Pancreaticobiliary maljunction.

Related Articles Pancreaticobiliary maljunction. Clin Gastroenterol Hepatol. 2009 Nov;7(11 Suppl):S84-8 Authors: Kamisawa T, Takuma K, Anjiki H, Egawa N, Kurata M, Honda G, Tsuruta K, Sasaki T Pancreaticobiliary maljunction (PBM) is a congenital anomaly defined as a junction of the pancreatic and bile ducts located outside the duodenal wall, usually forming a markedly long common channel. In PBM patients, this anomaly allows regurgitation between the pancreatobiliary and biliopancreatic tract. Since hydrostatic pressure within the pancreatic duct is usually higher than that in the common bile duct, pancreatic juice frequently refluxes into the bile duct. As a result, pancreatic enzyme levels are generally very high in the bile and there is a related high incidence of biliary cancer. PBM can be divided into PBM with biliary dilatation (congenital choledochal cyst [CCC]) and PBM without biliary dilatation (maximal diameter of the bile duct

Differential diagnosis and treatment of biliary strictures.

Related Articles Differential diagnosis and treatment of biliary strictures. Clin Gastroenterol Hepatol. 2009 Nov;7(11 Suppl):S79-83 Authors: Inui K, Yoshino J, Miyoshi H Biliary tract strictures present both diagnostic and therapeutic challenges to clinicians. Advances in imaging and endoscopic techniques have improved our ability to differentiate between benign and malignant lesions. Intraductal ultrasonography (IDUS), using an endoscopic approach, has the potential to aid in separating benign and malignant biliary lesions. In a series of 93 patients, a majority of whom had cancer, we found that IDUS had a sensitivity and specificity of 89.7% and 84%, respectively, for diagnosing biliary strictures. However, benign strictures associated with untreated autoimmune pancreatitis and/or the intrapancreatic portion of the distal common bile duct could not be easily distinguished from malignant strictures. Direct visualization of biliary mucosa using a percutaneous transhepatic endoscopic approach also helps separate benign from malignant biliary strictures. Further, the ability to obtain multiple directed biopsies using a percutaneous approach also increases diagnostic accuracy. A final advantage of the percutaneous approach is that once a suitable sized tract has been established, biliary strictures and stents can be placed. IDUS and percutaneous biliary endoscopy are promising new modalities for the diagnosis and treatment of biliary strictures. PMID: 19896104 [PubMed - in process]

Intrahepatic cholangiocarcinoma progression: prognostic factors and basic mechanisms.

Related Articles Intrahepatic cholangiocarcinoma progression: prognostic factors and basic mechanisms. Clin Gastroenterol Hepatol. 2009 Nov;7(11 Suppl):S68-78 Authors: Sirica AE, Dumur CI, Campbell DJ, Almenara JA, Ogunwobi OO, Dewitt JL In this review, we will examine various molecular biomarkers for their potential to serve as independent prognostic factors for predicting survival outcome in postoperative patients with progressive intrahepatic cholangiocarcinoma. Specific rodent models of intrahepatic cholangiocarcinoma that mimic relevant cellular, molecular, and clinical features of the human disease are also described, not only in terms of their usefulness in identifying molecular pathways and mechanisms linked to cholangiocarcinoma development and progression, but also for their potential value as preclinical platforms for suggesting and testing novel molecular strategies for cholangiocarcinoma therapy. Last, recent studies aimed at addressing the role of desmoplastic stroma in promoting intrahepatic cholangiocarcinoma progression are highlighted in an effort to underline the potential value of targeting tumor stromal components together with that of cholangiocarcinoma cells as a novel therapeutic option for this devastating cancer. PMID: 19896103 [PubMed - in process]

Diagnosis of pancreatic disorders using contrast-enhanced endoscopic ultrasonography and endoscopic elastography.

Related Articles Diagnosis of pancreatic disorders using contrast-enhanced endoscopic ultrasonography and endoscopic elastography. Clin Gastroenterol Hepatol. 2009 Nov;7(11 Suppl):S63-7 Authors: Hirooka Y, Itoh A, Kawashima H, Ohno E, Ishikawa T, Matsubara H, Itoh Y, Nakamura M, Miyahara R, Ohmiya N, Niwa Y, Ishigami M, Katano Y, Goto H Contrast-enhanced endoscopic ultrasonography (CE-EUS) and EUS-elastography are cutting-edge diagnostic modalities for pancreatic disorders. Each pancreatic disorder has characteristic hemodynamics. CE-EUS uses color Doppler flow imaging to classify pancreatic lesions into a spectrum of solid and cystic patterns. Although there is overlap in the patterns generated by specific types of tumors, some types of tumors tend to produce distinct flow images. EUS-elastography can assess tissue hardness by measuring its elasticity. This parameter appears to correlate with the malignant potential of the lesions. Tissue elasticity studies can provide information on both its pattern and distribution. The former is the conventional method of morphologic diagnosis, but it is restricted to observations made in a region of interest. The latter is an unbiased analysis that can be performed by image analysis software and is theoretically constant, regardless of regions of interest. The evolving modalities of CE-EUS and EUS-elastography might provide clinical utility in the diagnosis of pancreatic disorders. PMID: 19896102 [PubMed - in process]

Distinguishing pancreatic cancer from autoimmune pancreatitis: a comparison of two strategies.

Related Articles Distinguishing pancreatic cancer from autoimmune pancreatitis: a comparison of two strategies. Clin Gastroenterol Hepatol. 2009 Nov;7(11 Suppl):S59-62 Authors: Sugumar A, Chari ST Autoimmune pancreatitis is a rare disease which closely mimics pancreatic cancer in its presentation. It is important for clinicians to distinguish one from the other due to vastly different therapeutic and prognostic implications. We compared 2 recently proposed strategies, 1 from Japan and the other from the United States, to distinguish autoimmune pancreatitis from pancreatic cancer. While both strategies have inherent strengths and weaknesses, we believe that the best features of both need prospective validation. The strategy proposed from Japan is simple to use, but is based on a small number of patients and is heavily dependent on imaging criteria. The American strategy while based on a bigger sample of patients is complicated and is most useful in expert hands. Additionally, differences in clinical practice and local preference in the use of certain diagnostic tests need to be considered while adopting either strategy. PMID: 19896101 [PubMed - in process]

Differentiating neoplastic from benign lesions of the pancreas: translational techniques.

Related Articles Differentiating neoplastic from benign lesions of the pancreas: translational techniques. Clin Gastroenterol Hepatol. 2009 Nov;7(11 Suppl):S55-8 Authors: Khalid A There has been substantial recent progress in our ability to image and sample the pancreas leading to the improved recognition of benign and premalignant conditions of the pancreas such as autoimmune pancreatitis (AIP) and mucinous lesions (mucinous cystic neoplasms [MCN] and intraductal papillary mucinous neoplasms [IPMN]), respectively. Clinically relevant and difficult situations that continue to be faced in this context include differentiating MCN and IPMN from nonmucinous pancreatic cysts, the early detection of malignant degeneration in MCN and IPMN, and accurate differentiation between pancreatic cancer and inflammatory masses, especially AIP. These challenges arise primarily due to the less than perfect sensitivity for malignancy utilizing cytological samples obtained via EUS and ERCP. Aspirates from pancreatic cysts are often paucicellular further limiting the accuracy of cytology. One approach to improve the diagnostic yield from these very small samples is through the use of molecular techniques. Because the development of pancreatic cancer and malignant degeneration in MCN and IPMN is associated with well studied genetic insults including oncogene activation (eg, k-ras), tumor suppressor gene losses (eg, p53, p16, and DPC4), and genome maintenance gene mutations (eg, BRCA2 and telomerase), detecting these molecular abnormalities may aid in improving our diagnostic accuracy. A number of studies have shown the utility of testing clinical samples from pancreatic lesions and bile duct strictures for these molecular markers of malignancy to differentiate between cancer and inflammation. The information from these studies will be discussed with emphasis on how to use this information in clinical practice. PMID: 19896100 [PubMed - in process]

Roles of pancreatic stellate cells in pancreatic inflammation and fibrosis.

Related Articles Roles of pancreatic stellate cells in pancreatic inflammation and fibrosis. Clin Gastroenterol Hepatol. 2009 Nov;7(11 Suppl):S48-54 Authors: Masamune A, Watanabe T, Kikuta K, Shimosegawa T Over a decade, there is accumulating evidence that activated pancreatic stellate cells (PSCs) play a pivotal role in the development of pancreatic fibrosis. In response to pancreatic injury or inflammation, quiescent PSCs are transformed (activated) to myofibroblast-like cells, which express alpha-smooth muscle actin. Activated PSCs proliferate, migrate, produce extracellular matrix components, such as type I collagen, and express cytokines and chemokines. Recent studies have suggested novel roles of PSCs in local immune functions and angiogenesis in the pancreas. If the pancreatic inflammation and injury are sustained or repeated, PSC activation is perpetuated, leading to the development of pancreatic fibrosis. In this context, pancreatic fibrosis can be defined as pathologic changes of extracellular matrix composition in both quantity and quality, resulting from perpetuated activation of PSCs. Because PSCs are very similar to hepatic stellate cells, PSC research should develop in directions more relevant to the pathophysiology of the pancreas, for example, issues related to trypsin, non-oxidative alcohol metabolites, and pancreatic cancer. Indeed, in addition to their roles in chronic pancreatitis, it has been increasingly recognized that PSCs contribute to the progression of pancreatic cancer. Very recently, contribution of bone marrow-derived cells to PSCs was reported. Further elucidation of the roles of PSCs in pancreatic fibrosis should promote development of rational approaches for the treatment of chronic pancreatitis and pancreatic cancer. PMID: 19896099 [PubMed - in process]

Desmoplasia of pancreatic ductal adenocarcinoma.

Related Articles Desmoplasia of pancreatic ductal adenocarcinoma. Clin Gastroenterol Hepatol. 2009 Nov;7(11 Suppl):S44-7 Authors: Pandol S, Edderkaoui M, Gukovsky I, Lugea A, Gukovskaya A Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and is characterized by remarkable desmoplasia. The desmoplasia is composed of extracellular matrix (ECM) proteins, myofibroblastic pancreatic stellate cells, and immune cells associated with a multitude of cytokines, growth factors, and ECM metabolizing enzymes. The mechanisms of participation of this complex matrix process in carcinogenesis are only starting to be appreciated. Recent studies showed key roles for stellate cells in the production of ECM proteins as well as cytokines and growth factors that promote the growth of the cancer cells all present in the desmoplastic parts of PDAC. In addition, interactions of ECM proteins and desmoplastic secreted growth factors with the cancer cells of PDAC activate intracellular signals including reactive oxygen species that act to make the cancer cells resistant to dying. These findings suggest that the desmoplasia of PDAC is a key factor in regulating carcinogenesis of PDAC as well as responses to therapies. A better understanding of the biology of desmoplasia in the mechanism of PDAC will likely provide significant opportunities for better treatments for this devastating cancer. PMID: 19896098 [PubMed - in process]

Ras activity in acinar cells links chronic pancreatitis and pancreatic cancer.

Related Articles Ras activity in acinar cells links chronic pancreatitis and pancreatic cancer. Clin Gastroenterol Hepatol. 2009 Nov;7(11 Suppl):S40-3 Authors: Logsdon CD, Ji B The relationship between chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) is unclear. CP is a risk factor for PDAC, CP is found within the vicinity of PDAC, and both share many similar genetic alterations. However, it has been long thought that PDAC arises only from duct cells. However, we have recently found that excessive activity within the Ras signaling pathway can lead to acinar cell death or metaplasia and is associated with the development of fibrosis resembling CP and the development of PDAC from acinar cells through the full complement of preneoplastic (pancreatic intraepithelial neoplasia) lesions. Therefore, it is time to reevaluate the relationship between CP and PDAC. We proposed a new model in which Ras activity is the direct link between these 2 diseases. Here we will briefly review the shared properties between CP and PDAC and describe the new model. PMID: 19896097 [PubMed - in process]

Molecular pathology of pancreatic cancer: implications for molecular targeting therapy.

Related Articles Molecular pathology of pancreatic cancer: implications for molecular targeting therapy. Clin Gastroenterol Hepatol. 2009 Nov;7(11 Suppl):S35-9 Authors: Furukawa T Pancreatic cancer develops through ductal dysplastic lesions or pancreatic intraepithelial neoplasia (PanIN). The origin of pancreatic cancer remains controversial. Some of the molecular origins of pancreatic cancer have been described. For example, KRAS, SHH, CDKN2A, TP53, SMAD4, and DUSP6 are crucial molecules in the development and progression of pancreatic cancer. Understanding the mechanisms of carcinogenesis could help researchers find the Achilles' heel of pancreatic cancer. Molecular targeting is a promising strategy for curing this devastating disease. PMID: 19896096 [PubMed - in process]

Recent developments in acute pancreatitis.

Related Articles Recent developments in acute pancreatitis. Clin Gastroenterol Hepatol. 2009 Nov;7(11 Suppl):S3-9 Authors: Talukdar R, Vege SS The incidence of acute pancreatitis (AP) has been increasing worldwide, but the major etiologies remain gallstones and alcohol. Several studies have reported that smoking is an independent risk factor for developing AP. Classification of AP has traditionally used the categories of mild and severe disease. However, a new intermediate category of moderately severe AP has been described with intermediate characteristics including a high incidence of local complications but a low mortality. Assessment criteria that can serve as early predictors of AP severity are often complex and not sufficiently accurate. However, several recently described criteria that rely on criteria such as the body mass index, physical findings, and simple laboratory measurements could prove useful if validated in large prospective studies. Many issues related to the therapy of AP are still unresolved. Although preliminary studies support the importance of early volume expansion for the treatment of acute pancreatitis, optimization of the amount and type of fluids will require further studies. Similarly, preliminary studies suggest that enteral nutrition might benefit patients with AP and could even be useful early in the course of disease. However, the timing and type of fluids as well as the intestinal infusion site require further study. Finally, issues related to the prophylactic use of antibiotics in patients with severe AP have not been resolved. While the process of clinical investigation moves slowly, progress has been made in clinical studies of AP. PMID: 19896095 [PubMed - in process]

Germ-line mutations, pancreatic inflammation, and pancreatic cancer.

Related Articles Germ-line mutations, pancreatic inflammation, and pancreatic cancer. Clin Gastroenterol Hepatol. 2009 Nov;7(11 Suppl):S29-34 Authors: Whitcomb D, Greer J The fundamental problem underlying pancreatic cancer is altered genetics. Rare germ-line mutations lead to familial cancer syndromes that may include pancreatic cancer. But why do some people develop pancreatic cancer while others develop cancer in other organs, or not at all? We discuss the possibility that other common germ-line mutations diminish the ability of pancreatic cells to protect themselves from environmental or metabolic stressors, resulting in reactive molecules that lead to cell injury and DNA damage-with a series of lucky hits knocking out key tumor-suppressor genes and activating oncogenes in at least one cell with clonal growth potential. Inflammation likely accelerates this process, whether or not it is clinically evident. We also note the significant effects of smoking, alcohol, antioxidants, and diet on risk, and that together they confer a major portion of attributable risk that may be linked to the injury-inflammation-cancer pathway. Because we cannot change our genes, lifestyle choices are currently the best way to reduce pancreatic cancer risk until more effective preventative strategies are developed. PMID: 19896094 [PubMed - in process]

Chronic pancreatitis and pancreatic cancer: prediction and mechanism.

Related Articles Chronic pancreatitis and pancreatic cancer: prediction and mechanism. Clin Gastroenterol Hepatol. 2009 Nov;7(11 Suppl):S23-8 Authors: Shimosegawa T, Kume K, Satoh K We investigated the SPINK 1 mutations in 156 sporadic pancreatic cancer (PCa), and 8 pancreatic cancer with chronic pancreatitis (CPPCa) patients, and in 527 healthy subjects. The results demonstrated that 3 of 8 patients with CPPCa (37.5%) had the SPINK 1 gene N34S mutation. In addition, 3 of 156 sporadic PCa patients (1.9%) and 1 of them (0.6%) had the N34S and IVS3+2T>C mutation, respectively. The combined frequency of 2.5% was significantly higher than that of healthy subjects (0.38%), suggesting that the SPINK 1 mutation is an important risk factor for the development of pancreatic cancer. To investigate the genetic difference between sporadic PCa and CPPCa, we investigated several factors involved in the pathogenesis of PCa in 6 CPPCa and 15 sporadic PCa patients. The factors examined were genes including K-ras, p53, smad 4, p-smad 1, CXCL 14, NF-kB subunit p65 and Wnt 5a. No significant difference was found in the comparative examination of these factors, suggesting that the molecular disorders appeared to occur similarly in CPPCa as well as sporadic PCa. To assess the role of fibrosis in pancreatic carcinogenesis, we investigated the effects of pancreatic stellate cells (PSCs), which are largely responsible for pancreatic fibrogenesis, on duct cells, in vitro and in vivo. Activated PSCs were found surrounding precancerous duct cells in the tissues of a dimethylbenzanthracene mouse model and those of human PCa. Consistently, human pancreatic epithelial duct cells cultured with PSC conditioned media showed increased cell proliferation and colony formation, suggesting that PSCs may promote pancreatic ductal tumorigenesis. PMID: 19896093 [PubMed - in process]

Long-term follow-up of autoimmune pancreatitis: characteristics of chronic disease and recurrence.

Related Articles Long-term follow-up of autoimmune pancreatitis: characteristics of chronic disease and recurrence. Clin Gastroenterol Hepatol. 2009 Nov;7(11 Suppl):S18-22 Authors: Kawa S, Hamano H, Ozaki Y, Ito T, Kodama R, Chou Y, Takayama M, Arakura N Autoimmune pancreatitis is a unique disease, characterized by lymphoplasmacytic inflammation in the acute stages. However, the active clinical features are unlikely to persist for long periods. Through long-term follow-up, we investigated the disease course in 51 patients with autoimmune pancreatitis. We found recurrence in 21 (41%) patients and pancreatic stone formation in 9 (18%) patients. Pancreatic stone formation was significantly more frequent in the recurrence group (7/21, 33%), compared with the nonrecurrence group (2/30, 7%). Moreover, we found high serum immunoglobulin G4 concentrations in 13 of 175 (7.4%) patients with ordinary chronic pancreatitis. This suggested that pancreatic stone formation is closely associated with recurrence and that autoimmune pancreatitis might transform into ordinary chronic pancreatitis after several recurrences. We found that the immune complex level, with a cutoff value of 10 microg/dL, served as a good predictor of recurrence, with high sensitivity (61.9%), specificity (70.0%), and efficacy (66.7%). We also confirmed that HLA and cytotoxic T-lymphocyte antigen-4 polymorphisms were useful predictors for AIP recurrence. PMID: 19896092 [PubMed - in process]

Long-term prognosis of acute pancreatitis in Japan.

Related Articles Long-term prognosis of acute pancreatitis in Japan. Clin Gastroenterol Hepatol. 2009 Nov;7(11 Suppl):S15-7 Authors: Takeyama Y This study was undertaken to evaluate the long-term prognosis of acute pancreatitis (AP) in Japan and to identify factors that predict major complications. In 1987, 2533 patients with moderate or severe acute pancreatitis were registered in a national survey in Japan. Follow-up studies were done in 2000 and in 2004 to evaluate recurrence of acute pancreatitis, transition to chronic pancreatitis, development of diabetes mellitus, and mortality. The relationship between incidence of complications and alcohol consumption during follow-up period was also analyzed. Valid replies were obtained from 714 cases in 2000 and 450 cases in 2004. Recurrence of acute pancreatitis occurred in 145 cases, and the recurrence rate was significantly higher in alcoholic pancreatitis compared with other etiologies. A transition to chronic pancreatitis occurred frequently in alcoholic pancreatitis and inversely correlated with existence of pancreatic necrosis in the initial disease. Complication with diabetes mellitus and the transition to chronic pancreatitis strongly correlated with persistent alcohol intake during follow-up period. During the follow-up period, 199 patients died, and 43 died of malignant disease. Recurrence of acute pancreatitis and a transition to chronic pancreatitis frequently occurred in alcoholic pancreatitis. Transition to chronic pancreatitis was inversely correlated with the existence of pancreatic necrosis at the initial presentation. Mortality as a result of malignant disease was not excessive in the patients with history of acute pancreatitis. PMID: 19896091 [PubMed - in process]

The acinar cell and early pancreatitis responses.

Related Articles The acinar cell and early pancreatitis responses. Clin Gastroenterol Hepatol. 2009 Nov;7(11 Suppl):S10-4 Authors: Gorelick FS, Thrower E Pathologic responses arising from the pancreatic acinar cell appear to have a central role in initiating acute pancreatitis. Environmental factors that sensitize the acinar cell to harmful stimuli likely have a critical role in many forms of pancreatitis, including that induced by alcohol abuse. Activation of zymogens within the acinar cell and an inhibition of secretion are critical, but poorly understood, early pancreatitis events. While there is firm evidence relating trypsinogen activation to pancreatitis, the importance of other zymogens has been less studied. Preliminary studies suggest that trypsin may be activated by mechanisms that are distinct from other zymogens. Further, unlike the small intestine, it may not catalyze the activation of other zymogens. These features could affect strategies aimed at inhibiting proteases to treat pancreatitis. Specific intracellular signals are required to activate pancreatitis pathways in the acinar cell. The most important is calcium. Recent studies have suggested that calcium release through specific calcium channels in the endoplasmic reticulum is the means by which pathological elevations in cytosolic calcium occur. Although the targets of abnormal calcium signaling are unknown, calcineurin, a calcium-dependent phosphatase, may serve such a role. Finally, recent work suggests that an acute acid load might sensitize the acinar cell to pancreatitis responses. Therapies aimed at preventing or reversing the effects of an acid load on the pancreas may be important for treatment. PMID: 19896090 [PubMed - in process]

Inflammation and carcinogenesis in the pancreas and biliary tract: mechanisms and practice.

Related Articles Inflammation and carcinogenesis in the pancreas and biliary tract: mechanisms and practice. Clin Gastroenterol Hepatol. 2009 Nov;7(11 Suppl):S1-2 Authors: Shimosegawa T, Gorelick FS PMID: 19896089 [PubMed - in process]

Indecent exposures

I have a potential conflict regarding the following discussion. I am a gastroenterologist, a Division Chief and a member of the Board of Trustees of the American College of Gastroenterology (ACG). I perform colonoscopies, a large component of my Division's income is derived from performing

Pediatrics: Amitriptyline and placebo in children with functional gastrointestinal disorders

Pediatrics: Amitriptyline and placebo in children with functional gastrointestinal disorders Nature Reviews Gastroenterology & Hepatology 6, 687 (2009). doi:10.1038/nrgastro.2009.190 Author: Isobel Franks

Colonoscopy: Unsedated colonoscopy is a feasible primary screening tool for colorectal cancer

Colonoscopy: Unsedated colonoscopy is a feasible primary screening tool for colorectal cancer Nature Reviews Gastroenterology & Hepatology 6, 688 (2009). doi:10.1038/nrgastro.2009.188 Author: Rachel Jones

Cancer: Human bacterium induces colon tumors in mice through activation of TH17 cells

Cancer: Human bacterium induces colon tumors in mice through activation of TH17 cells Nature Reviews Gastroenterology & Hepatology 6, 688 (2009). doi:10.1038/nrgastro.2009.189 Author: Joana Osório

Targeting Ras in HCC

Targeting Ras in HCC Nature Reviews Gastroenterology & Hepatology 6, 689 (2009). doi:10.1038/nrgastro.2009.191 Author: Ezzie Hutchinson

IBD: Sargramostim for corticosteroid-dependent Crohn's disease

IBD: Sargramostim for corticosteroid-dependent Crohn's disease Nature Reviews Gastroenterology & Hepatology 6, 689 (2009). doi:10.1038/nrgastro.2009.192 Author: Natalie J. Wood

Ulcerative proctitis: Potential therapeutic role for appendicectomy

Ulcerative proctitis: Potential therapeutic role for appendicectomy Nature Reviews Gastroenterology & Hepatology 6, 689 (2009). doi:10.1038/nrgastro.2009.194 Author: Rachel Jones

Liver transplantation: Predicting infectious complications after OLT

Liver transplantation: Predicting infectious complications after OLT Nature Reviews Gastroenterology & Hepatology 6, 690 (2009). doi:10.1038/nrgastro.2009.187 Author: Ezzie Hutchinson

Fecal incontinence: Efficacy of biofeedback

Heymen, S. et al. Randomized, controlled trial shows biofeedback to be superior to pelvic floor exercises for fecal incontinence. Dis. Colon Rectum52, 1730–1737 (2009).Biofeedback has long been proposed as an effective treatment for

Primary sclerosing cholangitis: The importance of treating stenoses and infections

The treatment of primary sclerosing cholangitis is a major challenge. Complications such as dominant bile duct stenoses and biliary infections are associated with poor outcomes. Data from a new prospective study with a follow-up of 20 years now show that dominant stenosis and fungal, but not bacterial infections reduce survival free of liver transplantation.

