Neurodevelopmental outcome of patients with congenital gastrointestinal malformations: a systematic review and meta-analysis.

AIM: Children with congenital gastrointestinal malformations may be at risk of neurodevelopmental impairment due to challenges to the developing brain, including perioperative haemodynamic changes, exposure to anaesthetics and postoperative inflammatory influences. This study aggregates existing evidence on neurodevelopmental outcome in these patients using meta-analysis. METHOD: PubMed, Embase and Web of Science were searched for peer-reviewed articles published until October 2019. Out of the 5316 unique articles that were identified, 47 studies met the inclusion criteria and were included. Standardised mean differences (Cohen's d) between cognitive, motor and language outcome of patients with congenital gastrointestinal malformations and normative data (39 studies) or the studies' control group (8 studies) were aggregated across studies using random-effects meta-analysis. The value of (clinical) moderators was studied using meta-regression and diagnostic subgroups were compared. RESULTS: The 47 included studies encompassed 62 cohorts, representing 2312 patients. Children with congenital gastrointestinal malformations had small-sized cognitive impairment (d=-0.435, p<0.001; 95% CI -0.567 to -0.302), medium-sized motor impairment (d=-0.610, p<0.001; 95% CI -0.769 to -0.451) and medium-sized language impairment (d=-0.670, p<0.001; 95% CI -0.914 to -0.425). Patients with short bowel syndrome had worse motor outcome. Neurodevelopmental outcome was related to the number of surgeries and length of total hospital stay, while no relations were observed with gestational age, birth weight, age and sex. INTERPRETATION: This study shows that children with congenital gastrointestinal malformations exhibit impairments in neurodevelopmental outcome, highlighting the need for routine screening of neurodevelopment during follow-up.

[Surgical treatment of common bile duct malformations in children]. / Khirurgicheskoe lechenie mal'formatsii obshchego zhelchnogo protoka u detei.

The review is devoted to the current classifications of common bile duct malformations, authors' opinion regarding surgical approach and reconstruction of the bile ducts. The authors describe the modern modifications of bile duct reconstructions and estimate their effectiveness. PubMed database, Google Scholar and National Scientific Electronic Library eLIBRARY.ru databases were used. We analyzed the complications in children depending on various reconstructions, anatomical form, timing of reconstructive surgery and early diagnosis of this pathology.

Currarino syndrome: does the presence of a genetic anomaly correlate with a more severe phenotype? A multicentre study.

BACKGROUND/PURPOSE: Currarino syndrome (CS) phenotype, initially described as the triad of hemisacrum, anorectal malformation (ARM) and presacral mass, can be extremely variable. The triad is often incomplete and 3 main CS phenotypical subtypes have been described: Complete, Mild and Minimal. Various associated malformations are often present. Mutations in the MNX1 gene are the main genetic background of CS, although they are not present in almost half of the cases. Aim of our study is to analyze the distribution of the 3 CS subtypes and the incidence of associated malformations in a large sample of patients and to add information about the role of the genetic testing in guiding the diagnostic and prognostic evaluation of CS patients. METHODS: A multicentre retrospective data collection was performed. CS patients' phenotype was accurately analyzed according to a diagnostic-therapeutic standardized data collection sheet. The distribution of the three CS types and the frequency of each associated malformation were calculated. The phenotype of the patients with a known genetic anomaly was compared to the phenotype of the population with no genetic diagnosis, in order to determine whether the presence of a known genetic defect could correlate with a more severe CS phenotype. RESULTS: Data from 45 patients were analyzed. Twenty patients (44.5%) presented a Complete CS type, 19 (42.2%) a Mild CS and 6 (13.3%) a Minimal CS. In addition to the classical triad elements, 38 (84.5%) patients showed associated anomalies. The group of patients who resulted positive for a MNX1 mutation comprised a higher number (56.5%) of Complete CS cases than the group of patients that did not carry any MNX1 mutation (13%) (p = 0.0085). We could not find any relationship between CS subtype and the number of associated anomalies (p = 0.5102). CONCLUSIONS: The presence of a MNX1 mutation seems to correlate with a more severe CS phenotype. MNX1 seems the main responsible for the expression and the severity of the CS triad, while the associated anomalies appear to be prevalently determined by genes sited on different loci. A thorough multidisciplinary diagnostic overview of CS patients should always include genetic counseling and analysis, both in postnatal and prenatal settings. TYPE OF STUDY: Retrospective Study. LEVEL OF EVIDENCE: II.

