The prevalence and impact of small intestine bacterial overgrowth in biliary atresia patients.

BACKGROUND: Acute cholangitis is an ominous complication in biliary atresia (BA) patients. We investigated the prevalence of small intestine bacterial overgrowth (SIBO) in BA patients and its role in predicting acute cholangitis. METHODS: There are 69 BA patients with native liver recruited into this study prospectively. They received hydrogen and methane-based breath testing (HMBT) to detect SIBO after recruitment and were followed prospectively in our institute. RESULTS: There are 16 (23.19%) subjects detected to have SIBO by HMBT. BA subjects with SIBO were noted to have higher serum alanine aminotransferase levels than others without SIBO (P = 0.03). The risk of acute cholangitis is significantly higher in BA patients with SIBO than in others without SIBO (62.50% vs. 15.09%, P < 0.001). The logistic regression analysis demonstrated that BA subjects with SIBO have a higher risk of acute cholangitis than others without SIBO (odds ratio = 9.38, P = 0.001). Cox's proportional hazard analysis further confirmed the phenomena in survival analysis (hazard ratio = 6.43, P < 0.001). CONCLUSIONS: The prevalence of SIBO in BA patients is 23.19% in this study. The presence of SIBO is associated with the occurrence of acute cholangitis in BA patients. IMPACT: What is the key message of your article? Acute cholangitis is common in BA, and is associated with SIBO after hepatoportoenterostomy in this study. What does it add to the existing literature? This study demonstrated that SIBO is common in BA after hepatoportoenterostomy, and is predictive of acute cholangitis and elevated serum ALT levels in BA. What is the impact? This prospective cohort study provides data regarding the significance of SIBO on the risk of acute cholangitis in BA patients.

Clinical utility of anal sphincter relaxation integral in water-perfused and solid-state high-resolution anorectal manometry.

BACKGROUND/PURPOSE: We investigated the diagnostic performance of the anal sphincter relaxation integral (ASRI) for infants with Hirschsprung's disease (HD). METHODS: We performed water-perfused high-resolution anorectal manometry (HRAM) in 18 infants (9 with HD), and solid-state HRAM in another 18 infants (4 with HD). We calculated the ASRI during the rectoanal inhibitory reflex (RAIR) maneuver at pressure cutoffs of <10 mmHg (ASRI 10) and <15 mmHg (ASRI 15). We investigated the diagnostic performance of the ASRI for HD in infants undergoing water-perfused and solid-state HRAM. RESULTS: HD infants who underwent either water-perfused or solid-state HRAM had significantly lower ASRI 10 and ASRI 15 values, compared with non-HD infants (P < 0.05 and P < 0.05, respectively). Using the water-perfused HRAM system, ASRI 10 and ASRI 15 values of <7 and <29 mmHg s.cm, respectively, exhibited good diagnostic performance for HD (88.89% and 88.89%, respectively). Receiver operating characteristic curve analysis indicated that ASRI 10 and ASRI 15 values of <5.5 and <20 mmHg s.cm, respectively, were optimal for the diagnosis of HD infants when using the solid-state HRAM system, with high diagnostic accuracies of 83.33% and 83.33%, respectively. CONCLUSION: ASRI may assist the diagnosis of HD infants using either water-perfused or solid-state HRAM. These systems require different catheter-specific ASRI cutoffs for the prediction of HD.

Risk factors for digestive morbidities after esophageal atresia repair.

Esophageal atresia with/without tracheoesophageal fistula (EA/TEF) is a congenital digestive tract anomaly that represents a major therapeutic challenge. Postoperative digestive morbidities such as gastroesophageal reflux disease (GERD) and esophageal stricture are common. The aim of this study was to identify the incidence of and potential risk factors for digestive morbidities after EA/TEF repair. We retrospectively reviewed all EA/TEF patients who underwent repair at a single institution between January 1999 and December 2018, excluding patients who died prior to discharge. Patient demographics, perioperative management, and postoperative GERD and esophageal stricture rates were collected. We performed univariate and multivariate analyses to examine risk factors associated with postoperative GERD and esophageal stricture. The study enrolled 58 infants (58.6% male, 17.2% with type A EA/TEF, 62.1% with associated anomalies). Postoperative GERD occurred in 67.2% of patients and was the most common digestive morbidity. Esophageal stricture occurred in 37.9% of patients after EA/TEF repair. Multivariate analysis showed that long-gap EA/TEF and postoperative GERD were independent risk factors for esophageal stricture after repair surgery.Conclusion: The incidence of postoperative GERD and esophageal stricture was 67.2% and 37.9%, respectively. The risk factors for postoperative esophageal stricture were long-gap EA/TEF and postoperative GERD. What is Known: • EA/TEF is a congenital digestive tract anomaly with a high postoperative survival rate but can be complicated by many long-term morbidities. What is New: • Long-gap EA/TEF and postoperative GERD are risk factors of anastomotic stricture after repair. • Surgeons and pediatricians should be highly experienced in managing anastomotic tension and the GERD.

