The orchestration of gene expression and the editing role of microRNA.

In this short educational communication the ESPU Research Committee presents the role of non-coding RNA and how these can affect gene expression. In particular we discuss the role of microRNA on post transcriptional changes and how these may cause pathological conditions within Pediatric Urology and how microRNA could be useful in future clinical practice.

Primary bladder exstrophy closure in neonates: challenging the traditions.

PURPOSE: We describe a novel approach to neonatal bladder exstrophy closure that challenges the role of postoperative immobilization and pelvic osteotomy. MATERIALS AND METHODS: We reviewed the primary management of bladder exstrophy at our institutions between 2007 and 2011. In particular we compared postoperative management in the surgical ward using epidural analgesia to muscle paralysis and ventilation in the intensive care unit. Clinical outcome measures were time to full feed, length of stay, postoperative complications and redo closure. Cost-effectiveness was also evaluated using hospital financial data. Data are expressed as median (range). Significance was explored by Fisher exact test and unpaired t-test. RESULTS: A total of 74 patients underwent primary closure without osteotomy. Successful closure was achieved in 70 patients (95%). A total of 48 cases (65%) were managed on the ward (group A) and 26 (35%) were transferred to the intensive care unit (group B). The 2 groups were homogeneous for gestational age (median 39 weeks, range 27 to 41) and age at closure (3 days, 1 to 152). Complications requiring surgical treatment were noted in 4 patients (8.3%) in group A and 3 (11.5%) in group B (p = 0.609). Length of stay was significantly shorter for the group managed on the ward (11 vs 18 days, p <0.0001). Median costs were $42,732 for patients admitted to the intensive care unit and $16,214 for those admitted directly to the surgical ward (p <0.0001). CONCLUSIONS: Primary closure of bladder exstrophy without lower limb immobilization and osteotomy is feasible. Postoperative care on the surgical ward using epidural analgesia results in shorter hospitalization.

The role of parenteral nutrition following surgery for duodenal atresia or stenosis.

PURPOSE: In our institution, some children routinely receive parenteral nutrition (PN) following surgery for duodenal atresia/stenosis, while others do not. Our aim was to compare growth and infection rate between these two treatment strategies. METHODS: This was a retrospective study of all children undergoing surgery for duodenal atresia/stenosis over 7 years. RESULTS: Of the 54 children, 19 commenced PN soon after surgery (the 'Initial PN' group). Of the remaining 35 children, 13 (37 %) subsequently required PN (the 'Delayed PN' group). The remaining 22 never received PN (the 'Never PN' group). The proportion of patients experiencing clinically suspected sepsis was higher in those receiving PN ('Initial' plus 'Delayed'; 41 %) compared with those who never received PN (14 %; p = 0.04). The 'Initial PN' and 'Never PN' groups did not show a significant change in weight Z score over time. However, the 'Delayed PN' group showed a significant decrease in weight Z scores from the time of operation to the time of achieving full enteral feeds, and failed to catch up by the time of last follow-up. CONCLUSION: Children with duodenal atresia/stenosis can be managed without PN. However, a third of these children subsequently require PN, lose weight centiles, and have a high rate of sepsis.

[Technical aspects of experimental intestinal transplant]. / Aspectos técnicos del trasplante intestinal experimental.

PURPOSE: Our objective is to analyze the variables that influence the outcome of Small Bowel Transplantation (SBT) in rats in an experimental microsurgery program. The surgical technique and perioperative care are described in detail. METHODS: Retrospective study of the SBT in rats conducted in our experimental surgery laboratory from 2002 to 2010. The animals were divided into group A (those who survived more than 48 hours) and group B (those who died earlier without justificable cause). We compared in both groups: number of transplants performed by the surgeon, warm ischemia time, cold ischemia time and duration of the procedure. RESULTS: Five surgeons with different degrees of microsurgical training participated in the study. A total of 521 SBT were performed with an overall survival of 48%. The first successful transplant was performed after a median of 46 (25-68) transplants. Total procedure time (3.5 vs 2.9 hours) and warm ischemia time (51 vs 35 minutes) were higher in group B (p < 0.05). DISCUSSION: The number of transplants required for learning the technique is high. However, survival is acceptable when the time needed for vascular anastomosis is reduced. The SBT in rats is a valuable model for surgical training and research of the phenomena related to SBT.

