Treatment of jejunoileal atresia by primary anastomosis or enterostomy: Double the operations, double the risk of complications.

PURPOSE: No study has evaluated complication rates of the combined operations needed for temporary Enterostomy compared to primary anastomosis in the treatment of Jejunoileal Atresia. Therefore the aim of this study is: 1) to compare the occurrence of severe postoperative complications (defined as Clavien-Dindo ≥III within 30 days) and 2) to compare the occurrence of different short- and long-term complications following treatment for Jejunoileal atresia either by primary anastomosis or the combined Enterostomy procedures. METHODS: All consecutive neonates treated for Jejunoileal Atresias between January 1998 and February 2021 at our tertiary academic centres were retrospectively included. Perioperative characteristics and severity of postoperative complications (Clavien-Dindo) were extracted and evaluated, using chi-squared statistics, following each operation per treatment. RESULTS: Eighty patients were included of whom 48 (60%) received a primary anastomosis and 32 (40%) an Enterostomy. Perioperative baseline characteristics were comparable, apart from significantly more patients with a gastroschisis and significantly less patients with jejunum atresia in the Enterostomy group. Our results showed that 1) significantly (p ≤ 0.01) more CD ≥III occur following treatment by Enterostomy. 2) Both short-term (surgical site infection, wound dehiscence) and long-term (short bowel syndrome, adhesive bowel obstruction) complications occurred significantly more in those treated by Enterostomy. We showed no significant difference in anastomotic leakage/stenosis and mortality rates between both treatment strategies. CONCLUSION: Although perioperative factors might necessitate an Enterostomy, we advise a low threshold for performing a primary anastomosis when in doubt, taking into account the double risk of major complications found in patients treated with a temporary Enterostomy.

Gut lumen formation defect can cause intestinal atresia: evidence from histological studies of human embryos and intestinal atresia septum.

Intestinal atresia (IA), a common cause of neonatal intestinal obstruction, is a developmental defect, which disrupts the luminal continuity of the intestine. Here, we investigated (i) the process of lumen formation in human embryos; and (ii) how a defective lumen formation led to IA. We performed histological and histochemical study on 6-10 gestation week human embryos and on IA septal regions. To investigate the topology of embryonic intestine development, we conducted 3D reconstruction. We showed that a 6-7th gestation week embryonic gut has no lumen, but filled with mesenchyme cells and vacuoles of a monolayer of epithelial cells. A narrow gut lumen was formed by gestation week-9, the gut was filled with numerous vacuoles of different sizes, some vacuoles were merging with the developing embryonic gut wall. At gestation week-10, a prominent lumen was developed, only few vacuoles were present and were merging with the intestine wall. At IA septal regions, vacuoles were located in the submucous layer, covered by a single layer of epithelium without glandular structure, and surrounded with fibrous tissue. The mucosal epithelium was developed with lamina propria and basement membrane, but the submucosa and the longitudinal smooth muscle layers were not properly developed. Hence, the vacuoles in IA septum could represent a remnant of vacuoles of embryonic gut. In conclusion, the fusion of vacuoles with the developing intestine wall associates with the disappearance of vacuoles and gut lumen formation in human embryos, and perturbation of these developmental events could lead to IA.

Congenital Glucagon-like Peptide-1 Deficiency in the Pathogenesis of Protracted Diarrhea in Mitchell-Riley Syndrome.

