Chronic rejection (CR) remains a challenging complication after liver transplantation. Everolimus, which is a mammalian target of rapamycin inhibitor, has an anti-fibrosis effect. We report here the effect of everolimus on CR. Case 1 was a 7-year-old girl who underwent living donor liver transplantation (LDLT) shortly after developing fulminant hepatitis at 10 months of age. Liver function tests (LFTs) did not improve after transplantation despite treatment with tacrolimus + mycophenolate mofetil (MMF). Antithymoglobulin (ATG) and steroid pulse therapy were also ineffective. The patient was diagnosed with CR, and everolimus was started with a target trough level of about 5 ng/mL. LFTs improved and pathological examination showed no progression of hepatic fibrosis. Case 2 was a 10-year-old girl with Alagille syndrome who underwent LDLT at 1 year of age. She had biopsy-proven acute cellular rejection with prolonged LFT abnormalities beginning 3 years after transplantation. She was treated with steroid pulse therapy, followed by MMF, tacrolimus, and prednisolone. Her condition did not improve, even after subsequent ATG administration. CR was suspected based on liver biopsy in the fourth postoperative year, and everolimus was introduced. The target trough level was around 5 ng/mL, but was reduced to 3 ng/mL due to stomatitis. Four years have passed since the initiation of everolimus, and LFTs are stable with no progression of liver biopsy fibrosis. We describe 2 cases in which everolimus was administered for CR. In both cases, LFTs improved and fibrosis did not progress, suggesting that everolimus is an effective treatment for CR after LDLT.

Pediatric living donor liver transplantation (LDLT) in patients with advanced portopulmonary hypertension (PoPH) is associated with poor prognoses. Recently, novel oral medications, including endothelin receptor antagonists (ERAs), phosphodiesterase 5 (PDE5) inhibitors, and oral prostacyclin (PGI2) have been used to treat PoPH. Pediatric patients with PoPH who underwent LDLT from 2006 to 2016 were enrolled. Oral pulmonary hypertension (PH) medication was administered to control pulmonary arterial pressure (PAP). Four patients had PoPH. Their ages ranged from 6 to 16 years, and their original diseases were biliary atresia (n = 2), portal vein obstruction (n = 1), and intrahepatic portal systemic shunt (n = 1). For preoperative management, 2 patients received continuous intravenous PGI2 and 2 oral medications (an ERA alone or an ERA and a PDE5 inhibitor), and 2 received only oral drugs (an ERA and a PDE5 inhibitor). One patient managed only with intravenous PGI2 died. In the remaining 3 cases, intravenous PGI2 or NO was discontinued before the end of the first postoperative week. Postoperative medications were oral PGI2 alone (n = 1), an ERA alone (n = 1), or the combination of an ERA and a PDE5 inhibitor (n = 1). An ERA was the first-line therapy, and a PDE5 inhibitor was added if there was no effect. New oral PH medications were effective and safe for use in pediatric patients following LDLT. In particular, these new oral drugs prevent the need for central catheter access to infuse PGI2.

Breast FA is the most common breast tumor diagnosed in young women. Female renal transplant recipients on CsA have an increased risk of developing FA. However, reports of FA after LDLT have not been described. Our objectives were to determine the incidence of FA, analyze risk factors for FA, and evaluate treatment strategies in adolescent females after LDLT. A total of 18 female patients aged 10-19years who underwent LDLT and survived at least one year after transplantation were enrolled in our study. The incidence of FA was 11.1%. To determine pre- or post-transplant conditions that are associated with FA after transplantation, the patients were divided into two groups according to the presence or absence of FA: FA group (n=2) and non-FA group (n=16). There were no differences in mean age at LDLT, mean age at breast evaluation, and mean duration between transplantation and breast evaluation between the two groups. However, there was a difference in the immunosuppressive regimen between the two groups. The FA group was maintained on CsA, whereas the non-FA group was maintained on tacrolimus. CsA might be implicated in FA development in adolescent females after LDLT.

