Ömer Faruk Beşer

Shear wave elastography in the evaluation of liver fibrosis in children.

Background: Shear-wave elastography (SWE) is a novel noninvasive method that involves application of local mechanical compression on soft tissue using focused ultrasonography and acquiring strain images that show tissue response. In this study, our goal was to assess the performance of SWE in the staging of liver fibrosis in children with chronic liver disease. Methods: The study involved measuring SWE values in the right lobe of the liver in a patient group of 76 children with chronic liver disease and a control group of 50 healthy subjects. In the patient group, the shear elastic modulus values were correlated with biopsy results according to the Brunt scoring system (F0: portal fibrosis, F1: perisinusoidal or portal/periportal fibrosis, F2: both perisinusoidal and portal/periportal fibrosis, F3: bridging fibrosis, and F4: cirrhosis). Performance of SWE in estimating liver fibrosis in children was determined based on a receiver-operating characteristics (ROC) analysis. Results: Mean SWE values of the control group and F0 group were not statistically significantly different (P = 0.106). The mean SWE values of the F1, F2, F3, and F4 groups were higher than that of the control group (all P < 0.001). Based on kiloPascal measurement values, the area under the ROC curve was 95.2% (95% confidence interval [CI] 92.1–99.5), with a sensitivity for diagnosing liver fibrosis of 91.5%, a specificity of 94.0%, a positive predictive value of 93.1%, and a negative predictive value of 92.6%. Based on meter-per-second measurement values, the area under the ROC curve was 96.3% (95% CI 92.7–99.8), with a sensitivity for diagnosing liver fibrosis of 93.2%, a specificity of 94.0%, a positive predictive value of 93.2%, and a negative predictive value of 94.0%. Mean SWE values for patients with nonalcoholic steatohepatitis were higher than those in the remainder of the study group. Conclusions: Although liver fibrosis can be detected using SWE, differentiation of fibrosis stages could not be achieved. The presence of steatosis significantly increased the mean SWE values on elastography and so care should be taken when assessing children with nonalcoholic steatohepatitis.

The Incidence of Irritable Bowel Syndrome in Children Using the Rome III Criteria and the Effect of Trimebutine Treatment

Background/Aims Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders and when compared to the vast knowledge pertaining to adults with IBS, very little is known about IBS in children and adolescents. We aimed to explore the prevalence of IBS, identify symptoms and contributing factors and also to examine the efficacy of trimebutine maleate in children and adolescents. Methods The study involved 345 children and adolescents (4-18 years) and parents were requested to fill in a questionnaire, Rome III criteria was used to diagnose IBS. To exclude organic disease, all patients underwent medical investigations. Half of the randomly selected IBS patients were treated with trimebutine maleate while the rest of IBS patients were not. The IBS patients were reevaluated at the end of 3 weeks. Results The prevalence of IBS according to Rome III criteria in children and adolescents was 22.6% and IBS with constipation was the predominant subtype. Back pain (OR, 6.68), headache (OR, 4.72) and chronic fatigue (OR, 3.74) were significantly higher in IBS group. The prevalence of IBS in both parents and depression in mothers was greater for the patient group than the healthy controls (P < 0.0001). The prevalence of functional dyspepsia in IBS group was 80.8% and was significantly higher than control group. Clinical recovery was seen in 94.9% of the trimebutine maleate group versus spontaneous recovery in 20.5% of the non-medicated group. The difference was significant (P < 0.0001). Conclusions IBS is a common disorder in children and adolescents. IBS is closely associated with somatic and familial factors. Trimebutine maleate is effective for pediatric IBS patients.

Clinical features of interleukin 10 receptor gene mutations in children with very early-onset inflammatory bowel disease.

