Fatigue and Physical Activity Patterns in Children With Inflammatory Bowel Disease.

OBJECTIVES: Fatigue is a common symptom in children with inflammatory bowel disease (IBD). Diagnostic tests to evaluate biological causes of fatigue commonly include markers of inflammation and hemoglobin (Hb), yet functional parameters have been inadequately studied in pediatric IBD. In this study, we compared fatigued and non-fatigued children with IBD from both a biological and functional point of view. METHODS: A cross-sectional study of 104 pediatric IBD patients with mild to moderately active IBD was conducted. Fatigued children were defined as those with a Pediatric Quality of Life Inventory Multidimensional Fatigue Scale z score <-2.0. Non-fatigued children had a z score ≥-2.0. Disease-specific quality of life (measured with IMPACT-III score), C-reactive protein (CRP), fecal calprotectin (FC), hemoglobin z score (Hb z score), and physical activity tests including 6-minute walking distance z score (6MWD z score) and triaxial accelerometry (TA) were evaluated. RESULTS: Fatigued children (n = 24) had a significant lower IMPACT-III score than non-fatigued children (n = 80). Hb z scores, CRP, FC, and 6MWD z scores were not significantly different between groups. TA was performed in 71 patients. Wear time validation requirements were met in only 31 patients. Fatigued patients spent significant shorter median time in moderate-to-vigorous activity than non-fatigued patients (18.3 vs 37.3 minutes per day, P = 0.008). CONCLUSION: Biological parameters did not discriminate fatigued from non-fatigued patients. TA possibly distinguishes fatigued from non-fatigued patients; the potential association may provide a target for interventions to combat fatigue and improve quality of life.

Complications of Gastrostomy and Gastrojejunostomy: The Prevalence in Children.

Purpose: This study aimed to provide an overview of the prevalence of the complications of a gastrostomy or a gastrojejunostomy with a low-profile gastric tube in children. The study also examined the effect of presence of the gastrostomy tube on the prevalence of complications. Methods: In this cross-sectional study, parents were invited to complete an online questionnaire. Children aged 0-16 years with a low-profile gastrostomy or gastrojejunostomy tube were included in the study. Results: A total of 67 complete surveys were conducted. The mean age of the included children was seven years. The most common complications during the past week, were skin irritation (35.8%), abdominal pain (34.3%), and the formation of granulation tissue (29.9%). The most common complications during the past six months were skin irritation (47.8%), vomiting (43.4%), and abdominal pain (38.8%). Most complications occurred within the first year after gastrojejunostomy placement and gradually decreased as the duration since the placement of the gastrojejunostomy tube increased. The prevalence of severe complications was rare. Parental confidence in caring for the gastrostomy positively correlated with increases in the duration of the gastrostomy tube. Even so, parental confidence in the care of the gastrostomy tube was reduced in some parents more than a year after its placement. Conclusion: The prevalence of gastrojejunostomy complications in children is relatively high. The incidences of severe complications after the placement of a gastrojejunostomy tube were rare in this study. A lack of confidence in the care of the gastrostomy tube was noted in some parents more than a year after its placement.

Aberrant Mucin Expression Profiles Associate With Pediatric Inflammatory Bowel Disease Presentation and Activity.

BACKGROUND: Intestinal mucosal healing is nowadays preferred as the therapeutic endpoint in inflammatory bowel disease (IBD), but objective measurements at the molecular level are lacking. Because dysregulated mucin expression is suggested to be involved in mucosal barrier dysfunction in IBD, we investigated mucin expression in association with barrier mediators and clinical characteristics in colonic tissue of a pediatric IBD population. METHODS: In this cross-sectional monocentric study, we quantified messenger RNA (mRNA) expression of mucins, intercellular junctions, and cell polarity complexes in inflamed and noninflamed colonic biopsies from pediatric IBD (n = 29) and non-IBD (n = 15) patients. We then validated mucin expression at protein level and correlated mucin mRNA expression with expression of barrier mediators and clinical data. RESULTS: The expression of MUC1, MUC3A, MUC4, and MUC13 was increased in the inflamed colon of pediatric IBD patients compared with the noninflamed colon of non-IBD control subjects. Especially MUC13 mRNA expression associated with the expression of barrier mediators, including CDH1, OCLN, and TJP2. MUC1 and MUC3B mRNA expression in combination with calprotectin levels most accurately discriminated IBD patients from non-IBD control subjects (90.6% area under the receiver-operating characteristic curve [AUCROC], 92.0% sensitivity, 73.7% specificity), whereas aberrant mRNA expression of MUC1, MUC3A, MUC4, and MUC13 was distinctive for ulcerative colitis and of MUC3B for Crohn's disease. Furthermore, expression of MUC3A, MUC3B, and MUC4 correlated with clinical disease activity (ie, Pediatric Ulcerative Colitis Activity Index and Pediatric Crohn's Disease Activity Index), and of MUC1, MUC2, MUC4, and MUC13 with endoscopic colitis severity in ulcerative colitis patients. CONCLUSIONS: Colonic mucin expression is disturbed in pediatric IBD patients and associates with disease activity and presentation, suggesting its use as molecular marker to aid in disease diagnosis and management.

