Takuya Kimura

Abstract: We describe our new technique for laparoscopic herniorrhaphy with subumbilical single-site access to treat inguinal hernias in children. First, we inserted a transparent 3-mm trocar and a 2-mm minitrocar at the umbilicus. We then inserted a 3-mm 45° camera through the 3-mm trocar and needle-grasping forceps through the 2-mm trocar. We closed the hernia defect by using a 19-gauge hooked injection needle with a nonabsorbable suture. We treated 11 consecutive female children with inguinal hernia using this operation. The mean operating time was 26.7 min (range 21-36 min) and the procedure was technically successful, without the need for additional trocars, in all 11 patients. There were no intraoperative complications and all the patients were discharged on the same day after the surgery. Single-site laparoscopic herniorrhaphy using needle instruments is feasible and seems to be safe. Further studies are required to determine whether this approach would benefit patient compared with standard laparoscopic herniorrhaphy.

Abstract: This study analyzed the inside appearance of the trachea and the main bronchus at the time of performing the Nuss procedure to test the hypothesis that the trachea and the main bronchus might be deformed by compression from great vessels due to sternal depression.

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Abstract: Duct-to-duct biliary reconstruction (DD) is currently a standard procedure in adult live donor liver transplantation (LDLT). Its pediatric feasibility, however, has rarely been reported. The goal of this study is to assess the incidence and treatment of biliary complication after pediatric LDLT with DD or Roux-en-Y hepaticojejunostomy (RY).

Abstract: INTRODUCTION: Induction therapy with daclizumab or alemtuzumab has been recently introduced for intestinal transplantation; however, the impact of such induction therapy on bacterial infections remains to be clarified. The purpose of this study was to evaluate the impact of induction therapy on the incidence of bacterial infections and long-term patient survival. PATIENTS AND METHODS: Over the past seven yr, we performed 39 intestinal (ITx) and multivisceral (MTVx) transplants in 38 adult patients. In the early period, daclizumab was used for induction, and tacrolimus and steroids were administered for maintenance [daclizumab and tacrolimus (DT) group; n = 11]. From 2002, we used alemtuzumab for induction, with low-dose tacrolimus maintenance [alemtuzumab and tacrolimus (AT) group; n = 23]. The incidence of bacterial infections and patient outcome were compared between the two groups. RESULTS: There were no significant differences in recipient and donor demographics, procedure (ITx vs. MTVx), and cold and warm ischemic time between the two groups. Within 30 d after ITx, bacterial infections were observed in seven patients (64%) in the DT and in 14 patients (64%) in the AT group. Between 30 and 180 d after ITx, a total of 17 episodes of bacterial infections were observed in the DT and 26 episodes in the AT group. Three patients in the DT and eight in the AT group died, and all of the deaths were related to infectious complications except one each in DT and AT. CONCLUSION: There was no difference in incidence of bacterial infections and long-term patient survival between the two groups.

Abstract: NICCD is an autosomal recessive genetic disorder, characterized by cholestasis, coagulopathy, hypoglycemia, fatty liver and multiple amino acidemia. NICCD develops in the neonatal/infantile period and has been reported as a "naturally curable" disease within one yr of life. Recently, we experienced an infantile NICCD who developed progressive liver failure, and required subsequent LT using a heterozygote living donor at eight months of age. Diagnosis of NICCD was established before transplantation, and donor evaluation included mutation in the SLC25A13 gene for exclusion of individuals with citrin deficiency citrullinemia. LDLT, from blood type identical mother using a left lateral segment graft, was performed without serious complication. Plasma amino acid concentration was normalized rapidly, and the patient was discharged 30 days after transplant. During one yr follow up, the recipient has been doing well without additional medication for NICCD. NICCD should be considered in the differential diagnosis as a cause of neonatal/infantile cholestatic disease. LT using a heterozygote living donor is an effective alternative in countries where a deceased donor is not available.

Abstract: ABSTRACT Volvulus of the gallbladder has been reported mostly in elderly women and is rarely reported in children. In this paper, we report a recent case of successful detorsion and removal of the gallbladder via minimal access surgery, which was diagnosed as gallbladder volvulus preoperatively by means of magnetic resonance imaging (MRI). An 11-year-old boy presented with an acute abdomen, and acute cholecystitis was suspected, based on the findings of ultrasound and computed tomography. However, a diagnosis of gallbladder volvulus was established through MRI, and emergency laparoscopic surgery was subsequently performed. Laparoscopy revealed a hemorrhagic, gangrenous gallbladder that floated anteriorly. The gallbladder was rotated twice around its pedicle in a counterclockwise direction. It was untwisted through laparoscopy, and a cholecystectomy was performed without difficulty. To achieve an early, prompt preoperative diagnosis, MRI could be an effective alternative to conventional imaging modalities. The advent of laparoscopic detorsion and cholecystectomy as a treatment for gallbladder volvulus allows less invasive treatment, a shorter hospital stay, and better cosmesis, which are highly desirable in children.

Abstract: BACKGROUND/AIMS: Patients with hepatocellular carcinoma on the waiting list for liver transplantation are excluded due to causes related to liver failure and tumor progression. We analyze the various factors to suggest a new liver transplant priority. METHODOLOGY: We evaluated the outcome on the list of 309 patients with hepatocellular carcinoma and causes of drop-out from the list were divided as death, "too sick" and tumor progression. The impact of model for end stage liver disease score, tumor stage and waiting time on the causes of drop-outs was evaluated. RESULTS: During the study period, 197 patients had a liver transplantation, 50 were still on the list and the remaining 62 were removed from the list (28 deaths, 30 tumor progressions, and 4 "too sick"). The receiver operating characteristic curves analysis showed that the model for end stage liver disease score predicted the rate of deaths on the list at 1-year (p<0.001). The waiting time and the tumor stage predicted the rate of drop-outs for tumor progression at 1-year on the list (p<0.05). CONCLUSIONS: Patients with hepatocellular carcinoma on the waiting list should have priority based on their model for end stage liver disease score, waiting time with tumor and tumor stage.

