照井 慶太

Congenital esophageal stenosis (CES) is an extremely rare malformation, and standard treatment have not been completely established. By years of clinical research, evidence has been accumulated. We conducted systematic review to assess outcomes of the treatment for CES, especially the role of endoscopic modalities. A total of 144 literatures were screened and reviewed. CES was categorized in fibromuscular thickening, tracheobronchial remnants (TBR) and membranous web, and the frequency was 54%, 30% and 16%, respectively. Therapeutic option includes surgery and dilatation, and surgery tends to be reserved for ineffective dilatation. An essential point is that dilatation for TBR type of CES has low success rate and high rate of perforation. TBR can be distinguished by using endoscopic ultrasonography (EUS). Overall success rate of dilatation for CES with or without case selection by using EUS was 90% and 29%, respectively. Overall rate of perforation with or without case selection was 7% and 24%, respectively. By case selection using EUS, high success rate with low rate of perforation could be achieved. In conclusion, endoscopic dilatation has been established as a primary therapy for CES except TBR type. Repetitive dilatation with gradual step-up might be one of safe ways to minimize the risk of perforation.

PURPOSE: The optimal surgical approach for neonatal congenital diaphragmatic hernia (CDH) remains unclear. We conducted a systematic review and meta-analysis of the effectiveness of endoscopic surgery (ES) for neonatal CDH. METHODS: A systematic literature search was conducted using MEDLINE and the Cochrane Library. Studies that compared surgical approaches for neonatal CDH were selected. Mortality and recurrence of herniation were analyzed as primary endpoints. Each study was evaluated following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS: Eight observational studies comparing ES and open surgery (OS) met the criteria. As compared with the OS group, the ES group showed both a significantly lower mortality rate [risk ratio (RR) 0.18, 95 % confidence interval (CI) 0.09-0.38, p < 0.0001] and a significantly higher recurrence rate (RR 3.10, 95 % CI 1.95-4.88, p < 0.00001). However, serious selection bias was seen in seven of the eight studies-because the indication of ES had been determined intentionally, the ES groups may have included less severe cases. CONCLUSION: Although the evidence was insufficient, ES was clearly associated with more recurrence than was OS. Therefore, ES should not be the routine treatment for every neonate. It is crucially important to select suitable cases for ES.

OBJECTIVES: To explore the evidence for viral infections triggering human biliary atresia (BA) by reviewing archival original articles that analyzed human samples via polymerase chain reaction (PCR) experiments, considering the recent experimental trend of extensive use of rotaviral BA animal models. METHODS: A PubMed search retrieved original articles that reported the results of PCR experiments for detecting viral DNA or RNA in patient samples as proof of past infection. Search terms included the often-debated DNA or RNA viruses and BA. Special focus was directed toward PCR analyses that targeted reovirus and rotavirus, where PCR accuracy, specimen characteristics and their interpretations were compared. RESULTS: Nineteen studies were conducted on 16 different kinds of viruses using PCR, with 5 studies on reovirus, 3 on rotavirus, 10 on cytomegalovirus, 5 on Epstein-Barr virus, 4 on parvovirus B19, and so on. Among the papers suggesting a possible viral link to only BA, there was no study on reovirus, 1 on rotavirus, 3 on cytomegalovirus, 1 on EB virus, and 1 on papillomavirus. Of the 6 PCR studies on Reoviridae, 3 on reovirus and 2 on rotavirus were evaluated rigorously for experimental accuracy, including their sensitivity. Two research groups analyzed preoperative stool samples in addition to generic hepatobiliary tissue obtained at surgery. Sample collection timing varied widely, with storage period prior to PCR experimentation not revealed in most reports on Reoviridae. CONCLUSION: Although a considerable number of PCR studies have sought to clarify a viral role in the pathogenesis of BA using human samples, the findings have been contradictory and have not succeeded in achieving an obvious differentiation between causative and accidental infection of the focused virus. Reproducible and convincing evidence for a causative Reoviridae infection has been lacking based on objective data from highly sensitive PCR experiments. Even though the possibility remains of viral disappearance at the timing of collection, to avoid further ambiguous interpretations of PCR results, rigorous and meticulous collection of large numbers of specimens at carefully planned timing, along with a strictly adjusted and finely tuned PCR system, is strongly recommended for obtaining more reliable and consistent results.

