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Neuroblastoma, one of the most common pediatric solid tumors, is characterized by two extreme disease courses, spontaneous regression and life-threatening progression. Here, we conducted a genome-wide search for differences in DNA methylation that distinguish between neuroblastomas of the two types. Three CpG islands (CGI) and two groups of CGIs were found to be methylated specifically in neuroblastomas with a poor prognosis. By quantitative analysis of 140 independent cases, methylation of all the five CGI (groups) was shown to be closely associated with each other, conforming to the CpG island methylator phenotype (CIMP) concept. The presence of CIMP was sensitively detected by methylation of the PCDHB CGIs and associated with significantly poor survival (hazard ratio, 22.1; 95% confidence interval, 5.3-93.4; P < 0.0001). Almost all cases with N-myc amplification (37 of 38 cases) exhibited CIMP. Even in 102 cases without N-myc amplification, the presence of CIMP (30 cases) strongly predicted poor survival (hazard ratio, 12.4; 95% confidence interval, 2.6-58.9; P = 0.002). Methylation of PCDHB CGIs, located in their gene bodies, did not suppress gene expression or induce histone modifications. However, CIMP was significantly associated with methylation of promoter CGIs of the RASSF1A and BLU tumor suppressor genes. The results showed that neuroblastomas with CIMP have a poor prognosis and suggested induction of silencing of important genes as an underlying mechanism.

Supplementary Tables 1-3 from CpG Island Methylator Phenotype Is a Strong Determinant of Poor Prognosis in Neuroblastomas

Supplementary Figure Legends from CpG Island Methylator Phenotype Is a Strong Determinant of Poor Prognosis in Neuroblastomas

Purpose To identify the impact of the histological diagnosis on the prognosis of prenatally diagnosed sacrococcygeal teratoma (SCT), we analyzed the data obtained during prenatal surveillance and assessed the postnatal outcomes in a large cohort of fetuses with SCT in Japan. Methods A nationwide retrospective cohort study was conducted among 97 fetuses prenatally diagnosed with SCT between 2000 and 2009. Of these, 84 had a histological diagnosis. In addition, we conducted a second surveillance program of the prognosis of 72 patients who were reported to be alive at the initial surveillance conducted 2 years previously. Results The tumors comprised 51 (61 %) mature teratomas, 33 (39 %) immature teratomas and 0 (0 %) malignant teratomas. Immature teratomas were also associated with a significantly higher mortality rate (immature teratomas: 8/31, mature teratomas: 2/48). Late recurrence was observed in six of 72 cases (8.3 %). Among these six cases, recurrence with a malignant component was observed in four patients. All six patients were successfully treated. Conclusions Mature teratoma was the most common histological type observed in this study. The patients with immature teratomas exhibited an increased risk of mortality. Late recurrence was observed in 8.3 % of the cases.

Hepatocellular carcinoma (HCC) in children is rare, and the prognosis has been poor because of its advanced stage at diagnosis and unresponsiveness to chemotherapy. We report a 13-year-old boy with ruptured HCC in the left trisegment. When hemostasis of the ruptured surface was achieved in the emergency operation, the left branch of the portal vein and the left hepatic artery were ligated at the same time. The volume of the future liver remnant (FLR), that is, his right posterior sector, increased from 56% on admission to 70% of his standard liver volume on day 2. Blood level of serum protein induced by vitamin K absence or antagonist ІІ started to decrease immediately. Left trisegmentectomy was successfully performed 10 days later, followed by chemotherapy. He has been well with a 2-year survival without recurrence. When the FLR is considered relatively small for a major hepatic resection, the selective ligation of the portal vein and the hepatic artery, which feed HCC, seems to be beneficial. This is because it may induce enlargement of the FLR, increasing the safety of the hepatectomy as preoperative portal vein embolization does before a major hepatectomy in adult patients with HCC, and the latter suppresses the tumor while waiting for the planned hepatectomy.

Objectives To document outcome and to explore prognostic factors in fetal left congenital diaphragmatic hernia (CDH). Methods This was a multicenter retrospective study of 109 patients with prenatally diagnosed isolated left CDH born between 2002 and 2007. The primary outcome was intact discharge, defined as discharge from hospital without major morbidities, such as a need for respiratory support including oxygen supplementation, tube feeding, parenteral nutrition or vasodilators. All patients were managed at perinatal centers with immediate resuscitation, gentle ventilation (mostly with high-frequency oscillatory ventilation) and surgery after stabilization. Prenatal data collected included liver and stomach position, lung-to-head ratio, gestational age at diagnosis and presence or absence of polyhydramnios. Stomach position was classified into four grades: Grade 0, abdominal; Grade 1, left thoracic; Grade 2, less than half of the stomach herniated into the right chest; and Grade 3, more than half of the stomach herniated into the right chest. Results Overall intact discharge and 90-day survival rates were 65.1% and 79.8%, respectively. Stomach herniation was classified as Grade 0 in 19.3% of cases, Grade 1 in 45.9%, Grade 2 in 13.8% and Grade 3 in 21.1%. Multivariate analysis revealed that liver position was the strongest prognostic variable for intact discharge, followed by stomach position. Based on our results, we divided patients into three groups according to liver (up vs. down) and stomach (Grade 0–2 vs. Grade 3) position. Intact discharge rates declined significantly from liverdown (Group I), to liver-up with stomach Grade 0–2 (Group II), to liver-up with stomach Grade 3 (Group III) (87.0%, 47.4% and 9.5% of cases, respectively). Conclusion Current status and outcomes of prenatally diagnosed left CDH in Japan were surveyed. Stomach herniation into the right chest was not uncommon and its grade correlated with outcome. The combination of liver and stomach positions was useful to stratify patients into three groups (Group I–III) with different prognoses. Copyright  2011 ISUOG. Published by John Wiley & Sons, Ltd.

This report describes a case of fetal mediastinal teratoma complicated by hydrops fetalis managed successfully by aspiration of the tumor cyst fluid. Fetal mediastinal teratomas are rare tumors that cause hydrops fetalis or fetal demise in the prenatal period and respiratory distress in the neonatal period. The patient presented with a large cystic mass in the thoracic cavity complicated by hydrops fetalis. The hydrops resolved after fetal aspiration of the tumor cyst fluid. The infant was born without respiratory distress, and tumor resection was performed at the age of 30 days. The postoperative course was uneventful, and the patient was in good health 6 months postoperatively.