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Abstract: Little is known about the safety of LRLTx in children with end stage liver disease associated with congenital cardiac anomalies. We report the successful LRLTx in a case with extrahepatic biliary atresia associated with cTGA, VSD, and PS. Preoperative cardiac function was evaluated by cardiac echogram and cardiac catheterization. The recipient's cardiac function was preserved (EF; 54%); however, because of the left to right shunt disease, oxygen saturation was 91%. At operation, carbon dioxide insufflation into the abdominal cavity was attempted to prevent sudden air embolism. Hemodynamic variables were stabilized during partial clamping of the inferior vena cava, and at reperfusion of the portal vein. However, a sudden decrease in blood oxygenation was observed during hepatico-jejunostomy, which was easily normalized by graft mobilization. Post-operatively, neither heart failure nor cerebral infarction because of air embolism was observed. In conclusion, together with preserved cardiac function and carbon dioxide insufflation, LRLTx was successful. Further studies are required to establish the algorithm for the strategy of treating both congenital cardiac anomalies and liver failure.

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Abstract: The effect of blocking the expression of the mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in a graft by an antibody, and immunohistochemical changes in the graft were monitored, using a rat small intestinal transplantation model. Dark Agouti (DA) rat small intestines were heterotopically transplanted into Lewis (LEW) rats. The graft was treated with or without an anti-MAdCAM-1 antibody, F(ab')(2), during the operation. The survival of the grafts and histological changes, such as lymphocyte infiltration and destruction of the intestinal architecture in epithelium villus thickness, villus height and submucosal thickness of the graft, were examined. The expression of MAdCAM-1 and beta 7 integrin in the graft was also checked by immunostaining. Furthermore, graft infiltrating lymphocytes, in mesenteric lymph nodes (MLN) and Peyer's patches (PP) were measured by FACS analysis. Survival was prolonged in the DA graft with anti-MAdCAM-1 F(ab')(2) treatment; DA to LEW: 7.0+/-3.3, DA to LEW with the antibody: 24.6+/-8.4 days (p<0.05). Histological findings and scoring of the grafts were consistent with this conclusion. Moreover, MAdCAM-1 expression itself was suppressed in grafts of the antibody-treated group. While a FACS analysis showed no difference in the % of CD4+ T cells and CD8+ T cells in the PP of the graft, CD4+ T cells in the MLN of the antibody-treated graft were significantly low. A strategy directed at blocking the adhesion molecule, MAdCAM-1, in the small intestinal grafts could be useful in the prevention of acute rejection.

Abstract: PURPOSE: Infants and children with congenital dilatation of the bile duct (CDBD) usually also have some degree of liver fibrosis, which occasionally persists after diversion surgery, leading to liver cirrhosis. We conducted this study to evaluate the histological degree of liver fibrosis using intraoperative biopsy and to determine whether it affects the postoperative clinical course. METHODS: The subjects were 43 infants and children with CDBD. The age at operation ranged from 1 month to 14 years. Histological classification was defined as follows: grade 0, no fibrosis; grade 1, fibrosis confined to the portal area; grade 2, bridge formation with the neighboring portal area; grade 3, widened bridging fibrosis; and grade 4, pseudolobule formation, representative of cirrhosis. RESULTS: There were 21 (48.8%) patients with grade 0, 17 (39.5%) with grade 1, 4 (9.3%) with grade 2, 1 (2.3%) with grade 3, and 0 (0%) with grade 4 fibrosis. There were no differences in preoperative serum total bilirubin, total bile acid, aspartate aminotransferase, or gamma-glutamyl transpeptidase levels among the four groups. On the other hand, the grade 2 and 3 groups tended to include patients with a lower age at operation, and lower amylase levels in the serum and bile. Postoperatively, clinical symptoms resolved and laboratory data normalized in all patients. Two patients underwent liver biopsy for other reasons 3 and 4 years after surgery, which confirmed disappearance of the liver fibrosis. These patients had originally had grade 1 and grade 2 fibrosis, respectively. CONCLUSION: Mild to moderate liver fibrosis is present in almost half of all children with CDBD; however, if it is graded as less than moderate, it will probably not affect the postoperative clinical course.

Abstract: Feasibility of duct-to-duct biliary reconstruction in adult living related liver transplantation (LRLTx) has been recently reported; however, little has been known of its surgical outcome in children. To assess the feasibility and safety of duct-to-duct biliary reconstruction in children, the surgical outcomes of duct-to-duct biliary reconstruction were retrospectively analyzed. The subjects were three children who underwent LRLTx in our hospital each utilizing allografts with a right lobe, a left robe and a lateral segment, respectively. The cause of end-stage liver disease in each of them was fulminant Wilson's disease, fulminant hepatic failure and unresectable hepatoblastoma. Duct-to-duct anastomosis was performed in younger patients and adolescents with interrupted and continuous sutures, respectively. The diameter of bile duct in allografts was from 4 to 6 mm and 12 or 13 stitches were required for anastomosis. Post-operative choledochography from the external tube showed neither stenosis nor leakage and the tube was evacuated within 3 months after LRLTx. No biliary complications were observed with the median follow-up of 28 months. In conclusion, our results show that duct-to-duct biliary reconstructions in pediatric LRLTx seemed to be feasible and safe. Further studies are required to elucidate its real impact on pediatric LRLTx.

Abstract: We report a case of a two-yr-old boy with hepatoblastoma resectable only by total hepatectomy including the vena cava. Successful LTx was performed with a living donor segment without vena cava reconstruction. The tumor was located in the bilateral lobe, surrounding the IVC. In spite of the high-dose chemotherapy, the tumor did not become resectable. LTx was performed using left lateral segment after removal of the IVC combined with total hepatectomy. Because the collaterals were well developed, the patient tolerated the procedure well. The serum AFP level decreased from 186 699 to 8 ng/mL in 11 months after LTx without local recurrence or distant metastasis.