AIM OF THE STUDY: Few follow-up studies focused on the recurrence regarding the postoperative course of congenital diaphragmatic hernia (CDH) survivors. The aim of this study was to report on risk factor for CDH patients who had the recurrence during the follow-up. MATERIALS AND METHODS: A multicenter retrospective survey was conducted on neonates diagnosed to have CDH between January 2006 and December 2010. Follow-up survey was conducted between September 2013 and October 2013 (ethical approval: No. 25-222). Nine institutions agreed to participate in this survey. Out of 228, 182 (79.8%) patients were alive and 180 patients were included in this study. Two patients were excluded because the defect had not repaired at the primary operation. The patients were divided into the recurrence group (n=21) and the nonrecurrence group (n=159). Postnatal and postoperative variables were compared between these two groups. Baseline variables which showed significance in univariate analysis were entered into multiple logistic regression analysis for analyzing the recurrence. A value of p<0.05 was considered to be statistically significant by using the JMP software program (version 9; SAS Institute, Inc, Cary, North Carolina, United States). MAIN RESULTS: Out of 180, 21 (11.7%) CDH neonates had the recurrence during the course of the follow-up. Five (2.8%) patients had the recurrence before primary discharge and 16 (8.9%) patients had the recurrence after discharge. Univariate analysis showed that liver herniation (crude odds ratio [OR], 7.4; 95% confidence interval [CI], 2.73-23.68), defect size C and D, proposed by the CDH Study Group (crude OR, 7.09; 95% CI, 2.73-19.99) and patch repair (crude OR, 5.00; 95% CI, 1.91-14.70) were risk factors. Multivariate logistic regression analysis showed liver herniation (adjusted OR, 3.96; 95% CI, 1.01-16.92) was the risk factor for the recurrence. CONCLUSION: A wide spectrum of the disease severity and the rarity of the disease mask the risk of the recurrence for CDH patients. This study showed the only factor to predict the recurrence was the liver herniation. These data will be helpful for providing information for the long-term follow-up of the CDH patients.

Minimally invasive surgery has become widely recognized and is commonly used for the diagnosis and treatment of neuroblastoma. However, in post-chemotherapy status or during reoperations, it is occasionally difficult to precisely locate small neuroblastoma lesions, and this becomes prominent in endoscopic surgeries, in which tactile sense is essentially lost. Herein, we report our preliminary experience in two abdominal neuroblastoma cases undergoing laparoscopic tumor resection with aid of intraoperative (123)I- metaiodobenzylguanidine (MIBG) radioguidance using a specifically designed gamma-probe. The procedure enables easier localization of viable neuroblastoma tissue, provided that the tumor shows moderate to high MIBG uptake.

Intestinal obstruction is a common complication after Ladd procedure. Ninety-three cases who had undergone the Ladd procedure between 1977 and 2013 treated at our own institution were retrospectively reviewed to identify the causes and risk factors for intestinal obstruction. The Ladd procedure has been performed without any intestinal fixing. Of the 87 cases who survived to discharge, intestinal obstruction was observed in 22 (25.3%). Among the cases with intestinal obstruction, 13 (59.1%) showed intestinal ischemia at the initial operation; this incidence was notably high, although it is low when only those cases with another concurrent surgical digestive disease are considered. All cases of intestinal obstruction were caused not by recurrent volvulus, but by adhesion between the intestine and the mesentery. Intestinal fixing is not required to prevent recurrent volvulus, but it is important to achieve adequate widening of the mesenteric base. The risk of intestinal obstruction after the Ladd procedure, on the other hand, is high. Moreover, patients with intestinal ischemia have an increased risk of intestinal obstruction.

