Delayed diagnosis of imperforate anus: an unacceptable morbidity.

PURPOSE: Diagnosis of imperforate anus is usually made shortly after birth with physical examination. Nonetheless, a significant number of patients have presented beyond the neonatal period without recognition of anorectal malformation. We reviewed our experience of anorectal malformations, with particular emphasis on the timing of diagnosis. METHODS: This retrospective study reviewed patients with imperforate anus between 1999 and 2009. Documentation included gender, time of diagnosis, complications, and classification. Delayed diagnosis was defined as diagnosis made >48 h of life. RESULTS: Ninety-nine patients with imperforate anus were managed, of whom 21 presented with delayed diagnosis. The condition was classified as perineal (n = 11), recto-urethral (n = 3), vestibular fistula (n = 3) and without fistula (n = 4). Patients showed at least one of the following symptoms: abdominal distension (61.9%), bilious vomiting (38.1%), delayed passage of meconium (19.0%), and sepsis (9.5%). Delayed diagnosis was made on day 4 in median (range 3-43). This delay was associated with bowel perforation in 9.5%. CONCLUSION: Despite routine physical examination postpartum, one in five neonates born with imperforate anus had a delayed diagnosis. This delay may lead to avoidable, serious morbidity. Therefore, we emphasise the practice of thorough perineal examination during the initial newborn examination to identify the presence of anorectal malformations.

A novel association of gastric ischaemia and aortic coarctation.

We report a newborn who presented with acute abdominal distension secondary to gastric ischaemia with an associated undiagnosed coarctation of the descending aorta. This is the first description of such a previously unrecognised association, which is discussed further with reference to the current literature.

Susceptibility to experimental biliary atresia linked to different hepatic gene expression profiles in two mouse strains.

AIM: To compare hepatic gene expression during the development of experimental biliary atresia (BA) in two different mouse strains. METHODS: Balb/c mice and C57Black/6 (Black/6) mice were infected with rhesus rotavirus (RRV) postpartum, clinical signs of BA and survival were noted. Liver sections were assessed for cluster of differentiation antigen (CD) 3, CD4 and CD8 expression, and the hepatic virus load was determined. Second, mice of both strains were sacrificed three days after infection. Isolated hepatic RNA was subjected to gene expression analysis using Affymetrix Gene Chip MOE 430 2.0. RESULTS: The incidence of BA was significantly lower in Black/6 mice compared to Balb/c mice (13.5% vs. 67%, P < 0.05). The mean virus titers were higher in mice with BA compared to mice without BA. Different gene profiles three days after virus infection were noted, with differential expression of 201 genes, including those regulating apoptosis, nucleic acid binding, transport function and particularly the immune response (chemokine C-C motif ligand 2, toll-like receptor 3, CD antigen 14, chemokine (C-X-C motif) ligands 10 and 11). This correlated with a significant increase of CD4 positive cells only in Balb/c mice with BA compared to healthy mice (13.5 vs. 5.0; P < 0.05). Black/6 mice did not exhibit any significant increase of CD3 or CD4 leukocytes despite cholestasis. CONCLUSION: The different susceptibility to experimental BA was associated with an increase of CD4 T-cells in the liver of Balb/c mice, which is linked to different gene profiles at the onset of bile duct obstruction.

Endoscopic retrograde cholangiopancreaticography prior to explorative laparotomy avoids unnecessary surgery in patients suspected for biliary atresia.

BACKGROUND/AIMS: Timely diagnosis of biliary atresia (BA) requires key investigations that are less invasive but as accurate as possible. Non-invasive imaging preselects patients before explorative laparotomy is performed. The purpose of this prospective study was to evaluate the accuracy of endoscopic retrograde cholangiopancreaticography (ERCP) in these patients and to discuss its relevance to future diagnostic guidelines in neonatal jaundice. METHODS: Over a 7-year period, ERCP was routinely performed in cholestatic patients less than 6 months of age suspected for an extrahepatic origin of cholestasis, most likely BA. Endoscopic diagnosis was correlated with intraoperative findings. RESULTS: In 140 consecutive patients (mean age: 60 days; weight: 4 kg), ERCP excluded BA in 34 (25%) but failed in 18 newborns (13%) for technical reasons. The average procedure time was 23 min, and no severe complications occurred. Explorative laparotomy was performed in 106 patients and revealed BA in 80 cases. In this series, the sensitivity of ERCP for diagnosing biliary atresia was 92% and specificity was 73%. CONCLUSIONS: In preselected patients, ERCP is not an alternative to non-invasive imaging, but it avoids unnecessary surgical procedures in almost 25% of the cases. Hence, ERCP is recommended prior to explorative laparotomy in all patients suspected for BA.

Conversion of a neonatal hepatic hemangioma to focal nodular hyperplasia.

Hepatic hemangioma and focal nodular hyperplasia are both frequently observed benign lesions of the liver. Whereas hepatic hemangioma is the most frequent benign liver tumor in children, focal nodular hyperplasia occurs predominantly in adult patients. Concomitance of both entities has been described in adults, suggesting a similar pathogenesis. We report on a 6-month-old child with a continuously shrinking hepatic hemangioma after interventional therapy and a growing hepatic mass 5 years later, which emerged as focal nodular hyperplasia at the site of the former hemangioma. Diagnostic and therapeutic strategies regarding this patient are discussed. The present case supports the theory that these two entities may share a similar pathomechanism.

Impact of mitochondria and NADPH oxidases on acute and sustained hypoxic pulmonary vasoconstriction.

Hypoxic pulmonary vasoconstriction (HPV) matches lung perfusion with ventilation to optimize pulmonary gas exchange. However, it remains unclear whether acute HPV (occurring within seconds) and the vasoconstrictor response to sustained alveolar hypoxia (developing over several hours) are triggered by identical mechanisms. We investigated the effect of mitochondrial and NADPH oxidase inhibitors on both phases of HPV in intact rabbit lungs. These studies revealed that the sustained HPV is largely dependent on mitochondrial complex I and totally dependent on complex IV, whereas NADPH oxidase dependence was only observed for acute HPV. These findings were reinforced by an alternative approach employing lungs from mice deficient in the NADPH oxidase subunit p 47(phox). In these mice (which lack a subunit suggested to be important for the function of most NADPH oxidase isoforms), but not in gp 91(phox)-deficient mice (which represent only one isoform of NADPH oxidases), acute HPV was significantly reduced, while non-hypoxia-induced vasoconstrictions elicited by the thromboxane mimetic U46619 were not affected. We concluded that the acute phase and the sustained phase of HPV are differentially regulated, with NADPH oxidase activity predominating in the acute phase, while a strong dependence on mitochondrial participation was observed for the second phase.