Background. Patients with intestinal failure (IF) are candidates for intestinal transplantation (ITx). In Japan, these patients have few opportunities to undergo cadaveric ITx because of low rates of organ donation. The donor criteria and recipient priority for ITx are still unknown. We reviewed our cases of IF to investigate which patients should be prioritized for ITx.Methods. Patients with IF who were registered as candidates for cadaveric ITx between January 2010 and November 2015 in our institute were included in this retrospective study. Their data were gathered from their charts and analyzed.Results. Five patients were included. Their primary diseases included total colon aganglionosis (n = 1), chronic idiopathic intestinal pseudo-obstruction syndrome (n = 2), superior mesenteric vein embolization (n = 1), and graft loss after ITx (n = 1). Two patients died of liver failure (LF) during the waiting period. The remaining three are now alive and waiting for transplantation. The lengths of the remaining intestine were more than 20 cm in living cases but less than 20 cm in fatal cases. In the fatal cases, they had several episodes of catheter-related blood stream infection, which caused LF and acute renal failure.Conclusions. We identified two patients with less than 20 cm residual small bowel who died after acute deterioration of liver function. Patients with ultra-short bowel could have a higher risk of LF. Therefore, they should be referred as soon as possible to a specialized hospital where ITx is a choice of treatment for IF.

Background. Hypercalcemia has been observed in patients after liver transplantation. However, it is rare that the hypercalcemia induced disseminated tissue calcification and heart failure.Case Report. We report a rare case of heart failure caused by disseminated metastatic tissue calcification that involved extensive progressive myocardial calcification after liver transplantation. A 20-year-old man with end-stage liver disease due to biliary atresia underwent ABO-incompatible living donor liver transplantation. After successful transplantation, he suffered from antibody-mediated rejection. Subsequently, ABO-matched cadaveric liver retransplantation was successfully performed. Hypercalcemia developed gradually following the second transplantation. His serum calcium level increased to 18.3 mg/dL with sudden onset of ventricular tachycardia. Although he was resuscitated with a cardiopulmonary support device, he died of heart and liver failure. Histopathologic examination revealed systemic disseminated metastatic tissue calcification, including massive myocardial calcification.Conclusion. Progressive worsening of hypercalcemia resulted in disseminated metastatic tissue calcification and massive metastatic myocardial calcification, which led to heart failure after liver transplantation. Because hypercalcemia after liver transplantation can cause fatal tissue calcification, early intervention for hypercalcemia should be considered.

Background. Pediatric living donor liver transplant (LDLT) patients sometimes develop graft fibrosis after non-recurrent diseases such as biliary atresia (BA). Donor-specific antibodies (DSA) have recently been shown to play a possible role in graft damage after liver transplantation. We report the impact of DSA on pediatric LDLT for BA patients.Methods. Patients under age 18 years who received LDLT for BA at our institution and who had at least 5 years' follow-up were identified, and 23 were eventually enrolled in this study. Pathological findings were assessed with the use of the last available biopsy. Patients were divided into 2 groups, DSA-positive and DSA-negative. Graft fibrosis after LDLT was assessed according to DSA groups.Results. The mean patient age at transplant was 2.6 years. The mean time to the last available biopsy after LDLT was 8.2 years (4.8-15.6 years); 6 patients (26%) showed no fibrosis, whereas fibrosis was graded as F1, F2, or F3 in 8 patients (35%), 8 patients (35%), and 1 patient, respectively. DSA were observed in 12 patients (52%). Moderate graft fibrosis (F2 and F3) was found in 7 (58%) of the DSA-positive group, but only 2 (18%) of the DSA-negative group, showing a statistically significant difference (P < .05). Pre-transplant cross matching was performed in 17 patients. The 2 patients with a positive cross-match were DSA-positive. Six cross-match-negative patients developed de novo DSA after LDLT.Conclusions. Graft fibrosis was observed after LDLT for BA during long-term follow-up, more commonly in DSA-positive patients. DSA may play a role in fibrosis formation.