INTRODUCTION: Little information exists about the physical growth of patients with congenital diaphragmatic hernia (CDH). This study aimed to assess the growth of patients with CDH during long follow-up periods, and to identify growth retardation (GR) risk factors. PATIENTS AND METHODS: A multicenter retrospective observational study was conducted in 2013. Of the 228 patients with CDH born between 2006 and 2010, 182 (79.8%) survived to discharge, and 174 cases were included in the study. Body weights and heights were measured at 1.5, 3, and 6 years of age. GR was defined as a Z-score relating to the weight or height of < - 2.0. Cases with GR at 1.5, 3, or 6 years of age comprised the GR group. The clinical variables of the GR and non-GR groups were compared using univariate analysis. Multiple logistic regression analyses were conducted successively on the factors that were significant at p < 0.01 in the univariate analysis and had low correlations with other factors (r < 0.7). The numerical data were divided into two groups based on a cutoff value that was calculated from a receiver operating characteristic curve. RESULTS: The GR group comprised 35 cases (22.7%). The rates of GR at 1.5, 3, and 6 years of age were 19.5 (26/133), 14.4 (16/111), and 13.5% (5/37), respectively. The body weight Z-scores improved in cases with GR between the ages of 1.5 and 3 years (p = 0.036). As the patients aged, the wasting type of GR decreased in frequency (31, 0, and 0% at 1.5, 3, and 6 years of age, respectively) and the stunting type of GR increased in frequency (27, 31, and 100% at 1.5, 3, and 6 years of age, respectively). The univariate analysis showed that birth weight and height, liver-up, large defect size of the diaphragm, use of nitric oxide, patch repair, long hospital stay, home oxygen treatment (HOT), and vasodilator administration at discharge were significant risk factors of GR. The multivariate analysis determined that a birth weight of < 2,698 g (odds ratio [OR] = 5.5, 95% confidence interval [CI] = 2.1-16.8, p < 0.001) and HOT (OR = 5.8, 95%CI = 1.6-23.8, p = 0.007) were significant risk factors for GR. CONCLUSION: GR was observed in 22.7% of the CDH survivors. Body weight improved between 1.5 and 3 years of age in the GR cases, but some patients developed chronic malnutrition via acute malnutrition. Low birth weight and the need for HOT were GR risk factors. Aggressive management of acute malnutrition may improve the growth of patients with CDH.

Malignant rhabdoid tumor (MRT) is a rare and aggressive malignancy associated with poor outcomes. MRT of the liver is even rarer, and little information has been described. We report the case of an 8-month-old boy with MRT of the liver. The tumor showed aggressive progression despite a multidisciplinary approach, and the patient died due to multiple organ failure 14 days after admission. Autopsy revealed the liver tumor and multiple metastases with negative immunohistochemistry for INI1/BAF47. A review of 53 cases of pediatric MRT of the liver is provided.

INTRODUCTION: Thoracoscopic lobectomy for congenital pulmonary airway malformation has been indicated from the neonatal period to adolescence. However, it is difficult to approach the pulmonary artery for lobectomy in congenital lung malformations with incomplete or absent interlobar fissures. Multidetector computed tomographic images and computed tomography pulmonary angiography gave us helpful information before the operation. We performed thoracoscopic lobectomy for congenital pulmonary airway malformations with absent interlobar fissures and adhesions in accordance with information from multidetector computed tomographic images. CASE PRESENTATION: A 14-year-old Japanese girl received a diagnosis of congenital pulmonary airway malformation when she presented with pneumonia. Using multidetector computed tomography and three-dimensional reconstruction provides meticulous characterization of the anatomy in pediatric patients. We confirmed that her left A4+5 artery arose from her left pulmonary artery medial to A6. Her left pulmonary artery was divided just proximal to the A6 origin before the lobes were separated safely. We took advantage of using a stapler to divide the fissureless thick parenchyma. Perioperative diagnosis was congenital cystic adenomatoid malformation. CONCLUSIONS: We used preoperative multidetector computed tomography to outline the bronchovascular anatomy and guide hybrid video-assisted thoracoscopic surgery for a congenital cystic adenomatoid malformation in a fissureless left lung.

