Impact of the histological type on the prognosis of patients with prenatally diagnosed sacrococcygeal teratomas: the results of a nationwide Japanese survey.

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.

Sacrococcygeal yolk sac tumor developing after teratoma: a clinicopathological study of pediatric sacrococcygeal germ cell tumors and a proposal of the pathogenesis of sacrococcygeal yolk sac tumors.

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 7.1months. 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 30months 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≤4months 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 3months for≥3years after SCT resection.

Outcomes of prenatally diagnosed sacrococcygeal teratomas: the results of a Japanese nationwide survey.

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.

Maternal administration of busulfan before in utero transplantation of human hematopoietic stem cells enhances engraftments in sheep.

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.

Interleukin 6 and interleukin 8 play important roles in systemic inflammatory response syndrome of meconium peritonitis.

PURPOSE: Meconium peritonitis is caused by an intestinal perforation that may occur in the fetus, followed by severe chemical peritonitis, resulting in high morbidity. METHODS: We have experienced six patients with meconium peritonitis. Cystic drainage was performed soon after birth for all patients. We investigated the concentrations of several cytokines and a chemokine (interleukin 8) in the ascites from the six patients with meconium peritonitis. In two patients we also measured the serum cytokines and chemokine level just after birth. RESULTS: Interleukin 6 and interleukin 8 concentrations were very high in the cyst or ascites just after birth. In the serum taken from two patients, the levels of interleukin 6 and interleukin 8 were also high. In five patients who underwent drainage of cysts after birth, systemic inflammation could not be completely suppressed before curative surgery. CONCLUSIONS: Interleukin 6 and interleukin 8 play important roles in the inflammatory response syndrome associated with meconium peritonitis, and drainage of cystic fluid did not completely suppress this inflammation. To lessen the high morbidity of meconium peritonitis, efforts should be made to suppress the inflammatory response using new treatment strategies, such as administration of steroids or anti-cytokine therapy to supplement cystic drainage.

Prenatal risk stratification for isolated congenital diaphragmatic hernia: results of a Japanese multicenter study.

BACKGROUND/PURPOSE: 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). METHODS: 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. RESULTS: 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 ratio <0.08 or liver-up with L/T ratio ≥0.08 (n = 35), and group C of infants showing liver-up with L/T ratio <0.08 (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. CONCLUSIONS: 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.

[Strategy for surgery in neonates with coexisting congenital heart diseases].

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.

Selective ligation of portal vein and hepatic artery for ruptured hepatocellular carcinoma in a 13-year-old boy.

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.

Sialolipoma of the submandibular gland in a child.

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.

Reliability of the lung to thorax transverse area ratio as a predictive parameter in fetuses with congenital diaphragmatic hernia.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The Japanese experience with prenatally diagnosed congenital diaphragmatic hernia based on a multi-institutional review.

PURPOSE: To review the recent Japanese experience with prenatally diagnosed congenital diaphragmatic hernia (CDH) based on a multi-institutional survey. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Successful management of a large fetal mediastinal teratoma complicated by hydrops fetalis.

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.

[Present status of pediatric living-donor liver transplantation in National Center for Child Health and Development].

PURPOSE: 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. SUBJECTS AND METHODS: 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. RESULTS: 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%. CONCLUSION: 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.

Histopathologic improvement in biliary cirrhosis after definitive surgery for choledochal cyst.

Choledochal cyst causes liver fibrosis, the extent of which varies with each case. Liver damage seldom progresses to cirrhosis, but when it does, it is generally irreversible. We report an infantile case of liver cirrhosis associated with choledochal cyst in which complete clinical resolution was achieved by surgery. Pancytopenia caused by splenomegaly, massive ascites, hypoalbuminemia, and coagulation abnormality that were observed during the early postoperative period had disappeared within 4 months after surgery. Needle liver biopsy performed at 1 year after surgery revealed marked improvement in liver fibrosis.

A novel association of duodenal atresia, malrotation, segmental dilatation of the colon, and anorectal malformation.

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.

Repeat STEP procedure to establish enteral nutrition in an infant with short bowel syndrome.

The serial transverse enteroplasty (STEP) procedure is a safe and successful way to lengthen the small bowel in patients with short bowel syndrome. However, postoperative dilatation of the intestine may occur, which induces bacterial overgrowth and malabsorption leading to liver failure. We describe the case of an infant boy with short bowel syndrome caused by jejunal atresia requiring the STEP procedure twice. The first STEP improved the liver function, and the second STEP allowed 80% of the total calorie intake to be tolerated enterally. One should not hesitate to perform a second STEP if after the initial bowel lengthening procedure the patient develops small bowel dilatation that interferes with enteral nutrition.

Outcome of pediatric renal tumor treated using the Japan Wilms Tumor Study-1 (JWiTS-1) protocol: a report from the JWiTS group.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Growth spurt-related recurrence after Nuss procedure.

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.

Improved efficacy and safety of in utero cell transplantation in sheep using an ultrasound-guided method.

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; P < 0.01). 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%, P < 0.05) 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.