Management of collagenous gastritis in children: Case series and literature review.

Collagenous gastritis (CG) is a rare histopathological finding on gastric biopsies in children. It is associated with abdominal pain and iron deficiency anemia, usually not respondent to oral iron supplements. The aim of this study was to describe our experience in the management of pediatric patients with CG. Moreover, we propose to review the literature on this topic. We retrospectively reviewed all pediatric patients diagnosed with CG at our centre from January 2014 to January 2019. Three pediatric patients (2 F, mean age 12.3) were diagnosed with CG during the study period. Two presented with moderate and one with severe anemia. Symptoms were abdominal pain, asthenia and headache in two and asthenia and abdominal pain in one. All underwent upper and lower gastrointestinal endoscopy. All were firstly started with oral iron supplements with no benefit, principally due to poor compliance secondary to the worsening of the epigastric pain and proton pump inhibitor resistance. Therefore, they underwent ferric carboxymaltose (FCM) infusion with good clinical and laboratory response. Patients received a mean of two infusions/year, with stable hemoglobin levels and no adverse outcomes. Our review failed to identify a consistent response to specific treatments. Considering the apparent benign nature of the disease, symptomatic and supportive treatments are advisable. Iron deficiency anemia is largely present and therapy with oral iron supplements is not always successful. In our study, FCM infusion was effective in increasing the key blood indices in patients who poorly tolerated oral supplements.

Evaluation of Risk for Thromboembolic Events in Pediatric Inflammatory Bowel Disease.

OBJECTIVES: The occurrence of thrombotic events in adult patients with inflammatory bowel disease (IBD) is linked to multiple interactions between hereditary and acquired risk factors. There are few published data concerning children with iBD. The aim of this study was to investigate the presence of thromboembolic risk factors also in children with iBD. METHODS: We enrolled three groups of children: one with Crohn disease (cD), one with ulcerative colitis (Uc), and a control group of healthy subjects. For all the participants the potential thromboembolic risk was evaluated clinically and with laboratory tests. RESULTS: We studied: 30 children (25.6%) with CD, 28 (23.9%) with UC, and 59 (50.4%) healthy control subjects. Regarding Pediatric Crohn Disease Activity Index, no significant differences between thromboembolic risk factors and disease activity were detected. Instead, in the patients with UC, stratified with the Pediatric Ulcerative Colitis Activity Index, there was a statistically significant difference in serum fibrinogen levels between patients with mild and moderate/severe disease [3.8 (3.2-4.5) g/L vs 5.7 (4.8-6.2) g/L, P  < 0.0032]. serum homocysteine levels were lower in healthy controls than in CD (P = 0.176) and UC (P = 0.026). An increased level ofhomocysteine in UC with a homozygous mutation in the methylene tetrahydrofolate reductase C677T gene was also observed. CONCLUSIONS: Our study showed that children with IBD have clinical features, acquired and congenital factors that can increase thrombotic risk, similarly to adults.

Paradoxical Psoriasis Induced by Anti-TNFα Treatment: Evaluation of Disease-Specific Clinical and Genetic Markers.

Paradoxical psoriasis (PP) may occur during treatment with anti-tumor necrosis factor-alpha (TNF-α) drugs in various chronic immune-mediated diseases, mainly inflammatory bowel diseases (IBD) and psoriasis. In this study, clinical and genetic characteristics of PP arising in IBD and psoriatic patients were investigated to identify disease-specific markers of the paradoxical effect. A total of 161 IBD and psoriatic patients treated with anti-TNF-α drugs were included in the study. Of these patients, 39 developed PP. All patients were characterized for the main clinical-pathologic characteristics and genotyped for six candidate single nucleotide polymorphisms (SNPs) selected for their possible role in PP susceptibility. In IBD patients, the onset of PP was associated with female sex, presence of comorbidities, and use of adalimumab. IBD patients with PP had a higher frequency of the TNF-α rs1799964 rare allele (p = 0.006) compared with cases without the paradoxical effect, and a lower frequency of the human leucocyte antigen (HLA)-Cw06 rs10484554 rare allele (p = 0.03) compared with psoriatic patients with PP. Overall, these findings point to specific clinical and genetic characteristics of IBD patients with PP and provide data showing that genetic variability may be related to the paradoxical effect of anti-TNF-α drugs with possible implications into clinical practice.