To review the recent Japanese experience with prenatally diagnosed congenital diaphragmatic hernia (CDH) based on a multi-institutional survey. A multicenter, retrospective cohort study was conducted on 117 patients born between 2002 and 2007 with isolated prenatally diagnosed CDH. All patients were managed by maternal transport, planned delivery, immediate resuscitation and gentle ventilation. The primary outcome measurements were the 90-day survival and intact discharge. The examined prenatal factors included gestational age (GA) at diagnosis, lung-to-head ratio (LHR), lung-to-thorax transverse area ratio (L/T) and liver position. Physical growth and motor/speech development were evaluated at 1.5 and 3 years of age. Data were expressed as the median (range). The mean GA at diagnosis was 29 (17–40) weeks. The LHR and L/T were 1.56 (0.37–4.23) and 0.11 (0.04–0.25), respectively. There were 48 patients with liver up. The mean GA at birth was 38 (28–42) weeks. The 90-day survival rate and intact discharge rate were 79 and 63%, respectively. Twelve patients had major morbidity at discharge, and 71% of these patients had physical growth or developmental retardation at 3 years of age. This multicenter study demonstrated that the 90-day survival rate of isolated prenatally diagnosed CDH was 79%, and that subsequent morbidity remained high. A new treatment strategy is needed to reduce the mortality and morbidity of severe CDH.

An accurate prenatal assessment of the patients' severity is essential for the optimal treatment of individuals with congenital diaphragmatic hernia (CDH). The purpose of this study was to clarify the reliability of the lung to thorax transverse area ratio (L/T) as a prenatal predictive parameter.A multicenter retrospective cohort study was conducted on 114 isolated CDH fetuses with a prenatal diagnosis during the period between 2002 and 2007 at five participating centers in Japan. The relationship between the gestational age and the L/T was analyzed. The most powerful measurement point and accurate cutoff value of the L/T was determined by an analysis of a receiver operating characteristic curve, which was verified by comparing the patients' severity.There was a negative correlation between the gestational age and the L/T in the non-survivors, and no correlation in the survivors. There were significant differences in the parameters which represented the patients' severity including the respiratory and circulatory status, the surgical findings, and the final outcomes between the groups divided at 0.080 in the minimum value of the L/T during gestation.The L/T was not strongly influenced by the gestational age, and it was found to be a reliable prenatal predictive parameter in fetuses with isolated CDH.

In 1996, the Japan Wilms Tumor Study (JWiTS) group was founded to elucidate the efficacy and safety of the regimen established by the National Wilms Tumor Study (NWTS) group in the USA, and a multicenter cooperative study (JWiTS-1) was started in Japan. This report reviews the results of JWiTS-1.A total of 307 patients with malignant renal tumor were enrolled in the JWiTS-1 study between 1996 and 2005. Central pathological diagnosis and follow-up data were available in 210 cases. The protocol regimens were similar to the NWTS-5 regimens. Clinical stage was classified according to the Japanese Staging System.Five-year overall survival (OS) rate was 91.1% for nephroblastoma, 72.9% for clear cell sarcoma of the kidney (CCSK), and 22.2% for rhabdoid tumor of the kidney (RTK). In the nephroblastoma patients, 5-year OS was 90.5% for stage I disease, 92.2% for stage II, 90.9% for stage III, 86.7% for stage IV, and 78.7% for stage V.The OS of patients in the JWiTS-1 study were comparable with the results of other multicenter studies in the USA and Europe. The outcome for patients with nephroblastoma and CCSK was fair. In contrast, the cure rate for those with RTK was not satisfactory. New treatment strategies are needed for patients with RTK.

We report 2 cases of growth spurt-related recurrence after Nuss procedure. Each of the 2 cases underwent bar insertion at the age of 6 and 11 years, respectively. The support bar was removed 2 years later followed by severe redepression during the growth spurt. One patient underwent redo Nuss procedure elsewhere. The other patient was diagnosed as idiopathic precocious puberty and is in treatment. The possibility of growth spurt-related recurrence must be explained to those who undergo early correction before surgery, and follow-up is mandatory at least until patients' puberty is over.

In the present study, we investigated the suitability of two methods for the transplantation of cells into ovine fetuses. The first method was an ultrasound-guided cell injection via the uterine wall. The second involved hysterotomic cell injection with an incision in the uterine wall exposing the amnion. Monkey embryonic stem (ES) cell-derived hematopoietic cells were used as donor cells. After transplantation, the abortion rate associated with the hysterotomic injection method was significantly higher than that of the ultrasound-guided injection method (8/13 versus 4/24; P0.01). The fetuses were delivered to examine the engraftment of transplanted monkey hematopoietic cells. Monkey cells were detected in one of the five animals (20%) in the hysterotomic injection group, and 14 of 20 animals (70%, P0.05) in the ultrasound-guided injection group. Therefore, the ultrasound-guided method was effectively shown to be minimally invasive for in utero transplantation and can produce a higher rate of engraftment for transplanted cells.

Purpose Although various urologic complications have been reported after abdominoperineal pull-through and posterior sagittal anorectoplasty for the treatment of high-type imperforate anus, reports regarding complications after laparoscopically assisted anorectoplasty (LAARP) are surprisingly rare. Here, we discuss the potential complications of LAARP. Methods A retrospective study was conducted of 24 patients treated with LAARP from 2000 to 2006. The clinical and operative records were reviewed. Of the 24 patients, 18 were evaluated postoperatively by screening magnetic resonance imaging (MRI). Results The 24 participants are composed of patients with rectoprostatic urethral fistula (n = 15), rectal agenesis (n = 3), rectovesical fistula (n = 2), rectovaginal fistula (n = 2), and cloaca (n = 2). Defecatory function after LAARP was satisfactory. None of the patients had dysuria or urinary infection postoperatively. Cystic formations posterior to the urethra were demonstrated in 9 of the 18 cases examined by MRI. Postoperative voiding cystourethrography failed to demonstrate the lesion in 6 of 9 patients. The types of imperforate anus in this subgroup were rectoprostatic urethral fistula (n = 7), rectovesical fistula (n = 1), and rectal agenesis without fistula (n = 1). Average cyst diameter was 22 ± 19 mm. Two patients with large cysts (62 and 42 mm) underwent surgical resection. Conclusions Although satisfactory fecal continence could be achieved by LAARP, we experienced 2 cases with a large residual fistula that required surgical resection. In addition, screening MRI demonstrated the presence of cystic formations in 9 of 18 patients. We recommend that MRI be performed routinely during follow-up of patients treated with LAARP.

