ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development.

Previously genome-wide association methods in patients with classic bladder exstrophy (CBE) found association with ISL1, a master control gene expressed in pericloacal mesenchyme. This study sought to further explore the genetics in a larger set of patients following-up on the most promising genomic regions previously reported. Genotypes of 12 markers obtained from 268 CBE patients of Australian, British, German Italian, Spanish and Swedish origin and 1,354 ethnically matched controls and from 92 CBE case-parent trios from North America were analysed. Only marker rs6874700 at the ISL1 locus showed association (p = 2.22 × 10-08). A meta-analysis of rs6874700 of our previous and present study showed a p value of 9.2 × 10-19. Developmental biology models were used to clarify the location of ISL1 activity in the forming urinary tract. Genetic lineage analysis of Isl1-expressing cells by the lineage tracer mouse model showed Isl1-expressing cells in the urinary tract of mouse embryos at E10.5 and distributed in the bladder at E15.5. Expression of isl1 in zebrafish larvae staged 48 hpf was detected in a small region of the developing pronephros. Our study supports ISL1 as a major susceptibility gene for CBE and as a regulator of urinary tract development.

Outcome after Computer-Assisted (Robotic) Nissen Fundoplication in Children Measured as Pre- and Postoperative Acid Reducing and Asthma Medications Use.

PURPOSE: This study aims to report the clinical outcome of computer-assisted fundoplication (CAF) in children. METHODS: As our center changed policy to using computer-assisted surgery only, a prospectively studied cohort of 40 children underwent CAF, during the period from January 2006 through May 2013. The collected data include patient demographics and postoperative complications as well as medication, 24-hour pH measurements and DeMeester scores before and after surgery. RESULTS: In the studied group, the median percentage of the duration of the 24-hour pH < 4 decreased postoperatively from 11 (range, 5-39) to 1% (range, 0-12) (p < 0.001); the DeMeester score decreased from 40 (range, 17-137) to 5 (range, 1-42) (p < 0.001). All 40 patients required antireflux medication before the fundoplication. This number decreased significantly to 8 (20%) after the fundoplication (p < 0.001). Before the fundoplication, 22 children (55%) were using asthma medication and 12 (30%) after the fundoplication (p = 0.04). CONCLUSIONS: The CAF significantly reduced the acid reflux from the stomach to the esophagus and the use of antireflux as well as asthma medication during the median observation period of 5 years. The evidence of advantages compared with conventional laparoscopic fundoplication remain to be confirmed.

Bowel symptoms in children with anorectal malformation - a follow-up with a gender and age perspective.

BACKGROUND: Gender specific outcome for children with anorectal malformations (ARM) is rarely reported although it is important for medical care and in parent counseling. PURPOSE: To assess bowel function according to the Krickenbeck system in relation to ARM-subtype, gender and age. METHOD: All children born with ARM in 1998-2008 and referred to two centers in two different countries were followed up. The bowel function in 50 girls and 71 boys, median age 8 years, was analyzed. RESULTS: Among those with a perineal fistula, incontinence occurred in 42% of the females and in 10% of the males (p=0.005) whereas constipation occurred in 62% of the females and 35% of the males (p<0.001). No bowel symptoms differed between the females with perineal and vestibular fistulas (p>0.3 for every symptom). Sacral malformations were associated with incontinence only in males with rectourethral fistulas. Constipation among the males differed between the age groups: 58% versus 26% (p=0.013). Bowel symptoms did not change with age among the females. CONCLUSION: Gender differences in outcome for children with ARM must be considered. Males with perineal fistulas had less incontinence and constipation than the females with perineal fistulas. The females with perineal and vestibular fistulas had similar outcomes.

A case with bladder exstrophy and unbalanced X chromosome rearrangement.

INTRODUCTION: Bladder exstrophy is a rare congenital malformation of the bladder and is believed to be a complex disorder with genetic and environmental background. We describe a young adult female with an isolated bladder exstrophy and with an X chromosome aberration. Patients and METHODS: Karyotyping identified an X chromosome rearrangement that was further characterized with array comparative genomic hybridization (CGH) and confirmed by multiplex ligation-dependent probe amplification and fluorescence in situ hybridization (FISH) analysis. RESULTS: The identified X chromosome rearrangement in our index patient consists of a gain of chromosomal material in region Xq26.3- > qter and loss in region Xp22.12- > pter. This aberration was also carried by her mother and sister, none with bladder exstrophy. All three have a disproportionate short stature, as expected due to the deletion of one of the copies of the SHOX gene on Xp22.3. X-inactivation studies revealed a complete skewed inactivation pattern in carriers. Crossover events in the maternal germline furthermore resulted in different genetic material on the rearranged X chromosome between the index patient and her sister. CONCLUSION: Our findings suggest an X-linked genetic risk factor for bladder exstrophy.

Adolescents with anorectal malformation: physical outcome, sexual health and quality of life.

BACKGROUND: The necessity of referring adolescents with anorectal malformation (ARM) from pediatric units to adult care is unclear. The issue requires knowledge about the health of the adolescent. OBJECTIVE: To examine the physical outcome, sexual health and quality of life (QoL) in adolescents with ARM. METHODS: At medical counseling, 24 adolescents with ARM, 15-21 years of age, answered questionnaires about physical outcome according to the Krickenbeck follow-up and QoL according to SF 36 and gastrointestinal quality of life (Giqli). Matched control groups were used; 15 adolescents participated in deep interviews about sexual health and body imaging. RESULTS: Fecal soiling, constipation and gas incontinence were much higher for ARM patients compared with controls (p<0.05). QoL regarding large bowel function was lower for both genders compared with controls (p<0.05). Females scored lower in physically related QoL (p<0.05). Social and sexual adaption to the symptoms was obvious in the deep interviews. CONCLUSION: Adolescents with ARM have considerable intestinal symptoms, which influence QoL and require adaption in intimate situations. A referral to adult care seems to be important, and continuous cooperation between the pediatric surgeon and adult care is suggested.