Ferric Carboxymaltose Versus Ferrous Fumarate in Anemic Children with Inflammatory Bowel Disease: The POPEYE Randomized Controlled Clinical Trial.

OBJECTIVE: To determine whether intravenous (IV) or oral iron suppletion is superior in improving physical fitness in anemic children with inflammatory bowel disease (IBD). STUDY DESIGN: We conducted a clinical trial at 11 centers. Children aged 8-18 with IBD and anemia (defined as hemoglobin [Hb] z-score < -2) were randomly assigned to a single IV dose of ferric carboxymaltose or 12 weeks of oral ferrous fumarate. Primary end point was the change in 6-minute walking distance (6MWD) from baseline, expressed as z-score. Secondary outcome was a change in Hb z-score from baseline. RESULTS: We randomized 64 patients (33 IV iron and 31 oral iron) and followed them for 6 months. One month after the start of iron therapy, the 6MWD z-score of patients in the IV group had increased by 0.71 compared with -0.11 in the oral group (P = .01). At 3- and 6-month follow-ups, no significant differences in 6MWD z-scores were observed. Hb z-scores gradually increased in both groups and the rate of increase was not different between groups at 1, 3, and 6 months after initiation of iron therapy (overall P = .97). CONCLUSION: In this trial involving anemic children with IBD, a single dose of IV ferric carboxymaltose was superior to oral ferrous fumarate with respect to quick improvement of physical fitness. At 3 and 6 months after initiation of therapy, no differences were discovered between oral and IV therapies. The increase of Hb over time was comparable in both treatment groups. TRIAL REGISTRATION: NTR4487 [Netherlands Trial Registry].

The Challenges of Crizotinib Treatment in a Child With Anaplastic Large Cell Lymphoma.

Survival in cases involving childhood malignancy is reaching nearly 80% in high-income countries, yet cancer remains one of the leading disease-related causes of death in children. In adult oncology the role of targeted therapies is established, but information regarding the use of these therapies in children is limited, largely because targeted therapies were developed in the context of adult pathologies. The few pediatric reports regarding crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, seem promising. This case of an 8-year-old male with an ALK-positive anaplastic large cell lymphoma highlights the challenges of treating children with crizotinib. Our experience with crizotinib was more challenging than described in the limited pediatric reports. Not only was the tumor response poorer than described in the reports, but a substantial amount of side-effects and practical difficulties, such as the method of administration and dosing, made management challenging. Many challenges for the use of targeted therapy in pediatric care currently persist. The limited research in pediatric populations leaves uncertainty regarding efficacy and short- and long-term side effects as well as practical difficulties. Despite a clear underlying biological rationale for certain targeted therapies, their contribution toward improving the outcome of childhood cancer remains largely unclear.

Test Strategies to Predict Inflammatory Bowel Disease Among Children With Nonbloody Diarrhea.