A dependence of Gallium hydride (GaHx: x = 1, 2, 3) production on the growth rate of GaN crystals grown by the gallium hydride vapor phase epitaxy (GaH-VPE) method was investigated. By this method, GaN crystals are synthesized in a reaction between GaHx and NH3. The growth rate of GaN crystals has been as low as 20 μm/h at a maximum because the poor reactivity of H2 gas with Ga metal limits the production of GaHx. In this study, the interfacial area between Ga metal and H2 gas was enlarged to increase the GaHx synthesis, which thereby enabled an increase in the growth rate to 68 μm/h. We showed clearly that the growth rate of GaN by the GaH-VPE method is limited by the efficiency of the reaction between the Ga metal and H2 gas. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Background Late-presenting congenital diaphragmatic hernia (CDH) is a rare subset of CDH, most of the information derived from small series or case reports. The aim of this study was to document the clinical manifestations of late-presenting CDH using a large multicenter database. Methods Information about late-presenting CDH (diagnosed at later than 30 days of age) was identified from the database of the CDH Study Group (3098 cases collected during 1995-2004) and reviewed retrospectively. Results Seventy-nine cases (2.6%) from 30 centers met the inclusion criteria. Seven cases had a Morgagni hernia. There were 50 males (65%) and 27 females (35%). The mean age at diagnosis was 372 days (32 days to 15 years). Major associated anomalies (10 cardiac and 7 chromosomal abnormalities) were identified in 12 cases (15%). Presenting symptoms were respiratory in 20 (43%), gastrointestinal in 15 (33%), both in 6 (13%), and none (asymptomatic) in 5 (11%). The hernia was left-sided in 53 (69%), right-sided in 21 (27%), and central or bilateral in 3 (4%). Patients with gastrointestinal symptoms invariably had left-sided hernias (n = 19), whereas patients with respiratory symptoms (n = 24) seemed equally likely to have right- or left-sided lesions. A primary repair without patch was done in all cases with 100% survival. Conclusions Presenting symptoms of late-onset CDH can be respiratory or gastrointestinal, but presentation with gastrointestinal problems was more common in left-sided hernias, whereas respiratory symptoms predominated in right-sided lesions. The prognosis is excellent once the correct diagnosis is made.

This study deals with the advancement process of neuroblastoma through clinical observations and circulating tumor cell exploration. Clinical feature, tumor biology, and circulating tumor cell detected by the previously described polymerase chain reaction (PCR) method were analyzed in 31 patients with advanced neuroblastoma treated in our department since 1991 through 2004. Treatment was completed in 28 patients, of whom 17 are alive without the disease and 11 died. The primary lesion was not confirmed in 2 patients with disseminated metastasis, both of whom showed positive circulating tumor cell. Circulating tumor cell was positive in 6 of 9 examined at their first appearance at the hospital, all had stage 4 disease, and 4 of the 6 (66.7%) died of systemic spread of the disease. N-myc was amplified in 15 patients, of whom only 2 (13.3%) died of systemic metastasis. N-myc amplification did not correlate with positive circulating tumor cell. A certain population of neuroblastoma may provide circulating tumor cells from the early period of the disease to form metastatic lesions independently of the primary lesion, which must be regulated by factors other than N-myc. Circulating tumor cells may suggest higher risk for systemic dissemination and poor prognosis.

Gastric rupture is extremely rare in childhood beyond the neonatal period. We describe a previously healthy 6-year-old girl with a large laceration along the greater curvature on the posterior wall of the stomach. The patient was admitted to a neighboring hospital because of vertigo with 1-day history of intractable vomiting and epigastric pain. Although abdominal distension was noticed during the physical examination, muscular rigidity was not detected on palpation. Laboratory data showed severe hypotonic dehydration and moderate metabolic acidosis with hyperkalemia. She suddenly developed cardiac arrest within an hour after admission. After resuscitation, surgical consultation was obtained. Abdominal X-ray and ultrasound revealed abdominal free air and massive cloudy ascites. At laparotomy, there was a large laceration on the greater curvature of the stomach. Pathology of the gastric wall showed mucosal necrosis while the musculature remained intact consistent with an acute gastric ulcer. Since clinical condition of gastric rupture deteriorates rapidly, early diagnosis and appropriate treatment is essential for good prognosis. One should consider that ulcer formation might cause gastric rupture in childhood.

Neuroblastoma, one of the most common pediatric solid tumors, is characterized by two extreme disease courses, spontaneous regression and life-threatening progression. Here, we conducted a genome-wide search for differences in DNA methylation that distinguish between neuroblastomas of the two types. Three CpG islands (CGI) and two groups of CGIs were found to be methylated specifically in neuroblastomas with a poor prognosis. By quantitative analysis of 140 independent cases, methylation of all the five CGI (groups) was shown to be closely associated with each other, conforming to the CpG island methylator phenotype (CIMP) concept. The presence of CIMP was sensitively detected by methylation of the PCDHB CGIs and associated with significantly poor survival (hazard ratio, 22.1; 95% confidence interval, 5.3-93.4; P < 0.0001). Almost all cases with N-myc amplification (37 of 38 cases) exhibited CIMP. Even in 102 cases without N-myc amplification, the presence of CIMP (30 cases) strongly predicted poor survival (hazard ratio, 12.4; 95% confidence interval, 2.6-58.9; P = 0.002). Methylation of PCDHB CGIs, located in their gene bodies, did not suppress gene expression or induce histone modifications. However, CIMP was significantly associated with methylation of promoter CGIs of the RASSF1A and BLU tumor suppressor genes. The results showed that neuroblastomas with CIMP have a poor prognosis and suggested induction of silencing of important genes as an underlying mechanism.

Background. Although directed differentiation of human embryonic stem (ES) cells would enable a ready supply of cells and tissues required for transplantation therapy, the methodology is limited. We have developed a novel method for hematopoietic development from primate ES cells. We first cultured cynomolgus monkey ES cells in vitro and transplanted the cells in vivo into fetal sheep liver, generating sheep with cynomolgus hematopoiesis. Methods. Cynomolgus ES cells were induced to mesodermal cells on murine stromal OP9 cells with multiple cytokines for 6 days. The cells (average 4.8×10 7 cells) were transplanted into fetal sheep in the liver (n=4) after the first trimester (day 55-73, full term 147 days). The animals were delivered at full term, and two of them were intraperitoneally administered with human stem-cell factor (SCF). Results. Cynomolgus hematopoietic progenitor cells were detected in bone marrow at a level of 1% to 2% in all four sheep up to 17 months posttransplant. No teratoma was found in the lambs. After SCF administration, the fractions of cynomolgus hematopoiesis increased by several-fold (up to 13%). Cynomolgus cells were also detected in the circulation, albeit at low levels (