Gastrointestinal bleeding: Carvedilol—the best β-blocker for primary prophylaxis?

Endoscopic band ligation (EBL) and nonselective β-blockade are two effective strategies in the primary prevention of variceal bleeding. Meta-analyses have shown an advantage of EBL over propranolol with regard to bleeding rates but not mortality. By contrast, a recent randomized, controlled trial shows less bleeding associated with the use of carvedilol compared with EBL.

Chronic anal fissure: Surgical or reversible neurochemical sphincterotomy?

The management of chronic anal fissure has received renewed interest and has been re-evaluated over the past 20 years. The use of botulinum toxin seems to be a promising and safe approach, particularly in patients at high risk for incontinence. A recent meta-analysis investigated the efficacy of botulinum toxin injection compared with lateral internal sphincterotomy for the management of this condition.

GERD: Is laparoscopic surgery cost-effective?

A Markov model using data from a randomized, controlled trial has demonstrated that laparoscopic fundoplication is a cost-effective intervention for the management of chronic GERD. However, there are some limitations of the model, discussed below, which suggest that the results should be viewed cautiously until longer follow-up is reported.

Hepatocellular adenoma: Should phenotypic classification direct management?

The Bordeaux group has made major progress in the genotyping and phenotyping of hepatocellular adenomas. Their efforts have allowed the classification of hepatocellular adenomas into subtypes, which enhances our understanding of this benign liver lesion. The clinical relevance of their findings is open to debate.

Epidemiology of pancreatic cancer: an overview

Pancreatic cancer, although infrequent, has an exceptionally high mortality rate, making it one of the four or five most common causes of cancer mortality in developed countries. The incidence of pancreatic cancer varies greatly across regions, which suggests roles for lifestyle factors, such as diet,

Anastomoses of the lower gastrointestinal tract

Patients with gastrointestinal anastomoses are treated by physicians of multiple specialties, including gastroenterologists, radiologists and surgeons. This Review provides an overview of the surgical principles and techniques involved in the creation of lower intestinal anastomoses, including some of the mechanisms of healing. Anatomical configurations of

Endoscopy for upper gastrointestinal bleeding: is routine second-look necessary?

The benefit of routine repeat endoscopy after endoscopic hemostasis in the management of peptic ulcer bleeding is controversial. The aim of this Review is to evaluate the efficacy of second-look endoscopy by examining the evidence from published, randomized, clinical trials. Outcome measurements included recurrent bleeding,

Stem cells in gastroenterology and hepatology

Cellular and tissue regeneration in the gastrointestinal tract and liver depends on stem cells with properties of longevity, self-renewal and multipotency. Progress in stem cell research and the identification of potential esophageal, gastric, intestinal, colonic, hepatic and pancreatic stem cells provides hope for the use

CT and radiation-related cancer risk—time for a paradigm shift?

The use of CT in the US has been increasing exponentially over the past decade. The greatest increases in CT use have been in pediatric diagnosis and adult screening. Unfortunately, there is little cognizance among health-care providers (or their patients) about the relative latent cancer

Risk of ischemic stroke in patients with Crohn's disease: A population-based nested case-control study

Observational studies have linked Crohn's disease (CD) to an increased risk of venous thromboembolic complications. Case reports of ischemic stroke in CD patients have raised the question of a similar association, but data from observational studies are lacking.Using data from the UK General Practice Research Database we conducted a nested case-control analysis within a population-based cohort of 8054 patients with and 161,078 patients without CD. A total of 1748 cases of ischemic stroke were identified to whom 17,348 controls were matched on age, sex, and year of cohort entry. Adjusted odds ratios (ORs) of ischemic stroke associated with CD were calculated by conditional logistic regression. Stratified analyses were performed for age and sex.While CD was not associated with an overall increased risk of ischemic stroke (OR 1.10, 95% confidence interval [CI] 0.85-1.43), stratified analyses revealed an increase in risk in younger patients (<50 years: OR 2.93; 95% CI 1.44-5.98) but not in elderly patients ([ge]50 years: OR 0.99; 95% CI 0.75-1.30; P for interaction <0.01). The interaction with age remained statistically significant even after changing the cutoff value for the younger and older age group to 45, 55, or 60 years in a sensitivity analysis. There was no interaction with sex (P = 0.79).The study indicates that younger patients with CD may be under an increased risk of ischemic stroke. Inflamm Bowel Dis 2010

Low-dose naltrexone for treatment of duodenal Crohn's disease in a pediatric patient

No abstract.

Characterization of the novel ST2/IL-33 system in patients with inflammatory bowel disease

ST2 has been proposed to be a regulator of inflammation and Th1/Th2 balance. ST2L is the IL-33 membrane receptor and belongs to the IL-1R family. The soluble variant, ST2s, is identical to the extracellular region of ST2L and competes for IL-33 binding, inhibiting receptor signaling. Although ST2s has been associated with inflammatory processes in patients with sepsis, trauma, asthma, and autoimmunity, until now there are no reported studies showing the role of ST2/IL-33 in inflammatory bowel disease (IBD).Expression of ST2 and IL-33 was determined in serum and colonic biopsies from IBD patients. ST2 transcript and protein was determined by reverse-transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA)/immunoblot, respectively, and IL-33 protein by ELISA. Intestinal mucosa localization of ST2 and IL-33 was conducted by immunofluorescence.ST2s transcript in the colonic mucosa was mainly expressed in UC patients rather than Crohn's disease or control; however, ST2L mRNA remained constant in all samples. Total ST2 protein was significantly higher in mucosa samples from patients with active UC, with a predominant induction of ST2s that strongly correlates with serum ST2 levels. Mucosa IL-33 levels were higher in UC patients and serum levels were barely detected in all patient groups. ST2 and IL-33 are both abundantly expressed in the cytoplasm of epithelial cells of control subjects; however, in ulcerative colitis patients ST2 decreases and IL-33 showed cytoplasm-nuclear redistribution.The novel association between the ST2/IL-33 system and IBD seems to identify that variations in this axis might regulate the inflammatory process in these diseases. Inflamm Bowel Dis 2010

Genome wide association (GWA) predictors of anti-TNF[alpha] therapeutic responsiveness in pediatric inflammatory bowel disease

Interindividual variation in response to anti-TNF[alpha] therapy may be explained by genetic variability in disease pathogenesis or mechanism of action. Recent genome-wide association studies (GWAS) in inflammatory bowel disease (IBD) have increased our understanding of the genetic susceptibility to IBD. The aim was to test associations of known IBD susceptibility loci and novel "pharmacogenetic" GWAS identified loci with primary nonresponse to anti-TNF[alpha] in pediatric IBD patients and develop a predictive model of primary nonresponse.Primary nonresponse was defined using the Harvey Bradshaw Index (HBI) for Crohn's disease (CD) and partial Mayo score for ulcerative colitis (UC). Genotyping was performed using the Illumina Infinium platform. Chi-square analysis tested associations of phenotype and genotype with primary nonresponse. Genetic associations were identified by testing known IBD susceptibility loci and by performing a GWAS for primary nonresponse. Stepwise multiple logistic regression was performed to build predictive models.Nonresponse occurred in 22 of 94 subjects. Six known susceptibility loci were associated with primary nonresponse (P < 0.05). Only the 21q22.2/BRWDI loci remained significant in the predictive model. The most predictive model included 3 novel "pharmacogenetic" GWAS loci, the previously identified BRWD1, pANCA, and a UC diagnosis (R2 = 0.82 and area under the curve [AUC] = 0.98%). The relative risk of nonresponse increased 15-fold when number of risk factors increased from 0-2 to [ge]3.The combination of phenotype and genotype is most predictive of primary nonresponse to anti-TNF[alpha] in pediatric IBD. Defining predictors of response to anti-TNF[alpha] may allow the identification of patients who will not benefit from this class of therapy. Inflamm Bowel Dis 2010

Elevated IL-13R[alpha]2 in intestinal epithelial cells from ulcerative colitis or colorectal cancer initiates MAPK pathway

Chronic inflammation in ulcerative colitis (UC) is a sizeable risk factor for colorectal cancer (CRC). Interleukin-13 (IL-13) is elevated in the UC mucosa and may induce dysregulated signaling in neighboring intestinal epithelial cells (IECs) and thus function as a tumorogenic cytokine.Expression of IL-13 receptor chains on IECs obtained from control or chronically inflamed mucosa and colonic tumors was quantified by flow cytometry and immunoblot. IL-13R[alpha]1 and IL-13R[alpha]2 expression was significantly increased on IEC from UC and CRC patients compared to control and Crohn's disease (CD) subjects. Purified IEC from these subjects and cell lines expressing varying ratios of IL-13R[alpha]1 and IL-13R[alpha]2 chains were stimulated with IL-13 in vitro to investigate by immunoblot the activation of the signal transducer and activator of transcription 6 (STAT6) and mitogen activated protein kinase (MAPK) signaling pathways.Despite similarly elevated receptor expression in UC and CRC, IL-13 does not activate the STAT6 or MAPK pathways in UC, while in colonic tumors only the STAT6 pathway is activated. Using neutralizing antibodies and cell lines expressing a range of surface densities for IL-13R[alpha]1 and IL-3R[alpha]2, we demonstrate that IL-13R[alpha]2 serves a dual role, initiating MAPK signaling at low concentrations and as an inhibitory, decoy receptor at high IL-13R[alpha]2 to IL-13R[alpha]1 ratios.IL-13R[alpha]2 is both a decoy receptor and induces MAPK signal transduction, depending on its relative expression and the local concentration of IL-13, which together modulate the balance and intensity of the signaling pathways initiated in UC and CRC. Inflamm Bowel Dis 2010

Efficacy and safety of certolizumab pegol induction therapy in an unselected Crohn's disease population: Results of the FACTS survey

Switzerland was the first country to approve certolizumab pegol (Cimzia, CZP) for the treatment of patients with moderate to severe Crohn's disease (CD) in September 2007. This phase IV study aimed to evaluate the efficacy and safety of CZP in a Swiss multicenter cohort of practice-based patients.Baseline and Week 6 evaluation questionnaires were sent to all Swiss gastroenterologists in hospitals and private practices. Disease activity was assessed with the Harvey-Bradshaw Index (HBI) and adverse events were evaluated according to WHO guidelines.Fifty patients (31 women, 19 men) were included; 56% had complicated disease (stricture or fistula) and 52% had undergone prior CD-related surgery. All patients had prior exposure to systemic steroids, 96% to immunomodulators, 78% to infliximab, and 50% to adalimumab. A significant decrease in HBI was observed at Week 6 (versus Week 0) following induction therapy with CZP 400 mg subcutaneously at Weeks 0, 2, and 4 (12.6 ± 4.7 Week 0 versus 6.2 ± 4.4 Week 6, P < 0.001). Response and remission rates at Week 6 were 54% and 40%, respectively. We identified 8/11 CD patients undergoing a 50% fistula response (P = 0.021). The frequency of adverse drug reactions attributed to CZP was 6%. CZP was continued in 80% of patients beyond Week 6.In a population of CD patients with complicated disease behavior, CZP induced a response and remission in 54% and 40% of patients, respectively. This series provides the first evidence of the effectiveness of CZP in perianal fistulizing CD. Inflamm Bowel Dis 2010

Ocular manifestations in a community-based cohort of patients with inflammatory bowel disease

Ophthalmologic diseases in patients with inflammatory bowel disease (IBD) have been reported with varying frequency, mostly from tertiary referral centers. The aim was to describe the spectrum of ophthalmologic conditions in patients with IBD in a community setting and to compare it with a control non-IBD cohort.A prospective cohort of patients with Crohn's disease (CD), ulcerative colitis (UC), and non-IBD controls underwent evaluation by an ophthalmologist, including visual acuity, slit-lamp exam, and assessment of lacrimal output.The ophthalmologic exam was completed in 112 subjects; 48 with CD, 40 with UC, and 24 controls. Active intestinal disease was present in 52/88 (59%) of the IBD patients, and 79/88 (89%) were taking 5-aminosalicylates (5-ASAs). The IBD and control populations had similar age and gender profiles. Patients with IBD were more likely to report ocular symptoms (odds ratio [OR] 5.6, 95% confidence interval [CI] 1.5-20), particularly dry eyes (OR 5.3, 95% CI 1.4-19), than the control population. On objective exam, 42% of IBD patients had evidence of dry eyes. In a univariate analysis, 5-ASA use was associated with an increased risk of ocular symptoms (OR 7.4, 95% CI 0.9-64), and 5-ASA use >3 g per day was associated with an increased odds ratio of dry eyes (OR 15, 95% CI 1.9-122). Active disease was not associated with eye symptoms or dry eyes. Other eye conditions such as episcleritis, uveitis, or cataracts were infrequent in this cohort.Patients with IBD in the community frequently have dry eyes. This is associated with 5-ASA use, particularly doses >3 g per day. Whether this is a surrogate marker of disease severity is unclear. Inflamm Bowel Dis 2010

Can fecal calprotectin or lactoferrin identify postoperative recurrence in Crohn's disease?

No abstract.

Interleukin 21 expression is increased in rectal biopsies from patients with ulcerative colitis

No abstract.

CD24 is upregulated in inflammatory bowel disease and stimulates cell motility and colony formation

We investigated whether CD24 (reportedly a stem cell marker and adhesion molecule) was expressed in regenerative mucosa in inflammatory bowel disease (IBD) and whether it could be functionally relevant.CD24 expression was examined in 10 cases of IBD and the relationship of CD24 with Wnt signaling was tested using dominant negative (DN)-TCF4 expression. For functional evaluation, CD24 was 1) cloned and forcibly expressed in HCT116 (which expresses very low levels of CD24) and 2) knocked-down by RNA interference in HT29 (which expresses high levels of CD24). The effect of altered CD24 expression on proliferation/apoptosis, staurosporine-induced apoptosis, colony formation in soft agar, migration, and invasion was examined.CD24 was not expressed in normal tissue, while 10/10 cases of IBD showed CD24 upregulation. Inhibition of Wnt signaling with DN-TCF4 caused CD24 downregulation. Forced expression of CD24 did not influence cell proliferation, apoptosis, or staurosporine-induced apoptosis but it did significantly enhance colony forming efficiency (P < 0.01). Furthermore, there was increased transwell migration (P < 0.001) and invasion (P < 0.03) and there was increased cell migration in wounding assays. Conversely, knockdown of CD24 reduced transwell migration (P < 0.01) and invasion (P < 0.01) and reduced cell motility in wounding assays. CD24 knockdown did not influence proliferation, apoptosis resistance, or staurosporine-induced apoptosis.This is the first study to report upregulation of CD24 in regenerating tissue in IBD. This may be regulated by Wnt signaling and can confer enhanced colony forming ability and enhanced cell motility - features that may be important in tissue healing in the colon. Inflamm Bowel Dis 2010

Quality and publication success of abstracts of randomized clinical trials in inflammatory bowel disease presented at Digestive Disease Week

The incorporation of abstracts from scientific meetings into systematic reviews and practice guidelines may reduce publication bias and delays in implementing therapeutic interventions.All abstracts of Phase III randomized controlled trials in inflammatory bowel disease accepted at Digestive Disease Week (1998-2003) were identified. MedLine, PubMed (1997-current), EMBASE, and Google Scholar were searched for subsequent full publications. Characteristics of methodology and outcomes of the abstracts and articles were analyzed.The 5-year cumulative publication rate of the 82 eligible abstracts was 78%. Abstracts that presented negative results were less likely to be published than those with positive findings, particularly after the first 2 years (hazard ratio 6.45; 95% confidence interval [CI]: 2.22-18.7) with 5-year cumulative publication rates of (50% versus 91%, respectively, P < 0.001). The median time to publication was longer for negative than positive abstracts (58 versus 26 months, P < 0.001). Abstracts selected for oral presentation were more likely to be published than poster presentations (89% versus 69%; P = 0.03). A change in primary outcome results was observed in 28% (n = 18) of abstracts compared to that in the final publication, and 6% (n = 4) had a statistically significant change resulting in a change of study conclusions.Our findings suggest that the use of abstract data would enable detection and mitigation of publication bias. Improving the uniformity and quality of abstract reporting of randomized clinical trials at scientific meetings may facilitate their incorporation in practice guidelines and systematic reviews. Inflamm Bowel Dis 2010

Nutriose, a prebiotic low-digestible carbohydrate, stimulates gut mucosal immunity and prevents TNBS-induced colitis in piglets

We investigated a prebiotic low-digestible carbohydrate (LDC) as a possible food ingredient to stimulate bowel functions in the treatment of inflammatory bowel disease. The study aimed to assess a fermentable dextrin fiber (Nutriose) and its relationship to the immune management of the disease and the microbiota profile in colitis-bearing piglets.In a randomized placebo-controlled parallel blind preclinical study, 32 male piglets were fed LDC (4% Nutriose) or dextrose placebo for 44 days before being challenged with trinitrobenzene sulfonic acid (TNBS) to induce colitis. We followed the microbiota profile using real-time polymerase chain reaction (PCR) targeted to 9 bacterial genera. Secretory IgA was evaluated by enzyme-linked immunosorbent assay (ELISA). Inflammatory protein profiles were monitored in blood and colonic tissues. Both histological scoring of biopsy samples and live endoscopic scoring were used to measure colitis development.Prior and continuing LDC supplementation alleviated the symptoms of colitis (body weight loss, bloody stools) induced by a TNBS challenge. This effect was associated with an improvement in endoscopic and histological scores. LDC was shown to selectively downregulate some of the proinflammatory factors and their concomitant pyretic events and to stimulate the Th2-related immune pathway (IL-10 and s-IgA).At the dose tested, LDC is a well-tolerated prebiotic agent able to not only stimulate butyrogenic bacteria strains and reduce intestinal transit disorders and energy intake, but also to prevent chronic inflammatory intestinal injuries. Inflamm Bowel Dis 2010

Asymmetric endoscopic inflammation of the ileal pouch: A sign of ischemic pouchitis?

Pouchitis is associated with dysbiosis and dysregulated mucosal immunity, although secondary pouchitis with special etiologic factors, such as ischemia, can occur. The aim was to describe a disease phenotype of the ileal pouch with an endoscopic appearance suggestive of ischemia.We identified consecutive patients with endoscopic asymmetric inflammation of the pouch (inflammation of side of the pouch with a completely normal other limb of the pouch one limb and a sharp demarcation along the staple suture line). Patients with Crohn's disease (CD) of the pouch or antibiotic-responsive pouchitis, matched for duration of the pouch, served as controls. Histology slides of mucosal biopsies were re-reviewed independently by 2 blinded gastrointestinal pathologists. Demographic, clinical, endoscopic, histologic, and imaging characteristics were compared between the groups.Ten patients with "ischemic" pouchitis, 15 with CD of the pouch, and 15 with antibiotic-responsive pouchitis were studied. Pyloric gland metaplasia was observed only in the groups with CD of the pouch (23.1%) or antibiotic-responsive pouchitis (13.3%). Of patients with "ischemic" pouchitis, 80% had extracellular hemosiderin or hematoidin deposits (versus 30.8% those with CD of the pouch and 13.3% of those with pouchitis, P = 0.003). The majority of patients (80%) with "ischemic" pouchitis did not respond to conventional antibiotic therapy. It appeared that subsequent abdominal surgeries after pouch construction and a history of postoperative portal vein thrombi were associated with "ischemic" pouchitis.Endoscopic asymmetric inflammation of the pouch may represent an ischemia-associated pouchitis with characteristic clinical, radiographic, and histologic features. Its hemodynamic, cellular, and molecular basis of mechanism warrants further study. Inflamm Bowel Dis 2010

Health-related quality of life of youth with inflammatory bowel disease: A comparison with published data using the PedsQL 4.0 generic core scales

This study compared youth and parent-proxy reports of health-related quality of life (HRQoL) among youth with inflammatory bowel disease (IBD) to published comparison group data and examined concordance between youth and parent-proxy reports of HRQoL.One hundred thirty-six youth and parent-proxy reports on the PedsQL 4.0 Generic Core Scales were compared to published data from chronically ill, acutely ill, and healthy comparison groups using independent samples t-tests. Reporter agreement was examined using paired samples t-tests and intraclass correlations (ICCs).Youth with IBD reported lower psychosocial functioning than the healthy comparison group, higher physical and social functioning than the chronically ill group, and lower school functioning than all published comparison groups. Parent-proxy reports of youth HRQoL were higher than the chronically ill group, but lower than the healthy group on all scales except psychosocial functioning. Youth with active IBD reported lower physical health domain scores than youth with inactive disease. Concordance between youth and parent-proxy reports was moderate, with the lowest agreement in school and social functioning.Youth with IBD and their parents rate HRQoL as lower than healthy youth but do not perceive the impact of IBD to be as limiting as in other chronic conditions. Youth report suggests that IBD may be particularly detrimental to HRQoL in the school functioning domain. Moderate agreement between parent and youth reports substantiates continued use of multiple informants in studies of pediatric HRQoL. Inflamm Bowel Dis 2010

The path to Crohn's disease: Is mucosal pathology a secondary event?

