Interleukin-32 production associated with biliary innate immunity and proinflammatory cytokines contributes to the pathogenesis of cholangitis in biliary atresia.

Biliary atresia (BA) is thought to be associated with infections by viruses such as Reoviridae and is characterized histologically by fibrosclerosing cholangitis with proinflammatory cytokine-mediated inflammation. Interleukin (IL)-32 affects the continuous inflammation by increasing the production of proinflammatory cytokines. In this study, the role of IL-32 in the cholangitis of BA was examined. Immunohistochemistry for IL-32 and caspase 1 was performed using 21 samples of extrahepatic bile ducts resected from BA patients. Moreover, using cultured human biliary epithelial cells (BECs), the expression of IL-32 and its induction on stimulation with a Toll-like receptor [(TLR)-3 ligand (poly(I:C)] and proinflammatory cytokines was examined. BECs composing extrahepatic bile ducts showing cholangitis expressed IL-32 in BA, but not in controls. Caspase 1 was expressed constantly on BECs of both BA and control subjects. Furthermore, poly(I:C) and proinflammatory cytokines [(IL-1ß, interferon (IFN)-γ and tumour necrosis factor (TNF)-α] induced IL-32 expression strongly in cultured BECs, accompanying the constant expression of TLR-3 and caspase 1. Our results imply that the expression of IL-32 in BECs was found in the damaged bile ducts of BA and induced by biliary innate immunity via TLR-3 and proinflammatory cytokines. These findings suggest that IL-32 is involved initially in the pathogenic mechanisms of cholangitis in BA and also plays an important role in the amplification and continuance of periductal inflammatory reactions. It is therefore tempting to speculate that inhibitors of IL-32 could be useful for attenuating cholangitis in BA.

Prenatal diagnosis and management of congenital subglottic stenosis associated with congenital esophageal atresia type C.

Most patients with congenital esophageal atresia (EA) have congenital tracheobronchial abnormalities, which may cause respiratory distress, be difficult to treat and have a poor prognosis. The authors report a neonate with EA and congenital subglottic stenosis (SGS) who exhibited severe respiratory distress immediately after birth. After emergency endotracheal intubation with a narrow endotracheal tube, the authors performed total correction of EA and anterior cricoid split (ACS) on day 1 of age. The postoperative course was uneventful. Some reports have stated that it is difficult to make a prenatal diagnosis when SGS is associated with EA and tracheoesophageal fistula (TEF). The anterior cricoid split technique may be suitable for managing moderate SGS even in neonates with EA. Partial resection of the hypertrophic cricoid cartilage is considered effective in preventing restenosis.

Effectiveness of Bortezomib in a Patient With Acute Rejection Associated With an Elevation of Donor-Specific HLA Antibodies After Small-Bowel Transplantation: Case Report.

BACKGROUND: A significant association between donor-specific antibody (DSA) and graft rejection has recently been documented. However, confirmed strategy has not been established for DSA-associated rejection after intestinal transplantation (ITx). CASE REPORT: A 20-year-old male patient with chronic intestinal obstruction caused by hypoganglionosis of the entire intestine underwent cadaveric donor ITx with grafting performed on 232 cm of the small intestine, cecum, and a part of the ascending colon. On post-operative day (POD) 14, a histological evaluation showed an acute rejection of indeterminate grade. The patient had severe acute rejection on POD 16, which prompted us to administer bolus steroids and polyclonal anti-thymocyte antibody, along with baseline maintenance immunosuppression. The histopathological findings of the graft indicated typical acute cellular rejection, although C4d was positive. We then detected donor-specific HLA antibody. The patient initially responded well to the therapy and showed decreased histological rejection signs. However, the refractory low-grade rejection persisted in the graft. During this period, the patient showed increased levels of DSA, and we speculated that the persistent rejection was associated with DSA; thus, bortezomib was administered at this stage as a salvage therapy. This rejection was thereafter successfully controlled without severe adverse effect. Twenty-three months after ITx, the patient is currently alive with complete enteral autonomy. CONCLUSIONS: A case of acute graft rejection followed by a marked elevation of DSA is presented. In this particular case, a modified treatment protocol using bortezomib in addition to the typical immunosuppressive agents was effective.

Remodeling of the alveolar structure in the paraquat lung of humans: a morphometric study.

