Ulcerative Colitis: Escher JC

Oliva-Hemker M, Escher JC, Moore D, Dubinksy M, Hildebrand H, Koda YK, Murch S, Sandhu B, Seo JK, Tanzi MN, Warner B, Anonymous00097. · Division of Pediatric Gastroenterology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, MD 21287-2631, USA. · J Pediatr Gastroenterol Nutr. · Pubmed #18664886 No free full text.

This publication has no abstract.

Cucchiara S, Escher JC, Hildebrand H, Amil-Dias J, Stronati L, Ruemmele FM. · Pediatric Gastroenterology Unit, University of Rome La Sapienza, University Hospital Umberto I, Rome, Italy. · J Pediatr Gastroenterol Nutr. · Pubmed #19274777 No free full text.

Abstract: Inflammatory bowel diseases (IBDs) are lifelong inflammatory gastrointestinal diseases starting in about one third of patients during childhood. Treatment strategies aim to control this chronic inflammatory process. Owing to recent advances in the understanding of IBD, immunosuppressive agents (mainly against TNFalpha directed) as well as biological drugs are more and more often used. This therapeutic approach clearly improved the clinical condition of the majority of patients with IBD. However, with this more aggressive treatment strategy, safety concerns clearly arise. Recently, the description of a series of a particularly severe form of T cell lymphoma in pediatric and young adult patients with IBD under immunomodulator and biological combination therapy raised the question of the risks of treatment-induced side effects or complications. As reviewed in the present article, there is a slightly increased risk of not only lymphoma development in IBD patients, potentially related to the inflammatory process, but also to the use of immunosuppressive therapies. On the basis of the literature data, were analyzed current treatment strategies for children with moderate-to-severe IBD, who are candidates to receive immunomodulator and/or biological agents potentially accelerating the risk of lymphoma development. Comparative clinical studies in IBD are still missing; however, it is prudent to think about adapting immunosuppressive therapies to the inflammatory process of the underlying disorder and if possible to reduce them to monotherapy. Alternative treatment strategies for heavy immunosuppression exist (eg, enteral nutrition in Crohn disease or colectomy in patients with ulcerative colitis) and should be considered whenever appropriate. There is a major need for comparative studies before evidence-based guidelines can be established for safest and best treatment strategies of pediatric patients with IBD.

van Lierop PP, Samsom JN, Escher JC, Nieuwenhuis EE. · Department of Pediatric Gastroenterology, Erasmus MC Sophia Children's Hospital-University Medical Center, Rotterdam, The Netherlands. · J Pediatr Gastroenterol Nutr. · Pubmed #19179875 No free full text.

Abstract: Crohn disease and ulcerative colitis are chronic inflammatory diseases of the intestinal tract commonly denoted as inflammatory bowel diseases. It has been proposed that these diseases result from aberrant mucosal immune responses to nonpathogenic microbial residents of the intestines. Recently, it was established that continuous interactions between the innate and the adaptive intestinal immune cells and the microbiota are directly involved in maintaining the physiological noninflammatory state of the intestinal mucosa. In light of the complexity of this mucosal homeostasis, it is astonishing that the inflammatory bowel diseases are relatively rare. Recently, altered functions of the innate immune system have been identified. As such, both hyperresponsiveness and hyporesponsiveness of innate cells have been implicated in the pathogenesis of inflammatory bowel diseases.

van Dieren JM, van der Woude CJ, Kuipers EJ, Escher JC, Samsom JN, Blumberg RS, Nieuwenhuis EE. · Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, and Department of Pediatric Gastroenterology, Sophia Children's Hospital, Rotterdam, the Netherlands. · Inflamm Bowel Dis. · Pubmed #17476670 links to  free full text

Abstract: Natural killer T (NKT) cells are a subset of lymphocytes that express cell surface molecules of both conventional T cells and natural killer cells and share the features of both innate and adaptive immune cells. NKT cells have been proposed to make both protective and pathogenic contributions to inflammatory bowel diseases (IBD). On the one hand, recent studies have shown that these cells are involved in the maintenance of mucosal homeostasis. On the other, NKT cells were shown to play a pathogenic role in human ulcerative colitis. Similar contrasting data have been generated in murine models of IBD. Whether the apparent differences in NKT response patterns depend on variations in NKT antigens and/or on the presence of specific subsets of mucosal NKT cells remains to be elucidated. In this article we review the current literature on intestinal NKT cells and their roles in IBD pathogenesis. Specifically, the nomenclature, NKT antigens, and immune mechanisms of NKT cells within the intestinal mucosa are discussed.

Escher JC, Taminiau JA, Nieuwenhuis EE, Büller HA, Grand RJ. · Department of Pediatric Gastroenterology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, The Netherlands. · Inflamm Bowel Dis. · Pubmed #12656136 No free full text.