Current models of Crohn's disease (CD) invoke an initial disturbance of the epithelial interface between the gut mucosa and intestinal microbiota. This "outside-in" paradigm, mirroring the pathophysiology of acute gastroenteritis, suggests that mucosal damage by luminal bacteria is an early, initiating factor in the etiopathogenesis of disease. However, a number of features of CD argue against a primary mucosal process, including phenotypic studies of CD patients that point to a macrophage defect and genetic studies that predict impaired innate immunity to intracellular bacteria. Intracellular pathogens, such as Listeria, Salmonella, and Mycobacteria, invade via the gastrointestinal tract with minimal or no acute mucosal pathology. These organisms then infect and persist in lymphatic tissues before inducing pathology, in the gut or elsewhere, as a secondary process. In a disease resulting from impaired macrophage responses to intracellular pathogens, mucosal damage could instead represent a terminal event in the pathogenesis of disease. Such an "inside-out" model is also compatible with observations on postoperative disease relapses where subepithelial pathology precedes ulceration. This alternative disease paradigm suggests that clinical and experimental research efforts should be directed at deeper processes in the gut wall and attached mesentery to understand how intracellular bacteria could initiate or exacerbate this chronic inflammatory disease. (Inflamm Bowel Dis 2010)

Ulcerative colitis in northern Portugal and Galicia in Spain

Clinical and therapeutic patterns of ulcerative colitis (UC) are variable in different world regions. The purpose of this study was to examine two close independent southern European UC populations from 2 bordering countries and observe how demographic and clinical characteristics of patients can influence the severity of UC.A cross-sectional study was conducted during a 15-month period (September 2005 to December 2006) based on data of 2 Web registries of UC patients. Patients were stratified according to the Montreal Classification and disease severity was defined by the type of treatment taken.A total of 1549 UC patients were included, 1008 (65%) from northern Portugal and 541 (35%) from Galicia (northwest Spain). A female predominance (57%) was observed in Portuguese patients (P < 0.001). The median age at diagnosis was 35 years and median years of disease was 7. The majority of patients (53%) were treated only with mesalamine, while 15% had taken immunosuppressant drugs, and 3% biologic treatment. Most patients in both groups were not at risk for aggressive therapy. Extensive colitis was a predictive risk factor for immunosuppression in northern Portugal and Galicia (odds ratio [OR] 2.737, 95% confidence interval [CI]: 1.846-4.058; OR 5.799, 95% CI: 3.433-9.795, respectively) and biologic treatment in Galicia (OR 6.329, 95% CI: 2.641-15.166). Younger patients presented a severe course at onset with more frequent use of immunosuppressors in both countries.In a large population of UC patients from two independent southern European countries, most patients did not require aggressive therapy, but extensive colitis was a clear risk factor for more severe disease. (Inflamm Bowel Dis 2010)

Subepithelial dendritic B cells in orofacial granulomatosis

Orofacial granulomatosis (OFG) is a chronic, disfiguring, granulomatous inflammation of the lips and oral mucosa. The pathogenesis is unknown, but it has been linked previously to Crohn's disease (CD) and more recently to dietary sensitivity. The oral mucosa is an immunologically responsive site associated with the generation of protective mucosal and systemic immune responses to vaccination and also hyperresponsiveness to allergens in some individuals. Classically, immune responses in oral mucosa are considered to be mediated by mucosa-associated lymphoid tissues (MALT), secondary lymphoid follicles that are intimately associated with epithelia.Immunohistochemistry was used to investigate the inflammatory infiltrate in OFG and control tissue samples. Polymerase chain reaction (PCR), cloning of PCR products, and sequencing were used to characterize the local immunoglobulin gene profile in OFG.We describe large, active, dendritic B cells in oral mucosa that were not associated with any organized lymphoid tissues in the local subepithelial microenvironment. They express activation induced cytidine deaminase, which is essential for immunoglobulin gene diversification by somatic hypermutation and class switch recombination. IgE is also expressed by these B cells. They do not align with any other previously described B-cell subset in secondary lymphoid tissues in terms of morphology, proliferative activity, or phenotype.These subepithelial dendritic B cells may contribute to the immune responsiveness of the oral mucosa, including IgE-mediated allergic responses. In patients with OFG, further understanding of the role these cells play in oral immunity may lead to novel therapeutic possibilities. (Inflamm Bowel Dis 2010)

Magnetic resonance follow-through imaging for evaluation of disease activity in ileal Crohn's disease: An observational, retrospective cohort study

Magnetic resonance follow-through (MRFT) is a new cross-sectional imaging modality with the potential to accurately stage ileal Crohn's disease (CD), while avoiding ionizing radiation and the discomfort associated with enteroclysis. We aimed to assess the reliability of this technique in assessing the extent and activity of ileal CD, and to assess its influence on subsequent management.Out of a total of 342 patients undergoing MRFT between 2004 and 2008, 221 were performed in 191 patients with confirmed CD. Case notes were reviewed in detail with documentation of all investigations pre- and post-MRFT. Agreement between inflammatory markers, histopathology, and MRFT findings was determined.Overall, 116/221 (52.5%) of MRFTs showed active ileal CD, and 76/221 (34.4%) quiescent CD, while 29/221 (13.1%) were suboptimal. Overall, 66 strictures and 18 fistulae were identified. There was substantial agreement between active ileal CD on MRFT and histopathology (n = 59; [kappa] = 0.66; P = 0.0006; sensitivity 85.1%, specificity 85.7%) and fecal calprotectin (n = 14; [kappa] = 0.72; P = 0.047), while C-reactive protein (CRP) showed moderate agreement (n = 107; [kappa] = 0.402; P = 0.00028). Management was influenced by MRFT reports following active (52/84, 62% treated medically) or quiescent (48/62, 77.4% managed conservatively) disease. Fibrotic strictures were predominantly treated surgically (7/14, 50%). In all, 13/32 (40.6%) patients with inflammatory ileal strictures required surgery, mostly due to steroid-resistant disease. Overall, 75 MR findings were documented in 221 MRFTs, including 1 renal cancer.MRFT provides accurate information on ileal CD activity, with close agreement to inflammatory markers and histopathology. It represents a substantial advance in the staging of CD, while avoiding painful enteroclysis and radiation exposure in young patients. (Inflamm Bowel Dis 2010)

Targeting TGF-[beta]1 by employing a vaccine ameliorates fibrosis in a mouse model of chronic colitis

Intestinal fibrosis and stricture formation are major complications of inflammatory bowel disease (IBD), for which there are currently few effective treatments. We sought to investigate whether targeting transforming growth factor-beta1 (TGF-[beta]1), a key profibrotic mediator, with a peptide-based virus-like particle vaccine would be effective in suppressing intestinal fibrosis by using a mouse model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced chronic colitis.The vaccine was prepared by inserting a peptide derived from mouse TGF-[beta]1 into a carrier hepatitis B core antigen using gene recombination methods. Chronic colitis was induced in BALB/c mice by 8 weekly TNBS administrations. Mice were subcutaneously injected with vaccine, carrier, or phosphate-buffered saline (PBS) in 2 separate studies: either before or after acute inflammatory responses commenced.Sera from vaccinated mice exhibited significantly elevated levels of TGF-[beta]1-specific immunoglobulin G (IgG), which inhibited TGF-[beta]1-induced luciferase production in mink lung epithelial cells. In the chronic colitis model, mice receiving vaccine showed improved body weight gain and significantly reduced colonic collagen deposition. Hematoxylin and eosin staining and semiquantitative scoring indicated that vaccination even ameliorated colonic inflammation. Cytokine profile analysis revealed that levels of TGF-[beta]1, interleukin (IL)-17, and IL-23 in vaccinated mouse colon tissues were decreased, and that percentages of IL-17-expressing CD4+ lymphocytes in mesenteric lymph node cells were reduced. Furthermore, Smad3 phosphorylation, a key event in TGF-[beta] signaling, was decreased in colonic tissue in vaccinated mice.This TGF-[beta]1 peptide-based vaccine, which suppressed excessive TGF-[beta]1 bioactivity, may prevent the development of intestinal fibrosis and associated complications, presenting a novel approach in the treatment of IBD. (Inflamm Bowel Dis 2010)

Methotrexate for maintenance of remission in chronic active Crohn's disease: Long-term single-center experience and meta-analysis of observational studies

According to current guidelines methotrexate (MTX) should be considered as a second-line immunomodulator in patients with chronic active Crohn's disease (CD) if purine analogs are not tolerated or there is a lack of efficacy. However, its therapeutic role remains controversial to the present day.Medical records of all eligible patients treated in the outpatient clinic of the Johann Wolfgang Goethe-University Hospital between December 2000 and January 2009 were reviewed.Sixty-three patients were identified. The mean duration of treatment was 100 weeks (range, 2-364 weeks) with a mean cumulative dose of MTX of 2130 mg (range, 40-9005 mg). In 50 (79%) patients started on MTX clinical remission could be achieved within 3 months of treatment. The cumulative probability of these patients to maintain remission was 95.3%, 89.5%, 70.6%, and 62.8% at 6 months, 1, 2, and 3 years of treatment, respectively. The respective figures of the meta-analysis were 94%, 86%, 75%, 53%, and 43. Drug-related side effects were reported in 50 patients (79%), leading to withdrawal of MTX in 21 cases (33%).Along with previous observations our data demonstrate the efficacy of MTX as a second-line immunomodulator in chronic active CD. However, its use is limited due to intolerable side effects in a large proportion of patients. The results should encourage further research in order to establish the definite significance of MTX in chronic active CD. (Inflamm Bowel Dis 2010)

Impact of prior irregular infliximab dosing on performance of long-term infliximab maintenance therapy in Crohn's disease

Infliximab is efficacious in the management of moderate to severe Crohn's disease (CD). There are limited data regarding performance of infliximab in patients who require reinitiation of maintenance dosing following previous irregular exposure.This was a retrospective, observational study of CD patients treated with maintenance infliximab beyond 3 years. Maintenance infliximab infusion regimens were categorized as scheduled maintenance (SM) (maintenance infusions q [le]8 weeks after loading) or prior irregular (PI) (no loading, gap in therapy >8 weeks prior to or during maintenance therapy). We examined differences in need for medical and surgical hospitalizations as well as associated healthcare costs between the 2 groups.In all, 104 CD patients met criteria for 3-year maintenance infliximab treatment (SM n = 64; PI n = 40). The rates of CD-related surgeries (60.9% and 55.0%, P = not significant [N.S.]) and medical hospitalizations (35.9% and 37.5%, P = N.S.) prior to infliximab initiation was similar between the 2 groups. However, the rate of medical (26.5% versus 47.5%, P = 0.035) and surgical hospitalizations (21.8% versus 48.7%, P = 0.009) were significantly lower in the SM compared to the PI group. During the third year of treatment the excess costs per patient for the PI group compared to the SM group amounted to $11,464 in spite of both cohorts being on SM therapy.Patients who begin and continue an uninterrupted maintenance dosing regimen had a lower incidence of hospitalization and surgery than those who received an irregular or interrupted regimen prior to beginning an SM regimen. (Inflamm Bowel Dis 2010)

Lipopolysaccharide exposure is linked to activation of the acute phase response and growth failure in pediatric Crohn's disease and murine colitis

Systemic exposure to lipopolysaccharide (LPS) has been linked to clinical disease activity in adults with inflammatory bowel disease (IBD). We hypothesized that markers of LPS exposure and the acute phase response (APR) would be increased in pediatric IBD patients with growth failure, and that LPS signaling would be required for induction of the APR in murine colitis.Serum markers of LPS exposure, endotoxin core IgA antibody (EndoCAb), and the APR, LPS binding protein (LBP) were quantified in pediatric IBD patients and controls. LBP and cytokine production were determined after administration of trinitrobenzene sulfonic acid (TNBS) enemas to mice with genetic deletion of Toll-Like receptor 4 (TLR4), and wildtype (WT) controls.Serum EndoCAb and LBP were significantly elevated in patients with Crohn's disease (CD), compared to disease controls with ulcerative colitis (UC) and healthy controls (P < 0.001). This was independent of disease activity or location. CD patients with elevated serum EndoCAb and LBP exhibited linear growth failure which persisted during therapy. Serum LBP increased in WT mice following TNBS administration, in conjunction with increased serum TNF-[alpha], IL-6, and IL-10, and expansion of regulatory T-cell numbers. Both the APR and expansion of foxp3+ T cells were abrogated in TLR4-deficient mice, in conjunction with a reduction in acute weight loss.LPS exposure and a persistent APR are associated with growth failure in pediatric CD. LPS signaling is required for the APR in murine colitis. Therapies targeting this pathway may benefit the subset of patients with refractory growth failure. (Inflamm Bowel Dis 2010)

Randomized, double-blind, placebo-controlled trial of the oral interleukin-12/23 inhibitor apilimod mesylate for treatment of active Crohn's disease

Interleukin-12 (IL-12) and interleukin-23 (IL-23) are inflammatory cytokines linked to the Th-1 and Th-17 phenotypes associated with Crohn's disease (CD). We investigated the activity and safety of apilimod mesylate (formerly STA-5326), an oral IL-12 and IL-23 inhibitor, in patients with active CD.We performed a multicenter, Phase 2, randomized, double-blinded, placebo-controlled study to evaluate the efficacy of apilimod mesylate in treating 220 adult patients with moderate-to-severe CD (Crohn's Disease Activity Index [CDAI] score 220-450). Patients were stratified according to C-reactive protein (CRP) levels and corticosteroid use and were randomly assigned to receive placebo or apilimod mesylate 50 mg daily or 100 mg daily. The study was divided into an induction phase (43 days) and a maintenance phase (125 days). The primary analysis involved a comparison of the proportion of patients experiencing clinical response, defined as at least a 100-point decrease in CDAI score from baseline at day 29. Data on adverse events were also collected.In all, 220 of the planned 282 patients were enrolled when the Data Monitoring Committee determined that the drug was not efficacious as a treatment and closed enrollment. A clinical response was experienced by 18 patients (24.7%) in the 50-mg daily (QD) group (n = 73) and 19 patients (25.7%) in the 100 mg QD group (n = 74), as compared with 21 patients (28.8%) in the placebo group (n = 73) on day 29 (P = 0.71 for each comparison). No significant adverse safety signal was observed.Apilimod was well-tolerated but did not demonstrate efficacy over placebo in patients with active CD. (Inflamm Bowel Dis 2009)

Validation of the Spanish version of a questionnaire to measure quality of care through the eyes of patients with inflammatory bowel disease (QUOTE-IBD)

Crohn's disease (CD) and ulcerative colitis (UC) are chronic immunoinflammatory diseases that place a considerable burden on patients, their families, and society. Quality of care plays an important role for patients. A questionnaire to measure quality of care through the eyes of patients with inflammatory bowel disease (QUOTE-IBD) has been designed and validated specifically for the English language and culture. The objective was to translate the QUOTE-IBD into Spanish and to determine its validity in patients with IBD.This is a prospective study in 2 phases: first, translation and validation of the Spanish QUOTE-IBD. Translation was based on the validated QUOTE-IBD. Second, once the complete translation was finished, comprehension of the items was assessed with a specific questionnaire in a reduced number of patients. Criterion validity was assessed with the Pearson's correlation coefficient between scores of the QUOTE-IBD and visual analog scales (VAS). In order to analyze the reproducibility of the Spanish QUOTE-IBD, the questionnaire was completed by stable patients twice, with a span of time of at least 4 weeks.A total of 103 patients (CD: 61, UC: 42) were included in the study. Pearson's correlation coefficient between total care Spanish QUOTE-IBD and VAS of health care items was 0.34 (P < 0.001). Correlations among all 6 care dimensions score of Spanish QUOTE-IBD and VAS were statistically significant (P < 0.01). Results of first and second administration of total care and dimensional care scores of Spanish QUOTE-IBD in 46 stable patients were not different.The Spanish QUOTE-IBD has proved to be a valid instrument to measure the quality of health care for patients with CD and UC. (Inflamm Bowel Dis 2009)

Single-port access laparoscopic surgery for complex Crohn's disease

No abstract.

Outcome of medical treatment of stricturing and penetrating Crohn's disease: A retrospective study

Outcomes of medical treatment in patients with stricturing and penetrating Crohn's disease (CD) are not well characterized.Adults with stricturing and penetrating CD who underwent medical treatment from 2004 to 2008 were evaluated. We assessed response rates to medical treatment, time to relapse or surgery, and postoperative complications.In all, 53 patients underwent medical therapy. 60% had stricturing disease, 11% had penetrating, and 28% had both. Disease location was ileal in 38%, colonic in 2%, and ileocolonic in 60%. At 30, 60, and 90 days, 54%, 60%, and 64% experienced a response to medical therapy, respectively. At 30 days, 75% of patients with ileal CD responded to therapy compared to 38% of patients with ileocolonic CD (P = 0.026). Overall, 64% of patients required surgery. Patients with ileocolonic disease required surgery at 0.55 years versus 1.07 years in patients with ileal disease (P = 0.023). 24% of patients experienced an anastomotic leak, fistula, or abscess (IASC). 29% of patients with penetrating disease developed IASC compared to 6% of patients with stricturing disease (P = 0.047). 32% of patients on biologic therapy had IASC compared to 0% of those not on biologics (P = 0.059).The outcomes of medical treatment of stricturing or penetrating CD are poor, as 64% ultimately require surgery. Important factors that seem to be associated with either failed therapy include ileocolonic or colonic disease location. We report a high rate of IASC, especially in patients with penetrating disease and those treated with biologic therapy. This should be considered prior to attempted medical therapy. (Inflamm Bowel Dis 2009)

TLR9 mRNA expression is upregulated in patients with active ulcerative colitis

No abstract.

Angiopoietin-2 in experimental colitis

The pathophysiology of inflammatory bowel disease (IBD) includes leukocyte infiltration, blood and lymphatic remodeling, weight loss and protein enteropathy. The roles of angiopoietin-2 (Ang-2) in initiating gut inflammation, leukocyte infiltration and angiogenesis are not well understood.Disease activity index, histopathological scoring, myeloperoxidase assay, immunohistochemistry and sodium dodecyl sulphate- polyacrylamide gel electrophoretic methods were employed in the present study to addess the roles of Ang-2 in experimental colitis.Several important differences were seen in the development of experimental IBD in Ang-2-/- mice. Although weight change and disease activity differ only slightly in WT and Ang-2-/- + DSS treated mice, leukocyte infiltration, inflammation and blood and lymphatic vessel density is significantly attenuated compared to WT + DSS mice. Gut capillary fragility and water export (stool blood and form) appear significantly earlier in Ang-2-/- + DSS mice vs. WT. Colon lengths were also significantly reduced in Ang-2-/- and gut histopathology was less severe in Ang-2-/- compared to WT + DSS. Lastly, the decrease in serum protein content in WT + DSS was less severe in Ang-2-/- + DSS, thus protein losing enteropathy (PLE) a feature of IBD is relieved by Ang-2-/-.These data demonstrate that in DSS colitis, Ang-2 mediates inflammatory hemangiogenesis, lymphangiogenesis and neutrophil infiltration to reduce some, but not all clinical features of IBD. The implications for Ang-2 manipulation in the development of IBD and other inflammatory diseases and treatments involving Ang-2 are discussed. (Inflamm Bowel Dis 2009)

Fine-scale geographic variations of inflammatory bowel disease in France: Correlation with socioeconomic and house equipment variables

In a previous study we found a north-south gradient for Crohn's disease (CD) incidence in France. The aim of the present study was to determine if socioeconomic factors may influence the geographic distribution of CD and ulcerative colitis (UC) in France.Using the national health insurance databases, incidence rates of CD and UC were estimated for each of 341 metropolitan "job areas" in 2000-2002. Relationships between incidence rates and relevant contextual variables from the 1999 French census were tested for significance using a Poisson regression. Mapping of smoothed relative risks (sRR) for CD and UC at the scale of job areas, using a Bayesian approach and adjusting for significant contextual variables, was carried out in order to search for geographic variations.CD incidence rates were negatively related to the percentage of farmers and to the percentage of housing with bathroom and toilets and positively related to the unemployment rate and to the percentage of households below the poverty threshold. Mapping of sRR for CD showed a clear north-south gradient, which was slightly improved after including the percentage of farmers and the percentage of housing with toilets. In UC we found no significant correlation between either incidence and socioeconomic variables or incidence and house equipment variables, and there was no north-south gradient. However, there was a positive and significant correlation between CD and UC incidence.The present study shows that geographic risk factors of CD in France are northern latitude, nonrural areas, and areas with poor sanitary house equipment. Among these factors the most important is northern latitude. (Inflamm Bowel Dis 2009)

Exogenous alkaline phosphatase for the treatment of patients with moderate to severe ulcerative colitis

Increased activity of intestinal alkaline phosphatase (AP) occurs locally in patients with ulcerative colitis (UC), aimed at repairing inflammatory tissue damage. We evaluated the safety and preliminary efficacy of exogenous AP administered to patients with UC in an open-label, first-in-patient exploratory trial, conducted in the Internal Medicine and Gastroenterology hospital departments in the Czech Republic and Italy.Twenty-one patients were enrolled (13 females), age 23-54 years, with steroid- and/or immunosuppressant-refractory, moderate/severe UC (Mayo score 6-11). Oral AP enzyme 30,000 U was administered daily for 7 days, intraduodenally. Efficacy outcomes were changes in Mayo score at Day 21 posttreatment; changes in Modified Truelove-Witts Severity index (MTWSI) at Days 21, 63; C-reactive protein and stool calprotectin levels at Days 7, 21, 63. Safety evaluations were adverse events and laboratory abnormalities reported up to Day 63 posttreatment.No clinically relevant adverse events causing withdrawal or considered serious, or laboratory abnormalities or antibody formation against AP were observed. Mayo scores were significantly decreased at Day 21, and MTWSI at Days 21 and 63. C-reactive protein and stool calprotectin levels were decreased at Days 21 and 63. Clinical response on the Mayo score after a single 7-day AP course was 48% at Day 21.In this uncontrolled trial, administration of exogenous AP enzyme daily over a 7-day course to patients with UC was associated with short-term improvement in disease activity scores, with clinical effects being observed within 21 days and associated with reductions in C-reactive protein and stool calprotectin. AP enzyme treatment was well tolerated and nonimmunogenic. (Inflamm Bowel Dis 2009;)

Babesiosis in a patient on infliximab for Crohn's disease

No abstract.

Campylobacter concisus and other Campylobacter species in children with newly diagnosed Crohn's disease

Campylobacter concisus and other members of the Campylobacter genus have recently been suggested as possible etiological agents of Crohn's disease (CD). To further investigate this issue we determined the prevalence of these organisms in pediatric patients newly diagnosed with CD.DNA was extracted from fecal specimens collected from 54 children with CD, 27 noninflammatory bowel disease (non-IBD), and 33 healthy controls and subjected to polymerase chain reaction (PCR) sequencing.Detection of C. concisus DNA using a newly developed PCR assay targeting the 16S rRNA gene of C. concisus showed that 65% (35/54) of fecal samples from CD children were positive, a prevalence significantly higher than that in the healthy (33%, 11/33, P = 0.008) and non-IBD controls (37%, 10/27, P = 0.03). The prevalence of all Campylobacter DNA using genus-specific primers in children with CD was 72% (39/54), which was significantly higher than the 30% (10/33, P = 0.0002) and 30% (8/27, P = 0.0003) observed in healthy and non-IBD controls, respectively.Given the strengthening evidence for a significantly higher prevalence of C. concisus and other non-jejuni Campylobacter species in pediatric CD, investigation into the role of these non-jejuni Campylobacter species in the initiation of human IBD is clearly a priority. (Inflamm Bowel Dis 2009;)

Safety of immunomodulators and biologics for the treatment of inflammatory bowel disease during pregnancy and breast-feeding

The aim of this article is to critically review available data regarding the safety of immunomodulators and biological therapies during pregnancy and breast-feeding in women with inflammatory bowel disease. Methotrexate and thalidomide can cause congenital anomalies and are contraindicated during pregnancy (and breast-feeding). Although thiopurines have a Food and Drug Administration (FDA) rating D, available data suggest that these drugs are safe and well tolerated during pregnancy. Although traditionally women receiving azathioprine or mercaptopurine have been discouraged from breast-feeding because of theoretical potential risks, it seems that these drugs may be safe in this scenario. Treatment with cyclosporine for steroid-refractory ulcerative colitis (UC) during pregnancy can be considered safe and effective, and the use of this drug should be considered in cases of severe UC as a means of avoiding urgent surgery. Breast-feeding is contraindicated for patients receiving cyclosporine. Biological therapies appear to be safe in pregnancy, as no increased risk of malformations has been demonstrated. Therefore, the limited clinical results available suggest that the benefits of infliximab and adalimumab in attaining response and maintaining remission in pregnant patients might outweigh the theoretical risks of drug exposure to the fetus. Stopping therapy in the third trimester may be considered, as it seems that transplacental transfer of infliximab is low prior to this. Certolizumab differs from infliximab and adalimumab in that it is a Fab fragment of an antitumor necrosis factor alpha monoclonal antibody, and therefore it may not be necessary to stop certolizumab in the third trimester. The use of infliximab is probably compatible with breast-feeding. (Inflamm Bowel Dis 2009;)

Diagnostic value of noninvasive combined fluorine-18 labeled fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography enterography in active Crohn's disease

The role of combined localized positron emission tomography (lPET) and computed tomography enterography (CTe) in Crohn's disease is unclear. We examined if this imaging modality using fluorine-18 labeled-fluoro-2-deoxy-D-glucose (FDG) could more effectively identify disease activity.52 lPET-CTe scans were analyzed in this retrospective study. CTe scores and FDG uptake were quantified. Correlations of CTe scores and standard uptake value (SUV) with C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), short Inflammatory Bowel Disease Questionnaire (sIBDq), and Harvey-Bradshaw index (HBI) were estimated using Pearson analysis. Imaging scores were compared to medical outcome by logistics regression model.CTe scores correlated with SUV, but additional abnormal segments of small bowel were not identified. In all, 38 (79%) abnormal CTe segments demonstrated increased FDG uptake with mean SUVmax 4.77; 10 (21%) abnormal CTe segments lacked FDG accumulation, with mean SUVmax 1.27. There was no correlation between SUVmax and CRP, ESR, sIBDq, or HBI. There were no significant differences in clinical indices, biochemical parameters, and presence of multiple abnormal segments between medical responders and uptake were associated with failed medical therapy (P = 0.001).PET scanning added to CTe did not identify additional abnormal segments when compared to CTe alone. Abnormal segments with mucosal enhancement on CTe that did not accumulate FDG were significantly associated with failure of medical therapy. A larger trial is warranted to confirm if combined lPET-CTe has an important role in the clinical management of stricturing Crohn's disease. (Inflamm Bowel Dis 2009;)

Prevalence of hepatitis B and C and risk factors for nonvaccination in inflammatory bowel disease patients in Northeast France

