Naomi Iwai

Long-term outcomes after hepaticojejunostomy for choledochal cyst: a 10- to 27-year follow-up

INTRODUCTIONnCholedochal cyst (CC) is closely associated with anomalous arrangement of the pancreaticobiliary duct, which is considered a high-risk factor for biliary tract malignancy. Early diagnosis and early treatment for CC could lead to a good prognosis. This study investigated late complications and long-term outcomes after surgery for CC.nnnPATIENTS AND METHODSnFifty-six patients with CC and over 10 years of postoperative follow-up were analyzed retrospectively. All patients had undergone total resection of the extrahepatic bile duct and hepaticojejunostomy.nnnRESULTSnSix patients showed liver dysfunction manifested in the first 10 years after surgery, but all returned to normal thereafter. Dilatation of intrahepatic bile ducts persisted in 6 postoperatively, and in 3, this was still apparent more than 10 years after. Recurrent abdominal pain was encountered in 3, 1 had pancreas divisum with a pancreatic stone, and 1 had adhesive small bowel obstruction. Two patients developed biliary tract malignancy. A 14-year-old girl died of recurrent common bile duct cancer 2 years after the initial resection of CC with adenocarcinoma. A 26-year-old man with repeated cholangitis owing to multiple intrahepatic bile stones developed cholangiocarcinoma 26 years after the initial resection of CC. Event-free survival rate and overall survival rate were 89% (50/56) and 96% (54/56), respectively.nnnCONCLUSIONSnCholedochal cyst generally has an excellent prognosis with early total resection and reconstruction. Long-term surveillance for the development of malignancy is still essential, especially if there is ongoing dilatation of the intrahepatic bile duct or biliary stones.

Development of bile duct cancer in a 26-year-old man after resection of infantile choledochal cyst

Anomalous arrangement of the pancreaticobiliary duct is considered to be a high-risk factor for biliary tract malignancy. We report a case of intrahepatic cholangiocarcinoma in a 26-year-old man after total resection of choledochal cyst with anomalous arrangement of the pancreaticobiliary duct at the age of 5 months. He had been doing well after total resection of the choledochal cyst; however, he suddenly presented with a spiky fever and abdominal pain in the right upper quadrant at the age of 26 years. Computed tomographic scan and percutaneous transhepatic cholangioscope revealed multiple stones and stenosis of the hepatic duct and the left intrahepatic bile duct. Histologic examination of a biopsy specimen obtained from the stenotic site showed adenocarcinoma of the intrahepatic bile duct. Left lobectomy with re-reconstruction by right hepaticojejunostomy was performed, and his postoperative course was uneventful. One year after the operation, however, he died of carcinomatous peritonitis with recurrence of cholangiocarcinoma. This report warns us that bile stasis owing to stenosis of the intrahepatic bile duct and repeated cholangitis with multiple stones are high-risk factors for carcinogenesis of the intrahepatic bile duct even after total resection of the infantile choledochal cyst.

Significance of ductal plate malformation in the postoperative clinical course of biliary atresia

PURPOSEnDuctal plate malformation (DPM) is one of the etiologic theories for the development of biliary atresia (BA). In this study, we investigated the significance of DPM in the postoperative clinical course of BA, especially as a predictive factor of jaundice clearance.nnnMETHODSnBetween 1988 and 2005, 31 patients with uncorrectable BA underwent hepatoportoenterostomy and steroid therapy. Immunohistochemistry was used to characterize biliary structures using cytokeratin 19. Specimens were defined as DPM-positive if a concentric cellular arrangement was detected. This retrospective study included comparisons of preoperative characteristics, the postoperative jaundice period, and cumulative steroid doses between patients with and without DPM.nnnRESULTSnOf the 31 patients with uncorrectable BA, 25 (80.6%) became jaundice-free. Ductal plate malformation was detected in 11 (35.5%) of the 31. Between the 2 groups, there were no differences in preoperative characteristics or in the postoperative jaundice-free rate. Among those who became anicteric, the postoperative jaundice period was 145.3 +/- 69.9 days in the DPM-positive group (n = 9) and 81.8 +/- 44.7 days in the DPM-negative group (n = 16) (P < .05). The total administered steroids were 149.7 +/- 78.2 and 95.0 +/- 60.2 mg/kg, respectively (P = .09).nnnCONCLUSIONnDuctal plate malformation may disturb bile flow and require more steroid to improve bile drainage. Therefore, the presence of DPM in the liver predicts poor bile flow after hepatoportoenterostomy in infants with BA.

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

BACKGROUND/PURPOSEnThere 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.nnnPATIENTS AND METHODSnA 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.nnnRESULTSnThe 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).nnnCONCLUSIONnBenefits 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.

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/PURPOSEnRetinoid-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.nnnMETHODSnPregnant ICR-Slc mice were administered 100u2009mg/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).nnnRESULTSnOver 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.nnnCONCLUSIONnATRA 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.

Management strategies for infants with total intestinal aganglionosis

PURPOSEnThis study investigated appropriate management strategies for infants with total intestinal aganglionosis (TIA), focusing on surgical and medical managements.nnnMETHODSnSix infants with TIA or near TIA treated in our institution between 1980 and 2007 were reviewed retrospectively. Surgery was performed as a simple jejunostomy, 65 to 70 cm below the ligament of Treitz (LOT) in 2 infants, and 30 cm below LOT in 1 without extended myectomy-myotomy (EMM). Jejunostomy with EMM 30 to 35 cm below LOT were performed in 3.nnnRESULTSnTwo infants with jejunostomy 65 cm or 70 cm distal from LOT died of sepsis at 7 months and 8 months of age, respectively. One infant with jejunostomy 30 cm from LOT without EMM died of cholestatic liver failure at the age of 1 year and 8 months. To date, the remaining 3 infants with jejunostomy 30 cm or 35 cm distal from LOT in addition to EMM have survived 10 years, 3 years and 10 months, and 2 years of age, respectively. Nutritional managements such as parenteral nutrition with 80 to 100 kcal/kg/day and oral feeding with elemental diet (ED) were preferable to reduce the occurrence of enteritis, sepsis, and cholestatic liver dysfunction.nnnCONCLUSIONnA good combination of cyclic parenteral nutrition and oral intake with elemental diet after short proximal jejunostomy with EMM may be a key for the survival of infants with TIA. In addition, in infants whose absorptive function was not ameliorated by EMM, medical management such as GH administration might be worth trying.

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

AIMS OF STUDYnRetinoid-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.nnnMETHODSnRetinoic 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.nnnRESULTSnIn 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.nnnCONCLUSIONnThe 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.

INTRODUCTIONnWe 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.nnnMATERIAL AND METHODSnTAC 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).nnnRESULTSnThe 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.nnnCONCLUSIONnThe 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.