Search

Ovarian immature teratomas (ITs) are relatively rare among all pediatric ovarian tumors. The histological grading for ovarian ITs, which ranges from 1 to 3, is based on the proportion of immature neuroepithelial component. Higher-grade ITs in adults are treated as malignant neoplasms and require adjuvant chemotherapy. However, there is no consensus on the therapeutic management of pediatric ovarian ITs. The aim of our study was to analyze the histological grades and clinical characteristics of ovarian ITs in pediatric patients. This retrospective chart review consisted of seven patients, including one, three, and three patients with histological grade 1, 2, and 3 pediatric ovarian ITs, respectively, who were treated at our institute between 2000 and 2016. Collected data comprised age, alpha-fetoprotein (AFP) level, clinical stage, tumor size, treatment, and prognosis. The median age and AFP levels of patients with grade 1, 2, and 3 ovarian ITs were 8, 7, and 10 years and 37, 112, and 221 ng/ml, respectively. All cases were Children Oncology Group (COG) stage I and International Federation of Gynecology and Obstetrics (FIGO) stage IA. All patients had unilateral tumors in the right ovary. The median tumor sizes of the grade 1, 2, and 3 IT patients were 104, 160, and 100 cm2, respectively. All patients underwent primary open surgery alone. Two patients, including one patient each with grade 2 and 3 ITs, underwent tumor enucleation as ovary-sparing surgery, whereas the remaining five patients underwent unilateral salpingo-oophorectomy. The median follow-up was seven years, and all cases achieved event-free survival. Clinical characteristics of patients with grade 3 ovarian ITs were relatively older and had higher AFP levels than those with lower-grade ITs. According to our patient's clinical course and prognosis, COG stage I pediatric ITs should be treated by surgery alone and that postoperative chemotherapy is unnecessary even for those with grade 3 ITs as well as patients with rather low AFP levels. IV [ABSTRACT FROM AUTHOR]

Purpose Persistent pulmonary hypertension remains a major cause of mortality and morbidity in cases of congenital diaphragmatic hernia (CDH). Recently, RhoA/Rho-kinase-mediated vasoconstriction has been reported to be important in the pathogenesis of pulmonary hypertension (PH). Several recent reports have described that fasudil, a potent Rho-kinase inhibitor and vasodilator, could represent a potential therapeutic option for PH. We designed this study to investigate the hypothesis that the expression level of RhoA is increased in the nitrofen-induced CDH rat model. The expression level of Wnt11, an activator of RhoA, was also evaluated. Methods Pregnant rats were treated with or without nitrofen on gestational day 9 (D9). Fetuses were sacrificed on D17, D19 and D21 and were divided into control and CDH groups. Quantitative real-time polymerase chain reaction was performed to determine the pulmonary gene expression levels of both Wnt11 and RhoA. An immunofluorescence study was also performed to evaluate the expression and localization of RhoA. Results The relative mRNA expression levels of pulmonary Wnt11 and RhoA on D21 were significantly increased in the CDH group compared with the control group (p = 0.016 and p = 0.008, respectively). The immunofluorescence study confirmed the overexpression of RhoA in the pulmonary vessels of CDH rats on D21. Conclusions Our results provide evidence that the RhoA/Rho-kinase-mediated pathway is involved in the pathogenesis of PH in the nitrofen-induced CDH rat model. Our data also suggest that the fasudil, a Rho-kinase inhibitor, could represent a therapeutic option for the treatment of PH in CDH. [ABSTRACT FROM AUTHOR]

Abstract: Background/Purpose: The aim of this study is to clarify the clinical features and risk factors of pre- and postoperative pancreatic complications in pediatric choledochal cysts. Methods: A retrospective chart review was carried out on pediatric patients with choledochal cysts who underwent radical operation at our department. Results: Twenty-one, 24, and 24 patients were classified into the Todani Ia, Ic, and IV-A choledochal cyst, respectively. Preoperative acute pancreatitis and protein plugs were observed in 31 (43.7%) and 11 (15.5%) patients, respectively. Patients with preoperative pancreatitis were more likely to have fusiform dilatation of choledochal cysts (79.3% vs. 35.0%) and a dilated common channel (53.9% vs. 23.1%) compared to those without preoperative pancreatitis. Compared to patients without preoperative protein plugs, those with protein plugs were more likely to have fusiform dilatation (90.9% vs. 46.5%) and pancreatic divisum with communicating ducts and a dilated ductal system (60.0% vs. 2.5%). Postoperatively, three patients (4.2%) experienced acute pancreatitis. One of these and all 3 had protein plugs and preoperative pancreatitis, respectively. Conclusions: Fusiform-type choledochal cyst is a significant risk factor for preoperative pancreatic complications in choledochal cysts. While postoperative pancreatic complications were relatively rare, preoperative pancreatic complications might be risk factors for postoperative pancreatitis. [Copyright &y& Elsevier]