Data regarding the prevalence of hepatitis C (HCV) and hepatitis B (HBV) in inflammatory bowel disease (IBD) patients are conflicting.In all, 315 IBD (252 Crohn's disease [CD] and 63 ulcerative colitis [UC]) patients were consecutively recruited between June 2005 and May 2009.The median age was 33 years (interquartile range [IQR]: 24-43) and median disease duration was 5 years (IQR: 2-11). Present and/or past HBV and HCV infection was found in 2.86% of 315 patients (CD: HBsAg 0.79%, anti-HBc 2.78%, anti-HCV 0.79%; UC: HBsAg 1.59%, anti-HBc 1.59%, anti-HCV 1.59%). Effective vaccination (anti-HBs without anti-HBc) was present in 48.9% of 315 patients. In multivariate analysis, age at diagnosis over 31 years (odds ratio [OR] 0.29; 95% confidence interval [CI] 0.15-0.58; P = 0.005), disease duration over 7 years (OR 0.43; 95% CI 0.23-0.83; P = 0.005), age at inclusion over 33 years (OR 0.44; 95% CI 0.20-0.94; P = 0.005), and CD (OR 0.29; 95% CI 0.15-0.58; P = 0.005) were associated with the lack of effective vaccination. Two HBsAg-positive patients, including 1 under curative nucleoside/nucleotide analog treatment, had received 6 and 7 infliximab infusions, and 1 HCV RNA-positive subject had been receiving corticosteroid and azathioprine therapies for 12 and 33 months, respectively. No viral reactivation occurred in these patients.The prevalence of HBV and HCV infection in French IBD patients is similar to that of the general population. While the ECCO recommends an effective HBV vaccination in IBD, half of the patients were not vaccinated. The nonvaccination risk factors identified in our study may allow targeted vaccination coverage. (Inflamm Bowel Dis 2009;)

Tissue factor -1208D>I polymorphism is associated with D-dimer levels in patients with inflammatory bowel disease

No abstract

Novel model of TH2-polarized chronic ileitis: The SAMP1 mouse

SAMP1/Yit mice develop spontaneous, segmental, transmural ileitis recapitulating many features of Crohn's disease (CD). The ileitic phenotype may have arisen during crosses of SAMP1 mice selected for the presence of skin lesions. We hereby describe that the original SAMP1 strain similarly develops ileitis. Our aim was to characterize the histopathological and immunological features of this model and assess its responsiveness to standard inflammatory bowel disease (IBD) therapy.The time course of histopathological features of ileitis was assessed. Immune compartments were characterized by flow cytometry. Ileal cytokine profiles and transcription factors were determined by real-time reverse-transcription polymerase chain reaction (RT-PCR). Finally, response to corticosteroid therapy and its effect on immune compartments and cellularity was evaluated.Histological features and time course of disease were conserved, compared to those reported in SAMP1/Yit strains, with similar expansion of CD19+, CD4+, and CD8+ effector (CD44high CD62Llow), and central memory lymphocytes (CD44highCD62Lhigh). However, different from SAMP1/YitFc mice, analysis of ileal cytokine profiles revealed initial TH1 polarization followed by TH2-polarized profile accompanied by prominent eosinophilia during late disease. Lastly, corticosteroids attenuated ileitis, resulting in decreased lymphocyte subsets and cellularity of compartments.Here we report that the ileitic phenotype of SAMP1-related strains was already present in the original SAMP1 strain. By contrast, the cytokine profile within the terminal ilea of SAMP1 is distinct from the mixed TH1/TH2 profile of SAMP1/YitFc mice during late disease, as it shows predominant TH2 polarization. Dissemination of these strains may advance our understanding of CD pathogenesis, which in 60% of patients involves the terminal ileum. (Inflamm Bowel Dis 2009)

Cdcs1 a major colitis susceptibility locus in mice; Subcongenic analysis reveals genetic complexity

The cytokine-deficiency-induced colitis susceptibility (Cdcs)1 locus is a major modifier of murine inflammatory bowel disease (IBD) and was originally identified in experimental crosses of interleukin-10-deficient (Il10-/-) mice. Congenic mice, in which this locus was reciprocally transferred between IBD-susceptible C3H/HeJBir-Il10-/- and resistant C57BL/6J-Il10-/- mice, revealed that this locus likely acts by inducing innate hypo- and adaptive hyperresponsiveness, associated with impaired NF-[kappa]B responses of macrophages. The aim of the present study was to dissect the complexity of Cdcs1 by further development and characterization of reciprocal Cdcs1 congenic strains and to identify potential candidate genes in the congenic interval.In total, 15 reciprocal congenic strains were generated from Il10-/- mice of either C3H/HeJBir or C57BL/6J genetic backgrounds by 10 cycles of backcrossing. Colitis activity was monitored by histological grading. Candidate genes were identified by fine mapping of congenic intervals, sequencing, microarray analysis, and a high-throughput real-time reverse-transcription polymerase chain reaction (RT-PCR) approach using bone marrow-derived macrophages.Within the originally identified Cdcs1-interval, 3 independent regions were detected that likely contain susceptibility-determining genetic factors (Cdcs1.1, Cdcs1.2, and Cdcs1.3). Combining results of candidate gene approaches revealed Fcgr1, Cnn3, Larp7, and Alpk1 as highly attractive candidate genes with polymorphisms in coding or regulatory regions and expression differences between susceptible and resistant mouse strains.Subcongenic analysis of the major susceptibility locus Cdcs1 on mouse chromosome 3 revealed a complex genetic structure. Candidate gene approaches revealed attractive genes within the identified regions. (Inflamm Bowel Dis 2009;)

MDP-NOD2 stimulation induces HNP-1 secretion, which contributes to NOD2 antibacterial function

Human neutrophil peptide 1 (HNP-1) is a defensin with antibacterial activity secreted by various cells as a component of the innate immune host defense. NOD2 is a cytoplasmic protein that recognizes bacterial derived muramyl dipeptide, and is involved in bacterial clearance. The aim of the present study was to investigate the relationship between antibacterial activity of NOD2 and HNP-1 expression in epithelial cell lines.Gentamicin protection assay using Salmonella typhimurium was performed in Caco-2 cells. The mRNA level was determined by quantitative reverse-transcription polymerase chain reaction (RT-PCR) and defensin expression was assessed by Western blot and enzyme-linked immunosorbent assay (ELISA). Nuclear factor-[kappa]B activation was assessed using pIV luciferase and Renilla plasmids. A NOD2 mutant was generated by site-directed mutagenesis.Among the defensins tested, only HNP-1 expression is induced in colonic epithelial model HCT116 cells after MDP-LD stimulation. HNP-1 secretion is significantly increased after MDP-LD stimulation in the cell supernatant of intestinal epithelial cells expressing endogenous NOD2, but not in cells that lack endogenous NOD2 expression. HNP-1 is required for NOD2-dependent NF-[kappa]B activation after MDP-LD stimulation since hnp-1 siRNA transfection abrogated the response to MDP-LD stimulation. The antibacterial function of NOD2 against S. typhimurium was impaired when expression of HNP-1 was blocked by siRNA.HNP-1 secretion depends on NOD2 stimulation by MDP-LD and contributes to antibacterial activity in intestinal epithelial cells expressing endogenous NOD2, but not NOD2 3020insC mutant associated with increased susceptibility to Crohn's disease. (Inflamm Bowel Dis 2009)

Surgery for low-grade colorectal dysplasia in ulcerative colitis: Decisions, decisions

No abstract.

A33 antigen-deficient mice have defective colonic mucosal repair

A33 antigen is a transmembrane protein expressed predominantly in normal intestinal epithelium and most colon cancers and cell lines. The function of A33 antigen is unclear, but indirect evidence indicates a role in cell adhesion, trafficking, and the gut immune response. The aim of this study was to determine the contribution made by A33 antigen in mediating colonic repair following colitis induction in the A33 antigen-deficient mutant mouse.Colitis was induced by treatment with TNBS/ethanol. A33 antigen-deficient or wildtype mice were sacrificed at 0, 3, 7, and 14 days after colitis induction and morphological damage, mucosal proliferation, and inflammatory cell infiltration were quantified. In a subsequent study, following the induction of colitis mice were monitored for 22 days and morbidity and mortality determined.Mice lacking A33 antigen expression were compromised in their ability to resolve TNBS-induced damage and exhibited distinct crypt pathology. In A33 antigen-deficient mice morphological damage remained unresolved at 14 days postcolitis induction. Increases in colonic cell proliferation were delayed in A33 antigen-deficient mice, and the rate of crypt fission was increased after TNBS treatment. Commensurate with these observations, polymorphonuclear cell infiltration was suppressed in the absence of A33 antigen. Mortality following colitis induction was 20% higher in A33 antigen-deficient mice than in wildtype controls.Mice deficient in A33 antigen expression show impaired resolution of hapten-induced mucosal damage, leading to increased mortality, associated with impaired epithelial cell proliferation and a suppressed adaptive immune response. This study suggests a contribution for A33 antigen in the colonic healing response following mucosal damage. (Inflamm Bowel Dis 2009)

TL1A produced by lamina propria macrophages induces Th1 and Th17 immune responses in cooperation with IL-23 in patients with Crohn's disease

Tumor necrosis factor (TNF)-like protein 1A (TL1A) is a member of the TNF superfamily and contributes to the pathogenesis of Crohn's disease (CD) by stimulating T-helper (Th) 1 cells. In addition to Th1, recent studies have focused on the role of Th17 cells in the pathogenesis of CD. Here we tried to clarify the role of TL1A in Th1 and Th17 immunity in CD.TL1A expression was assessed by quantitative reverse-transcription polymerase chain reaction (RT-PCR) in lamina propria (LP) macrophages (LP-M[phis]s) from normal controls (NC) and patients with CD or ulcerative colitis (UC). Purified LP CD4+ T cells were stimulated with TL1A and/or IL-23 and interferon gamma (IFN-[gamma]) and interleukin (IL)-17 levels were analyzed. We also examined the effect of TL1A on naïve CD4+ T-cell differentiation.We found that LP-M[phis]s are a major producer of TL1A. TL1A expression was markedly enhanced in LP-M[phis]s from CD patients compared with NC or UC patients. IL-23, in addition to TL1A, was induced in LP-M[phis]s by commensal bacteria stimulation. TL1A and IL-23 synergistically promoted the production of IFN-[gamma] and IL-17 by LP T cells, while TL1A alone did not induce cytokine production. Furthermore, TL1A promoted Th17 differentiation from naïve T cells by LP-M[phis]s; however, IL-23 did not show any synergistic effects on Th17 differentiation.TL1A expressed in LP-M[phis]s might play an important role in the pathogenesis of CD by inducing Th1 and Th17 immunity. IL-23 differentially regulated these functions of TL1A on memory and naïve T cells. Inflamm Bowel Dis 2009

Natural history of Crohn's disease: Comparison between childhood- and adult-onset disease

Childhood-onset Crohn's disease (CD) might reflect a more severe form of disease. To test this hypothesis we analyzed the long-term natural history of CD in an adult cohort of patients with childhood-onset compared to adult-onset CD.We selected 206 childhood-onset CD patients among 2992 adult patients with a diagnosis of CD established before December 31, 2000. Disease characteristics were prospectively assessed during follow-up until December 2007 and compared to adult-onset CD patients matched 2 to 1 on gender, year of CD diagnosis, and disease location.Compared to adult-onset CD, patients with childhood-onset CD were more likely to have a severe disease, with an increased year-by-year disease activity index (37% of patient-years in childhood-onset group versus 31% in the adult-onset group, P < 0.001). Immunosuppressant requirement was also increased with a 10-year cumulative risk of 54 ± 3% in childhood-onset CD group versus 45 ± 2%, in the adult-onset CD group (P < 0.001). Cumulative risks of stricturing and penetrating complications and surgical resections were not statistically different between groups. Accordingly, these events occurred at a younger age in the childhood-onset CD group. At the age of 30 years the actuarial risk of having undergone an extensive intestinal resection was 48 ± 5% in the childhood-onset group versus 14 ± 2% in the adult-onset group (P < 0.001).Patients with childhood-onset CD exhibit a more active disease and require more immunosuppressive therapy. This feature is observed irrespective of the disease location, suggesting an intrinsic more severe phenotype. Inflamm Bowel Dis 2009

Interleukin-19 protects mice from innate-mediated colonic inflammation

Inflammatory bowel disease (IBD) results from the chronic dysregulation of the mucosal immune system and the aberrant activation of both the innate and the adaptive immune responses. We used two complementary models of colonic inflammation to examine the roles of interleukin (IL)-19 in colonic inflammation and thus its possible role in IBD.Using gene-targeting, we generated IL-19-deficient mice. To study the activation of the innate immune response during colonic inflammation we characterized an innate immune-mediated model of colitis induced by dextran sulfate sodium (DSS). DSS can induce not only acute colitis but also chronic colitis. In addition to the acute DSS-induced colitis model, we used a chronic DSS-induced colitis model that is associated with the activation of both Th1 and Th2 cytokines as well as innate immune response in the colon.We show that IL-19-deficient mice are more susceptible to experimental acute colitis induced by DSS, and this increased susceptibility is correlated with the accumulation of macrophages and the increased production of IFN-[gamma], IL-1[beta], IL-6, IL-12, TNF-[alpha], and KC. Additionally, cytokine production in IL-19-deficient macrophages was enhanced on stimulation of lipopolysaccharide (LPS) through reduced phosphorylation of STAT1 and STAT3. Moreover, our results clearly demonstrate that IL-19 is required for B-cell infiltration during chronic DSS-induced colitis, which may be mediated by IL-13 and IL-6.The finding that IL-19 drives pathogenic innate immune responses in the colon suggests that the selective targeting of IL-19 may be an effective therapeutic approach in the treatment of human IBD. Inflamm Bowel Dis 2009

Inflammatory bowel disease in young people: The case for transitional clinics

The incidence of inflammatory bowel disease (IBD) is increasing among adolescents. In all, 25% of patients are diagnosed before the age of 16, when they are traditionally transferred from the pediatric to the adult service.We conducted a retrospective case-controlled study to characterize patients treated in a novel transitional adolescent-young adult IBD clinic. This compared disease extent, radiation exposure, therapeutic strategy, and requirement for surgery in 100 adolescents with controls from our adult IBD clinic matched for disease duration.The median (range) ages for the adolescent and adult population was 19 (16-28) and 43 (24-84), with a median age at diagnosis of 15 (3-26) and 39 (13-82) respectively (P < 0.001). Crohn's disease was significantly more common in the adolescents. Disease distribution was ileocolonic in 69% of adolescents and 28% of adults, restricted to the ileum in 20% of adolescents and 47% of adults, and colonic only in 11% and 22%, respectively. Upper gastrointestinal involvement occurred in 23% of adolescents, but was not seen in adults (P < 0.01). Total ulcerative colitis was seen in 67% of adolescents and 44% of adults (P < 0.01). Contrary to previous data adolescents did not receive more ionizing radiation than adults. Requirement for immunosuppressive therapy was higher in the adolescent group (53% versus 31%, respectively, P < 0.01). Likewise, 20% of adolescents had required biological therapy compared to only 8% in the adult cohort (P < 0.05).Gastroenterologists should recognize that IBD is more complex when presenting in adolescence and our data support the creation of specific adolescent transitional clinics. Inflamm Bowel Dis 2009

Genome-wide gene expression analysis of mucosal colonic biopsies and isolated colonocytes suggests a continuous inflammatory state in the lamina propria of patients with quiescent ulcerative colitis

Genome-wide gene expression (GWGE) profiles of mucosal colonic biopsies have suggested the existence of a continuous inflammatory state in quiescent ulcerative colitis (UC). The aim of this study was to use DNA microarray-based GWGE profiling of mucosal colonic biopsies and isolated colonocytes from UC patients and controls in order to identify the cell types responsible for the continuous inflammatory state.Adjacent mucosal colonic biopsies were obtained endoscopically from the descending colon in patients with active UC (n = 8), quiescent UC (n = 9), and with irritable bowel syndrome (controls, n = 10). After isolation of colonocytes and subsequent extraction of total RNA, GWGE data were acquired using Human Genome U133 Plus 2.0 GeneChip Array (Affymetrix, Santa Clara, CA). Data analysis was carried out by principal component analysis and projection to latent structure-discriminant analysis using the SIMCA-P 11 software (Umetrics, Umeå, Sweden).A clear separation between active UC, quiescent UC, and control biopsies were found, whereas the model for the colonocytes was unable to distinguish between quiescent UC and controls. The differentiation between quiescent UC and control biopsies was governed by unique profiles containing gene expressions with significant fold changes. These primarily belonged to the family of homeostatic chemokines, revealing a plausible explanation for the abnormal regulated innate immune response seen in patients with UC.This study has demonstrated the presence of a continuous inflammatory state in quiescent UC, which seems to reflect an altered gene expression profile of lamina propria cells. Inflamm Bowel Dis 2009

Magnetic resonance imaging for Crohn's disease: Is this really the end of colonoscopy?

No abstract

The good, the bad, and the ugly: Adverse events and Crohn's therapies

No abstract

Perianal fistulae in Crohn's Disease: Current and future approaches to treatment

Perianal fistulae are common in Crohn's disease but rarely heal without treatment. The main aim of treatment is to effectively close the fistula without affecting sphincter integrity and continence. Traditional surgical and medical approaches are not without their limitations and may result in either comorbidity, such as fecal incontinence, or incomplete healing of the fistulae. Over the last 2 decades these limitations have led to a paradigm shift toward the use of biomaterials, and more recently cell-based therapies, which have met with variable degrees of success. This review discusses the traditional and current methods of treatment, as well as emerging and possible alternative approaches that may improve fistula healing. Inflamm Bowel Dis 2009

Fecal calprotectin variability in Crohn's disease

No abstract

A further cause of secondary restless legs syndrome: Crohn's disease

No abstract.

Colocolic intussusception in a patient with ulcerative colitis

No abstract.

Clostridium difficile and inflammatory bowel disease: More questions than answers?

No abstract.

Crohn's disease patient with right lower quadrant abdominal pain for 20 years due to an appendiceal neuroma (Fibrous obliteration of the appendix)

No abstract.

Ulcerative colitis in a Southern European country: A national perspective

The incidence, prevalence, and even the clinical behavior of ulcerative colitis (UC) are highly variable in different world regions. In previous studies, Portugal was reported as having a milder clinical behavior. The aim of this study was to apply the Montreal Classification in a large group of UC Portuguese patients in order to describe their clinical characteristics and evaluate variables potentially useful for outcome prediction.A cross-sectional study based on data collected from a nationwide online registry was undertaken.In all, 2863 patients with UC were included. Twenty-one percent had ulcerative proctitis, 52% left-sided colitis, and 28% extensive colitis. Sixty percent of patients had taken steroids, 14% immunosuppressors, 1% biologicals, and 4.5% were submitted to surgery. Patients with extensive colitis had more severe activity, needing more steroids, immunosuppressors, and surgery. At the time of diagnosis 61% were less than 40 years old and 5% less than 16. Younger patients also had a more aggressive initial course. Thirty-eight percent of patients had only taken salicylates during the disease course and were characterized by a lower incidence of systemic symptoms at presentation (3.8% versus 8.8%, P < 0.001), fewer extraintestinal manifestations (7.7% versus 24.0%, P < 0.001), and a higher prevalence of proctitis (32.1% versus 10.0%).A more aggressive phenotype was found in extensive colitis and in the initial course of younger patients, with an increased need for steroids and immunosuppressors. In addition, a significant percentage of patients, particularly with proctitis, showed a milder clinical evolution and were maintained in remission only with salicylates. (Inflamm Bowel Dis 2009)

Cerebral thromboembolic events in pediatric patients with inflammatory bowel disease

There is a recognized association between pediatric inflammatory bowel disease (IBD) and cerebral thromboembolic events (CTEs). Historical reporting had described the association as strongest between ulcerative colitis (UC), rather than Crohn's disease (CD). We describe the incidence and outcome of CTE in pediatric IBD patients from a single center over 5 years and the relative proportion of stroke reported in the literature in patients with UC and CD before and after January 2000.Demographic data were extracted on all newly diagnosed cases of IBD in our center from January 2003 to January 2008 to ascertain patient characteristics, disease type, risk factors for CTE, modality of neuroimaging, and outcome. A literature search was performed to identify all articles describing stroke in pediatric IBD. All identified studies were stratified into those published before and after January 1 2000.In all, 154 new patients diagnosed with IBD (male 56%) (UC 30%, CD 64%, IBD unclassified [IBDU] 6%) were reviewed. Four cases of CTE occurred in our population over 5 years (2.6%). All patients had a risk factor for CTE. Fifteen case series were identified with 32 patients. There was a significant increase in the proportion strokes affecting patients with CD reported after January 2000 (P = 0.02).CTE affects a proportion of pediatric IBD patients. Although resolution of physical impairment is the norm, significant morbidity exists. Our study suggests a secular trend toward CTE in CD. Primary prevention with the identification and amelioration of identifiable risk factors should be the clinical objective in future studies. (Inflamm Bowel Dis 2009)

Mycobacterium avium subsp. Paratuberculosis (MAP) as a modifying factor in Crohn's disease

Crohn's disease (CD) is a multifactorial syndrome with genetic and environmental contributions. Mycobacterium avium subspecies paratuberculosis (MAP) has been frequently isolated from mucosal tissues of patients with CD but the cellular immune response to this bacterium has been poorly described. Our aim was to examine the influence of MAP on T-cell proliferation and cytokine responses in patients with inflammatory bowel disease (IBD).Peripheral blood mononuclear cells (PBMCs) and mesenteric lymph node cells (MLNCs) were obtained from IBD patients and non-IBD controls. PBMC T-cell proliferation in response to MAP was determined using CFSE labeling and flow cytometry. The specificity of cytokine responses to MAP was controlled by parallel exposure to Listeria monocytogenes (LM) or Salmonella typhimurium (ST).Coincubation of PBMCs with MAP induced significantly more T-cell proliferation (P < 0.0001) in PBMCs isolated from CD patients compared to PBMCs obtained from ulcerative colitis (UC) patients or healthy volunteers. In addition, PBMCs from CD patients secreted significantly higher (P < 0.05) levels of tumor necrosis factor-alpha (TNF-[alpha]; 2302 ± 230 pg/mL) and interleukin (IL)-10 (299 ± 48 pg/mL) in response to MAP compared to UC patients (TNF-[alpha]: 1219 ± 411 pg/mL; IL-10: 125 ± 19 pg/mL) and controls (TNF-[alpha]: 1447 ± 173 pg/mL; IL-10: 127 ± 12 pg/mL). No difference in cytokine responses was observed in response to LM or ST. MLNCs from both CD and UC patients secreted significantly more TNF-[alpha] and IL-8 in response to MAP compared to MLNCs from non-IBD control patients.Increased proliferation of T cells and an altered cytokine response suggest that prior exposure to MAP and engagement of the immune system is common in patients with CD. This does not imply causation but does support further examination of this bacterium as an environmental modifying factor. (Inflamm Bowel Dis 2009)

Association between blood flow and inflammatory state in a T-cell transfer model of inflammatory bowel disease in mice

Adoptive transfer of naive T-lymphocyte subsets into lymphopenic mice initiates chronic gut inflammation that mimics several aspects of inflammatory bowel disease (IBD). Patients with IBD can have profound alterations in intestinal blood flow, but whether the same is true in the T-cell transfer model has yet to be determined.In the current study, chronic intestinal inflammation was induced in recombinase-activating gene-1-deficient (RAG-/-) mice by adoptive transfer of CD4+ T-lymphocytes obtained from interleukin-10 deficient (IL-10-/-) mice.Four weeks later, widespread colonic inflammation was observed in the reconstituted recipients, in contrast to 2 control sets of mice injected with a different subset of lymphocytes or with vehicle alone. We observed that the resulting pathology induced in the reconstituted RAG-/- mice was divided distinctly into 2 subsets: 1 with blood flow near normal with very high inflammation scores, and the other with severely attenuated blood flow but with much lower signs of inflammation. Colonic and ileal blood flow rates in the latter subset of CD4+ mice averaged only [ap]30% compared to the mice with higher inflammation scores. The lower blood flow rates were associated with greatly reduced red blood cell concentrations in the tissue, suggesting a possible loss of vascular density.In this model of chronic intestinal inflammation, mild inflammation was associated with significant decreases in blood flow. Inflamm Bowel Dis 2009

Turner's syndrome, autoimmune thyroiditis, and Crohn's disease in the same patient: A combination emphasizing the role of X-chromosome in inflammatory bowel disease patients

No abstract.

Recurrent cytomegalovirus infection in ileal pouch-anal anastomosis for ulcerative colitis

No abstract.