Transient elastography is useful in diagnosing biliary atresia and predicting prognosis after hepatoportoenterostomy.

We investigated the utility of transient elastography (TE) for diagnosing biliary atresia (BA) in cholestatic infants and predicting the outcome of BA. Forty-eight cholestatic infants (9-87 days of age) with direct bilirubin level >1 mg/dL were enrolled. Liver stiffness measurement (LSM) by TE was performed during the cholestasis workup, and 15 subjects were diagnosed as BA. We assessed liver histology using liver biopsies from 36 subjects and graded fibrosis status using the METAVIR score. BA infants had significantly higher LSM values and METAVIR scores than non-BA cholestatic infants. A receiver operating characteristic (ROC) curve analysis showed that an LSM >7.7 kPa was predictive of BA among cholestatic infants (sensitivity = 80%; specificity = 97%; area under the curve [AUC] = 85.3%; P = 0.0001). Cholestatic infants with an LSM >7.7 kPa were more likely to be diagnosed with BA (odds ratio [OR] = 128; P < 0.001). Very early measurement of LSM after hepatoportoenterostomy (HPE) is associated with occurrence of thrombocytopenia, splenomegaly, and esophageal varices 6 months post-HPE. Five of the BA subjects were awaiting or had received liver transplantation (LT), and they had a significantly higher LSM measured 1 week post-HPE than that in the other BA subjects (26.0 vs. 10.8 kPa; P = 0.006). A Cox proportional analysis demonstrated that the need for LT was significantly higher in BA subjects with LSM >16 kPa measured 1 week post-HPE than other BA subjects (hazard ratio [HR] = 10.16; P = 0.04). CONCLUSION: LSM assessment during the workup of cholestatic infants may facilitate the diagnosis of BA. LSM post-HPE may predict complications and the need for early LT in infants with BA. (Hepatology 2018).

Mosaic paternal haploidy in a patient with pancreatoblastoma and Beckwith-Wiedemann spectrum.

Pancreatoblastoma is a rare type of pancreatic cancer in children. Here, we describe a case in which Beckwith-Wiedemann syndrome (BWS) was first suspected because of placental mesenchymal dysplasia. Although the baby did not show the stigmata characteristic of BWS or abnormal peripheral blood methylation, she developed a massive pancreatoblastoma 2 months later. She survived after partial excision of the tumor and chemotherapy. The methylation pattern of the pancreatoblastoma tissue was typical of BWS. Single nucleotide polymorphism (SNP) array analyzes revealed that the pancreatoblastoma tissue had genome-wide loss of maternal alleles. Peripheral blood and nontumor pancreatic tissue showed normal biparental genomic contribution. Interphase fluorescence in situ hybridization analysis with centromeric probes for chromosomes 2 and 11 revealed haploid pancreatoblastoma cells, whereas the placental mesenchymal dysplasia tissue and nontumor pancreas tissue showed diploidy. SNP genotype analysis suggested the presence of mosaicism with the pancreatoblastoma tissue having a different paternal haplotype than that of the peripheral blood and nontumor pancreatic tissue. We report for the first time mosaic paternal haploidy associated with pancreatoblastoma. Babies with placental mesenchymal dysplasia, even those without a definitive diagnosis of BWS, need to be closely followed for the occurrence of embryonic tumors.

Extracorporeal membrane oxygenation for neonatal congenital diaphragmatic hernia: The initial single-center experience in Taiwan.

