Bile duct ligation in neonatal rats: Is it a valid experimental model for biliary atresia studies?

BA is the most important disease requiring liver transplantation in children. Common BDL in rats is a classic experimental model to study biliary obstruction. The response of the neonatal animal to BDL has yet to be completely understood and few reports have focused on the behavioral differences of the liver between neonatal and adult animals. Ninety newborn Wistar rats aged six days, weighing 8.0-13.9 g, and 90 adult Wistar rats weighing 199.7-357.0 g, were submitted to BDL. After surgery, they were randomly divided and killed on the 3rd, 5th, 7th, 14th, 21st and 28th day post-BDL. Hepatic biopsies were obtained and the following were measured: (i) semiquantification of the bile ductule proliferation and inflammatory infiltrate by HE stain, (ii) quanti. cation of portal and periportal fibrosis with the Sirius-red stain. Although the initial response of ductule proliferation and inflammatory infiltrate were less intense in the newborn animal, the portal and periportal fibrosis were higher when compared with adult animals (p < 0.0491). These findings may contribute to the understanding of the pathophysiology of BA.

Should patients with esophageal atresia be submitted to esophageal substitution before they start walking?

P>Esophagocoloplasty and gastric transposition are two major methods for esophageal substitution in children with esophageal atresia, and there is broad agreement that these operations should not be performed before the children start walking. However, there are some reported advantages of performing such operations in the first months of life or in the neonatal period. In this study, we compared our experience with esophageal substitution procedures performed in walking children with esophageal atresia, with the outcomes of children who had the operation before the third month of life reported in the literature. The purpose of this study was to establish if we have to wait until the children start walking before indicating the esophageal replacement procedure. From February 1978 to October 2009, 129 children with esophageal atresia underwent esophageal replacement in our hospital (99 colonic interpositions and 30 gastric transpositions). The records of these patients were reviewed for data regarding demographics, complications (leaks, graft failures, strictures, and graft torsion), and mortality and compared with those reported in the two main articles on esophageal replacement in the neonatal period or in patients less than 3 months of age. The main complication of our casuistic was cervical anastomosis leakage, which sealed spontaneously in all except in four patients. One patient of the esophagocoloplasty group developed graft necrosis and three patients in the gastric transposition group had gastric outlet obstruction, secondary to axial torsion of the stomach placed in the retrosternal space. The long-term outcome of the patients in both groups was considered good to excellent in terms of normal weight gain, absence of dysphagia, and other gastrointestinal symptoms. The comparisons of the main complications and mortality rates in walking children with esophageal substitutions performed in the first months of life showed that the incidences of cervical anastomotic leaks and graft failures were similar, but mortality rate in the first few months of life was significantly greater than that observed in our group of patients (P = 0.001). Based on the comparison of our results with those of published series, we conclude that the recommendation of performing esophagocoloplasty or total gastric transposition in children with esophageal atresia after they start walking is still valid.

Orthotopic Liver Transplantation in Biliary Atresia: A Single-Center Experience

Introduction. Biliary atresia (BA) is the leading indication for orthotopic liver transplantation (OLT) among children. However, there are technical difficulties, including the limited dimensions of anatomical structures, hypoplasia and/or thrombosis of the portal vein and previous portoenterostomy procedures. Objective. The objective of this study was to present our experience of 239 children with BA who underwent OLT between September 1989 and June 2010 compared with OLT performed for other causes. Methods. We performed a retrospective analysis of patient charts and analysis of complications and survival. Results. BA was the most common indication for OLT (207/409; 50.6%). The median age of subjects was 26 months (range, 7-192). Their median weight was 11 kg (range, 5-63) with 110 children (53.1%) weighing <= 10 kg. We performed 126 transplantations from cadaveric donors (60.8%) and 81 from living-related donors (LRD) (39.2%). Retransplantation was required for 31 recipients (14.9%), primarily due to hepatic artery thrombosis (HAT; 64.5%). Other complications included the following: portal vein thrombosis (PVT; 13.0%), biliary stenosis and/or fistula (22.2%), bowel perforation (7.0%), and posttransplantation lymphoproliferative disorder (PTLD; 5.3%). Among the cases of OLT for other causes, the median age of recipients was 81 months (range, 11-17 years), which was higher than that for children with BA. Retransplantation was required in 3.5% of these patients (P < .05), mostly due to HAT. The incidences of PVT, bowel perforation, and PTLD were significantly lower (P < .05). There was no significant difference between biliary complications in the 2 groups. The overall survival rates at 1 versus 5 years were 79.7% versus 68.1% for BA, and 81.2% versus 75.7% for other causes, respectively. Conclusions. Children who undergo OLT for BA are younger than those engrafted for other causes, displaying a higher risk of complications and retransplantations.

