Intellectual development of patients with biliary atresia who underwent living donor liver transplantation in infancy.

BACKGROUND: The impact of pediatric liver transplantation on intellectual development has yet to be determined. We investigated the intellectual outcomes of school-aged patients after living donor liver transplantation for biliary atresia in infancy. METHODS: The Wechsler Intelligence Scale for Children-fourth edition test was administered to 20 patients who survived [Formula: see text] 5 years after living donor liver transplantation. Borderline full scale intelligence quotient was defined as ≤ 85. Pre-, peri-, and postoperative data were compared between patients with > 85 and ≤ 85 to identify predictive factors of borderline performance. RESULTS: The one-sample t test demonstrated that the mean full scale intelligence quotient of patients after transplantation for biliary atresia was significantly lower than that of the general population (91.8 vs. 100.0, p = 0.026) and 7 (35%) were classified as intellectual borderline functioning. Multivariable logistic regression models were unable to identify any factors predictive of full scale intelligence quotients of ≤ 85. CONCLUSION: This is the first study to indicate that the mean full scale intelligence quotient among school-aged patients who underwent living donor liver transplantation for biliary atresia in infancy is significantly lower than that of the general population.

Ethanol lock therapy in pediatric patients: A multicenter prospective study.

BACKGROUND: Ethanol lock therapy (ELT) has been performed for the purpose of preserving central venous catheters (CVC) in central venous catheter-related blood stream infection (CRBSI), but evidence for its effectiveness is not established. We conducted a multicenter, prospective study on the ELT protocol to ascertain its safety and effectiveness against CRBSI. METHODS: The subjects were patients aged over 1 year with potential for developing CRBSI who had long-term indwelling silicone CVCs. After culturing the catheterized blood, a 70% ethanol lock was performed daily for 2-4 h for 7 days. The effectiveness rate of ELT for single and multiple courses, the presence or absence of relapse of CRBSI within 4 weeks of treatment, and whether the CVC could be salvaged after 4 weeks were examined. RESULTS: From September 2014 to August 2018, 49 cases from six hospitals were enrolled in the study. Catheter blockage was seen in one case and the CVC was removed. A single course of ELT was effective in episodes 88% (42/48). In the remaining three episodes that failed after a single course of ELT, a second ELT was performed; however, all were ineffective. In episodes 93% (40/42), no CRBSI relapse was seen up to 4 weeks after the end of treatment. In episodes 84% (41/49), the catheter could be preserved for 4 weeks or more after the end of treatment. Facial flushing was seen in two cases as an adverse event; however, this was transient and soon disappeared. CONCLUSION: ELT is effective for 88% of CRBSI and 84% of catheters can be salvaged; therefore, this protocol is considered useful. TRIAL REGISTRATION: UMIN000013677.

Diagnosing native liver fibrosis and esophageal varices using liver and spleen stiffness measurements in biliary atresia: a pilot study.

BACKGROUND: Biliary atresia commonly leads to liver fibrosis and cirrhotic complications, including esophageal varices. OBJECTIVE: To evaluate liver and spleen stiffness measurements using acoustic radiation force impulse (ARFI) imaging for diagnosing grade of liver fibrosis and predicting the presence of esophageal varices in patients treated for biliary atresia. MATERIALS AND METHODS: ARFI imaging of the spleen and native liver was performed in 28 patients with biliary atresia. We studied the relation between ARFI imaging values and liver histology findings (n=22), upper gastrointestinal endoscopy findings (n=16) and several noninvasive test results. Diagnostic accuracy was assessed using receiver operating characteristic curve analyses. RESULTS: Liver stiffness measurements exhibited a significant difference among the different grades of liver fibrosis (P=0.009), and showed higher values in patients with high-risk esophageal varices than in the other patients (P=0.04). The areas under the receiver operating characteristic curves of liver stiffness measurements for liver fibrosis grades ≥ F2, ≥F3 and = F4 were 0.83, 0.93 and 0.94, respectively. Patients with high-risk esophageal varices were preferentially diagnosed by the combined liver and spleen stiffness measurements (area under the curve, 0.92). CONCLUSION: Liver and spleen stiffness measurements using ARFI imaging are potential noninvasive markers for liver fibrosis and esophageal varices in patients treated for biliary atresia.