OBJECTIVES: We evaluated 4 diagnostic strategies to predict the presence of inflammatory bowel disease (IBD) in children who present with chronic nonbloody diarrhea and abdominal pain. METHODS: We conducted a prospective cohort study including 193 patients aged 6 to 18 years who underwent a standardized diagnostic workup in secondary or tertiary care hospitals. Each patient was assessed for symptoms, C-reactive protein (>10 mg/L), hemoglobin (<-2 SD for age and sex), and fecal calprotectin (≥250 µg/g). Patients with rectal bleeding or perianal disease were excluded because the presence of these findings prompted endoscopy regardless of their biomarkers. Primary outcome was IBD confirmed by endoscopy or IBD ruled out by endoscopy or uneventful clinical follow-up for 6 months. RESULTS: Twenty-two of 193 (11%) children had IBD. The basic prediction model was based on symptoms only. Adding blood or stool markers increased the AUC from 0.718 (95% confidence interval [CI]: 0.604-0.832) to 0.930 (95% CI: 0.884-0.977) and 0.967 (95% CI: 0.945-0.990). Combining symptoms with blood and stool markers outperformed all other strategies (AUC 0.997 [95% CI: 0.993-1.000]). Triaging with a strategy that involves symptoms, blood markers, and calprotectin will result in 14 of 100 patients being exposed to endoscopy. Three of them will not have IBD, and no IBD-affected child will be missed. CONCLUSIONS: Evaluating symptoms plus blood and stool markers in patients with nonbloody diarrhea is the optimal test strategy that allows pediatricians to reserve a diagnostic endoscopy for children at high risk for IBD.

Endogenous pain modulation in children with functional abdominal pain disorders.

Functional abdominal pain disorders (FAPDs) are common among young individuals. To date, relatively little is known regarding the function of the endogenous analgesic mechanisms in this vulnerable group. Therefore, this case-control study aimed to compare conditioned pain modulation (CPM), pressure algometry, and psychosocial variables in 39 young children (aged 6-12 years) with FAPD and 36 age- and sex-matched pain-free controls. Pressure algometry was used to assess pressure pain thresholds (PPTs) at both symptomatic (umbilicus) as remote (trapezius and tibia) test sites. Conditioned pain modulation was recorded as an increase in the PPT at the trapezius test site in response to experimental conditioning pain imposed by the cold pressor task (12 ± 1°C). The assessors were blinded to the diagnoses. Parent-proxy and/or self-reported questionnaires were used to assess child's pain intensity, functional disability, pain-related fear, and parental pain catastrophizing. Compared with pain-free controls, young children with FAPD showed lower PPTs at all test sites (P < 0.05), a lower CPM response (P = 0.02), more functional disability (P < 0.001), and pain-related fear (P < 0.001). Parents of children with FAPD catastrophized more about their child's pain than parents of healthy children (P < 0.001). No sex differences were found for the experimental pain measurements (P > 0.05), nor was there a significant correlation between the child- and parent-reported questionnaires and the CPM effect (P > 0.05). In summary, young children with FAPD demonstrated secondary hyperalgesia and decreased functioning of endogenous analgesia.

Fatigue in children and adolescents with inflammatory bowel disease.

AIM: To identify factors other than active disease and anemia that contribute to fatigue in pediatric inflammatory bowel disease (IBD). METHODS: We performed an electronic search in Medline and EMBASE from their inception to May 2017 using the search term "fatigue" or the related keywords "physical impairment" and "inflammatory bowel disease" with the filter "child" (age 0-18 years). Cross-sectional and case-control studies were included. We restricted our search to studies published in English. We used the PRISMA checklist and flow diagram. Duplicate articles were manually deleted in End Note. To identify further relevant studies, we checked the reference lists of the selected articles. RESULTS: We identified 149 papers, of which 19 were retrieved for full text review. Eleven studies were subsequently excluded because fatigue was not evaluated as an outcome measure. Eight papers focused on the desired topic and were discussed in the final analysis. A lack of uniformity of outcome measures made the pooling of data impossible. In all but one study, questionnaires were used to evaluate fatigue. In the remaining study, an accelerometer was used to measure daily activities, sleeping time and their relationships with fatigue in a more quantifiable manner. Adolescents with IBD are significantly more fatigued than healthy controls. In addition to active disease, increased anxiety or depression and disturbed family relationships were frequently reported predictors of fatigue. Quantitative measurement of physical activity in patients with Crohn's disease showed a reduction in the number of steps per day, and patients with ulcerative colitis had a shorter duration of physical activity during the day. CONCLUSION: Fatigue in pediatric IBD is related to a combination of biological, functional and behavioral factors, which should all be taken into account when managing fatigue.

No association between abdominal pain and Dientamoeba in Dutch and Belgian children.

