Growth from Birth to 30 months for Infants Born with Congenital Gastrointestinal Anomalies and Disorders.

OBJECTIVE: This study aimed to investigate growth among neonates with gastrointestinal disorders. STUDY DESIGN: Inclusion criteria included neonates with gastroschisis, omphalocele, intestinal atresia, tracheoesophageal fistula, Hirschsprung's disease, malabsorption disorders, congenital diaphragmatic hernia, and imperforate anus born between 2010 and 2018. Anthropometrics were collected for the first 30 months, and a subgroup analysis was performed for gastroschisis infants. RESULTS: In 61 subjects, 13% developed severe growth failure within the first month. One-, four-, and nine-month weight and length z-scores were less than birth weight in all infants (p < 0.05). In infants with gastroschisis, a similar pattern was observed for weight z-scores only (p < 0.05). From birth to 15 months, head circumference z-score increased over time in all infants (p = 0.001), while in gastroschisis infants, weight, length, and head circumference z-scores increased over time (p < 0.05). CONCLUSION: In a cohort of infants with gastrointestinal disorders, growth failure was followed by catch-up growth.

The effect of pre- and post-remote ischemic conditioning reduces the injury associated with intestinal ischemia/reperfusion.

PURPOSE: Midgut volvulus is associated with intestinal ischemia/reperfusion (IR) injury and can progress to severe intestinal damage. Remote ischemic conditioning (RIC) reduces IR-induced injury in distant organs. The aim of this study was to investigate whether RIC protects the intestine from IR injury. METHODS: We investigated intestinal IR injury in 3 weeks old SD rats. Animals underwent: (i) sham laparotomy, (ii) intestinal IR injury, (iii) intestinal IR + RIC during ischemia, or (iv) intestinal IR + RIC after reperfusion. Intestinal IR injury was achieved by 45 min occlusion of superior mesenteric artery followed by de-occlusion. RIC was administered via four cycles of 5 min of hind limb ischemia followed by 5 min reperfusion. Animals were sacrificed 24 h after surgery and the ileum was harvested for evaluation. RESULTS: Intestinal injury was present after IR. However, this injury was reduced in both IR + RIC groups. Expression of inflammatory cytokine IL6 was lower in IR + RIC groups compared to IR alone. Carbonyl protein was also significantly lower in IR + RIC compared to IR, indicating lower oxidative stress in both IR + RIC groups. CONCLUSION: Remote ischemic conditioning attenuated intestinal injury, inflammation, and oxidative stress in experimental intestinal ischemia/reperfusion injury. Remote ischemic conditioning may be useful in children with midgut volvulus to reduce the intestinal injury. LEVEL OF EVIDENCE: Experimental study. TYPE OF STUDY: Animal experiment.

HLX is a candidate gene for a pattern of anomalies associated with congenital diaphragmatic hernia, short bowel, and asplenia.

Isolated congenital diaphragmatic hernia is often a sporadic event with a low recurrence risk. However, underlying genetic etiologies, such as chromosome anomalies or single gene disorders, are identified in a small number of individuals. We describe two fetuses with a unique pattern of multiple congenital anomalies, including diaphragmatic hernia, short bowel and asplenia, born to first-cousin parents. Whole exome sequencing showed that both were homozygous for a missense variant, c.950A>C, predicting p.Asp317Ala, in the H.20-Like Homeobox 1 (HLX1) gene. HLX is a homeobox transcription factor gene which is relatively conserved across species. Hlx homozygous null mice have a short bowel and reduced muscle cells in the diaphragm, closely resembling the anomalies in the two fetuses and we therefore suggest that the HLX mutation in this family could explain the fetal findings.

Meconium Peritonitis: Correlation of Antenatal Diagnosis and Postnatal Outcome - An Institutional Experience over 10 Years.

