintaining long term remission. Combination therapy with

#### X Preface

infliximab and azathioprine demonstrated superior rates of sustained clinical remission, when compared to standard therapy. In ulcerative colitis, potential treatment goals include sustained clinical remission, sustained mucosal healing and reduction of rates of colorectal dysplasia and cancer. Although tumor necrosis factor antagonists are effective for the treatment of Crohn's disease and ulcerative colitis, lack and loss of clinical response is a clinical challenge. Accordingly, the use of therapeutic drug monitoring has been proposed as a means to optimize treatment. Several observational studies have demonstrated a relationship between anti-TNF agent serum drug concentrations and/or antidrug antibody presence, and various symptomatic and objective clinical endpoints. However, these relationships are not absolute, and although some algorithms for the use of therapeutic drug monitoring in clinical practice have been proposed, none have yet been validated in a prospective clinical trial.

> **Dr. Sami Karoui**  Department of Gastroenterology A. La Rabta Hospital Tunis

X Preface

clinical trial.

infliximab and azathioprine demonstrated superior rates of sustained clinical remission, when compared to standard therapy. In ulcerative colitis, potential treatment goals include sustained clinical remission, sustained mucosal healing and reduction of rates of colorectal dysplasia and cancer. Although tumor necrosis factor antagonists are effective for the treatment of Crohn's disease and ulcerative colitis, lack and loss of clinical response is a clinical challenge. Accordingly, the use of therapeutic drug monitoring has been proposed as a means to optimize treatment. Several observational studies have demonstrated a relationship between anti-TNF agent serum drug concentrations and/or antidrug antibody presence, and various symptomatic and objective clinical endpoints. However, these relationships are not absolute, and although some algorithms for the use of therapeutic drug monitoring in clinical practice have been proposed, none have yet been validated in a prospective

**Dr. Sami Karoui** 

Tunis

Department of Gastroenterology A. La Rabta Hospital

**Part 1** 

**Pathogenesis of Inflammatory Bowel Disease** 
