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Background/purpose: Advances in the management for biliary atresia (BA) have improved the prognosis and has greatly increased the number of long-term survivors. Even the long-term survivors, however, still face some problems. This retrospective review was performed to assess pregnancy-associated issues in long-term survivors after surgery for BA., Materials and Methods: Of 55 patients with BA surviving for 16 years or more without liver transplantation, 9 patients have experienced pregnancy and delivery. Clinical courses, the outcome of pregnancy and delivery, and current statuses were retrospectively evaluated from their clinical records., Results: The study revealed 14 pregnancies and 11 deliveries. Before pregnancy, no patient showed visible jaundice, but 6 patients had some complications such as episodes of cholangitis and portal hypertension. Two of the patients had both conditions and 2 others developed visible jaundice after pregnancy. One intrauterine fetal death occurred., Conclusions: Our retrospective review suggests that the previously mentioned conditions can be risk factor for cholangitis and gastrointestinal bleeding during or after pregnancy but are not considered to be contraindications for pregnancy and delivery. Complications can occur with pregnancy even during the normal course. Thus, careful observation is recommended.

Purpose: This retrospective study reviews the long-term outcome of type I biliary atresia (BA)., Methods: Three hundred twenty-three patients with BA, including 50 with type I, underwent corrective surgery. The surgical results, role of cholangiograms during the corrective surgery, late complications, and current statuses were evaluated., Results: The overall survival rate of the nontransplant type I patients was better than that of the type II/III patients (52% vs 33%, P = .0009). Cholangiograms of 32 patients were classified into 3 types: cloudy (48%), treelike (13%), and mixed (39%). Of 26 patients who underwent corrective surgery in 1972 or later, 7 (50%), 7 (78%), and 3 (100%) patients of the cloudy type, mixed type, and treelike type, respectively, have survived without liver transplantation (LTx). Of 18 type I patients who survived more than 20 years without LTx, 7 developed severe late complications. Two of them eventually required LTx after 20 years old., Conclusions: Use of cholangiograms during corrective surgery might have a long-term prognostic value. The overall survival rate of type I BA was better than that of type II/III. The incidence of late complications was, however, considerably high in the type I survivors. All patients required careful long-term follow-up.

The authors report a case of primary tracheal schwannoma (neurilemoma) causing symptoms of airway obstruction in a 9-year-old girl. Computerized tomography scan showed a polypoid intratracheal mass obstructing 73% of the lumen. Partial tracheal resection with primary anastomosis was performed. Histologic analysis showed a benign neurogenic tumor of Schwann cell origin.

Purpose: Members of the Japanese Biliary Atresia Society were surveyed to determine their current practice regarding early use of corticosteroids after Kasai's operation., Methods: Questions included the patient's background data, dosage, timing, complications, and outcome. Anicteric survival with the native liver was statistically compared between groups categorized by steroid dosage using Kaplan-Meier analysis., Results: Among 54 institutions surveyed, a total of 222 patients with uncorrectable BA were collected from 34 responders, including 208 patients who received steroid therapy and 14 without it. Prednisolone was started during the first postoperative week in 31% and during the second week in 64%. Perforation and peritonitis occurred in 1 patient given 3 mg/kg/d of prednisolone on postoperative day 1. The survival rates of the steroid and nonsteroid groups were 58.0% and 35.7%, respectively (P = .052). The initial dose of prednisolone was or=4.0 mg/kg/d in 108 patients. The survival rates of the group receiving >or=4.0 mg/kg/d and the nonsteroid group were 58.9% and 35.7%, respectively (P = .0494)., Conclusions: (1) Most surgeons use steroids. (2) Although the anicteric survival rate was higher in the steroid group, the number of patients in the nonsteroid group was too small to draw conclusions. (3) The recommended initial steroid dose is >or=4.0 mg/kg/d. (4) Complications are uncommon if administration is not started too early.

Background/purpose: A retrospective review was performed to assess the utility of diagnostic imaging (DI), efficacy of treatment, and outcome of late cholangitis in long-term survivors after surgery for biliary atresia., Methods: Sixty-one patients surviving without liver transplantation (LTx) for more than 20 years were divided into 2 groups depending on whether cholangitis developed after age 20. Clinical factors including the type of obstruction, the age at the initial operation, and the early complication with cholangitis were compared between the 2 groups. DI such as computed tomography scan and magnetic resonance imaging, clinical courses after treatment of cholangitis, and current status of the patients were also evaluated., Results: Thirteen patients had cholangitis after age 20. There was no statistical difference in the clinical factors studied between the 2 groups. Abnormal DI findings including dilatation of intrahepatic bile ducts and hepatic fibrosis were seen in 10 patients with late cholangitis. One patient died, and 2 ultimately underwent LTx. The remaining 10 patients including 4 with normal or near-normal liver function have survived without LTx., Conclusions: Although the majority of the patients had potential predisposing factors for cholangitis such as dilatation of intrahepatic bile ducts, a few patients unexpectedly had cholangitis without such abnormal findings after an excellent, long-term postoperative course.