Abstract: PURPOSE: Exploratory laparotomy with cholecystocholangiography is often performed for the definitive diagnosis of biliary atresia (BA) when radiological and biochemical studies are inconclusive. Laparoscopic cholecystocholangiography (LCC) has recently been introduced as an alternative procedure to avoid unnecessary laparotomy. We discuss the advantages and indications of LCC based on our experience of performing this diagnostic procedure in four infants with prolonged direct hyperbilirubinemia. METHODS: We performed LCC in four infants by direct percutaneous puncture of the gallbladder by inserting a cholangiocatheter into the gallbladder or cystic duct. The decision to perform LCC was based on ultrasonography and computed tomography findings of an atrophic gallbladder with a patent lumen, although analysis of duodenal juice and hepatobiliary scintigraphy showed no sign of the excretion of bile into the small intestine. RESULTS: In three infants, LCC did not show the entire biliary system, and laparotomy was necessary to confirm the diagnosis of BA. However, in the other patient LCC showed a normal biliary system and BA was excluded. CONCLUSION: Laparoscopic cholecystocholangiography may be useful for the differential diagnosis of BA in patients with a patent gallbladder when imaging and biochemical findings are inconclusive. Furthermore, unnecessary exploratory laparotomy may be avoided in patients without BA.

Abstract: PURPOSE: To clarify the correlation between portal hypertensive gastropathy (PHG) and clinical features after surgery for biliary atresia (BA). METHODS: Routine upper gastrointestinal endoscopies were done over 3 years in 27 children who underwent surgery for BA. We reviewed the recorded endoscopic findings, and retrospectively diagnosed PHG according to McCormack's criteria. The differences in clinical features, such as endoscopically treated gastroesophageal varices and the results of routine laboratory tests, were compared between the children with PHG (PHG group) and those without PHG (non-PHG group). RESULTS: Nine (33%) of the 27 children had PHG. Although there was no significant difference in age between the PHG and non-PHG groups, the frequency of past endoscopic variceal treatments was significantly higher in the PHG group (3.0 +/- 3.0 vs 0.6 +/- 1.5 times, P = 0.01). The PHG group also had lower white blood cell and platelet counts, at 3008 +/- 2411 vs 5527 +/- 2938/mm3 (P < 0.05) and 6.0 +/- 3.4 vs 13.9 +/- 4.7 x 10(4)/mm3 (P = 0.0001), respectively; higher serum aspartate aminotransferase, total bile acid, and total bilirubin levels at 80 +/- 31 vs 46 +/- 29 U/l (P < 0.05), 161 +/- 93 vs 64 +/- 88 U/l (P < 0.05), and 4.8 +/- 5.6 vs 1.0 +/- 0.8 mg/dl (P < 0.01), respectively; and lower prothrombin time, albumin, and cholinesterase levels, at 66 +/- 16 vs 79% +/- 14% (P < 0.05), 3.6 +/- 0.8 vs 4.1 +/- 0.5 g/dl (P < 0.05), and 2158 +/- 925 vs 3376 +/- 700 U/l (P < 0.001), respectively. CONCLUSION: Portal hypertensive gastropathy was found in 33% of children after surgery for BA. The factors contributing to the development of PHG were frequent endoscopic treatments of gastroesophageal varices, liver dysfunction, and hypersplenism.

Abstract: We herein report a rare case of recurrent pancreatitis caused by malrotation of the intestine. Since the age of 10 years, a female patient showed recurrent epigastralgia and was diagnosed at age 16 years as suffering from acute pancreatitis. Upper gastrointestinal series showed that the duodenal bulb was elongated and rotated caudally. Endoscopic retrograde cholangiopancreatography showed that the descending portion of the duodenum was rotated and occluded the papilla of Vater. Under laparoscopy, the duodenal bulb was tracted caudally by the Ladd's ligament. By incision of this ligament, the entire duodenum was mobilized, with subsequent reduction of the rotation and compression of the pancreatic head. The girl's postoperative course was uneventful, and she has been asymptomatic for the last 3 years. In conclusion, malrotation of the intestine may be a rare cause of recurrent pancreatitis, and laparoscopic Ladd's procedure may be a less invasive and useful treatment.

Abstract: BACKGROUND: For giant gastric varices in association with portal hypertension, endoscopic treatment often is difficult. Although balloon-occluded retrograde transvenous obliteration (B-RTO) has been performed successfully in adult cirrhotic patients, there has been no report in pediatric patients. METHODS: A 10-year-old girl with biliary atresia (BA) who had been free of jaundice after hepatic portoenterostomy was detected to have isolated gastric fundal varices by routine endoscopy. They gradually enlarged up to 4 cm in diameter, showing a tense appearance, so prophylactic treatment was conducted. Magnetic resonance angiography showed the blood flow of the varices mainly drained by a large gastrorenal shunt. A balloon catheter was introduced into the gastrorenal shunt via the femoral vein and was inflated to occlude the outflow of the varices. Five percent ethanolamine oleate was injected into the varices, and the outflow occlusion was kept for more than 30 minutes. Extensive thrombosis was achieved by an additional embolotherapy after 17 months. Throughout the course, the patient has been doing well without bleeding or worsening of the liver function tests. CONCLUSIONS: B-RTO for isolated gastric fundal varices has been performed safely in a pediatric patient and seems effective in reducing the variceal size and tension.

Abstract: Congenital portosystemic shunt is a rare clinical entity that may progress to jaundice, severe encephalopathy, and pulmonary hypertension and require surgical correction or coil embolization. We present a novel approach to the management of children with congenital portosystemic shunt by means of a minimally invasive surgical technique. Congenital portosystemic shunts were identified between the superior mesenteric vein and inferior vena cava in case 1 and between the splenic vein and left renal vein in case 2. Both of them were successfully ligated by laparoscopic approach, and catheters were subsequently replaced to monitor portal venous pressure. The patients tolerated the procedure well, and short-term results were excellent. Laparoscopic ligation of congenital portosystemic shunt is technically feasible and less invasive to the management of patients with congenital portosystemic shunts, preventing late onset, life-threatening complications.