MRI reveals different Crohn's disease phenotypes in children and adults.

OBJECTIVES: To identify differences between two cohorts of adult and pediatric patients affected by Crohn's disease (CD), with regard to lesion location in the small intestine and colon-rectum, lesion activity, and prevalence of perianal disease (PD), using MRI as the main diagnostic tool. METHODS: We retrospectively reviewed 350 consecutive MRI examinations performed between 2013 and 2016 in outpatients or inpatients with histologically proven CD, monitored by the Gastroenterology and Pediatric Units of our Hospital. The magnetic resonance enterography (MRE) protocol for adult and pediatric CD patients routinely includes evaluation of nine different intestinal segments (from jejunum to rectum) and of the anal canal. Intestinal activity was also calculated using a validated score. Perianal disease (PD) was staged. Fisher's exact test was used and the odds ratio (OR) was calculated. RESULTS: Two hundred and nineteen out of 350 MRI studies (118 adults and 101 children) were included. The prevalence of PD was 34.6% in children and 16.1% in adults (OR = 2.8; p = 0.0017). Pediatric patients showed more frequent rectal involvement (29.7% vs 13.5%, OR = 2.7; p = 0.0045) and higher risk of PD in the presence of rectal disease (p = 0.043; OR = 4.5). In pediatric patients with severe colorectal disease, the prevalence of PD was twofold (86.7% vs 40%; p = 0.072). Using the clinical Montreal classification for lesion location, no significant differences emerged between the two patient populations. CONCLUSIONS: MRI showed a significantly higher prevalence of rectal involvement and perianal disease in the pediatric population. These results may have a relevant clinical impact and deserve further investigation. KEY POINTS: • To our knowledge, this is the largest morphological comparative study available in the literature using MRI as the main diagnostic tool to compare adult patients and children with Crohn's disease. • Our study showed significant differences between adults and children: a higher prevalence of rectal and perianal fistulous disease (PD) in pediatric patients and an increased prevalence of PD in the presence of severe colon-rectum involvement. • The association of rectal and perianal disease implies a poorer clinical prognosis and a higher risk of disabling complications in pediatric patients.

Predictors of Long-term Clinical and Endoscopic Remission in Children With Crohn Disease Treated With Infliximab.

OBJECTIVES: We aimed to identify early noninvasive predictors of clinical and endoscopic remission in children with Crohn disease (CD) under infliximab (IFX). METHODS: Prospective observational study conducted in children with moderate-to-severe CD starting IFX. All patients underwent weighted pediatric CD activity index (wPCDAI) assessment, C-reactive protein and fecal calprotectin (FC) at week 0, 14, and 48. Endoscopy was performed at 0 and 48 weeks. The primary outcome was to determine the ability of 14-week wPCDAI, C-reactive protein, and FC to predict 1-year steroid-free clinical remission and mucosal healing. As a secondary outcome we evaluated their concordance with Simple Endoscopic Score for CD (SES-CD) at week 48. RESULTS: Forty-one children were enrolled. At 1 year, 21 (51%) and 16 (39%) were in clinical and endoscopic remission. Only combined postinduction FC and wPCDAI were able to predict 1-year clinical and endoscopic remission (hazard ratio 4.81 [95% confidence interval 1.76-20.45], P = 0.05 and hazard ratio 5.51 [95% confidence interval 1.83-26.9], P = 0.03). One-year SES-CD moderately correlated with FC (r = 0.52; P = 0.001). The FC cut-off value for mucosal healing was 120.5 µg/g (area under the curve 0.863, 83% sensitivity, 75.5% specificity; P = 0.005). The concordance between wPCDAI and SES-CD was excellent and good for severe disease and remission (k 0.87 and 0.76). CONCLUSIONS: Post induction FC combined with wPCDAI can predict 1-year clinical and endoscopic response to IFX in pediatric CD. FC shows a moderate correlation with SES-CD, whereas wPCDAI has a good concordance with endoscopic remission or severe disease, but not with mild and moderate disease.

A Treat to Target Strategy Using Panenteric Capsule Endoscopy in Pediatric Patients With Crohn's Disease.