Classification and diagnostic criteria of variants of Hirschsprung's disease.

"Variants of Hirschsprung's disease" are conditions that clinically resemble Hirschsprung's disease (HD), despite the presence of ganglion cells in rectal suction biopsies. The diagnosis and management of these patients can be challenging. Specific histological, immunohistochemical and electron microscopic investigations are required to characterize this heterogeneous group of functional bowel disorders. Variants of HD include intestinal neuronal dysplasia, intestinal ganglioneuromatosis, isolated hypoganglionosis, immature ganglia, absence of the argyrophil plexus, internal anal sphincter achalasia and congenital smooth muscle cell disorders such as megacystis microcolon intestinal hypoperistalsis syndrome. This review article systematically classifies variants of HD based on current diagnostic criteria with an additional focus on pathogenesis, epidemiology, clinical presentation, management and outcome.

Abnormalities of digestive tract innervation in rat fetus treated with ethylenethiourea.

PURPOSE: The pathophysiology of abnormalities associated with myenteric plexus lesions remains imperfectly understood. Such abnormalities have been correlated with subocclusive intestinal conditions in children with Hirschsprung's disease, cases of chronic constipation and, postoperatively, in cases of anorectal anomalies. This study evaluated abnormalities of the myenteric plexus in fetus from female rats that received ethylenethiourea. METHODS: Female rats were exposed to ethylenethiourea on the 11(th) day of pregnancy (experimental group) or to 0.9% physiological solution (control group). Abnormalities were only found in the experimental group. The digestive tract muscle layer was analyzed morphometrically and changes to the frequencies of nerve plexus cells and interstitial cells of Cajal were evaluated, using hematoxylin-eosin, S-100 protein, neuron-specific enolase and C-Kit, respectively. RESULTS: Muscle and skeletal abnormalities were observed in 100%, anorectal anomalies in 86%, absent tail in 71%, short tail in 29%, duodenal atresia in 5%, esophageal atresia in 5% and persistent omphalomesenteric duct in 5%. Histopathological analysis showed a thinner muscle layer associated with lower frequencies of ganglion cells and interstitial cells of Cajal, in all gastrointestinal tract. CONCLUSION: Severe nerve plexus abnormalities associated with muscle layer atrophy were observed throughout the gastrointestinal tract in newborn rats exposed to ethylenethiourea.

Abnormalities of digestive tract innervation in rat fetus treated with ethylenethiourea / Anomalias da inervação do trato digestório de fetos de ratas expostas à etilenotioureia

PURPOSE: The pathophysiology of abnormalities associated with myenteric plexus lesions remains imperfectly understood. Such abnormalities have been correlated with subocclusive intestinal conditions in children with Hirschsprung's disease, cases of chronic constipation and, postoperatively, in cases of anorectal anomalies. This study evaluated abnormalities of the myenteric plexus in fetus from female rats that received ethylenethiourea. METHODS: Female rats were exposed to ethylenethiourea on the 11th day of pregnancy (experimental group) or to 0.9 percent physiological solution (control group). Abnormalities were only found in the experimental group. The digestive tract muscle layer was analyzed morphometrically and changes to the frequencies of nerve plexus cells and interstitial cells of Cajal were evaluated, using hematoxylin-eosin, S-100 protein, neuron-specific enolase and C-Kit, respectively. RESULTS: Muscle and skeletal abnormalities were observed in 100 percent, anorectal anomalies in 86 percent, absent tail in 71 percent, short tail in 29 percent, duodenal atresia in 5 percent, esophageal atresia in 5 percent and persistent omphalomesenteric duct in 5 percent. Histopathological analysis showed a thinner muscle layer associated with lower frequencies of ganglion cells and interstitial cells of Cajal, in all gastrointestinal tract. CONCLUSION: Severe nerve plexus abnormalities associated with muscle layer atrophy were observed throughout the gastrointestinal tract in newborn rats exposed to ethylenethiourea.