Abstract: Purpose: The aim of this study is to investigate the clinical characteristics of cases of duodenal atresia (DA) which present with bowel gas distal to a typical double-bubble sign through an anomalous bile duct conduit. Methods: Medical records of 57 neonates with duodenal obstruction (atresia or stenosis), presenting with a double-bubble sign and treated at our institute from 1978 to 2010, were retrospectively reviewed. Results: Thirteen (23%) of 57 neonates presented with bowel gas distal to the double-bubble sign. Passage of gas through the duodenal stenosis may have occurred in 3 cases, whereas in 9 cases, gas may have bypassed the atresia through an anomalous bifurcated bile duct termination and through the pancreatic duct from the accessory to the main pancreatic duct in one case. A preoperative upper gastrointestinal series was performed in 9 cases, and an anomalous bifurcated bile duct conduit was demonstrated in 5 cases. Severe and prolonged cholestasis necessitating evaluation for biliary atresia was found in 2 patients with anomalous bile duct anatomy. Conclusions: Neonatal DA presenting with distal bowel gas via an anomalous bifurcated bile duct conduit is more common than initially thought and occurs more frequently than duodenal stenosis. These patients might be at risk for cholestasis, possibly owing to duodeno-biliary reflux through the ampulla. [Copyright &y& Elsevier]

Abstract: Purpose: The aim of the study was to identify the clinical characteristics and outcome of patients with liver fibrosis in choledochal cyst (CC). Methods: Forty patients with CC who underwent liver biopsy were included. Liver fibrosis was classified as follows: grade 0, no fibrosis; grade 1, mild fibrosis localized in the portal area; grade 2, moderate fibrosis with occasional bridging; and grade 3, severe fibrosis with diffuse bridging. Results: Fourteen patients (35%) had liver fibrosis. Patients in the fibrosis group were significantly younger (1.2 vs 2.7 years) and had higher total bilirubin (5.3 vs 2.6 mg/dL). Severity of liver fibrosis was inversely correlated with age (P = .044). Amylase and lipase in bile were significantly lower in the fibrosis group (amylase, 531 vs 15,000 U/L; lipase, 783 vs 23,100 U/L). Postoperative serum analysis demonstrated no differences between the two groups. Most patients in both groups had normal aspartate aminotransferase, alanine aminotransferase, total bilirubin, and γ-glutamyl transpeptidase regardless of severity of fibrosis. Postoperative biliary complication or cholangiocarcinoma was not found in the fibrosis group. Conclusions: Our data suggest that liver fibrosis is mainly influenced by obstructive cholangiopathy rather than refluxed pancreatic secretion. Prognosis of patients with CC and liver fibrosis was as good as that of patients without fibrosis. [Copyright &y& Elsevier]

Abstract: Background/Purpose: The relationship of the developing lung and kidney is not completely understood. Renal enlargement has been reported in association with pulmonary hypoplasia in congenital diaphragmatic hernia (CDH). Recent studies suggest that retinoids may be involved in the pathogenesis of CDH. The aims of this study were to investigate the effects of pulmonary hypoplasia on renal development and to evaluate retinoids status of kidneys in the nitrofen model of CDH. Methods: Pregnant rats were exposed to either olive oil or 100 mg of nitrofen on day 9.5 of gestation. Fetuses were recovered at term and divided into 3 groups: 1, control (n = 69); 2, nitrofen without CDH (n = 25); and 3, nitrofen with CDH (n = 40). Kidneys were dissected, weighed, and processed for biochemical measurements of DNA, proteins, total retinol content, and for immunohistochemical staining of proliferating cells. Results: Kidneys were smaller in nitrofen-exposed animals vs control animals (group 3, 0.65 ± 0.08; group 2, 0.62 ± 0.09 vs group 1, 0.73 ± 0.09% of body weight, P < .001), and there were no differences between right and left kidney weight in all the 3 groups. Regression of total kidney weight on body weight showed a linear direct correlation between them in all the groups. Total amount of DNA was significantly reduced in nitrofen-exposed animals vs controls (group 3, 80.58 ± 35.65; group 2, 64.71 ± 20.28 vs group 1, 110.34 ± 42.15 μg, P < .01), but the DNA concentration remained the same in the 3 groups (group 3, 3.59 ± 1.26; group 2, 3.06 ± 1.19; group 1, 3.43 ± 1.05 μg DNA/mg kidney). Total protein content (group 3, 1145.59 ± 500.36; group 2, 993.2 ± 276.62; group 1, 1287.48 ± 312.52 μg), protein concentration (group 3, 49.76 ± 11.12; group 2, 43.95 ± 6.79; group 1, 47.38 ± 6.93 μg protein/mg kidney), and protein-to-DNA ratio (group 3, 15.12 ± 5.98; group 2, 16.22 ± 6.85; group I, 16.16 ± 7.02 μg/μg) were similar in all groups. Retinol concentration was significantly reduced in both nitrofen-exposed groups compared with the control group (group 3, 1.35 ± 0.24; group 2, 1.28 ± 0.11; group 1, 2.53±0.61 μg retinol/g kidney). Proliferation index was similar in all 3 groups (group 3, 50.43 ± 8.81; group 2, 47.96 ± 6.01; group 1, 47.64 ± 5.76% of proliferating cells). Conclusions: Our data clearly show that renal enlargement in association with pulmonary hypoplasia is not seen in the nitrofen-induced CDH. These results rule out any possible relationship between lung and kidney development. Moreover, kidneys are hypoplastic in both nitrofen-exposed groups and have reduced retinol content, suggesting that a retinoid pathway disruption could be the common mechanism in the pathogenesis of lung and kidney hypoplasia in the nitrofen model of CDH. [Copyright &y& Elsevier]