BACKGROUND & AIMS: Pan-enteric capsule endoscopy (PCE) is effective for assessment of small intestinal and colonic Crohn's disease (CD) in pediatric patients. We aimed to determine whether PCE can be used to monitor mucosal healing and deep remission, in a treat to target strategy for pediatric patients with CD. METHODS: We performed a prospective study of 48 children with a diagnosis of CD at a tertiary care pediatric gastroenterology unit; 46 patients were included in the final analysis. Biomarker, imaging, and PCE analyses were performed at baseline and after 24 and 52 weeks. Small bowel and colonic mucosal healing were defined by Lewis scores <135 and simple endoscopic score for CD ≤1, respectively. Clinical remission was defined as defined as a pediatric CD activity index score <10 and biomarker-based remission based on normal levels of biomarkers; deep remission was defined as a combination of clinical remission, biomarker-based remission, and mucosal healing. Treatments were adjusted based on findings from PCE (imaging was considered only for patients with negative findings from PCE). Therapies were introduced, optimized, switched, or combined at the discretion of treating clinicians. The primary outcome was the ability of PCE to assess mucosal healing and deep remission at 3 timepoints and to guide a treat to target strategy. RESULTS: PCE detected inflammation in 34 patients (71%) at baseline, 22 patients (46%) at week 24, and 18 patients (39%) at week 52 (P for comparison among timepoints <.05). Findings from PCE led to a change in therapy for 34 patients (71%) at baseline and 11 patients (23%) at 24 weeks, whereas only 2 patients with negative results from PCE (4%) changed therapies based on findings from imaging. When the treat to target strategy was applied, proportions of patients with mucosal healing and deep remission increased from 21% at baseline, to 54% at week 24, to 58% at week 52 (P for comparison among timepoints <.05); 2 patients (4%) did not respond to treatment. CONCLUSION: In a prospective study of 48 children with CD, we found a treat to target strategy, based on findings from PCE, to significantly increase the proportions of patients with mucosal healing and deep remission. CLINICAL TRIAL: gov no: NCT03161886.

Therapeutic Drug Monitoring is More Cost-Effective than a Clinically Based Approach in the Management of Loss of Response to Infliximab in Inflammatory Bowel Disease: An Observational Multicentre Study.

BACKGROUND AND AIMS: Empirical dose intensification and therapeutic drug monitoring [TDM] of infliximab [IFX] trough levels [ITLs] and antibody to infliximab [ATI] assays are recognized approaches for managing loss of response [LoR] in patients with inflammatory bowel disease [IBD]. The aim of the study was to compare these two interventions in a clinical setting, in terms of effectiveness and cost savings. METHODS: Consecutive IBD patients experiencing LoR were clinically managed according to a TDM algorithm. A historical group of empirically treated patients, for whom sera for ITLs and ATI assays had been collected, served as the control group. Clinical outcomes 12 weeks after the therapeutic interventions were compared between the two groups. A cost-minimization analysis was performed to compare the economic impact of these two approaches. RESULTS: Ninety-six patients were enrolled prospectively and compared with 52 controls. The two cohorts were similar in characteristics and in the distribution of TDM results. In the prospective cohort, however, we observed less IFX dose escalations compared with in the controls [45% versus 71%, p = 0.003]. Also, more patients were switched to a different anti-TNFα in the prospective cohort than in the control cohort [25% versus 4%, p = 0.001]. The percentages of patients achieving a clinical response at 12 weeks were 52% and 54% for the prospective and control groups, respectively. By cost analysis, we estimated a savings of 15% if the TDM algorithm was applied. CONCLUSIONS: In our population, applying a TDM algorithm for LoR to IFX resulted in less dose escalations, without loss of efficacy, compared with empirical adjustment. In addition, the TDM approach was cost-effective.

A promising medium-term follow-up of pediatric sclerosing cholangitis: Mild phenotype or early diagnosis?

