F. Bracci

Clinical role of calprotectin assay in determining histological relapses in children affected by inflammatory bowel diseases

Background: Inflammatory bowel diseases (IBD) are characterized by periods of remission with recurrent episodes of symptom exacerbation because of acute intestinal inflammation, which is correctly evaluated by endoscopy with biopsy sampling. However, many surrogate markers of intestinal inflammation, including fecal calprotectin (FC), are detected as potential predictors of mucosal inflammation in IBD patients. The aim of our study was to retrospectively assess the clinical efficacy of the calprotectin assay in determining histological relapses of pediatric IBD patients. Methods: We retrospectively reviewed the histological examinations, clinical records, and FC values of patients who had undergone colonoscopy at our hospital over an 8‐year period, from December 31, 1998, to December 31, 2006. Only patients with a first histological examination showing a quiescent IBD who submitted to a second histological examination during the next 3 years were selected. Results: Seventy‐three IBD patients, all with a first biopsy showing a quiescent IBD, were studied; at the second histological examination, 32 presented with relapse and 41 presented with remission. Relapsed patients showed significantly increased FC levels compared with nonrelapsed patients. A FC value of 275 &mgr;g/g achieved sensitivity and negative predictive value of 97% and specificity and positive predictive value of 85% in predicting histological relapse. Conclusions: FC seems to be a direct measure of intestinal inflammation and therefore a good marker of the risk of histological relapse in pediatric IBD patients. The application of this test in clinical practice may enable the avoidance of invasive tests as well as targeting treatment.

Long-term treatment with autologous red blood cells loaded with dexamethasone 21-phosphate in pediatric patients affected by steroid-dependent Crohn disease.

Background: Inflammatory bowel disease (IBD) present in childhood in 15% to 25% of cases. The aim of therapy in children is not only to guarantee normal growth but also to prevent relapse and to maintain remission. Steroids are effective to induce remission; however, resistance, dependency, and irreversible side effects can develop. The aim of this study was to determine whether treatment with repeated infusions of autologous red blood cells (RBCs) loaded with dexamethasone 21-phosphate (Dex 21-P) is safe and allows maintenance of long-term remission in children with steroid-dependent Crohn disease (CD). Patients and Methods: Eighteen consecutive pediatric patients who met the inclusion criteria were admitted to the study. Infusions of autologous RBCs loaded with Dex 21-P were performed every 4 weeks; the mean duration of treatment was 24 months. At the beginning of treatment and after 6, 12, and 24 months, we performed clinical evaluation according to the Pediatric Crohn Disease Activity Index (pCDAI). Assessment of body mass indexamethasone and bone mineral density by means of computerized bone mineralometry-dual energy x-ray absorptiometry, endoscopic evaluation, and hematic morning cortisol determination were also performed. Results: During treatment, the mean pCDAI significantly decreased (P < 0.05); 78% of patients discontinued steroids. Determination of morning cortisol showed suppression only on the first day after infusion, followed by normalization of values. Endoscopic findings showed remission in 44% of patients. None of the patients experienced serious side effects. Conclusions: These data suggest that repeated infusions of RBCs loaded with Dex 21-P can be safe and useful to maintain long-term remission in pediatric patients with moderately active CD.

Diagnostic Work-up of Inflammatory Bowel Disease in Children: The Role of Calprotectin Assay

Background: Some reports highlight the potential application of fecal calprotectin as a direct biomarker of intestinal inflammation and, therefore, as support in choosing candidates for endoscopy. The value of 100 &mgr;g/g was recently assumed as the best cutoff for this assay. The purpose of this study was to assess the diagnostic precision of the fecal calprotectin assay, compared to histology, as a stool‐screening biomarker for inflammatory bowel disease (IBD) among a group of prospectively identified patients referred for recurrent abdominal pain and altered bowel habits. Methods: Between 1999 and 2007 we prospectively evaluated the calprotectin assay in a cohort of patients with recurrent abdominal pain and altered bowel habits associated or not with other symptoms suggestive of IBD. All patients suspected of IBD, according to Rome and Porto criteria, provided stool specimens for the calprotectin assay and subsequently underwent endoscopic procedures. Results: Compared to histology, the cutoff of 100 &mgr;g/g reached a sensitivity and specificity of 100% and 68%, respectively, and a likelihood ratio (LR) of 3.1. The cutoff value of 160 &mgr;g/g, however, in our series produced the best joint estimate of sensitivity and specificity: 100% and 80%, respectively, with an LR of 5. Conclusions: In pediatric patients with recurrent abdominal pain and changes in stool habits, a positive calprotectin assay is closely associated with IBD; its systematic employment, therefore, seems to improve the process of endoscopy referral. This test, simple and inexpensive, could be included in the first noninvasive phase of an IBD diagnostic work‐up. (Inflamm Bowel Dis 2010)