CONTEXT: Mitchell-Riley syndrome due to RFX6 gene mutations is characterized by neonatal diabetes and protracted diarrhea. The RFX6 gene encodes a transcription factor involved in enteroendocrine cell differentiation required for beta-cell maturation. In contrast to the pathway by which RFX6 mutations leads to diabetes, the mechanisms underlying protracted diarrhea are unknown. OBJECTIVE: To assess whether glucagon-like peptide-1 (GLP-1) was involved in the pathogenesis of Mitchell-Riley syndrome protracted diarrhea. METHODS: Two case report descriptions. in a tertiary pediatric hospital. "Off-label" treatment with liraglutide. We describe 2 children diagnosed with Mitchell-Riley syndrome, presenting neonatal diabetes and protracted diarrhea. Both patients had nearly undetectable GLP-1 plasma levels and absence of GLP-1 immunostaining in distal intestine and rectum. The main outcome was to evaluate whether GLP-1 analogue therapy could improve Mitchell-Riley syndrome protracted diarrhea. RESULTS: "Off-label" liraglutide treatment, licensed for type 2 diabetes treatment in children, was started as rescue therapy for protracted intractable diarrhea resulting in rapid improvement during the course of 12 months. CONCLUSION: Congenital GLP-1 deficiency was identified in patients with Mitchell-Riley syndrome. The favorable response to liraglutide further supports GLP-1 involvement in the pathogenesis of protracted diarrhea and its potential therapeutic use.

A rare case of intrauterine intussusception causing ileal atresia.

Intrauterine intussusception is a rare but evident cause of intestinal atresia and is usually detected intraoperatively. We report on a term neonate who presented to the Department of Paediatric Surgery, Sabah Women and Children's Hospital, Malaysia with delayed passage of meconium and intestinal obstruction, wherein the lower contrast showed a claw sign. This was a good clue that this neonate had intrauterine intussusception and this suspicion was confirmed upon laparotomy. We found an ileo-ileal intussusception causing ileal atresia, requiring resection and primary anastomosis.

Endoscopic balloon dilation in duodenal stenosis secondary to intestinal lymphoma in a heart transplant patient.

Intestinal lymphoma can appear as a result of a state of immunosuppression, secondary to the transplantation of solid organs. Treatment with chemotherapy can result in various complications such as intestinal stenosis due to fibrotic scar tissue, which is a complication barely described in the literature. We present the case of a 12-year-old male with a heart transplant, who was diagnosed with intestinal lymphoma. After chemotherapy treatment, he developed 1-2 daily vomiting episodes as a result of intestinal stenosis due to fibrosis without tumor infiltration. Endoscopic balloon dilation was used and the symptoms were resolved without the need for surgical treatment.

Closing gastroschisis: The good, the bad, and the not-so ugly.

PURPOSE: The diagnosis of "closing" or "closed gastroschisis" is made when bowel is incarcerated within a closed or nearly closed ring of fascia, usually with associated bowel atresia. It has been described as having a high morbidity and mortality. METHODS: A retrospective review of closing gastroschisis cases (n = 53) at six children's hospitals between 2000 and 2016 was completed after IRB approval. RESULTS: A new classification system for this disease was developed to represent the spectrum of the disease: Type A (15%): ischemic bowel that is constricted at the ring but without atresia; Type B (51%): intestinal atresia with a mass of ischemic, but viable, external bowel (owing to constriction at the ring); Type C (26%): closing ring with nonviable external bowel +/- atresia; and Type D (8%): completely closed defect with either a nubbin of exposed tissue or no external bowel. Overall, 87% of infants survived, and long-term data are provided for each type. CONCLUSIONS: This new classification system better captures the spectrum of disease and describes the expected long-term results for counseling. Unless the external bowel in a closing gastroschisis is clearly necrotic, it should be reduced and evaluated later. Survival was found to be much better than previously reported. TYPE OF STUDY: Retrospective case series with no comparison group. LEVEL OF EVIDENCE: Level IV.

Nutritional role of amniotic fluid: clues from infants with congenital obstruction of the digestive tract.