Rex Shunt for Acute Portal Vein Thrombosis After Pediatric Liver Transplantation in Children With Biliary Atresia

Background/Purpose. Posttransplantation portal vein thrombosis (PVT) can have severe health consequences, and portal hypertension and other consequences of the long-term privation of portal inflow to the graft may be hazardous, especially in young children. The Rex shunt has been used successfully to treat PVT patients since 1998. In 2007, we started to perform this surgery in patients with idiopathic PVT and late posttransplantation PVT. Herein we have reported our experience with this technique in acute posttransplantation PVT. Methods. Three patients of ages 12, 15, and 18 months underwent cadaveric (n = 1) or living donor (n = 2) orthotopic liver transplantation (OLT). All patients had biliary atresia with portal vein hypoplasia; they developed acute PVT on the first postoperative day. They underwent a mesenteric-portal surgical shunt (Rex shunt) using a left internal jugular vein autograft (n = 2) or cadaveric iliac vein graft (n = 1) on the first postoperative day. Results. The 8-month follow-up has confirmed shunt patency by postoperative Doppler ultrasound. There have been no biliary complications to date. Conclusions. The mesenteric-portal shunt (Rex shunt) using an autograft of the left internal jugular or a cadaveric vein graft should be considered for children with acute PVT after OLT. These children usually have small portal veins; reanastomosis is often unsuccessful. In addition, this technique has the advantage to avoid manipulation of the hepatic hilum and biliary anastomosis. Although this study was based on a limited experience, we concluded that this technique is feasible, with great benefits to and low risks for these patients.

Atrioventricular septal defect with coexisting tricuspid atresia

We describe two infants having an atrioventricular septal defect in the setting of a double inlet atrioventricular connection, but with patency of the left-sided valvar orifice and an imperforate right-sided valvar component, and a further case with atrioventricular septal defect and an imperforate Ebstein`s malformation, all producing the haemodynamic effect of tricuspid atresia. We make comparisons with the arrangement in trisomy 16 mice, in whom deficient atrioventricular septation is seen at times with the common atrioventricular junction exclusively connected to the left ventricle, a situation similar to that seen in two of our infants. We also review previous reports emphasising the important theoretical implication of the findings despite their rarity.

Classe II divisão 1 associada à deficiência transversal maxilar. Tratamento com disjuntor tipo Hyrax e aparelho de Herbst: relato de caso clínico

A má oclusão de Classe II divisão 1 de Angle é, frequentemente, acompanhada da atresia maxilar. Esse problema transversal da maxila deve ser corrigido, sempre que possível, antes da correção anteroposterior, sendo que os aparelhos de expansão rápida são os mais utilizados para isso. Para a correção da Classe II, atualmente, os aparelhos funcionais fixos são os mais estudados e empregados, por serem aparelhos intrabucais e necessitarem de menor colaboração do paciente. O objetivo deste estudo é demonstrar a estabilidade dos resultados obtidos após seis anos de tratamento com expansor tipo Hyrax, seguido do aparelho funcional fixo de Herbst e aparelho fixo. Após uma revisão da literatura, será apresentado um caso clínico, com atresia maxilar e má oclusão de Classe II divisão 1, tratado com essa terapia. O tratamento foi realizado em um curto período de tempo, com resultados funcionais e estéticos satisfatórios e mantidos ao longo dos anos.

Orthodontic-surgical treatment of class III malocclusion with mandibular asymmetry

Class III skeletal malocclusion may present several etiologies, among which maxillary deficiency is the most frequent. Bone discrepancy may have an unfavorable impact on esthetics, which is frequently aggravated by the presence of accentuated facial asymmetries. This type of malocclusion is usually treated with association of Orthodontics and orthognathic surgery for correction of occlusion and facial esthetics. This report presents the treatment of a patient aged 15 years and 1 month with Class III skeletal malocclusion, having narrow maxilla, posterior open bite on the left side, anterior crossbite and unilateral posterior crossbite, accentuated negative dentoalveolar discrepancy in the maxillary arch, and maxillary and mandibular midline shift. Clinical examination also revealed maxillary hypoplasia, increased lower one third of the face, concave bone and facial profiles and facial asymmetry with mandibular deviation to the left side. The treatment was performed in three phases: presurgical orthodontic preparation, orthognathic surgery and orthodontic finishing. In reviewing the patient's final records, the major goals set at the beginning of treatment were successfully achieved, providing the patient with adequate masticatory function and pleasant facial esthetics.