AIM: Sclerosing cholangitis (SC) is a chronic cholestatic liver disease that is being increasingly diagnosed in childhood. The long-term course and prognosis of pediatric SC are poorly described. METHODS: We reviewed data of pediatric SC patients, followed in two referral centers, during a period of up to 20 years. We aimed to evaluate long-term outcomes according to SC phenotype. RESULTS: Among 45 patients (median age, 10.4 years; male patients, 73.4%) 29 (64.4%) were asymptomatic at presentation. Twenty patients (44%) had a concomitant inflammatory bowel disease (SC/IBD). Autoimmune features were found in 20 patients (44%). Liver biopsy showed severe fibrosis or cirrhosis in 32% of cases. Patients with SC alone had a higher rate of interface hepatitis at liver biopsy than SC/IBD patients. All children received ursodeoxycholic acid at diagnosis, and 17 received steroids and/or azathioprine. After a mean follow-up of 8.7 ± 5.6 years, all patients were alive and seven developed at least one liver-related complication. At the end of follow-up, 10 patients stopped immunosuppressants and two had no therapy. Only two patients underwent liver transplantation. Complication-free survival did not differ between SC/IBD and SC patients, but survival was longer in patients without autoimmune features. CONCLUSIONS: In our early diagnosed cohort, the 9-year survival with native liver was better than that reported in other studies. Approximately 15% of patients developed liver-related disease complications, less than previously reported. The long-term course of SC was negatively influenced by the presence of autoimmune features, but not by concomitant IBD.

Aortic, carotid intima-media thickness and flow- mediated dilation as markers of early atherosclerosis in a cohort of pediatric patients with rheumatic diseases.

The aims of this study were to identify the presence of endothelial dysfunction as a marker of early atherosclerosis by measuring aortic and carotid intimal-medial thickness (aIMT and cIMT) and flow-mediated dilation (FMD) and their correlation with traditional and no traditional risk factors for atherosclerosis in children with rheumatic diseases. Thirty-nine patients (mean age 15.3 ± 5.7 years), 23 juvenile idiopathic arthritis, 9 juvenile spondyloarthropathies, 7 connective tissue diseases (mean disease duration and onset respectively 5 ± 3.6 and 10 ± 5 years), and 52 healthy children matched for sex and age were enrolled. Demographic data (age, sex, familiarity for cardiovascular disease), traditional risk factors for atherosclerosis (BMI, active and passive smoking, dyslipidemia), activity disease indexes (reactive count protein, erythrocyte sedimentation rate) autoantibodies, and complement tests were collected. aIMT, cIMT, and FMD were assessed following a standardized protocol by high-resolution ultrasonography. Patients resulted significantly more exposed to passive smoking and had a lower BMI and higher homocysteine level than controls. cIMT and aIMT were significantly higher in patients than controls (p < 0.001) and correlated with age at diagnosis (p < 0.001 r 0.516 and 0.706, respectively) but not with mean disease duration. FMD % was significantly reduced in patients compared to controls (p < 0.001). Subclinical atherosclerosis occurs in pediatric rheumatic diseases, mainly in early onset forms, and aIMT is an earlier marker of preclinical atherosclerosis. Premature endothelial dysfunction could be included in the follow-up of children with rheumatic disorders to plan prevention strategies of cardiovascular disease already in pediatrics.

Looking Beyond Mucosal Healing: Effect of Biologic Therapy on Transmural Healing in Pediatric Crohn's Disease.

BACKGROUND: Crohn's disease is a chronic inflammatory disease characterized by a progressive transmural bowel damage leading to complications. Anti-TNFα therapy is effective in achieving mucosal healing (MH), but its efficacy on transmural inflammation has been poorly investigated. The aim of this study is to evaluate, in pediatric Crohn's disease, the efficacy of anti-tumor necrosis factor α agents in inducing transmural healing (TH) as assessed by ultrasonography (US). METHODS: Children with Crohn's disease requiring anti-tumor necrosis factor α therapy were prospectively enrolled. Clinical activity, laboratory tests, endoscopic activity, and transmural disease assessed by small intestine contrast US (SICUS) were evaluated at baseline (T0) and then after 9 to 12 months of therapy (T1). We evaluated US quantitative and qualitative parameters: disease extension (centimeters), bowel wall (BW) thickness >3 mm, BW vascularity and stratification strictures, and prestenotic dilatation. TH was defined as a BW thickness <3 mm and normalization of all US parameters at T1. RESULTS: Thirty-two patients were included. Patients with mucosal healing (MH) showed a significant decrease of BW thickness and disease extension at T1 (4.3 ± 1.4 mm and 8 ± 6.3 cm versus 6.1 ± 2.3 mm and 13 ± 5 cm at baseline, respectively) (P < 0.001). Increased vascularity of the BW was found in 80% of patients at T0 and in 18% at T1 (P < 0.001). These parameters did not change in patients without MH, despite clinical and laboratory remission. The presence of stenosis and prestenotic dilatation did not modify in any group. A complete TH was achieved in 14% of patients, all of them showing complete MH. CONCLUSIONS: Biologics induce clinical and laboratory remission and MH in pediatric CD. Although caution is needed due to the small sample size, our data suggest that transmural inflammation also improves during therapy, but a complete TH is achieved only in a small percentage of patients.