A 21-month-old Japanese boy was admitted with cough and hypoxemia. Chest X-ray showed massive right pleural effusion, which consisted of chyle. Computed tomography showed poor contrast area at superior and anterior mediastinum. Magnetic resonance imaging showed granular T2-low area at the same area. Lymphangioscintigraphy revealed a hot spot at superior mediastinum. These findings lead us to diagnose as mediastinal lymphangioma accompanied with chylothorax. Noninvasive treatments including total parenteral nutrition, administration of octreotide and sclerotherapy were tried, but all of them proved to be ineffective. Transfusions of blood products were frequently needed during these therapies. On the 48th hospital day, the mediastinal tumor and the thymus were excised through a median sternotomy. A leakage point of lymph into the intrathoracic space was not found, in spite of preoperative administration of milk with dye. Since the pleural effusion had continued to be drained, pleuroperitoneal shunt was placed on the 90th hospital day. The shunting amount continued to decline soon after the shunting, and had been under 10 ml/day since the 142nd day. The shunt was removed on the 148th day. There has been no reaccumulation of the pleural effusion and no recurrence of the mediastinal tumor for 1 year of observation.

BACKGROUND: The significance of pediatric endoscopic retrograde cholangiopancreatography (ERCP) according to age or disease variation is inconclusive. This study aimed to evaluate the usefulness of pediatric ERCP in diagnosing or treating small children with pancreaticobiliary disorders, including choledochal cyst (CC) and biliary atresia (BA). METHODS: From 1980 to 2011, 235 ERCPs were performed in 220 pediatric patients (median age, 2 years) at our institution. Underlying pathology was CC in 92 patients (3 years), BA in 62 patients (55 days), and others in 66 patients. Success and complication rates, and ERCP findings were retrospectively analyzed. RESULTS: The overall success rate was 96%. Rates for individual pathologies were 99% for CC, 92% for BA, and 96% for others. The success rate was 100% among children >3 years, but 92% when limited to infants. Post-ERCP hyperamylasemia and duodenal perforation occurred in 9% and 0.4% of cases, respectively. Regarding preoperative evaluation of the pancreaticobiliary system in CC, ERCP clearly delineated pancreaticobiliary maljunction (79%) and the pancreatic duct (94%), whereas it visualized the common bile duct and intrahepatic bile duct at relatively low rates (77% and 33%, respectively). ERCP successfully identified 16 cases (18%) with non-BA of 90 patients with suspected BA. Moreover, ERCP demonstrated only pancreatic duct in 70% of all BA. CONCLUSIONS: ERCP among children including infants with CC and BA can be performed with fairly satisfactory results. Although pediatric ERCP can also help describe the pancreaticobiliary system in detail, its indication should be deliberately considered when anatomical information from less-invasive imaging modalities is insufficient.

PURPOSE: Gastroesophageal reflux disease (GERD) is one of the concomitant problems in infants with congenital diaphragmatic hernia (CDH). We assessed risk factors of GERD in CDH patients. METHODS: The retrospective observational study for CDH infants was conducted. Cases of CDH who were born between January 2006 and December 2010, were operated in the 9 participating institutions, and survived to discharge were included. Completion of medical therapy for GERD and incidence of surgery were primary outcomes. Kaplan-Meier survival analysis and Cox proportional hazards regression were used. RESULTS: In 182 cases of CDH, the medical therapies for GERD were performed in 23.8% (40/168), and were completed in 60.0% (24/40). Prenatal detection of CDH (HR 5.87, CI 1.6-18.8, p = 0.012) and tube feeding at discharge (HR 5.04, 95% CI 1.3-33.1, p = 0.016) were significantly correlated with unsuccessful weaning from medical therapy. Surgery for GERD was performed in 10.7% (18/169). Gestational age (HR 4.78, 95% CI 1.5-21.1, p = 0.006) and diaphragmatic defect of more than 75% (HR 4.3, 95% CI 1.6-12.9, p = 0.005) were significantly correlated with need for antireflux surgery. CONCLUSION: Diaphragmatic defect of more than 75% was risk factor of future need for antireflux surgery.

PURPOSE: In the recent years in Japan, an increasing number of patients with neuroblastoma (NB) are being treated by the "delayed local treatment (DL)" policy, undergoing surgery after the completion of high-dose chemotherapy with hematopoietic stem cell rescue (HDC). We reviewed the histopathological findings of second-look operations, including those of patients treated with DL. PATIENTS: From 1998 to 2013, 26 patients with high-risk NB underwent radical operation following chemotherapy. Surgery was performed after induction chemotherapy in 17 cases (standard; STD), whereas 9 cases completed induction chemotherapy and HDC before undergoing tumor resection (DL). The amount of necrosis and the degree of differentiation within the post-treatment tumor were assessed. RESULTS: Eighty-eight percent of the tumors showed necrosis in more than 1/3 of the specimen. Two DL cases showed complete disappearance of viable tumor cells. Amount of necrosis did not affect the prognosis of the patient. Tumors with immature, poorly differentiated phenotypes showed an extremely aggressive thereafter. Though not statistically proven, (123)I-MIBG (metaiodobenzylguanidine) uptake may be correlated with the amount of viable cells remaining within the tumor, but not with the degree of differentiation. CONCLUSIONS: Our results support the previous reports advocating that tumors that sustain unfavorable histology after chemotherapy behave aggressively thereafter.