OBJECTIVE: To identify the fetal and neonatal imaging characteristics of meconium peritonitis (MP) and their clinical outcome. We also studied the role of prenatal ultrasound (US) in antenatal diagnosis and its use in predicting the need for surgical intervention postnatally. MATERIAL AND METHODS: We conducted a retrospective analysis of a cohort of 18 infants with MP from April 2004 to March 2014. RESULTS: Prenatal US detected MP-related abnormalities in 15/18 (83.3%) fetuses. The median gestational age at initial diagnosis of MP was 24 weeks (range 19-31). Fetal ascites (93.3%) was the most common prenatal US finding. Of the 18 infants, 12 (66.7%) required surgical intervention. The overall survival rate was 94.4%. All infants with a prenatal US scan showing meconium pseudocyst or bowel dilatation required surgical intervention postnatally. DISCUSSION: A combination of ascites, intraperitoneal calcification, and echogenic bowel on fetal US raises a high suspicion of MP. Surgical intervention is indicated in the presence of meconium pseudocyst on fetal or postnatal US scan. Antenatal US has high specificity (100%) but low sensitivity (22.2%) in detecting meconium pseudocyst. A favorable outcome can be expected with early antenatal diagnosis and timely surgical intervention in a tertiary hospital.

[Surgical treatment of rare combination of intestinal malrotation with secondary lymphangiectasia].

The rare combination of intestinal lymphangiectasia with malrotation of the duodenum in a child of three months of life is described. Basing on the literature review only 3 similar cases were described in the world practice. The boy with protein-losing enteropathy was examined at Moscow Scientific Centre of Children's Health. The child had vomiting, diarrhea, loss in body weight, hypoproteinemia, lymphopenia. The infectious nature of the disease was excluded. It had been suggested the Waldman desease (primary intestinal lymphangiectasia). The prognosis for such disease is unfavorable. An examination of the child was continued against the backdrop of ongoing symptomatic therapy. Complete physical examination included monitoring laboratory blood tests, X-ray examination with contrast, CT-scan, gastroduodenoscopy with biopsy of the mucosa of the small intestine. Malrotation duodenum with the recurrent mid-gut volvulus with the development of secondary intestinal lymphangiectasia was diagnosed. Modern methods of examination and multidisciplinary approach made it possible to diagnose the case. Operation to eliminate fixation duodenum resulted in the recovery of the patient. At the present time the child grows and develops according to age and does not require treatment. The prognosis for this disease is regarded as favorable.

Currarino syndrome: report of five consecutive patients.

INTRODUCTION: The Currarino syndrome is regarded as a developmental disorder based on its recognized etiological heterogeneity. This syndrome is thought to result from abnormal separation of the neuroectoderm from the endoderm. Our aim was to report the neurosurgical management of Currarino syndrome in children and adults and to describe what clinician could do if the Currarino triad was suspected. CASE REPORTS: We present five cases of Currarino triad who underwent surgical intervention. All patients had sacral bony deformity, anorectal malformations, and anterior sacral meningocele. A 40-year-old-male had chronic constipation. He was incidentally diagnosed with Currarino syndrome. A 19-year-old-female suffered from a slight weakness in lower extremities and urinary incontinence. Her past medical history was remarkable for anal atresia. The other three cases were children. CONCLUSION: When an anterior sacral meningocele is encountered, Currarino syndrome should be taken into consideration. Although it is rarity, the Currarino syndrome might be one of the causes of chronic constipation. Endoscopic or endoscope-assisted surgery via a posterior sacral route can be feasible for treatment of some of the patients with anterior sacral meningocele. Anterior meningocele pouch associated with Currarino syndrome will regresses over time following transdural ligation of its neck.

[Features of clinical picture and diagnostic aspects of intestional rotation and fixation disorders in children].

Clinical manifestations and diagnostic methods of particular anatomical variants of intestinal rotation and fixation disorders were discussed by the authors in 208 children of different age groups. There was revealed the tendency to reduce rotation abnormalities diversity with the increase of age group. At the same time the frequency of occurrence of the colon fixation anomalies characterized by chronic recurrent process and progressing colostasis was enlarged.