Abstract: BACKGROUND: The pediatric end stage liver disease (PELD) score has been used widely to prioritize children awaiting cadaveric liver transplantation (LTx). To establish the objective parameter for optimal timing of living-related LTx (LRLTx), we have assessed our cases using the PELD score. METHODS: From 1997 to 2002, 24 children were evaluated 28 times for the indication of LRLTx. Among them, 15 were for jaundice and nine for growth failure, hepatopulmonary syndrome, and variceal bleeding. Nine of 24 children underwent LRLTx. They were divided into several groups according to their clinical course. The PELD score consisted of age, albumin, total bilirubin, prothrombine time-international ratio (INR) and growth failure. A cut-off value was obtained by the highest positive and negative predictive value. RESULTS: The PELD score in cases whose indication for LRLTx was approved was significantly higher compared with the cases who were not, and a cut-off value of 4 was obtained. The PELD score in cases who were alive after LRLTx was significantly lower compared with the cases who died after LRLTx or evaluation of the indication, and a cut-off value of 22 was established. CONCLUSION: LRLTx may be considered when the PELD score exceeds 4, and LRLTx may be required immediately when the PELD score exceeds 22.

Abstract: This study was designed to elucidate whether the fibrosis index (FI), which was measured as a ratio of histological fibrotic tissue area to the whole area using an image analyzer, could reflect liver function and long-term prognosis in biliary atresia (BA). Liver biopsies were performed in 46 BA patients at hepatic portoenterostomy (HPE) and stoma closure. The chronological difference rate of FI (FIDR) was the monthly FI difference between HPE and stoma closure. FI at HPE and stoma closure was significantly higher than in the control. FI at HPE and at stoma closure significantly correlated with gammaGTP or T.Bil, D.Bil, cholinesterase and total bile acid, respectively. FIDR in jaundice-free group was significantly lower than in jaundiced group at 5 years after HPE. FIDR in V-2 (varices with red-color sign) was significantly higher than in V-0 (no varices) or V-1 (varices without red-color sign). ICG-K value significantly correlated with FIDR. FI at stoma closure or FIDR was significantly lower in living patients than in patients who eventually died or underwent liver transplantation. In conclusion, FI can reflect the degree of cholestasis in BA. FIDR would be useful for predicting long-term outcome in BA.

Abstract: We performed laparoscopic liver biopsy in a 10-year-old girl with acute myelocytic leukemia and coagulopathy. Each biopsy was taken under laparoscopic ultrasound (LUS) guidance, and hemostasis was achieved with an argon beam coagulator (ABC). These instruments were introduced through one 10/12-mm port, which also allowed the insertion of surgical gauze for direct compression. By using LUS, ABC, and one full-sized working port, laparoscopic liver biopsy becomes a viable and safer alternative, even for children with coagulopathy.

Abstract: BACKGROUND: Effective immunosuppression is a critical determinant of graft survival in small-bowel transplantation (SBTx). The present study was designed to determine the potency of FTY720, a newly synthesized immunosuppressant, in rat SBTx and examine the phenotype of graft-infiltrating cells to evaluate its effect on intestinal allografts. MATERIALS AND METHODS: A segment of intestine of Dark Agouti rats was transplanted heterotopically into Lewis rats. The recipients were treated with or without oral FTY720 at a dose of 1 mg/kg per day. Six days after surgery, peripheral blood lymphocytes and lymphocytes from the mesenteric lymph nodes, Peyer's patches, intraepithelial site, and lamina propria of the intestinal allograft were isolated. After the number of lymphocytes in each site was counted, the lymphocyte subpopulations in the intestinal allograft were evaluated by means of a FACScan flow cytometer using several monoclonal antibodies. RESULTS: FTY720 treatment significantly prolonged recipient survival and strongly inhibited rejection histologically in comparison with control rats. FTY720 immunosuppression resulted in a marked reduction of lymphocyte number in the graft epithelium and lamina propria and the proportion of CD8+ and CD25+ cells. FTY720 also significantly decreased T-cell receptors and increased B cells in the graft Peyer's patches. CONCLUSION: FTY720 promoted long-term SBTx recipient survival and maintained the architecture of intestinal allografts. FTY720 immunosuppression may be associated with a reduction of T-cell recruitment subsequent to the redistribution of lymphocyte subpopulations to control the proliferation and activation of graft-infiltrating cells in intestinal allografts.

Abstract: This report describes a patient with biliary atresia (BA) associated with polysplenia syndrome who showed a rapid progression of intrapulmonary arteriovenous shunting (IPS), resulting in a fatal outcome. Intrauterine ultrasonography at 36 weeks of gestation revealed fetal abnormalities, including situs inversus, absent retrohepatic inferior vena cava, and azygous connection. She was diagnosed postnatally as BA because of persistent acholic stool and neonatal jaundice. She underwent hepatic portoenterostomy at age 158 days. The gallbladder and the hepatic ducts were hypoplastic, and the common bile duct was absent. Magnetic resonance image and operative findings also identified polysplenia and an absent portal trunk. Liver histology showed cirrhotic changes and bile duct proliferation. Postoperatively, she achieved good bile secretion, with gradual decrease of total bilirubin. However, she had repeated febrile episodes, and computerized tomography at age 7 months showed multiple liver cysts. Thereafter, she presented with exertional dyspnea. Contrast-enhanced echocardiography showed IPS with a degree of 2/III at age 8 months and 3/III at 10 months. (99m)Technetium-labeled macroaggregated albumin ((99m)Tc-MAA) scintigraphy revealed a shunt ratio of 25.5% at 9 months and 39.7% at 10 months. Percutaneous transhepatic drainage of the bile cysts was performed without success. Sludged bile was obtained. However, respiratory distress rapidly progressed, and she died at age 11 months. In the present patient, the association of polysplenia syndrome and absent portal vein with BA, as well as liver cirrhosis, seemed to be contributing factors to rapid progression of IPS in early life.

