Search Results (99)

Objective. Limited evidence is available concerning the surgical outcomes of patients with congenital gastrointestinal malformations and perioperative SARS-CoV-2 infection. This study examines the scientific evidence on SARS-CoV-2 infection and congenital gastrointestinal malformations requiring surgery in children. Material and Methods. We performed a systematic review of studies reporting data on children with congenital gastrointestinal malformations and SARS-CoV-2 infection, published in international databases (PubMed and Embase) from pandemic inception up to August 2024. Studies not reporting data on the SARS-CoV-2 infection status on patients with congenital digestive malformation were excluded. We assessed the quality of the included studies according to the Joanna Institute (JBI) appraisal checklist, adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, and registered the protocol with the PROSPERO database (CRD42024550744). Results. From the 902 titles retrieved, eight observational studies met the inclusion criteria comprising 29 patients from countries with different socioeconomic statuses. Most patients were neonates (75%) with a median age of 3 days at diagnosis and male to female ratio of 2:1. In total, 18 (62%) presented upper gastrointestinal tract anomalies, including esophageal atresia ± tracheoesophageal fistula (n = 10, 34.48%), duodenal atresia (n = 3, 10.3%), and congenital hypertrophic pyloric stenosis (n = 5, 17.2%). Lower digestive tract malformations (11, 38%) included anorectal malformations (n = 6, 20.6%), intestinal atresia (n = 3, 10.3%), Hirschsprung disease (n = 1, 3.44%), and Meckel’s diverticulum (n = 1, 3.44%). Surgeries were primarily emergency or urgent procedures and only pyloromyotomy (5/5) was consistently operated minimally invasively. SARS-CoV-2 infection was identified mainly on routine screening (>95%). Of 29 patients, 85% were discharged home, and no postoperative surgical mortality and significant complications directly associated with COVID-19 were identified, although routine postoperative morbidity not linked to SARS-CoV-2 was observed. Conclusions. Pediatric patients with congenital gastrointestinal malformationsand perioperative SARS-CoV-2 infection typically have mild illness and favorable surgical outcomes. SARS-CoV-2 positivity alone should not delay essential surgery when infection control measures are ensured. Standardized, multicenter studies are needed to clarify perioperative risks to and inform management of this high-risk group. Full article

Frozen section (FS) analysis is a rapid intraoperative tool that provides real-time pathological assessment, guiding surgical decisions in gastrointestinal and hepatobiliary disease. Its main applications include confirming diagnoses, assessing resection margins, staging lymph nodes, and evaluating unexpected intraoperative findings. Drawing on a 14-year experience at Queen’s Medical Centre, Nottingham, this review highlights the strengths and limitations of FS in gastrointestinal and hepatopancreato-biliary surgery. Concordance with final paraffin diagnoses exceeded 97%, underscoring its reliability when performed under optimal conditions. FS is particularly valuable in complex scenarios such as distinguishing benign from malignant hepatic or pancreatic lesions, identifying metastatic disease, and evaluating conditions like Hirschsprung disease. Although interpretive artefacts and sampling errors remain challenges, careful technique and close clinical–pathological communication mitigate these issues. Beyond diagnosis, FS also supports molecular applications through targeted tissue selection for genomic testing. Overall, FS remains an essential adjunct to modern surgical pathology, enhancing intraoperative decision-making and contributing to precision oncology. Looking ahead, the integration of FS with artificial intelligence, telepathology, and minimally invasive surgical platforms is poised to expand its accuracy, accessibility, and impact in real-time precision surgery. Full article