Teduglutide, a novel mucosally active analog of glucagon-like peptide-2 (GLP-2) for the treatment of moderate to severe Crohn's disease

Teduglutide, an analog of glucagon-like peptide-2 (GLP-2), is associated with trophic effects on gut mucosa. Its role in the treatment of active Crohn's disease (CD) was assessed in a pilot, randomized, placebo-controlled, double-blinded, dose-ranging study.Subjects with moderate-to-severe CD were randomized 1:1:1:1 to placebo or 1 of 3 doses of teduglutide (0.05, 0.10, or 0.20 mg/kg daily) delivered as a daily subcutaneous injection for 8 weeks. The primary outcome measure was the percentage of subjects in each group that responded to treatment, defined as a decrease in Crohn's Disease Activity Index (CDAI) score to 100 points. At week 8 there was an optional 12-week open-label period of treatment with teduglutide 0.10 mg/kg/d.One hundred subjects were enrolled and 71 completed the study. The mean baseline CDAI score was 290.8 ± 57.6 and was similar across groups. There were numerically higher response and remission rates in all teduglutide-treated groups as compared with placebo, although the percentage of subjects who achieved a clinical response or remission was more substantial, and seen as early as week 2 of treatment in the highest dose (0.2 mg/kg/d) group (44% response and 32% remission versus 32% response and 20% remission in the placebo group). Of subjects who had not achieved remission during the 8-week placebo-controlled phase in the higher-dose group, 50% achieved remission during the more prolonged, open-label treatment phase. Plasma citrulline was similar across groups at baseline, but increased substantially over time in all teduglutide groups when compared with placebo at week 8. Adverse events were not different between placebo and active treatment groups.Teduglutide is a novel and potentially effective therapy for inducing remission and mucosal healing in patients with active moderate-to-severe CD. Further clinical investigation of this growth factor is warranted. Inflamm Bowel Dis 2009

The position of the amino group on the benzene ring is critical for mesalamine's improvement of replication fidelity

Individuals with ulcerative colitis are at high risk of developing colitis-associated cancer. 5-Aminosalicylate (5-ASA) protects from cancer by its antiinflammatory activity as well as by altering cell growth, inducing apoptosis, and reducing replication errors. So far neither 5-ASA's structural specificity nor its pharmacophore group have been identified. Here we compared 5-ASA with its analogs (4-ASA and 3-ASA) and its metabolite N-acetyl-5-ASA (NAc-5-ASA).Superoxide scavenging was analyzed by lucigenin-amplified chemiluminescence. Cell growth, cell cycle distribution, and replication fidelity at a (CA)13 microsatellite were measured in HCT116 and HT29 colon epithelial cells by MTT and flow cytometry. Nuclear protein extracts were blotted for replication protein A (RPA), claspin, p53, and p53Ser15.All compounds inhibited the growth of colon epithelial cells at a similar level and displayed potent scavenging properties, with 3-ASA being the most active, followed by 5-ASA, 4-ASA, and NAc-5-ASA. Besides 5-ASA, only 4-ASA caused an increase in the S-phase population (56%-69% and 49%-62% in HCT116 and HT29 cells, respectively). This was accompanied by nuclear recruitment of replication proteins RPA and claspin as well as phosphorylation of p53Ser15, both of which were weaker or absent with 3-ASA or NAc-5-ASA. 5-ASA was the only compound that lowered mutations at a (CA)13 microsatellite.5-ASA shares its growth inhibitory and superoxide scavenging properties with its structural analogs and metabolite, but the position of the amino group is critical for reducing replication errors. Inflamm Bowel Dis 2009

Pityriasis lichenoides chronica induced by adalimumab therapy for Crohn's disease: Report of 2 cases successfully treated with methotrexate

No abstract.

Relationships between inflammatory bowel disease and perinatal factors: Both maternal and paternal disease are related to preterm birth of offspring

The aims of this study were to explore the influences of familial, maternal, and paternal inflammatory disease (IBD) on perinatal outcomes in the offspring and the risk for development of IBD related to perinatal factors.Eighty-five patients with Crohn's disease (CD) and 86 with ulcerative colitis (UC) were included from a population-based incidence study enrolled 1990-1994. Family and birth records of these patients, as well as of their 207 infants, were drawn from the Norwegian Medical Birth Registry, established in 1967, and compared with the national birth cohort from the same period.Maternal (odds ratio [OR] = 2.15, 95% confidence interval [CI]: 1.36, 3.39) and paternal IBD (OR = 3.02, 95% CI: 1.82, 5.01) influenced the risk of preterm birth (<37 weeks), which further increased if the affected parents had a first-degree relative with IBD (OR = 4.29, 95% CI: 1.59, 11.63). Maternal CD was associated with lower birth weight in the offspring (crude difference: 271.79 g, 95% CI: 87.83, 455.77, versus controls). Maternal UC increased the risk of perinatal bacterial infection in the offspring (OR = 6.03, 95% CI: 2.03, 17.91). IBD patients (2.3%) were less likely to be delivered by cesarean section than controls (8.1%) (OR = 0.27, CI: 95%: 0.10, 0.73).Familial, maternal, and paternal IBD were linked to preterm birth, which might be explained by genetic mechanisms. The present protective effect of cesarean sections needs further clarification in future studies. Inflamm Bowel Dis 2009

Small bowel resection rates in Crohn's disease and the indication for surgery over time: Experience from a large tertiary care center

Our primary aim was to determine if the rate of small bowel resection (SBR) has declined over time among Crohn's disease (CD) patients seen at a single academic institution. A secondary aim was to establish whether the indication for surgery has changed.Patients with a primary or secondary ICD-9 code for CD (555.0-555.9) who underwent SBR at the University of Pittsburgh were included. Patients were divided into 4 separate time periods based on when they had surgery: 1995-1998 (Period 1), 1999-2001 (Period 2), 2002-2004 (Period 3), and 2005-2007 (Period 4). Medical records were reviewed for the 6 months preceding surgery. Use of 5-ASAs, immunomodulators (IMs), tumor necrosis factor (TNF) antagonists, and corticosteroids were noted. Disease behavior was defined as nonstricturing, nonpenetrating (B1), stricturing (B2), and penetrating (B3). Proportions of patients undergoing SBR were calculated according to calendar cohort and these rates were examined for time trends.In all, 227 unique patients were analyzed for a total of 236 surgeries. The rates of 5-ASA, IM, and corticosteroid use were similar across the 4 time periods. By contrast, TNF antagonist usage progressively increased over time (0%, 18%, 34%, 35%; P = 0.0002). The annual rate of SBR per period did not change (1.6%, 1.9%, 1.6%, 1.9%; P = 0.93). Similarly, the disease behavior did not change over time.While the frequency of TNF antagonist use in CD at the University of Pittsburgh has increased over time, the rate of SBR and indication for surgery has remained unchanged. These findings may be explained by long-standing, complicated disease refractory to medical therapy. Inflamm Bowel Dis 2009

Perforin deficiency attenuates inflammation and tumor growth in colitis-associated cancer

Patients with inflammatory bowel disease (IBD) have a markedly increased risk to develop colon cancer, but there are only limited data about the host antitumor response in such colitis-associated cancer. In the present study we aimed at assessing the role of perforin-dependent effector mechanisms in the immune response in a murine model of colitis-associated colon cancer.Wildtype and perforin-deficient mice were analyzed in a mouse model of colitis-associated colon cancer using azoxymethane (AOM) and dextran sodium sulfate (DSS).Tumors of wildtype mice showed infiltration of CD4+, CD8+ T cells, natural killer (NK) cells, high numbers of apoptotic cells, and expression of the transcription factor eomesodermin and cytotoxic effector proteins, suggesting a potential role of the antitumor immune response in AOM/DSS tumorigenesis. Furthermore, perforin deficiency resulted in reduced apoptosis of epithelial cells as compared to wildtype mice, whereas tumor infiltration by NK cells, CD8+, and CD4+ T cells was unchanged. However, perforin-deficient mice surprisingly developed significantly fewer tumors than wildtype mice. Subsequent studies identified an important role of perforin in regulating colitis activity, as perforin deficiency caused a significant reduction of DSS colitis activity and proinflammatory cytokine production as compared to wildtype controls.Perforin is involved in both the antitumor immune response and the regulation of activity of mucosal inflammation in colitis-associated cancer. Our data emphasize the possible consequences for therapeutic strategies targeting colitis-associated colon cancer. (Inflamm Bowel Dis 2009;)

Mapping of inflammatory bowel disease in northern France: Spatial variations and relation to affluence

Geographic variations in the incidence of inflammatory bowel disease (IBD) may reflect variations in the distribution of environmental etiologic factors. We assessed spatial variation in the incidence of IBD in northern France and analyzed its association with a deprivation index.All cases of IBD included in the EPIMAD registry between 1990 and 2003 were extracted. The standardized incidence ratio (SIR) was calculated for each canton in the region. The association between incidence and deprivation was assessed using the Townsend deprivation index.The mean annual incidence rates of Crohn's disease (CD) and ulcerative colitis (UC) were 6.2 × 10-5 and 3.8 × 10-5, respectively. The mean cumulative numbers of cases by canton were 18.4 (1-183) for CD and 11.3 (0-148) for UC. For both CD and UC, mapping depicted spatial heterogeneity in the SIR with spatial autocorrelation. A high relative risk (RR) of CD was observed in mainly rural and periurban cantons of the region. For UC, a high RR was found in cantons of the south and the center of Pas-de-Calais. No significant correlation was observed between spatial variations in IBD and deprivation.The incidence of IBD is associated with spatial heterogeneity in northern France. The noteworthy predominance of CD in agricultural areas warrants further investigations. (Inflamm Bowel Dis 2009;)

Transmission ratio distortion of DLG5 R30Q: Evidence for prenatal selection?

No abstract.

Butyrate utilization by the colonic mucosa in inflammatory bowel diseases: A transport deficiency

The short-chain fatty acid butyrate, which is mainly produced in the lumen of the large intestine by the fermentation of dietary fibers, plays a major role in the physiology of the colonic mucosa. It is also the major energy source for the colonocyte. Numerous studies have reported that butyrate metabolism is impaired in intestinal inflamed mucosa of patients with inflammatory bowel disease (IBD). The data of butyrate oxidation in normal and inflamed colonic tissues depend on several factors, such as the methodology or the models used or the intensity of inflammation. The putative mechanisms involved in butyrate oxidation impairment may include a defect in beta oxidation, luminal compounds interfering with butyrate metabolism, changes in luminal butyrate concentrations or pH, and a defect in butyrate transport. Recent data show that butyrate deficiency results from the reduction of butyrate uptake by the inflamed mucosa through downregulation of the monocarboxylate transporter MCT1. The concomitant induction of the glucose transporter GLUT1 suggests that inflammation could induce a metabolic switch from butyrate to glucose oxidation. Butyrate transport deficiency is expected to have clinical consequences. Particularly, the reduction of the intracellular availability of butyrate in colonocytes may decrease its protective effects toward cancer in IBD patients. (Inflamm Bowel Dis 2009;)

CXCL12 Is a constitutive and inflammatory chemokine in the intestinal immune system

Inflammatory bowel disease (IBD) is characterized by increased lymphocytic infiltrate to the lamina propria (LP) and upregulation of inflammatory chemokines and receptors. CXCL12 is a constitutive chemokine involved in lung, brain, and joint inflammation. We hypothesized that CXCL12 and its receptor, CXCR4, would have a constitutive and inflammatory role in the gut.Intestinal epithelial cells (IECs) and T lymphocytes were isolated from intestinal mucosa of IBD and control patients undergoing bowel resection. Autologous T cells were isolated from peripheral blood (PB). CXCL12 and CXCR4 expression by IECs was assessed by polymerase chain reaction and immunohistochemistry, lymphocyte phenotype by flow cytometry, and migration by Transwells.IECs expressed CXCL12 and expression was increased and more diffuse in IBD compared to normal crypts (ulcerative colitis [UC] > Crohn's disease [CD], inflamed > noninflamed). CXCR4 was expressed by IECs, LP T cells (LPTs), and PB T cells (PBTs), and CXCR4+ cells were increased in IBD LP in situ. PBTs and LPTs from all patients had a high and comparable migration toward CXCL12 (P < 0.0001 and P < 0.05 vs. medium, respectively). Migration toward IBD-IEC-derived supernatant was significantly higher compared to normal. Antibodies against CXCR4 and CXCL12 blocked migration.CXCL12 is expressed by normal IECs and upregulated and differentially distributed in IBD IECs. CXCR4 is expressed by IECs and LPTs, and CXCR4+ cells are significantly increased in IBD LP. CXCL12 is chemotactic for both PBTs and LPTs. Thus, CXCL12 and CXCR4 have a constitutive and inflammatory role in the intestinal mucosa and their selective therapeutic manipulation may be considered in IBD management. (Inflamm Bowel Dis 2009;)

Does psychological counseling alter the natural history of inflammatory bowel disease?

There is increasing evidence that psychological stress can increase mucosal inflammation and worsen the course of inflammatory bowel disease (IBD). We have now assessed whether psychotherapy by a counselor specially trained in the management of IBD can influence the course of disease.Using retrospective case note review, we compared the course of IBD in 24 patients (13 ulcerative colitis; 11 Crohn's disease), during the year before (year 1) and the year after referral (year 2) for supportive outpatient psychotherapy to an IBD counselor, to that of 24 IBD controls who were matched to individual cases for age, sex, disease, duration of disease, medication at baseline, and for relapse rate in year 1. Counselor assessments were made using a visual analog scale 0-6 (0 denotes poor, 6 excellent response to counseling). The results are shown as median (range).Patients were referred for counseling because of disease-related stress (14 patients), work problems (3), concerns about surgery (5), and bereavement (2); they received 6 (1-13) 1-hour sessions in year 2. In the year after starting counseling (year 2), patients had fewer relapses (0 [0-2]) and outpatient attendances (3.5 [1-10]) than in the year before referral (year 1) (2 [0-5], P = 0.0008; and 6.5 [1-17], P = 0.0006, respectively; furthermore, steroid usage (1 course [0-4] before, 0 [0-2] after, P = 0.005) and relapse-related use of other IBD medications declined during psychotherapy (1 drug [0-5] before, 0 [0-2] after, P = 0.002). There were no differences in any of these measures between years 1 and 2 in the control group. Numbers of hospital admissions did not change between year 1 and 2 in either group. In the 20 patients who attended >1 session counseling helped solve stress-related difficulties (counselor's score 4 [3-5]), the counselor scored them 4 (3-6) overall in psychological well-being after the counseling sessions.IBD-focused counseling may improve not only psychological well-being, but also the course of IBD in individuals with psychosocial stress. (Inflamm Bowel Dis 2009;)

TLR5 is not required for flagellin-mediated exacerbation of DSS colitis

The two forms of human inflammatory bowel disease, Crohn's disease (CD) and ulcerative colitis (UC), are both associated with loss of tolerance to gut microbial antigens. The dominant antigen recognized by antibody and T-cell responses in patients with CD is bacterial flagellin. Flagellin is also the only known ligand for Toll-like receptor 5 (TLR5), a key protein in innate immunity. Although flagellin activates TLR5 to produce inflammatory responses in many cell types in the gut, there is conflicting evidence as to whether TLR5 is harmful or protective in CD and murine colitis models. A recent study found that administration of flagellin enemas to mice along with dextran sodium sulfate (DSS) made their colitis worse.We sought to determine whether this exacerbation was due to TLR5 ligation, or to TLR5-independent adaptive immune responses to flagellin as an antigen, by using a transposon insertional mutant of the Escherichia coli H18 flagellin, 2H3, which lacks TLR5 stimulatory activity.We found that flagellin enemas produced only a mild exacerbation of DSS colitis, and that 2H3 was equivalent to or worse than wildtype flagellin. Moreover, we found that DSS colitis was more severe in TLR5-/- mice than wildtype C57BL/6 mice.Together, these results suggest that flagellin-mediated exacerbation of colitis is independent of TLR5. (Inflamm Bowel Dis 2009;)

5-aminosalicylic acid interferes in the cell cycle of colorectal cancer cells and induces cell death modes

Epidemiological data suggests that 5-aminosalicylic acid (5-ASA), a nonsteroidal antiinflammatory drug used in the treatment of inflammatory bowel diseases, prevents colorectal cancer development in these patients, although the mechanisms remain incompletely understood.Here we report that 5-ASA prevents growth of several colorectal cancer cell lines by interfering in the cell cycle, i.e., an S-phase and G2/M phase arrest, dependent on 5-ASA dosage and concentration, together with an increased mitotic index. In addition, prolonged cell cycle arrest by repeated 5-ASA treatment induced apoptosis and caused abnormal spindle organization leading to mitotic catastrophe, another form of cell death.These observations illustrate that 5-ASA has chemopreventive and chemotherapeutic properties. (Inflamm Bowel Dis 2009;)

Association between Helicobacter pylori infection and inflammatory bowel disease: A meta-analysis and systematic review of the literature

Epidemiologic data suggest a protective effect of Helicobacter pylori infection against the development of autoimmune disease. Laboratory data illustrate H. pylori's ability to induce immune tolerance and limit inflammatory responses. Numerous observational studies have investigated the association between H. pylori infection and inflammatory bowel disease (IBD). Our aim was to perform a systematic review and meta-analysis of this association.Medline, EMBASE, bibliographies, and meeting abstracts were searched by 2 independent reviewers. Of 369 abstracts reviewed, 30 promising articles were reviewed in detail. Twenty-three studies met our inclusion criteria (subject N = 5903). Meta-analysis was performed with the metan command in Stata 10.1.Overall, 27.1% of IBD patients had evidence of infection with H. pylori compared to 40.9% of patients in the control group. The estimated relative risk of H. pylori infection in IBD patients was 0.64 (95% confidence interval [CI]: 0.54-0.75). There was significant heterogeneity in the included studies that could not be accounted for by the method of IBD and H. pylori diagnosis, study location, or study population age.These results suggest a protective benefit of H. pylori infection against the development of IBD. Heterogeneity among studies and the possibility of publication bias limit the certainty of this finding. Further studies investigating the effect of eradication of H. pylori on the development of IBD are warranted. Because environmental hygiene and intestinal microbiota may be strong confounders, further mechanistic studies in H. pylori mouse models are also necessary to further define the mechanism of this negative association. (Inflamm Bowel Dis 2009;)

Analysis of 39 Crohn's disease risk loci in Swedish inflammatory bowel disease patients

No abstract.

Epstein-Barr virus and parvovirus B19 coinfection in a Crohn's disease patient under azathioprine

No abstract.

Ileal pouch for everyone, even when we are not sure of the diagnosis before or at colectomy?

No abstract.

Body mass index and disease activity at treatment initiation: Potential new predictors of response to azathioprine therapy in IBD

No abstract.

Current thinking on recurrence: Does anastomotic surgical technique affect recurrence rates in Crohn's patients?

No abstract.

Incidence of stricturing and penetrating complications of Crohn's disease diagnosed in pediatric patients

The development of disease complications is poorly characterized in pediatric patients with Crohn's disease (CD).We retrospectively determined the cumulative incidence of stricturing and penetrating complications of CD prior to first surgery utilizing data from 989 consecutively enrolled CD patients (age 0-17 years at diagnosis) collected between January 2000 and November 2003 and stored in the Pediatric IBD Consortium Registry.Mean age at diagnosis was 11.5 ± 3.8 (standard deviation) years. Median follow-up time was 2.8 years. Prior to first surgery, the cumulative incidence of stricturing or penetrating complications was 27% at 5 years and 38% at 10 years from the diagnosis of inflammatory bowel disease. The cumulative incidence of complicated disease was lowest in isolated colonic disease (P = 0.009). Penetrating complications that followed stricturing complications prior to first surgery occurred within 2 years of stricturing complications (cumulative incidence was 13% at 2 years from diagnosis of stricturing disease). Stricturing complications that followed penetrating complications prior to first surgery occurred within 8 years of penetrating complications (cumulative incidence was 26% at 8 years from diagnosis of penetrating complications).Strictures, abscesses, and fistulas are common in pediatric CD. Earlier aggressive management may be indicated. Prospective study is required to identify genetic and serologic markers that predict a patient's risk for the development of complicated disease and to determine optimal treatment regimens. (Inflamm Bowel Dis 2009;)

Plasma chromogranin A in patients with inflammatory bowel disease: A possible explanation

No abstract.

Effect of EP4 agonist (ONO-4819CD) for patients with mild to moderate ulcerative colitis refractory to 5-aminosalicylates: A randomized phase II, placebo-controlled trial

No abstract.

Lessons from geographic mapping of IBD in France

No abstract.

Adalimumab for cutaneous metastatic Crohn's disease

No abstract.

Getting the steak without the sizzle: Is MR enterography as good as CT enterography?

No abstract.

Antigen-presenting cells exposed to Lactobacillus acidophilus NCFM, Bifidobacterium bifidum BI-98, and BI-504 reduce regulatory T cell activity

The effect in vitro of six different probiotic strains including Lactobacillus acidophilus NCFMTM, Lactobacillus salivarius Ls-33, Lactobacillus paracasei subsp. paracasei YS8866441, Lactobacillus plantarum Lp-115, Bifidobacterium bifidum BI-504 and BI-98 was studied on splenic enteroantigen-presenting cells (APC) and CD4+CD25+ T-regulatory cells (Tregs) in splenocyte-T cell proliferation assays.Splenocytes exposed to enteroantigen +/- probiotics were used to stimulate cultured CD4+CD25- T cells to which titrated numbers of Tregs were added. Cytokine assays were performed by use of neutralizing antibodies and ELISA.Exposure of APCs to enteroantigens and the series of probiotic strains mentioned above did not influence the stimulatory capacity of APCs on proliferative enteroantigen-specific T cells. However, exposure to B. bifidum BI-98, BI-504 and L. acidophilus NCFMTM consistently reduced the suppressive activity of Tregs. The suppressive activity was analyzed using fractionated components of the probiotics, and showed that a component of the cell wall is responsible for the decreased Treg activity in the system. The probiotic-induced suppression of Treg function is not mediated by changes in APC-secretion of the inflammatory cytokines IL-6 or IL-1b.We conclude that certain probiotic strains can modify APCs to cause reduced Treg activity. This effect apparently depends on a direct APC-to-Treg cell contact. The APC-mediated suppressive effect on Treg function of certain probiotic strains may constrain the anti-inflammatory activity, which is often desired from probiotic therapy. This unexpected function of certain probiotic strains should be taken into consideration when designing adjuvant therapies with these bacteria, or when probiotic strains are selected for improvement of gut-associated inflammation like IBD. (Inflamm Bowel Dis 2009;)

Ablation of gly96/immediate early gene-X1 (gly96/iex-1) aggravates DSS-induced colitis in mice: Role for gly96/iex-1 in the regulation of NF-[kappa]B

Inflammatory bowel diseases (IBDs) result from environmental and genetic factors and are characterized by an imbalanced immune response in the gut and deregulated activation of the transcription factor NF-[kappa]B. Addressing the potential role of gly96/iex-1 in the regulation of NF-[kappa]B in IBD, we used the dextran sodium sulfate (DSS) colitis model in mice in which the gly96/iex-1 gene had been deleted.C57BL/6 mice of gly96/iex-1-/- or gly96/iex-1+/+ genotype were treated continuously with 4% DSS (5 days) and repeatedly with 2% DSS (28 days) for inducing acute and chronic colitis, respectively. In addition to clinical and histological exploration, colon organ culture and bone marrow-derived cells (BMCs) were analyzed for chemo/cytokine expression and NF-[kappa]B activation.Compared to wildtype littermates, gly96/iex-1-/- mice exhibited an aggravated phenotype of both acute and chronic colitis, along with a greater loss of body weight and colon length. Colonic endoscopy revealed a higher degree of hyperemia, edema, and bleeding in gly96/iex-1-/- mice, and immunohistochemistry detected massive mucosal infiltration of leukocytes and marked histological changes. The expression of proinflammatory chemo- and cytokines was higher in the colon of DSS-treated gly96/iex-1-/- mice, and the NF-[kappa]B activation was enhanced particularly in the distal colon. In cultured BMCs from gly96/iex-1-/- mice, Pam3Cys4 treatment induced expression of proinflammatory mediators to a higher degree than in gly96/iex-1+/+ BMCs, along with greater NF-[kappa]B activation.Based on the observation that genetic ablation of gly96/iex-1 triggers intestinal inflammation in mice, we demonstrate for the first time that gly96/iex-1 exerts strong antiinflammatory activity via its NF-[kappa]B-counterregulatory effect. (Inflamm Bowel Dis 2009;)

Distribution of peroxisome proliferator-activated receptor-gamma polymorphisms in Chinese and Dutch patients with inflammatory bowel disease

As peroxisome proliferator-activated receptor-gamma (PPAR-[gamma]) is frequently expressed in colon, its genetic polymorphism may play a role in the etiology of inflammatory bowel disease (IBD). The aims of the present study were to determine the distribution of PPAR-[gamma] polymorphisms Pro12Ala and C161T and to explore the association between the PPAR-[gamma] genotypes and phenotypes of IBD patients.A total of 244 IBD patients [212 ulcerative colitis (UC) and 32 Crohn's disease (CD)] and 220 controls in the Chinese population and 603 IBD patients (302 UC and 301 CD) and 180 controls in the white Dutch population were enrolled in the study. The phenotypes of Chinese IBD patients were grouped according to disease location. The PPAR-[gamma] polymorphisms Pro12Ala and C161T were genotyped by PCR-based methods.In the Chinese population, T carriers of the PPAR-[gamma] C161T polymorphism were more common in UC patients than in the controls [37.7% vs. 25.5%, odds ratio 1.77, 95% confidence interval 1.18-2.68, P = 0.007], whereas Ala carriers of the Pro12Ala polymorphism showed no significant association in UC patients, but there was a significant association of Ala carriers with more extensive disease among the UC patients (P = 0.002); Pro12Ala and C161T genotypes did not show any associations with CD patients. No associations were found for the PPAR-[gamma] C161T SNP studied in the Dutch IBD population.Our study showed the potential association between the PPAR-[gamma] C161T polymorphism and UC patients in the central Chinese population. This finding was not replicated in the Dutch population. Further studies are necessary to explore the functional implication of the PPAR-[gamma] C161T polymorphism in Chinese UC patients. (Inflamm Bowel Dis 2009;)

Age distribution of IBD hospitalization

No abstract.