Abstract: We report 2 cases of umbilical cord ulcer associated with fetal jejunal atresia. Both of them developed a severe intrauterine hemorrhage, followed by fetal heart rate decelerations, and underwent emergency cesarean section. Bloody amniotic fluid and umbilical cord ulcers were observed in both cases. Although both cases were successfully resuscitated, neurological impairment and renal failure developed in 1 case due to prolonged asphyxia. In a review of the literature, umbilical cord ulcer was associated only with congenital duodenal atresia or jejunal atresia, but not with ileal atresia. Although the prenatal diagnosis of duodenal or upper jejunal atresia has been established, the prenatal diagnosis of this complication has not been reported. In such cases, detailed examination of the umbilical cord by ultrasonography may be useful for the prenatal diagnosis of this disease.

Abstract: To determine the role of redo hepatic portoenterostomy (HPE) in biliary atresia (BA) patients with insufficient bile excretion after the initial HPE, 25 patients (type I, correctable: 2; type III, uncorrectable: 23) undergoing the initial HPE at 25 to 119 days of age were studied. Four patients achieved disappearance of jaundice (total bilirubin [T.Bil] < 2 mg/dl) postoperatively. A redo HPE was performed at 2 to 8 months of age with sufficient and extensive removal of granulation and scar tissue at the hepatic hilum. Five patients became free of jaundice in 3 to 6 months (group 1), while the remaining 20 did not (group 2). Disappearance of jaundice after the initial HPE had been achieved in 2 of 5 patients (40%) in group 1 and 2 of 20 (10%) in group 2 ( P < 0.05). Age, serum T.Bil, aspartate aminotransferase albumin, prothrombin time, cholinesterase, total cholesterol, and Fischer's ratio at redo HPE showed no significant differences between the two groups. On liver histology obtained at redo HPE, cirrhosis and hepatocyte degeneration were seen in 1 of 5 cases (20%) in group 1 and 12 of 20 (60%) in group 2 ( P < 0.05). Redo HPE may thus be effective in BA patients with insufficient bile drainage who achieved disappearance of jaundice after the initial HPE and have not developed cirrhosis.

Abstract: Serum total bile acid levels (STBA), a sensitive indicator of cholestasis, were measured during the long-term postoperative period in patients with congenital bile-duct dilatation (CBDD) (choledochal cyst) and the factors contributing to elevation of STBA were analyzed in 44 patients. Their ages at operation ranged from 1 month to 16 years. A STBA level over 12 nmol/ml on two or more measurements during outpatient follow-up was considered abnormal. Patients were classified into three groups: group 1, STBA, 12-50 nmol/ml; group 2, STBA > or = 50 nmol/ml; group N, STBA normal. In 19 patients (43.2%) STBA was normal. Of the 25 patients (56.8%) with elevated STBA, groups 1 and 2 comprised 12 (27.3%) and 13 patients (29.5%), respectively. The mean age in group N was 5.1 +/- 4.2 years, which was higher than in groups 1 (2.6 +/- 2.3) and 2 (2.3 +/- 2.5 years) ( P< 0.05). Preoperative STBA and total bilirubin were higher in group 2 (79.2 +/- 75.1 nmol/ml resp. 5.2 +/- 4.2 mg/dl) than in groups N (20.1 +/- 32.6, 1.3 +/- 1.4) and 1 (22.8 +/- 37.2, 1.4 +/- 1.0) ( P< 0.05). Preoperative alkaline phosphatase and gamma-glutamyl transpeptidase were higher in group 2 (1,006 +/- 872 IU/l, 452 +/- 326 IU/l) than in group N (573 +/- 371, 205 +/- 238) ( P< 0.05). Histologic findings on liver biopsy showed fibrosis in 38.5% of group 2 patients, which was significantly higher than in groups N (15.8%) and 1 (16.7%) ( P< 0.05). Cholestasis was detected in 41.7% of group 1 and 61.5% of group 2 patients, compared to 10.5% of group N patients ( P< 0.05). Postoperative elevation of STBA may thus persist in more than one-half of patients with CBDD, and is likely to occur in patients of young age who have severe cholestasis or liver fibrosis preoperatively. Further investigations may be required in regard to the development of postoperative complications.

Abstract: It has not been fully determined whether isolated small bowel transplantation (ISBTx) can reverse liver dysfunction caused by intestinal failure requiring long-term total parenteral nutrition (TPN). A boy with congenital microvillus inclusion disease presented with vomiting and severe diarrhea since the first day of life and had been managed by TPN since then. He suffered from catheter-related sepsis several times. At 14 yr of age he developed progressive hepatosplenomegaly with thrombocytopenia and coagulopathy. He underwent ISBTx with an ileal graft from his blood-identical grandmother at the age of 16 yr. Oral feeding was started on the 14th day after ISBTx and gradually increased. TPN was completely withdrawn after 5 months. Liver was palpated 5 cm below the costal margin before ISBTx, while it became non-palpable 5 months after ISBTx. Serum liver enzyme levels and prothrombin time normalized in the 5 months following ISBTx. Liver biopsy showed marked steatosis, slight cholestasis, and mild bridging fibrosis before ISBTx. Although histological examination of liver biopsy revealed complete disappearance of steatosis 7 and 11 months after ISBTx, liver fibrosis remained unchanged. This clinical experience has shown that although steatosis and cholestasis are reversible after successful ISBTx and withdrawal of TPN, liver fibrosis may remain unchanged.

Abstract: We reported successful laparoscopic fundoplication in 2 pediatric cases with VPS and discuss the safety and feasibility of the procedure. Case 1: A 13-year-old girl with VPS underwent laparoscopic fundoplication. Case 2: a 9-year-old boy with VPS underwent laparoscopic fundoplication. In both cases, laparoscopic Nissen fundoplication was performed with a standard five-port technique with a low pressure of a pneumoperitoneum. The VPS system had no effect on port layout and intraabdominal manipulation and no adverse complications were observed in either case. The effect of a pneumoperitoneum in the VPS system remains controversial, however, the author emphasized that advanced laparoscopic surgery can be performed safely with creating a low pressure of a pneumoperitoneum.