Gastrointestinal symptoms often persist in children with Hirschsprung’s disease (HD) even after “corrective” pull-through surgery. Alteration of the gut microbiota (“dysbiosis”) has emerged as a potential contributing factor. Animal studies show gut ecosystem changes that are both intrinsic to HD and caused by bowel resection itself, but human studies comparing the intestinal microbiota of children with HD and healthy children are limited. We collected food frequency dietary surveys, clinical and symptom data, and stool samples from 15 post-operative children with HD and 15 healthy controls (HCs). We performed 16S rRNA gene sequencing from the stool samples and quantified faecal calprotectin as a measure of gastrointestinal inflammation. Despite no global changes in the microbiota between HD and HC cohorts and no differences between individuals with and without a history of HD-associated enterocolitis (HAEC), we identified evidence of altered microbiota development and inflammatory trajectories in HD. In HCs, alpha diversity increased with age (r = 0.83, p < 0.001), while calprotectin levels declined (Spearman’s ρ = −0.53, p = 0.04). These age-related patterns were absent in HD. Across the combined cohort, lower alpha diversity was associated with higher faecal calprotectin (Spearman’s ρ = −0.47, p = 0.01). In HD, Fusobacteria abundance showed a strong positive correlation with calprotectin (Spearman’s ρ = 0.76, adjusted p = 0.02). Pediatric Quality of Life (PedsQL) and gastrointestinal disease-specific symptom scores were lower in HD compared to HC but were not directly linked to microbial diversity or inflammation. Overall, we observed a divergence from healthy peers in the typical developmental trajectory of gut microbial communities and inflammation in children with HD that may involve Fusobacteria. Children with HD reported reduced health-related quality of life compared with HC, consistent with ongoing gastrointestinal symptoms. No microbiota differences were associated with HAEC history, though this may reflect limited sample size. Full article

Obstruction differential diagnosis involves tumors, “acute abdomen”, and chronic pseudo-obstruction (CIPO). Pediatric CIPO cases have different backgrounds than adults’ and impairs development. The cases are rare; diagnosis and treatment are still not well established. Diagnosis is complex; clinical, radiological, molecular, and manometric pathologic data are essential. The performance of broad radiological investigations and manometry is cumbersome in a small intestine. Herein, we present cases of a 14-year-old girl and 11-year-old boy with visceral myopathies (VMs). Presented cases show unique hardship in the analysis of standing and contrast bedside X-ray images—the colon distension alone speaks to Hirschsprung, and the clinicians could not confirm suspected short-segment disease for a long time. VMs are usually diagnosed up to 12 months of life and accompanied by other organ dysfunctions, which are herein absent. The key features here were also the involvement of the small intestine, lack of distant colon contraction, and for the long-lasting case in the boy, loss of haustration. The initial diagnosis relied on clinical data (vomiting, malabsorption, >6-month obstruction, and uncharacteristic biochemical tests), radiology (lack of tumor, enlargement of diameter, and fluid in small and large intestines), and manometry (presence of propagation wave and of anal inhibitory reflex in recto–anal manometry). Examination of intestinal muscle biopsies involved hematoxylin-eosin, trichrome-Masson staining, and immunohistochemistry. The characteristics were fibrosis, small vacuoles, muscle layer thinning, and decreased expression of smooth muscle actin and desmin. The localization of biopsies was chosen after X-ray examination, due to interruption and with various degree changes. The final diagnosis was put forward after the analysis of all accessible data. The diagnosis of VM underlines the importance of interdisciplinary co-work. An earlier intestine muscle biopsy and well-designed molecular panel might fasten the process of diagnosis. Deeper exploration of phenotype–genotype correlation of various VM presentations in the future is crucial for personalized treatment. Full article

Objective: Functional constipation affects up to one third of children. When standard treatments fail, the child may be referred to rectal biopsy on the suspicion of Hirschsprung’s disease (HD), but only 7–28% will have a confirmed HD. For those with a negative biopsy for HD, there is limited evidence of the post-biopsy utilization of healthcare services. This study aimed to investigate gastrointestinal-related healthcare utilization after rectal biopsy in non-HD children compared to matched healthy controls and patients diagnosed with HD. Methods: This nationwide registry-based cohort study included all Danish children <18 years who underwent rectal biopsy for HD during the period from 1998 to 2018. The cohort was matched 1:10 to form a control cohort. Outcomes included gastrointestinal surgeries, endoscopies, and imaging procedures pre- and post-biopsy. Results: Among the 1105 children included in the cohort, 128 were diagnosed with Hirschsprung’s disease (HD), while 977 were non-HD. Compared to the control group, the non-HD showed significantly higher rates of post-biopsy surgery (11.2% vs. 1.6%, p < 0.001), endoscopy (9.4% vs. 0.5%, p < 0.001), and imaging (37.1% vs. 7.8%, p < 0.001) related to the gastrointestinal tract. Conclusions: Children with a HD-negative rectal biopsy had 5–10 fold increased frequency of gastrointestinal-related surgeries, endoscopies or imaging during the follow-up period compared to the background population. Full article