Cytomegalovirus frequency in neonatal intrahepatic cholestasis determined by serology, histology, immunohistochemistry and PCR

AIM: To determine cytomegalovirus (CMV) frequency in neonatal intrahepatic cholestasis by serology, histological revision (searching for cytomegalic cells), immunohistochemistry, and polymerase chain reaction (PCR), and to verify the relationships among these methods. METHODS: The study comprised 101 non-consecutive infants submitted for hepatic biopsy between March 1982 and December 2005. Serological results were obtained from the patient's files and the other methods were performed on paraffin-embedded liver samples from hepatic biopsies. The following statistical measures were calculated: frequency, sensibility, specific positive predictive value, negative predictive value, and accuracy. RESULTS: The frequencies of positive results were as follows: serology, 7/64 (11%); histological revision, 0/84; immunohistochemistry, 1/44 (2%), and PCR, 6/77 (8%). Only one patient had positive immunohistochemical findings and a positive PCR. The following statistical measures were calculated between PCR and serology: sensitivity, 33.3%; specificity, 88.89%; positive predictive value, 28.57%; negative predictive value, 90.91%; and accuracy, 82.35%. CONCLUSION: The frequency of positive CMV varied among the tests. Serology presented the highest positive frequency. When compared to PCR, the sensitivity and positive predictive value of serology were low. (C) 2009 The WJG Press and Baishicleng. All rights reserved.

Immunohistochemical detection of polyductin and co-localization with liver progenitor cell markers during normal and abnormal development of the intrahepatic biliary system and in adult hepatobiliary carcinomas

The longest open reading frame of PKHD1 (polycystic kidney and hepatic disease 1), the autosomal recessive polycystic kidney disease (ARPKD) gene, encodes a single-pass, integral membrane protein named polyductin or fibrocystin. A fusion protein comprising its intracellular C-terminus, FP2, was previously used to raise a polyclonal antiserum shown to detect polyductin in several human tissues, including liver. In the current study, we aimed to investigate by immunohistochemistry the detailed polyductin localization pattern in normal (ductal plate [DP], remodelling ductal plate [RDP], remodelled bile ducts) and abnormal development of the primitive intrahepatic biliary system, known as ductal plate malformation (DPM). This work also included the characterization of polyductin expression profile in various histological forms of neonatal and infantile cholestasis, and in cholangiocellular carcinoma (CCC) and hepatocellular carcinoma (HCC). We detected polyductin expression in the intrahepatic biliary system during the DP and the RDP stages as well as in DPM. No specific staining was found at the stage of remodelled bile ducts. Polyductin was also detected in liver biopsies with neonatal cholestasis, including mainly biliary atresia and neonatal hepatitis with ductular reaction as well as congenital hepatic fibrosis. In addition, polyductin was present in CCC, whereas it was absent in HCC. Polyductin was also co-localized in some DP cells together with oval stem cell markers. These results represent the first systematic study of polyductin expression in human pathologies associated with abnormal development of intrahepatic biliary tree, and support the following conclusions: (i) polyductin expression mirrors developmental properties of the primitive intrahepatic biliary system; (ii) polyductin is re-expressed in pathological conditions associated with DPM and (iii) polyductin might be a potential marker to distinguish CCC from HCC.

Frequency of 22q11.2 microdeletion in sporadic non-syndromic tetralogy of Fallot cases

Background: Tetralogy of Fallot (TOF) is a congenital conotruncal heart defect commonly found in DiGeorge (DGS) and velocardiofacial (VCFS) syndromes. The deletion of chromosome 22q11 has also been demonstrated in sporadic or familial cases of TOF. The aim of the present study was to investigate the frequency of del22q11 in patients with non-syndromic TOF seen at a tertiary Pediatric Cardiology care center. Method: One hundred and twenty three non-syndromic TOF patients were selected and evaluated by history, physical examination and review of medical records. Venous blood was drawn for genomic DNA extraction after informed consent 22q11 microdeletion diagnosis was conducted through a standardized SNP genotyping assay and consecutive homozygosity mapping. Phenotype-genotype correlations regarding cardiac anatomy were conducted. Results: We evaluated 123 non-syndromic TOF patients for a 22q11 deletion. 105 (85.4%) patients presented pulmonary stenosis and 18 (14.6%) had pulmonary atresia. Eight patients (6.5%) were found to have a deletion. Of the deleted patients, three (37.5%) presented pulmonary atresia. We have verified a tendency towards a higher prevalence of pulmonary atresia when comparing TOF patients with and without 22q11 microdeletion. Conclusions: 22q11.2 deletion in non-syndromic TOF patients is present in approximately 6% of patients. We suggest a tendency towards a higher prevalence of pulmonary atresia in non-syndromic TOF patients with 22q11 microdeletion. Molecular genetic screening of non-syndromic TOF patient may be important for the correct care of these patients and a more specific genetic diagnostic and counseling. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