Widespread but not localized neoplasia in inflammatory bowel disease worsens the prognosis of colorectal cancer

Patients with inflammatory bowel disease (IBD) are at increased risk of colorectal cancer (CRC). Recently, new phenotypes of CRC in IBD have been suggested. Studies of the prognosis of CRC in IBD have shown conflicting results. The aim of the study was to analyze factors for prognosis in CRC-IBD, including the impact of the new phenotypes.By using the nationwide, population-based Cancer Registry of Norway, we compared survival of a CRC-IBD cohort with CRC in the background population (all-CRC), adjusting for the topographical distribution of dysplasia at cancer diagnosis (widespread versus localized neoplasia in IBD) and other factors. We also analyzed prognostic factors within CRC-IBD.The mean age at CRC diagnosis was 43 years in widespread, 52 years in localized neoplasia IBD, and 70 years in all-CRC (P < 0.05). Adjusted for cofactors, prognosis of CRC-IBD was poorer compared to all-CRC (mortality rate ratio [MRR] 3.71, 95% confidence interval [CI]: 2.54-5.42, P < 0.001). Prognosis of widespread neoplasia IBD was poorer compared to all-CRC (MRR 4.27, 95% CI: 2.83-6.44, P < 0.001) and compared to localized neoplasia IBD (MRR 3.58, 95% CI: 0.87-14.72, P = 0.076). Survival was not significantly different between localized neoplasia IBD and all-CRC (P = 0.132).The results demonstrate lower age and poorer survival of CRC in IBD compared to CRC in the background population. The unfavorable effect of IBD on prognosis of CRC was pronounced in widespread neoplasia IBD. The diagnosis of this phenotype seems to be an important prognostic sign in patients with CRC in IBD. (Inflamm Bowel Dis 2009;)

High gene expression of MDR1 (ABCB1) is associated with medical treatment response and long-term remission in patients with ulcerative colitis

No abstract.

A new tool to measure the burden of Crohn's disease and its treatment: Do patient and physician perceptions match?

Health-related quality of life (HRQOL) is difficult to efficiently measure in the clinic setting. Our aim was to develop and test a simple tool to measure the burden of Crohn's disease (CD) and its treatment and to compare how patients and their physicians perceive the impact of CD on HRQOL.A cross-sectional, self-administered questionnaire was distributed to patients with CD. The questionnaire included a feeling thermometer to measure disease and treatment burden, which was compared to the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). At that visit, the patient's physician completed a questionnaire containing the feeling thermometer and the Harvey Bradshaw index (HBI). Nonparametric tests were use to report results.In all, 113 surveys were completed. The median age of respondents was 40 years and 68% were female. Using the feeling thermometer (scale 0-100), patients reported their current health as a median of 70 (interquartile range [IQR] 50-80) and their disease specific burden as 20 (IQR 10-40). Treatment-specific burden was 6.9 (IQR 1.3-20). Physicians perceived their patients' current health as a median of 71.3 (IQR 57.5-90) with a disease burden of 12.5 (IQR 5-30). Spearman's rho between the burden of symptoms measured by the feeling thermometer and the SIBDQ was -0.71. The correlation between patient and physician perception of current health was 0.73.Two questions using the feeling thermometer provide a quick and accurate assessment of the burden of CD on patients. Physicians' perception of the burden of disease was similar to their patients. (Inflamm Bowel Dis 2009;)

Platelet-activating factor-induced NF-[kappa]B activation and IL-8 production in intestinal epithelial cells are Bcl10-dependent

Platelet-activating factor (PAF), a potent proinflammatory phospholipid mediator, has been implicated in inducing intestinal inflammation in diseases such as inflammatory bowel disease (IBD) and necrotizing enterocolitis (NEC). However, its mechanisms of inducing inflammatory responses are not fully understood. Therefore, studies were designed to explore the mechanisms of PAF-induced inflammatory cascade in intestinal epithelial cells.Nuclear factor kappa B (NF-[kappa]B) activation was measured by luciferase assay and enzyme-linked immunosorbent assay (ELISA), and interleukin 8 (IL-8) production was determined by ELISA. B-cell lymphoma 10 (Bcl10), caspase recruitment domain-containing membrane-associated guanylate kinase protein 3 (CARMA3), and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) mRNA and protein levels were assessed by real-time reverse-transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. siRNA silencing of Bcl10 was used to examine its role in PAF-induced NF-[kappa]B activation and IL-8 production. The promoter region of the Bcl10 gene was cloned with the PCR method and promoter activity measured by luciferase assay.The adaptor protein Bcl10 appeared to play an important role in the PAF-induced inflammatory pathway in human intestinal epithelial cells. Bcl10 was required for PAF-induced I[kappa]B[alpha] phosphorylation, NF-[kappa]B activation, and IL-8 production in NCM460, a cell line derived from normal human colon, and Caco-2, a transformed human intestinal cell line. PAF also stimulated Bcl10 interactions with CARMA3 and MALT1, and upregulated Bcl10 expression in these cells via transcriptional regulation.These findings highlight a novel PAF-induced inflammatory pathway in intestinal epithelial cells, requiring Bcl10 as a critical mediator and involving CARMA3/Bcl10/MALT1 interactions. The proinflammatory effects of PAF play prominent roles in the pathogenesis of IBD and this pathway may present important targets for intervention in chronic inflammatory diseases of the intestine. (Inflamm Bowel Dis 2009;)

Circulating levels of chemerin and adiponectin are higher in ulcerative colitis and chemerin is elevated in Crohn's disease

Chemerin is an adipokine that stimulates chemotaxis of cells of the innate immune system. Inflammatory bowel disease (IBD) is linked to an impaired immune response and, therefore, we hypothesized that systemic chemerin may be altered in IBD patients.Serum was collected from patients with Crohn's disease (CD, 230 patients), ulcerative colitis (UC, 80 patients), and healthy controls (HC, 80 probands). Chemerin and adiponectin, which has already been measured in the serum of similar cohorts by others, were determined by enzyme-linked immunosorbent assay (ELISA).Chemerin was elevated in IBD compared to HC and was higher in male CD than UC patients. Female and male CD patients had lower adiponectin levels compared to UC, and adiponectin was lower in female CD patients compared to female HC. Adiponectin tended to be higher in female and male UC patients compared to HC and this difference became significant in the whole study group. Correlations with disease activity were only found in males. Here, chemerin was higher in CD patients on remission but was reduced in UC with nonactive disease. Adiponectin was higher in UC with inactive disease. Treatment with corticosteroids was linked to elevated adiponectin in male CD patients and higher chemerin in female UC patients. Unlike adiponectin, which was elevated in female serum in all cohorts, chemerin was only higher in female UC patients.These findings further indicate potential regulatory functions of adipokines in intestinal inflammation that are partly gender-dependent and that may even be associated with the distinct immunopathogenesis of UC and CD. (Inflamm Bowel Dis 2009;)

Female gender and surgery impair relationships, body image, and sexuality in inflammatory bowel disease: Patient perceptions

There is a paucity of literature on the impact of inflammatory bowel disease (IBD) on relationships, body image, and sexual function from a patient perspective. This study sought to describe patients' perceptions of these issues.In all, 347 patients, age 18-50 years, from a hospital-based IBD database were surveyed by post. Quantitative and qualitative data were obtained on demographics, relationships, quality of life (QoL), body image, and sexual function. Comparisons were made by diagnosis, gender, and operative status. Univariate and multivariable analyses and logistic regressions were performed; P < 0.05 was regarded as significant.The response rate was 62.5%. Overall, 88.5% reported impaired QoL; 50.2% a negative effect on relationship status; and 66.8% impaired body image (females 74.8% versus males 51.4%, P = 0.0007; operated 81.4% versus nonoperated 51.3%, P = 0.0003). A greater proportion of women reported decreased frequency of sexual activity, as did operated subjects (female 66.3% versus male 40.5%, P < 0.0001; operated 68.5% versus nonoperated 50.4%, P = 0.0113). Women and operated subjects also more often reported decreased libido (female 67.1% versus male 41.9% P = 0.0005; operated 67.4% versus nonoperated 52.6%, P = 0.035). 9.7% omitted medication because of perceived negative effect(s) on sexual function. Logistic regression revealed that female gender negatively affected body image, libido, and sexual activity, while limited resection surgery negatively affected body image (all P < 0.005).A large proportion of patients perceive IBD to negatively affect many aspects of sexuality. Females and operated subjects more frequently perceived these negative effects. These findings are important in overall clinical care of patients with IBD and should be addressed. (Inflamm Bowel Dis 2009;)

Crohn's proctitis: A distinct entity

No abstract.

Mesalamine (pentasa)-induced painful skin lesions

No abstract.

Prospective randomized open-label multicenter phase I/II dose escalation trial of visilizumab (HuM291) in severe steroid-refractory ulcerative colitis

Visilizumab is a humanized IgG2 monoclonal anti-CD3 antibody. We evaluated its safety and dose response in severe intravenous steroid-refractory ulcerative colitis (UC).In all, 104 patients were treated. In Stage I, 73 patients were randomly assigned to receive intravenous visilizumab 5, 7.5, 10, or 12.5 [mu]g/kg/day for 2 consecutive days. In Stage II, 33 patients received visilizumab at the optimal clinical dose (OCD) of 5 [mu]g/kg/day for 2 days. Symptomatic response and remission were defined by the modified Truelove-Witts severity index. Clinical response and remission were defined by the Mayo score.The rates of symptomatic response at day 15 in the 5, 7.5, 10, or 12.5 [mu]g/kg dose groups were 71%, 70%, 50%, and 61%, respectively, in Stage I and in 54% in Stage II. The symptomatic remission rates were 35%, 5%, 22%, and 11% in Stage I and 18% in Stage II. The rates of clinical response at day 30 in the 5, 7.5, 10, or 12.5 [mu]g/kg dose groups were 71%, 65%, 50%, and 67%, respectively, in Stage I and 55% in Stage II. The clinical remission rates were 6%, 5%, 0%, and 11% in Stage I and 6% in Stage II. All patients experienced adverse events. Serious adverse events included abdominal abscess, cytomegalovirus infection, atrial fibrillation, herpes zoster, and esophageal candidiasis.Treatment with visilizumab induced symptomatic response and clinical response. Results with 5 [mu]g/kg/day were similar to those observed with higher doses (NCT00267306 at ). (Inflamm Bowel Dis 2009;)

Course of inflammatory bowel disease in patients infected with human immunodeficiency virus

Human immunodeficiency virus (HIV) infection depletes CD4+ lymphocytes, which may benefit patients with inflammatory bowel disease (IBD). The aim was to compare the course of IBD in HIV patients with a matched group of IBD seronegative patients.A total of 20 IBD (14 Crohn's disease, 6 ulcerative colitis) HIV infected patients and 40 matched control seronegative IBD patients (2 controls per case) were compared regarding relapse of their disease. The CD4+ count was followed every 6 months and a value of [le]500 cells/[mu]L was used to define patients with immunosuppression. Relapse rates per year of follow-up were compared among the 2 groups and survival curves for cumulative remission rates were compared with a log-rank test. Multivariate analysis was used to discriminate among the impact of different variables on the risk of IBD relapse.The median duration of follow-up was 8.4 years (range 0.6-18 years). The mean relapse rate for the HIV+IBD group was 0.016/year of follow-up as compared to 0.053/year of follow-up for the IBD-matched control group (P = 0.032). Regarding the HIV-positive/IBD group, 14 patients were immunosuppressed at any given time during the follow-up period. None of these patients experienced an IBD relapse, whereas 3 out of the 6 without immunosuppression relapsed (P = 0.017). According to the multivariate analysis, HIV status was the only risk factor independently associated with a lower probability of IBD relapse.HIV infection reduces the relapse rates in IBD patients and this may be attributed to the lower CD4+ counts seen in these patients. (Inflamm Bowel Dis 2009;)

Glucocorticoid bioactivity does not predict response to steroid therapy in severe pediatric ulcerative colitis

The pathophysiological basis for corticosteroid (CS) failure in ulcerative colitis (UC) is unknown. A transactivation glucocorticoid bioassay (GBA) was developed to measure the biological activity of CS by quantifying glucocorticoid response elements. This approach eliminates differences in bioavailability, chemistry, affinity, and other potential differences between the various steroids regarding their ability to activate the glucocorticoid receptor. In this multicenter prospective study, we aimed to evaluate whether CS bioavailability plays a role in CS refractoriness in severe pediatric UC.GBA (using COS-1 transfected cells) was measured in the serum of 50 children (52% males, age 13.4 ± 3.5 years) admitted for acute severe UC on the third day of CS treatment. Demographic, clinical, and laboratory data were prospectively recorded.Of the children enrolled, 16 (32%) failed CS therapy and required infliximab (n = 14) or colectomy (n = 2) within a median of 10 days (interquartile range [IQR] 6.5-14.5). Reflecting internal validity of the assay, GBA was highly correlated with the last CS dose and the time interval to bloodletting (r = -0.41 and r = -0.54, respectively; P < 0.001). There was no statistically significant difference in the GBA levels between responders and nonresponders (249 nM versus 200 nM cortisol equivalent, P = 0.18). In a multivariate regression model adjusted for time elapsed from CS and the administered dose, GBA did not predict response to CS (P = 0.34).The lack of correlation of GBA level and treatment outcome lends support to the hypothesis that the bioavailability, type, and dosing of intravenous CS are not associated with response or failure to the drug. (Inflamm Bowel Dis 2009;)

Oral valganciclovir for colonic dilatation in ulcerative colitis associated with human cytomegalovirus infection

No abstract.

Detailed haplotype-tagging study of germline variation of MUC19 in inflammatory bowel disease

No abstract.

T-cell regulation of neutrophil infiltrate at the early stages of a murine colitis model

T-cells are a main target for antiinflammatory drugs in inflammatory bowel disease. As the innate immune system is also implicated in the pathogenesis of these diseases, T-cell suppressors may not only inhibit T-cell-dependent production of proinflammatory mediators but also affect innate immune cell function. Specifically, these drugs may impair innate immune cell recruitment and activation through inhibition of T-cells or act independent of T-cell modulation. We explored the extent of immune modulation by the T-cell inhibitor tacrolimus in a murine colitis model.We assessed the effects of tacrolimus on trinitro-benzene sulphonic acid (TNBS) colitis in wildtype and Rag2-deficient mice. The severity of colitis was assessed by means of histological scores and weight loss. We further characterized the inflammation using immunohistochemistry and by analysis of isolated intestinal leukocytes at various stages of disease.Tacrolimus-treated wildtype mice were less sensitive to colitis and had fewer activated T-cells. Inhibition of T-cell function was associated with strongly diminished recruitment of infiltrating neutrophils in the colon at the early stages of this model. In agreement, immunohistochemistry demonstrated that tacrolimus inhibited production of the neutrophil chemoattractants CXCL1 and CXCL2. Rag2-deficient mice displayed an enhanced baseline level of lamina propria neutrophils that was moderately increased in TNBS colitis and remained unaffected by tacrolimus.Both the innate and the adaptive mucosal immune system contribute to TNBS colitis. Tacrolimus suppresses colitis directly through inhibition of T-cell activation and by suppression of T-cell-mediated recruitment of neutrophils. (Inflamm Bowel Dis 2009)

Guillain-Barré syndrome during a relapse of ulcerative colitis: A case report

No abstract.

Age distribution of IBD hospitalization

The ages of patients with Crohn's disease (CD) and ulcerative colitis (UC) are characterized by a bimodal distribution. The present study used hospital statistics to compare the age distribution of inflammatory bowel disease (IBD) among different countries.Hospital statistics from the period 1994 to 2007 were obtained through special requests to the national statistical offices of 9 European countries. Hospitalization was expressed as age- and sex-specific rates per 10,000 living people.Hospitalization rates of different countries varied between 1.2 and 4.3 discharges per 10,000 for CD and between 0.7 and 4.7 discharges per 10,000 for UC. Countries with high CD rates were associated with similarly high UC rates (r = 0.955, P < 0.0001). In all countries alike, the age-distribution of CD hospitalization was characterized by a large peak in younger patients followed by a small peak in older patients. UC hospitalization was characterized by a small peak in younger patients followed by a large peak in older patients.The bimodal age distribution of IBD hospitalization can be explained in terms of varying exposure to 2 separate environmental risk factors that affected consecutive age groups differently over the course of the 20th century. (Inflamm Bowel Dis 2009)

Effect of natural commensal-origin DNA on toll-like receptor 9 (TLR9) signaling cascade, chemokine IL-8 expression, and barrier integritiy of polarized intestinal epithelial cells

The intestinal epithelium is constantly exposed to high levels of genetic material like bacterial DNA. Under normal physiological conditions, the intestinal epithelial monolayer as a formidable dynamic barrier with a high-polarity structure facilitates only a controlled and selective flux on components between the lumen and the underlining mucosa and even is able to facilitate structure-based macromolecules movement. The aim of this study was to test the effect of natural commensal-origin DNA on the TLR9 signaling cascade and the barrier integrity of polarized intestinal epithelial cells (IECs).Polarized HT-29 and T84 cells were treated with TNF-[alpha] in the presence or absence of DNA from Lactobacillus rhamnosus GG (LGG) and Bifidobacterium longum. TLR9 and interleukin-8 (IL-8) mRNA expression was assessed by semiquantitative and TaqMan real-time reverse-transcription polymerase chain reaction. Expression of TLR9 protein, degradation of inhibitor of kappa B alpha (I[kappa]B[alpha]), and p38 mitogen-activated protein kinase (p38 MAP) phosphorylation were assessed by Western blotting. To further reveal the role of TLR9 signaling, the TLR9 gene was silenced by siRNA. IL-8 secretion was measured by an enzyme-linked immunosorbent assay. Nuclear factor-kappa B (NF-[kappa]B) activity was assessed by the electrophoretic mobility shift assay (EMSA) and NF-[kappa]B-dependent luciferase reporter gene assays. As an indicator of tight junction formation and monolayer integrity of epithelial cell monolayers, transepithelial electrical resistance (TER) was repetitively monitored. Transmonolayer movement of natural commensal-origin DNA across monolayers was monitored using qRT-PCR and nested PCR based on bacterial 16S rRNA genes.In response to apically applied natural commensal-origin DNA, polarized HT-29 and T84 cells enhanced expression of TLR9 in a specific manner, which was subsequently associated with attenuation of TNF-[alpha]-induced NF-[kappa]B activation and NF-[kappa]B-mediated IL-8 expression. TLR9 silencing abolished this inhibitory effect. Apically applied LGG DNA attenuated TNF-[alpha]-enhanced NF-[kappa]B activity by reducing I[kappa]B[alpha] degradation and p38 phosphorylation. LGG DNA did not decrease the TER but rather diminished the TNF-[alpha]-induced TER reduction. Translocation of natural commensal-origin DNA into basolateral compartments did not occur under tested conditions.Our study indicates that TLR9 signaling mediates, at least in part, the anti-inflammatory effects of natural commensal-origin DNA on the gut because TLR9 silencing abolished the inhibitory effect of natural commensal-origin DNA on TNF-[alpha]-induced IL-8 secretion in polarized IECs. The nature of the TLR9 agonist, the polarity of cells, and the tight junction integrity of IECs has to be taken into account in order to predict the outcome of TLR9 signaling. (Inflamm Bowel Dis 2009)

Assessing disease activity in ulcerative colitis: Patients or their physicians?

We aimed to determine the optimal approach to assess disease activity (i.e., biological inflammation) in ulcerative colitis (UC) by comparing patients' and physicians' rating of the disease.This was a prospective, multicenter, double-cohort study. The first cohort was composed of 94 children with UC (parent proxy when required) and their physicians who provided independent clinical report and global assessment of disease, rated on a 100 mm visual analog scale. Constructs of disease activity (including mucosal inflammation, laboratory tests, Mayo score, and the Pediatric UC Activity Index), were scored by an independent blinded physician and used to compare validity of the assessment. Of the 94 children, 43 were seen at a follow-up visit and provided a global rating of change in disease activity. To ascertain whether age influences assessment accuracy, a second cohort of 86 adult UC patients were analyzed in a similar way.In both cohorts the physician global assessment had higher correlations with all constructs of disease activity than did the patient' global assessment (for colonoscopic score r = 0.76 vs. r = 0.29, P = 0.002). Even with abdominal pain, a subjective item, the physician's rating had higher correlation than the patient's rating. Similarly, the physician rating of change better reflected change in disease activity than that of the patient rating.For indirect measurement of biological activity on the basis of symptoms and signs, clinician assessments are superior to those of patients. Patient assessments, physician assessments, and direct measurement of disease activity provide complementary information in clinical research. (Inflamm Bowel Dis 2009)

Value of fractional exhaled nitric oxide (FENO) for the diagnosis of pulmonary involvement due to inflammatory bowel disease

Pulmonary involvement due to inflammatory bowel disease (IBD) is frequent when evaluating a patient with IBD and pulmonary involvement remains complicated. Most of the patients are asymptomatic and the methods used are mostly invasive or expensive procedures. The aim of this prospective study is to evaluate the value of the fractional exhaled nitric oxide (FENO) level for the diagnosis of pulmonary involvement due to IBD and to investigate any correlation between FENO level and disease activity.Thirty-three nonsmoker patients with IBD (25 ulcerative colitis [UC] and 8 Crohn's Disease [CD]) who were free of corticosteroid treatment and 25 healthy subjects as a control group were enrolled in this study. All patients with IBD were investigated for pulmonary involvement with medical history, physical examination, chest roentgenogram, oxygen saturation, blood eosinophil levels, pulmonary function tests (PFTs), high-resolution computed tomography (HRCT), and FENO level.Pulmonary involvement was established in 15 patients (45.5%) with IBD. The FENO level was higher in patients with pulmonary involvement than without pulmonary involvement and healthy controls independent from the pulmonary symptoms, eosinophil count, duration of disease, activity of disease, and surgery history (FENO: 32 ± 20; 24 ± 8; 14 ± 8 ppb, respectively) (P < 0.05). In addition, diffusion capacity (DLCO) was found to be significantly lower in patients with CD compared with UC (P < 0.05).This study showed that an increased FENO level may be used for identifying patients with IBD who need further pulmonary evaluation. Inflamm Bowel Dis 2009

Azathioprine maintains long-term steroid-free remission through 3 years in patients with steroid-dependent ulcerative colitis

Studies assessing the efficacy of azathioprine (AZA) in steroid-dependent ulcerative colitis (SD-UC) are scarce. The purpose of this trial was to explore the efficacy of AZA in maintaining steroid-free remission in SD-UC patients and the factors associated with sustained response.In this observational cohort study, 42 subjects with SD-UC were recruited for AZA therapy during a 3-year period. AZA was adjusted for a target dose of 2-3 mg/kg/day. Steroid therapy was tapered off following a standardized regimen. The primary endpoint was the annual rate of steroid-free response to AZA. Secondary endpoints included clinical recurrence, yearly steroid dose, and safety of treatment.On an intention-to-treat basis, the proportion of patients remaining in steroid-free remission at 12, 24, and 36 months was 0.55, 0.52, and 0.45, respectively. A significant decrease in the flare-ups rate and in requirement for steroids were observed during 3 years on AZA compared with the previous year (P = 0.000 for both). Patients with and without sustained response were comparable according to demographics, extent of disease, dose of AZA, steroids, and 5-aminosalicylate (5-ASA) use. Only disease duration <36 months was associated with off-steroids remission (P = 0.02, odds ratio [OR] 3.12, 95% confidence interval [CI] 1.89-7.64). The AZA benefit-risk profile was favorable.In this open-label observational trial AZA showed sustained efficacy for maintenance of clinical remission off steroids and steroid sparing through 3 years of therapy in SD-UC. Patients with earlier UC are those who most probably will have sustained steroid-free remission at the end of 12 months while on AZA. Inflamm Bowel Dis 2009

Prevalence of Clostridium difficile infection in Polish pediatric patients with inflammatory bowel disease

No abstract.