Aspectos técnicos del trasplante intestinal experimental / Technical aspects of experimental intestinal transplant

Introducción. Nuestro objetivo es analizar las variables que in-fluyen en los resultados del trasplante de intestino delgado (TID) en ratas en un programa de microcirugía experimental. Se describe con detalle la técnica quirúrgica y los cuidados perioperatorios con objeto de favorecer el aprendizaje de la técnica. Material y métodos. Estudio retrospectivo de los TID en ratas realizados en nuestro laboratorio de cirugía experimental desde el año 2002 al 2010. Dividimos los animales en grupo A (los que sobrevivieron más de 48 horas) y grupo B (los que fallecieron precozmente sin causa justificable). Comparamos en ambos grupos: número de trasplantes realizados por el cirujano, tiempo de isquemia caliente, tiempo de isquemia fría y duración total del procedimiento. Resultados. Cinco cirujanos con distinto grado de formación microquirúrgica participaron en el estudio. Se realizaron en total 521 TID con una supervivencia global del 48%. El primer trasplante con éxito se realizó tras una mediana de 46 (25-68) trasplantes. El tiempo total del procedimiento (3,5 vs. 2,9 horas) y el tiempo de isquemia caliente (51 vs. 35 minutos) fueron superiores en el grupo B (p<0,05). Discusión. El número de trasplantes necesarios para el aprendizaje de la técnica es elevado. Sin embargo, la supervivencia es aceptable al reducir el tiempo empleado en las anastomosis vasculares. El TID en ratas constituye un modelo muy valioso para la formación del cirujano y para la investigación de los fenómenos relacionados con el TID (AU)

Purpose. Our objective is to analyze the variables that influence the outcome of Small Bowel Transplantation (SBT) in rats in an experimental microsurgery program. The surgical technique and perioperative care are described in detail. Methods. Retrospective study of the SBT in rats conducted in our experimental surgery laboratory from 2002 to 2010. The animals were divided into group A (those who survived more than 48 hours) and group B (those who died earlier without justificable cause). We compared in both groups: number of transplants performed by the surgeon, warm ischemia time, cold ischemia time and duration of the procedure. Results. Five surgeons with different degrees of microsurgical training participated in the study. A total of 521 SBT were performed with an overall survival of 48%. The first successful transplant was performed after a median of 46 (25-68) transplants. Total procedure time (3.5 vs 2.9 hours) and warm ischemia time (51 vs 35 minutes) were higher in group B (p<0.05).Discussion. The number of transplants required for learning the technique is high. However, survival is acceptable when the time needed for vascular anastomosis is reduced. The SBT in rats is a valuable model for surgical training and research of the phenomena related to SBT (AU)

Maldevelopment of the cerebral cortex in the surgically induced model of myelomeningocele: implications for fetal neurosurgery.

PURPOSE: The purpose of this study is to describe the malformations of cortical development detected in a model of cerebrospinal fluid (CSF) leakage and the influence of surgical closure technique on developmental outcome. METHODS: Using a surgically induced model of myelomeningocele (MMC) in sheep, we studied the effects of different repair methods upon the development of hydrocephalus, the presence of the Arnold-Chiari II (AC-II) hindbrain malformation, and cerebral cortex developmental anomalies using gross and histologic (hematoxylin and eosin and Nissl staining) study techniques. RESULTS: A malformed cerebral cortex, including 2 anomalous cortical folding patterns, and lower brain weights were observed in the untreated animals. Hydrocephalus and AC-II malformations were also found in this group. These malformations were mostly prevented with prenatal 2-layer closure. CONCLUSIONS: Cerebral cortical malformations and hydrocephalus, in addition to the AC-II hindbrain malformation, are disorders caused by fetal CSF leakage. These malformations were prevented with the technique of MMC closure currently used in humans. Both observations magnify the importance of the second hit associated with chronic CSF leakage, in addition to the primary defect causing the MMC, in the development of the malformation complex.

Brain malformations in the sheep model of myelomeningocele are similar to those found in human disease: preliminary report.

PURPOSE: To examine if brain malformations, similar to those which account for cognitive disorders seen in human disease, are present in an ovine model of myelomeningocele (MMC). METHODS: An MMC-like lesion was surgically created in 16 fetal lambs between 60 and 80 days of gestation. Ten did not undergo fetal repair (group A), 2 were repaired with an open two-layer closure (group B), 2 with open bioglue coverage (group C) and 2 with fetoscopic coverage (group D). Lambs were killed and their brains were examined. Two brains from normal unoperated lambs served as controls. RESULTS: Thirteen lambs died in utero (81%). Two lambs in group A and 1 in group B were delivered at term. Group A brains showed hydrocephalus and extensive areas of polymicrogyria. There was also an extensive denudation of the ependymal lining under the polymicrogyric areas and the corpus callosum was thinner than normal. No hindbrain herniation was observed. Brains from group B and the control did not show any of these abnormalities. CONCLUSIONS: Some of the central nervous system abnormalities associated to MMC in human patients are also found in the uncorrected fetal lamb model of MMC but not in the only survivor to intrauterine coverage. Further studies are necessary to ascertain if these abnormalities can be prevented by coverage of the defect.