Neonatal intestinal volvulus and preduodenal portal vein associated with situs ambiguus: report of a case.

Situs ambiguus is a rare lateralization anomaly that is frequently associated with other malformations, including preduodenal portal vein (PDPV), intestinal malrotation, and cardiovascular anomalies. This is a case report on a newborn that was clinically diagnosed with situs ambiguus and midgut volvulus. During surgery the patient was found to have intestinal malrotation, Meckel's diverticulum, and PDPV that was not a direct cause of duodenal obstruction. The patient was treated with Ladd's procedure and resection of Meckel's diverticulum. It is important to be familiar with the spectrum of situs anomalies to prevent trauma to the portal vein with serious complications during surgery.

Laparoscopic completely extraperitoneal repair of inguinal hernia in children: a single-institute experience with 1,257 repairs compared with cut-down herniorrhaphy.

BACKGROUND: Conventional open herniorrhaphy in children has been reported to have 0.3-3.8% recurrence and 5.6-30% postoperative contralateral hernia rates. We developed a unique technique to achieve completely extraperitoneal ligation of PPV without any skip areas under laparoscopic control. This report introduces our technique and results compared with the cut-down herniorrhaphy. METHODS: A consecutive series of 1,585 children with inguinal hernia/hydrocele (1996-2006) was analyzed. In laparoscopic patent processus vaginalis (PPV) closure (LPC), an orifice of PPV was encircled with a 2-0 suture extraperitoneally by a specially devised Endoneedle and tied up from outside of the body achieving completely extraperitoneal ligation of the ring. The round ligament was included in the ligation, whereas the spermatic cord and testicular vessels were excluded by advancing the needle across them behind the peritoneum. Cut-down herniorrhaphy (CD), with or without diagnostic laparoscopy, or LPC was selected according to parental preference under informed consent. RESULTS: Parents gave more preference to LPC (LPC in 1,257 children, CD in 308, and miscellaneous in 20). Age ranges were equal for both groups. Sex distribution showed female preponderance in the LPC group (44.8% vs. 26.6%, p < 0.001) and umbilical hernia/cysts were predominantly included in the LPC group (11.9% vs. 2.9%, p < 0.001). Mean operation times were equal for both groups for unilateral repair (28.2 +/- 9.2 for LPC vs. 27.8 +/- 13.5 for CD) and were shorter for bilateral repair in the LPC group (35.8 +/- 11.6 vs. 46.7 +/- 17.7). The incidence of postoperative hernia recurrence and contralateral hernia in the LPC group was 0.2% and 0.8%. Two children in the CD group had injuries to their reproductive system during the operation (0.6%). CONCLUSIONS: The advantages of our technique include following: technically simple, short operation time, inspection of bilateral IIRs with simultaneous closure of cPPV, reproductive systems remain intact, routine addition of umbilicoplasty if desired, and essentially indiscernible wounds.

Morphology-based investigation of metachronous inguinal hernia after negative laparoscopic evaluation - is it acquired indirect inguinal hernia?

PURPOSE: Patients who developed apparent metachronous contralateral inguinal hernia (MCIH) after negative laparoscopic diagnosis have been reported. We performed this study to investigate the morphological characteristics and etiology of this phenomenon. PATIENTS AND METHODS: A consecutive series of 1,747 patients (858 boys and 889 girls) with symptomatic unilateral inguinal hernia were studied. During laparoscopic percutaneous completely extraperitoneal closure, morphological appearances at the asymptomatic groin were inspected for contralateral patent processus vaginalis (CPPV) with definitive criteria. If positive CPPV was identified, it was closed by the same technique used for the affected side. The patients were reviewed for occurrence of metachronous contralateral hernia. RESULTS: A total of 755 patients (43.2%) had positive CPPV. Of the 992 patients whose CPPVs were evaluated as true negative, eight (seven boys, one girl) developed MCIH (time taken, three months to five years six months). During second-look operations, morphological appearances of the CPPV that was originally considered as true negative CPPV was found to be wide open. CONCLUSIONS: Despite a true negative evaluation by laparoscopy, there was a 0.8% chance of developing a MCIH. This phenomenon was male-oriented and may be acquired indirect inguinal hernia without preceding of CPPV.