BACKGROUND/PURPOSE:As minimal invasive surgery, laparoscopically assisted anorectal pull-through has been reported with new devices. However, it is not easy to create an accurate pull-through canal (PTC) because of the narrow space between the urethra and puborectal sling. The authors describe a new method using perineal ultrasonography.METHODS:The rectourethral prostatic fistula was dissected laparoscopically. Externally, electrostimulation identified the center of the muscle contraction, over which a 1.2-cm skin incision was made, and the lower part of PTC was created by hemostat forceps guided by electrostimulation. An ultrasonographic probe applied to the perineum demonstrated the urethra, and the forceps was advanced behind the urethra into the pelvic cavity using the ultrasonographic guide. Anorectal pull-through was performed after dilatation of the PTC with dilators.RESULTS:The authors applied this procedure in 5 cases of male high and intermediate anomalies. Surgical damages to the urethra and the levator and vertical muscles were not encountered. Postoperative fluoroscopic study demonstrated good anterior angulation and intact contraction and relaxation of those muscles.CONCLUSION:The combination of laparoscopic dissection, pinpointing the center of anal sphincter by electrostimulation, and identification of the urethra by ultrasonographic images from the perineum facilitated creation of appropriate PTC in the muscle complex.

BACKGROUND/PURPOSE:Recent advances including prenatal diagnosis, high-frequency oscillatory ventilation, and nitric oxide inhalation therapy have gradually improved the survival of high-risk congenital diaphragmatic hernia. However, the factors affecting the long-term outcome of these patients have not been well established. METHODS:Thirty-three children with ages 4.1 +/- 2.5 years underwent clinical examination including growth measurements, echocardiography, ventilation, and perfusion scintigraphy. RESULTS:No late death was observed. Common complications were frequent respiratory tract infection (13 patients) and bowel obstruction (5 patients underwent surgery). Although frequent respiratory tract infection decreased with increasing age, patients with frequent respiratory tract infection had a decreased uptake of lung ventilation and perfusion scintigraphy on the affected side and had a decreased height for age and weight for height. No significant difference in lung ventilation and perfusion scintigraphy was observed between patients treated with and without extracorporeal membrane oxygenation, those requiring oxygen more than 1 month, and between those with and without prenatal diagnosis. Patients with a patch repair had decreased uptake on lung perfusion scintigraphy. Although frequent respiratory tract infection may be owing to hypoplasia of the ipsilateral lung, it may impair recovery of the hypoplastic lung. CONCLUSION:These results indicate that monitoring for respiratory tract infection in addition to nutritional assessment should be required in the follow-up of patients with congenital diaphragmatic hernia at high risk.

Background/Purpose: As endoscopic equipment and instruments have been improved, the indication for endoscopic surgery has been extended. The authors achieved endoscopic membranectomy for congenital membranous stenosis in the upper gastrointestinal tract.Methods: Case 1 was a 3-year-old girl with membranous stenosis in the descending duodenum. Case 2 was a 1-year-old boy with esophageal membranous stenosis. In case 1, a flexible endoscope with a banding chamber, the inside of which had a tiny groove for a high-frequency-wave snare, was inserted into the duodenum. The diaphragm was drawn into the chamber by endoscopic suction and tied with the snare around its base, then dissected by electrifying the snare. In case 2, the diaphragm was resected with a high-frequency-wave cutter, assisted by a balloon catheter pulling up the diaphragm from the distal side.Results: In both cases, the stenosis was released adequately without complications, and oral feeding was restarted in a day after the procedure.Conclusions: Endoscopic membranectomy using a high-frequency wave snare/cutter was achieved safely and effectively in 2 children with congenital membranous stenosis in the upper gastrointestinal tract. (c) 2005 Elsevier Inc. All rights reserved.

The use of memory metallic stents for the urinary tract in pediatric patients has not been reported. The authors report on 2 patients with urinary tract disorders who were successfully treated with a memory metallic stent. A thermoexpandable, nickel-titanium alloy stent was placed at the urethroureteral junction of a 4-year-old boy with ureteral stenosis associated with cloacal exstrophy for 18 months and at the urethra of a 2-year-old girl with ischuria after a repair of cloacal anomaly for 6 months. Temporary insertion of a memory metallic stent is a safe and effective alternative for organic stricture or functional obstruction of the urinary tract in pediatric patients.

