Tomoki Tsuda

Ultrasonographic detection of intrauterine intussusception resulting in ileal atresia complicated by meconium peritonitis

Abstract A neonate with ileal atresia (IA) complicated by meconium peritonitis (MP) whose prenatal ultrasonography (US) detected an intrauterine intussusception (IUI) is reported. Fetal ascites, dilated bowel loops, and abdominal calcifications were identified on serial US from 25 weeks of gestation. Intestinal loops with high echogenecity and a “target-like” appearance suggestive of IUI were detected in the right lower quadrant. The 2,680-g male was delivered vaginally at term and underwent a laparotomy. Fibrous adhesions and small calcifications were scattered throughout the peritoneal cavity. IA (interrupted type) was confirmed 17.0 cm cranial to the ileocecal valve (ICV). An ileo-ileal intussusception was also found between 16.5 cm and 9.0 cm cranial to the ICV. Partial resection of the ileum and an ileo-ileal anastomosis was performed. The postoperative course was uneventful. In this case, the pathological process of IUI resulting in IA and MP was demonstrated sonographically by identifying the “target-like” appearance in the fetus.

Laparoscopic versus open abdominoperineal rectoplasty for infants with high-type anorectal malformation

BACKGROUND/PURPOSE There has not been any study comparing laparoscopic abdominoperineal rectoplasty (ARP) with open ARP. This study investigated the true benefits of the laparoscopic approach in infants with high anorectal malformation. PATIENTS AND METHODS A retrospective analysis was performed in 28 infants with high anorectal malformation treated between 1990 and 2007. Fifteen were treated by open ARP, and 13 were treated by laparoscopic ARP. Surgical durations, amount of bleeding, complications, anorectal pressure measurements, barium enema study, and clinical assessment were compared between the 2 groups. RESULTS The amount of intraoperative bleeding was significantly less in laparoscopic ARP (12 ± 11 g) than in open ARP (65 ± 44 g) (P = .003). Anal resting pressure was 34 ± 9 cm H(2)O after laparoscopic ARP and 31 ± 14 cm H(2)O after open ARP. Anorectal reflex was positive in 1 (7%) of 15 after open ARP and 3 (23%) of 13 after laparoscopic ARP. There was no significant difference in barium enema study and clinical assessment between the 2 groups. With regard to postoperative complications, mucosal prolapse occurred in 10 (67%) of 15 after open ARP and in none of 13 after laparoscopic ARP (P = .003). CONCLUSION Benefits of the laparoscopic approach were reduced intraoperative bleeding and a lower incidence of postoperative anal mucosal prolapse. These results indicate that minimal dissection of the mesorectum in laparoscopic ARP may provide those better outcomes.

Bowel function after surgery for anorectal malformations in patients with tethered spinal cord

Tethered spinal cord (TC) is an anomaly frequently recognized in association with anorectal malformations (ARM). However, the influence of TC on bowel function in children with ARM remains unknown. Furthermore, there are few studies that have assessed anorectal function in children with ARM and TC. The aim of this study was to evaluate anorectal function in ARM patients with TC using clinical assessment and anorectal manometry. Among 258 patients with ARM, this retrospective investigation included 35 patients who underwent spinal magnetic resonance imaging (MRI) after surgery for ARM. The patients were divided into two groups based on the presence or absence of TC, and bowel function was assessed by Kelly’s clinical score and anorectal manometry. Tethered cord was found in nine of the 35 patients (26%) with ARM. Of the ARM patients, TC was noted in four of 11 (36%) with high type anomalies, one of 8 (13%) with intermediate type anomalies, two of 14 (14%) with low type anomalies, and two of two patients (100%) with cloacal anomalies. Kelly’s clinical score did not significantly differ between the two groups. However, two of the nine patients with TC had poor bowel function (Kelly’s score; 2–0 points). On the contrary, patients without TC did not have poor bowel function. Anorectal manometry did not show a significant difference between patients with and without TC. However, the two patients with TC who had poor bowel function by Kelly’s score had low anal resting pressure, which was essential for achieving fecal continence. In conclusion, the present study showed that tethered cord was more frequently found in patients with more severe anorectal anomalies. Patients with TC were more likely to have poor bowel function, but this did not reach statistical significance.

Results of biofeedback therapy for fecal incontinence in children with encopresis and following surgery for anorectal malformations.

INTRODUCTION Some children with fecal incontinence respond to biofeedback therapy. However, whether they can achieve fecal continence posttherapeutically has not been clarified. We studied the serial results of biofeedback therapy and discuss the necessity of providing repeated biofeedback therapy at home. METHODS Nineteen children with encopresis underwent one session of biofeedback therapy. Seven of 15 children with fecal incontinence that developed after surgery for anorectal malformations underwent three to eight sessions of biofeedback therapy; the remaining 8 underwent one (mean, 2.9) session only. The patients were hospitalized for one session of biofeedback therapy. To monitor the clinical outcome of intervention, we used serial score assessments from three months to two years posttherapeutically. RESULTS Seventeen of 19 (90 percent) patients with encopresis showed clinical improvement after one session of therapy (P < 0.0001). Six months after treatment, however, six of ten (60 percent) patients with encopresis reported recurrent fecal incontinence after one therapeutic session. Clinical improvement was noted in 5 of 15 (33 percent) patients who had fecal incontinence after surgery for anorectal malformations. All five patients showed clinical improvement from six months to two years after several sessions of biofeedback therapy (P < 0.05). CONCLUSIONS Biofeedback therapy is effective in most children with encopresis and in some children with anorectal malformations. However, some patients need repeated sessions of biofeedback therapy to achieve fecal continence. Therefore, a new portable biofeedback apparatus for the treatment of fecal incontinence at home may be helpful.