Mind-body complementary alternative medicine use and quality of life in adolescents with inflammatory bowel disease

Mind-body complementary and alternative medicine (CAM) modalities (e.g., relaxation or meditation) for symptom management have not been well studied in adolescents with inflammatory bowel disease (IBD). The purposes of this study were to: 1) determine the prevalence of 5 types of mind-body CAM use, and consideration of use for symptom management; 2) assess characteristics associated with regular mind-body CAM use; and 3) examine whether regular and/or considered mind-body CAM use are associated with health-related quality of life (HRQOL).Sixty-seven adolescents with IBD ages 12-19 recruited from a children's hospital completed a questionnaire on CAM use and the Pediatric Quality of Life Inventory. Logistic regression models were estimated for regular and considered CAM use.Participants mean (SD) age was 15.5 (2.1) years; 37 (55%) were female; 53 (79%) were white; and 20 (30%) had moderate disease severity. Adolescents used prayer (62%), relaxation (40%), and imagery (21%) once/day to once/week for symptom management. In multivariate analyses, females were more likely to use relaxation (odds ratio [OR] = 4.38, 95% confidence interval [CI] = 1.25-15.29, c statistic = 0.73). Younger adolescents were more likely to regularly use (OR = 0.63, 95% CI = 0.42-0.95, c statistic = 0.72) or consider using (OR = 0.77, 95% CI = 0.59-1.00, c statistic = 0.64) meditation. Adolescents with more severe disease (OR = 4.17, 95% CI = 1.07-16.29, c statistic = 0.83) were more willing to consider using relaxation in the future. Adolescents with worse HRQOL were more willing to consider using prayer and meditation for future symptom management (P < 0.05).Many adolescents with IBD either currently use or would consider using mind-body CAM for symptom management. Inflamm Bowel Dis 2009

Looking in the mouth for Crohn's disease

It is widely acknowledged among gastroenterologists that the oral cavity may be involved in Crohn's disease (CD). However, the specific manifestations are poorly appreciated. Although oral aphthous ulceration is probably not diagnostically useful in patients with suspected CD, disease-specific manifestations do occur and are particularly common in children presenting with CD. These manifestations can be subtle, often are subclinical, yet commonly harbor diagnostically useful material (granulomas). Orofacial granulomatosis (OFG) is conventionally used to describe patients with overt oral disease without obvious involvement of the gastrointestinal tract. However, many patients with OFG have subclinical intestinal CD or will progress to develop overt intestinal CD with time. The management of severe oral disease is challenging and lacks a clear evidence base. Inflamm Bowel Dis 2009

Significant association of appendiceal neoplasms and ulcerative colitis rather than Crohn's disease

No abstract.

Exposure of mouse colon to dietary bile acid supplement induces sessile adenomas

No abstract.

On the role of ischemia in the pathogenesis of IBD: A review

Inflammatory bowel disease (IBD) is a chronic intestinal disorder comprising 2 distinct but often overlapping diseases: Crohn's disease and ulcerative colitis. Although much research to identify the etiology of IBD has focused on genetic constitution, infectious causes, and immune dysregulation, its exact cause and pathogenesis remain incompletely understood. Mesenteric blood flow, the intestinal microcirculation, and intestinal ischemia also have been proposed as etiologic, although they remain less-explored themes despite evidence suggesting a contributory role in IBD pathogenesis. The anatomy, architecture, and function of the splanchnic microcirculation will be reviewed here with regard to the development of intestinal microvascular ischemia, a pathologic process that appears to precede the classic changes that characterize IBD. Inflamm Bowel Dis 2009

Veto on vedolizumab (MLN0002) for Crohn's disease

No abstract.

Fecal calprotectin mirrors inflammation of the distal ileum and bowel function after restorative proctocolectomy for pediatric-onset ulcerative colitis

The goal was to cross-sectionally assess fecal calprotectin after restorative proctocolectomy for pediatric-onset ulcerative colitis (UC).Fecal calprotectin, histology of the distal ileum, inflammation biochemistry, episodes of pouchitis, and bowel function were cross-sectionally determined at early adulthood in 32 patients who had undergone proctocolectomy with ileoanal anastomosis for UC at a mean (SD) age of 12.0 ± 4.1 years.A total of 15 (47%) patients showed increased (>100 [mu]g/g) fecal calprotectin (669 ± 866 [mu]g/g), although their serum C-reactive protein (5.2 ± 3.8 mg/L), erythrocyte sedimentation rate (13 ± 13 mm/h), and white blood cell count (6.7 ± 1.7 E9/L) were normal or slightly elevated. Calprotectin correlated positively with the histological neutrophil count of the distal ileum (r = 0.715; P < 0.001), the frequency of pouchitis (r = 0.468; P < 0.01), and with the maximum daily frequency of bowel actions (r = 0.610; P < 0.001). Mean fecal calprotectin was 71 ± 50 [mu]g/g among patients with no history of pouchitis (n = 10), 290 ± 131 [mu]g/g among patients with a single episode of pouchitis (n = 15), and 832 ± 422 [mu]g/g among those with recurrent pouchitis (P = 0.019 between recurrent pouchitis and no pouchitis). Sensitivity, specificity, positive predictive value, and negative predictive value for fecal calprotectin concentration over 300 [mu]g/g to detect recurrent pouchitis were 57%, 92%, 67%, and 89%, respectively.Neutrophilic inflammation of the distal ileum, as reflected by fecal calprotectin, is common after restorative proctocolectomy for pediatric-onset UC. Inflamm Bowel Dis 2009

Do 5-ASAs prevent colorectal neoplasia in patients with ulcerative colitis? Still no answers

No abstract.

Appendicitis, not appendectomy, is protective against ulcerative colitis, both in the general population and first-degree relatives of patients with IBD

No abstract.

Association of the novel serologic anti-glycan antibodies anti-laminarin and anti-chitin with complicated Crohn's disease behavior

We tested a panel of novel serological anti-glycan antibodies including the previously unpublished anti-laminarin IgA (Anti-L) and anti-chitin IgA (Anti-C) carbohydrate antibodies for the presence in Crohn's disease (CD) patients, diagnosis and differentiation of CD, association with complicated disease behavior, and marker stability over time.The presence of Anti-L, Anti-C, anti-chitobioside IgA (ACCA), anti-laminaribioside IgG (ALCA), anti-mannobioside IgG (AMCA), and anti-Saccaromyces cervisiae IgG (gASCA) carbohydrate antibodies were tested in serum samples from 824 participants (363 CD, 130 ulcerative colitis [UC], 74 other gastrointestinal diseases, and 257 noninflammatory bowel/gastrointestinal disease controls) of the German IBD-network by enzyme-linked immunosorbent assay (ELISA; Glycominds, Lod, Israel) and for perinuclear antineutrophil cytoplasmic antibody (pANCA) by immunofluorescence.In all, 77.4% of the CD patients were positive for at least 1 of the anti-glycan antibodies. gASCA or the combination of gASCA/pANCA remained most accurate for the diagnosis of CD, but the combined use of the antibodies improved differentiation of CD from UC. Several single markers as well as an increasing antibody response were independently linked to a severe disease phenotype, as shown for the occurrence of complications, CD-related surgery, early disease onset, and ileal disease location. This was observed for both quantitative and qualitative antibody responses. The antibody status remained stable over time in most IBD patients.A panel of anti-glycan antibodies including the novel Anti-L and Anti-C may aid in differentiation of CD from UC, is associated with complicated CD behavior and IBD-related surgery, and is stable over time in a large patient cohort. Inflamm Bowel Dis 2009

Cytokine mRNA expression in steroid-naïve patients with ulcerative colitis

No abstract.

Identification of a novel staining pattern of bile duct epithelial cells in primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is an inflammatory disease of the bile ducts with an unknown etiology. A number of autoantigens have been proposed, but an early diagnostic marker is still lacking. Our aim was to identify such an autoantigen.Immunostaining was performed on normal human bile duct with sera from patients with PSC and controls. To identify an autoantigen a cDNA library from normal human choledochus was constructed and immunoscreened with patient sera. Using in vitro transcription and translation and immunoprecipitation we examined the immunoreactivity against PDZ domain containing 1 (PDZK1) in 35 patients with PSC, 198 control patients, and 94 healthy controls.We observed a previously unpublished staining pattern in which cytoplasmatic granules and apical cell membranes of biliary epithelial cells were stained by PSC sera. Strong immunoreactivity to these structures was obtained with 12 out of 35 PSC sera (34%) but not with sera from healthy controls. By screening the cDNA library we identified PDZK1 as a candidate antigen. Immunoreactivity against PDZK1 was detected in 9% of PSC patients, 2% of inflammatory bowel disease (IBD) patients, 8% of autoimmune pancreatitis patients, 18% of Grave's disease patients, and 1% of healthy controls.Previously unpublished, specific, and strong autoantibodies against epithelial cells of the bile duct in PSC sera were identified. Furthermore, PDZK1 is suggested as a potential new autoantigen. Inflamm Bowel Dis 2009

Characterization of single-nucleotide polymorphisms relevant to inflammatory bowel disease in commonly used gastrointestinal cell lines

The era of genome-wide association studies (GWAS) has led to the identification of many inflammatory bowel disease (IBD)-associated single-nucleotide polymorphisms (SNPs) with unknown function. The next step would be to identify the functional consequences of these polymorphisms in order to target them efficiently for therapeutic purposes. One way to study this type of genetic variation is the use of cell line models. However, to characterize the functional effect of a SNP, it is important to know if the selected cell line model itself carries the studied genetic variation. Here, we genotyped 50 IBD markers across 32 susceptibility genes in 9 commonly used gastrointestinal cell lines.We used Sequenom, TaqMan, and DNA sequencing for the genotyping. To determine the expression profile of the selected genes, we conducted real-time RT-PCR.We found variant SNPs in all analyzed cell lines. Almost every minor allele was carried by at least one of the tested cell lines. We analyzed the effect of 4 SNPs in more detail using quantitative real-time RT-PCR (qRT-PCR) comprising genes ATG16L1, CD14, MDR1, and OCTN2. According to our data, only 2 of the commonly studied SNPs in MDR1 and CD14 have an impact on gene expression.We have identified genotype variants in all analyzed cell lines. Some of them are functional and alter the response to drugs (MDR1) or affect bacterial recognition (TLR4, NOD2). Our results highlight that the genotype should not be neglected in experimental design when using model cell lines. Inflamm Bowel Dis 2009

Endoscopic ultrasound to guide the combined medical and surgical management of pediatric perianal Crohn's disease

Perianal fistulas are a debilitating manifestation of Crohn's disease (CD) in the pediatric population and present a management challenge. The aims of this study were to describe our experience using endoscopic ultrasound (EUS) to guide management of perianal CD (PCD) in a pediatric population, and determine whether using EUS to monitor healing after seton placement improves outcomes.We conducted a retrospective study of 2 cohorts: pediatric subjects with PCD who underwent EUS and pediatric subjects who underwent seton placement between 2002 and 2007.In all, 25 children underwent a total of 42 EUS procedures. Of 28 EUSs performed to evaluate suspected perianal disease, complex fistulizing disease was identified in 15 (54%). Setons were placed after most EUSs demonstrating complex fistulizing disease and after none demonstrating superficial or no fistulizing disease. Of 14 EUSs performed to monitor healing around a seton, 7 (50%) demonstrated persistent peri-seton inflammation. Setons were more often left in place after an EUS revealing persistent inflammation (86% versus 0%), and the patients were more likely to have a biologic initiated or changed (57% versus 0%). Among all subjects who underwent seton placement, time from seton removal to recurrence was longer for those followed by EUS compared to those followed by physical exam only; however, we were not powered to test for statistical significance.EUS to guide the combined medical and surgical management of PCD is feasible in the pediatric population. Larger prospective studies are needed to determine if EUS-directed management improves outcomes in pediatric patients with PCD. Inflamm Bowel Dis 2009

Similar geographic variations of mortality and hospitalization associated with IBD and Clostridium difficile colitis

Superinfection with Clostridium difficile can aggravate the symptoms of preexisting inflammatory bowel disease (IBD). The study served to assess whether the geographic variation of IBD within the United States might be influenced by C. difficile infection.Hospitalization data of the Healthcare Cost and Utilization Project (HCUP) from 2001-2006 and mortality data from 1979-2005 of the US were analyzed by individual states. Hospitalization and mortality associated with Crohn's disease (CD), ulcerative colitis (UC), and C. difficile colitis were correlated with each other, using weighted least square linear regression with the population size of individual states as weight.Among the hospitalization rates, there were strong correlations between both types of IBD, as well as each type of IBD with C. difficile colitis. Similarly, among the mortality rates there were strong correlations between both types of IBD, as well as each type of IBD with C. difficile colitis. Lastly, each type of hospitalization rate was also strongly correlated with each type of mortality rate. In general, hospitalization and mortality associated with IBD tended to be frequent in many of the northern states and infrequent in the Southwest and several southern states.The similarity in the geographic distribution of the 3 diseases could indicate the influence of C. difficile colitis in shaping the geographic patterns of IBD. It could also indicate that shared environmental risk factors influence the occurrence of IBD, as well as C. difficile colitis. Inflamm Bowel Dis 2009

Does primary sclerosing cholangitis impact quality of life in patients with inflammatory bowel disease?

Impairment of health-related quality of life (HRQoL) is an important concern in inflammatory bowel disease (IBD; ulcerative colitis [UC], Crohn's disease [CD]). Between 2%-10% of patients with IBD have primary sclerosing cholangitis (PSC). There has been limited examination of the disease-specific HRQoL in this population compared to non-PSC IBD controls.This was a retrospective, case-control study performed at a tertiary referral center. Cases comprised 26 patients with a known diagnosis of PSC and IBD (17 UC, 9 CD). Three random controls were selected for each case after matching for IBD type, gender, age, and duration of disease. Disease-specific HRQoL was measured using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Disease activity for CD was measured using the Harvey-Bradshaw index (HB) and using the UC activity index for UC. Independent predictors of HRQoL were identified.There was no significant difference in the age, gender distribution, or disease duration between PSC-IBD and controls. There was no difference in use of immunomodulators or biologics between the 2 groups. Mean SIBDQ score was comparable between PSC-IBD patients (54.5) and controls (54.1), both for UC and CD. Likewise, the disease activity scores were also similar (2.8 versus 3.1, P = 0.35). On multivariate analysis, higher disease activity score (-1.33, 95% confidence interval [CI] 95% CI -1.85 to -0.82) and shorter disease duration were predictive of lower HRQoL. Coexisting PSC did not influence IBD-related HRQoL. There was a higher proportion of permanent work disability in PSC-IBD (7.7%) compared to controls (0%).PSC does not seem to influence disease-specific HRQoL in our patients with IBD but is associated with a higher rate of work disability. Inflamm Bowel Dis 2009

Survival of the probiotic Escherichia coli Nissle 1917 (EcN) in the gastrointestinal tract given in combination with oral mesalamine to healthy volunteers

Mesalamine and the probiotic E. coli Nissle 1917 (EcN) are both effective agents for the treatment of ulcerative colitis. A combined therapy may have more than additive efficacy. However, mesalamine may have antimicrobial effects on EcN.In this prospective, randomized, double-blind, placebo-controlled study, 48 healthy volunteers took EcN in a run-in phase for 17 days (5-50 × 109 viable bacteria od). If stool samples became positive for EcN, volunteers received combination treatment with EcN plus either mesalamine (1500 mg twice a day) or placebo for 1 week. Fecal samples were further tested for EcN in 2- to 3-day intervals until a maximum of 48 weeks after treatment. Patient diaries, blood, and urine were checked to assess safety, compliance, and tolerance.During run-in, viable EcN were detected in 45 of the 48 volunteers (94%); 2 volunteers were positive before taking EcN. From days 1 to 7 of combination treatment (n = 40), the number of EcN-positive volunteers varied between 70% and 80% in the mesalamine group and between 85% and 95% in the placebo group. Differences between the groups were not significant (normal approximation: day 3, P > 0.15; day 5, P > 0.25; day 7, P > 0.076). At treatment discontinuation, 16 of 20 volunteers in the mesalamine group and 15 of 20 volunteers in the placebo group were EcN positive, whereas this figure dropped continuously up to week 12 after discontinuation (mesalamine, 7 of 20; placebo, 4 of 20). No differences between the groups were seen with regard to tolerance and safety.The combination of EcN and mesalamine has no significant effect on the survival of EcN in healthy volunteers. Inflamm Bowel Dis 2009

Fontolizumab in moderate to severe Crohn's disease: A phase 2, randomized, double-blind, placebo-controlled, multiple-dose study

The safety and efficacy of fontolizumab, a humanized anti-interferon gamma antibody, was investigated in patients with Crohn's disease (CD). Elevated gut mucosal levels of interferon gamma, a key cytokine involved in the inflammatory process of CD, are associated with disease symptoms.A total of 201 patients with Crohn's Disease Activity Index (CDAI) scores between 250 and 450 were randomized to receive an initial intravenous dose of 1.0 or 4.0 mg/kg fontolizumab or placebo, followed by up to 3 subcutaneous doses of 0.1 or 1.0 mg/kg fontolizumab or placebo every 4 weeks. Clinical response at day 29, the primary efficacy endpoint, was defined as a decrease in the CDAI of at least 100 points from baseline levels.Of 201 patients, 135 (67%) completed the study. Day 29 response rates were similar in all treatment groups (31%-38%). At subsequent timepoints a significantly greater proportion of patients in the 1.0 mg/kg intravenous / 1.0 mg/kg subcutaneous fontolizumab group had clinical response and significantly greater improvement in the CDAI score compared with patients who received placebo. All fontolizumab groups had significant improvement in C-reactive protein levels. The overall frequency of adverse events was similar in all groups (58%-75%); most events were related to exacerbation of CD. There was a low frequency (5.2%) of neutralizing antibodies to fontolizumab.Although a strong clinical response to fontolizumab was not observed, significant decreases in C-reactive protein levels suggest a biological effect. Fontolizumab was well tolerated, and further studies to assess its efficacy are warranted. Inflamm Bowel Dis 2009

Efficacy of infliximab in refractory pouchitis and Crohn's disease-related complications of the pouch: A Belgian case series

Up to 25% of inflammatory bowel disease (IBD) patients undergoing surgery with an ileal pouch-anal anastomosis (IPAA) will develop chronic pouchitis not responding to antibiotics. In case reports, thiopurine analogs and infliximab (IFX) have been proposed as effective therapy in this setting. We analyzed the long-term efficacy of IFX in Belgian patients with refractory pouch complications.We identified 28 IPAA patients who received IFX for refractory luminal inflammation (pouchitis and/or pre-pouch ileitis, n = 25) and/or pouch fistula (n = 7). Patients with elements of Crohn's disease after review of the colectomy specimen were excluded. Clinical response was defined as complete in case of cessation of diarrhea, blood loss, and abdominal pain, and as partial in case of marked clinical improvement. Fistula response was defined as complete in case of cessation and as partial in case of reduction of fistula drainage.Eighty-two percent of patients were concomitantly treated with immunomodulatory agents. At week 10 following start of IFX, 88% of patients with refractory luminal inflammation showed clinical response (14 partial, 8 complete), while 6 patients (86%) showed fistula response (3 partial, 3 complete). The mPDAI dropped significantly from 9.0 (interquartile range [IQR] 8.0-10.0) to 4.5 (3.0-7.0) points (P < 0.001). After a median follow-up of 20 (7-36) months, 56% showed sustained clinical response while 3 out of 7 fistula patients showed sustained fistula response. Five patients needed permanent ileostomy.In this series, IFX was effective long-term in IPAA patients with refractory luminal inflammation and pouch fistula. These results warrant a prospective multicenter randomized controlled trial. Inflamm Bowel Dis 2009

Need for standardization in population-based quality of life studies: A review of the current literature

In this systematic review we focus on the current use of and knowledge on health related quality of life in unselected, population-based IBD cohorts. We made a systematic literature search and included for comprehensive review papers that described a population-based cohort and that used validated HRQoL instruments. We show that even studies defined by the authors as population-based do not always meet the criteria set for being population-based. The heterogeneity of the study populations we have reviewed emphasizes that "population-based" must be defined very meticulously and that study populations need to be scrutinized with regard to all characteristics of the cohort before one can compare their results. Different definitions of study populations as population-based affect outcomes. We also show that use of the same HRQoL questionnaires does not guarantee comparable results as there are several different versions of the questionnaires, the different translations are not always comparable and at last there are several methods of computing and presenting the data. Detailed accumulation of knowledge and thorough meta analyses is therefore difficult hence we find it necessary to raise a discussion on the need of standardization in this field of research and we make some simple recommendations on factors we find important. Inflamm Bowel Dis 2009

Assessment of appropriateness of indications for CT enterography in younger patients

The small potential risk of radiation-induced cancer is increased in younger patients undergoing serial imaging with computed tomography enterography (CTE). We sought to determine the appropriateness of CTEs based on clinical indication in patients [le]35 years old, and the potential impact of evolution of practice to alternative magnetic resonance enterography (MRE).Over a 7-year period, the medical records of all patients [le]35 years old undergoing CTE were reviewed to determine the clinical indications for each CTE exam. An interdisciplinary consensus panel evaluated the appropriateness of all CTE exams based on American College of Radiology appropriateness criteria and peer-reviewed literature, classifying indications into "appropriate" or "inappropriate." For repeat CTEs, an "alternative MRE suggested" pathway was created. Criteria for evolution of practice to "alternative MRE" were suspicion of obstruction and evaluation of disease activity/therapeutic response in the absence of new symptoms.In all, 2022 patients [le]35 years old underwent 2295 CTEs. Ninety-nine percent (2008/2022) of first-time CTE exams were "appropriate" by the defined criteria. A total of 197 patients (9.7%) underwent multiple exams, with 73% of these patients having Crohn's disease. Repeat exams occurred in 9% (18/197) with obstructive symptoms and evaluation of disease activity/therapeutic response in the absence of new symptoms in 41% (80/197).A multidisciplinary expert panel concluded that the vast majority of young patients underwent clinically appropriate first-time CTE exams. However, a shift in clinical practice to MRE appears warranted for approximately half of young patients undergoing repeat CTE examinations. Inflamm Bowel Dis 2009

Importance of mucosal healing in ulcerative colitis

Treatment of patients with ulcerative colitis (UC) has traditionally focused on improving symptoms, with the main objective of inducing and maintaining symptomatic remission. However, new evidence suggests that concentrating exclusively on clinical outcome measures may not be adequate to achieve long-term treatment success. Indeed, physicians should also be assessing the reduction of endoscopic activity, with the intention of achieving complete mucosal healing (defined as the absence of all mucosal ulceration, both microscopic and macroscopic, providing a sigmoidoscopy score of 0, as assessed on the Ulcerative Colitis Disease Activity Index). As a consequence of the customary reliance on symptomatic outcome measures, relatively few clinical trials have used mucosal healing or a composite including mucosal healing as a primary endpoint. This situation may soon change as new guidelines recommend the incorporation of mucosal healing into the primary endpoint of all new clinical trials in patients with UC. These recommendations are derived, in part, from data that have illustrated a correlation between mucosal healing and several important factors including long-term remission rates, disease-related complications (e.g., risk of colorectal cancer), healthcare utilization (e.g., need for colectomy), and patient quality of life. We already have drugs available to us that can effectively induce and maintain complete mucosal healing over long periods of time. This review evaluates the effect of medical therapy on mucosal healing in patients with UC and explores the importance of this outcome measure, both from the patient's perspective and clinical trial experience. Inflamm Bowel Dis 2009

Book Review - G.I. Joe: The Life and Career of Joseph B. Kirsner

No abstract.

Sulfasalazine-induced nephrotic syndrome in a patient with ulcerative colitis

No abstract.