Objectives: In the present study, we studied a cohort of patients with very early onset inflammatory bowel disease (IBD) to determine the frequency of mutations in the interleukin 10 (IL10) receptor genes as a cause of early-onset IBD. Methods: Sanger sequencing was performed to determine the presence of IL10 and/or IL10 receptor mutations in 17 patients with a diagnosis of very early onset IBD (disease onset <2 years of age in 15 patients, between 3 and 4 years in the other 2). Mutation screening was performed including all of the coding regions of the IL10, IL10RA, and IL10RB genes. We then compared the follow-up findings of the patients with IL10 receptor mutations in terms of demographic, clinical, laboratory, and treatment response properties with those of patients diagnosed as having very early onset IBD with no mutation. Results: We identified 3 patients bearing mutations in the IL10 or IL10 receptor genes, including 1 mutation in IL10RB that has been described recently (c.G477A, p.Trp159*) and 2 novel mutations affecting the IL10RA gene (c.T192G, p.Tyr64* and c.T133G, p.Trp45Gly). Collectively, these mutations thus provided genetic etiology for 17.6% of the cohort under investigation. The presence of a family history of IBD and the clinical course of Crohn disease differed between patients with mutations in the IL-10 pathway and those without such mutations. Although perianal fistulas were found in all of the patients with IL10 receptor mutations, they were found in only 14.3% of those without such mutations. The lower values of weight-for-age and height-for-age z scores, necessity for more intensive therapy, achievement of longer periods until remission, and frequent relapses in the patients bearing mutations in the IL10 receptor genes all underlined the severity of the disease and its relatively poor response to treatment. Conclusions: In spite of the small number of patients with mutations affecting the IL-10 signaling pathway in our study, in all of the patients with IL10 receptor mutations, the disease onset occurs at an early age, the prognosis is poor, and the response to treatment is insufficient.

CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis

Background Studies of monogenic gastrointestinal diseases have revealed molecular pathways critical to gut homeostasis and enabled the development of targeted therapies. Methods We studied 11 patients with abdominal pain and diarrhea caused by early‐onset protein‐losing enteropathy with primary intestinal lymphangiectasia, edema due to hypoproteinemia, malabsorption, and less frequently, bowel inflammation, recurrent infections, and angiopathic thromboembolic disease; the disorder followed an autosomal recessive pattern of inheritance. Whole‐exome sequencing was performed to identify gene variants. We evaluated the function of CD55 in patients’ cells, which we confirmed by means of exogenous induction of expression of CD55. Results We identified homozygous loss‐of‐function mutations in the gene encoding CD55 (decay‐accelerating factor), which lead to loss of protein expression. Patients’ T lymphocytes showed increased complement activation causing surface deposition of complement and the generation of soluble C5a. Costimulatory function and cytokine modulation by CD55 were defective. Genetic reconstitution of CD55 or treatment with a complement‐inhibitory therapeutic antibody reversed abnormal complement activation. Conclusions CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein‐losing enteropathy (the CHAPLE syndrome) is caused by abnormal complement activation due to biallelic loss‐of‐function mutations in CD55. (Funded by the National Institute of Allergy and Infectious Diseases and others.)

Association of inflammatory bowel disease with familial Mediterranean fever in Turkish children.

Background and Aims: Inflammatory bowel disease (IBD) and familial Mediterranean fever (FMF) share common clinical and biological features. The prevalence of other inflammatory diseases, including IBD, is increased in FMF. We investigated the presence of IBD accompanying FMF in patients who were being followed up with a diagnosis of FMF and the relation of IBD with the MEFV gene mutation. Methods: A total of 78 children with FMF were enrolled in the study. The patients were included in the study independent of the presence of complaints. Colonoscopy for IBD was performed if any of the following was present: blood mixed with mucus in the stool; chronic diarrhea (loose and frequent stools lasting >4 weeks); abdominal pain incompatible with FMF (localized in a certain part of the abdomen, not occurring during attacks, >3 days); and positive IgA and IgG anti-Saccharomyces cerevisiae antibodies and perinuclear antineutrophil cytoplasmic antibodies. MEFV gene mutations were analyzed in patients diagnosed as having IBD and FMF. Results: Of the 78 patients with a diagnosis of FMF, colonoscopy was performed and biopsy samples were taken in 20 patients (25.6%) who had abdominal pain incompatible with FMF, chronic diarrhea, bloody stools, and/or positive perinuclear anti-neutrophil cytoplasmic antibody or anti-Saccharomyces cerevisiae antibody. Histopathological examination resulted in a diagnosis of IBD in 12 of the 78 patients (15.4%). MEFV gene mutations were present in all 12 patients diagnosed as having IBD. We observed M694 V mutations in 5 of 12 patients (41.7%), M680I mutations in 3 (25%), K695R mutations in 3 (25%), and E148Q mutations in 1 (8.3%). Conclusions: We found that the number of patients with FMF was higher than the number with IBD in the general population. When IBD accompanied FMF, the most common mutation was M694 V; however, the high rate (25%) of K695R mutation in our patients with FMF and IBD was not observed in previous studies.