Background/purpose: The authors created a new artificial anal sphincter using a shape memory alloy (AS-SMA) to treat fecal incontinence and evaluated its validity., Methods: AS-SMA consists of 2 Ti-Ni plates to sandwich the intestine and generates a pressure of 55 mm Hg at its resting position. With the electric power supply, the 2 metals bend to form an almondlike shape making a maximum gap of 33 mm between each other at the temperature of 55 degrees C. The device was attached to the colostomy in a piglet and was operated several times a day for 1 month. Fecal continence, bowel movements, and general condition of the piglet were recorded. After the experiment, tissue damage around the device was investigated., Results: Fecal continence was obtained while the device was in the resting position. When it was operated, bowel movements were observed. The bowel movements to operations ratio was 82:105 (78%). During the experiment, the animal had neither abdominal distension nor vomiting. At the autopsy, there was mild inflammation and shallow burns around the device. No compression injury was detected., Conclusions: AS-SMA achieved fecal continence of the colostomy. With reduction of the associated side effects, it would be a potential substitute for an impaired anal sphincter.

Purpose: To elucidate the role of partial splenic embolization (PSE) procedures, long-term outcome was assessed in terms of the recurrence of thrombocytopenia., Methods: A retrospective study was performed after 41 PSE procedures in 36 patients for hypersplenism owing to portal hypertension. The underlying disease was biliary atresia in 32 patients, extrahepatic portal obstruction in 3, and idiopathic cirrhosis in 1., Results: The average volume embolized was 70.1%. The patients were followed up from 20 days to 182 months (average, 70.8 months). Five patients subsequently died, and 6 underwent liver transplantation. The causes of death or the reasons for liver transplantation were not related to hypersplenism. Eleven patients (30.6%) had recurrence of thrombocytopenia (<100,000/mm3). There was no significant difference in the volume embolized or platelet count before PSE between the patients with and without recurrence of thrombocytopenia. The peak value of platelet count after PSE was significantly lower in the patients with recurrence of thrombocytopenia (P =.0091). In 17 of 24 survivors without liver transplantation, platelet counts remained normal throughout the follow-up period., Conclusions: PSE is a safe and effective procedure. Hematologic indices improved in all 36 patients after PSE, and its long-term efficacy was shown in 70% of the survivors.

Purpose: Technetium 99m DTPA-galactosyl human serum albumin (GSA) liver scintigraphy was performed in follow-up patients with biliary atresia, and its clinical significance was investigated., Methods: Between 1994 and 2001, GSA liver scintigraphy was performed 153 times in 57 follow-up patients. HH15, LHL15, and H/L15 (HH15/LHL15) were obtained. Patients were divided into 3 groups according to the clinical status (good, n = 17; fair, n = 24; poor, n = 16). The correlation between these parameters and liver function tests was examined. Twenty-six patients of the 57 underwent 3 serial GSA scintigraphies and also were divided into 3 groups (good, n = 13; fair, n = 8; poor, n = 5). (3rd/1st)H/L15 (3rd H/L15/1st H/L15) was obtained and compared., Results: H/L15 had a correlation with serum albumin and serum cholinesterase. H/L15 was statistically different among 3 groups (good, 0.97 +/- 0.15; fair, 0.94 +/- 0.09; poor, 1.12 +/- 0.21; P <.05). Although most patients in the good (10 patients; 76.9%) and fair (7 patients; 87.5%) groups showed (3rd/1st)H/L15 of less than 1.1, 3 patients (60%) in the poor group showed (3rd/1st)H/L15 of more than 1.1. (3rd/1st)H/L15 in the poor group was significantly higher than those in good and fair groups (P <.05)., Conclusions: Technetium 99m-GSA liver scintigraphy is useful to assess the functional hepatic reserve in follow-up patients with biliary atresia. Serial assessment with GSA scintigraphy can provide the trend of the patient's liver condition and can estimate the prognosis of the liver.

