Overexpression of hepatic inducible nitric oxide synthase in biliary atresia.

AIMS: Biliary atresia (BA) is a rare and serious liver disease in infants characterized by progressive inflammatory cholangiopathy. The aims of this study were to investigate hepatic expression of inducible nitric oxide synthase (iNOS) in BA and to associate the iNOS expression with their early therapeutic outcome. METHODS: Hepatic iNOS expression was determined using immunohistochemistry from liver biopsies of 24 BA patients, and 16 non-BA patients whose liver tissues were needed in the treatment process. Six months after surgery, the BA patients were categorized into two groups;good and poor outcome. The iNOS expression of hepatocyte areas was evaluated based on its intensity using ImageJ software. Unpaired t-tests were used for the comparisons of iNOS expression between groups. RESULTS: Hepatic iNOS expression of BA patients was significantly stronger than that of non-BA patients (P < 0.0001). The largest area of hepatic iNOS expression was the area of hepatocytes. Subgroup analysis of BA patients at 6 months post-op revealed that there was no difference in iNOS expression between the patients with good outcome and those with poor outcome (P = 0.732). CONCLUSIONS: Overexpression of hepatic iNOS in BA patients was demonstrated. Within liver tissues, hepatocytes were the major source of hepatic iNOS production. However, the expression was not associated with the early therapeutic outcome. These results suggest that iNOS plays a role in the liver pathology of BA but its expression cannot be used as a predictor for therapeutic outcome.

Resection for primary liver tumors in children: an experience of 52 cases at one institution.

OBJECTIVE: To review the authors' experiences of liver resection for primary tumors in children. MATERIAL AND METHOD: The children who had undergone liver resection for any masses between January 1996 and December 2005 were studied. Their clinical data and pathological reports were reviewed for descriptive study. Surgical data including the extent of lesions, type of resection, and post-operative complications within 60 days after surgery were analyzed. Data are expressed as mean and standard deviation (SD). RESULTS: Fifty-two children, with a male to female sex ratio of 28:24, underwent resection for primary liver tumors. Their average age was 36.64 +/- 4.05 months and average weight was 12.02 +/- 6.76 Kg. Asymptomatic mass was the main complaint. Ultrasonography was the initial investigation and CT scan was performed later in all patients with suspected liver mass to confirm the diagnosis and to assess the resectability. CT scan was also useful for the diagnosis of liver tumor in six cases which ultrasonography could not differentiate from other abdominal tumors. The tumors were assessed to be unresectable in 28 of 52 (53.8%) patients who had preoperative chemotherapy and became resectable later. Surgical procedures were as follows: 39 hepatic lobectomies, six extended hepatic lobectomies, and seven segmentectomies. Mean operative time was 251.04 +/- 89.22 min. Mean ICU stay was 2.8 +/- 3.2 days. Pathology revealed 38 hepatoblastomas, five hemangioendotheliomas, four hepatomas, two harmatomas, and three other lesions. Post-operative complications occurred in 15 children (29%) including intra-abdominal bleeding (3), subphrenic collection (1), acute liver failure (3), wound infection (2), and atelectasis (6). No mortality within 60 days after surgery occurred. Most of the patients were discharged within 10 days after surgery. CONCLUSION: With the advancement of preoperative evaluation, more accurate diagnosis of liver tumors, and the extent of lesions has led to the proper more effective surgical resection and further treatment, then led to zero mortality rate related to liver resection for primary tumors in the present series. Although there were significant complications, mostly minor problems and all both minor and major complications were manageable; their fatal potentials should not be underestimated.

Short-term results of Kasai operation for biliary atresia: experience from one institution.

BACKGROUND: The purpose of this study is to review the short-term outcome of patients with biliary atresia (BA) treated by the Kasai operation at our institution. METHODS: Ninety-two BA patients treated by the Kasai operation between January 1996 and December 2002 were reviewed. The diagnosis of BA was confirmed by intraoperative cholangiography. The outcome of treatment was categorized into two groups: jaundice-free (total bilirubin < 2 mg%) and persistent jaundice (>or= 2 mg%). The outcome of Kasai operation was evaluated 1 year after surgery. Data are expressed as mean +/- SD. RESULTS: Average age at the time of surgery was 90.26 +/- 36.44 days. Only 22.8% (21/92) of patients had Kasai operation before 60 days of age. Histologically, 49 patients (54.4%) had liver fibrosis at the time of surgery. Of 92 patients, 17 were not included in outcome evaluation as they were less than 1-year postsurgery. Therefore, 75 patients could be evaluated for the outcome. Thirty-eight patients (50.67%) were jaundice-free 1 year after surgery. Liver histology and age at the time of the Kasai operation did not influence early outcome. The most common complication was ascending cholangitis. CONCLUSION: Half of our BA patients who underwent Kasai operation were jaundice-free 1 year after surgery. The lack of impact of age and liver pathology on outcome is presumably due to the briefness of the follow-up. In general, our patients underwent Kasai procedure too late. It is therefore important for us to conduct a campaign to highlight the plight of these patients and the urgency of referral for neonates with jaundice.