Difference in the late ergosterol biosynthesis between yeast spheroplasts and intact cells.

A comparative study on post-squalene sterol synthesis in intact yeast cells and spheroplasts was carried out with strains from three genera (Saccharomyces cerevisiae, Schizosaccharomyces pombe, Pichia pastoris) as well as with engineered S. cerevisiae cells altered in regard to the late ergosterol synthesis pathway. A common outcome of incubation experiments with radioactive acetate was that in intact cells the metabolic pathway flows till its specific end product (ergosterol and its precursor, depending on the enzyme deficiency), whereas in spheroplasts the pathway was stalled some step upstream. For example, in spheroplasts from wt strains, non-cyclic triterpenes squalene and oxidosqualene accumulated as though the metabolic path was kept from producing steroid-shaped molecules different from the end product. Accumulation of non-cyclic triterpenes was observed also in spheroplasts from S. cerevisiae cells lacking 3-ketosteroid reductase activity, an enzyme belonging to the C4-demethylase complex. When production of cyclic triterpenes was compromised by loss or poor functionality of oxidosqualene cyclase (EC 5.4.99.7), the difference between intact cells and spheroplasts was still remarkable, yet limited to the different oxido/dioxidosqualene ratio. The characteristics of spheroplasts as non-proliferating cells may partially explain the observed differences in post-squalene pathway from intact cells. We cannot say if the difference in metabolic pathways in spheroplasts and intact cells is a rule. We think, however, that it is worthwhile to search for an answer, as a wider picture of the points where the metabolic pathways are stalled in spheroplasts could provide original ideas about the metabolic network in yeast.

Prospective Evaluation of the Achievement of Mucosal Healing with Anti-TNF-α Therapy in a Paediatric Crohn's Disease Cohort.

BACKGROUND AND AIMS: There is growing evidence that in Crohn's disease the achievement and maintenance of mucosal healing (MH) through anti-TNFα antibodies may change the natural history of the disease. Few studies evaluating such outcome as a therapeutic goal are available in paediatrics. The primary aim of the study was to assess the efficacy of biologics in obtaining MH in a paediatric Crohn's disease cohort. The secondary aims were: (1) to assess response based on early or late treatment introduction and on combination therapy with immunomodulators versus biologics alone; and (2) to evaluate clinical outcome 2 years after the second endoscopy. METHODS: Biologic-naive paediatric Crohn's disease patients starting anti-tumour necrosis factor α (TNFα) treatment were enrolled. Patients' demographic and treatment data were recorded. Clinical [Pediatric Crohn's Disease Activity Index (PCDAI)] and endoscopic [Simple Endoscopic Score for Crohn's Disease (SES-CD)] evaluations were performed at time 0 (T0) and after 9-12 months (follow-up). Appropriate induction and maintenance therapeutic schemes were applied. RESULTS: Thirty-seven patients were enrolled. At enrolment, mean age was 12.3 ± 3.4 years and mean disease duration was 13.0 ± 16 months. At follow-up there was a significant decrease in PCDAI and SES-CD compared with T0 (p < 0.01). No statistical difference in frequency of MH between the early and late treatment introduction groups was found. Combination therapy was superior in obtaining complete plus partial MH (p < 0.01). One and 2 years after the second endoscopy, all and 79% of patients with complete MH and 75 and 67% of those with partial MH were still in clinical remission, respectively. CONCLUSIONS: Biologics improve mucosal lesions, apparently more effectively if given in combination with immunomodulators. MH appears to sustain a better disease course.

Aortic Intima-Media Thickness as an Early Marker of Atherosclerosis in Children With Inflammatory Bowel Disease.