AIMS: To investigate the role played by amniotic fluid in late fetal nutrition by analysis of infants born with digestive tract atresia. METHODS: Birth weight (BW), gestational age and gender of infants born with oesophageal (OA), duodenal (DA), jejunal (JA) and ileal atresia (IA) were recorded and BW Z-scores compared. Infants with incomplete obstruction (stenosis), chromosomal or syndromic conditions and multiple congenital malformations were excluded. Term infants admitted with suspected postnatal intestinal obstruction in whom no congenital malformation was found were used as a control group. RESULTS: A total of 584 infants were identified comprising 148 OA, 60 DA, 26 JA and 57 IA with 293 in the control group. Infants with OA and DA had statistically significantly lower BW Z-score than controls. However, BW Z-score for infants with more distal atresia (JA and IA) was similar to controls. When compared with infants with OA, BW Z-score for infants with more distal atresia was higher than that for OA. BW Z-score in infants with OA was significantly lower in those born at term compared with those born preterm (mean±SD -0.92±1.0 vs -0.48±0.87; p=0.01) with a significant negative correlation between BW Z-score and increasing gestational age (R2=0.12; p<0.0001). This effect of gestational age was not seen in other atresias. CONCLUSION: These observations support the concept that reduced enteral absorption of amniotic fluid due to high digestive tract obstruction in utero reduces fetal growth. The effect is greater when the obstruction is more proximal and with advancing gestation.

Maternal antihypertensive medication use and selected birth defects in the National Birth Defects Prevention Study.

BACKGROUND: There are limited data on the relationship between antihypertensive medication use in early pregnancy and risk of birth defects. METHODS: Using data from the National Birth Defects Prevention Study, we examined associations between specific antihypertensive medication classes and 28 noncardiac birth defects. We analyzed self-reported data on 17,038 case and 11,477 control pregnancies with estimated delivery dates during 1997-2011. We used multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals, adjusted for maternal age, race/ethnicity, body mass index, parity, pregestational diabetes, and study site, for associations between individual birth defects and antihypertensive medication use during the first trimester of pregnancy. We compared risk among women reporting early pregnancy antihypertensive medication use to normotensive women. RESULTS: Hypertensive women who reported early pregnancy antihypertensive medication use were more likely to be at least 35 years old, non-Hispanic Black, obese, multiparous, and to report pregestational diabetes than normotensive women. Compared to normotensive women, early pregnancy antihypertensive medication use was associated with increased risk of small intestinal atresia (adjusted OR 2.4, 95% CI 1.2-4.7) and anencephaly (adjusted OR 1.9, 95% CI 1.0-3.5). Risk of these defects was not specific to any particular medication class. CONCLUSIONS: Maternal antihypertensive medication use was not associated with the majority of birth defects we analyzed, but was associated with an increased risk for some birth defects. Because we cannot entirely rule out confounding by the underlying hypertension and most ORs were based on small numbers, the increased risks observed should be interpreted with caution.

[Mesenteric edema as a prenatal ultrasound sign of poor prognosis in gastroschisis]. / El edema mesentérico como signo ecográfico prenatal de mal pronóstico en gastrosquisis.

INTRODUCTION/AIM OF THE STUDY: Gastroschisis is a congenital malformation with an easy and early prenatal diagnosis, however, it has a variable post-natal outcome. Our aim was to determine if certain ultrasound markers or early delivery were related with a worse postnatal outcome. PATIENTS AND METHODS: Retrospective study of a cohort of patients with gastroschisis diagnosed between 2005-2014, with emphasis on prenatal ultrasounds, gestational age at delivery and post-natal outcome. Oligohydramnios, peel, mesenteric edema, fixed and dilated bowel with loss of peristalsis and small wall defect were considered ultrasonographic markers associated with poor prognosis. Outcome variables included: length-of-stay, complications, nutritional and respiratory factors. Non-parametric statistical analysis were used with p < 0,05 regarded as significant. RESULTS: Clinical charts of 30 patients with gastroschisis were reviewed (17M/13F). Gestational age at diagnosis was 20 (12-31) and at delivery 36 (31-39) weeks (33% of the patients over 36+3 weeks). A 73% of the patients presented at least one ultrasonographic marker factor during follow-up. Univariate analysis showed that mesenteric edema was associated with poor outcome variables: short-bowel syndrome (p= 0,000), PN-dependence (p= 0,007) and intestinal atresia (p= 0,02). The remaining risk factors analysed, including late delivery (> 36+3 weeks) were not associated with length-of-stay, ventilatory support, digestive autonomy, complications or mortality. CONCLUSIONS: Neither the presence of ultrasonographic markers classically associated with unfavorable outcomes, nor early delivery (< 36 weeks) resulted in worse postnatal outcome. Mesenteric edema was the only alarming ultrasound marker and that may suggest the need of closer follow-up.