OBJETIVO: As anomalias associadas a lesões dos plexos mioentéricos permanecem sem plena compreensão da sua fisiopatologia. Alterações nos plexos nervosos têm sido correlacionadas com quadros suboclusivos intestinais em crianças portadoras de doença de Hirschsprung, em constipação crônica e no pós-operatório de anomalias anorretais. Este estudo avaliou as anomalias do plexo mioentérico em fetos de ratos fêmea que ingeriram etilenotioureia (ETU). MÉTODOS: Ratos fêmea foram expostos no 11º dia de gestação a ETU 1 por cento no Grupo Experimento e a solução fisiológica 0,9 por cento no Grupo Controle. Foram observadas anomalias apenas no Grupo experimento, sendo realizada morfometria da camada muscular e avaliadas alterações da frequência celular nos gânglios do plexo mioentérico e nas células intersticiais de Cajal (CIC) utilizando hematoxilina-eosina, P S-100, Enolase Neurônio Específica e C-KIT. RESULTADOS: Foram observadas anomalias musculoesqueléticas (100 por cento), anorretais (86 por cento), ausência de cauda (71 por cento), cauda curta (29 por cento), atresia duodenal (5 por cento), atresia esofágica (5 por cento) e conduto onfalomesentérico persistente (5 por cento). A análise histopatológica mostrou adelgaçamento da camada muscular associada às alterações da frequência das células ganglionares e das CIC em todos os segmentos do trato gastrointestinal. CONCLUSÃO: Foram observadas alterações graves nos plexos nervosos associadas ao adelgaçamento da camada muscular de todo o trato gastrointestinal nos fetos expostos a ETU.

Anatomical classification of the shape and topography of the stomach.

The aim of the study was to present the classification of anatomical variations of the stomach, based on the radiological and historical data. In years 2006-2010, 2,034 examinations of the upper digestive tract were performed. Normal stomach anatomy or different variations of the organ shape and/or topography without any organic radiologically detectable gastric lesions were revealed in 568 and 821 cases, respectively. Five primary groups were established: abnormal position along longitudinal (I) and horizontal axis (II), as well as abnormal shape (III) and stomach connections (IV) or mixed forms (V). The first group contains abnormalities most commonly observed among examined patients such as stomach rotation and translocation to the chest cavity, including sliding, paraesophageal, mixed-form and upside-down hiatal diaphragmatic hernias, as well as short esophagus, and the other diaphragmatic hernias, that were not found in the evaluated population. The second group includes the stomach cascade. The third and fourth groups comprise developmental variations and organ malformations that were not observed in evaluated patients. The last group (V) encloses mixed forms that connect two or more previous variations.

Disease-specific quality of life in children and adults with anorectal malformations.

PURPOSE: The aim of the present study was to analyze disease-specific quality of life, as assessed by the Hirsch-sprung Disease/Anorectal Malformation Quality of Life (HAQL) questionnaire, in children and adults with ano-rectal malformations (ARM). METHODS: As much as 175 children and 62 adults who were members of the Italian Association for Anorectal Malformations were asked to complete the Italian version of the HAQL questionnaire developed for this study. For children under 16 years of age, mothers were asked to fill up the questionnaires. Patients were also asked to identify their type of malformation from a list of eight choices. RESULTS: Most subscales of the Italian HAQL had acceptable reliability. Compared to children, adults reported significantly lower levels of QL on subscales measuring emotional functioning, body image, and physical symptoms. CONCLUSIONS: Longitudinal studies are needed to clarify whether these results can be attributed to improvements in surgical techniques that have contributed to improved QL in younger cohorts, or if, instead, quality of life in patients with ARM decreases over time. Intervention efforts should focus on bowel management and psychological treatment for ARM-related emotional and body image distress.

Double common bile duct: a case report.

The aim of our study is to present a case of double common bile duct. Specifically, we found a common bile duct that was divided into two distinct ducts, one the main and the other the accessory duct, during its course downwards. The two bile ducts had a parallel course emerging from the common bile duct after its formation and reuniting just above the head of the pancreas. Finally, they drained into the second portion of the duodenum at the site of major duodenal papilla. This anomaly is of great importance because the duplication of the common bile duct can lead to severe intraoperative injury to one of the two common bile ducts, which can be mistaken for the cystic duct and be ligated. Moreover, we present the relative international literature and the clinical significance of our finding.