Abstract: The physician treating children with inflammatory bowel disease is confronted with a number of specific problems, one of them being the lack of randomized, controlled drug trials in children. In this review, the role of nutritional therapy is discussed with a focus on primary treatment, especially for children with Crohn's disease. Then, the available medical therapies are highlighted, reviewing the evidence of effectiveness and side effects in children, as compared with what is known in adults. Nutritional therapy has proven to be effective in inducing and maintaining remission in Crohn's disease while promoting linear growth. Conventional treatment consists of aminosalicylates and corticosteroids, whereas the early introduction of immunosuppressives (such as azathioprine or 6-mercaptopurine) is advocated as maintenance treatment. If these drugs are not tolerated or are ineffective, methotrexate may serve as an alternative in Crohn's disease. Cyclosporine is an effective rescue therapy in severe ulcerative colitis, but only will postpone surgery. A novel strategy to treat Crohn's disease is offered by infliximab, a monoclonal antibody to the proinflammatory cytokine tumor necrosis factor (TNF)-alpha. Based on the best-available evidence, suggested usage is provided for separate drugs with respect to dosage and monitoring of side effects in children.

Wiersma H, Escher JC, Dilger K, Trenk D, Benninga MA, van Boxtel CJ, Taminiau J. · Department of Clinical Pharmacology and Pharmacotherapy, Academic Medical Center, Amsterdam, The Netherlands. · Inflamm Bowel Dis. · Pubmed #15472525 No free full text.

Abstract: Mesalazine is a first-line drug in pediatric inflammatory bowel disease (IBD), and is customarily used to induce and maintain remission in mild to moderate disease. In children, pharmacokinetic data are scarce, and dosage recommendations are largely extrapolated from studies in adults. Aim of the study was to obtain the pharmacokinetic profile of a new mesalazine pellet formulation in children with ulcerative colitis and Crohn's colitis. A single oral dose of 20 mg/kg mesalazine was administered to 13 patients (age 6-16 years). Serial blood and urine sampling for determination of mesalazine and acetylmesalazine was performed before and during 24 hours following ingestion. Maximum plasma concentration of mesalazine (Cmax) was 1332 ng/mL (geometric mean, geometric coefficient of variation [CV]: 0.57), obtained 3.7 hours (tmax; CV: 0.31) after drug administration. Systemic exposure as determined by area under the plasma concentration-time curve (AUC(0-infinity) ) was 8712 ng/ml*h (CV: 0.44). Terminal half-life of elimination of mesalazine was 3.5 hours (t(1/2); CV: 1.43). This study presents extensive pharmacokinetic data on mesalazine in children with mild-moderately active ulcerative colitis and Crohn's colitis. In comparison with previous experience in adults, pharmacokinetics of mesalazine administered as pellets appear to be similar in both populations.

Damen GM, Hol J, de Ruiter L, Bouquet J, Sinaasappel M, van der Woude J, Laman JD, Hop WC, Büller HA, Escher JC, Nieuwenhuis EE. · Department of Pediatric Gastroenterology and Laboratory of Pediatrics, Erasmus MC-Sophia Children's Hospital, University Medical Center, Dr. Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands. · J Pediatr Gastroenterol Nutr. · Pubmed #16456405 No free full text.

Abstract: OBJECTIVES: Inflammatory bowel diseases (IBD) represent an aberrant immune response by the mucosal immune system to luminal bacteria. Because the oral mucosa harbors the first epithelial cells that interact with microorganisms, we assessed the immunologic activity of buccal epithelium in children with IBD and adults with Crohn disease. METHODS: Buccal epithelial cells were obtained from 17 children and 14 adults with Crohn disease, 18 children with ulcerative colitis, and 40 controls. Cells were cultured with and without microbial stimulation. Chemokine levels were determined in culture supernatants by cytometric bead array and enzyme-linked immunoabsorbent assay. CXCL-8 production was studied by immunohistochemical analysis of these cells. CXCL-8 production by lipopolysaccharide stimulated monocyte-derived dendritic cells from these patients was determined. RESULTS: Compared with controls, pediatric ulcerative colitis patients, and adult Crohn disease patients, only in children with Crohn disease did buccal epithelial cells exhibit enhanced production of CXCL-8, CXCL-9, and CXCL-10. In vitro stimulation with lipopolysaccharide or zymosan resulted in a further increase of chemokine levels only in cells from pediatric Crohn disease patients. CXCL-8 production by stimulated monocyte-derived dendritic cells from children with Crohn disease was equal to that of children with ulcerative colitis. CONCLUSIONS: Buccal epithelium of children with Crohn disease is immunologically active, even in the absence of oral lesions. The enhanced chemokine production is associated with pediatric Crohn disease and appears restricted to cells derived from the epithelial barrier. Assessment of chemokine production by buccal epithelial cells may become a new, rapid, noninvasive test for screening and classification of IBD in children.

van der Zaag-Loonen HJ, Casparie M, Taminiau JA, Escher JC, Pereira RR, Derkx HH. · Emma Children's Hospital, AMC, Amsterdam, the Netherlands. · J Pediatr Gastroenterol Nutr. · Pubmed #15076631 No free full text.