Development and Validation of a Novel Fibrosis Marker in Biliary Atresia during Infancy.

OBJECTIVES: Most biliary atresia (BA) patients suffer from liver fibrosis and often require liver transplantation. The aim of this study was to develop and validate a novel fibrosis marker for BA patients aged <1 year-the infant BA liver fibrosis (iBALF) score-subsequent to the previously reported fibrosis marker for BA patients aged ≥1 year. METHODS: From three institutions for pediatric surgery, BA patients and their native liver histology examinations performed at the age of <1 year were retrospectively identified and assigned to a development cohort (58 patients and 73 examinations) or validation cohort (92 patients and 117 examinations) according to their institutions. Histological fibrosis stages (F0-F4), blood test results, and clinical information at the time of liver histology examination were reviewed. The iBALF score was determined using multivariate ordered logistic regression analysis and was assessed for its associations with histological fibrosis stages. RESULTS: The iBALF score equation was composed of natural logarithms, including serum total bilirubin level, blood platelet counts, and days of age. The score revealed a strong correlation with fibrosis stage (r=0.80 and 0.73 in the development and validation cohorts, respectively; P<0.001). The areas under the receiver-operating characteristic curves for diagnosing each fibrosis stage were 0.86-0.94 in the development cohort and 0.86-0.90 in the validation cohort (P<0.001), indicating good diagnostic power. In addition, no patient with an iBALF score >6 (equivalent to F4) at the initial surgery survived with their native liver at 1 year of age (n=9). CONCLUSIONS: The iBALF score that was developed was a good noninvasive marker of native liver fibrosis for BA patients aged <1 year.

An investigation on the mechanism of contralateral manifestations after unilateral herniorrhaphy in children based on laparoscopic evaluation.

BACKGROUND/PURPOSE: No straightforward theoretical descriptions explaining the discrepant incidences of metachronous contralateral hernia and positive contralateral patent processus vaginalis (cPPV) exist. The indications for contralateral groin repair are still not clearly defined. METHODS: During laparoscopic herniorrhaphy, the intraoperative appearances of the internal inguinal rings (IIRs) were characterized and classified in 211 children with symptomatic unilateral inguinal hernias. A total of 125 boys and 86 girls with 130 right-sided and 81 left-sided indirect inguinal hernias were examined. The morphological appearances of the IIRs in patients with cPPV were compared before and after the ligation of the symptomatic IIRs. RESULTS: Of 211 children, 108 (51%) had positive cPPV findings. The cPPVs had significantly smaller orifices and shorter lengths than those on the side of the symptomatic hernia. Among these children, 24 (22%) patients exhibited morphological changes in their cPPVs, characterized by an upward movement of the overlying peritoneal veil after the closure of the symptomatic hernia. CONCLUSION: Metachronous contralateral hernia might occur because of morphological changes to the cPPV resulting from closure of the symptomatic IIRs. The predicted incidence of contralateral hernia in this series was 11.2%.

Hepatopulmonary syndrome can show spontaneous resolution: possible mechanism of portopulmonary hypertension overlap?