OBJECTIVES: The aims of this study were to determine the presence of endothelial dysfunction by measuring aortic intima-media thickness (aIMT) and carotid intima-media thickness (cIMT) and to evaluate the role of traditional risk factors for premature atherosclerosis in children with inflammatory bowel disease (IBD). METHODS: Thirty-four children with IBD (25 Crohn disease [CD] and 9 ulcerative colitis [UC]; mean age 11.1 years) and 27 healthy subjects matched for sex and age were enrolled. In all of the patients, demographic characteristics and risk factors for atherosclerosis (age, sex, body mass index, blood pressure, dyslipidemia, active and passive smoking, and family history for cardiovascular diseases), CD and UC clinical activity scores, and inflammatory markers were evaluated. aIMT and cIMT were measured by high-resolution B-mode ultrasound. RESULTS: aIMT was significantly higher in patients than in controls (P < 0.0005). No significant differences were found for cIMT, although the carotid thickness was higher in patients with IBD than in healthy subjects. At a univariate analysis, inflammatory markers levels and tobacco smoking exposure were significantly related to higher aIMT values, whereas in a multivariate regression model, the inflammatory status was the only independent variable correlated with high aIMT. CONCLUSIONS: aIMT is an earlier marker of preclinical atherosclerosis than cIMT in young children with active IBD. The inflammatory status and the smoking exposure are significantly correlated with the premature endothelial dysfunction. These data emphasize the importance of controlling the chronic intestinal inflammation and endorsing smoke-free environments for children and adolescents with IBD.

The cholesterol biosynthesis enzyme oxidosqualene cyclase is a new target to impair tumour angiogenesis and metastasis dissemination.

Aberrant cholesterol homeostasis and biosynthesis has been observed in different tumour types. This paper investigates the role of the post-squalenic enzyme of cholesterol biosynthesis, oxidosqualene cyclase (OSC), in regulating tumour angiogenesis and metastasis dissemination in mouse models of cancer. We showed that Ro 48-8071, a selective inhibitor of OSC, reduced vascular density and increased pericyte coverage, with a consequent inhibition of tumour growth in a spontaneous mouse model of pancreatic tumour (RIP-Tag2) and two metastatic mouse models of human colon carcinoma (HCT116) and pancreatic adenocarcinoma (HPAF-II). Remarkably, the inhibition of OSC hampered metastasis formation in HCT116 and HPAF-II models. Ro 48-8071 induced tumour vessel normalization and enhanced the anti-tumoral and anti-metastatic effects of 5-fluorouracil (5-FU) in HCT116 mice. Ro 48-8071 exerted a strong anti-angiogenic activity by impairing endothelial cell adhesion and migration, and by blocking vessel formation in angiogenesis assays. OSC inhibition specifically interfered with the PI3K pathway. According to in vitro results, Ro 48-8071 specifically inhibited Akt phosphorylation in both cancer cells and tumour vasculature in all treated models. Thus, our results unveil a crucial role of OSC in the regulation of cancer progression and tumour angiogenesis, and indicate Ro 48-8071 as a potential novel anti-angiogenic and anti-metastatic drug.

Magnetic resonance enterography, small-intestine contrast US, and capsule endoscopy to evaluate the small bowel in pediatric Crohn's disease: a prospective, blinded, comparison study.

BACKGROUND: Small-bowel (SB) disease is a severe clinical entity among the phenotypes of Crohn's disease (CD). OBJECTIVE: To assess sensitivity, specificity, and accuracy of magnetic resonance enterography (MRE), small-intestine contrast US (SICUS), and capsule endoscopy (CE) in the diagnosis of pediatric SB-CD. DESIGN: Prospective, blinded, comparison study. SETTING: Tertiary center for pediatric inflammatory bowel disease. PATIENTS: Children with known or suspected CD. Diagnosis of SB obstruction at SICUS or MRE excluded patients from the study. INTERVENTION: Patients underwent ileocolonoscopy, MRE, SICUS, and CE over a 7-day period. For the imaging evaluation, SB was divided into 3 segments: jejunum, proximal and mid ileum, and terminal ileum. MAIN OUTCOME MEASUREMENTS: The performance of each method was compared to a consensus reference standard for upper SB and to ileocolonoscopy for the terminal ileum. RESULTS: Twenty-five patients completed the study. In the jejunum, the sensitivity of SICUS and CE was 92%, which was not significantly higher than MRE (75%); the specificity of CE (61%) was significantly lower than that of MRE (P = .04). In the proximal and mid ileum, MRE and CE did not have significantly higher sensitivity (100%) than SICUS (80%), but CE was less specific (P > .05). At the terminal ileum, SICUS and MRE were slightly more sensitive than CE (94% vs. 81%); however, the latter was more specific. LIMITATIONS: Use of the consensus reference standard for upper SB. Small number of patients. CONCLUSION: SICUS, MRE, and CE are all effective options for imaging SB. An integrated use of different tools should be suggested to achieve a complete assessment of the SB in children with suspected or confirmed CD.