Abstract: BACKGROUND: The incidence of inflammatory bowel disease (IBD) seems to be rising. Incidence studies could provide more insight into geographical differences and thereby lead to the identification of etiological factors. The aim of this study was to prospectively assess the incidence of pediatric IBD in the Netherlands from 1999 to 2001, using both an active physician case-reporting registry and a nationwide pathology database. METHODS: All pediatricians in the Netherlands were sent monthly identification cards to be returned if they had diagnosed a new case of IBD in a pediatric patient. Follow-up questionnaires were sent to physicians reporting new cases of IBD. The pathology database contains reports from all cytologic and histologic diagnoses made in the Netherlands. Two independent raters searched the database for new IBD cases. Cases identified from the pathology database were labeled as "probable IBD" and "possible IBD." Cases were cross-checked across databases on the basis of gender, date of birth, date of biopsy, and place of residence. Age-specific incidence rates were calculated for the Dutch population for the year 2000. RESULTS: Five hundred forty-six probable cases of IBD were identified; 217 cases were labeled as possible. The incidence rate was 5.2 new cases per 100000 children (<18 years) per year. An increase in incidence with age was observed. Only 24% of the cases were ascertained through the clinical registry. CONCLUSION: The incidence of IBD cases in the Netherlands is comparable with that reported in other European countries. Epidemiological studies using case reporting by physicians may be underestimates of true incidence rates.

Escher JC, ten KF, Lichtenbelt K, Schornagel I, Büller H, Derkx B, Taminiau J. · Department of Pediatric Gastroenterology, Emma Children's Hospital, University of Amsterdam, The Netherlands. · Inflamm Bowel Dis. · Pubmed #11837934 No free full text.

Abstract: BACKGROUND: In children with inflammatory bowel disease (IBD), treatment depends on the type and extent of disease. Therefore, maximal effort should be made to provide a correct diagnosis. The aim of this study was to assess the value of a histologic diagnosis made on the basis of either ileal and colonic or rectosigmoid biopsies. METHODS: In 42 children with a known diagnosis of IBD, biopsies from rectum and sigmoid were reassessed by an expert, blinded pathologist. This histologic diagnosis was compared with the diagnosis based on (ileo)colonic biopsies and the final diagnosis. RESULTS: In patients with IBD, diagnostic accuracy of rectosigmoid histology was 0.4524. For (ileo)colonic biopsies, diagnostic accuracy was 0.7619. CONCLUSIONS: Histology on biopsies from rectum and sigmoid is insufficient for a correct diagnosis of Crohn's disease or ulcerative colitis in children. At initial presentation, an ileocolonoscopy with biopsies should therefore be performed in all children.

Escher JC, Taminiau JA. · Dept. of Paediatric Gastroenterology and Nutrition, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, The Netherlands. · Scand J Gastroenterol Suppl. · Pubmed #11768561 No free full text.

Abstract: Of all patients with Crohn disease and ulcerative colitis, the first presentation of inflammatory bowel disease (IBD) is at a paediatric or adolescent age in 20% to 30%, most children being prepubertal at diagnosis. It is essential to provide an accurate diagnosis in children suspected of IBD, as the initial treatment of Crohn disease and ulcerative colitis in children is not the same as it is in adults. While the role of enteral feeding in the treatment of Crohn disease in adults continues to be controversial, there is firm evidence to support the use of enteral feeding as primary therapy for Crohn disease in children. Nutrition is improved by enteral feeding, and growth and pubertal development are promoted, while the systemic toxicity of corticosteroid therapy is avoided. Supplementary nocturnal enteral nutrition (with daytime intake of normal diet) after primary therapy and remission induction may be associated with the prolongation of remission. Drug treatment in children with IBD is characterized by a lack of evidence from controlled trials.

Damen GM, van Lierop P, de Ruiter L, Escher JC, Donders R, Samsom JN, Nieuwenhuis EE. · No affiliation provided · Gut. · Pubmed #18791123 No free full text.

This publication has no abstract.

van Lierop PP, Damen GM, Escher JC, Samsom JN, Nieuwenhuis EE. · No affiliation provided · Lancet. · Pubmed #16905017 No free full text.

This publication has no abstract.