The authors report a case of laryngeal atresia (congenital high airway obstruction syndrome [CHAOS]) that was diagnosed prenatally. The patient underwent successfully tracheostomy by ex utero intrapartum treatment (EXIT). The fetal ultrasonography and magnetic resonance imaging MRI showed a typical CHAOS pattern with expanded hyperechogenic lungs, inverted diaphragms, and a dilated trachea. Recently, 3 cases of prenatally diagnosed CHAOS were reported to be treated successfully by EXIT. The clinical manifestation and course of this case was not similar to these 3 cases. The 3 previous patients did not fare as well during gestation and were delivered earlier than that in our case. In our case, fetal hydrops was seen at 23 gestational weeks, but it gradually subsided and disappeared at 30 gestational weeks. The fetus was stable and well. After delivery at 39 weeks, the baby received respiratory assistance by ventilator assistance. After 3 days, she could breath well on her own. The patient also had chromosome 5p deletion syndrome and perineal groove. More experience in treating CHAOS cases with EXIT to fully estimate its clinical course and prognosis is needed.

Background To achieve human embryonic stem (ES) cell-based transplantation therapies, allogeneic transplantation models of nonhuman primates would be useful. We have prepared cynomolgus ES cells genetically marked with the green fluorescent protein (GFP). The cells were transplanted into the allogeneic fetus, taking advantage of the fact that the fetus is so immunologically immature as not to induce immune responses to transplanted cells and that fetal tissue compartments are rapidly expanding and thus providing space for the engraftment. Methods Cynomolgus ES cells were genetically modified to express the GFP gene using a simian immunodeficiency viral vector or electroporation. These cells were transplanted in utero with ultrasound guidance into the cynomolgus fetus in the abdominal cavity (n=2) or liver (n=2) at the end of the first trimester. Three fetuses were delivered 1 month after transplantation, and the other, 3 months after transplantation. Fetal tissues were examined for transplanted cell progeny by quantitative polymerase chain reaction and in situ polymerase chain reaction of the GFP sequence. Results A fluorescent tumor, obviously derived from transplanted ES cells, was found in the thoracic cavity at 3 months after transplantation in one fetus. However, transplanted cell progeny were also detected (approximately 1%) without teratomas in multiple fetal tissues. The cells were solitary and indistinguishable from surrounding host cells. Conclusions Transplanted cynomolgus ES cells can be engrafted in allogeneic fetuses. The cells will, however, form a tumor if they "leak" into an improper space such as the thoracic cavity.

After more than 2 decades of experimental and clinical work, fetal surgery is an accepted treatment option for highly selected fetuses with life-threatening anomalies. Fetal lung masses associated with hydrops are nearly 100% fatal. These lesions can be resected in utero if they are predominantly solid or multicystic. Thoracoamniotic shunt placement may be effective in the setting of a single large cyst. Fetuses diagnosed with left congenital diaphragmatic hernia before 26 weeks' gestation with associated liver herniation and a low right lung to head circumference ratio have a relatively poor prognosis with conventional therapy after birth, but in utero therapeutic approaches have yet to show a comparative survival benefit. A prospective randomized trial is required to critically evaluate the efficacy of fetal tracheal occlusion for severe diaphragmatic hernia. Fetal sacrococcygeal teratoma complicated with progressive high output cardiac failure may benefit from in utero resection of the tumor.

The authors report a case of congenital extrahepatic portocaval shunt with a hypoplastic portal vein. This type of shunt is called an Abernethy type 2 shunt, where the portal vein and inferior vena cava are connected side to side, and a hypoplastic portal flow exists in the liver parenchyma. This case of a young girl is complicated with a cardiac anomaly and a large hyperplastic nodule in the liver. This phenotype usually is seen in the Abernethy type 1 shunt, which is a side-to-end shunt with the complete absence of a portal vein. In this context, the current case is very unique in its clinical manifestation, and this phenotype has never been reported. Therefore, it is important to speculate the etiology and treatment of this kind of abnormality and its associated hepatic mass.

The benign epithelial neoplasm liver cell adenoma is rare, especially in childhood. We report 2 such cases, 1 of which was associated with Prader-Willi syndrome. Differential diagnosis of the liver cell adenomas on the basis of histopathologic findings proved difficult and was based on the absence of cellular and nuclear atypia, mitotic activity, and invasive growth. In both cases, immunohistochemical staining demonstrated the nuclear accumulation of β-catenin, and in 1 case, the tumor cells carried a mutation of the β-catenin gene. Recently, disregulation of the Wnt/β-catenin pathway, attributable to abnormalities of the β-catenin gene, has been reported to be a major event in the development of hepatocellular carcinomas and hepatoblastomas. Our report may be the first to describe the β-catenin abnormalities in childhood liver cell adenoma. These findings imply that abnormalities of β-catenin can be an early initiating event in human liver tumorigenesis. H UM P ATHOL 33:852-855. Copyright 2002, Elsevier Science (USA). All rights reserved.

Background/Purpose: Cellular differentiation of pulmonary hyperplasia has not been reported in human cases. The authors studied surfactant protein expression and ultrastructure of pulmonary epithelial cells in fetal hyperplastic lungs associated with congenital tracheal agenesis. Methods: The maturation of pulmonary epithelial cells was assessed by immunohistochemical examination for surfactant proteins (SP-A, mature SP-B, proSP-B, proSP-C, and SP-D) and transmission electron microscopy. As controls normal lung portions of 8 fetuses born at 21 weeks gestation were used. Results: Mature SP-B and SP-D was detected in terminal airways in this case, but not in controls. In electron microscopy, lamellar bodies were recognized, and glycogen granules were less abundant in terminal airway cells. Conclusion: The differentiation of pulmonary epithelial cells appeared to be more advanced for the gestational age in pulmonary hyperplasia with congenital tracheal agenesis. J Pediatr Surg 36:1845-1848. Copyright © 2001 by W.B. Saunders Company.