Purpose: The aim of this study was to elucidate the epidemiology and short- and long-term results of biliary atresia in Japan analyzing the data of the Japanese Biliary Atresia Registry (JBAR)., Methods: In 1989, the Japanese Biliary Atresia Society started a nationwide registry, JBAR, to investigate all aspects of biliary atresia. A total of 1,381 patients, 863 girls, 507 boys, and 11 unknown, were registered between 1989 and 1999. JBAR includes an initial and follow-up questionnaires. Using these patients' data, the incidence, sex distribution, associated anomalies, the type of obstruction, the type of operation, and the surgical results were evaluated. The 5- and the 10-year results of 735 patients who were registered initially in or before 1994 also were analyzed., Results: The incidence of biliary atresia was 1 in 9,640 live births. One hundred sixty-four patients (11.9%) had type I atresia of the common bile duct, 34 (2.5%) had type II atresia of the hepatic ducts, and 1,162 (84.1%) had type III atresia at the porta hepatis. Congenital associated anomalies were found in 19.6% of the patients including 33 cases associated with polysplenia. Impact of the age at operation on bile flow was not clear until 90 days of age, and after 90 days the bile flow rate worsened. The original Roux-en-Y procedure had been used in more than 50% of the patients since 1995. In 1999, 96% of the patients underwent the original Roux-en-Y procedure or the Roux-en-Y with an intestinal valve, and only 3 patients (3.5%) underwent other modifications. There were no significant differences in either the rate of disappearance of jaundice or the incidence of cholangitis among these 3 procedures. Of the 735 patients registered in or before 1994, 19 patients (2.6%) were lost to follow-up. The 5-year survival rates of patients registered in 1989, 1990, 1991, 1992, 1993, and 1994 were 62%, 64.5%, 61.3%, 59.0%, 58.7%, and 52.7% without liver transplantation (LTx), and 69.4%, 74.2%, 75.2%, 79.5%, 78%, and 78.3% with LTx, respectively. Although the overall 5-year survival rate changed from 69.4% to 78.3%, the difference was not statistically significant. According to the 10-year follow-up results of the 108 patients initially registered in 1989, 72 (66.7%) and 57 (52.8%) survived with and without the aid of LTx, respectively., Conclusions: The overall 5- and 10-year survival rates were 75.3% (553 of 734) and 66.7% (72 of 108), respectively. In spite of the increasing number of survivors after LTx, there was no significant improvement in the 5-year survival rate. It was shown that the JBAR system was functioning well with only 19 patients lost to follow-up among the 743 patients registered from 1989 to 1994.

Purpose: The aim of this study was to review 14 patients with congenital esophageal stenosis (CES) from diagnostic and therapeutic points of view., Methods: From 1976 to 1999, 14 patients with CES were treated at the authors' hospital. In each diagnostic examination, an esophagogram, 24-hour pH monitoring, a manometric study, and an endoscopy were performed. The medical, radiologic, and operative reports of these patients were reviewed., Results: Esophagogram results showed an abrupt stenosis in 5 patients and a tapered stenosis in 9. After 24-hour pH monitoring and an endoscopy, we were able to rule out the possibility of gastroesophageal reflux with esophagitis in most of the patients. Of the 11 patients who initially underwent bougienage or balloon dilatation, 8 of them had recurrent stenosis. Eleven patients required surgical treatment, including the 8 who had recurrent stenosis after undergoing dilatation. Nine of the patients underwent a resection of the stenotic segment and esophago-esophagostomy. An antireflux procedure was performed on 2 patients. Another patient had an esophageal rupture, which required a jejunal interposition. A histopathologic study showed that tracheobronchial remnants were present in 6 patients, and fibromuscular thickening was found in 4 patients., Conclusions: The efficacy of dilatation seems to be limited and may even result in severe complications such as an esophageal rupture. In this study, most patients ultimately required surgical treatment. Surgical repair for CES is the authors' preferred treatment, although initial dilatation may be effective for some patients., (Copyright 2003, Elsevier Science (USA). All rights reserved.)

Background/purpose: Low level of Insulinlike growth factor-I (IGF-I) has been reported in children with chronic liver disease like biliary atresia (BA) awaiting liver transplantation. However, there has been no report on IGF-I in BA managed without liver transplantation., Methods: The authors measured IGF-I and growth hormone (GH) in 21 postoperative BA, and 17 choledochal cysts (CC) as a control with normal liver function. To avoid an influence of aging, IGF-I was analyzed after converting them into a newly defined index "IGF%." IGF% is proportional to the lower limit of the value of IGF-I in gender- and age-matched normal control previously reported in literature., Results: IGF% in BA was significantly lower than that in CC. IGF% tended to be lower in Kasai's type III (atresia at the porta hepatis) and higher in the jaundice-free group. IGF% in patients with esophageal varices was significantly lower. The correlation between choline esterase and IGF% was positive and that for TTT and IGF% was negative., Conclusions: Low level of IGF-I is a characteristic finding in BA, especially in patients without need of liver transplantation. And it may reflect the severity of pathologic changes (ie, hepatic fibrosis and reduced volume of normally functioning liver) in BA liver., (Copyright 2003, Elsevier Science (USA). All rights reserved.)