There is no association between K469E ICAM-1 gene polymorphism and biliary atresia.

AIM: To determine whether there was an association between inter-cellular adhesion molecule-1 (ICAM-1) gene polymorphism and biliary atresia (BA), and to investigate the relationship between serum soluble ICAM-1 (sICAM-1) and clinical outcome in BA patients after surgical treatment. METHODS: Eighty-three BA patients and 115 normal controls were genotyped. K469E ICAM-1 polymorphism was analyzed using PCR assay. Serum sICAM-1 was determined using ELISA method from 72 BA patients. In order to evaluate the association between these variables and their clinical outcome, the patients were categorized into two groups: patients without jaundice and those with persistent jaundice. RESULTS: There were no significant differences between BA patients and controls in terms of gender, K469E ICAM-1 genotypes, and alleles. The proportion of patients having serum sICAM-1 >=3 500 ng/mL in persistent jaundice group was significantly higher than that in the other group. In addition, there was no association between K469E ICAM-1 polymorphism and the status of jaundice in BA patients after Kasai operation. CONCLUSION: ICAM-1 possibly plays an important and active role in the disease progression. However, the process is not associated with genetic variation of K469E ICAM-1 polymorphism.

Factors influencing outcome after hepatic portoenterostomy for biliary atresia: a logistic regression analysis.

BACKGROUND/OBJECTIVE: The association of many factors with the outcome in Biliary atresia (BA) after hepatic portoenterostomy has drawn the attention of many pediatric hepatologists and hepatobiliary surgeons. Understanding these factors will become an important subject in prediction of the postoperative status and in indicating further proper management. MATERIAL AND METHOD: During the last 9 years, 159 BA babies were treated by hepatic portoenterostomy. The authors reviewed the following factors and how they related to outcome: age at operation, total bilirubin (TB) level, type of BA, postoperative bile drainage, hepatic histological features at operation, preoperative and postoperative cholangitis. A multiple logistic regression analysis was used to indicate the factors which significantly influenced the outcome. RESULTS: Of the 159 BA babies, clearing of jaundice confirmed by the color of stool and postoperative serum bilirubin level less than 2 mg % was observed in 54 patients (Group A). Bile drainage with mild jaundice (TB 2-5 mg %) was detected in 65 patients (Group B). The operation failed to create bile flow clinically and biochemically in 40 patients (Group C). Some patients in the last group died during follow-up due to hepatic disease. The multiple logistic regression analysis revealed that the age at operation (> 8 weeks of age), and the presence of portal and parenchymal inflammation at operation significantly related to the failure of portoenterostomy which was followed by portal hypertension with or without esophageal varices. The presence of cholangitis was also significantly related to a poor outcome. CONCLUSION: The age at operation, portal and parenchymal inflammation and the presence of cholangitis are significant factors which relate to the poor prognosis of BA. Recognition of these will lead to proper long-term management.

Novel, high-definition 3-D endoscopy system with real-time compression communication system to aid diagnoses and treatment between hospitals in Thailand.