The high mortality rate of congenital diaphragmatic hernia (CDH) is ascribed generally to pulmonary hypoplasia and persistent pulmonary hypertension characterized by associated pulmonary arterial structural changes. Prenatal tracheal occlusion (TO) accelerates lung growth, but the effect of TO on pulmonary arterial structure in CDH has not been well defined. The authors hypothesized that TO could reverse the pulmonary arterial structural changes observed in CDH. To address this hypothesis, we utilized the nitrofen-induced rat model of CDH to examine the effect of TO on pulmonary arterial morphology of CDH lungs.Left-sided CDH was induced by administering 100 mg of nitrofen to pregnant Sprague-Dawley rats on day 9 of gestation. TO was performed on day 19, and the fetuses were harvested on day 21.5 of gestation. After the ductus arteriosus was ligated, the pulmonary arteries were injected with a barium-gelatin mixture, and the lungs were inflation fixed. Coronal sections of the lungs were stained with elastin van Gieson. External diameter (ED), internal diameter (ID), and medial and adventitial wall thickness of the pulmonary arteries were measured using a computer image analyzer, and the percent medial thickness (%MT) and adventitial thickness (%AT) were calculated. The lungs from nitrofen-exposed fetuses with left-sided CDH (CDH group), trachea-occluded left-sided CDH (CDH+TO group), non-CDH (non-CDH group), and normal fetuses (normal group) were compared.The %MT was significantly increased in all sizes of arteries in CDH compared with non-CDH and normal groups (P.01). Compared with the CDH group, the CDH+TO group had significantly reduced %MT in all sizes of arteries (P.01), to values comparable or less than the non-CDH and normal groups. The %AT of the CDH group was significantly increased in larger arteries compared with non-CDH and normal control groups (P.01). CDH+TO had significantly decreased %AT compared with CDH in both larger (P.01), and smaller arteries (P.05) and that was comparable with the non-CDH and normal control groups.TO in hypoplastic CDH lung can reverse the pulmonary arterial structural changes that are seen in the nitrofen-induced fetal rat model of CDH. These data suggest that TO may reduce pulmonary vascular reactivity, and the risk of postnatal persistent pulmonary hypertension observed in human neonates with severe CDH. J Pediatr Surg 36:839-845.

Background/Purpose: Prenatal tracheal occlusion (TO) has been shown to accelerate lung growth in animal models and models of pulmonary hypoplasia. However, these models may not mimic early events in human congenital diaphragmatic hernia (CDH). The authors previously have developed a model of TO in the rat. The purpose of this study was to apply this technique to characterize TO-induced lung growth in the early onset nitrofen-induced model of CDH, and to address the clinically important questions of the effect of timing of TO and maternal infusion of terbutaline on TO-induced lung growth. Methods: Left-sided CDH was induced in the fetuses of time-dated pregnant Sprague-Dawley rats by feeding 100 mg of nitrofen on day 9 of gestation. TO was performed via maternal laparotomy and hysterotomy at 19 days' gestation. At harvest (21.5 days' gestation), lungs from nitrofen-exposed fetuses without CDH (non-CDH), with CDH (CDH), and with CDH and TO (CDH-TO) were compared by analysis of wet and dry weight, DNA and protein content, and stereologic morphometry. A second study was performed to assess relative lung growth achieved by equal intervals of TO after "early" (19 days) versus "late" (20 days) gestational TO. Finally, the effect of maternal infusion of terbutaline, a commonly used tocolytic for fetal surgery, on TO-induced lung growth was analyzed. Results: Analysis of lung growth showed consistent and significant lung growth in CDH-TO lungs. Lung growth after TO was proliferative and characterized by an increase in parenchymal volume as manifest by increased total saccular number and surface area and radial saccular count. Although visceral reduction was partially achieved, herniated liver was reduced incompletely. The majority of lung growth occurred during the latter half of the TO period. Early gestational age at TO and maternal terbutaline administration adversely influenced lung growth in CDH-TO fetuses. Conclusions: Prenatal TO induces dramatic lung growth in the early onset, nitrofen-induced rat model of CDH. TO is more effective later in gestation presumably because of the advanced stage of lung development and lung fluid production. This effect could be counterbalanced by the use of β-mimetic tocolytic, which inhibits fetal lung fluid production late in gestation. Multiple factors including fetal lung fluid production and absorption, pharmacologic agents, space-occupying herniated viscera, and timing and duration of TO may be important clinical variables. The development of the rat model should facilitate further studies into the cellular and molecular mechanisms responsible for TO-induced lung growth. J Pediatr Surg 36:251-259. Copyright © 2001 by W.B. Saunders Company.

Prenatal tracheal occlusion (TO) has been shown to accelerate fetal lung growth, yet the mechanism is poorly understood. The goal of this study was to determine the relationship between fetal intratracheal pressure (Pitr) and fetal lung growth after TO. Fetal lambs underwent placement of an intratracheal catheter and a reference catheter at 115--120 days gestation (term, 145 days). Fetal Pitr was continuously controlled at three levels (high, 8 mmHg; moderate, 4 mmHg; low, 1 mmHg) by a servo-regulated pump. The animals were killed after 4 days, and the parameters of lung growth were compared. Lung volume (136.0 +/- 16.7, 94.9 +/- 9.7, 55.5 +/- 12.4 ml/kg), lung-to-body weight ratio (6.31 +/- 0.70, 4.89 +/- 0.38, 3.39 +/- 0.22%), whole right lung dry weight (3.01 +/- 0.29, 2.53 +/- 0.15, 2.07 +/- 0.24 g/kg), right lung DNA (130.0 +/- 11.3, 116.7 +/- 8.6, 97.5 +/- 10.9 mg/kg), and protein contents (1,865.5 +/- 92.5, 1,657.6 +/- 106.8, 1,312.0 +/- 142.5 mg/kg) in high, moderate, and low groups, respectively, all increased in the moderate compared with the low group and increased further in the high compared with the moderate group. Morphometry confirmed a stepwise increase in the volume of respiratory region and alveolar surface area. We conclude that lung growth in the first 4 days after TO is closely correlated with fetal Pitr, offering additional evidence that an increase in lung expansion is one of the major factors responsible for TO-induced lung growth.

This article presents a microscopic MR technique for imaging small mammalian fetuses in utero and in vivo which can be used as a tool for studying normal and abnormal development in small animal fetal models, for targeting in utero intervention in such models, and for following development serially. This new method is applied to a rat model of congenital diaphragmatic hernia (CDH). Pregnant Sprague-Dawley rats were fed nitrofen at 9.5 days postcoitus to induce CDH in the fetuses. The dams were imaged to identify fetuses with CDH for targeted in utero intervention, which consisted of fetal tracheal ligation. Following tracheal ligation, the fetuses were followed serially with our MR technique. For MR imaging, the dam was anesthetized with intramuscular ketamine and intraperitoneal pentobarbital. In utero imaging was performed on a 4 Tesla MRI system using a multislice, fast spin echo sequence with a long TR and short effective TE. These results were validated by examining individual fetuses postmortem using high-resolution MR and anatomic dissection. The in utero, in vivo MR technique is highly accurate for diagnosing CDH and following the effects of surgical intervention, and shows promise as a tool for the study of embryogenesis in small animal models. Magn Reson Med 44:331–335, 2000. © 2000 Wiley-Liss, Inc.