BACKGROUND/PURPOSE: Extracorporeal membrane oxygenation (ECMO) is a treatment option for stabilizing neonates with congenital diaphragmatic hernia (CDH) in a critical condition when standard therapy fails. However, the use of this approach in Taiwan has not been previously reported. METHODS: The charts of all neonates with CDH treated in our institute during the period 2007-2014 were reviewed. After 2010, patients who could not be stabilized with conventional treatment were candidates for ECMO. We compared the demographic data of patients with and without ECMO support. The clinical course and complications of ECMO were also reviewed. RESULTS: We identified 39 neonates with CDH with a median birth weight of 2696 g (range, 1526-3280 g). Seven (18%) of these patients required ECMO support. The APGAR score at 5 minutes differed significantly between the ECMO and non-ECMO groups. The survival rate was 84.6% (33/39) for all CDH patients and 57.1% (4/7) for the ECMO group. The total ECMO bypass times in the survivors was in the range of 5-36 days, whereas all nonsurvivors received ECMO for at least 36 days (mean duration, 68 days). Surgical bleeding occurred in four of seven patients in the ECMO group. CONCLUSION: The introduction of ECMO rescued some CDH patients who could not have survived by conventional management. Prolonged (i.e., > 36 days) ECMO support had no benefit for survival.

The magnetic resonance imaging and age-adjusted matrix metalloproteinase-7 assist the diagnosis of biliary atresia.

BACKGROUND: We investigated the utilities of the liver-to-psoas apparent diffusion coefficient ratios (LTPAR) yielded by diffusion-weighted magnetic resonance imaging (DWMRI) and the age-adjusted serum matrix metalloproteinase-7 (MMP-7) for the diagnosis of biliary atresia (BA) in cholestatic infants. METHODS: In total, 170 cholestatic infants were recruited, of whom 50 (29.41%) were diagnosed with BA after cholestatic workups. The LTPAR and MMP7 levels were assessed. RESULTS: The LTPAR was significantly lower in BA infants, and the age-adjusted MMP7 ratio was significantly higher, compared to other cholestatic infants (both p < 0.001). Receiver operating characteristic curve analysis yielded a cutoff > 0.1 ng/mL.day for the age-adjusted MMP-7 ratio, and an LTPAR < 1.01 for the optimal prediction of BA (both p < 0.001). Univariate logistic regression analysis revealed that both an age-adjusted MMP-7 ratio > 0.1 ng/mL.day and an LTPAR < 1.01 were significant predictors of BA among cholestatic infants (odds ratio = 30.98 and 13.28; p < 0.001 and < 0.001, respectively). The significance of the age-adjusted MMP-7 ratio and the LTPAR persisted on multivariate logistic regression analysis after adjusting for sex and the serum gamma-glutamyl transferase level (p < 0.001 and < 0.001, respectively). The negative predictive values (NPVs) for BA were 91.49% and 94.17%, respectively, for the LTPAR and age-adjusted MMP-7 ratio. CONCLUSION: The age-adjusted MMP-7 ratio and the LTPAR are both significant non-invasive predictors of BA. The consideration of both serum and imaging parameters may enhance BA diagnostic performance in cholestatic infants.

Choledochal cyst originating from primary sclerosing cholangitis in a child.

Choledochal cysts are common in Asian children. Primary sclerosing cholangitis (PSC), which is characterized by inflammation and fibrosis and may lead to bile duct stricture over the intrahepatic or extrahepatic bile duct, is rare in children. Here we report a case of a 10-year-old boy who presented with a choledochal cyst originating from PSC. He had suffered from repeated abdominal pain and cholangitis for 3 years. A type IV choledochal cyst was suspected from the ultrasound and computed tomography image showing a distended gallbladder and dilatation of the bilateral intrahepatic duct at the hepatic hilar area and common bile duct (CBD). During laparotomy, a markedly distended gallbladder was noted and was shown to have no communication with the CBD by intraoperative cholangiogram. Choledochal cysts with extrahepatic and intrahepatic duct dilatation at the hilar area and marked stenosis with nearly total obstruction of the distal CBD were noted. Hepaticojejunostomy was performed. The histopathologic findings demonstrated a typical PSC picture. The patient's postoperative course was uneventful for 8 months after surgery, and he received no medication during a regular follow-up.

Case Report: Kasai Operation in Biliary Atresia After Extensive Bowel Resection.