INTRODUCCION: La gastrosquisis es una anomalía congénita de fácil diagnóstico prenatal y pronóstico postnatal variable. Nuestro objetivo es determinar si los signos ecográficos prenatales o el momento del parto se relacionan con peor pronóstico postnatal. PACIENTES Y METODOS: Se realiza un estudio retrospectivo de la cohorte de pacientes con gastrosquisis diagnosticados entre 2005-2014, registrando las ecografías prenatales, edad gestacional al parto y evolución postnatal. Se valoraron los hallazgos ecográficos prenatales: oligohidramnios, peel, edema mesentérico, asas fijas, aperistálticas y/o dilatadas y defecto pequeño de pared. Se consideraron variables resultado: la estancia hospitalaria, complicaciones, mortalidad y factores nutricionales y respiratorios. Se utilizaron pruebas no paramétricas, considerándose significativo un valor p < 0,05. RESULTADOS: Se analizaron 30 pacientes con gastrosquisis (17V/13M). La edad gestacional al diagnóstico fue de 20 (12-31) y al parto de 36 (31-39) semanas (33% mayores de 36+3 semanas). El 73% de los pacientes presentaron al menos un signo ecográfico de mal pronóstico. El análisis univariante asoció el edema mesentérico al síndrome de intestino corto (p= 0,000), falta de autonomía digestiva (p= 0,007) y mayor incidencia de atresia (p= 0,02). El resto de los factores, incluyendo la edad gestacional > 36+3 semanas, no tuvieron repercusión negativa en términos de estancia, asistencia respiratoria, autonomía digestiva, complicaciones o mortalidad. CONCLUSIONES: Ni la presencia de signos ecográficos considerados generalmente como desfavorables ni la tendencia a acercar el parto a la semana 36ª tienen repercusiones significativas en el curso postnatal. Únicamente el edema mesentérico parece un signo alarmante que sugiere la necesidad de aumentar la frecuencia de intervenciones (ecografías, pruebas de bienestar fetal).

Neonatal intestinal obstruction associated with situs inversus totalis: two case reports and a review of the literature.

BACKGROUND: The association of neonatal intestinal obstruction with situs inversus totalis is extremely rare with only few cases reported in the literature to date. This association poses dilemmas in management. We present two such cases (of Indian origin), and briefly discuss the pertinent literature and measures to prevent unfavorable outcome. CASE PRESENTATION: Case 1: a 1-month-old preterm (1300 g) male neonate belonging to Hindu (Indian) ethnicity presented with recurrent bile-stained vomiting, non-passage of stools and epigastric fullness. A babygram and upper gastrointestinal contrast studies revealed situs inversus and suggested proximal jejunal obstruction with midgut volvulus. Exploration confirmed situs inversus totalis along with reverse rotation and midgut volvulus. There was a small gangrenous area in the proximal jejunal loop. A Ladd's procedure, resection of the gangrenous jejunal loop, and jejunojejunal anastomosis was performed. Note was made of the unusual appearance of the intestines suggestive either of fibrous or fatty infiltration. Postoperatively, our patient developed septicemia and died. Case 2: a 4-day-old female neonate belonging to Hindu (Indian) ethnicity, small (1320 g) for gestation, presented with history of non-passage of meconium since birth, refusal to accept feeds, and episodes of recurrent bilious vomiting with abdominal distension. A plain radiogram revealed situs inversus and proximal jejunal obstruction. Ultrasonography of her abdomen revealed renal dysplastic changes in both her kidneys. Laparotomy confirmed multiple jejunoileal atresias with situs inversus totalis. Resection anastomoses was performed for multiple atresias. Our patient passed a few pellets of meconium stools postoperatively; feeds were started gradually on the sixth day. Our patient gradually developed oliguria and renal failure, followed by respiratory distress and generalized edema requiring ventilatory support. She died later due to multiorgan failure. CONCLUSIONS: Clinicians should have high index of suspicion for malrotation with midgut volvulus or intestinal atresias in neonates of situs inversus presenting with bilious vomiting. The surgical treatment should follow the same surgical principles. In situs inversus, because of transposition of viscera, midgut volvulus may occur in an anticlockwise direction, hence derotation is performed clockwise. Prognosis was poor in our series because of low birth weight, late presentation, presence of gangrenous locus in the small bowel and development of septicemia in our first case and multiorgan fibrosis/dysplasia in our second case. Early diagnosis and timely referral is paramount for favorable outcome.