A practical guide for the diagnosis of primary enteric nervous system disorders.

OBJECTIVE: Primary gastrointestinal neuropathies are a heterogeneous group of enteric nervous system (ENS) disorders that continue to cause difficulties in diagnosis and histological interpretation. Recently, an international working group published guidelines for histological techniques and reporting, along with a classification of gastrointestinal neuromuscular pathology. The aim of this article was to review and summarize the key issues for pediatric gastroenterologists on the diagnostic workup of congenital ENS disorders. In addition, we provide further commentary on the continuing controversies in the field. RESULTS: Although the diagnostic criteria for Hirschsprung disease are well established, those for other forms of dysganglionosis remain ill-defined. Appropriate tissue sampling, handling, and expert interpretation are crucial to maximize diagnostic accuracy and reduce interobserver variability. The absence of validated age-related normal values for neuronal density, along with the lack of correlation between clinical and histological findings, result in significant diagnostic uncertainties while diagnosing quantitative aberrations such as hypoganglionosis or ultrashort Hirschsprung disease. Intestinal neuronal dysplasia remains a histological description of unclear significance. CONCLUSIONS: The evaluation of cellular quantitative or qualitative abnormalities of the ENS for clinical diagnosis remains complex. Such analysis should be carried out in laboratories that have the necessary expertise and access to their own validated reference values.

[Central neuroaxial blocade and metabolic stress-answer in a newborn and babies in surgical diseases].

Investigation of markers of humoral stress was conducted in 25 babies (the main group), in whom a central neuroaxial blocade was performed while doing various surgical interventions. In a control group there were included 20 babies, in whom a standard atharalgesia was applied. The best efficacy was achieved while anesthesia using central neuroaxial blocade.

Urodynamic findings in patients with Currarino syndrome.

PURPOSE: Currarino syndrome is an inherited disorder consisting of a triad of anorectal anomaly, sacrococcygeal defect and presacral mass. We evaluated the urological issues in patients with Currarino syndrome and sought to determine whether spinal cord detethering improves urinary tract function. MATERIALS AND METHODS: We retrospectively reviewed 14 patients diagnosed with Currarino syndrome. We evaluated urinary signs/symptoms and urodynamic findings before and after spinal cord detethering. RESULTS: All patients with Currarino syndrome having a sacral defect and presacral mass were diagnosed between birth and 6 years. Of the patients 86% had a tethered spinal cord that was surgically detethered between 8 months and 6 years (average 3 years). Overall 10 of 12 children who underwent surgery had voiding complaints postoperatively, including urgency, frequency and incontinence. Five patients had recurrent urinary tract infections, of whom 3 had vesicoureteral reflux that resolved spontaneously. Three patients had mild unilateral hydronephrosis without reflux. Ten of 12 patients who underwent spinal cord detethering underwent comprehensive urodynamic evaluation. Of the 5 patients who underwent preoperative and postoperative urodynamic evaluation 3 showed improvement with resolution of detrusor overactivity or dyssynergia postoperatively, and 2 demonstrated no change. Of the 5 patients who underwent only postoperative urodynamic evaluation 4 had abnormal findings, including small capacity, poor compliance, detrusor overactivity, detrusor sphincter dyssynergia and/or high voiding pressure. No progressive denervation was seen on electromyography preoperatively or postoperatively. CONCLUSIONS: Currarino syndrome is a rare congenital disorder with few published reports regarding the long-term implications. Although no solid conclusions could be drawn regarding urodynamic improvement postoperatively due to our small sample size, spinal cord detethering did not lessen ongoing voiding complaints in the study patients.

Making the case for using donor human milk in vulnerable infants.