OBJECTIVE: To study the association between Dientamoebafragilis colonisation and faecal calprotectin to see whether the parasite is a harmless commensal or a gut pathogen. DESIGN: Cross-sectional study of previously collected stool samples. SETTING AND PATIENTS: Two hundred stool samples originated from children aged 5-19 years with chronic abdominal pain and diarrhoea, who were seen in paediatric clinics in the Netherlands and Belgium and in whom somatic gastrointestinal disorders were excluded. Another 122 samples came from a healthy community-based reference population of the same age. All stool samples were analysed with real-time PCR for the detection of D. fragilis and with an ELISA for calprotectin-a biomarker of gastrointestinal inflammation. MAIN OUTCOME MEASURES: Prevalence of D. fragilis colonisation and results of stool calprotectin testing. RESULTS: D. fragilis was detected in 45% (95% CI 38% to 51%) of patients and in 71% (95% CI 63% to 79%) of healthy children. Median (IQR) concentrations of calprotectin in patients and healthy children with a positive PCR result were not different from those with a negative PCR result (40 (40-55) µg/g vs 40 (40-75) µg/g, respectively). CONCLUSION: Since D. fragilis colonisation is most prevalent in healthy children and is not associated with an increase in faecal calprotectin concentration, our data do not support the inference that D. fragilis is a pathogenic parasite. Routinely testing for D. fragilis in children with chronic abdominal pain should therefore be discouraged.

Recurrent pericarditis as an extra-intestinal manifestation of ulcerative colitis in a 14-year-old girl.

Pericarditis is a known complication of mesalazine in the treatment of ulcerative colitis. This case study illustrates that after diagnostic work-up, pericarditis should not always be attributed to the use of mesalazine. It may be the presentation of an extra-intestinal manifestation of ulcerative colitis. Restarting of mesalazine should be considered.

Gastric fluid composition in a paediatric population: Age-dependent changes relevant for gastrointestinal drug disposition.

This work aimed to (i) expand the dataset on gastric fluid composition in the paediatric population (0-18 years old) and (ii) improve our understanding of age-dependent changes in gastric fluid characteristics involved in gastrointestinal drug disposition. For this purpose, gastric fluids from preterm neonates, term neonates, infants, children and adolescents were collected during routine medical procedures. Gastric fluid constituents relevant for gastrointestinal drug disposition were characterized i.e., pH, osmolality and bile salts (concentration + composition). Differences in gastric fluid composition compared to adults were most prominent in neonates. In this context, the fact that neonates are rarely fasted due to frequent feedings should be taken into account during paediatric drug product development. It remains to be explored to what extent the observed variability and differences in gastric fluid characteristics within and between age groups translates to variability and/or differences in oral drug disposition.

Predicting inflammatory bowel disease in children with abdominal pain and diarrhoea: calgranulin-C versus calprotectin stool tests.

OBJECTIVE: Calgranulin-C (S100A12) is a new faecal marker of inflammation that is potentially more specific for inflammatory bowel disease (IBD) than calprotectin, since it is only released by activated granulocytes. We compared calgranulin-C and calprotectin to see which of the two tests best predicted IBD in children with chronic abdominal pain and diarrhoea. DESIGN: Delayed-type cross-sectional diagnostic study. SETTING AND PATIENTS: Previously undiagnosed patients aged 6-17 years, who were seen in paediatric clinics in the Netherlands and Belgium, sent in a stool sample for analysis. Patients with a high likelihood of IBD underwent upper and lower endoscopy (ie, preferred reference test), while those with a low likelihood were followed for 6 months for latent IBD to become visible (ie, alternative reference test). We used Bayesian modelling to correct for differential verification bias. MAIN OUTCOME MEASURES: Primary outcome was the specificity for IBD using predefined test thresholds (calgranulin-C: 0.75 µg/g, calprotectin: 50 µg/g). Secondary outcome was the test accuracy with thresholds based on receiver operating characteristics (ROC) analysis. RESULTS: IBD was diagnosed in 93 of 337 patients. Calgranulin-C had significantly better specificity than calprotectin when predefined thresholds were used (97% (95% credible interval (CI) 94% to 99%) vs 71% (95% CI 63% to 79%), respectively). When ROC-based thresholds were used (calgranulin-C: 0.75 µg/g, calprotectin: 400 µg/g), both tests performed equally well (specificity: 97% (95% CI 94% to 99%) vs 98% (95% CI 95% to 100%)). CONCLUSIONS: Both calgranulin-C and calprotectin have excellent test characteristics to predict IBD and justify endoscopy. TRIAL REGISTRATION NUMBER: NCT02197780.