Detection of Crohn disease lesions of the small and large bowel in pediatric patients: diagnostic value of MR enterography versus reference examinations.

OBJECTIVE: The purpose of this article is to prospectively determine the accuracy of MR enterography in detecting Crohn disease lesions from the jejunum to the anorectal region in pediatric patients, in comparison with main reference investigations. SUBJECTS AND METHODS: Fifty consecutive children with known Crohn disease underwent MR enterography with oral contrast agent and gadolinium-chelate intravenous injection. Two radiologists detected and localized lesions by dividing the bowel into nine segments (450 analyzed segments in 50 patients). Ileocolonoscopy, barium studies, intestinal ultrasound, and capsule endoscopy were considered as first- and second-level reference examinations and were performed within 15 days of MR enterography. RESULTS: MR enterography detected lesions in 164 of 450 segments, with 155 true-positive and nine false-positive findings; overall sensitivity, specificity, and positive and negative predictive values for small- and large-bowel lesions were 94.5%, 97%, 94.5%, and 97%, respectively (ĸ = 0.93; 95% CI, 0.89-0.97). Sensitivity and specificity values were 88% and 97%, respectively, for the jejunum, 100% and 97% for the proximal-to-mid ileum, 100% and 100% for the distal ileum, 93% and 100% for the cecum, 70% and 97% for the ascending colon, 80% and 100% for the transverse colon, 100% and 92% for the descending colon, 96% and 90% for the sigmoid colon, and 96% and 88% for the rectum. From jejunum to rectum, the AUC value ranged between 0.916 (jejunum) and 1.00 (distal ileum). Perianal fistulas were diagnosed in 15 patients, and other complications were found in 13 patients. CONCLUSION: MR enterography showed an accuracy comparable to that of reference investigations, for both small- and large-bowel lesions. Because MR enterography is safer and more comprehensive than the reference examinations, it should be considered the primary examination for detecting Crohn disease lesions in children.

Ultrasonography of the colon in pediatric ulcerative colitis: a prospective, blind, comparative study with colonoscopy.

OBJECTIVES: To evaluate the usefulness of colonic ultrasonography (US) in assessing the extent and activity of disease in pediatric ulcerative colitis (UC) and to compare US findings with clinical and endoscopic features. STUDY DESIGN: Consecutive pediatric patients (n = 60) with a diagnosis of UC and suspected disease flare-up were prospectively enrolled; of these, 50 patients were eligible for the study. All underwent clinical evaluation, bowel US with color Doppler examination and colonoscopy. Blind US was performed the day before endoscopy in all patients. The US assessed variables were bowel wall thickness >3 mm, bowel wall stratification, vascularity, presence of haustra coli, and enlarged mesenteric lymph nodes. RESULTS: The endoscopic extent of disease was independently confirmed in 47 patients by US that yielded a 90% concordance with endoscopy (95% CI 0.82-0.96). Multiple regression analysis showed that US measurements with an independent predictive value of severity at endoscopy were increased bowel wall thickness (P < .0008), increased vascularity (P < .002), loss of haustra (P = .031), and loss of stratification of the bowel wall (P = .021). Each variable was assigned a value of 1 if present. The US score strongly correlated with clinical (r = 0.94) and endoscopic activity (r = 0.90) of disease (P < .0001). CONCLUSIONS: Colonic US is a useful first line noninvasive tool to assess the extent and activity of disease in children with UC and to estimate the severity of a flare-up, prior to further invasive tests.

Biological therapy in a pediatric Crohn disease population at a referral center.