TNF-[alpha] is an important pathogenic factor contributing to reactivation of cytomegalovirus in inflamed mucosa of colon in patients with ulcerative colitis: Lesson from clinical experience

No abstract.

Development of glomerulonephritis early in the course of Crohn's disease

No abstract.

Gastrointestinal manifestations in primary immune disorders

The gastrointestinal tract is the largest lymphoid organ in the body containing T and B lymphocytes, macrophages, and dendritic cells. Despite the fact that these cells are constantly confronted with antigen primarily in the form of food and bacteria, immune responses in the gut are tightly regulated to maintain homeostasis. Without this balance of active immunity and tolerance, mucosal inflammation may ensue, and manifest as Crohn's disease, ulcerative colitis, pernicious anemia, or celiac sprue. Therefore, it is not unreasonable that inflammatory diseases of the gut are commonly encountered in patients with primary immune deficiencies. The exact pathogenesis of gastrointestinal diseases in the setting of primary immunodeficiency remains unknown, however, both humoral and cell-mediated immunity appear to play a role in preventing intestinal inflammation. Patients presenting with atypical gastrointestinal disease and/or failure to respond to conventional therapy should be evaluated for an underlying primary immune disorder in order to initiate appropriate treatment, such as immunoglobulin or in more severe cases bone marrow transplantation, to prevent long term complications. Inflamm Bowel Dis 2009

Salmonella septic arthritis in a patient with Crohn's disease on infliximab

No abstract.

Acute lymphoid leukemia in a Crohn's disease patient during treatment with adalimumab after a prolonged treatment with azathioprine and steroids

No abstract.

Reduced muscle mass and bone size in pediatric patients with inflammatory bowel disease

Decreased bone mineral density has been reported in children with inflammatory bowel disease (IBD). We used peripheral quantitative computed tomography (pQCT) to assess bone mineralization, geometry, and muscle cross-sectional area (CSA) in pediatric IBD.In a cross-sectional study, pQCT of the forearm was applied in 143 IBD patients (mean age 13.9 ± 3.5 years); 29% were newly diagnosed, 98 had Crohn's disease, and 45 had ulcerative colitis. Auxological data, cumulative glucocorticoid dose, disease activity indices, laboratory markers for inflammation, and bone metabolism were related to the results of pQCT.Patients were compromised in height (-0.82 ± 1.1 SD), weight (-0.77 ± 1.0 SD), muscle mass (-1.12 ± 1.0 SD), and total bone cross-sectional area (-0.79 ± 1.0 SD) compared to age- and sex-matched healthy controls (z-scores). In newly diagnosed patients, the ratio of bone mineral mass per muscle CSA was higher than in those with longer disease duration (1.00 versus 0.30, P = 0.007). Serum albumin level and disease activity correlated with muscle mass, accounting for 41.0% of variability in muscle mass (P < 0.01). The trabecular bone mineral density z-score was on average at the lower normal level (-0.40 ± 1.3 SD, P < 0.05).Reduced bone geometry was explained only in part by reduced height. Bone disease in children with IBD seems to be secondary to muscle wasting, which is already present at diagnosis. With longer disease duration, bone adapts to the lower muscle CSA. Serum albumin concentration is a good marker for muscle wasting and abnormal bone development. Inflamm Bowel Dis 2009

Granulocyte-macrophage colony-stimulating factor elicits bone marrow-derived cells that promote efficient colonic mucosal healing

Granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy is effective in treating some Crohn's disease (CD) patients and protects mice from colitis induced by dextran sulfate sodium (DSS) administration. However, its mechanisms of action remain elusive. We hypothesized that GM-CSF affects intestinal mucosal repair.DSS colitic mice were treated with daily pegylated GM-CSF or saline and clinical, histological, and inflammatory parameters were kinetically evaluated. Further, the role of bone marrow-derived cells in the impact of GM-CSF therapy on DSS colitis was addressed using cell transfers.GM-CSF therapy reduced clinical signs of colitis and the release of inflammatory mediators. GM-CSF therapy improved mucosal repair, with faster ulcer reepithelialization, accelerated hyperproliferative response of epithelial cells in ulcer-adjacent crypts, and lower colonoscopic ulceration scores in GM-CSF-administered mice relative to untreated mice. We observed that GM-CSF-induced promotion of mucosal repair is timely associated with a reduction in neutrophil numbers and increased accumulation of CD11b+ monocytic cells in colon tissues. Importantly, transfer of splenic GM-CSF-induced CD11b+ myeloid cells into DSS-exposed mice improved colitis, and lethally irradiated GM-CSF receptor-deficient mice reconstituted with wildtype bone marrow cells were protected from DSS-induced colitis upon GM-CSF therapy. Lastly, GM-CSF-induced CD11b+ myeloid cells were shown to promote in vitro wound repair.Our study shows that GM-CSF-dependent stimulation of bone marrow-derived cells during DSS-induced colitis accelerates colonic tissue repair. These data provide a putative mechanism for the observed beneficial effects of GM-CSF therapy in Crohn's disease. (Inflamm Bowel Dis 2009;)

Severe sporotrichoid fishtank granuloma following infliximab therapy for Crohn's disease

No abstract.

Osteoporosis in patients over 50 years of age following restorative proctocolectomy for ulcerative colitis: Is DXA screening warranted?

Ulcerative colitis (UC) and increasing age are associated with an increased risk of osteoporosis. Screening of postmenopausal women and men older than 50 years with ulcerative colitis for osteoporosis is recommended. The prevalence of osteoporosis in restorative proctocolectomy (RPC) patients more than 50 years old is not known.Fifty-three consecutive patients older than age 50 who had undergone RPC for UC underwent a bone density scan (DXA). Sex, smoking status, age at diagnosis of UC, duration of UC, age at RPC, years since RPC, age at DXA, and pouch histological inflammatory score were recorded. The Kruskal-Wallis test and Spearman's correlation coefficient were used to analyze the data.Fifty-three patients were studied; their median age was 58 years, and the median age at RPC was 45. The prevalence of osteopenia and osteoporosis was 43.4% and 13.2%, respectively. Age at RPC was negatively correlated with bone density (P = 0.041, r = 0.281), and there was a negative correlation approaching significance with age at the time of DXA (P = 0.071, r = -0.250). No other factor studied correlated with bone density.The prevalence of osteoporosis and osteopenia found in this study is similar to that reported for UC patients who have not undergone RPC. Patients having RPC should be screened in line with current UC guidelines, targeting those older than 50 years. (Inflamm Bowel Dis 2009)

Splenic tuberculosis in a patient with Crohn's disease on infliximab: Case report

No abstract.

Sterile seroma after surgical drainage of purulent psoas abscess in Crohn's disease

No abstract.

Potential for amino acids supplementation during inflammatory bowel diseases

The pathophysiology of inflammatory bowel diseases (IBDs) is multifactorial and involves interactions of gut luminal content with mucosal barrier and especially immune cells. Malnutrition is a frequent issue during IBD flares, especially in Crohn's disease (CD) patients, and nutritional support is frequently used to treat malnutrition but also in an attempt to modulate intestinal inflammation. The use of oral or enteral nutrition intervention in IBDs may be effective, alone or in combination with drugs, to achieve and maintain remission. However, standard diets are less effective than new-generation biotherapies and could be improved by supplementation with specific immunomodulatory amino acids. Experimental studies evaluating glutamine, the preferential substrate for enterocytes, are promising. Some clinical studies with oral glutamine in CD are until now disappointing, but new formulations and targeting could enhance glutamine efficacy at the site of mucosal lesions. The role of arginine, involved in nitric oxide and polyamines synthesis, still remains debated. However, the effects of these amino acids in IBD have been poorly documented in humans. Other candidates like glycine, cysteine, histidine, or taurine should also be evaluated in the future. Inflamm Bowel Dis 2009

Circulating midkine in Crohn's disease: Clinical implications

A noninvasive marker facilitating differential diagnosis in Crohn's disease (CD) is sought after. Midkine is a heparin-binding growth factor of angiogenic and chemotactic properties, positively evaluated as a tumor marker, and a possible association with CD has not yet been investigated.Circulating midkine was measured in 91 CD patients and 108 controls and related to disease clinical and biochemical activity, inflammation severity, and angiogenesis. Midkine diagnostic value in comparison with C-reactive protein (CRP) was evaluated by receiver operating characteristic (ROC) analysis.Circulating midkine was elevated both in quiescent and active disease compared to controls (147, 506, and 93 pg/mL, respectively), and corresponded well with disease activity (r = 0.49, P < 0.001). Midkine significantly correlated with inflammatory indices: CRP (r = 0.49), erythrocyte sedimentation rate (r = 0.31), leukocytes (r = 0.48), platelets (r = 0.52), albumin (r = -0.49), transferrin (r = -0.47), and IL-6 (r = 0.54); hematological variables: hemoglobin (r = -0.38), hematocrit (r = -0.43), and iron (r = -0.58); angiogenic factors: vascular endothelial growth factor-A (r = 0.42), fibroblast growth factor-2 (r = 0.54), and platelet-derived growth factor-BB (r = 0.57). Midkine elevation corresponded well (r = -0.41) with the drop in paraoxonase-1 activity - a quorum-quenching factor. Midkine as a marker of active CD had sensitivity and specificity of 86% and 97%, respectively, whereas CRP was 83% and 92%.CD is associated with an elevation of midkine, which corresponds well with disease activity and reflects the severity of inflammatory response and exacerbation of pathological angiogenesis. Midkine performance as a disease marker was slightly better than that of CRP. Its high specificity and likelihood ratios for positive test results might recommend midkine as a possible "ruling in" marker in CD. Inflamm Bowel Dis 2009

Hospitalizations are increasing among minority patients with Crohn's disease and ulcerative colitis

Rates of inflammatory bowel disease (IBD) appear to be increasing among nonwhite populations outside the United States, but national data describing the incidence and prevalence of IBD are not available for minority patients. The aim of this study was to examine time trends of hospital discharge among minority patients with IBD.Nationally representative data describing hospital discharges were obtained from the National Hospital Discharge Survey for the years 1994 to 2006. Race-specific annual proportions of hospitalizations including a discharge diagnosis of ulcerative colitis and Crohn's disease were calculated. Trends in proportions were assessed for statistical significance using the extended Mantel-Haenszel [chi]-square test for trend.The proportion of hospitalizations including a discharge diagnosis of IBD increased significantly from 1994 to 2006 among the total population and among Asian, black, and white patients separately. Increases were statistically significant when analysis was performed for Crohn's disease and ulcerative colitis combined and separately. Marked increases were seen among Asians.The proportion of hospitalizations including a discharge diagnosis of IBD increased significantly among minority and nonminority patients from 1994 through 2006. The causes underlying these changes are not certain and should be further investigated. Inflamm Bowel Dis 2009

Overall and cause-specific mortality in Crohn's disease: A meta-analysis of population-based studies

An overview of mortality risk among unselected patients with Crohn's disease (CD) is lacking. We therefore performed a systematic review and meta-analysis of population-based studies on overall and cause-specific mortality in CD.MEDLINE (January 1965 to February 2008), abstracts from international conferences and reference lists of selected articles were searched systematically. All articles fulfilling the predefined inclusion criteria were scrutinized for data on population size, time of follow-up, gender, age, and observed to expected deaths. STATA meta-analysis software was used to calculate overall and cause-specific pooled standardized mortality ratios (SMR, observed/expected).Nine studies were included with overall SMRs ranging from 0.72-3.2, resulting in a significantly increased pooled SMR of 1.39 (95% confidence interval [CI]: 1.30-1.49). Regarding cause-specific mortality, a significantly increased risk of death from cancer (SMR 1.50, 95% CI: 1.18-1.92), in particular of pulmonary cancer (SMR 2.72, 95% CI: 1.35-5.45), as well as chronic obstructive pulmonary disease (SMR 2.55, 95% CI: 1.19-5.47), gastrointestinal diseases (SMR 6.76, 95% CI: 4.37-10.45), and genitourinary diseases (SMR 3.28, 95% CI: 1.69-6.35) was observed.Among unselected patients with CD, overall mortality was slightly but significantly higher than in the general population - primarily explained by deaths from gastrointestinal, respiratory, and genitourinary diseases. Notably, mortality from colorectal cancer was not increased. Inflamm Bowel Dis 2009

Cerebral venous thrombosis in inflammatory bowel diseases

No abstract.

Does methotrexate induce mucosal healing in Crohn's disease?

No abstract.

Atrioventricular block associated with Crohn's relapsing colitis in a 12-year-old child

No abstract.

Comparison of several activity indices for the evaluation of endoscopic activity in UC: Inter- and intraobserver consistency

This study evaluated inter- and intraobserver agreement in the assessment of ulcerative colitis (UC) activity using 4 established indices and a newly designed Modified 6-point Activity Index.In all, 279 endoscopic pictures of inflammatory lesions from 93 UC patients were displayed twice to 4 expert and 4 trainee endoscopists, at an interval of 1 month. Each picture was assessed for inflammatory changes using established indices (Matts, Schroeder [a.k.a. Mayo Score], Baron, and Blackstone) and our new Modified 6-point Activity Index. Weighted kappa statistics were used to estimate intra- and interobserver variation.The Matts and Schroeder indices gave a "good" degree of concordance for expert endoscopists in terms of inter- and intraobserver agreements (0.74-0.78); this was not so evident with the Baron and Blackstone indices (0.61-0.73). For trainee endoscopists, all scores for inter- and intraobserver weighted kappa values using established indices (0.41-0.51) were lower than for the experts. The degree of concordance using the Modified 6-point Activity Index was rated as "good" for inter- and intraobserver agreements for expert endoscopists (0.65 and 0.79), and as "moderate" for trainee endoscopists (0.54 and 0.64).Accurate assessment of UC disease activity from endoscopic findings benefited from experience. For expert endoscopists, the Matts and Schroeder indices proved the most reliable of the 4 established indices. Current endoscopic technologies may be adequate for assessing UC activity, particularly if modified to permit a finer classification of disease severity based on 6 grades, as with our newly developed Modified 6-point Activity Index. (Inflamm Bowel Dis 2009;)

Crohn's disease is associated with restless legs syndrome

Extraintestinal manifestations of Crohn's disease (CD) have not previously included the central nervous system (CNS). Restless legs syndrome (RLS) is a CNS disorder that is either idiopathic or secondary to a number of diseases. The aim of this study was to determine if RLS was associated with CD because both are associated with iron deficiency, inflammation, and bacterial overgrowth.Consecutive CD outpatients (N = 272) were prospectively surveyed at 4 centers for criteria for RLS. Incidence (having RLS at any point in time), prevalence (having RLS at time of survey), clinical characteristics, risk factors, and potential qualitative relationship between RLS and gastrointestinal symptoms were queried.The incidence of RLS in patients with CD was 42.7%. Prevalence was 30.2% compared with 9% of spouses. CD patients with and without RLS had a mean age of 46.8 versus 42.6 years, small intestine involvement in 77.9% versus 66.7%, colon involvement in 39.7% versus 63.2%, and prior iron deficiency anemia in 49.3% versus 33.1%. There was no difference between the CD groups with respect to current iron deficiency, RLS family history, or rare prevalence of concomitant RLS disorders. In 91.8% of patients with RLS and CD, RLS started during or after the onset of CD diagnosis. Among 73 patients with RLS, 67 (44.5%) stated there was a relationship between qualitative RLS symptom improvement with overall CD symptom improvement.These results demonstrate that RLS occurs frequently in CD and appears to be a possible extraintestinal manifestation. The potential relationship of RLS with CD activity warrants further investigation. (Inflamm Bowel Dis 2009;)

Elevated serum chromogranin A in irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD): A shared model for pathogenesis?

No abstract.

Endoscopy and MR enteroclysis: Equivalent tools in predicting clinical recurrence in patients with Crohn's disease after ileocolic resection

Ileocolonoscopy poses the gold standard in the evaluation of postoperative recurrence of Crohn's disease (CD) at the site of ileocolonic anastomosis. Magnetic resonance enteroclysis (MRE) on the other hand is a promising technique for small bowel imaging. The aim was to compare MRE and ileocolonoscopy for predicting clinical recurrence in CD patients who have undergone ileocolonic resection.We included 29 patients in the study. The median time since index operation was 35 months and between ileocolonoscopy and MRE was 3 days. Patients were followed up for a maximum of 2 years unless clinical recurrence occurred earlier. Endoscopic findings were evaluated on a 5-grade scale (i0-i4), whereas MRE findings on the neoterminal ileum and anastomosis were assessed according to a previously validated 4-grade scale MR score (MR0-MR3).By classifying patients into subgroups of endoscopic severity of postoperative recurrence using as a threshold an endoscopic score of i3, we found that 10% of patients in the i0 to i2 group had a clinical recurrence during the 2-year follow-up period as compared to 52.6% of subjects with i3 to i4 (P = 0.043). The corresponding clinical exacerbation rates in the subgroups based on MRE severity assessment were 12.5% for MR0 to MR1 and 50% for MR2 to MR3 (P = 0.09).Our data suggest that colonoscopy and MR enteroclysis are of similar value to predict the risk of clinical recurrence in postoperative patients with Crohn's disease. Inflamm Bowel Dis 2009

Efficacy of oral tacrolimus on intestinal Behcet's disease

No abstract.

Current smoking, not duration of remission, delays Crohn's disease relapse following azathioprine withdrawal

No abstract.

Thyroid disorders and inflammatory bowel diseases: Retrospective evaluation of 909 patients from an Italian Referral Center

No abstract.

Adalimumab-induced psoriasis of the scalp with diffuse alopecia: A severe potentially irreversible cutaneous side effect of TNF-alpha blockers

No abstract.

Solitary rectal ulcer syndrome in association with ulcerative colitis: A case report

No abstract.

Adalimumab as therapy for fistulizing orofacial Crohn's disease

No abstract.

Physicians may inadequately address Sexuality in women with inflammatory bowel disease

No abstract.

Varicella pneumonia in an immunocompromised inflammatory bowel disease patient

No abstract.

Endoscopic healing should be a goal for everyone with ulcerative colitis

No abstract.

Journals RSS : Gourt

Inflammation and carcinogenesis of the biliary tract: update on endoscopic treatment.

Pancreaticobiliary maljunction.

Differential diagnosis and treatment of biliary strictures.

Intrahepatic cholangiocarcinoma progression: prognostic factors and basic mechanisms.

Diagnosis of pancreatic disorders using contrast-enhanced endoscopic ultrasonography and endoscopic elastography.

Distinguishing pancreatic cancer from autoimmune pancreatitis: a comparison of two strategies.

Differentiating neoplastic from benign lesions of the pancreas: translational techniques.

Roles of pancreatic stellate cells in pancreatic inflammation and fibrosis.

Desmoplasia of pancreatic ductal adenocarcinoma.

Ras activity in acinar cells links chronic pancreatitis and pancreatic cancer.

Molecular pathology of pancreatic cancer: implications for molecular targeting therapy.

Recent developments in acute pancreatitis.

Germ-line mutations, pancreatic inflammation, and pancreatic cancer.

Chronic pancreatitis and pancreatic cancer: prediction and mechanism.

Long-term follow-up of autoimmune pancreatitis: characteristics of chronic disease and recurrence.

Long-term prognosis of acute pancreatitis in Japan.

The acinar cell and early pancreatitis responses.

Inflammation and carcinogenesis in the pancreas and biliary tract: mechanisms and practice.

Indecent exposures

Pediatrics: Amitriptyline and placebo in children with functional gastrointestinal disorders

Colonoscopy: Unsedated colonoscopy is a feasible primary screening tool for colorectal cancer

Cancer: Human bacterium induces colon tumors in mice through activation of TH17 cells

Targeting Ras in HCC

IBD: Sargramostim for corticosteroid-dependent Crohn's disease

Ulcerative proctitis: Potential therapeutic role for appendicectomy

Liver transplantation: Predicting infectious complications after OLT

Fecal incontinence: Efficacy of biofeedback

Primary sclerosing cholangitis: The importance of treating stenoses and infections

Gastrointestinal bleeding: Carvedilol—the best β-blocker for primary prophylaxis?

Chronic anal fissure: Surgical or reversible neurochemical sphincterotomy?

GERD: Is laparoscopic surgery cost-effective?

Hepatocellular adenoma: Should phenotypic classification direct management?

Epidemiology of pancreatic cancer: an overview

Anastomoses of the lower gastrointestinal tract

Endoscopy for upper gastrointestinal bleeding: is routine second-look necessary?

Stem cells in gastroenterology and hepatology

CT and radiation-related cancer risk—time for a paradigm shift?

Risk of ischemic stroke in patients with Crohn's disease: A population-based nested case-control study

Low-dose naltrexone for treatment of duodenal Crohn's disease in a pediatric patient

Characterization of the novel ST2/IL-33 system in patients with inflammatory bowel disease

Genome wide association (GWA) predictors of anti-TNF[alpha] therapeutic responsiveness in pediatric inflammatory bowel disease

Elevated IL-13R[alpha]2 in intestinal epithelial cells from ulcerative colitis or colorectal cancer initiates MAPK pathway

Efficacy and safety of certolizumab pegol induction therapy in an unselected Crohn's disease population: Results of the FACTS survey

Ocular manifestations in a community-based cohort of patients with inflammatory bowel disease

Can fecal calprotectin or lactoferrin identify postoperative recurrence in Crohn's disease?

Interleukin 21 expression is increased in rectal biopsies from patients with ulcerative colitis

CD24 is upregulated in inflammatory bowel disease and stimulates cell motility and colony formation

Quality and publication success of abstracts of randomized clinical trials in inflammatory bowel disease presented at Digestive Disease Week

Nutriose, a prebiotic low-digestible carbohydrate, stimulates gut mucosal immunity and prevents TNBS-induced colitis in piglets

Asymmetric endoscopic inflammation of the ileal pouch: A sign of ischemic pouchitis?

Health-related quality of life of youth with inflammatory bowel disease: A comparison with published data using the PedsQL 4.0 generic core scales

The path to Crohn's disease: Is mucosal pathology a secondary event?

Ulcerative colitis in northern Portugal and Galicia in Spain

Subepithelial dendritic B cells in orofacial granulomatosis

Magnetic resonance follow-through imaging for evaluation of disease activity in ileal Crohn's disease: An observational, retrospective cohort study

Targeting TGF-[beta]1 by employing a vaccine ameliorates fibrosis in a mouse model of chronic colitis

Methotrexate for maintenance of remission in chronic active Crohn's disease: Long-term single-center experience and meta-analysis of observational studies

Impact of prior irregular infliximab dosing on performance of long-term infliximab maintenance therapy in Crohn's disease

Lipopolysaccharide exposure is linked to activation of the acute phase response and growth failure in pediatric Crohn's disease and murine colitis

Randomized, double-blind, placebo-controlled trial of the oral interleukin-12/23 inhibitor apilimod mesylate for treatment of active Crohn's disease

Validation of the Spanish version of a questionnaire to measure quality of care through the eyes of patients with inflammatory bowel disease (QUOTE-IBD)

Single-port access laparoscopic surgery for complex Crohn's disease

Outcome of medical treatment of stricturing and penetrating Crohn's disease: A retrospective study

TLR9 mRNA expression is upregulated in patients with active ulcerative colitis

Angiopoietin-2 in experimental colitis

Fine-scale geographic variations of inflammatory bowel disease in France: Correlation with socioeconomic and house equipment variables

Exogenous alkaline phosphatase for the treatment of patients with moderate to severe ulcerative colitis

Babesiosis in a patient on infliximab for Crohn's disease

Campylobacter concisus and other Campylobacter species in children with newly diagnosed Crohn's disease

Safety of immunomodulators and biologics for the treatment of inflammatory bowel disease during pregnancy and breast-feeding

Diagnostic value of noninvasive combined fluorine-18 labeled fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography enterography in active Crohn's disease

Prevalence of hepatitis B and C and risk factors for nonvaccination in inflammatory bowel disease patients in Northeast France

Tissue factor -1208D>I polymorphism is associated with D-dimer levels in patients with inflammatory bowel disease

Novel model of TH2-polarized chronic ileitis: The SAMP1 mouse

Cdcs1 a major colitis susceptibility locus in mice; Subcongenic analysis reveals genetic complexity

MDP-NOD2 stimulation induces HNP-1 secretion, which contributes to NOD2 antibacterial function

Surgery for low-grade colorectal dysplasia in ulcerative colitis: Decisions, decisions

A33 antigen-deficient mice have defective colonic mucosal repair

TL1A produced by lamina propria macrophages induces Th1 and Th17 immune responses in cooperation with IL-23 in patients with Crohn's disease