[Intestinal complications in twin-to-twin transfusion syndrome (TTTS) treated by laser coagulation (LC)]. / Complicaciones intestinales en el síndrome de trasfusión feto fetal (STFF).

AIM OF THE STUDY: The hemodynamic imbalance due to placental vascular anastomoses in TTTS but also vascular changes generated after intrauterine treatment may lead to hypoxic-ischemic complications. Different intestinal complications in TTTS are reviewed in this paper. METHODS: Retrospective review of TTTS cases treated by laser coagulation (LC) from 2012-2015. Demographic data, fetal therapy, prenatal diagnosis (US, MRI) and perinatal outcome were recorded. We describe cases with intestinal complications and their postnatal management. Results are expressed by median and range. RESULTS: 29 monochorionic pregnancies with TTTS were treated (23 LC, 4 cord occlusions and 2 cord occlusions after LC). The diagnosis was made at 19 (16-26) weeks and 86% presented stage of Quintero ≥ II. In 70% of mothers survived at least one fetus with a median of 31 (24-37) weeks at birth. Four patients had intestinal complications (1 jejunal atresia, 2 ileal atresia, 1 perforated necrotizing enterocolitis), half of them had prenatal diagnosis. Postnatal resections of the affected segments and ostomies were performed. Intestinal transit was restored and there were no severe digestive sequelae after 21 (8-38) months of follow up. CONCLUSIONS: Different types of intestinal complications were associated with TTTS and LC. US and MRI enable prenatal diagnosis of these complications and this allows prompt decisions after birth.

INTRODUCCION: El desequilibrio hemodinámico secundario a la presencia de anastomosis vasculares placentarias en el STFF así como los cambios hemodinámicos generados durante y tras su tratamiento mediante fotocoagulación con láser (FC) puede dar lugar a complicaciones hipóxico-isquémicas en distintos sistemas. Revisamos nuestra experiencia en el tratamiento del STFF con FC y presentamos las complicaciones intestinales encontradas. MATERIAL Y METODOS: Estudio retrospectivo de casos tratados intraútero entre 2012 y 2015. Recogimos datos sociodemográficos, terapia fetal, pruebas diagnósticas prenatales (ecografía, RM) y resultados perinatales. Expresamos las medidas en medianas y rangos. RESULTADOS: Se procedió al tratamiento intraútero de 29 gestaciones monocoriales complicadas con STFF (23 FC, 4 oclusiones de cordón y 2 FC seguidas de oclusión). La edad gestacional en el procedimiento fue 19 (16-26) semanas y en el 86% de los casos se trataba de un estadio de Quintero ≥ II. El 70% de las madres tuvieron al menos 1 recién nacido vivo, con mediana de edad gestacional al parto de 31 (24-37) semanas. Presentaron problemas intestinales 4 pacientes (1 atresia yeyunal, 2 atresias ileales, 1 enterocolitis necrotizante con perforación), con sospecha prenatal diagnóstica en 2 de ellos. Postnatalmente se realizó resección del segmento afecto y ostomía. Actualmente se ha restablecido el tránsito intestinal en todos sin secuelas digestivas graves tras 21(8-38) meses de seguimiento. CONCLUSIONES: Hemos descrito distintos tipos de complicaciones intestinales asociadas al STFF y/o su tratamiento con FC. Es posible hacer el diagnóstico prenatal de dichas complicaciones mediante ecografía y RM. Su conocimiento pone al cirujano en alerta y es importante en la toma de decisiones postnatales.