Irreversible Intestinal Failure : Prevalence and Prognostic Factors

Background and Aim: Parenteral nutrition (PN) is the primary treatment for intestinal failure, which is considered irreversible in patients who remain partially or fully dependent on PN. Causes of irreversible intestinal failure are short bowel syndrome (SBS), motility disorders (MD), and severe protracted diarrhea (SPD). The aim of this study was to report the clinical outcome in these patients in relation to the underlying disease. Patients and Methods: From January 1, 1989 to December 31, 2006, 218 intestinal failure patients were observed in our center, but only 96 (48 SBS, 39 SPD, and 9 MD) were included because they required at least 50% of their total calories as PN for not less than 3 months. In these patients, survival and complication rates were evaluated. Results: The survival rate was significantly higher in SBS patients than in the other groups (P < 0.01). SBS patients showed a higher rate of major complications, although only intestinal failure–associated liver disease was significantly higher (P < 0.001). In our series, MD was the main cause of irreversible intestinal failure. Conclusions: The potential for bowel adaptation is higher in surgical than in medical causes of intestinal failure and does not seem to be influenced by complications of intestinal failure. SBS, although worsened by the major number of complications, was not the main category contributing to intestinal failure.

The clinical implications of thalidomide in inflammatory bowel diseases

Thalidomide has anti-inflammatory and anti-angiogenetic activity that makes it suitable for treating inflammatory bowel diseases (IBD). The recent guidelines from the European Crohn’s and Colitis Organization/European Society for Pediatric Gastroenterology Hepatology and Nutrition conclude that thalidomide cannot be recommended in refractory pediatric Crohn’s disease but that it may be considered in selected cohorts of patients who are not anti-TNFα agent responders. The main adverse effect is the potential teratogenicity that renders the long-term use of thalidomide problematic in young adults due to the strict need for contraceptive use. In short-term use it is relatively safe; the most likely adverse effect is the neuropathy, which is highly reversible in children. So far the use of thalidomide is reported in 223 adult and pediatric IBD patients (206 with Crohn’s disease). In the following sections, the authors will discuss efficacy and safety of thalidomide, in the short-term treatment of IBD.

Chronic pancreatitis as presentation of Crohn's disease in a child.

It is reported that a pancreatic disease may precede the diagnosis of inflammatory bowel disease (IBD) both in children and in adults. Idiopathic chronic pancreatitis, however, occasionally co-exists with the IBD, mainly at pediatric age. We report a case of a patient who progressively developed the features of a chronic pancreatitis, before the diagnosis of Crohns Disease (CD). Ten months after the onset of the first episode of pancreatitis the patient developed bloody diarrhea, mucus stools and biochemical findings of inflammation. The colonoscopy revealed a diffuse colitis without involvement of the last loop and the gastroscopy showed inflammation of the iuxta-papillary area. The histological findings confirmed the diagnosis of CD that involved the colon and the duodenum. In conclusion, in children the idiopathic chronic pancreatitis may be an unusual presentation of CD. Thus, if other known cause of chronic pancreatitis are not found, a not invasive work up to exclude the IBD should be warranted. An early coincidental diagnosis of the IBD may delay the progression of the pancreatic disease.

Association between celiac disease and primary lactase deficiency.

Primary lactase deficiency (PLD) is a common inherited condition caused by a reduced activity of lactase. Two single-nucleotide polymorphisms C/T-13910 and G/A-22018 upstream of the lactase gene are associated with lactase nonpersistence. In celiac disease (CD) patients, lactose intolerance could be due to secondary lactase deficiency and to PLD. The aim of this study were to evaluate the association of PLD and CD using genetic test, and to define the prevalence of PLD in celiac subjects compared with a control population. A total of 188 controls and 92 biopsy-proven CD patients were included in the study. More than 70% of all subjects were found homozygous for the polymorphisms. Differences in the prevalence of PLD were not found between CD patients and controls.In conclusions, the hereditary lactase deficiency is frequent in Italian CD children as in control population.