Background/purpose The authors experienced 3 cases of persistent pulmonary hypertension of the neonate (PPHN) associated with duodenal atresia with paradoxical dilatation of the distal blind end of the duodenum. The aim of this study was to clarify the characteristics of this novel association. Methods The medical charts of the patients were reviewed retrospectively. Results Case 1 was a 2,862-g male infant with a prenatal diagnosis of duodenal atresia. The dilated intestine was identified as the distal blind end of the duodenum during duodeno- duodenostomy. PPHN developed after surgery, and the patient died despite treatment with inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO). Lung biopsy results showed alveolar capillary dysplasia (ACD) with misalignment of pulmonary vessels. Case 2 was a 2,244-g female infant with duodenal atresia. Surgery could not be performed because of refractory PPHN, which resulted in death. Autopsy results showed ACD with misalignment of pulmonary vessels and duodenal atresia associated with dilatation of the distal blind end. Case 3 was a 2,462-g female infant with a prenatal diagnosis of duodenal atresia associated with dilatation of the distal blind end. Enlarged echogenic fetal lungs were noted antenatally. PPHN developed after surgery, and she was extubated successfully under combined therapy with iNO and intravenous prostacyclin. Unfortunately, she finally died of refractory PPHN. A retrospective review of the prenatal ultrasonographic findings showed enlarged echogenic fetal lungs as in the first 2 cases. Conclusions The characteristics of this novel association are enlarged echogenic fetal lungs, duodenal atresia associated with paradoxical dilatation of the distal blind end, and refractory PPHN resistant to iNO.

Background/Purpose: Laparoscopically assisted endorectal pull-through (EPT) via a perineal approach using a prolapsing technique (PA) for Hirschsprung's disease (HD) has been reported. However, the clinical outcome after this approach has not been reported. The purpose of this study was to compare the clinical outcome of PA and the conventional transabdominal approach (TA).Methods: In the period between 1990 and 2001, 20 cases of HD underwent EPT with TA (group 0), and 21 underwent EPT with PA (group L). There was no difference in age and weight distribution between the 2 groups. Clinical outcome was assessed 3 years after surgery.Results: The operation time was comparable in the 2 groups (4.9 +/- 0.8 v 5.2 +/- 0.8 hr), whereas blood loss (98 +/- 52 v 36 +/- 30 mL) and postoperative complications requiring surgical intervention (26% v 0%) were significantly lower in group L. The incidence of postoperative enteritis (27% v 28%) and voluntary defecation (more than once every/2 days) were compatible in the 2 groups (70% v 87%). Soiling (small amount of involuntary stooling; >1 per month) was significantly less frequent in group L (45% v 14%).Conclusions: Laparoscopically assisted ETP with PA is less invasive and can provide a better clinical outcome compared with TA in terms of postoperative soiling. (C) 2004 Elsevier Inc. All rights reserved.

Purpose: Children with neurologic and neuromuscular handicaps frequently have various symptoms related to gastroesophageal reflux (GER) disease. The long-term efficacy of antireflux surgery remains controversial in such children with GER. The clinical results of such patients who underwent laparoscopic fundoplication were examined in the current study.Methods: Between 1997 and 2003, laparoscopic fundoplication was performed in 56 handicapped children (mean age, 6 years), and gastrostomy was performed concurrently in 52. The main symptoms were emesis/hematemesis in 40 and respiratory symptoms, including repeated respiratory infection and distress, in 31.Results: There were no severe postoperative complications or operative mortality. Emesis/hematemesis was controlled adequately in those without recurrence. Respiratory symptoms were controlled unsuccessfully in 16 patients (52%), 8 of whom required further respiratory care including nasal airway tube, tracheostomy, and laryngotracheal separation. Recurrence of GER disease occurred in 10 patients, 7 of whom underwent a second Nissen fundoplication successfully. Thirteen died within the median follow-up period of 14 months.Conclusions: Laparoscopic fundoplication is effective in controlling emesis/hematemesis, but its efficacy is limited in terms of respiratory problems in handicapped children. Further refinements in diagnostic and treatment strategies are mandatory to improve the quality of life in such patients. (C) 2004 Elsevier Inc. All rights reserved.