Background/purpose: Portoenterostomy is an accepted method of achieving bile drainage in biliary atresia, but there is a paucity of data, including formal quality-of-life (QoL) studies, on long-term survivors. This report includes survival analysis and QoL studies from the world's largest series of cases treated in Japan (1951 to 1998). The Japanese QoL results are compared with a matched group of UK patients from King's College Hospital, London., Methods: One hundred fifteen Japanese surviving portoenterostomy patients were studied and comparison of trends in survival calculated from 6-year period cohorts. Liver function and hematologic status in a group of 30 long-term survivors (14 to 24 years) were compared with 25 patients from England, (14 to 23 years). Twenty-five Japanese and 21 UK patients (SF-36) completed a QoL questionnaire., Results: Median survival times in Japanese patients before 1975 were less than 1 year but increased to 18 years after 1975. Hematologic and liver function test results did not show any significant differences between the Japanese and UK patients. QoL studies in the UK patients showed no significant difference from normative, general population data. Japanese patients underperformed in general health (P = .01), role emotional (P = .05) and role physical (P = .07) but, overall, there was no significant difference between the Japanese and UK patients except for marginal differences in indices of general health and vitality (P = .06 and .04, respectively)., Conclusions: Long-term survival rate in the Japanese patients increased dramatically from 1 year to 17 years after 1975. The QoL of survivors was comparable in Japan and England. The satisfactory comparison with normative population data suggests that we should continue to use portoenterostomy as the primary treatment for biliary atresia. J Pediatr Surg 36:892-897., (Copyright 2001 by W.B. Saunders Company.)

Background/purpose: The aim of this study was to investigate the problems and the quality of life during and after pregnancy of the patients who had undergone Kasai operation and to find out a strategy for follow-up during the period of their pregnancy., Methods: A questionnaire was sent to 134 institutions of the Japanese Biliary Atresia Society with the following questions: (1) Do you have any pregnancy cases in patients who had undergone Kasai operation? (2) Did she have any menstrual problem? (3) Did she have any problem during pregnancy and delivery? (4) Did she have any change in liver function tests after delivery? (5) Did she have any early and long-term problem after delivery? (6) Did the baby have any problem? (7) Was there any special care or comment about the pregnancy of the biliary atresia patients? The responses were analyzed., Results: Fourteen institutions reported 16 cases of pregnancy, 23 cases of delivery, and 2 cases of abortion. The causes of abortion in the 2 cases were attributed to hemorrhagic shock after massive bleeding from esophageal varices and serious atopic dermatitis, respectively. Other problems during pregnancy were abruption of placenta, fetal distress leading to caesarian section, and development of liver dysfunction leading liver transplantation. Problems after delivery included deterioration of liver function in 6 patients (37.5%), attacks of ascending cholangitis in 4 patients (25.0%), and severe fatigue with liver dysfunction from nursing the baby leading to liver transplantation. Only 3 of 16 (18.8%) patients were free of any problems. No abnormality was seen in the babies., Conclusions: Even if the patients with biliary atresia lead a good postoperative course, unexpected complications can occur when they become pregnant. Close long-term follow-up is required for proper management of pregnancy in biliary atresia patients.

Purpose: The aim of this study was to compare the in situ expression of CD14 between early and late stage of biliary atresia (BA) to determine if a time course of CD14 expression exists in BA., Methods: Immunohistochemical analysis of membrane-bound CD14 expression was carried out in periodate-lysine-paraformaldehyde (PLP)-fixed frozen sections from 9 early- (obtained during Kasai procedure) and 6 late- (obtained during liver transplantation) stage cases of BA. Normal liver (n = 3) and choledochal cysts (n = 5) served as normal controls and disease controls respectively., Results: In the early stage, 6 patients (66.66%) showed extensive CD14 expression (grade 3 [G(3)], more than 50% positive cells), whereas no CD14-positive cells could be detected in 4 patients (66.66%) in the late stage. In both stages, most of the positive cells were observed in the parenchyma of the hepatic lobules where Kupffer cells and sinusoidal endothelial cells stained positive. Arterial and venous endothelium, bile duct cells, and hepatocytes were negative for CD14. Double immunohistochemistry in the early stage showed a higher colocalization rate of CD14 and CD68 in the sinusoidal locations (33.69 +/- 9.270% [mean +/- SEM]) than in the portal tract (7.6+/-4.64% [mean +/- SEM]; P<.05). Similar pattern of colocalization also was observed in the late stage. In the normal controls no expression of CD14 could be detected, whereas in the disease controls only 1 case showed mild expression (grade 1 [G(1)], 1% to 10% positive cells) and the rest showed no expression of CD14., Conclusion: These results suggest that CD14 expression in BA is a dynamic phenomenon having time-related change with overexpression in the early stage and reduced expression in the late stage.