We describe two female neonates who suffered from four gastrointestinal anomalies, including duodenal stenosis or atresia, malrotation, segmental dilatation of the colon, and anorectal malformation. Each patient was managed by two or three operations, resulting in good bowel movements. Since this is the first report of four gastrointestinal anomalies, these cases may provide clues to elucidate the etiology of gastrointestinal tract developmental abnormalities.

After more than two decades of experimental and clinical work, fetal surgery has become an accepted treatment modality for selected fetuses with life-threatening anomalies. Color Doppler ultrasound and ultrafast fetal magnetic resonance imaging have enhanced the accuracy of prenatal evaluation traditionally made by ultrasound alone. Fetal lung masses associated with hydrops are nearly 100% fatal. These lesions can be resected in utero if they are predominantly solid or multicystic. Thoracoamniotic shunting may be effective in the setting of a single large predominant cyst. Fetuses diagnosed with left congenital diaphragmatic hernia before 26 weeks' gestation with liver herniation and a sonographic right lung to head circumference ratio (LHR) of less than one may benefit from fetal tracheal occlusion. Fetal sacrococcygeal teratoma complicated with placentomegaly, hydrops, or progressive high output heart failure may benefit from in utero resection of the tumor. Although preterm labor still remains the Achilles heel of open fetal surgery, effective tocolysis may, in the future, expand the scope of fetal surgery.

High temperature growth was investigated as a way of improving the crystallinity and surface morphology of the gallium hydride vapor phase epitaxy (GaH-VPE) crystal growth method. In this method, gallium hydride (GaHx: x=1, 2, 3) is characteristically used as a Ga source to grow GaN crystals. We previously confirmed that the growth rate of GaN increased with GaHx supply and could attain almost the same rate as that of the hydride vapor phase epitaxy (HVPE) method. However, an improvement of the surface morphology and crystallinity of GaN crystals was required. In the present study, the dependence of growth temperature on the crystallinity and the surface morphology of grown crystals was investigated, resulting in both a flat surface and an improvement in crystallinity at temperatures higher than 1150 °C. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Prenatal tracheal occlusion accelerates fetal lung growth, but the mechanism of this phenomenon is unknown. Previous animal models have been limited by expense, lack of species-specific molecular probes, or the stage of lung development when studies could be performed. To provide a model that is more amenable to systematic analysis, we have developed an in vivo rat model of prenatal tracheal occlusion.Time-dated pregnant rats underwent laparotomy at 19 days' gestational age (term, 22 days). The fetal head and neck were exteriorized through a hysterotomy, and the trachea was ligated under a dissecting microscope. The fetus was returned to the amniotic cavity, and the uterine and maternal abdominal incisions were closed. The dam and the fetuses were killed at 21.5 days' gestational age, and the fetal lungs were assessed for lung growth and compared with nonoperated littermate controls.Thirty-two of 50 manipulated fetuses survived. Of the 32 survivors, successful tracheal ligation was confirmed in 20, and these 20 fetuses were compared with 33 littermate controls. Fetal body weight (4.81+/-0.26 g v 4.87+/-0.41 g) and heart weight (0.05+/-0.01 g v 0.05+/-0.01 g) were not significantly different between ligated fetuses and littermate controls, whereas the wet lung weight (0.30+/-0.06 g v 0.13+/-0.02 g, P.01), lung-to-body-weight ratio (6.34+/-1.16% v 2.64+/-0.41%, P.01), dry lung weight (17.4+/-2.45 mg v 12.1+/-1.87 mg, P.01), total lung DNA (1210+/-371 microg v 828+/-208 microg, P.01), and total lung protein (14.3+/-5.3 mg v 8.7+/-1.7 mg, P.01) were increased significantly in the ligated fetuses. The enlarged lung demonstrated normal histology findings after inflation fixation.Prenatal tracheal occlusion during the canalicular stage of lung development accelerates lung growth in the rat. In comparison with other large animal models, this relatively inexpensive small animal model has the distinct advantages of a short gestation, a large number of fetuses per litter, the availability of a developmental model of congenital diaphragmatic hernia, and the availability of well-defined molecular probes to investigate the mechanism of tracheal occlusion-induced lung growth.

Purpose: The authors hypothesized that in utero tracheal occlusion would reverse the high impedance to pulmonary blood flow associated with congenital diaphragmatic hernia (CDH) and normalize the fetal physiological response to oxygen at term. Methods: Three experimental groups were studied. Six fetal lambs (CDH group) underwent creation of a left CDH at 80 days' gestation, an additional six fetal lambs underwent left CDH creation at 80 days' gestation followed by fetal tracheal occlusion performed at 108 days' gestation (CDH + TO group), and four control fetal lambs (control group) underwent a sham procedure at 80 days gestation. All lambs were followed up at 2-week intervals by pulse wave Doppler echocardiography. At each time-point the pulsatility index (PI) was calculated for the left branch pulmonary artery from the Doppler blood velocity waveform. Near term (term, 145 days gestation) at 136 days gestation, measurements were repeated under maternal normoxia and hyperoxia. The fetal lungs were harvested and processed for morphometric analysis by radial alveolar counts (RAC) and lung-to-body-weight ratios (LBWR) as measures of lung growth. Results: At 136 days' gestation the PI of the CDH + TO group (2.88 ± 0.29) and control group (3.97 ± 0.37) were significantly lower compared with the PI of the CDH group (9.02 ± 0.50). There was a significant decrease in the PI of both the CDH + TO group and the control group with maternal hyperoxia at term, whereas the CDH group showed no change. The lungs of the CDH group fetuses were significantly smaller by LBWR and RAC than both CDH + TO and control fetuses. Conclusions: An elevated PI is associated with pulmonary hypoplasia, fetal tracheal occlusion reverses this finding, and results in a normal fetal physiological response to changes in oxygen tension at term.

Subfractionation of serum alpha-fetoprotein (AFP) is a useful method to discriminate between yolk sac tumors, hepatic malignancies, and benign liver diseases in adults but has not been validated in infants and children. AFP subfractionation was performed on AFP-positive sera from 73 infants and children. AFP subfraction profiles were classified into three common types: (1) yolk sac type, (2) hepatoblastoma type, and (3) benign hepatic type, according to the reactivity of individual AFP samples to lectins. In 68 of 73 samples (93.2%), AFP subfraction profiles were accurately classified into these three types, and an atypical AFP subfraction profile resembling the hepatoblastoma type was found in sera from five infants (6.8%). Differentiation between hepatoblastoma and hepatitis when patients are very young can be difficult. Subfractionation is more accurate when patients are older. This technique was found to be useful in the diagnosis of neonatal ovarian tumors, in recurrent hepatoblastoma/ yolk sac tumor with low serum AFP, and in the differential diagnosis of hepatic mass (malignancy versus hyperplastic nodule) in the liver with long-standing cholestasis. Estimation of serum AFP subfraction profiles facilitates the differential diagnosis of various AFP-positive pediatric diseases, such as hepatoblastoma, hepatoma, hepatitis or germ cell tumors. This test is inexpensive, can be carried out within 48 hours, and should be performed for the differential diagnosis of pediatric liver disease.