The aim of this paper is to investigate the clinical courses of patients with biliary atresia (BA) during neonatal period. We examined 19 patients with BA, who underwent blood tests including direct bilirubin (D-Bil) within 20 days of age, in 3 tertiary hospitals in Japan. The first blood sample was collected at 8.4±6.5 days of age. The acholic stool was observed within 2 weeks of age in 16 cases (84.2%). Decrease of T-Bil was observed in all the subjects, with a range of reduction of 6.5±3.3 mg/dL, from 10.4±7.5 to 29.8±9.1 days of age. Decrease of D-Bil was also observed in 17 out of 19 cases (89%), with a range of reduction of 1.1±1.0 mg/dL, from 15.5±8.0 to 24.9±9.6 days of age. A significant decrease of D-Bil was observed in 2 cases of biliary atresia splenic malformation syndrome. We therefore conclude that clinicians treating icteric infants should not exclude a diagnosis of BA even if the level of D-Bil has a declining tendency.

Microvascular decompression is now a standard surgical technique for the treatment of trigeminal neuralgia. However, it is occasionally difficult to expose the trigeminal nerves because of the high anatomical variety of vascular or bony structures in the posterior fossa. We reported the case of a 59-year-old woman with trigeminal neuralgia whose site of neurovascular compression could not be observed in microvascular decompression. On approaching the trigeminal nerve, the suprameatal tubercle was so prominent that it prevented adequate visualization of the nerve tract. After drilling out the tubercle concealing the trigeminal nerve behind it, we exposed the nerve entirely and subsequently decompressed it from the superior cerebellar artery. Retrospectively, the suprameatal tubercle was found 3mm high above the posterior surface of the petrous bone. Then, we analyzed the height of suprameatal tubercles in 106 patients who underwent three-dimensional CT of the skull. Mean values of the suprameatal tubercles were 1.4-1.7mm in height, and 5.2% of them were higher than 3mm. The result suggested the high morphological variety of the petrous bone. We emphasize the importance of presurgical evaluation of the petrous bone in trigeminal neuralgia, because the neurovascular compression site may not be exposed sufficiently by the suprameatal tubercle in approximately 5% of the patients.

BACKGROUND: The serum level of amylase (sAm) is commonly used as a biochemical marker for diagnosis and management of pancreatic disorders. However, the use of the urine level of amylase (uAm) is limited in practice, because the diagnostic ability of uAm is inferior to that of sAm. In the present study, the possible concordance of uAm-rerated parameters with sAm was investigated, and evaluate the usefulness of uAm for management of hyperamylasemia. METHODS: From June 1995 to October 2009, 804 samples of both urine and blood were collected from 128 patients in order to measure the serum level of amylase (sAm) and the urine level of amylase (uAm) and creatinine (uCr). Concordance of parameters using uAm compared to sAm was assessed. Parameters used were uAm, amylase creatinine clearance ratio (ACCR), and the ratio of uAm to uCr (uAm/uCr). RESULTS: uAm/uCr had the best correlation with sAm (r = 0.779, p < 0.001) compared to uAm (r = 0.620, p < 0.001) and to ACCR (r = 0.374, p < 0.001), when sAm was over the standard level. The area under the receiver operating characteristic curve of uAm/uCr (0.884) was significantly higher than that of uAm (0.766) and of ACCR (0.666) (p < 0.001 for each). The cutoff value of uAm/uCr was 569.8, with a sensitivity of 81.0% and a specificity of 83.1%. CONCLUSIONS: The uAm/uCr ratio correlated with sAm, and may be an alternative to sAm for prediction of hyperamylasemia. Use of urine samples results in a decreased need for blood sampling, which is especially beneficial in pediatric patients.