Purpose: To determine if mast cells influence the clinical outcome in biliary atresia (BA), the authors examined the intrahepatic mast cell population in BA., Methods: Mast cells were identified histochemically using Toludin Blue and immunohistochemically using antimast cell tryptase antibody in formalin-fixed paraffin-embedded sections from 21 cases of BA. Patients were divided into 3 groups; group I (n = 8) with good liver function, group II (n = 8) with moderate liver dysfunction, and group III (n = 5) with severe liver dysfunction. Liver biopsies from patients with choledochal cysts (CDC, n = 5), and normal liver (NL, n = 4) served as controls. The results were compared among the groups., Results: Both histochemical and immunohistochemical methods showed similar data. Mast cells were seen mostly in the portal tracts. Mast cell numbers per medium power field (20 x magnification) were higher in BA than in the controls (15. 03 +/- 2.25 v 3.85 +/-.65, [mean +/- SEM], P <.05, BA v CDC; 15.03 +/- 2.25 v 1.73 +/-.06, [mean +/- SEM], P <.05, BA v NL, immunohistochemical data). Clinical correlation showed an association between higher mast cell number and liver dysfunction (32.62 +/-.80 v 8.52 +/-.87 [mean +/- SEM], group III v group I; P <. 05, immunohistochemical data)., Conclusion: Increased mast cell population in BA adversely affects liver function and raises the possibility that type I allergic reaction may play role in the pathology of BA.

Intestines resected from two patients with Hirschsprung's disease, both aged 6 months, were submitted to serial sectioning and three-dimensional reconstruction to visualize the overall structure of Auerbach's plexus and correlate its changes with functional abnormalities. Reconstruction was made possible by using a graphics computer system. In normal intestines taken from an autopsy case, both large and small, the plexus was shown extending along the intermuscular septum as a regular network. But in the large intestine, the density of the network was apparently higher and the individual bundles thicker than in the small intestines. This neural network was absent in the aganglionic zone in Hirschsprung's disease, as expected, where only hypertrophic extrinsic nerves were running in the septum. The "transitional zone" of Hirschsprung's disease was clearly definable as an area extending over a certain length, where the network meshes grow more irregular and the bundles taper more, toward the aganglionic zone. This finding was considered to be of profound significance in the design of a surgical strategy to prevent postoperative bowel dysfunction. In determining the range of resection, one must consider not only the presence or absence of nerve cells but also the grade of plexus hypoplasia.

Between 1952 and 1993, 289 patients with biliary atresia underwent surgery at the authors' institution. Twenty-two of them survived more than 20 years; one has since died of hepatic failure (at age 28 years). Of the 21 current survivors (age range, 20 to 39 years), 13 underwent hepatic portoenterostomy; the others had hepaticoenterostomy. None of these patients has undergone liver transplantation. Sixteen patients have led near-normal lives. This includes three married women, one of whom has given birth to a healthy baby boy. Of the six patients who had portal hypertension, three underwent both splenectomy and proximal splenorenal shunting in or before 1985. None of these patients has required additional treatment for portal hypertension. The quality of life of one patient has been severely affected by an unrelated condition (Turner's syndrome). A 22-year-old man was diagnosed as having intrahepatic stones 3 years ago. In another 22-year-old man, hepatic dysfunction developed after frequent episodes of cholangitis. He is now being considered for liver transplantation. The majority of the long-term survivors have good quality of life. However, a few continue to suffer from complications including recurrent cholangitis. Close long-term postoperative follow-up is required for patients with biliary atresia.

Nationwide neuroblastoma mass screening for 6-month-old infants (first screening) was introduced in Japan in 1985. About 110 neuroblastoma cases are detected annually by the first screening and treated, with a survival rate of 97%. Sensitivity of the first screening (positive cases/positive cases+false negative cases) is about 75%, and the prognosis of false-negative cases is unfavorable. A second screening at 18 months of age was started to rescue false-negative cases in Miyagi Prefecture in May 1992. Of 62 neuroblastoma cases treated in our hospital since 1985, 40 cases had received the first screening. Twenty cases were positive at first screening, 18 cases were false negative, and 2 cases were false negative and picked up by the second screening. Age distribution of false-negative cases ranged from 12 to 83 months and included 12 cases younger than 36 months old. Only 5 of 18 false-negative cases are alive without the disease. From May 1992 to November 1993, 14,282 infants had received the second screening (compliance rate: about 75%), and 2 neuroblastoma cases were detected. The first case was stage III with paraortic lymph node metastases, Shimada UH, aneuploidy and negative N-myc amplification. The second case was stage II with Shimada FH, aneuploidy, and negative N-myc amplification. Both cases are alive now without the disease after undergoing radical operation and chemotherapy. The first screening is effective for early detection of neuroblastoma cases, but the sensitivity is insufficient; the authors recommend a second screening to rescue false-negative cases.