Biliary atresia (BA) is a major and devastating cholestatic liver disease in infancy. The Kasai procedure is an operation to re-establish bile flow from the liver into the intestine that can prevent the young infant from progressing rapidly to cirrhosis. The standard Kasai procedure includes the removal of extrahepatic bile duct remnants and reconstruction. We report a case of BA with short bowel due to previous small intestinal volvulus. This full-term female infant received extensive small bowel resection after birth due to intestinal volvulus. The length of the residual small bowel was 55 cm with an intact ileocecal valve. Because of progressive cholestasis and clay stool, another laparotomy was performed under the diagnosis of BA on the 52 days old. After dissection of the hepatic portal area, a segment of the colon instead of intestine was used as a biliary conduit to avoid further shortening her small bowel. The patient recovered from the procedure uneventfully and the parenteral nutrition was discontinued 2 weeks later. Two episodes of cholangitis happened after discharge. She gradually resumed body weight gain and the bilirubin level returned to normal range 6 months after the operation. This unique case demonstrated successful use of this specific procedure in the patient with BA and short bowel that have never been reported in the literature.

Diagnostic Performance of Transient Elastography in Biliary Atresia Among Infants With Cholestasis.

Biliary atresia (BA) is a challenging liver disease in infancy. Early diagnosis of BA is important for timely hepatoportoenterostomy. We evaluated the age-specific diagnostic performance of transient elastography (TE) with a liver stiffness measurement (LSM) greater than 7.7 kPa in BA among infants with cholestasis. A total of 61 infants with cholestasis (5-121 days of age) were enrolled in this prospective follow-up study; 15 infants were BA. Four age groups were defined (≤30, 31-60, 61-90, and 91-180 days). Picrosirius red staining was performed to quantify the percentage of collagen fibers in liver specimens. The utility of an LSM greater than 7.7 kPa for diagnosis of BA among infants with cholestasis was compared among age groups. In all four groups, TE showed high diagnostic power for BA using the criterion of an LSM greater than 7.7 kPa. Positive predictive values were 100%, 100%, and 100% in the groups aged 30 days or younger, 31 to 60 days, and 61 to 90 days, respectively. Respective negative predictive values were 90.9%, 94.7%, and 100%, and respective diagnostic accuracies were 92.9%, 95.2%, and 100%. The positive predictive value, negative predictive value, and diagnostic accuracy were 100%, 100%, and 100%, respectively, for LSM greater than 8.8 kPa in the group aged 91 to 180 days. The LSM was positively correlated with the percentage of collagen fibers stained by picrosirius red (P = 0.03). Conclusion: In this prospective follow-up study, TE had good diagnostic accuracy for differentiation of BA from non-BA cholestasis in infants with cholestasis who were 90 days of age or younger. The LSM was significantly positive correlated with the liver fibrosis status stained by picrosirius red in infants with cholestasis.

Modified Paul-Mikulicz ileostomy in a Swine model of isolated small bowel transplantation.

BACKGROUND: Intestinal transplantation (ITx) is a life-saving procedure for patients with intestinal failure. The poorer outcome of ITx than of other organ transplantation, however, warrants more clinical and basic research on ITx. Herein, we developed a modified Paul-Mikulicz ileostomy procedure in a swine model of ITx, and investigated its feasibility for obtaining intestinal samples of both the graft and the recipient. MATERIALS AND METHODS: We performed ITx in 10 pairs of piglets, each weighing 15-20 kg. Procurement included an isolated segment of the small bowel, constituting a model of a living, related donor surgery. The recipient procedures included end-to-end anastomosis of vascular stumps, a proximal jejuno-jejunal anastomosis, and a distal modified Paul-Mikulicz ileostomy. The procedure differed from the classic Paul-Mikulicz ileostomy in that a common channel was created in a side-to-side fashion. RESULTS: Vascular thrombosis occurred in three pigs, resulting in immediate loss of the graft. All other pigs underwent ITx successfully and survived for at least 1 wk (7-180 d). No pig experienced anastomotic leaks, ileus, or stoma-related complications. Moreover, this technique enabled us to obtain tissue samples of both the graft and the native ileum without disturbing the natural bowel conduit. CONCLUSIONS: The modified Paul-Mikulicz ileostomy was feasible in a swine model of ITx. It facilitated the collection of intestinal samples of both the graft and the recipient.

Sliding inguinal hernia with incarceration of urinary bladder diverticulum in a child.