Abstract: Background: Lymphocyte-mediated inflammatory damage of the bile ducts has been proposed as a potential mechanism in the pathogenesis of biliary atresia (BA). Chemokines regulate leukocyte migration and act as critical organizers of cell distribution in inflammatory responses. The aim of this study was to analyze the infiltration of T lymphocytes and the expression of a chemokine receptor, CXCR3, predominantly expressed on type 1 polarized T cells (TH1, TC1) in the liver and excised biliary remnants in infants with BA. Methods: Immunohistochemistry for CD3, CD8, and CXCR3 was performed using liver biopsy specimens collected from the following 3 age-matched groups of patients: group 1, BA (nonsyndromic) at the time of Kasai portoenterostomy (n = 10); group 2, congenital choledochal dilatation (n = 2); and group 3, other cholestatic diseases including paucity of intrahepatic bile ducts and cholestasis (n = 3) related to total parenteral nutrition. Cellular staining on each section was graded from 0 to 4 and compared using nonparametric statistics. Results: Infiltrating CD3+ and CD8+ lymphocytes in the portal tracts were significantly increased in group 1 (3.1 ± 0.4, 2.8 ± 0.4), compared with groups 2 (1.0 ± 0.0, 1.0 ± 0.0) and 3 (1.7 ± 0.3, 1.5 ± 0.5) (P < .01, P < .05). CXCR3+ mononuclear cells were significantly increased in group 1 (2.6 ± 0.3) compared with groups 2 (0.5 ± 0.5) and 3 (0.7 ± 0.3) (P < .05). They were mainly found in the portal tracts with a similar distribution to CD3+ cells. CXCR3+ cells and CD3+ cells also showed a similar distribution in specimens of biliary remnants from just below the portal plate. Conclusions: Increased expression of CXCR3 associated with a significantly increased CD3 and CD8 T-cell infiltration suggests that CXCR3+ lymphocytes in a type 1 (TH1, TC1) cytokine milieu may play a role in the pathogenesis of BA. [Copyright &y& Elsevier]

Abstract: Purpose: Changes in vascular structures as well as vascular endothelial growth factor (VEGF) downregulation have been reported in hypoplastic lungs associated with congenital diaphragmatic hernia. We hypothesized that VEGF may accelerate branching morphogenesis and thus may modulate lung growth in normal and nitrofen-induced pulmonary hypoplastic lungs. Methods: A hypoplastic fetal lung model and a normal control lung model were induced by feeding pregnant rats with or without nitrofen, respectively. Fetal lungs harvested on day 13.5 were cultured at ambient oxygen tensions for 72 hours with 0, 25, 50, or 100 ng/mL of exogenous rat VEGF added daily in the serum-free medium. The rates of increase in bud count and airway contour were evaluated. Real-time polymerase chain reaction was carried out to evaluate the expression of surfactant protein C mRNA in the explants at the end of culture. Results: Vascular endothelial growth factor accelerated the increase in bud count and airway contour in normal and hypoplastic lung explants compared to controls. Surfactant protein C mRNA expression was significantly increased at 50 ng/mL VEGF compared to controls in both normal and hypoplastic lung explants. Conclusion: These data suggest that VEGF plays an important role in lung morphogenesis and may accelerate lung growth in nitrofen-induced hypoplastic lung. [Copyright &y& Elsevier]