Abstract: A 1-yr-old girl underwent a living-related liver transplant, with reconstruction of hepatic artery of 2 mm in diameter under microscopy. She developed intestinal perforation requiring closure on day 4 post-transplant and suffered from hepatic artery stenosis (HAS) on post-transplant day 9. Conservative therapies, such as intravenous or transluminal administration of anti-coagulants, vasodilators or fluids, were unsuccessful and caused remarkable general edema and multiple arrhythmias as a result of increased preload. On day 15 post-transplant, because flow velocity was remarkably reduced (as shown by Doppler ultrasound) the patient underwent percutaneous transluminal angioplasty (PTA) using a kit for coronary angioplasty. The balloon catheter was inflated [first: 1.5 mm diameter, 4 atmospheric pressure (a.p.) for 30 seconds (s); second: 2.0 mm diameter, 4 a.p. for 30 s; third: 2.5 mm diameter, 10 a.p. for 30 s]. The stenosis was successfully dilated without any complication. The patient has been doing well with normal liver functions for 4 months after PTA. From this experience, PTA can be performed for HAS after liver transplantation, even in an infantile case, with a careful technique and a special device.

Abstract: BACKGROUND/PURPOSE: To evaluate if thrombocytopenia may be related to plasma thrombopoietin level (P-TPO) in postoperative biliary atresia (BA). METHODS: Forty-three postoperative BA patients aged 1 to 20 years were included. P-TPO was measured by enzyme immunoassay. P-TPO was compared with platelet counts (Plt), Child's classification, presence of splenomegaly, and liver function tests. RESULTS: P-TPO significantly correlated with Plt, child's classification, serum albumin, and cholinesterase level, respectively. In 4 patients undergoing portal decompression procedure, preoperative and postoperative Plt and P-TPO were 87.5 +/- 69.1 x 10(3) and 50.3 +/- 28.0, 118.8 +/- 62.3 x 10(3)/mm3, and 53.0 +/- 55.0 pg/mL, respectively, without significant difference. In 6 patients undergoing liver transplantation (LTx), Plt and P-TPO after LTx was 157.5 +/- 83.5 x 10(3) and 143.5 +/- 75.2, respectively, which were significantly higher than those before LTx (55.0 +/- 15.6 x 10(3)/mm3 and 53.2 +/- 32.9 pg/mL). CONCLUSION: Thrombocytopenia in postoperative BA may be caused by decreased plasma TPO level in accordance with the severity of liver dysfunction rather than hypersplenism.

Abstract: Acute cellular rejection (ACR) and preservation injury (PI) are major complications occurring early after liver transplantation (LTx) and sometimes lead to severe graft dysfunction. We herein report an infant who developed marked hyperbilirubinemia as a result of combined ACR and PI in addition to ischemic damage from bleeding, but recovered without re-LTx. In a 1-yr-old-girl undergoing living-related LTx, liver biopsy (LBx) on post-operative day 7 showed ballooning of the hepatocytes, i.e. microvesicular steatosis (30%) and occasional centrolobular necrosis, consistent with mild-to-moderate PI and ACR with a rejection activity index (RAI) of 2.0. Because drainage of an intra-abdominal abscess was performed and a systemic infection was considered severe, the tacrolimus level was decreased and steroids were discontinued. The total bilirubin level started to rise, thereafter, reaching a maximum of 47.6 mg/dL at 1 month after LTx. LBx showed an RAI of 6.0 and steatosis of 10%. With good response to an increase of tacrolimus level and administration of steroid, the total bilirubin level gradually decreased, finally reaching the normal range in 3 months, and LBx showed no steatosis or finding of ACR. From this experience, ACR, if combined with mild-to-moderate PI or other ischemic damage, may lead to severe clinical manifestations after LTx, which, however, could remit with conservative therapy and without re-LTx.

Abstract: Although prenatal ultrasonographic (US) diagnosis has been reported in biliary atresia (BA), most cases are type I (correctable with cystic dilatation). We report three prenatal cases of type IIId BA (uncorrectable with cystic dilatation). Routine fetal US at 22 to 24 weeks of gestation showed two communicating cystic lesions 12 to 16 mm in diameter. On color Doppler US, the lesions were separate from the portal vein or hepatic artery. The size did not change during the prenatal period in any case. Choledochal cyst (CC) was considered the most likely diagnosis, although BA with cystic lesions was also considered. After birth, the patients developed acholic stools and prolonged neonatal jaundice. Hepatobiliary scintigraphy showed negative passage. Duodenal fluid showed a negative or slightly positive Gmelin test. The neonates underwent laparotomy at the age of 36, 46, and 32 days, respectively. Intraoperative cholangiography showed the gallbladder and slightly-dilated common-bile duct without entering the proximal or distal bile ducts in all cases. They were classified as type IIId BA and underwent excision of the cystic lesions and dissection of the portal bile-duct remnants, followed by hepatic portoenterostomy. Case 1 showed persistent jaundice and finally underwent liver transplantation (LTx), case 2 became anicteric. Case 3 remained jaundiced and is to undergo LTx. In conclusion, type IIId BA may be one of the differential diagnoses when a cystic lesion is detected under the hepatic hilum by fetal US. However, prenatal diagnosis of BA is still difficult with respect to differentiation from a CC or type I BA. Early postnatal diagnosis followed by immediate treatment is important, especially in type IIId BA.

Abstract: This report describes a 1-yr-old boy with biliary atresia (BA) and polysplenia syndrome (PS) who underwent successful living-related liver transplantation (LTx). At the time of initial hepatic portoenterostomy, he was noticed to have a preduodenal portal vein (PV), non-rotation of the intestine, and polysplenia. Because he did not achieve good bile excretion, he underwent a living-related LTx (using a left lateral segment from his mother) at the age of 14 months. Evaluation of the vascular anatomy was made by angiography, magnetic resonance imaging (MRI), computerized tomography (CT), and Doppler ultrasound. The PV was stenotic from the confluence of the superior mesenteric vein (SMV) and splenic vein (SpV) to the hepatic hilum. The retrohepatic inferior vena cava (IVC) was deficient cranially to the renal vein and was connected to the azygous vein. The supra-hepatic IVC was detected below the diaphragm and was connected to three hepatic veins. The common hepatic artery (HA) originated from the superior mesenteric artery. At LTx, the PV was dissected to the level of confluence of the SMV and the SpV, from which the venous graft was interposed using the donor's ovarian vein. Three hepatic veins were plastied into one orifice, which was anastomosed to the graft's hepatic vein under the diaphragm. The graft vascularity and function has been good for 1 yr after LTx. In the present case, sufficient pre-LTx evaluation of vascular anomalies seemed to help performance of the successful LTx.