To correlate the progression of fibrosing lung lesions with an impediment of respiratory function, autopsy lungs from 15 patients who died after ingesting paraquat were submitted to histopathologic and morphometric analysis. The basic lung lesion proved to be a remodeling of alveolar structure caused by deposition of matrix on the septal surface, with proliferating mesenchymal cells. Morphometry, using a geometric model, and stereology showed that the mean thickness D of septa, including the matrix, enlarged after an exponential function of days after ingestion, reaching the alveolar breadth of 200 microns on day 22 and showing the alveoli totally obliterated. The exponential nature of this finding suggested that the paraquat lung is a self-accelerating and therefore a malignant lesion, in contrast to the slowly progressing fibrosis that follows usual interstitial pneumonia. In a whole-lung distribution analysis performed in three cases, D was shown to become increasingly heterogenous over time, with ordinary alveolar tissue remaining in at least part of the lung even in the most advanced case. Thus, heterogenous distribution of the disease was considered to be a sine qua non for a lung disease to run a chronic course.

Biliary atresia.

Although the prognosis of biliary atresia has been dramatically improved in the era of liver transplantation, the Kasai operation is still the first line of surgical treatment. Successful hepatic portoenterostomy depends on early diagnosis and surgery, adequate surgical technique, prevention of cholangitis, and precise postoperative management.

A phase II study of 5-fluorouracil, cisplatin, and 4'-epirubicin in the treatment of advanced solid cancers.

This phase II study was designed to assess the therapeutic potential of intensive course treatment with three anticancer agents: 50 mg of cisplatin on day 1, 40 mg/m2 of epirubicin on day 2, and 250 mg of 5-fluorouracil on days 2 through 5. Drug courses were repeated every 2 weeks and most patients received between 4 and 6 courses. Thirty-five patients with measurable advanced solid cancers entered the study. They consisted of 16 gastric, 5 colorectal, 4 gallbladder, 3 pancreatic, 3 lung, 2 esophageal, 1 uterine, and 1 ovarian cancers. Of the 35 patients, 29 were evaluated for therapeutic effect of the regimen, and the overall response rate was 31.0% (5 CR + 4 PR/29). A 33.3% rate of tumor regression, consisting of 2 complete responses (CR) and 3 partial responses (PR) out of 15 patients (2 CR + 3 PR/15), was seen for gastric cancers. For the other types of tumors the responses were achieved in 2 lung cancers (1 CR + 1 PR/3). 1 uterine cancer (1 CR/1), and 1 ovarian cancer (1 CR/1). The esophageal, colorectal, pancreatic, and gallbladder cancers were unresponsive to this regimen. Toxicities of the drug treatment were clinically tolerable and consisted of general malaise, nausea, vomiting, stomatitis, alopecia, and leucopenia. However, two patients died of uncontrollable metabolic acidosis after 1 and 2 courses, respectively. This intensive course treatment appears to promote the regression of gastric, lung, and gynecologic cancers.

The expression of intestinal CYP3A4 in the piglet model.

PURPOSE: In our previous study, the blood levels of tacrolimus were higher in the short bowel and small bowel transplantation models than those in controls. Metabolism by intestinal cytochrome p450 3A4 (CYP3A4) has been reported to influence the blood level of orally administered tacrolimus. We performed immunohistochemistry to examine the localization of intestinal CYP3A4. MATERIALS AND METHODS: Twenty-four piglets were divided into three groups: group 1 were controls (n = 11); group 2, ileal resection of 2/3 proximal small intestine (n = 5); and group 3, total small intestinal resection followed by 1/3 allotransplantation of ileum (n = 8). Tacrolimus was orally administered from postoperative days 3 to 7. On day 7, blood samplings were performed for the trough level and the calculation of area under the concentration time curve (AUC). Intestinal specimens from the jejunum, ileum, colon, and ileal graft were obtained on days 0 and 10 for immunohistochemistry of CYP3A4. RESULTS: The trough and AUC values in group 2 were significantly higher than those in group 1. Furthermore those measurements in group 3 animals were higher than in group 2 (trough levels: 2.5 +/- 1.7, 11.2 +/- 2.1, 16.3 +/- 2.7 ng/mL and AUC values: 126 +/- 90, 319 +/- 155, 546 +/- 117 ng. h/mL). The expression levels of CYP3A4 were, jejunum > ileum > ileal graft > colon. CONCLUSIONS: The intensity and extent of CYP3A4 staining diminished in the ileal graft showing an inverse correlation to the blood concentrations.

The colon displays an absorptive capacity of tacrolimus.