PURPOSE: Gastric perforation (GP) of the newborn is a rare, serious, and life-threatening problem, and its etiology remains unclear. Although historically GP has often been described as "spontaneous'', some cases are non-spontaneous. The aim of the present study was to review cases of GP and to discuss its etiology in a single prefecture in Japan over a period of 20 years. METHODS: Eleven cases with GP that underwent surgery in 4 institutions in the Chiba Prefecture from 1991 to 2010 were reviewed and divided into 2 groups: the early (1991-2000, n = 7) and late (2001-2010, n = 4) groups. RESULTS: No factors were observed that could have caused GP other than malformations associated with distal obstruction (3 midgut volvulus, 1 jejunal stenosis, 1 diaphragm eventration). Distal obstruction was present in 1 case in the early group and all 4 cases in the late group (p = 0.015). While the incidence of GP did not change over the 20-year period reviewed, the incidence of GP without distal obstruction significantly decreased in the late group. CONCLUSION: The proportion of patients with GP and distal obstruction increased and true "spontaneous" cases of GP decreased over time. The possible presence of distal obstruction should be evaluated during surgery for GP.

F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) typically demonstrates prominent thymus uptake in normal children and young adults. A 12-year-old girl presenting with back pain and respiratory discomfort underwent an FDG PET/CT examination that demonstrated an anterior mediastinal mass with relatively low FDG uptake and an apparently separate FDG-positive nodular lesion superior to the larger mass. Surgical excision demonstrated a larger mature teratoma mass with a smaller thymic tissue nodule connected to the tumor with hourglass bridging.

BACKGROUND AND AIM: Inappropriate host immunological reactions against unknown ligands via the Toll-like receptor (TLR) cascades may trigger progressive inflammatory biliary destruction that manifests as biliary atresia (BA) in newborns or infants. The aim of the study was to clarify the role of the innate immune system in the development of BA. PATIENTS AND METHODS: Liver tissue was obtained from 49 patients with pediatric hepatobiliary diseases: 19 with BA, 21 with choledochal cysts, and 9 with other hepatobiliary diseases. BA samples obtained during the initial portoenterostomy and reoperation or liver transplantation (LT) were classified as early and late BA groups, respectively. Of the early BA group, those requiring LT were designated as the LT group, and the others were designated as the non-LT group. The mRNA expression levels of TLRs 2, 3, 4, 7, and 8 were determined by real-time quantitative reverse transcription-polymerase chain reaction and were compared between groups. The correlation between TLR mRNA expression level and age at sampling was examined for each TLR in the patients with BA. RESULTS: TLR8 mRNA, encoding the receptor for single-stranded RNA, was significantly higher in the early BA group, compared with non-BA groups (P = 0.008). Within the BA group, mRNA levels of TLRs 2 and 8 were significantly higher in the early group than in the late group (P = 0.02 and 0.006, respectively), despite there being no significant correlation between TLR mRNA expression and age at sampling, except for TLR7 (r = 0.77, P = 0.001). Compared with the non-LT group, the LT group demonstrated significantly higher mRNA expression of TLRs 3 and 7 (P = 0.02 and 0.01, respectively). CONCLUSIONS: Innate immune responses may contribute to the initiation and progression of BA. Severe inflammation characteristic of BA around the time of the first operation may abate postoperatively, but determination of selected TLR mRNA expression levels in the liver at the time of Kasai portoenterostomy may assist in predicting the prognosis of patients with BA.

Objective: Prognostic prediction in prenatally diagnosed congenital diaphragmatic hernia (CDH) is needed. The aim of the study was to evaluate magnetic resonance imaging (MRI) signal intensity of the fetal lung as a predictor of prognosis in CDH. Study Design: The subjects consisted of 12 fetuses with prenatally diagnosed CDH, who were treated soon after the birth in our institution. They all underwent MRI at 29 to 37 weeks of gestation. The ratio of the lung signal intensity to the spinal fluid signal intensity (L/SF) was calculated using region-of-interest analysis of T2-weighted images. The relationship between L/SF and clinical data was then examined. Result: L/SF were significantly larger in survivors compared with deaths (0.815 vs 0.614, P&lt;0.05). In survivors, L/SF significantly correlated with duration of tracheal intubation (rs = -0.938, P&lt;0.01). Conclusion: L/SF is a unique factor to predict the survival prognosis and likely to quantify the degree of pulmonary hypoplasia in CDH. Journal of Perinatology (2011) 31, 269-273; doi: 10.1038/jp.2010.119; published online 4 November 2010