Use of Laboratory Markers in Addition to Symptoms for Diagnosis of Inflammatory Bowel Disease in Children: A Meta-analysis of Individual Patient Data.

Importance: Blood markers and fecal calprotectin are used in the diagnostic workup for inflammatory bowel disease (IBD) in pediatric patients. Any added diagnostic value of these laboratory markers remains unclear. Objective: To determine whether adding laboratory markers to evaluation of signs and symptoms improves accuracy when diagnosing pediatric IBD. Data Sources: A literature search of MEDLINE and EMBASE from inception through September 26, 2016. Studies were identified using indexing terms and free-text words related to child, target condition IBD, and diagnostic accuracy. Study Selection: Two reviewers independently selected studies evaluating the diagnostic accuracy of more than 1 blood marker or fecal calprotectin for IBD, confirmed by endoscopy and histopathology or clinical follow-up, in pediatric patients with chronic gastrointestinal symptoms. Studies that included healthy controls and/or patients with known IBD were excluded. Data Extraction and Synthesis: Individual patient data from each eligible study were requested from the authors. In addition, 2 reviewers independently assessed quality with Quality Assessment of Diagnostic Accuracy Studies-2. Mean Outcomes and Measures: Laboratory markers were added as a single test to a basic prediction model based on symptoms. Outcome measures were improvement of discrimination by adding markers as a single test and improvement of risk classification of pediatric patients by adding the best marker. Results: Of the 16 eligible studies, authors of 8 studies (n = 1120 patients) provided their data sets. All blood markers and fecal calprotectin individually significantly improved the discrimination between pediatric patients with and those without IBD, when added to evaluation of symptoms. The best marker-fecal calprotectin-improved the area under the curve of symptoms by 0.26 (95% CI, 0.21-0.31). The second best marker-erythrocyte sedimentation rate-improved the area under the curve of symptoms by 0.16 (95% CI, 0.11-0.21). When fecal calprotectin was added to the model, the proportion of patients without IBD correctly classified as low risk of IBD increased from 33% to 91%. The proportion of patients with IBD incorrectly classified as low risk of IBD decreased from 16% to 9%. The proportion of the total number of patients assigned to the intermediate-risk category decreased from 55% to 6%. Conclusions and Relevance: In a hospital setting, fecal calprotectin added the most diagnostic value to symptoms compared with blood markers. Adding fecal calprotectin to the diagnostic workup of pediatric patients with symptoms suggestive of IBD considerably decreased the number of patients in the group in whom challenges in clinical decision making are most prevalent.

Long-term Outcomes with Anti-TNF Therapy and Accelerated Step-up in the Prospective Pediatric Belgian Crohn's Disease Registry (BELCRO).

BACKGROUND: Accelerated step-up or anti-tumor necrosis factor (TNF) before first remission is currently not recommended in pediatric Crohn's disease. METHODS: Five-year follow-up data from a prospective observational cohort of children diagnosed with Crohn's disease in Belgium were analyzed. Disease severity was scored as inactive, mild, or moderate to severe. Remission or inactive disease was defined as sustained if lasting ≥2 years. Univariate analyses were performed between anti-TNF-exposed versus naive patients and anti-TNF before versus after first remission and correlations assessed with primary outcomes average disease severity and sustained remission. RESULTS: A total of 91 patients (median [IQR] age 12.7 [10.9-14.8] yrs, 53% male) were included. Disease location was 12% L1, 23% L2, and 64% L3 with 76% upper gastrointestinal and 30% perianal involvement. Disease severity was 25% mild and 75% moderate to severe. Of 66 (73%) anti-TNF-exposed patients, 34 (52%) had accelerated step-up. Anti-TNF use was associated with age (13.1 [11.5-15.2] versus 11.8 [8.7-13.8] yrs; P < 0.05), L2 (29% versus 8%; P = 0.04), and average disease severity (1.7 [1.4-1.9] versus 1.4 [1.3-1.6]; P < 0.001). Duration of anti-TNF correlated with average disease severity (r = 0.32, P = 0.002). Accelerated step-up was also associated with age (13.3 [12.1-15.9] versus 12.5 [10.2-14.1]; P = 0.02) and average disease severity (1.8 [1.6-1.9] versus 1.6 [1.3-1.8]; P = 0.002). Duration of sustained remission was similar in all patients, and no serious infections, cancer, or deaths were reported. CONCLUSIONS: Anti-TNF therapy and accelerated step-up in older patients with more severe disease leads to beneficial long-term outcomes.