Background/Objectives: Intraoperative frozen biopsies are essential during surgery for Hirschsprung’s disease (HD). However, this method has several limitations with the need for a faster and real-time diagnostic alternative. For this, consistent histoanatomical and morphometric differences between aganglionic and ganglionic bowel must be established. The primary objective was to compare dimensions of bowel wall layers between aganglionic and ganglionic segments histopathologically in resected rectosigmoid specimens from children with HD. Secondary objectives were to design a diagnostic algorithm to distinguish aganglionosis from ganglionosis and assess whether full bowel wall thickness correlates with patient weight and age. Methods: Each histoanatomic bowel wall layer—mucosa, submucosa, and muscularis propria’s layers—was delineated manually on histopathological images. Mean thicknesses were calculated automatically using an in-house image analysis software. Paired parametric tests compared measurements in aganglionic and ganglionic segments. Results: Resected specimens from 30 children with HD were included. Compared to aganglionic bowel, ganglionic bowel showed a thicker muscularis interna (mean 0.666 mm versus 0.461 mm, CI −0.257–(−0.153), p < 0.001), and a higher muscularis interna/muscularis externa ratio (2.047 mm versus 1.287 mm, CI −0.954–(−0.565), p < 0.001). An algorithm based on these features achieved 100% accuracy in distinguishing aganglionosis from ganglionosis. No significant difference in full bowel wall thickness was found between aganglionic and ganglionic segments, nor any correlation with patient weight or age. Conclusions: Histoanatomic layer thickness differs between aganglionic and ganglionic bowel, forming the basis of a diagnostic algorithm. Full bowel wall thickness was independent of patient weight and age. Full article

Waardenburg syndrome (WS) is a rare genetic disorder that affects both hearing and pigmentation. The wide divergence of WS poses significant diagnostic and management challenges. This study investigated type 4 WS within an underrepresented Mongolian population. Whole-exome sequencing revealed that two unique heterozygous variants were identified in the SOX10 gene: c.393C>G (p.Asn131Lys) in a five-year-old female patient presenting with profound sensorineural hearing loss (SNHL), dystopia canthorum, and a white forelock; and c.535A>T (p.Lys179Ter) in a nine-year-old male patient presenting with profound SNHL, dystopia canthorum, and Hirschsprung’s disease. Temporal bone imaging revealed abnormalities in the inner ear structure in both patients. The genotypic and phenotypic characteristics were meticulously delineated, incorporating the deleterious effects of these variants, as evaluated by multiple predictive tools and the American College of Medical Genetics and Genomics (ACMG) criteria. In addition, structural characterizations were also presented using AlphaFold. The findings of this study contribute valuable genetic data to the limited literature on type 4 WS within this ethnic group and highlight the importance of genetic testing and multidisciplinary care for this rare disorder in settings with limited resources. Full article

Background: We proposed a comprehensive clinicopathological study involving the characterization of the study cohort and a comparative analysis of biopsies and surgical specimens from patients with Hirschsprung’s disease. The study was complemented by the diagnostic value of calretinin, CD56, and S-100 immunohistochemistry. Methods: Descriptive statistical analysis of diagnostic variables in the group of biopsy specimens (n = 32) and bowel resection specimens (n = 16) was performed. The pattern of calretinin and CD56 expression in Meissner’s plexus elements was analyzed and the maximum thicknesses of the nerve fibers were measured using morphometry with S100-immunostained sections. Conclusions: Coupled calretinin–CD56 immunohistochemistry is useful in diagnosing ganglion cell paucity biopsies or specimens with incomplete submucosa. In cases where there are no ganglion cells but there are calretinin-positive nerve fibrils in the lamina propria without nerve trunk (NT) hypertrophy, re-biopsy is the best solution. The significant differences in NT size between biopsies and surgical specimens highlight the importance of assessing NT diameter in all tissue samples examined. Full article