INTRODUCTION: Traditionally, laparoscopy has been based on 2-D imaging, which represents a considerable challenge. As a result, 3-D visualization technology has been proposed as a way to better facilitate laparoscopy. We compared the latest 3-D systems with high-end 2-D monitors to validate the usefulness of new systems for endoscopic diagnoses and treatment in Thailand. METHODS: We compared the abilities of our high-definition 3-D endoscopy system with real-time compression communication system with a conventional high-definition (2-D) endoscopy system by asking health-care staff to complete tasks. Participants answered questionnaires and whether procedures were easier using our system or the 2-D endoscopy system. RESULTS: Participants were significantly faster at suture insertion with our system (34.44 ± 15.91 s) than with the 2-D system (52.56 ± 37.51 s) (P < 0.01). Most surgeons thought that the 3-D system was good in terms of contrast, brightness, perception of the anteroposterior position of the needle, needle grasping, inserting the needle as planned, and needle adjustment during laparoscopic surgery. Several surgeons highlighted the usefulness of exposing and clipping the bile duct and gallbladder artery, as well as dissection from the liver bed during laparoscopic surgery. In an image-transfer experiment with RePure-L®, participants at Rajavithi Hospital could obtain reconstructed 3-D images that were non-inferior to conventional images from Chulalongkorn University Hospital (10 km away). CONCLUSION: These data suggest that our newly developed system could be of considerable benefit to the health-care system in Thailand. Transmission of moving endoscopic images from a center of excellence to a rural hospital could help in the diagnosis and treatment of various diseases.

Association between serum hepatocyte growth factor and survival in untreated hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common hepatic malignancy worldwide. Its nature of rapid growth results in a grave prognosis. Hepatocyte growth factor (HGF) is a mitogen for hepatocytes, responsible for their proliferation. The aim of the present study was to investigate the prognostic roles of serum HGF in untreated HCC patients. METHODS: Fifty-five patients with inoperable HCC were studied. The diagnosis of HCC was based on either liver histopathology or imaging evidence of a liver mass, together with elevated serum alpha-fetoprotein. Serum HGF levels of the patients, at the time of diagnosis, were compared to those of 28 healthy controls. All patients received only palliative treatments and were followed up until they died. Comparison of survival curves between patients with a serum HGF level of 1.0 ng/ml or more and those with lower serum HGF was performed, using the log-rank test. Data values are expressed as means and SD. RESULTS: Fifty-one men and four women with inoperable HCC were recruited. The mean age was 54.15+/-15.34 years. The serum HGF levels in the inoperable HCC patients were significantly higher than those in the controls (0.58+/-0.43 vs 0.14+/-0.04 ng/ml; P<0.001). The patients' mean survival time was 5.28+/-6.73 months (range, 0.1-33 months). Serum HGF levels exhibited a negative correlation with the survival time (P=0.032). In addition, HCC patients with serum HGF levels of 1.0 ng/ml or more had a shorter survival time than the other HCC patients (P=0.0025). CONCLUSIONS: Patients with inoperable HCC had higher levels of serum HGF than the healthy controls, and serum HGF was negatively correlated with the survival time. Serum HGF levels of 1.0 ng/ml or more in HCC patients are suggestive of a grave prognosis, indicating that HGF plays important and active roles in the disease progression. The detailed mechanisms need to be further investigated.

High-dose steroids do not improve early outcome in biliary atresia.

PURPOSE: Our objective was to evaluate the effects of steroids on early outcome in biliary atresia (BA). METHODS: Patients with BA between 2001 and 2005 were reviewed. The use of steroids (4 mg/kg per day at alternate days for 1 to 3 months) has been routinely implemented since 2003. Jaundice-free status and the occurrence of cholangitis at 6 months postoperatively between patients receiving steroids and those not receiving steroids were compared. RESULTS: Fifty-three patients with BA were studied. At 6 months postoperation, 30 patients (56.6%) were jaundice free and 24 patients (45.3%) experienced cholangitis at least once. Of the 53 patients, there were 33 patients in the steroid group and 20 patients in the nonsteroid group. The proportion of jaundice-free patients in the steroid group was higher than that in the nonsteroid group, and the proportion of patients with cholangitis in the steroid group was lower than that in the nonsteroid group. However, these discrepancies did not reach a statistically significant difference (jaundice-free status [steroid vs nonsteroid]: 20/33 [60.6%] vs 10/20 [50%], P = .57; cholangitis: 13/33 [39.4%] vs 11/20 [55%], P = .39). CONCLUSIONS: Although the use of steroids seems to have benefits, it did not statistically improve early outcome in patients with BA.

Elevated serum nitric oxide metabolites in biliary atresia.