Vulnerable infants are at an increased risk for feeding intolerance due to immaturity or dysfunction (ie, congenital anomaly or obstruction) of the gastrointestinal system and/or hemodynamic instability. Symptoms of feeding intolerance include vomiting, water-loss stools, increased abdominal girth, and increased gastric residuals. It has been well documented that human milk provides optimal nutrition for infants and decreases the incidence of feeding intolerance. Donor human milk can be used for these at-risk infants to supplement the mother's own milk supply if insufficient or if the mother has decided not to or is unable to provide human milk for her infant. Establishing a donor human milk program within your institution will allow an opportunity for all vulnerable infants to receive an exclusive human milk diet.

Pancreas divisum.

We review important new clinical observations in pancreas divisum (PD) made since 2007. PD is common and has the same prevalence in the general population and idiopathic pancreatitis (IP). Up to 53% of patients with PD and IP have underlying idiopathic chronic pancreatitis (CP), and in rigorous prospective clinical follow-up and/or natural history studies, many with idiopathic recurrent acute pancreatitis (IRAP) have idiopathic CP. According to retrospective studies, PD does not modify the natural course of nonalcoholic or alcoholic CP. CFTR and/or SPINK1 gene mutations associate with IP (idiopathic CP and IRAP) independently of the presence of PD. More than one third of patients with pancreatitis or presumed pancreaticobiliary pain respond to placebo. Authors of uncontrolled studies report a significant symptomatic response to surgery and endotherapy in patients with IP and PD, but the response remains unproven and is largely limited to those with IRAP and not idiopathic CP or chronic pain.

A role for Pten in paediatric intestinal dysmotility disorders.

PURPOSE: The enteric nervous system (ENS) is a network of neurons and glia that lies within the gut wall. It is responsible for the normal regulation of gut motility and secretory activities. Hirschsprung's disease (HD) is a congenital defect of the ENS, characterised by an absence of ganglia in the distal colon. Intestinal neuronal dysplasia (IND) is a condition that clinically resembles HD, characterised by hyperganglionosis, giant and ectopic ganglia, resulting in intestinal dysmotility. Intestinal ganglioneuromatosis is characterised by hyperplasia and hypertrophy of enteric neuronal cells and causes chronic intestinal pseudo-obstruction (CIPO). Phosphatase and tensin homolog deleted on chromosome 10 (Pten) is a phosphatase that is critical for controlling cell growth, proliferation and cell death. A recent study of Pten knockout mice showed evidence of ganglioneuromatosis in the ENS suggesting a role for this protein in ENS development. Ganglioneuromatosis patients have also been shown to have a decreased level of Pten expression in the colon. The aim of our study was to investigate Pten expression in the ENS of HD and IND patients compared to normal controls. METHODS: Resected tissue from 10 HD and 10 IND type B patients was fixed and embedded in paraffin wax. Normal control colon tissue was obtained from ten patients who underwent a colostomy closure for imperforate anus. Sections were cut and immunohistochemistry was carried out using a Pten antibody. Results were analysed by light microscopy. RESULTS: Staining showed that Pten was strongly expressed in ganglia of both the submucosal and myenteric plexus of normal and HD specimens from the ganglionic colon. Pten expression was significantly reduced in the giant ganglia in IND patients in both the myenteric and submucosal plexuses compared to the normal controls. Specimens from the aganglionic region of HD did not show Pten expression. CONCLUSION: To the best of our knowledge, this is the first study demonstrating a marked reduction of Pten expression in the myenteric and submucous plexuses of IND patients. Neuronal Pten deficiency in IND may disrupt the chemical pathway associated with the proliferation and development of neuronal cells forming mature ganglia and thus cause motility dysfunction.

[Surgical treatment of chronic coprostasis].

Surgical treatment of 27 patients with chronic colostasis and dolichocolon was analyzed. Groups of patients with cologenic and proctogenic colostasis were defined, diagnostic criteria were formulated and optimal surgical tactics were described for each group. Short and long-term results were analyzed and proved to be excellent and satisfactory in majority of patients.

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.