Fetal female urogenital anomalies are often difficult to evaluate by ultrasonography, especially in late gestation. We report a case of fetal hydrometrocolpos detected at 35 weeks of gestation. Ultrasonography revealed a large retrovesical septate hypoechogenic mass in the fetal abdomen, however the sonographic findings were inconclusive. Magnetic resonance imaging (MRI) confirmed that the abdominal mass was fluid-filled with a mid-plane septum in the midline posterior to the bladder, and showed a connection to the dilated uterus that was duplicated. These findings were consistent with a diagnosis of hydrometrocolpos with septate vagina and uterus didelphys. The neonate showed abdominal distension, ambiguous genitalia and anal atresia with a single perineal opening. Hydrometrocolpos was secondary to a urethral type of cloacal anomaly. Aspiration of the mass and a colostomy were performed on the first postnatal day, followed by anorectoplasty at 19 months of age. MRI is a useful complementary tool for assessing fetal urogenital anomalies when ultrasonography is inconclusive.

The authors report a case of a 9-year-old girl with a mediastinal germinoma that required emergent surgical extirpation because of tracheal compression and asphyxia. The tumor was successfully debulked under general anesthesia with the capability of extracorporeal circulation immediately available. Postoperatively, the tumor responded to adjuvant chemotherapy and irradiation and the patient survived without evidence of recurrence.

Pancreatoblastoma is a rare pancreatic tumor in children. Its biologic behavior is aggressive with frequent local invasion, recurrence, and metastasis , for which there has been no standard treatment regimen. A 13-year old Japanese girl had pancreatoblastoma arising from the pancreas head and body and invading the portal vein. The tumor was resected with pancreaticoduodenectomy combined with reconstruction of the portal and splenic vein using native left common iliac vein graft, followed by chemotherapy. The tumor recurred in the liver and periportal lymph node but was treated with surgical resection and chemotherapy followed by autologous peripheral blood stem cell transplantation. The reconstructed portal vein has been patent with no sign of stricture for 3.5 years after the first operation. She has been well with a second complete remission for 10 months. Complete surgical resection has been considered for long-term survival of patients with pancreatoblastoma. Portal venous involvement is not a contraindication of surgical resection of pancreatic tumors and may be aggressively treated by pancreaticoduodenectomy with portal venous reconstruction using a venous conduit. Autologous peripheral blood stem cell transplantation has been used in only two other pediatric cases in the literature for treating pancreatoblastoma. Although our follow-up period is short, aggressive surgical and chemotherapeutic regimen may hold therapeutic promise for managing advanced or relapsed pancreatoblastoma in children.

Two cases of esophageal duplication cyst associated with pulmonary cystic malformations (cystic bronchiectasis with pneumonia in one, intrapulmonary bronchogenic cysts with bronchial atresia in the other) are reported. The coexistence of these complex anomalies supports the recognition that esophageal duplication cyst also is an entity of a broad spectrum of developmental abnormalities caused by abnormal budding of the primitive foregut. Nine cases of similar complex anomalies in the lung and esophagus have been reported. Although rare, this malformation complex should be borne in mind in the treatment of pediatric mediastinal and pulmonary malformations.

Based on a review of operative notes of recurrent inguinal hernia cases from the authors' primary series, a surgical technique modified from the Marcy repair is described. With this technique, emphasis is placed on preservation of the intact internal spermatic fascia and reduction in the size of the internal inguinal ring. Through the inguinal approach, the sleeve-like extension of the internal spermatic fascia is incised longitudinally along the cord and up to the internal ring. The cord structures are dissected off the sac, and as much of the fascial tissue as possible is preserved intact. Both edges of the fascial defect are approximated with an unabsorbable suture; great care is taken to not penetrate the wall of the sac. The same suture is then used for high ligation, via a stay suture placed on the transversalis fascia on the other side of the neck, to reduce the size of the internal ring. The technique can be used in premature babies who have a flimsy, easily torn sac, and in some cases of giant hernia with a widely dilated internal inguinal ring, if the direct wall integrity remains adequate.

Purpose We evaluated the clinicopathological characteristics of pediatric sacrococcygeal germ cell tumors (SGCTs) and yolk sac tumors (YSTs) developing after sacrococcygeal teratoma (SCT) resection, and discussed the pathogenesis of sacrococcygeal YST. Methods We retrospectively analyzed pediatric SGCT patients attending 10 Japanese institutions. Results A total of 289 patients were eligible, of which 74.6% were girls. The mean age at surgery was 7.1 months. There were 194 mature and 47 immature teratomas, and 48 YSTs. YST developed after SCT resection in 13 patients (5.4% of SCTs), and was detected between 5 and 30 months after resection. At initial surgery, 9 of these 13 patients were neonates, 12 underwent gross complete resection with coccygectomy, and 9 had histologically mature teratoma without microscopic YST foci. Postoperative serum alpha-fetoprotein (AFP) levels were regularly examined in 11 patients. Intervals of AFP measurement ≤ 4 months helped to detect subclinical localized YSTs for resection. Conclusions The characteristics of SGCT in Japanese children were similar with those reported in Europe or the United States. YST developed after SCT resection not only in patients with previously reported risk factors. We recommend that patients undergo serum AFP monitoring every 3 months for ≥ 3 years after SCT resection.