Can Fecal Calprotectin Level Be Used as a Markers of Inflammation in the Diagnosis and Follow-Up of Cow's Milk Protein Allergy?

Purpose Calprotectin is a cytosolic protein with immunomodulatory, antimicrobial, and antiproliferative actions. The concentration of calprotectin increases in infection, inflammation, and malignancy. We determined if calprotectin can be used as a marker for the diagnosis and follow-up of bowel inflammation in cows milk protein allergy (CMPA). Methods In total, 32 patients newly diagnosed with CMPA were included (24 IgE-mediated, 8 non-IgE-mediated). In all subjects, a complete blood count, total IgE, cows milk-specific IgE, and fecal calprotectin (FC) were assessed before and after a cows milk protein (CMP) elimination diet was started. The results were compared with those of 39 healthy children. Results The mean FC value before the CMP elimination diet was 516±311 µg/g in the 32 patients with CMPA and 296±94 µg/g in the control group (P=0.011). The mean FC value after the diet in these patients was 254±169 µg/g, which was significantly different from the mean value before the CMP elimination diet (P<0.001). When we compared FC levels before the CMP elimination diet in the IgE-mediated group with the control group, we found no significant statistical difference (P=0.142). The mean FC value before the CMP elimination diet was 886±278 µg/g in the non-IgE-mediated group and 296±94 µg/g in the control group; this difference was statistically significant (P<0.001). In the IgE-mediated and non-IgE-mediated groups, FC values after CMP elimination diet were 218±90 µg/g and 359±288 µg/g, respectively, and FC values before CMP elimination diet were 392±209 µg/g and 886±278 µg/g, respectively; these differences were statistically significant (P=0.001 and P=0.025, respectively). Conclusions FC levels may be a useful marker for follow-up treatment and recurrence determination in CMPA.

Evaluation of malnutrition development risk in hospitalized children

OBJECTIVES Many screening methods, such as the Screening Tool Risk on Nutritional Status and Growth (STRONGkids) and the Pediatric Yorkhill Malnutrition Score (PYMS), have been developed to detect malnutrition in pediatric patients. We aimed to explore the prevalence of malnutrition risk in hospitalized children via symptoms and identification of contributing factors, and to examine the efficacy of malnutrition screening tools for hospitalized children. METHODS STRONGkids and PYMS were applied to 1513 inpatients at 37 hospitals in 26 cities from different regions of Turkey. Physical measurements were collected at hospital admission and at discharge. z-Scores of height-for-age, weight-for-age, weight-for-height, and body mass index-for-age were calculated. RESULTS Overall, 1513 patients were included in the study. A body mass index standard deviation score of less than -2 was present in 9.5% of the study population at hospital admission, whereas 11.2% of the participants had a weight-for-length/height score of less than -2 at hospital admission. According to STRONGkids results, the proportion of the patients with an underlying chronic disease was higher for the patients at high risk of malnutrition than for the patients at medium or low risk (91% compared with 47% or 45%, respectively). PYMS results indicated that patients at high risk of malnutrition have more chronic diseases (75%) than the patients at medium or low risk of malnutrition (55% and 44%, respectively). CONCLUSIONS Use of anthropometric measurements in addition to screening tools to identify hospital malnutrition (such as PYMS, STRONGkids) will prevent some nutritional risk patients from being overlooked.