Background/Objective: Hirschsprung-associated enterocolitis (HAEC) can occur before and after surgery, increasing the complication rates, hospital stay, and treatment costs. This study aims to determine the incidence of preoperative and postoperative Hirschsprung-associated enterocolitis HAEC and the related risk factors. Methods: This study is a prospective cohort study of Hirschsprung’s disease patients under 16 years of age at two Children’s Hospitals in Ho Chi Minh City, Vietnam from December 2022 to June 2024. The postoperative follow-up is 12 months. Results: We enrolled 84 pediatric patients, with a male-to-female ratio of 5.4/1 and an average age of 7.2 ± 1.07 months. Of the patients, 25% had preoperative enterocolitis at the time of admission. Statistical analysis revealed that risk factors for preoperative enterocolitis at admission included a history of enterocolitis (p = 0.024), low weight in hospital (p = 0.001), and lack of preoperative treatment (p = 0.01). Postoperative enterocolitis occurred in 14 patients (16.7%) at an average of 4.03 months postoperatively. Multiple logistic regression of postoperative enterocolitis was associated with a history of preoperative enterocolitis (p < 0.001), anastomotic stricture (p = 0.002), and the length of the aganglionic segment (p = 0.031). No statistically significant association was found between the surgical method and the risk of postoperative enterocolitis. Conclusions: A history of preoperative enterocolitis, low weight, and anastomotic stricture are significant risk factors for postoperative enterocolitis in patients with Hirschsprung’s disease. Therefore, preoperative medical treatment is recommended for the patients who have not yet undergone a definitive surgical procedure. Full article

Background: Multiple endocrine neoplasia type 2A (MEN 2A) is a rare hereditary cancer syndrome caused by pathogenic variants in the rearranged during transfection (RET) gene and is characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), primary hyperparathyroidism (PHPT), cutaneous lichen amyloidosis (CLA), and Hirschsprung’s disease. Phenotypic data on the RET C611Y variant remain sparse. Consequently, we aimed to establish a clinical risk profile. Methods: We conducted a nationwide study of all cases (n = 128) born after 1 January 1930 and recognized as carrying the RET C611Y variant in Denmark before 1 April 2021. Results: The median follow-up after birth was 47 years (range, 3–92). Age-related penetrance at age 70 years for MTC was 98% (CI, 91–100), for PHEO 24% (CI, 16–37), and for PHPT 10% (CI, 5–20). None had CLA or Hirschsprung’s disease. The age-related progression of MTC was significant (p < 0.001). The mean age at T0N0M0 was 16 years (CI, 12–20), at T1-4N0M0 38 years (CI, 34–42), at TxN1M0 45 years (CI, 38–53) and at TxNxM1 49 years (CI, 36–61). At the last follow-up, 56% of thyroidectomized cases (n = 103) were biochemically cured. Overall survival at 70 years was 74% (CI, 59–84). Conclusions: RET C611Y is associated with a very high penetrance of MTC and a low penetrance of PHEO and PHPT. CLA and Hirschsprung’s disease almost never occur. MTC seems moderately aggressive, but large variability can be seen. Overall survival may be comparable to that of the general population. Full article

The glycosylphosphatidylinositol (GPI) is a glycol–lipid that anchors several proteins to the cell surface. The GPI-anchor pathway is crucial for the correct function of proteins involved in cell function, and it is fundamental in early neurogenesis and neural development. The PIG gene family is a group of genes involved in this pathway with six genes identified so far, and defects in these genes are associated with a rare inborn metabolic disorder manifesting with a spectrum of clinical phenotypes in newborns and children. Among them, the PIGO gene encodes for phosphatidylinositol glycan anchor biosynthesis class O protein (PIGO), an enzyme participating in this cascade, and the loss of its function often leads to a severe clinical picture characterized by global developmental delay, seizures, Hirschsprung disease, and other congenital malformations. To date, 19 patients with confirmed PIGO deficiency have been described in the literature with a host of clinical and radiological manifestations. We report a case of a male term newborn with two compound heterozygous variants of the PIGO genes, presenting with encephalopathy, drug-resistant epilepsy, and gastrointestinal abnormalities. Brain MRI first showed diffusion restriction in the ponto-medullary tegmentum, ventral mesencephalon, superior cerebellar peduncles, cerebral peduncles, and globi pallidi. This pattern of lesion distribution has been described as part of the neuroradiological spectrum of PIG genes-related disorders. However, after one month of life, he also showed a previously undescribed MRI pattern characterized by extensive cortical and subcortical involvement of the brain hemispheres. The presence of two different mutations in both the PIGO genes may have been responsible for the particularly severe clinical picture and worse outcome, leading to the death of the newborn in the sixth month of life despite therapeutic attempts. This case expands the neuroradiological spectrum and may bring new insights on glycosylation-related disorders brain manifestations. Full article