Hepatopulmonary syndrome (HPS) (hypoxaemia due to intrapulmonary vasodilation and a right-to-left shunt associated with liver disease) resolves after liver transplantation. The authors describe a case of spontaneous resolution of HPS prior to liver transplantation. This patient was diagnosed with HPS associated with extra-hepatic biliary atresia when she was 10 years old. She exhibited digital clubbing, facial vascular dilation, cyanosis, and suffered from dyspnoea during exercise. The patient's PaO(2) at rest was 53.8 mm Hg in room air and a Technetium-99m macro-aggregated albumin lung perfusion scan demonstrated a right-to-left shunt. Although her symptoms and laboratory data supported a diagnosis of HPS, she nevertheless showed spontaneous resolution within 2 years. When she was 14 years old, pulmonary hypertension was evident upon examination of her echocardiogram. HPS may be improved or masked by an accidental overlap with pulmonary hypertension in the terminal stage of liver disease.

Life-threatening airway obstruction caused by mediastinal germinoma in a 9-year-old girl.

The authors report a case of a 9-year-old girl with a mediastinal germinoma that required emergent surgical extirpation because of tracheal compression and asphyxia. The tumor was successfully debulked under general anesthesia with the capability of extracorporeal circulation immediately available. Postoperatively, the tumor responded to adjuvant chemotherapy and irradiation and the patient survived without evidence of recurrence.

Biliary atresia, the next generation: a review of liver function, social activity, and sexual development in the late postoperative period.

PURPOSE: The current study aimed to establish the management for biliary atresia (BA) patients in the late postoperative period. METHODS: Of 165 BA patients operated on in the authors' department, 44 patients (16 boys, 28 girls) with a follow-up period of more than 15 years were reviewed retrospectively. RESULTS: Forty-one of 44 patients (93.2%) currently are employed or highly educated, 7 are married, whereas 2 (4.5%) died, and 10 (22.7%) required liver transplantation after puberty. Four babies have been born from BA parents without congenital anomalies. Four girls conceived 5 times and delivered 3 newborns weighing 2,330 to 2,474 g including one delivered after transplantation. Maternal portal hypertension uniformly deteriorated during pregnancy, and one pregnancy was terminated. Menstrual disorder correlated significantly with the biochemical data related to liver function at puberty such as serum choline esterase (266 +/- 70.4 in 19 normal patients v 159 +/- 34.3 IU/L in 9 abnormal patients, P =.00057), asparate aminotransferase (42 +/- 30.8 v 96.0 +/- 63.6 IU/L; P =.0031), and serum albumin (4.6 +/- 0.4 v 3.9 +/- 0.6 g/dL; P =.013). CONCLUSIONS: The long-term survivors of Kasai's operation, with or without liver transplantation, have reached the next generation. Transgenerational follow-up and management including conception and perinatal care should be required for BA patients.

The significance of human jagged 1 mutations detected in severe cases of extrahepatic biliary atresia.

Mutations of human jagged 1 (JAG1) gene are responsible for Alagille Syndrome (AGS), whose 2 main symptoms are intrahepatic bile duct hypoplasia and pulmonary stenosis. We examined the JAG1 mutation in extrahepatic biliary atresia (EHBA), which is similar in phenotype to AGS, although a different pathogenesis is suggested. In 102 cases of EHBA, 9 missense mutations were detected, including 2 intrafamilial expressions in the propositus and an aunt of one family. These mutations were all missense and sporadic except for those of this particular family. The JAG1 gene mutations were generally found in severely ill patients subjected to liver transplantation at less than 5 years of age. None of the 9 cases of EHBA revealed any of the 5 major symptoms of AGS nor any identical pathological findings after 3 years of follow-up. Our cases were clearly separated from AGS by pathological findings and clinical features, and could be diagnosed as EHBA and not as atypical AGS. The increase of interleukin 8 (IL-8) production induced by tumor necrosis factor alpha (TNF-alpha) in Huh 7 cells was suppressed by the coexistence of JAG1 protein. We examined the different influences between wild-type cells and the 3 kinds of mutants detected in EHBA on Huh 7 cells and found that 2 of 3 mutants showed about half of the repressed activity compared with that of wild type. In conclusion, these results suggest that the JAG1 gene abnormality may be an aggravating factor in EHBA.