Abdominal pain developing from a polyarteritis nodosa-induced hepatic aneurysm.

Systemic polyarteritis nodosa (PAN) is characterized by necrotizing inflammatory changes in medium and small-sized arteries (1). Because the range of symptoms is a wide and no specific serological test exists, diagnosis of PAN could be difficult. Gastrointestinal systems such as the liver, appendix, and gallbladder are rarely affected (2). A 9-year-old female patient was admitted with severe abdominal pain that started 15 days previously. She has a tenderness in the epigastric region. However, other systemic examinations were unremarkable. Laboratory values were as follows: hemoglobin, 11.2 g/dL; white blood cell count, 22,200/mL; platelet count, 663,000/ mL; erythrocyte sedimentation rate, 84 mm/h; and Creactive protein, 156 mg/dL (normal range, 0-5). Serum fibrinogen level was 468 mg/dL (normal range, 18-350 mg/dL) and ferritin level was 558.9 ng/mL (normal range, 7.0-276.8 ng/mL). Antinuclear antibody, antineutrophil cytoplasmic antibody, anticardiolipin antibody, lupus anticoagulant, and Hepatitis B surface antigen were negative. A gastroscopy showed normal findings. Abdominal ultrasonography revealed a large number of micro-aneurysmal dilatations in the liver. Magnetic resonance imaging (MRI) angiography showed multiple arterial microaneursyms and ruptured thromboses in the liver (Figure 1). These imaging findings were consistent with PAN. A diagnosis of PAN with hepatic involvement was established based on clinical and imaging findings. Combined therapy consisting of prednisone (2 mg/kg/ day), cyclosporin A (CPA) (1000 mg/m2/month, total six doses) and azathioprine (75 mg/day) was started. Her symptoms began to decline for the next 10 days, and at the control abdominal MRI angiography at the end of four months we observed that microaneursyms disappeared (Figure 2). The typical presentation of PAN in children is of isolated organ involvement with constitutional symptoms. But multiple organ systems could be involved in systemic PAN (3). Although involvement Turk J Gastroenterol 2014; 25: 739-40

Long-Term Follow-Up of Children with Inflammatory Bowel Disease: Evaluation of 53 Cases