Bannayan-Zonana syndrome is a rare disorder characterized by macrocephaly and multiple soft tissue and visceral hamartomas. This report presents a sporadic patient with macrocephaly, lipomas, hemangiomas, and lymphangiomas who died of cardiac and respiratory failure due to progressive cervicomediastinal arteriovenous fistulous hemangiomas at the age of 9 years.

The size and arrangement of each component of pancreaticobiliary ductal junction was investigated in 28 cases with biliary atresia in which cholangiography allowed visualization of the common bile duct, pancreatic duct, and duodenum and in which relevant data were available. As controls, seven cases of neonatal hepatitis and eight cases of intrahepatic bile duct hypoplasia were also studied. The following results were obtained. (1) The diameter of the common bile duct was shortest in biliary atresia, the value corresponding to about one-third of that for neonatal hepatitis. (2) The common bile duct was visualized in 100% of cases of intrahepatic bile duct hypoplasia and 78% of cases of biliary atresia, whereas the corresponding percentage was only 43% for neonatal hepatitis. The mean length of the common channel in cases of biliary atresia and that of intrahepatic bile duct hypoplasia was about 5 mm, which was longer than that of neonatal hepatitis. (3) The pancreatic duct type, in which the pancreatic duct merged into the bile duct, was frequent in cases of biliary atresia.

The surgical treatment of 100 cases with congenital dilatation of bile duct with special reference to late complications was analyzed. There were no deaths nor occurrences of malignancy. Among 91 patients who had undergone the standard operation, namely total excision of the dilated extrahepatic bile duct and reconstruction after Roux-en-Y hepaticojejunostomy, there were one early complication (pancreatic juice leakage) and five late complications (four intrahepatic gallstones and one liver abscess). The cause of intrahepatic gallstone formation after a total excisional operation was attributed to the remaining intrahepatic bile duct dilatation and the stenosis located between the intrahepatic bile duct dilatation and the common hepatic duct. Accordingly, these results support the total excisional procedure for this condition; however, with regard to the cases associated with cystic dilatation of intrahepatic bile ducts, completely free bile drainage from the dilated intrahepatic biliary system should be performed at the radical operation.

The enteric nervous system (ENS) is composed of two distinct neural components, extrinsic and intrinsic, and its supporting cells uniquely possess some characteristics of both central nervous system (CNS) astrocytes and peripheral nervous system (PNS) Schwann cells. To provide further insight into the neural defects in Hirschsprung's disease, the supporting cells in biopsied normal gut, ganglionic, and aganglionic segments from six cases of Hirschsprung's disease were investigated immunocytochemically for localization of three neuroglial markers, glial fibrillary acidic protein (GFAP), S-100 protein, and glutamine synthetase (GS), by the avidin-biotin-horseradish peroxidase complex method applied to free-floating thick cryostat sections. In normal control gut and ganglionic segments of Hirschsprung's colon, all of the GFAP, S-100, and GS were expressed strongly by the supporting cells of the myenteric and submucosal plexuses, interconnecting nerve fiber bundles of the plexuses, and fine nerve strands in the muscular layer. The nerve bundles of the subserosa merging into the muscular layer were also immunoreactive for GFAP and S-100, but negative or only faintly positive for GS. On the other hand, aberrantly proliferated nerve bundles in the aganglionic segment of the Hirschsprung's colon were accompanied by supporting cells strongly positive for GFAP and S-100, but negative or faintly positive for GS. These results indicate that the supporting cells of the enteric neurons proper, enteric glia, express GFAP, S-100, and GS, whereas the supporting cells of the extrinsic components, which accompany PNS axons, are negative or very weakly positive for GS. Thus, GS immunocytochemistry may delineate intrinsic and extrinsic neural components in the ENS, and may provide an important clue for differential diagnosis of Hirschsprung's disease.