PURPOSE: In our previous study, blood levels of orally administered tacrolimus were significantly higher in short bowel piglets than in control animals. It has been reported that the blood levels of tacrolimus are influenced by the metabolic activity of intestinal CYP3A4. If tacrolimus may be absorbed in the colon, direct administration of drug into this organ might be useful to augment bioavailability since the expression of CYP3A4 is low at this site. In the present study we evaluated the absorptive capacity of tacrolimus in the colon. MATERIALS AND METHODS: Piglets were divided into four groups: groups 1 and 2 were controls (n = 11 and 3, respectively); group 3 underwent resection of the entire small intestine (n = 8); and group 4 had a catheter placed in the cecum (n = 4). In groups 1 and 3, tacrolimus was administered orally; in group 2 it was given intravenously; and in group 4 it was injected into cecum through the catheter from postoperative days 3 to 7. On day 7, blood samples were obtained for drug measurements to calculate the area under the concentration time curve (AUC) values. RESULTS: The trough level and AUC values of tacrolimus in group 4 as well as in group 3 were significantly higher than those in group 1. In Group 4 animals showed a 60-minute time to peak concentration. CONCLUSIONS: Tacrolimus is absorbed by the colon. Since the blood levels were not influenced by the metabolic activity in the graft bowel, direct administration of tacrolimus into the colon might be useful in small intestinal transplantation.

A prospective randomized trial of delayed versus immediate repair of congenital diaphragmatic hernia.

From March 1990 to January 1993, a randomized prospective study was performed to determine the optimal timing of surgery for infants with high-risk congenital diaphragmatic hernia (CDH). Thirty-two CDH patients who presented with respiratory distress within 12 hours after birth were randomly divided into two groups: Group A had early repair (within 6 hours), and group B had delayed repair (at 96+ hours). Extracorporeal membrane oxygenation (ECMO) was initiated in both groups as necessary. Fourteen patients were assigned to group A, and 18 were assigned to group B. Two patients initially assigned to group A had acute deterioration, and their operations had to be postponed. Data were collected, but these patients were eliminated from the study. The two groups were comparable based on gestational age, birth weight, Bohn's criteria, and oxygenation and ventilatory index. Nine of 12 group A patients (75%) survived, and 13 of 18 group B patients (72%) survived (P > .05, not significant). The ECMO requirements for the two groups were not significantly different (8 of 12 (67%) v 16 of 18 (89%); P > .05). Surgical intervention for bleeding complications related to ECMO was required in three of eight (38%) with immediate repair and seven of 16 (44%) with delayed repair (P > .05). There was no difference in survival nor incidence of ECMO between the two groups. This is the first prospective study of timing of hernia repair that supports the conclusions of earlier reports of retrospective studies.

In situ CD14 expression in biliary atresia: comparison between early and late stages.

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.

Long-term follow-up after surgery for patients with biliary atresia.

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.

Management of splenic abscess in immunocompromised children.

Splenic abscess is an infrequent complication in the immunocompromised patient. Six patients underwent splenectomy for presumed splenic abscess from 1987 to 1991. Chemotherapy altered the immune system of four patients; the human immunodeficiency virus (HIV) rendered the other two vulnerable to infection. Five presented with fever but none had leukocytosis; only one exhibited palpable splenomegaly; three had abdominal pain. Cultures documented systemic infection in all but one, an HIV-positive individual. Respiratory embarrassment was the indication for surgery in one patient. In five cases the decision for surgical intervention was made after computed tomography (CT) indicated the presence of multiple splenic lesions and systemic antibiotics failed to resolve the fevers. CT additionally showed hepatic and/or renal microabscesses in four patients. Signs and symptoms experienced preoperatively resolved with splenectomy in all six patients. No additional surgery was required for the patients with extrasplenic abscesses. Surgical pathology determined that three spleens had fungal and two had mycobacterial abscesses. The other was shown to be a spindle cell sarcoma; no abscess was present. This patient had preoperative blood cultures positive for mycobacteria, and the same organism was recovered from retroperitoneal nodes sampled at the time of splenectomy for the sarcoma. Follow-up indicates that no patients experienced surgical complications or sequelae related to their splenic pathology. Splenectomy is necessary and effective in treating splenic abscesses in immunocompromised patients and is appropriate for diagnosis as well as therapy.

Problems during and after pregnancy of former biliary atresia patients treated successfully by the Kasai procedure.

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.

Intrahepatic mast cell population correlates with clinical outcome in biliary atresia.

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.

Survival patterns in biliary atresia and comparison of quality of life of long-term survivors in Japan and England.

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.

Current status of 21 patients who have survived more than 20 years since undergoing surgery for biliary atresia.

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.

Changing profile of abdominal wall defects in Japan: results of a national survey.