Two novel RFX6 variants in siblings with Mitchell-Riley syndrome with later diabetes onset and heterotopic gastric mucosa.

Mitchell-Riley syndrome, an autosomal recessive disorder caused by mutations in the RFX6 gene, is defined as a combination of neonatal diabetes mellitus and serious congenital gastrointestinal defects. We describe Mitchell-Riley syndrome in two sisters with two novel compound heterozygous variants in the RFX6 gene: c.1154G > A, p.(Arg385Gln), and c.1316_1319delTCTA, p.(Ile439Thrfs*13). Both sisters present milder forms of the syndrome, likely due to possible residual activity of the p.Arg385Gln variant, which is localized in a dimerization domain of the RFX6 transcription factor. We propose that the prognosis is dependent on patient RFX6 genotype and possible residual activity of RFX6 transcription factor. Both sisters had atypical later onset of diabetes, at 2 years and 10 months and 2 years and 7 months, respectively. This supports the need of extending the definition of diabetes in Mitchell-Riley syndrome from neonatal to childhood onset and regular glyceamia check in patients with gastrointestinal tract malformations typical for Mitchell-Riley syndrome. The clinical course in both sisters improved significantly after surgical removal of parts of the small intestine with heterotopic gastric mucosa. We suggest that gastric mucosa heterotopy is an important actionable part of Mitchell-Riley syndrome and could have been responsible for the malabsorption, failure to thrive and severe anemia present in previously reported patients with Mitchell-Riley syndrome.

Maternal occupational exposure to ionizing radiation and major structural birth defects.

BACKGROUND: Ionizing radiation (IR) is known to be carcinogenic and mutagenic, but little is known about the association between maternal occupational exposure to IR and birth defects. METHODS: We studied 38,009 mothers who participated in the National Birth Defects Prevention Study and delivered between 1997 and 2009. We assessed odds ratios [ORs] for the association between maternal occupations with potential exposure to IR and 39 birth defects. RESULTS: We observed significant odds ratios (ORs) for isolated hydrocephaly (adjusted OR [AOR], 2.1; 95% confidence interval [CI], 1.1-4.2), isolated anotia/microtia (AOR, 2.0; 95% CI, 1.0-4.0), isolated colonic atresia (crude OR, 7.5; 95% CI, 2.5-22.3), isolated omphalocele (AOR, 2.3; 95% CI, 1.1-4.6) and isolated anencephaly (crude OR, 0.23; 95% CI, 0.06-0.94). We also observed a nonsignificant OR for birth defects in aggregate (AOR, 2.0; 95% CI, 0.9-4.6) among mothers with potential occupational exposure to fluoroscopy. CONCLUSION: We assessed 39 birth defects, observing that maternal occupations with potential exposure to IR were associated with a significantly increased risk for 4 birth defects and a significantly protected risk for 1 birth defect. These results should be interpreted cautiously because our measurement of exposure is qualitative, some of these associations may be due to occupational exposures that are correlated with IR and some may be due to chance. However, these findings serve as the first evaluation of these relationships in a large study and may be useful for generating hypotheses for future studies.

Acquired ileal atresia induced by adhesive intestinal obstruction.

Three female infants, aged 13, 7 and 18 mo respectively with acquired ileal atresia induced by adhesive small bowel obstruction are reported. Case 1 was diagnosed with urachal cyst and cyst excision was performed when she was 7-mo-old. Case 2 was diagnosed with mesenteric cyst and cyst excision was performed by laparoscopic-assisted procedure when she was 3-mo-old. Case 3 had no history of abdominal operation previously. At laparotomy ileal atresia induced by adhesive band was found.