Background: Hirschsprung’s disease (HD) is a congenital malformation of the enteric nervous system clinically manifested by intestinal obstruction in the neonatal period or severe constipation in childhood. Several surveys on HD have been conducted to evaluate experiences in its management around the world. For the first time in Brazil, we analyze and report the management patterns of HD among pediatric surgeons in Brazil. Methods: A validated questionnaire was disseminated in print at the Congress of Pediatric Surgery in São Paulo-Brazil, and an online version was sent to all the active members of the Brazilian and Paulista Institute of Pediatric Surgery. Results: In total, 361 pediatric surgeons answered the survey. Of these, 329 completed all questions (response rate: 91%). Most Brazilian services treat fewer than 10 cases of HD annually. The preferred diagnostic method was rectal biopsy. For newborns (NBs) and infants, open biopsy was the most commonly used technique. For NBs with HD clinically stable 50% of specialists chose immediate surgery. In NBs and infants with classic HD, the Soave technique (69%) is the most common surgical intervention, and the transanal route (80%) is the preferred surgical approach. In children over 3 years of age with classic HD, the most-used technique is the Duhamel method (54%), with the open approach being the most common (52%). Conclusions: Our study in Brazil found that HD patient management aligns with scientific evidence and international guidelines. Full article

Introduction: The assessment of bowel function in patients with Hirschsprung disease (HD) remains controversial, as several different bowel function scores are used in the literature and are therefore not suitable for reliable comparison. Conference Section: The OASIS-Holistic Care in Hirschsprung Disease Network Group addressed this issue and evaluated the most commonly used scores for their utility in HD patients. Scoping Review and Expert Group Consensus were performed. It was agreed that the ideal score for patients with Hirschsprung disease should be a comprehensive, validated score that allows reliable assessment of bowel function and continence, depicts changes according to management and natural history, and quantifies baseline parameters. This score should also enable comparisons of bowel function in patients born with HD worldwide. Concluding Remarks: The OASIS-Holistic Care in Hirschsprung Disease Network Group agreed that this ideal score does not yet exist and is therefore a future goal of the group. Meanwhile, clinicians should use a score for comparable, standardized, objective assessment, and the Rintala Score is suggested. Future developments may also lead to easily accessible patient-reported outcome measures and semi-automated dashboards that allow automated data extraction from electronic health records. Full article

A growing number of patients with Hirschsprung disease are reaching adulthood, of whom a significant minority will require ongoing input from healthcare providers. In order to ensure patients receive the best care possible, it is essential to transition patients appropriately to adult services. This article describes the unmet need and some of the obstacles to this process and explores potential solutions, drawing on model examples for transitional care. Full article

Prokineticins (PKs) are low molecular weight proteins that exert their effects by binding to two seven-transmembrane G-protein-coupled receptors (prokineticin receptors, PKRs). The prokineticin system is an important player in the development of various diseases. Several polymorphisms that are associated with infertility, neuroendocrine disorders, Hirschsprung’s syndrome (HSCR), idiopathic central precocious puberty (CPP) and congenital disorders such as Kallmann syndrome (KS) have been described for both the PKs and PKR genes. The aim of this study is to summarize and describe the impact of PK/PKR polymorphisms on the pathogenesis and outcome of the above diseases, highlighting the PK system as a therapeutic target and diagnostic biomarker in pathological conditions. Full article