Abstract: BACKGROUND: This study evaluated zoom endoscopic findings according to four components in comparison with the histologic findings of acute cellular rejection (ACR) in a living-related small bowel transplantation (SBTx) patient. METHODS: A 16-year-old boy with microvillus inclusion disease underwent SBTx with a 150-cm-long ileal graft from a blood-identical living-related donor. The endoscope was inserted into the distal stoma of the graft, and the mucosal architecture was observed under zoom. The observed findings were expressed by the following four components and graded as 0 to 2: H, homogeneity of mucosal change, minimal (H-0), patchy (H-1), diffuse (H-2); V, appearance of villi, stringlike (V-0), tonguelike (V-1), domelike (V-2); W, widening of crypt area, narrow (W-0), slightly widened within a width of one villus (W-1), markedly widened beyond a width of one villus (W-2); E, erythema in crypt area: no redness (E-0), sporadic erythema (E-1), diffuse erythema (E-2). RESULTS: Histologic ACR was grade 0 in 27, grade 1 in 6, grade 2 in 3, and grade 3 in 0 occasions during 11 months after SBTx. In grade 0, 1, and 2 histology, H-0/H-1/H-2 was 85.2%/14.8%/0%, 33.3%/66.7%/0%, and 0%/100%/0%, respectively, with a significant difference among the groups by grade (P<0.05). V-0/V-1/V-2 was 48.1%/51.9%/0%, 0%/100%/0%, and 0%/66.7%/33.3% (P<0.05), W-0/W-1/W-2 was 85.2%/14.8%/0%, 0%/100%/0%, and 0%/66.7%/33.3% (P<0.05), and E-0/E-1/E-2 was 100%/0%/0%, 66.7%/33.3%/0%, and 0%/100%/0% (P<0.05), respectively. CONCLUSION: Zoom endoscopic findings, graded on four components, may reflect the histologic severity of ACR and minimize the performance of biopsies in SBTx.

Abstract: The feasibility of oral administration of tacrolimus in the presence of an intestinal stoma after liver transplantation (LTx) has not been adequately demonstrated. A 10-month-old girl underwent LTx with biliary reconstruction using a Roux-en Y loop. She developed intestinal perforation and underwent a jejunostomy at 40-50 cm distal to the jejunojejunostomy of the Roux-en Y loop on day 8 post-LTx. Tacrolimus was given twice daily via a nasogastric tube or orally; the initial dose of tacrolimus was 0.10 mg/kg/day. Until the time of intestinal perforation, the trough level of tacrolimus ranged from 13.0 to 19.6 ng/mL. The dose-normalized trough concentration (DNTC) of tacrolimus ranged from 130 to 196 ng.kg.day per mg.mL (control: 80-145 ng.kg.day per mg.mL). For a 2-week period when the patient was septic, the tacrolimus dose was reduced to 0.05 mg/kg/day, with a subsequent trough level of 3.6-5.1 ng/mL (DNTC: 72-102 ng.kg.day per mg.mL). After 3 weeks, the dose was increased to 0.175 mg/kg/day with the disappearance of infection; the trough level ranged from 8.5 to 9.7 ng/mL with a peak level of 26.3 ng/mL (DNTC: 48.5-55.4 ng.kg.day per mg.mL). After the initiation of oral feeding, the dose was slightly increased to 0.20 mg/kg/day with the trough level ranging from 8.1 to 9.8 ng/mL (DNTC: 40.5-49 ng.kg.day per mg.mL). After closure of the jejunostomy, the dose of tacrolimus was reduced to 0.075 mg/kg/day to maintain the same trough level (7.9-9.1 ng/mL) and the DNTC ranged from 105 to 121 ng.kg.day per mg.mL. In conclusion, oral administration of tacrolimus may achieve the therapeutic level, even in the presence of jejunostomy after LTx, although the bioavailability is decreased.

Abstract: BACKGROUND: Human herpesvirus 6 (HHV-6), a causative virus of exanthem subitum, may occasionally present with a severe clinical form in immunosuppressed patients after transplantation. In this study, HHV-6 DNA was sequentially measured with a polymerase chain reaction (PCR) method, a quick and sensitive modality in pediatric living-related liver transplantation (LTx). METHODS: Subjects consisted of 5 post-operative biliary atresia patients undergoing living-related LTx at ages from 8 months to 4 yr. Immunosuppression was performed with Tacrolimus (blood trough level 8-18 within 1 month and 5-10 ng/mL thereafter) and low-dose steroid. Specimens were peripheral blood mononuclear cells (PBMC), plasma, and liver biopsy tissue. The amount of HHV-6 DNA was semiquantified as follows: 1+, 1-10; 2+, 10-100; 3+, 100-1000; 4+, over 1000 copies/105 PBMCs. RESULTS: A total of 69 blood samples and three liver biopsies were provided for the examination. HHV-6 DNA in PBMC was positive in 2 donors and 3 recipients before LTx. Two patients with negative DNA were converted to 3+ at 2-3 wk after LTx and 3 with positive DNA remained 2+ to 3+ throughout the post-LTx period. Only 1 patient developed clinical symptoms, such as fever, liver dysfunction, petechiae, idiopathic thrombocytopenic purpura, and finally bone marrow suppression. HHV-6 DNA in the liver biopsy tissue and plasma in this patient were 4+ and 2+, respectively. CONCLUSION: HHV-6 DNA in PBMC measured by the PCR method may be persistently high in pediatric recipients after living-related LTx. Although HHV-6 DNA in PBMC may be positive in case of evident infection, positivity in PBMC may not be always associated with the clinical symptoms.