Biliary atresia (BA) remains one of the most intractable liver diseases in children. The aim of this study was to investigate the possible roles of nitric oxide (NO) in BA. Serum levels of nitrite and nitrate (NO production) were determined using a colorimetric method from 65 post-operative BA patients and 12 healthy children. The patients were categorized into two groups according to their jaundice status, and serum alanine aminotransferase (ALT, a marker for liver injury). Unpaired t tests were used. Data are expressed as mean and SD in terms of mumol/l. Age and gender between BA patients and controls were comparable. Serum NO metabolites of BA patients was higher than the controls (79.77+/-21.22 vs. 65.75+/-9.44, P=0.001). Subgroup analysis revealed that there was no difference in serum nitrate/nitrite levels of BA patients without jaundice compared to those with jaundice (78.85+/-23.23 vs. 80.90+/-18.76, P=0.70). However, patients with serum ALT> or =100 IU/l had higher levels of serum NO metabolites compared to those with serum ALT<100 IU/l. In conclusion, NO production was elevated in BA patients compared to normal controls. Serum NO was associated with serum ALT levels, but not with jaundice status, in BA patients. These suggest that NO plays a role in the pathophysiology of liver injury in post-operative BA.

Amelioration of intestinal reperfusion injury by moderate hypothermia is associated with serum sICAM-1 levels.

BACKGROUND: The aim of this study was to investigate the effects of moderate hypothermia on various serum markers involving in inflammation after intestinal ischemia-reperfusion (IR). MATERIALS AND METHODS: The model of 30 min intestinal ischemia +90 min reperfusion was used. Three groups of rats were studied, n=7-8 per group: 1) sham at normothermia, 36.5 to 37.5 degrees C; 2) IR at normothermia and; 3) IR at moderate hypothermia, 32 to 33 degrees C. Serum levels of TNF-alpha, lipopolysaccharide-inducible CXC chemokine (LIX), and soluble intercellular adhesion molecule-1 (sICAM-1) were determined using ELISA technique. Histological features of terminal ileum were also graded. RESULTS: Intestinal IR at normothermia caused remarkable tissue injury together with an elevation in serum TNF-alpha, LIX, and sICAM-1 levels. Moderate hypothermia significantly decreased the degree of mucosal damage and attenuated the elevation of serum sICAM-1 levels. However, there were no significant differences in serum TNF-alpha and LIX levels between IR at normothermia and IR at hypothermia. CONCLUSIONS: Intestinal IR at normothermia induces the elevation of serum TNF-alpha, LIX, and sICAM-1 levels. Moderate hypothermia protects the small intestine from reperfusion injury. This beneficial effect is associated with serum sICAM-1 levels but not with serum TNF-alpha and LIX levels. We speculate that one of the mechanisms, by which hypothermia blunts the tissue injury, is at the step of firm adhesion between leukocytes and endothelial cells.

Serum hepatocyte growth factor and clinical outcome in biliary atresia.

PURPOSE: Biliary atresia (BA) remains one of the most intractable liver diseases leading to liver fibrosis. Serum hepatocyte growth factor (HGF) has been shown to increase in cirrhotic patients. The aim of this study was to investigate the possible role of HGF in BA. METHODS: Serum levels of HGF were determined using an enzyme-linked immunosorbent assay from 28 BA patients and 25 healthy children. The patients were categorized into 3 groups according to their clinical outcomes (good, fair, and poor): group A (good), jaundice-free patients (total bilirubin [TB] < 2.0 mg%); group B (fair), patients with mild to moderate jaundice (TB, 2 to 10 mg%); and group C (poor), patients with marked jaundice (TB > 10 mg%). Unpaired t test and analysis of variance (ANOVA) with post-hoc tests were used. Data were expressed as mean and SEM. RESULTS: Serum HGF levels in BA patients were higher than the controls (P =.02). Subgroup analysis found that there were 12 patients in group A, 8 patients in group B, and 8 patients in group C. The mean age of patients in groups A, B, and C were 5.34 +/- 0.52, 7.45 +/- 1.98, and 5.49 +/- 1.57 years (P >.05). Serum HGF in controls and groups A, B, and C were 0.24 +/- 0.03, 0.28 +/- 0.04, 0.36 +/- 0.09, and 0.56 +/- 0.07 ng/mL, respectively. Serum HGF levels in BA patients with poor outcome were higher than patients with good outcome (P =.02). There was no difference in serum HGF of BA patients with fair outcome compared with other groups. CONCLUSIONS: Serum HGF is elevated in BA. Furthermore, BA patients with poor outcome have significantly elevated HGF compared with patients with good outcome. Serum HGF levels may be predictive of prognosis with respect to the progression of liver dysfunction. However, the results of HGF in patients with fair outcome are inconclusive, probably because of the small sample size. Further studies are needed to elucidate the detailed mechanisms.