BACKGROUND/PURPOSE: The incidence of gastroschisis has increased over the past 3 decades in a number of countries. To elucidate the Japanese status of anterior abdominal wall defects, the Japanese Society of Pediatric Surgeons conducted a national survey in Japan. METHODS: Information was obtained by sending out a questionnaire to 192 University Hospitals, Children's hospitals, and general hospitals that each had more than 200 beds. The characteristics of the patients including the birth date, birth weight, gestations, rate of associated anomalies, rate of antenatal diagnosis and prognosis, maternal age, gravidity, history of smoking, and drug use were analyzed. RESULTS: The authors obtained answers from 149 institutions, including 1,785 cases of omphalocele and 970 cases of gastroschisis, which were treated between 1975 to 1997. There was a significant increase in the incidence of gastroschisis, from 0.131 in 1975 to 1980, 0.269 in 1981 to 1985, 0.337 in 1986 to 1990, 0.461 in 1991 to 1995 to 0.467 per 10,000 births in 1996 to 1997. The incidence of omphalocele was 0.322 in 1975 to 1980, 0.567 in 1981 to 1985, 0.657 in 1986 to 1990, 0.741 in 1991 to 1995 to 0.626 per 10,000 births in 1996 to 1997, respectively. In the omphalocele group, 43.1% of the mothers were between 25 to 29 years of age, whereas in the gastroschisis group 42.6% of the mothers were 20 to 24 years of age. In the gastroschisis group, the number of primipara mothers was larger than that of multipara mothers. In the omphalocele group, approximately 10% of the mothers smoked during each period, whereas in the gastroschisis group, the percentage of smoking mothers increased chronologically from 12.9% in 1981 to 1985, 18.7% in 1986 to 1990, 23.5% in 1991 to 1995 and 29.3% in 1996 to 1997. A history of drug use by the mother was approximately 10% for both the omphalocele and gastroschisis groups. In the omphalocele group, 55.9% had associated anomalies against 21.8% in the gastroschisis group. Approximately 10% in the omphalocele group and less than 3% in the gastroschisis group showed chromosomal abnormalities. From 1986, a significant number of cases detected antenatally has been observed. CONCLUSIONS: There have been substantial changes in the incidence of anterior abdominal wall defects, particularly regarding gastroschisis in Japan. The reasons for such changes are most likely multifactorial, further epidemiological monitoring is thus called for.

Late complications in long-term survivors of biliary atresia.

Ninety patients with biliary atresia surviving more than 5 years were analysed with respect to late complications occurring after the age of 4 years. Thirty-five had complications including cholangitis, portal hypertension, hypersplenism, gastrointestinal bleeding, and esophageal varices. These complications occurred at various times. The background factors of late complications were past history of cholangitis soon after the operation, advanced age at operation, re-operation, high portal pressure at initial operation, and a long interval before disappearance of jaundice after surgery. These factors are mostly related to the first operation and its postoperative course. Therefore, we stress that late complications can be prevented by intensive treatment of the patient at the time of the first operation.

[Long-term outcome of surgery for biliary atresia].

Between 1953 and 1995, 300 patients with biliary atresia underwent surgery at Tohoku University Hospital. Among them, 31 patients survived more than 20 years, while one of these patients died of hepatic failure at the age of 28 years. Of the 30 surviving patients (10 males and 20 females, age range; 20 to 41 years), 20 underwent hepatic portoenterostomy, 8 underwent hepaticoenterostomy and the remaining 2 underwent hepatic portocholecystostomy. None of these patients has undergone liver transplantation. Twenty-two patients have led near normal lives. This includes three married women, one of whom gave birth to 2 healthy babies. The remaining 8 patients have had experienced some troubles due to cholangitis, portal hypertension and intrahepatic gallstones. Two of them who have progressive liver dysfunction are being considered as candidates for liver transplantation. The quality of life of one patient has been severely affected by an unrelated (Turner's syndrome). While the majority of long-term survivors of biliary atresia have good quality of life, close long-term postoperative follow-up is required.

[The present status and problems in the treatment of biliary atresia with special reference to surgical and long-term results].

The surgical results are not satisfactory yet in Japan and only 46% of the patients are free of jaundice 3 years ago. However, we found many presentations which reported jaundice disappearance rate with more than 80% in the last several years. The main cause of death in jaundiced patients with the failed hepatic portoenterostomy was hepatic failure. Other causes of deaths in these patients, including those died within one month after operation, were peritonitis, cardiac and/or renal failure, hemorrhagic tendency and lung edema. The main cause of death in jaundice-free patients was rupture of the esophageal varices. We examined 48 long-term survivors ranging in age from 10 to 33 years. There were 41 cases without and 7 with jaundice. Thirty-seven (77%) of 48 cases were leading their normal lives. Among them, 6 cases were enjoying their lives after overcoming the sequelae, such as portal hypertension. The morbidities of the remaining 11 (23%) long-term survivors were jaundice in 7, portal hypertension in 5, encephalopathy after splenorenal shunt in 1 and so on. The cured states of most cases without jaundice are satisfactory and eventually these former patients can achieve a favorable quality of life.