Midterm and long-term results of percutaneous endovascular treatment of venous outflow obstruction after pediatric liver transplantation

PURPOSE: To evaluate retrospectively the midterm and long-term results of percutaneous endovascular treatment of venous outflow obstruction after pediatric liver transplantation. MATERIALS AND METHODS: During a 9-year period, 18 children with obstruction of a hepatic vein (HV) or inferior vena cava (IVC) anastomosis underwent percutaneous transluminal angioplasty (PTA) with balloon dilation or stent placement in case of PTA failure after liver transplantation. Patients` body weights ranged from 7.7 kg to 42.6 kg (mean, 18.8 kg +/- 9). Potential predictors of patency were compared between balloon dilation and stent placement groups. RESULTS: Forty-two procedures were performed (range, 1-11 per patient; mean, 2). Technical and initial clinical success were achieved in all cases. Major complications included one case of pulmonary artery stent embolization and one case of hemothorax. Three children (25%) with HV obstruction were treated with PTA and nine (75%) were treated with stent placement. Three children with IVC obstruction (75%) were treated with PTA and one (25%) was treated with a stent. There were two children with simultaneous obstruction at the HV and IVC; one was treated with PTA and the other with a stent. Cases of isolated HV stenosis have a higher probability of patency with balloon-expandable stent treatment compared with balloon dilation (P < .05). Follow-up time ranged from 7 days to 9 years (mean, 42 months +/- 31), and the primary assisted patency rate was 100% when stent placement was performed among the first three procedures. CONCLUSIONS: In cases of venous outflow obstruction resulting from HV and/or IVC lesions after pediatric liver transplantation, percutaneous endovascular treatment with balloon dilation or stent placement is a safe and effective alternative treatment that results in long-term patency.

Fetal cystoscopy for severe lower urinary tract obstruction-initial experience of a single center

Objective To report the experience with fetal cystoscopy and laser fulguration of posterior urethral values (PUV) for severe lower urinary tract obstruction (LUTO). Methods Between July 2006 and December 2008, fetal cystoscopy was offered to 23 patients whose fetuses presented with severe LUTO. favorable urinary analysis and gestational age <26 weeks. Fetal urinary biochemistry was evaluated before and after cystoscopy. All infants were followed 6-12 months after birth. Abnormal renal function was defined when serum creatinine higher than 50 mu mol/L (2 Standard Deviation) or the necessity of dialysis or renal transplantation. Autopsy was always performed whenever fetal or neonatal deaths occurred. Results Eleven patients decided to undergo fetal therapy and 12 elected to continue with expectant observation. There was no difference between both groups in gestation age at diagnosis and referral examinations. Urethral atresia was diagnosed in 4/11 (36.4%) fetuses by fetal cystoscopy. At 26 weeks, fetuses that were managed expectantly presented with worse urinary biochemistry results (p < 0.05). Survival rates and percentage of infants with normal renal function were significantly higher in the cystoscopic group than in the expectant group (P < 0.05). Conclusions Percutaneous fetal cystoscopy is feasible using a thinner special cannula for prenatal diagnosis and therapy of LUTO. Prenatal laser ablation of the PUV under cystoscopy may prevent renal function deterioration improving postnatal outcome. Copyright (C) 2009 John Wiley & Sons, Ltd.