Long-term results after surgery for biliary atresia (BA) in 48 patients, ranging in age from 10 to 33 years, were examined. There were 19 males and 29 females. Twelve had correctable type BA and 36 had the noncorrectable type. Forty-one cases had no jaundice; seven did. Thirty-seven of the 48 cases were leading normal lives. Among them, six cases were enjoying their lives after overcoming sequelae, such as portal hypertension. The main morbidities of the remaining 11 long-term survivors were jaundice and portal hypertension. The growth of most cases were comparable to those of the normal Japanese population. The data of liver function tests were variable and disclosed a moderate degree of abnormality in patients mainly complicated by cholangitis. Eleven cases, including six jaundice cases, required treatment for esophageal varices and/or hypersplenism. In conclusion, the cured states of most cases without jaundice are satisfactory and these former patients have achieved a favorable quality of life. Early operations are essential to obtain good short-term results as well as good long-term results.

The portal vein pressure was measured and biopsies of the liver were taken during the corrective operation in 31 patients with biliary atresia and during relaparotomy in 16 patients free from jaundice 4 mo to 9 yr after a successful corrective operation. Because the portal vein pressure was higher than 200 mmH2O in about 70% of patients during the corrective operation, portal hypertension appears to have already developed in most of the patients with biliary atresia at 2-4 mo of age. In the patients who had had frequent episodes of postoperative cholangitis, the portal vein pressure was elevated and the amount of interstitial tissue in the liver was markedly increased at reoperation compared with those at the corrective operation. These results showed that postoperative cholangitis aggravated portal hypertension and fibrosis of the liver. On the contrary, the portal vein pressure declined in patients in whom active bile drainage had persisted and cholangitis had not been complicated after operation. An early corrective operation and prevention of postoperative cholangitis are of the greatest important for prevention of development of the portal hypertension and cirrhosis of the liver in long-term survivors after surgery for biliary atresia.

Fourteen patients with "noncorrectable" biliary atresia are living without jaundice for more than 2 yr after hepatic portoenterostomy or its modification. Retardation of physical growth was observed in one of them, and mental retardation in another, both of which seemed irrelevant to biliary atresia. Serial tests for liver function after operation revealed early recovery of serum bilirubin, transminase, and turbidity, and delayed improvement of alkaline phosphatase. Postoperative needle biopsy of the liver disclosed that changes in hepatic parenchyma and ductular proliferation were rapidly improved after successful operation. Improvement of fibrosis of the liver was delayed, and it was not satisfactory in patients whose preoperative changes in the liver were severe or in whom ascending cholangitis had been a frequent complication. Histologic features of hepatic cirrhosis were observed in the liver in three cases, in two of which there had been frequent episodes of cholangitis. Only one of these showed clinical signs of portal hypertension. Functional and morphologic cure can be achieved in "noncorrectable" biliary atresia by hepatic portoenterostomy or its modifications, although varying degree of hepatic fibrosis may remain according to severity of preoperative changes of the liver and postoperative complication of ascending cholangitis.

Of 245 patients undergoing corrective operations for biliary atresia, jaundice was cleared in 113. In January 1988, 84 of them were living and free of jaundice and the other 19 were alive with jaundice. A vast majority of long-term survivors showed normal growth and development, and were leading normal lives for their respective ages. Portal hypertension, a common late complication, improved spontaneously or after sclerotherapy in jaundice-free patients. Therefore, liver transplantation is not recommended for jaundice-free patients even with esophageal varices. Patients with persistent severe jaundice (serum bilirubin over 10 mg/dL) and those with moderate jaundice (serum bilirubin 5 to 10 mg/dL) and severe esophageal varices require liver transplantation. Patients with moderate jaundice having no or slight varices should be carefully followed. When varices become worse or serum bilirubin rises, liver transplantation is indicated. Patients with mild jaundice (serum bilirubin lower than 5 mg/dL) have a possibility of improvement in their condition before the age of 15 years, and are not recommended for liver transplantation. The high value of the lowest postoperative bilirubin level suggests the necessity of liver transplantation in early childhood. Liver transplantation as the primary treatment for biliary atresia may be indicated only for patients over 120 days of age with an enlarged and hard liver.

Three basic types of microscopic biliary structures at the portahepatis were distinguishable in infants with biliary atresia: bile ducts, collecting ductules of biliary glands, and biliary glands. Correlation between the type of biliary structure and the quantity and quality of post-operative bile flow was possible in 23 instances. At 2 weeks after operation, the 11 patients in whom a bile duct was identified had a daily bile flow of 68.0 +/- 11.5 mL. Bilirubin concentration in the bile was 13.6 +/- 3.3 mg/dL and total daily bilirubin excretion was 8.77 +/- 2.74 mg. In contrast, bile flow in 12 patients having only collecting ductules and/or biliary glands in the porta hepatis was 19.1 +/- 3.9 mL and bilirubin concentration in bile was 1.7 +/- 0.3 mg/dL. Thus, total daily bilirubin excretion was 0.34 +/- 0.08 mg (P less than 0.001). Postoperative cholangitis occurred only in patients with ducts. It is concluded that only bile ducts communicate with the intrahepatic biliary system and drain bile after hepatic portoenterostomy.