Selecting children with suspected inflammatory bowel disease for endoscopy with the calgranulin C or calprotectin stool test: protocol of the CACATU study.

INTRODUCTION: The introduction of the faecal calprotectin (FC) test to screen children with chronic gastrointestinal complaints has helped the clinician to decide whether or not to subject the patient to endoscopy. In spite of this, a considerable number of patients without inflammatory bowel disease (IBD) is still scoped. Faecal calgranulin C (S100A12) is a marker of intestinal inflammation that is potentially more specific for IBD than FC, as it is exclusively released by activated granulocytes. OBJECTIVE: To determine whether the specificity of S100A12 is superior to the specificity of FC without sacrificing sensitivity in patients with suspected IBD. METHODS: An international prospective cohort of children with suspected IBD will be screened with the existing FC stool test and the new S100A12 stool test. The reference standard (endoscopy with biopsies) will be applied to patients at high risk of IBD, while a secondary reference (clinical follow-up) will be applied to those at low risk of IBD. The differences in specificity and sensitivity between the two markers will be calculated. ETHICS AND DISSEMINATION: This study is submitted to and approved by the Medical Ethics Review Committee of the University Medical Center Groningen (the Netherlands) and the Antwerp University Hospital (Belgium). The results will be disseminated through a peer-reviewed publication, conference presentation and incorporation in the upcoming National Guideline on Diagnosis and Therapy of IBD in Children. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02197780 .

Genetic screening of Congenital Short Bowel Syndrome patients confirms CLMP as the major gene involved in the recessive form of this disorder.

Congenital short bowel syndrome (CSBS) is an intestinal pediatric disorder, where patients are born with a dramatic shortened small intestine. Pathogenic variants in CLMP were recently identified to cause an autosomal recessive form of the disease. However, due to the rare nature of CSBS, only a small number of patients have been reported to date with variants in this gene. In this report, we describe novel inherited variants in CLMP in three CSBS patients derived from two unrelated families, confirming CLMP as the major gene involved in the development of the recessive form of CSBS.

Faecal calprotectin in suspected paediatric inflammatory bowel disease.

OBJECTIVES: The diagnostic accuracy of faecal calprotectin (FC) concentration for paediatric inflammatory bowel disease (IBD) is well described at the population level, but not at the individual level. We reassessed the diagnostic accuracy of FC in children with suspected IBD and developed an individual risk prediction rule using individual patient data. METHODS: MEDLINE, EMBASE, DARE, and MEDION databases were searched to identify cohort studies evaluating the diagnostic performance of FC in paediatric patients suspected of having IBD. A standard study-level meta-analysis was performed. In an individual patient data meta-analysis, we reanalysed the diagnostic accuracy on a merged patient dataset. Using logistic regression analysis we investigated whether and how the FC value and patient characteristics influence the diagnostic precision. A prediction rule was derived for use in clinical practice and implemented in a spreadsheet calculator. RESULTS: According to the study-level meta-analysis (9 studies, describing 853 patients), FC has a high overall sensitivity of 0.97 (95% confidence interval [CI] 0.92-0.99) and a specificity of 0.70 (0.59-0.79) for diagnosing IBD. In the patient-level pooled analysis of 742 patients from 8 diagnostic accuracy studies, we calculated that at an FC cutoff level of 50 µg/g there would be 17% (95% CI 15-20) false-positive and 2% (1-3) false-negative results. The final logistic regression model was based on individual data of 545 patients and included both FC level and age. The area under the receiver operating characteristic curve of this derived prediction model was 0.92 (95% CI 0.89-0.94). CONCLUSIONS: In high-prevalence circumstances, FC can be used as a noninvasive biomarker of paediatric IBD with only a small risk of missing cases. To quantify the individual patients' risk, we developed a simple prediction model based on FC concentration and age. Although the derived prediction rule cannot substitute the clinical diagnostic process, it can help in selecting patients for endoscopic evaluation.