Intracardiac Cavopulmonary Connection in Patients with Univentricular Heart Using Intra-atrial Lateral Tunnel and Intra-atrial Conduit Techniques

Background: In this study, we analyzed the time course of hemodynamic efficiency and follow-up in Fontan candidates who underwent the bidirectional Glenn procedure for staged intracardiac cavopulmonary connection (ICPC). Methods: Between 1991 and 2008, 52 patients with univentricular heart (mean age, 3.3 years; range, 2-8 years; 27 female patients [51.9%]) underwent ICPC. The cardiac malformations were as follows: tricuspid atresia, 25 cases (48.0%); common ventricle, 16 cases (30.7%); and pulmonary atresia with intact ventricular septum, 11 cases (21.1%). The intracardiac cavopulmonary procedure was indicated for all 52 cases. In 42 patients (80.7%), an intra-atrial lateral tunnel was constructed with a bovine pericardium patch. In the last 10 consecutive cases (19.3%), we performed a modified surgical technique in which we implanted an intra-atrial corrugated bovine pericardium tube sutured around the superior and inferior vena cava ostium. In all cases, a 4-mm fenestration was made to reduce the intratunnel pressure. All 52 patients had previously undergone a Glenn operation. Results: There were 2 hospital deaths (3.8%) and no recorded late deaths. During the follow-up, all patients were medicated with antiplatelet drugs. To evaluate the hemodynamic performance, we used Doppler echocardiography, computed tomography, and magnetic nuclear resonance studies. There were no prosthesis thromboses during this follow-up period. To evaluate cardiac arrhythmias, we conducted a Holter study. The last 10 patients with an intra-atrial conduit (IAC) presented with sinus rhythm and no arrhythmias during the last 4 years. The 50 surviving patients (96.1%) have been followed up for 6 to 204 months; all these patients are free of reoperation. Conclusion: The Glenn operation, which is performed at an early age, prepares the pulmonary bed to receive the ICPC. The midterm results of the intracardiac Fontan procedure seem to be good. The modified surgical procedure (IAC) can be a good alternative technique to the Fontan procedure in suitable patients.

Effects of the administration of pentoxifylline and prednisolone on the evolution of portal fibrogenesis secondary to biliary obstruction-an experimental study in growing animals

Background: Many chronic liver diseases lead to progressive hepatic fibrosis, a condition that can ultimately result in loss of organ function and severe portal hypertension necessitating hepatic transplantation. Within the last few decades, studies have been conducted to demonstrate the possibility of drug modulation of hepatic fibrogenesis. Regarding biliary obstruction, it has been suggested that administration of corticosteroids could promote better late outcomes for children with biliary atresia submitted to Kasai`s portoenterostomy. Models used to test potential antifibrogenic drugs such as pentoxifylline (PTX) have not included growing animals. Methods: In this experimental study, 119 young rats (21st or 22nd days) were submitted to laparotomy and common bile duct ligation (CBDL) or to sham surgery (SHAM). Animals were allocated into 5 groups, according to surgical procedure, and administered the following solutions: (1) CBDL + distilled water, (2) SHAM + distilled water, (3) CBDL + PTX, (4) CBDL + prednisolone (PRED), and (5) CBDL + PTX + PRED (PTX + PRED). Each group was further divided into 2 subgroups according to the length of the experiment (15 or 30 days). At the end of the defined period, animals were weighed, and a hepatic fragment was collected from each one for analyses. Results: The PTX animals exhibited increased weight gain compared to animals in the PRED or PTX + PRED groups. Animals from the 3 therapeutic groups (PTX, PRED, and PTX + PRED) showed diminished collagen-filled area in portal spaces. Total portal space area was increased in the PTX group. Conclusions: Hepatic fibrosis induced by bile duct ligation in young rats could be modulated by pharmacologic interventions. Administration of PTX or PRED, or the combination of both, resulted in diminished collagen-filled areas in portal spaces. (C) 2009 Elsevier Inc. All rights reserved.

Posterior reversible encephalopathy syndrome after liver transplantation in children: A rare complication related to calcineurin inhibitor effects

PRES is a neuroclinical and radiological syndrome that results from treatment with calcineurin inhibitor immunosuppressives. Severe hypertension is commonly present, but some patients may be normotensive. We report herein two children who received liver transplants, as treatment for biliary atresia in the first case and for Alagille`s syndrome in the second one. In the early postoperative, both patients presented hypertension and seizures. In both cases, the image findings suggested the diagnosis of PRES. The CT scan showed alterations in the posterior area of the brain, and brain MRI demonstrated parietal and occipital areas of high signal intensity. Both children were treated by switching the immunosuppressive regimen and controlling arterial blood pressure. They displayed full recuperation without any neurologic sequelae. Probably, the pathophysiology of PRES results from sparse sympathetic innervation of the vertebrobasilar circulation, which is responsible for supplying blood to the posterior areas of the brain. In conclusion, all liver-transplanted children who present with neurological symptoms PRES should be considered in the differential diagnosis, although this is a rare complication. As treatment, we recommend rigorous control of arterial blood pressure and switching the immunosuppressive regimen.