Although inguinal herniorrhaphy is generally safe, certain complications can occur even with an experienced pediatric surgeon. We present a case of sliding right inguinal hernia with incarceration of urinary bladder diverticulum in a 2-year-old boy. A small perforation at the anterior wall of the urinary bladder, peritonitis, and kinking of the sigmoid colon occurred after the herniorrhaphy. He received exploratory laparotomy for repairing the urinary bladder perforation hole and drainage of the ascites. An anal tube was inserted to keep the sigmoid colon patent. The patient recovered from this insult gradually with an uneventful postoperative course 10 months after the operation, until the writing of this study. Surgeons should be aware of the possibility of urinary bladder diverticulum incarceration at the inguinal canal and should perform the operation meticulously.

Successful laparotomy in a 432 g extremely low-birth-weight infant with focal intestinal perforations.

Acute intra-abdominal abnormalities requiring emergency laparotomy in extremely low-birth-weight (ELBW) infants may increase morbidity and mortality. Focal intestinal perforations (FIPs) not due to necrotizing enterocolitis (NEC) are increasingly recognized in ELBW infants. We present an ELBW preterm male infant (24 weeks' gestation) with FIP who underwent successful abdominal surgery when the patient weighed 432 g. Three isolated intestinal perforations without any NEC were identified. The patient was stable and weighed 1142 g on the 100th day after surgery. Common morbidities associated with ELBW do not appear to be adversely affected by surgical intervention; however, long-term follow-up is essential to enhance future developmental outcomes upon survival.

Variations in interferon gamma receptor gene expression during liver regeneration after partial hepatectomy in rats.

Cell-mediated immunity, which includes interferon gamma (IFN-gamma) expression, is activated during the process of liver regeneration; however, the genetic pathway of this activation is still unclear. The present study evaluated variations in the interferon gamma receptor (IFN-gamma R) gene and its mRNA expression during liver regeneration after partial hepatectomy (PH). Male Wistar rats weighing approximately 200 g were subjected to PH (70 or 40%). IFN-gamma R gene expression in the remnant liver was measured by cDNA microarray, and mRNA expression was verified by real-time quantitative reverse transcription-polymerase chain reaction (Q-PCR) preoperatively and at 2, 4, 6, 12, 24, and 72 hours and 7 days postoperatively. The ratio of remnant liver weight to body weight increased markedly after 70 per cent PH and more gradually after 40 per cent PH. It reached near 90 per cent of the preoperative level at 72 hours after PH in both groups. The scanned spots of the genomic survey on the cDNA microarray chips were uneven and increased irregularly in number and density after PH. IFN-gamma R gene expression increased markedly in a single peak pattern, up to more than double the preoperative level, at 6 hours after 70 per cent PH. The curve in the 40 per cent PH group was flat and peaked at only 1.6 times the preoperative level. The variations in IFN-gamma R-related mRNA expression were verified by Q-PCR. Elevations in IFN-gamma R gene and mRNA expression were shown during the early stage of liver regeneration after PH. The genetic pathway of IFN-gamma/IFN-gamma R expression is activated during liver regeneration.

Effects of a medium-chain triacylglycerol/long-chain triacylglycerol fat emulsion containing a reduced ratio of phospholipid to triacylglycerol in pediatric surgical patients.

OBJECTIVE: Medium-chain triacylglycerol (MCT) has been shown to provide better nutritional support than long-chain triacylglycerol (LCT). We compared the efficacy of MCT/LCT fat emulsions containing a usual (0.12) or a decreased (0.06) ratio of phospholipid to triacylglycerol (PL:TG) in pediatric patients under surgical stress. METHODS: Three patient groups (n=10 in each) received equivalent amounts of glucose (12 g.kg(-1).d(-1)) and amino acids (2 g.kg(-1).d(-1)), but group A received a 10% MCT fat emulsion (PL:TG 0.06), group B received a 20% MCT fat emulsion (PL:TG 0.06), and group C received a 10% MCT/LCT fat emulsion (PL:TG 0.12) in amounts of 1.5 g.kg(-1).d(-1) in a randomized study. Total parenteral nutrition was given for 7 d. Blood samples were collected before total parenteral nutrition administration and on days 4 and 7 for determination of various biochemical indexes. RESULTS: Serum phospholipid concentrations were significantly higher in group C than in group A or B on days 4 and 7 (P<0.05). Serum triacylglycerol and cholesterol concentrations and the very-low-density lipoprotein percentage were also significantly higher in group C than in group A or B on days 4 and 7 (P<0.05). The high-density lipoprotein percentage was significantly higher in group B on days 4 and 7 (P<0.05). CONCLUSIONS: In pediatric patients under surgical stress, a total parenteral nutrition regimen containing an MCT/LCT fat emulsion with a decreased PL:TG ratio (0.06) is likely to result in partly better lipid and lipoprotein metabolism than an emulsion containing the usual ratio (0.12).