Endoscopically placed rectourethral guidewire facilitates the reconstruction of anus in children with anorectal malformations: a case report.

The aim of this report is to present a technical detail of use in the management of an anorectal malformation (ARM). A boy with ARM and a fistula to the urethra was operated on with a posterior sagittal anorectoplasty (PSARP). Before the PSARP operation, a videoendoscopy was performed through the distal stoma down to the distal end of the rectum. The rectourethral fistula was identified and a guidewire was passed through the endoscope, through the fistula, and out through the urethra. The endoscopically placed rectourethral guidewire was used as a landmark and facilitated the PSARP operation.

Paediatric computer-assisted retroperitoneoscopic nephrectomy compared with open surgery.

PURPOSE: Computer-assisted laparoscopic surgery (CALS) in children is increasingly used and has proven to be feasible and safe. However, its full potential remains unclear and clinical comparative studies hardly exist. The aim of this study was to prospectively evaluate our experience with CALS for performing retroperitoneal nephrectomies in children when compared with controls undergoing open surgery in terms of safety, operative time, blood loss, opoid requirements, the duration of hospital stay and complications. CHILDREN AND METHODS: Computer-assisted retroperitoneoscopic nephrectomy was undertaken in ten consecutive children, mean age at the time of surgery 6.4 (SD ± 4.5) years, and compared with a retrospectively collected control group of all other children, mean age 3.9 (SD ± 4.6) years, who underwent the same procedure by conventional open surgery between the years 2005 and 2009. The endpoint of the study was 1 month postoperatively. RESULTS: Nephrectomies were performed in all the children and no child was excluded from the study. There was no per-operative complication in any of the groups. The median (range) operative time was 202 (128-325) and 72 (44-160) min for the CALS and open group, respectively. The blood loss was minimal (<20 ml) for all the patients. The postoperative opoid requirements did not differ. The median (range) postoperative hospital stay was 1 (1-4) and 2 (1-7) days for the CALS and the open group, respectively. One complication in the form of an urinoma appeared 5 days after surgery in the CALS group. CONCLUSION: Computer-assisted retroperitoneoscopic nephrectomy is a safe, feasible and effective procedure in children. Even though operative times are longer the patients benefit from the lower morbidity, improved cosmetics and shorter hospitalization associated with the minimally invasive approach.

22q11.2 microduplication in two patients with bladder exstrophy and hearing impairment.

Bladder exstrophy is a congenital malformation of the bladder and urethra. The genetic basis of this malformation is unknown however it is well known that chromosomal aberrations can lead to defects in organ development. A few bladder exstrophy patients have been described to carry chromosomal aberrations. Chromosomal rearrangements of 22q11.2 are implicated in several genomic disorders i.e. DiGeorge/velocardiofacial- and cat-eye syndrome. Deletions within this chromosomal region are relatively common while duplications of 22q11.2 are much less frequently observed. An increasing number of reports of microduplications of this region describe a highly variable phenotype. We have performed array-CGH analysis of 36 Swedish bladder exstrophy patients. The analysis revealed a similar and approximately 3 Mb duplication, consistent with the recently described 22q11.2 microduplication syndrome, in two unrelated cases with bladder exstrophy and hearing impairment. This finding was confirmed by multiplex ligation-dependent probe amplification (MLPA) and FISH analysis. Subsequent MLPA analysis of this chromosomal region in 33 bladder exstrophy patients did not reveal any deletion/duplication within this region. MLPA analysis of 171 anonymous control individuals revealed one individual carrying this microduplication. This is the first report of 22q11.2 microduplication associated with bladder exstrophy and hearing impairment. Furthermore the finding of one carrier among a cohort of normal controls further highlights the variable phenotype linked to this microduplication syndrome.

Robotic fundoplication in children.

Since January 2006, robotic assistance has been used for performing minimal invasive laparoscopic fundoplications in children. These patients were compared with those operated on with either the open surgical technique or the laparoscopic procedure. The first six children operated on with a fundoplication using the operation robot, da Vinci Surgical System from Intuitive Surgical, were included prospectively. As controls, data from the latest six children operated on using the open surgical procedure and the latest six children operated on using the minimal invasive laparoscopic technique were selected retrospectively. All the patients were operated on due to gastroesophageal reflux and were comparable in the De Meester score. The main outcome measures were the operating time, the use of postoperative analgesics, the duration of the postoperative hospital stay and the short-term outcome. There was no significant difference between the three groups concerning age, body weight and preoperative 24 h pH measurement. The mean operating time for the robotic group, 213 min, was the longer one, but the operating time for the latest four patients in the robotic group was similar to that for the laparoscopic group, 189 min. The postoperative hospital stay was shorter and a reduction in the use of analgesics postoperatively was noted. The reduction in the postoperative hospital stay and in the use of analgesics had been already noted with the introduction of the minimal invasive laparoscopic technique. There was no difference in short-term clinical outcome; the gastroesophageal reflux symptoms disappeared in all the patients. Robot-assisted laparoscopic fundoplication is comparable with the standard laparoscopic surgical procedure in terms of duration of operation, postoperative hospital stay, use of postoperative analgesics and short-term clinical outcome. The robotic surgery adds qualities to the surgical work when compared with open or laparoscopic surgery. These include better visualisation for the surgeon and greater precision in the movements of the instruments used.