Pediatric inflammatory bowel disease: specificity of very early onset

ABSTRACT Introduction: The incidence of inflammatory bowel disease (IBD) has increased over the last 50 years. It is now recognized that several genetic defects can express an IBD-like phenotype at very early onset (<6 years). Areas covered: The aim of this review was to update knowledge concerning the specificity of IBD at onset <6 years, which can include conventional/standard IBD as well as monogenic IBD-like diseases. Expert commentary: We found that females are less prone than males to develop monogenic disorders, which have X-linked heritability in several cases. Furthermore, the Crohn’s Diseases (CD) subtype seems to be suggestive of monogenic disorders while Unclassified IBD (IBDU) subtype is predominantly found in conventional/standard IBD at onset <6 years. Isolated colonic location is prevalent in both the subsets of IBD at onset <6 years if compared to IBD at later onset. Monogenic disorders require more aggressive medical and surgical treatments and can be complicated by the occurrence of lymphomas.

Plasma citrulline in Crohn's disease as a marker of inflammation or disease localization

acute uncomplicated diverticulitis within 7 days after exclusion of complication, which is considered the only parameter avoiding early colonoscopy,12 and after a course of antibiotic therapy, without any early or late complication.13 Thus, an early endoscopic approach to acute diverticulitis (within 7 to 10d after an episode of uncomplicated diverticulitis) seems to be more effective than classic approach (4 to 6wk after hospital discharge). In this way, Schmilovitz-Weiss and colleagues did not perform an “early” colonoscopy, because they performed colonoscopy 4 to 6 weeks after hospital discharge—this is not an “early” timing but the “standard” timing in performing colonoscopy after an episode of acute diverticulitis.11 In my opinion, early colonoscopy is the only way to have a yield on the outcome of the patients. This is particularly true in patients with persistent diverticulitis. We know that diverticulitis, especially when uncomplicated, generally resolves within 3 days14,15: whether 7 to 10 days have passed without resolution (or whether significant improvement of symptoms is lacking), colonoscopy should be mandatory in order to explain why symptoms are still present. This is another point that should be taken into account in clinical practice. In fact Lahat et al16 found that colonoscopy detected other significant pathology in patients with persistent diverticulitis, which accounted for the clinical presentation in 17% of patients with persisting disease. 1. In conclusion, I mean that: colonoscopy is still mandatory in acute diverticulitis because:

Is colectomy still an option in the infliximab era

U lcerative colitis (UC) is a chronic inflammatory bowel disease that can affect both children and adults. Goals of treatment are induction and maintenance of remission to preserve the colon and its functions while minimizing the risks of treatment morbidities. Nevertheless, sometimes colectomy remains the only treatment option, especially in acute attacks. In the first 60 years of the last century, the majority of patients underwent colectomy. The introduction of corticosteroids in the 1960s reduced the colectomy rate by 60%, and recently, the use of cyclosporine reduced it by 80% (1). Recently, it has been demonstrated that infliximab (IFX) is an effective treatment for moderate-to-severe UC, including acute severe colitis. The ACT 1 and ACT 2 randomized trials conducted in adult UC patients (2) showed a colectomy rate of 10% in the IFX-treated arm, versus 17% in the placebo arm. A paediatric multicentre study by Turner et al (3) showed that IFX is effective as salvage medical therapy in 70% to 80% of affected children, reducing shortand long-term colectomy rate. Consequently, IFX has been used as a possible last treatment option, before colectomy in adult and children and has been recommended as rescue therapy for paediatric patients, failing intravenous corticosteroids before colectomy (4). The study of Nielsen et al (5) in this issue of the Journal of Pediatric Gastroenterology and Nutrition is a long-term retrospective multicentre paediatric study on a relatively large cohort of children, with chronic active or acute UC treated with IFX. Primary endpoints of the study were clinical response, risk of surgery, risk of new course of steroids, and safety in IFX treatment. It shows a total response rate (full or partial remission) in 69% of patients and 1 year and 2 year cumulative risk of colectomy, after IFX treatment of 21% and 26%, respectively, with no difference between patients in full or partial remission. It showed a lower risk of colectomy compared with a recent study by Hyams et al (6) in which the 1and 2-year colectomy rate was 28% and 39%, respectively. It also demonstrated a lower need of subsequent use of corticosteroids after starting IFX, as compared with the Hyams et al (6) study. Adverse effects were reported in 46% of patients, but only 7% discontinu-