Lysophosphatidic acid alters the expression profiles of angiogenic factors, cytokines, and chemokines in mouse liver sinusoidal endothelial cells.

BACKGROUND AND AIMS: Lysophosphatidic acid (LPA) is a multi-function glycerophospholipid. LPA affects the proliferation of hepatocytes and stellate cells in vitro, and in a partial hepatectomy induced liver regeneration model, the circulating LPA levels and LPA receptor (LPAR) expression levels in liver tissue are significantly changed. Liver sinusoidal endothelial cells (Lsecs) play an important role during liver regeneration. However, the effects of LPA on Lsecs are not well known. Thus, we investigated the effects of LPA on the expression profiles of angiogenic factors, cytokines, and chemokines in Lsecs. METHODS: Mouse Lsecs were isolated using CD31-coated magnetic beads. The mRNA expression levels of LPAR's and other target genes were determined by quantitative RT-PCR. The protein levels of angiogenesis factors, cytokines, and chemokines were determined using protein arrays and enzyme immunoassay (EIA). Critical LPAR related signal transduction was verified by using an appropriate chemical inhibitor. RESULTS: LPAR1 and LPAR3 mRNA's were expressed in mouse LPA-treated Lsecs. Treating Lsecs with a physiological level of LPA significantly enhanced the protein levels of angiogenesis related proteins (cyr61 and TIMP-1), cytokines (C5/C5a, M-CSF, and SDF-1), and chemokines (MCP-5, gp130, CCL28, and CXCL16). The LPAR1 and LPAR3 antagonist ki16425 significantly inhibited the LPA-enhanced expression of cyr61, TIMP-1, SDF-1, MCP-5, gp130, CCL28, and CXCL16, but not that of C5/C5a or M-CSF. LPA-induced C5/C5a and M-CSF expression may have been through an indirect regulation mechanism. CONCLUSION: LPA regulated the expression profiles of angiogenic factors, cytokines, and chemokines in Lsecs that was mediated via LPAR1 and LPAR3 signaling. Most of the factors that were enhanced by LPA have been found to play critical roles during liver regeneration. Thus, these results may prove useful for manipulating LPA effects on liver regeneration.

Laparoscopic Ladd's procedure for intestinal malrotation: report of three cases.

Ladd's procedure for laparoscopic repair of malrotation has many advantages over conventional surgical techniques, such as earlier feeding and discharge. However, this procedure is still not commonly used in Taiwan. This report describes the results of treatment of intestinal malrotation in three patients using laparoscopic Ladd's procedure. The patients, aged 8 days, 17 days, and 3 years, underwent laparoscopic Ladd's procedure between July 1999 and September 2000. All three patients had symptoms of intermittent vomiting and were shown to have intestinal malrotation by upper gastrointestinal series study. The procedure was performed using three trocars of 5 mm diameter placed at the infraumbilical ring and the right and left lower quadrants. All procedures were completed laparoscopically. The operative times were 4.8, 3.6, and 3.5 hours, respectively. Feeding was started on postoperative Day 2 to 5, and the hospital stay was 6 to 11 days. Our results suggest that laparoscopic Ladd's procedure can be performed safely in pediatric patients. In addition, patients are expected to benefit from the smaller incision, earlier feeding, shorter hospital stay, and fewer complications compared with traditional Ladd's procedure.

Lipocalin-2 gene expression during liver regeneration after partial hepatectomy in rats.