Management of congenital pouch colon based on the Saxena-Mathur classification.

BACKGROUND: Management guidelines with regard to congenital pouch colon (CPC) are not clearly defined with regard to the type of pouch present. The aim of this study was to outline the management strategy and surgical approach to CPC using the Saxena-Mathur classification based on anatomical morphology of the pouch. METHODS: During a 12-year period (1995-2007), 426 patients were surgically managed for anorectal malformations at the RNT Medical College, Udaipur. Congenital pouch colon was documented in 80 patients and categorized into 5 types according the anatomical morphology. The management strategy depended upon the location of the pouch and its condition at the time of the surgery. RESULTS: In type 1 and type 2 CPC, a 1-stage (pouch excision and pull-through) or 3-stage procedure (ileostomy, pouch-coloplasty with pull-through, and ileostomy closure) was performed depending on the condition of the pouch (ischemic or healthy). In type 3 and type 4 CPC, a 3-stage procedure (pouch excision with colostomy, pull-through, and colostomy closure) was performed in all patients. In type 5 CPC, a 3-stage procedure (distal pouch excision with proximal pouch-coloplasty with ileostomy, pull-through, and colostomy closure) was successful. CONCLUSION: Management of CPC patients according the Saxena-Mathur classification provides a well-defined algorithm in the surgical approach according to the anatomical morphology of the pouch.

Do low-type anorectal malformations have a better prognosis than the intermediate and high types? A preliminary report using the Krickenbeck score.

BACKGROUND: Following the development of the Wingspread classification for anorectal malformations, low-type lesions were considered to have a better functional prognosis than intermediate and high lesions. This study rejects this basic presumption following the establishment of the latest standards at Krickenbeck in May 2005. PATIENTS AND METHODS: The surgical approach, whether perineal (group A) or posterior sagittal anorectoplasty (group B), was determined depending on the presence or absence of a perineal fistula. Group C consisted of patients below the age of three years. Sacral anomalies were screened by lumbosacral radiography. Information on postoperative anorectal function (voluntary bowel movements, soiling, and constipation) was gathered by phone call. RESULTS: Eight of the 9 patients in group A, and 2 of the 7 in group B achieved voluntary bowel movements (p < 0.05). No significant differences were found between the two groups with respect to either the occurrence or severity of soiling and constipation. All subjects in group C (n = 4) had fewer than 3 daily stools with total cleanness between episodes but still suffered from constipation. CONCLUSIONS: Basic ideas about anorectal malformations will continue to be modified when the criteria are changed. The use of the Krickenbeck score will help to standardize the results of studies.

Anorectal malformations.

Anorectal malformations comprise a wide spectrum of diseases, which can affect boys and girls, and involve the distal anus and rectum as well as the urinary and genital tracts. They occur in approximately 1 in 5000 live births. Defects range from the very minor and easily treated with an excellent functional prognosis, to those that are complex, difficult to manage, are often associated with other anomalies, and have a poor functional prognosis. The surgical approach to repairing these defects changed dramatically in 1980 with the introduction of the posterior sagittal approach, which allowed surgeons to view the anatomy of these defects clearly, to repair them under direct vision, and to learn about the complex anatomic arrangement of the junction of rectum and genitourinary tract. Better imaging techniques, and a better knowledge of the anatomy and physiology of the pelvic structures at birth have refined diagnosis and initial management, and the analysis of large series of patients allows better prediction of associated anomalies and functional prognosis. The main concerns for the surgeon in correcting these anomalies are bowel control, urinary control, and sexual function. With early diagnosis, management of associated anomalies and efficient meticulous surgical repair, patients have the best chance for a good functional outcome. Fecal and urinary incontinence can occur even with an excellent anatomic repair, due mainly to associated problems such as a poorly developed sacrum, deficient nerve supply, and spinal cord anomalies. For these patients, an effective bowel management program, including enema and dietary restrictions has been devised to improve their quality of life.

Disseminated mixed intestinal dysmotility (DMID): a new intestinal ganglion cell disorder?