Abstract: Aim of Study: Lymphocyte-mediated inflammation within the liver and bile ducts has been proposed as a potential mechanism in the pathogenesis of biliary atresia (BA). Recent reports have suggested that BA is associated with upregulation of TH1-type inflammatory cytokines. Quantitative real-time polymerase chain reaction (qrt-PCR) is a useful tool to assess immune cell density and cytokine gene expression in tissues. The aim of this study was to characterize the inflammation in BA by quantifying lymphocyte density and expression of TH1 cytokines such as IL2 and tumor necrosis factor α (TNF-α) in liver biopsies using qrt-PCR. Methods: Total RNA was extracted from archival formalin-fixed paraffin-embedded liver biopsy specimens collected from three age-matched groups of patients: group I, nonsyndromic BA at the time of Kasai portoenterostomy (n = 10); group II, choledochal dilatation at the time of surgery (n = 2); group III, other cholestatic diseases including biliary hypoplasia and parenteral nutrition–associated cholestasis (n = 3). Qrt reverse transcription–PCR was performed to measure the relative levels of messenger RNA (mRNA) expression of CD4, CD8, IL2, and TNF-α. Their levels were normalized to the level of β-actin expression. The numbers of CD4+ and CD8+ lymphocytes infiltrating portal tracts were also measured using immunohistochemistry. Data were expressed as median and ranges, and statistical comparison and correlation was by nonparametric test (Kruskal-Wallis and Spearman rank). Results: CD8 mRNA expression was significantly increased in group I (median 0.26, range 0.11-6.29) compared with groups II and III (0.002, 0-0.004 and 0.02, 0-0.12) (P < .05). Levels of IL2 mRNA expression were also significantly increased in group I (1.22, 0.05-7.54) compared with groups II (0.58, 0-1.17) and III (0, 0-0.03) (P < .05). In contrast, there was no significant increase in CD4 and TNF-α expression in group I compared with groups II and III. There was a significant correlation between the number of CD8+ lymphocytes in portal tracts and the levels of CD8 mRNA expression. Conclusion: Increased expression of IL2 and increased CD8 T-cell infiltration in liver biopsy specimens from infants with BA suggest the possibility that IL2 plays a role in the pathogenesis of this condition. [Copyright &y& Elsevier]

Abstract: Purpose: Nitric oxide (NO) can accelerate branching morphogenesis of fetal rat lung explants in vitro, whereas its exact mechanism remains unclear. In this study, we investigate the effect of NO on the expression of fibroblast growth factor-10 (FGF10) and bone morphogenetic protein-4 (BMP4), which plays an important role in bud formation. Methods: Fetal rat lungs harvested on day 13.5 of gestation were cultured in serum-free medium for 72 hours with 0, 50, 100, and 200 μmol/L of an NO donor, DETA NONOate (DETA/NO) (n = 4, 3, 6, and 5). The ratio of bud increment of each cultured lung was calculated, and the FGF10 and BMP4 mRNA expression levels were analyzed by real-time reverse transcription polymerase chain reaction. Results: Bud increment ratio was significantly increased in 50, 100, and 200 μmol/L DETA/NO (3.3 ± 0.2, 3.0 ± 0.3, and 3.5 ± 0.5) compared to controls (1.9 ± 0.3) (P < .05). There was a significant increase in BMP4 mRNA expression in 100 μmol/L DETA/NO (190% ± 20%) compared to controls (100% ± 30%) (P < .05), whereas FGF10 mRNA expression was not significantly different between each DETA/NO group and controls. Conclusion: The NO donor not only promotes branching of fetal lung explants but also upregulates expression of BMP4, which is an important regulator of branching morphogenesis. [Copyright &y& Elsevier]

Abstract: We report the case of 2-week-old female infant with cystic lung disease who presented with mild tachypnea and had no history of mechanical ventilation. Chest CT demonstrated multiple air-filled cystic lesions in right upper lobe, and the patient subsequently underwent a right upper lobectomy. Histology revealed cystic lesions located in the pulmonary parenchyma and showed that the lesions were lined by lymphatic endothelium and were communicating with dilated lymphatic vessels in the interstitium. Additionally, multinucleated foreign body giant cells were attached to the lumen of the cyst. On the basis of these findings, we considered this a case of persistent interstitial pulmonary emphysema (PIPE) with massive pneumatic expansion of the lymphatic vessels, resulting in cystic lesions with lymphatic endothelium in the pulmonary parenchyma. While PIPE is extremely rare in term non-ventilated infants, our case demonstrated that this disease should be added to the differential diagnosis of cystic lung diseases with lymphatic endothelium even in infants without mechanical ventilation. When cystic lesions and symptoms persist despite conservative treatment, open or thoracoscopic resection is an appropriate option for diagnosis and treatment. [Copyright &y& Elsevier]