PCSK5 and GDF11 expression in the hindgut region of mouse embryos with anorectal malformations.

BACKGROUND/PURPOSE Retinoid-mediated signal transduction plays a crucial role in the embryonic development of various organs. We previously reported that retinoic acid induced anorectal malformations (ARM) in mice. GDF11 is a TGFβ superfamily molecule and is cleaved and activated by proprotein convertase subtilisin/kexin 5 (PCSK5). PCSK5 (PC5/6) mutations result in an abnormal expression of Hlxb9 and Hox genes, which include known GDF11 targets that are necessary for caudal development in vertebrate embryos. To determine a possible role of the retinoid-mediated signaling pathway in the pathogenesis of ARM, we investigated whether all-trans retinoic acid (ATRA) affected the expression patterns of PCSK5 and GDF11 in ARM-treated mouse embryos. METHODS Pregnant ICR-Slc mice were administered 100 mg/kg ATRA by gavage on embryonic day (E) 9.0. Embryos were harvested between days E12 and E18, and mid-sagittal sections of the hindgut region were prepared for immunohistochemistry using antibodies against PCSK5 (PC5/6) and GDF11 (GDF8/11). RESULTS Over 95% of the embryos treated with ATRA showed ARM, with rectourethral fistula or rectocloacal fistula, and a short tail. Furthermore, most of these embryos exhibited sacral malformations, tethered spinal cords, and presacral masses resembling those malformations found in caudal regression syndrome. By E14, normal mouse embryos formed a rectum and anus, and the somites behind the hindgut were positive for PC5/6 and GDF8/11. In contrast, in ARM embryos, the somites behind the hindgut were negative for PC5/6 and GDF8/11. CONCLUSION ATRA treatment affected the caudal development in mouse embryos, resulting in anorectal, sacral, and spinal malformations, and inhibited PCSK5 and GDF11 expression in the hindgut region. These findings indicate that the expression of PCSK5 and GDF11, which plays a crucial role in the organogenesis of the hindgut, was disturbed in the hindgut region when retinoid-mediated signaling was disrupted. This study offers a new insight into the pathogenesis of ARM in mice as affected by the interaction between ATRA and PCSK5/GDF11.

Establishment of a rescue program for anorectal malformations induced by retinoic acid in mice.

AIMS OF STUDY Retinoid-mediated signal transduction plays a crucial role in the embryogenesis of various organs. We previously reported the successful induction of anorectal malformations in mice using retinoic acid (RA). Retinoic acid controls the expression of essential target genes for cell differentiation, morphogenesis, and apoptosis through a complicated interaction in which RA receptors form heterodimers with retinoid X receptors. In the present study, we investigated whether the retinoid antagonist, LE135, could prevent the induction of anorectal malformations (ARMs) in mice. METHODS Retinoic acid was intraperitoneally administered as 100 mg/kg of all-trans RA on E9; and then the retinoid antagonist, LE135, was intraperitoneally administered to pregnant ICR strain mice on the eighth gestational day (E8), 1 day before administration of RA (group B) or on E9, simultaneously (group C) with RA administration. All of the embryos were obtained from the uteri on E18. Frozen sections were evaluated for concentric layers around the endodermal epithelium by hematoxylin and eosin staining. RESULTS In group A, all of the embryos demonstrated ARM with rectoprostatic urethral fistula, or rectocloacal fistula, and all of the embryos showed the absence of a tail. In group B, 36% of the embryos could be rescued from ARM. However, all of the rescued embryos had a short tail that was shorter than their hind limb. The ARM rescue rates in group B were significantly improved compared to those in group A (P < .01). In group C, 45% of the embryos were rescued from ARM, but all of the rescued embryos had short tail. The ARM rescue rate in group C was significantly improved compared to that in group A (P < .01). However, there was no significant difference in the ARM rescue rate between group B and Group C. CONCLUSION The present study provides evidence that in the hindgut region, RAR selective retinoid antagonist, LE135, could rescue embryos from ARM. However, the disturbance of all-trans RA acid was limited to the caudal region. Further study to establish an appropriate rescue program for ARM in a mouse model might suggest a step toward protection against human ARM in the future.

Congenital anomalies induced by triamcinolone acetonide in murine embryos.

INTRODUCTION We have studied the morphogenesis of anorectal malformations in mice using retinoids. Several investigators have reported an interaction between glucocorticoids and retinoids. It was supposed that glucocorticoids had some effects on the morphogenesis of murine embryos similar to retinoids. Therefore, we investigated alterations in the morphogenesis of murine embryos after triamcinolone acetonide (TAC) administration. MATERIAL AND METHODS TAC was administered in a single dose (15 mg/kg or 30 mg/kg body weight) to pregnant ICR-SLC mice on embryonic day 7 (E7), 8, 9, and 10. They were sacrificed on E18, and fetuses were examined for internal and external malformations. Randomly chosen fetuses were embedded in paraffin for immunohistochemical staining of the glucocorticoid receptor (GR). RESULTS The groups given 15 mg/kg TAC had one peak in the incidence of cleft palate on E9 (100 %) and the groups given 30 mg/kg TAC showed a biphasic pattern in the incidence of cleft palate on E7 and E10. No other anomalies were found. GR expression was marked in the subepithelial layer of palatal processes in the treated specimens. CONCLUSION The group given 15 mg/kg TAC on E9 provided a good model of cleft palate in ICR-SLC mice, and cleft palate was probably induced by various factors including disturbance of the bone morphogenetic protein (BMP) signaling pathway, shown by GR overexpression.