Intrahepatic portal veins were reconstructed from serial histologic sections of surgical liver specimens from patients with biliary atresia to explain the pathogenesis of portal hypertension, an important late postoperative complication of this disease. It was found that abnormal intrahepatic vasculature was already notable in an evidently reduced number of portal veins in the second month of age, and this was considered responsible for causing presinusoidal block that gave rise to the elevated resistance to intrahepatic portal flow. Reconstruction also revealed that restoration of ordinary portal structure was expectable if, after successful surgery, a patient was sufficiently protected from cholangitis and there was much room for portal veins to grow without being impeded by inflammatory and/or scarring processes. In contrast, the patient whose condition was complicated by cholangitis was shown to acquire a markedly hypoplastic portal system with apparently reduced vascularity.

A patient who died of hepatic failure nearly 29 years after hepatic portojejunostomy is reported. His death may be attributed to several faults in treatment. From our experiences it can be said that biliary atresia is a curable disease, although liver-transplantation is required in some patients in whom hepato portoenterostomy is unsuccessful.

From 1953 through 1984, we have operated on 225 cases of biliary atresia, and 95 patients are presently surviving. Portal hypertension with esophageal varices was endoscopically confirmed in 26 of 66 patients (39%) examined, 14 with and 52 without jaundice. All these patients except two had had frequent episodes of postoperative cholangitis. Eight patients have undergone treatment for portal hypertension. The treatment for variceal bleeding in jaundice-free infants with biliary atresia should be initiated conservatively, including endoscopic sclerotherapy. The results of our experience, however, justifies the employment of shunt procedures for patients older than 6 or 7 years of age.

Of 47 patients suffering from congenital dilatation of the bile duct whose intrahepatic bile ducts could be clearly demonstrated by operative cholangiogram or preoperative ERCP, 39 patients (83%) had dilatation of the intrahepatic bile ducts. Follow-up studies in infants and children ranging from 1 year to 11 years after their corrective operation for congenital dilatation of the common bile duct showed no morbidity that was attributed to the presence of the dilatation of the intrahepatic bile ducts. ECHO grams in 21 patients revealed marked decrease in size of the intrahepatic bile ducts except for two patients with huge cystic dilatation of the intrahepatic bile ducts. These findings justify the employment of the standard operative procedure for the treatment of congenital dilatation of the bile duct even if it is associated with dilatation of the intrahepatic bile ducts.

Twenty-seven reoperations were done on 23 patients among 100 infants with biliary atresia who have been treated at Tohoku University Hospital between 1971 and 1981. Nineteen patients had a single reoperation and 4 patients had 2 reoperations. We present the results and the role of reoperation in biliary atresia patients in our institution. Excellent bile drainage after reoperation was obtained in 13 of 15 patients with good bile flow after the initial operation. On the contrary, good bile drainage was not obtained by reoperation in 8 of 12 cases without active bile flow after the initial operation. Cessation of bile flow after successful initial operation is an absolute indication for reoperation. Aggressive reoperations under proper indications improve the surgical results in biliary atresia patients.

Copper metabolism was investigated in 33 infants with hepatobiliary disease. In 25 paients with biliary atresia, 37-135 days old, hepatic copper ranged from 5 to 133 microgram Cu/g wet weight (mean:43.3 microgram). In over two-thirds of the liver samples copper content was elevated above normal. There was no correlation between hepatic copper concentration and patients' age or degree of liver fibrosis. The mean hepatic copper content was also elevated in six infants with other hepatobiliary diseases (mean:41.6 microgram). Serial assays of copper excretion in bile were made in 25 infants having Kasai procedures for biliary atresia. The average daily excretion of biliary copper in 12 patients with successful operations was 3.3 to 33.7 microgram (mean:15.1 microgram), whereas in 13 patients without postoperative bile drainage, the daily values were 0.3-6.4 microgram (mean:2.7 microgram) (p < 0.0001). In five patients with active bile excretion who had repeated liver biopsies there was a steady decrease in hepatic copper concentration. The results indicate that derangement of copper homeostasis occurs frequently in infants with hepatobiliary disease and that in patients with biliary atresia successful reestablishment of bile flow effects a return toward normal copper metabolism probably because of enhanced biliary excretion.

Congenital diaphragmatic hernias were successfully produced in fetal rabbits. The lungs of these animals remained small and hypoplastic on gross examination, although histologically they have matured significantly from the original pseudoglandular stage. It is our impression that the so-called hypoplastic lung in diaphragmatic hernias is small in size but potentially functioning when relieved of compression.