We experienced two cases with disseminated HP and IND occurring with normal bowel in between (disseminated mixed intestinal dysmotility--DMID) and postulate whether it could be classified as a new intestinal motility disorder. Our cases, both boys, died at 3 and 7 months, respectively. Both had irregular stool passage, and abdominal distention with bilious vomiting since birth. On barium enema, both had rigid distal ileum and colon with narrow lumens, with dilated and atonic proximal ileum and jejunum. An ileostomy was created on days 3 and 2 of life, respectively, however, they did not function and jejunostomies were created, which also did not function well. Both boys died after repeated episodes of severe enterocolitis. In each case, three 10 cm specimens were obtained randomly from the jejunum and ileum, and two 5 cm specimens were obtained randomly from each of the ascending colon, transverse colon, descending colon, and rectum and treated with hematoxylin and eosin (H & E) staining, acetylcholine esterase (AchE) histochemistry, and protein gene product 9.5 (PGP9.5) and neural cell adhesion molecule (NCAM) immunohistochemistry for histopathologic assessment. All specimens showed a mixture of disseminated IND and HP, with normal intestine in between. There was abnormal expression of NCAM activity in the intestinal smooth muscle layers in small and large intestine. This is the first report about disseminated IND and HP occurring with normal bowel in between (DMID) and we suggest it should be classified as a new intestinal motility disorder. The present findings demonstrate that patients with DMID have a complicated abnormality of NMJ that may directly influence bowel motility and prognosis according to the severity of the abnormality.

The clinical relevance of non-classified dysganglionoses and implications for a new grading system.

In addition to the classified types of dysganglionosis, certain non-classified dysganglionoses (NCD) (types 1-4) were introduced by Meier-Ruge in 1992. Clinical data on these conditions are limited. Among 134 children with intestinal dysganglionoses (ID) treated from 1979 to 1999, 12 were identified to have a NCD. Their clinical course is presented. The existence of mild ID (type 1) is difficult to demonstrate. Current definitions and data on clinical relevance are not convincing. An indication for surgical treatment is not present. Isolated hypogenesis of the submucous plexus (SMP) (type 2, n = 8) is clinically a more severe kind of intestinal neuronal dysplasia type B and often requires early surgical intervention, but not resection. When associated with aganglionosis, its recognition is important for surgical strategy, to avoid complicated clinical courses, which are frequent if total or nearly-total resection is not performed. Hypogenesis of the myenteric plexus (MP) (type 5, n = 1) has received little attention so far. The sporadic appearance of heterotopic nerve cells of the SMP in the mucosa (type 3, n = 1) is physiologic; clusters of such cells, however, are probably of pathologic value, especially in combination with other types of ID in the same patient. Heterotopic nerve cells of the MP (type 4, n = 3) in the circular and longitudinal muscle layers are highly pathologic. This clearly-defined type is of major clinical relevance and requires complete resection. A severe disturbance of the migration process is the underlying cause. To simplify the terminology of IDs, a grading system based on the anatomic structures and clinical findings is proposed: innervation disturbances of the mucosa (grade I) are of limited clinical significance. Isolated malformations of the SMP (grade II) may require an enterostomy, but do not require resection except in certain cases associated with distal aganglionosis. Dysganglionosis of the MP (grade III) usually exhibits more severe symptoms and resection is indicated, especially with associated hypo- or aganglionosis. In aganglionic bowel (grade IV) resection is mandatory.

Pathological classification and diagnosis of intestinal duplication.

OBJECTIVE: To determine the pathological classification and the clinical characteristics of intestinal duplication. METHODS: Eighty-four pediatric patients with intestinal duplication were proved on operation in the last 20 years in the Second Hospital of Harbin Medical University and Harbin Children's Hospital. The pathological classifications were as follows: enteral septum type (2), parietal cyst type (9), parenteral canal type (31), parenteral cyst type (35), and solitary type (1). The clinical presentations and complications included: abdominal mass (24), illius (41), hemorrhage of digestive tract (15) and intestinal perforation with peritonitis (3). Two asymptomatic cases were discovered incidentally. RESULTS: Among the 84 patients, 82 healed, 1 newborn complicated by intestinal fistula died of septicemia, and the other one died of toxic shock. CONCLUSIONS: Recognizing the pathological types, common presentations and complications, and applying the corresponding examination methods timely, doctors may improve the diagnostic accuracy.