Öz Giriş: Bu çalışmada inflamatuvar barsak hastalığı (İBH) tanısı ile izlenen çocukların uzun dönem demografik, klinik, laboratuvar, tedaviye yanıt özelliklerinin belirlenmesi amaçlanmıştır. Gereç ve Yöntem: Çalışmaya 0-18 yaş aralığında İBH tanısı ile izlenmekte olan 53 olgu dahil edilmiştir. Hasta grubu; klinik, serolojik, endoskopik, histopatolojik ölçütlere göre İBH tanısı konulan hastaları içermiştir. Hastaların doğum tarihleri, özofagogastroduodenoskopi/kolonoskopi bulguları, tanı anındaki ve izlem sırasındaki laboratuvar tetkikleri, yakınmaları ve süreleri, daha önce almış olduğu ve şu an almakta olduğu tedaviler ve eşlik eden hastalık varlığı gözden geçirilmiştir. Tanı anındaki ve tedavi sonrasındaki boy ve vücut ağırlığı Z skorları hesaplanıp karşılaştırılmıştır. Hastaların fizik muayene bulguları ile ailede İBH ve otoimmün hastalık öyküleri sorgulanarak kayıt edilmiştir. Bulgular: Olgularımızın 18’i Crohn hastalığı (CH), 35’i ülseratif kolit (ÜK) tanısı ile izlenmekteydi. Erkek/kız oranı CH’de 3,5/1, ÜK’de 1,33/1 idi. On olgunun (%18,9) akrabalarından birisinde İBH tanılı başka bir hasta bulunmaktaydı ve bu olgularda yakınma başlama yaş ortalamasının ailesinde İBH olmayanlardan istatistiksel olarak anlamlı derecede düşük olduğunu saptadık (p=0,042). Olguların 20’sinin (%37,8) anne babaları arasında akrabalık olduğunu tespit ettik. Akrabalık saptanan 20 olgunun yakınma başlama yaş ortalamasının akrabalık olmayanlardan istatistiksel olarak anlamlı derecede düşük olduğunu gözlemledik (p=0,025). Yaşa göre ağırlık Z skoru %18,9 olguda -2’nin altındaydı ve bu olguların yedisi CH tanısı ile izlenmekteydi. Yaşa göre boy Z skoru %17 olguda -2’nin altındaydı ve bu olguların dokuzu yine CH tanısı ile takip edilmekteydi. Tanı anındaki beyaz küre sayılarının, eritrosit çökme hızının ve C-reaktif protein değerlerinin tedavi sonrasında istatistiksel olarak anlamlı derecede gerilediği gözlenmiştir (p<0,001). İlk basamak tedaviye direnç ÜK’de %14,3 iken CH’de %33,3 idi. Sonuç: Ailede İBH tanılı başka hastanın olması ve anne-baba arasında akrabalık olması gibi durumlarda etiyolojide genetik mutasyonların olabileceğini düşünerek hastalığın daha erken yaşta ortaya çıktığını saptadık. Büyüme geriliğinin, fizik muayene bulgularının ve laboratuvar göstergelerin tedaviyle normale gelmesi İBH’de aktif hasta izleminin değerini ortaya koymaktadır. Introduction: In this study it was aimed to determine the long-term demographic, clinical and laboratory characteristics, together with the responses to therapy, in children diagnosed with inflammatory bowel disease (IBD). Materials and Methods: Fifty-three cases, aged 0 to 18 years, followedup with the diagnosis of IBD were included in this study. The study group Ya zış ma Ad re si/Ad dress for Cor res pon den ce: Dr. Ömer Faruk Beşer, İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi, Çocuk Sağlığı ve Hastalıkları Anabilim Dalı, Çocuk Gastroenteroloji, Hepatoloji ve Beslenme Bilim Dalı, İstanbul, Türkiye Tel.: +90 506 556 66 23 E-posta: ofbeser@gmail.com Anah tar ke li me ler Crohn hastalığı, inflamatuvar barsak hastalığı, ülseratif kolit

697 Endoscopic and Histopathological Findings in Children with Upper Gastrointestinal Bleeding

Introduction The etiology changes according to the age of child for upper gastrointestinal system(GI) bleeding. Esophagogastroduodenoscopy (EGD) is used to determine the source of upper GI bleeding in 90% of children when performed in the first 24 hours. Aim In this study we aimed to determine the etiology of the upperGI bleeding in children. In order to determine the etiology we evaluated the EGD and biopsy findings. Methods We evaluated the EGD and biopsy findings of children who complaint of upperGI bleeding. Results Eighteen children were in newborn period. We detected that 12 of infants hematemesis was due to swallowed maternal blood by Apt-Downey test. EGD was performed to 6of newborns and 4of them had no pathology but 2 had vascular malformations. Eight children were below 1year of age. We detected Mallory Weiss tear in two infants and moderate severe esophagitis findings was seen on biopsy materials. Six of these cases have both macroscopic and microscopic findings of gastritis on antrum and H.pylori(+). There were 22 cases above 1year old. Four of them had ulcer on bulbus. Six of them had esophageal varices. Mallory Weiss tear was detected on 3 of 12 cases and their biopsies were consistent with moderate-svere esophagitis. Macrosopically gastritis on the antral part was detected in 9 cases and biopsies were consistent with active gastritis and also all ofthem was H.pylori (+). Conclusion In order to indicate the severity of bleeding it is very important to determine the bleeding site and etiology of bleeding. So that a detailed history and complete physical examination is very important. The importance of endoscopy in determintaion of etiology is undisputed.