Crohn’s disease (CD) is a progressive, multifactorial, immune-mediated disease characterized by chronic inflammation of any part of the gastrointestinal (GI) tract. Pediatric patients present with a more extensive form of the disease, especially in the upper GI tract with various histopathological inflammatory patterns. Our study aims to analyze the clinical, laboratory, endoscopic, and histopathological findings in children with diagnosed CD and compare results on the initial and follow-up tests. We have included 100 children and adolescents with CD, with performed endoscopic and histopathological (HP) procedures. The results of multiple biopsies executed in these 8 years were matched and compared. We found a statistically significant frequency reduction in stool changes (65.52% to 18.18%), weight loss (35.24% to 4%), and abdominal pain (41.86% to 6.67%) as presenting symptoms. There was an improvement in all laboratory values: fecal calprotectin (1000 to 60,8 μg/g), C-reactive protein (12.2 to 1.9 mg/L), and albumin (36 to 41 g/L). On esophagogastroduodenoscopy and ileo-colonoscopy 36.59% and 64.86% patients had specific findings, respectively. A total of 32 patients had evidence of Crohn’s disease in the upper GI tract. Non-caseating granulomas were found on 9% of oesophageal, 18% of gastric, and 12% of duodenal biopsies. In the lower GI tract, we have observed a disease progression in the rectum (72.29 to 82.22%) and descending colon (73.49 to 80%). There was no registered disease progression in the upper GI tract. Our study demonstrated a significant decline in the frequency of symptoms and an improvement in laboratory values on the follow-up examinations. More than a third of our patients had specific endoscopic and HP findings in the upper GI tract, and an additional 23% had HP findings highly suggestive of CD. We demonstrated the importance of regular clinical, laboratory, endoscopic, and histopathological assessments of pediatric CD patients.

Introduction/Aim: The aim of the study was to determine the frequency of various histopathological findings in biopsies of children with intestinal hypomotility and the incidence and characteristics of Hirschsprung disease (HD). Methods: Biopsies of colon and rectum taken due to intestinal hypomotility and chronic constipation at the Department of Pediatric Surgery of the University Children's Hospital in Belgrade over the 10-year period (from 2009 to 2018) were reviewed using pathology reports from the archive of the Institute of pathology, Faculty of Medicine, University of Belgrade. Results: A total of 287 patients with intestinal motility disorder were identified, with 554 biopsy samples. Of the total number of patients, 56% (161/287) were without any morphological changes in enteric nervous system (ENS). The most common histopathological findings were HD (69/287; 24%) and immaturity of ganglion cells (29/287; 10%). Isolated hypoganglionosis of ENS was found in 5 (2%) cases. Heterotopia of ganglion cells was the only finding in 8 (3%) cases. Rare causes of intestinal dysmotility were: eosinophilic proctitis/colitis (EPC) (4/287), neuronal intestinal dysplasia B (2/287), unclassified disganglionoses (3/287). Rectosigmoid variant of HD was the most frequent HD variant (80.3%). Acetylcholinesterase method and immunohistochemical staining were used in 19.5% cases. Conclusions: HD and immaturity of ganglion cells were the most common pathological findings in ENS of constipated children. It is important to differentiate EPC from other lesions of enteric plexuses due to different natural history and therapy.

Crohn’s disease (CD) is a progressive, multifactorial, immune-mediated disease characterized by chronic inflammation of any part of the gastrointestinal (GI) tract. Pediatric patients present with a more extensive form of the disease, especially in the upper GI tract with various histopathological inflammatory patterns. Our study aims to analyze the endoscopic and histopathological findings in children with diagnosed CD and compare results on the initial and follow-up tests. Our study included 100 children and adolescents with CD, with performed endoscopic and histopathological (HP) procedures. The results of multiple biopsies performed in these 8 years were matched and compared. We found a statistically significant decrease in stool changes, weight loss, and abdominal pain as presenting symptoms, and in the fecal calprotectin levels. On esophagogastroduodenoscopy and ileo-colonoscopy 36.59% and 64.86% patients had specific findings, respectively. Non-caseating granulomas were found on 9% of oesophageal, 18% of gas-tric, and 12% of duodenal biopsies. In the lower GI tract, we have observed a disease progression in the rectum and descending colon between the first and second biopsies. Our study showed that more than a third of patients had specific endoscopic (36.59%) and histopathologic (32%) findings in the upper GI tract, and an additional 23% had HP findings highly suggestive of CD. We demonstrated the importance of regular endoscopic and histopathological assessments of pediatric CD patients.