In utero transplantation (IUT) of human hematopoietic stem cells has been conducted in sheep, which are used as large animal models of human hematopoietic reconstitution and models for clinical IUT; however, the levels of engraftment have generally been low. Busulfan (BU), a myeloablative agent, is often administered to patients before hematopoietic stem cells transplantation to improve the engraftment. In this study, hematopoietic activity was evaluated in adult sheep after administering BU at different doses. Next, pregnant ewes were administered BU, and dams as well as their fetuses were evaluated, as BU readily crosses the sheep placenta. Then, the BU dose with the desired outcomes was selected and administered to pregnant ewes at 2 or 6 days before performing IUT using human cord blood CD34 + cells. The engraftment was evaluated in recipients that underwent IUT in the presence or absence of BU. As a result, hematopoietic activity was safely and transiently suppressed in adult sheep treated with 5 to 7.5 mg/kg BU. BU crossed the sheep placenta, and fetal sheep were indeed conditioned by administering 3 mg/kg BU to pregnant ewes. Engraftment of human CD34 + cells in fetal recipients was enhanced when IUT was carried out 6 days post-BU. Up to 3.3% engraftment levels (in terms of bone marrow colony-forming units) were achieved with the IUT of 0.72 to 2.4 million CD34 + cells when BU was used. BU can be administered to pregnant ewes to effectively condition the fetal recipient for IUT with enhanced engraftment of donor cells.

To determine the most appropriate treatment strategy for neonates with coexisting congenital heart diseases (CHD) requiring surgery, 408 neonates treated in our department between 2002 and 2009 were retrospectively reviewed. Of the 408 neonates, 37 (9.1%) had coexisting CHD. Among the pediatric diseases requiring surgery, esophageal atresia (46.7%), anorectal malformation (24.1%), and tracheobronchial anomalies (75.0%) were frequently associated with CHD, and the survival rate among patients with coexisting CDH was 24.3%, about 2-fold higher than among those without coexisting CHD. Clinical observations in the present series suggested that fatal conditions such as tracheoesophageal fistula should be repaired immediately after birth, followed by palliative cardiac surgery to stabilize the circulatory status if necessary. Thereafter, radical repair of cardiac and pediatric anomalies should be performed, taking into account the balance between surgical stress and cardiac reserve. For this purpose, proper assessment of surgical stress and cardiac function and collaboration among specialists in relevant fields are essential during the perinatal period to determine the treatment strategy for patients with multiple-organ anomalies.

Background/Purpose Few large multicenter surveys have been performed on sacrococcygeal teratomas (SCTs) describing both the prenatal and postnatal courses. The aim of this study was to review and report on the prenatal surveillance and postnatal outcome of a large cohort of fetuses with SCTs in Japan. Methods A nationwide retrospective cohort study was conducted on 97 fetuses prenatally diagnosed with SCTs between 2000 and 2009. The prenatal course, perinatal data, and postnatal outcome were reviewed. Results Eleven pregnancies were terminated before 22 weeks of gestation. Of the 86 remaining fetuses, 3 died in utero, and 83 were delivered. Three infants died before surgery, and 8 infants died after excisional surgery. The overall mortality was 26%, with a mortality excluding terminations of 16%. The gestational age at delivery was younger than 28 weeks in 5, 28 to 31 weeks in 13, 32 to 36 weeks in 27, and 37 weeks or more in 37 cases, with mortality rates of 60%, 38%, 11%, and 0%, respectively. The tumor component was predominantly cystic in 54 and predominantly solid in 32 cases, with mortality rates of 2% and 33%, respectively. Conclusions The overall mortality of prenatally diagnosed SCTs excluding terminations was 16%. Early delivery and predominantly solid component tumors were associated with an increased risk of mortality.

The aim of this study was to establish a prenatal prognostic classification system for risk-stratified management in fetuses with isolated congenital diaphragmatic hernia (CDH).A multi-institutional retrospective cohort study of isolated CDH, diagnosed prenatally in fetuses delivered during the 2002 to 2007 period at 5 participating institutions in Japan, was conducted. The risk stratification system was formulated based on the odds ratios of prenatal parameters for mortality at 90 days. The clinical severity in CDH infants were compared among the stratified risk groups.Patients were classified into the 3 risk groups: group A (n = 48) consisted of infants showing liver-down with contralateral lung-to-thorax transverse area ratio (L/T) ratio ≥0.08; group B of infants showing liver-down with L/T ratio0.08 or liver-up with L/T ratio ≥0.08 (n = 35), and group C of infants showing liver-up with L/T ratio0.08 (n = 20). The mortality at 90 days in groups A, B, and C were 0.0%, 20.0%, and 65.0%, respectively. The intact discharge rates were 95.8%, 60.0%, and 5.0%, respectively. This system also accurately reflected the clinical severity in CDH infants.Our prenatal risk stratification system, which demonstrated a significant difference in postnatal status and final outcome, would allow for accurate estimation of the severity of disease in fetuses with isolated CDH, although it needs prospective validation in a different population.

Thymolipoma, a rare benign mediastinal tumor, was found in a 6-year-old boy. Computed tomography scans, magnetic resonance imaging, and angiography of internal thoracic artery confirmed the diagnosis before surgery.

Ischiopagus tripus conjoined twins are rare. Only 13 reports describing the separation of this twins have been seen in the world literature so far. On the separation operation, repair of the large abdominal wall defect following separation often poses a more complex problem rather than separation itself. In this paper, a case of ischiopagus tripus conjoined twins is reported with particular emphasis on the primary closure of the large abdominal wall defect following separation. We tried the subcutaneous placement of tissue expanders, and pneumoperitoneum prior to separation. Tissue expanders had to be removed because of infection. Pneumoperitoneum, without any complication, was quite effective to obtain abdominal wall expansion. With the use of a vascularized pedicle graft made from the fused third limb, primary abdominal closure of the large abdominal wall defect was achieved without tension in each twin. No wound dehiscence or necrosis of the pedicle graft was seen in the postoperative course.

Sialolipoma is a new variant of salivary gland lipoma that was first proposed by Nagao et al (Histopathology 2001;38:30-36). Three cases of submandibular gland sialolipoma have been previously reported in the English literature, all of which were in adults. We report an unusual case of sialolipoma of the submandibular gland in a 3-year-old boy. This is the first reported case of submandibular gland sialolipoma in a child.

We reviewed our initial experience of pediatric living-donor liver transplantation (LDLT) in National Center for Child Health and Development and report the results herein.We have done 103 cases of LDLT during November 2005 through September 2009 in National Center for Child Health and Development. Variables including indication of liver transplantation/infectious/immunological outcome were reviewed.The indication for liver transplantation was cholestatic liver disease in 43.76%, followed by metabolic liver disease 24.3% and acute liver failure 18.5%. The mean age of recipient was 3.6 +/- 4.2 years and body weight was 14.4 +/- 11.1kg. Immunosuppression consisted of tacrolimus and low-dose steroids. The incidence of acute cellular rejection was 33.3%. The graft and patient survival were 92.2%.Satisfactory result can be achieved on LDLT program in National Center for Child Health and Development. The follow-up period was too short to make definitive conclusion, however, long-term observation may be necessary to collect sufficient data for the establishment of the treatment modality.