Abstract: BACKGROUND/PURPOSE: The aim of this study was to examine if the plasma endothelin-1 (ET-1), a potent vasoconstrictor, level may reflect the severity of portal hypertension associated with liver cirrhosis in biliary atresia (BA). METHODS: Forty-eight postoperative BA patients aged 6 months to 20 years were studied. Plasma ET-1 was measured by a sandwich method of enzyme immunoassay. ET-1 was compared with Child's score and laboratory data. ET-1 levels were compared among groups of patients with various degrees of histologic fibrosis and portal hypertension. RESULTS: Plasma ET-1 was 5.3 +/- 3.5 pg/mL in BA, higher than in controls (3.1 +/- 0.8, n = 27; P <.05). ET-1 correlated with Child's score, serum total bilirubin, direct bilirubin, aspartate aminotransferase, albumin, prothrombin time, hepaplastin test, fibrinogen, cholinesterase, total cholesterol, Fischer's molar ratio, prealubumin, and hyaluronic acid, respectively (P <.05). ET-1 also correlated with the severity of histologic fibrosis, gastroesophageal varices, the presence of splenomegaly, ascites, venous dilatation on the abdominal wall, or pulmonary vascular abnormalities. In 4 patients undergoing liver transplantation (LTx), ET-1 after LTx was lower than that before LTx (P <.05). CONCLUSION: Plasma ET-1 level may be a useful index reflecting the severity of cirrhosis and portal hypertension in BA.

Abstract: PURPOSE: This report presents biliary atresia (BA) patients with intrapulmonary arteriovenous shunting (IPS), which was evaluated suitably by contrast-enhanced echocardiography (CEC). METHODS: Of 88 BA patients seen in the last 20 years, 8 (9.1%) had IPS at 8 months to 16 years of age. Two were associated with polysplenia syndrome, 1 had persistent jaundice after hepatic portoenterostomy, and 2 underwent splenorenal shunt. According to the comparison between microbubbles in left atrium (LA) and in right atrium (RA) detected by CEC, IPS was classified as grade I, mild (LA << RA); grade II, moderate (LA < RA); grade II, severe (LA = RA). RESULTS: Grade I consisted of 4 patients whereas grade II and III held 2 patients each. Clinical symptoms such as cyanosis, exertional dyspnea, or clubbing were present in 50% of grade I and all of grade II and IlI. Mean PaO2 in grade I, II, and III was 70.5, 50.4, and 35.3 mm Hg, respectively. In 1 patient with grade I, IPS spontaneously disappeared, but pulmonary hypertension developed later. One patient in grade II died of pulmonary complications, and the other is considered a candidate for livertransplantation (LTx). One patient in grade III died of liver failure, whereas the other is free of IPS after LTx. CONCLUSION: IPS can lead to a life-threatening complication in postoperative BA patients, and CEC may be a convenient and useful method to evaluate the degree of IPS and determine therapeutic strategy.

Abstract: PURPOSE: The aim of this study was to clarify whether serum hyaluronic acid level (SHA) can reflect the degree of liver fibrosis in biliary atresia (BA). METHODS: SHA was measured in 44 postoperative BA patients at 7 months to 22 years of age, with sandwich enzyme method (Hy-A 100 kit). SHA was compared with T.Bil (group 1, T Bil < 2; group 2, 2 < or = T Bil < 5; group 3, T Bil > or = 5 mg/dL), fibrosis score (0-6, the number of abnormal values among Alb, PT, ChE, T Chol, Fischer's ratio, prealbumin), and histologic grading (0-IV). RESULTS: SHA was 499.8 +/- 332.5 in group 3, significantly higher than in the control, group 1, or group 2. As fibrosis score rose, SHA became higher, and SHA in Score 6 (430.1 +/- 366.1 ng/mL) and score-5 (172.9 +/- 141.8 ng/mL) was significantly higher than in the control and other scores, respectively. As the histologic grade rose, SHA became higher, and SHA in grade IV (444.8 +/- 323.5 ng/mL) and grade III (166.0 +/- 70.3 ng/mL) was significantly higher than in the control or other Grades. Serial change of SHA since before HPE was parallel to the clinical course in 8 patients. CONCLUSION: SHA may be a useful serum marker reflecting the degree of liver fibrosis in BA.

Abstract: Although transjugular intrahepatic portosystemic shunt (TIPS) is widely accepted in adults, there have been few successful reports in infants. The authors describe a 2-year-old boy with postoperative biliary atresia who underwent TIPS for uncontrollable lower intestinal bleeding and achieved hemostasis. Massive melena developed, which was not controlled by conservative therapy and devascularization. A shunt was created between the right hepatic vein and the right portal vein with a 6- x 50-mm Wallstent. After TIPS, the porto-systemic pressure gradient decreased from 15 to 11 mm Hg, and collaterals markedly reduced. He has not had recurrent bleeding for over 7 months. TIPS may be a technically feasible and effective treatment to control intestinal bleeding in infants. However, further experience and long-term follow-up will be required.

Abstract: Spontaneous perforation of the bile duct (SPBD) is a rare disease in children. Pancreatico-biliary maljunction (PBM) has been postulated to contribute to its etiology. We have treated three children with SPBD over 30 years, two of whom had PBM. There was one boy and two girls aged 10 months to 2 years with symptoms of abdominal distension, vomiting, abdominal pain, jaundice, and acholic stools. The diagnosis of SPBD was made by paracentesis showing biliary ascites, and primary biliary and intra-abdominal drainage was performed in all cases. The site of perforation was at the connection of the common bile duct (CBD) with the cystic duct in all cases. In two cases reflux of contrast into the pancreatic duct was noted, the common channel was long (17 and 12 mm, respectively), and the bile amylase level in the CBD was abnormally high (50,000 and 67,000 IU/l, respectively). In the third patient there was no reflux of contrast into the pancreatic duct and the bile amylase and trypsin levels in the CBD and gallbladder were not measurable. Thus, SPBD in children may not be due solely to PBM, but may involve multiple mechanisms.