Hypoxic-ischemic Encephalopathy (HIE) is one of the most common neurologic diseases in children and an important cause of cerebral palsy (CP). It is a permanent, non-progressive motor disorder that results in a delay in psychomotor development. Brain damage is followed by the activation of the immune system, and increased cytokine concentration in the plasma. Cytokines are circulating soluble proteins, mediators of communication for immune cells. The main biological activity of interleukin-6 (IL-6) is the stimulation of the liver to produce acute-phase proteins. Aim: The frequency of genotypes and alleles of the IL-6 gene polymorphism will be determined, analyzing the possible connection between IL-6 gene polymorphism and the onset of CP. Material and methods: This study involved 117 newborns who were treated in the Clinic of Neurology and Psychiatry for Children and Youth and the Clinic for Gynecology and Obstetrics of the University Clinical Centre of Serbia in Belgrade. Data was collected for each patient regarding their gender, gestational age, birth weight and Apgar score. Genotyping of rs1800795 in the IL-6 gene was performed by real-time PCR using a standardized TaqMan SNP assay. The difference in frequency of genotypes and alleles was analyzed by the X2 test. Results: The frequencies of genotypes in patients with CP were: 86.5% for GC + GG and 13.5% for CC, and in patients without CP were: 84.6% for GG + GC and 15.4% for CC. The frequency of alleles in patients with CP for G allele was 63.5% and for C allele 36.5%. In the group without CP, 56.2% had G allele and 43.8% C allele. No statistical significance has been demonstrated. Conclusion: No connection between IL-6 gene polymorphism with the development of cerebral palsy in newborns diagnosed with HIE at birth was demonstrated.

Diagnosing Hirschsprung disease (HD) and related disorders can be complex and demands a deep understanding of the mechanisms governing intestinal motility, which involves the enteric nervous system (ENS), interstitial cells of Cajal (ICCs), and the muscle layers of the intestine. The London classification identifies three groups of gastrointestinal neuromuscular disorders: neuropathies, myopathies, and ICC abnormalities. Hirschsprung disease, characterized by the absence of ganglion cells, is the most common intestinal neuropathy and it results from the impaired migration of neural crest cells during development. It affects about 1 in 5,000 live births and involves several genetic factors, notably the RET gene. HD typically affects the rectum and a part of the colon, with varying extents of aganglionosis. The diagnosis is based on the histopathological analysis of suction biopsies, the absence of ganglion cells, and the presence of thick submucosal nerves on a standard hematoxylin and eosin stain, supplemented by enzyme histochemistry (acetylcholinesterase method) or immunohistochemical methods (calretinin and other antibodies) staining. The treatment for HD involves surgical resection of affected bowel segments. Accurate intraoperative assessment of tissue margins is critical to preventing postoperative complications related to pseudoobstruction. Communication between surgeons and pathologists is essential to ensure successful treatment outcomes. Other intestinal neuropathies include intestinal hypoganglionosis, hyperganglionosis, delayed maturation of ganglion cells, and gliopathies. Enteric myopathies are exceptionally rare conditions, with typical morphological changes such as atrophy of the muscularis propria, intracellular vacuolization of smooth muscle cells, and interstitial fibrosis. Disruption in ICC network and arrangement forms the morphological basis of slow transit constipation. Each of aforementioned disorders has unique characteristics and diagnostic challenges. Understanding and diagnosing these conditions often require a combination of histological, histochemical, immunohistochemical, and sometimes genetic analyses. The integration of these techniques is vital for accurate diagnosis and effective treatment planning. In summary, the complexity of intestinal dysmotility disorders necessitates a thorough understanding of intestinal motility mechanisms and the utilization of advanced diagnostic methods to provide accurate diagnoses and effective treatments.