OBJECTIVE: The antitumor necrosis factor α (TNFα) antibodies infliximab and adalimumab are effective in inducing and maintaining remission in pediatric patients with Crohn disease (CD). The aim of the study was to evaluate the long-term efficacy and safety of biological therapy in pediatric patients with CD followed at a referral center. METHODS: This work is a retrospective observational study enrolling patients with CD treated with infliximab or adalimumab beyond the induction protocol. The patients' data were collected from the unit's IBD database (maximum follow-up evaluation after 36 months of treatment). The efficacy was evaluated by the Pediatric Crohn Disease Activity Index score and by analysis of the cumulative probability of continuing therapy; the safety was assessed in terms of adverse events. RESULTS: We enrolled 78 patients; the mean therapy duration was 27.2 ± 16.7 months, and the mean age at enrollment was 15 ± 3.1 years. The Kaplan-Meier analysis showed a cumulative probability of continuing therapy of 81%, 54%, and 33% at 1, 2, and 3 years, respectively, from the introduction of therapy. No association between the patients' baseline characteristics and the long-term outcome was found. The evaluation of the concomitant therapy with immunomodulators and anti-TNFα therapy versus anti-TNFα alone did not show a different outcome. No serious adverse events were recorded. CONCLUSIONS: The study indicates that biological therapy is effective and safe in pediatric patients with CD in a longer follow-up period. The response to treatment was not influenced by the patients' baseline characteristics or by the immunomodulator association.

Small intestine contrast ultrasonography in pediatric Crohn's disease.

OBJECTIVE: To evaluate the diagnostic accuracy of small intestine contrast ultrasonography (SICUS) in pediatric Crohn's disease (CD). STUDY DESIGN: A total of 51 consecutive patients (median age 15 years; range 3-20, 31 male patients), 21 with suspected and 30 with proven CD, were studied. All patients underwent standard ultrasonography (ie, transabdominal ultrasonography [TUS]), SICUS, small bowel follow-through, and upper and lower endoscopy. SICUS was performed in patients after they ingested an oral contrast solution. TUS and SICUS were compared with small bowel follow-through and endoscopy via use of the final diagnosis as reference standard. RESULTS: In undiagnosed patients, the sensitivity and specificity of TUS and SICUS in detecting CD small bowel lesions were 75% and 100% and 100% and 100%, respectively. In patients with proven CD, the sensitivity and specificity of TUS and SICUS were 76% and 100% and 96% and 100%, respectively. The agreement (k) with radiology for site of lesions was almost perfect for SICUS (0.93), both for jejunal and ileal lesions, and it was fair (0.40) for jejunal and substantial (0.68) for ileal lesions for TUS. Compared with radiology SICUS correctly assessed the length of lesions, whereas TUS underestimated it (P = .0001). CONCLUSIONS: The radiation-free technique SICUS is comparable with radiology and more accurate than TUS in assessing small bowel lesions in pediatric CD, mainly in the detection of proximal small bowel disease.

Presenting features and disease course of pediatric ulcerative colitis.

UNLABELLED: Clinical variables and disease course of pediatric ulcerative colitis (UC) have been poorly reported. The aim of this study was to retrospectively describe the phenotype and disease course of pediatric onset UC diagnosed at a tertiary referral Center for Pediatric Gastroenterology. PATIENTS AND METHODS: 110 patients with a diagnosis of UC were identified at our Department database. Records were reviewed for disease location and behavior at the diagnosis, family history for inflammatory bowel disease, pattern changes at the follow-up, need of surgery and cumulative risk for colectomy. RESULTS: Thirty-five % of patients had an early-onset disease (0-7 years). At the diagnosis, 29% had proctitis, 22% left-sided colitis, 15% extensive colitis and 34% pancolitis. Fifteen % presented with a rectal sparing, while a patchy colonic inflammation was reported in 18%. Rectal sparing was significantly related to the younger age (p: <0.05). Disease extension at the follow up was reported in 29% of pts. No clinical variables at the diagnosis were related to the subsequent extension of the disease. The cumulative rates of colectomy were 9% at 2 year and 14% at 5 years. An extensive disease as well as acute severe colitis and corticosteroid therapy at the diagnosis were significantly associated with an increased risk of colectomy. CONCLUSIONS: Pediatric UC is extensive and severe at the diagnosis, with an overall high rate of disease extension at the follow-up. Endoscopic atypical features are common in young children. The colectomy rate is related to the location and severity of the disease at the diagnosis.