BACKGROUND: Lipocalin-2 (Lcn2) is related to cell proliferation. We studied Lcn2 gene expression during liver regeneration after partial hepatectomy (PH). METHODS: Male Wistar rats were sacrificed before and 2, 4, 6, 12, 24, 72 h, 7 days after 70% or 40% PH. The remnant liver weight/body weight (RLW/BW) ratio, Lcn2 gene and mRNA expression in the remnant livers were measured. Hepatocytes and nonparenchymal cells were isolated from the remnant livers. Expression of Lcn2 related protein was detected by Western blot. RESULTS: The RLW/BW ratio increased to nearly 90% of the original liver 72 h after PH. Lcn2 gene expression showed upward curves from 4 to 72 h after PH in both 70% and 40% PH rats and peaked at 12 h (8 times vs 0 h). Lcn2 mRNA expression showed parallel upward curves from 2 to 72 h. The peak was significantly higher in 70% PH rats (2(7) times vs 0 h) than in 40% PH rats (2(5) times vs 0 h) 12 h after PH (p < 0.05). Lcn2 related protein in the isolated liver cells was markedly enhanced 24 h after PH, more in hepatocytes than in nonparenchymal cells. CONCLUSION: The expressions of Lcn2 gene and mRNA, and its related protein increased markedly after PH. Lcn2 might be important in the genetic regulation of liver regeneration after PH.

Interleukin-6 mediates angiotensinogen gene expression during liver regeneration.

BACKGROUND: Angiotensinogen is the precursor of angiotensin II, which is associated with ischemia-reperfusion injury. Angiotensin II reduces liver regeneration after hepatectomy and causes dysfunction and failure of reduced-size liver transplants. However, the regulation of angiotensinogen during liver regeneration is still unclear. AIMS: To investigate the regulation of angiotensinogen during liver regeneration for preventing angiotensin II-related ischemia-reperfusion injury during liver regeneration. METHODS: A mouse in vitro partial hepatectomy animal model was used to evaluate the expression of interleukin-6 (IL-6) and angiotensinogen during liver regeneration. Serum IL-6 and angiotensinogen were detected by enzyme immunoassay (EIA). Angiotensinogen mRNA was detected by RT-PCR. Tissue levels of angiotensinogen protein were detected by Western blot analysis. Primary cultures of mouse hepatocytes were used to investigate IL-6-induced angiotensinogen. Chemical inhibitors were used to perturb signal transduction pathways. Synthetic double-stranded oligodeoxynucleotides (ODNs) were used as 'decoy' cis-elements to investigate transcription. Ki 67 staining and quantification were used to verify liver regeneration. RESULTS: In the in vivo model, the levels of serum IL-6 and angiotensinogen correlated. In the in vitro model, IL-6 transcriptionally regulated angiotensinogen expression. Additionally, IL-6 mediated angiotensinogen expression through the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) and JAK/p38 signaling. Decoy ODN analyses revealed that STAT3 and nuclear factor-kB (NF-kB) also played critical roles in the transcriptional regulation of angiotensinogen by IL-6. IL-6-mediated signaling, JAK2, STAT3 and p38 inhibitors reduced angiotensinogen expression in the partially hepatectomized mice. CONCLUSION: During liver regeneration, IL-6-enhanced angiotensinogen expression is dependent on the JAK/STAT3 and JAK/p38/NF-kB signaling pathways. Interruption of the molecular mechanisms of angiotensinogen regulation may be applied as the basis of therapeutic strategies for preventing angiotensin II-related ischemia-reperfusion injury during liver regeneration.

Clinicopathological feature and surgical outcome of choledochal cyst in different age groups: the implication of surgical timing.

BACKGROUND/AIMS: Surgical resection of choledochal cysts (CC) has become standard treatment. However, surgery is not universally recommended in early infancy and/or asymptomatic patients. In order to investigate the optimal timing of CC excision, we analyzed clinicopathological data and surgical results from different age groups. MATERIAL AND METHODS: This retrospective review included 107 patients (77 females, 30 males) who underwent CC resection at the National Taiwan University Hospital between January 1988 and December 2005. Patient demographic, clinical, and surgical data were collected and analyzed. RESULTS: The patients were divided into three groups according to age at the time of surgery: <1 year old (group I, n = 26), 1-16 years old (group II, n = 48), and >16 years old (group III, n = 33). About two thirds of the patients in group I had jaundice, while abdominal pain related to inflammation was the commonest symptom in groups II and III. Group I suffered significantly fewer surgical complications and less severe liver fibrosis than groups II or III. CONCLUSION: CC surgery in infancy and in asymptomatic patients is safe and may prevent the complications of this condition. The results support a recommendation for early excision.