BACKGROUND: Biliary atresia (BA) is an idiopathic inflammatory obliterative cholangiopathy of neonates, leading to progressive biliary cirrhosis. Hepatoportoenterostomy (Kasai procedure) can cure jaundice in 30% to 80% of patients. Postoperative clearance of jaundice is one of the most important factors influencing long-term outcomes of BA patients. Multidrug resistance protein 2 (MRP2) is one of the canalicular export pumps located in hepatocytes; it exports organic anions and their conjugates (e.g., bilirubin) into bile canaliculus. Although MRP2 is an essential transporter for the excretion of bilirubin, its role in the clinical course of BA patients is unclear. The present study investigated the relationship between hepatic MRP2 expression and clinical course in BA patients, with particular emphasis in curing jaundice after hepatoportoenterostomy. RESULTS: No significant differences in hepatic MRP2 expression level were observed between BA and controls groups. There was no correlation between MRP2 expression and age at time of surgery in BA and control groups. In BA patients, MRP2 expression level in the jaundice and jaundice-free group did not differ significantly (2.0 × 10-4 vs 3.1 × 10-4, p = 0.094). Although the serum level of total bilirubin just before surgery did not correlate with MRP2 expression level (rs = 0.031, p = 0.914), the serum level of total bilirubin measured at 2 weeks (rs = -0.569, p = 0.034) and 4 weeks after surgery (rs = -0.620, p = 0.018) were significantly correlated with MRP2 expression level. Furthermore, MRP2 expression level was inversely correlated with ratio of change in serum total bilirubin level over 4 weeks (rs = -0.676, p = 0.008), which represents the serum bilirubin level measured at 4 weeks after surgery divided by value just before surgery. There was no correlation between expression level of MRP2 and nuclear receptors, such as retinoid × receptor α, farnesoid × receptor, pregnane × receptor, or constitutive androstane receptor. CONCLUSIONS: Hepatic MRP2 expression level was associated with postoperative clearance of jaundice in BA patients, at least within 1 month after hepatoportoenterostomy. This finding suggests that not only morphological appearance of the liver tissue but also the biological status of hepatocytes is important for BA pathophysiology.

Background. Standard choledochal cyst (CC) operations involve dilated extrahepatic bile duct excision followed by biloenterostomy. However biliary variants and associated intrahepatic bile duct (IHBD) stenoses or dilatations triggering postoperative sequelae require additional procedures. The usefulness of preoperative 3-dimensional magnetic resonance cholangiopancreatography (31) MRCP) and virtual cholangioscopy (VIES) for observing biliary morphology and pancreaticobilialy maljunction (PBM) was evaluated. Methods. In 16 pediatric CC patients (age range, 4 months to 9 years; median, 3 years), visualization of PBM and aberrant bile duct anatomy and 1171131) morphology at the hepatic hilum (HH), umbilical portion (UP), and posterior branch (POST) were compared between. 3D-MRCP and intraoperative cholangiography (IOC). VES and intraoperative cholangioscopy (IOS) findings were compared. Results. HH, UP, and POST visualization rates were 100%, 94%, and 94%, respectively, by 3D-MRCP, and 100%, 69%, and 69%, respectively, by IOC. IHBD stenosis detection rates at each region were 38%, 13%, and 13%, respectively, by 3D-MRCP, and 25%, 0%, and 9%, :respectively; by IOC. IHBD dilatation detection rates at each part were 75%, 47%, and 60%, respectively, by 3D-MRCP, and 88%, 82%, and 91%, respectively, by IOC. PBM was confirmed in 56% and 93% of cases on 3D-MRCP and IOC, respectively. Both 3D-MRCP and IOC showed biliary variants in 5 cases (31%). VIES showed membranous Mixtures at HH, UP, and POST in 6, 2, and 2 cases, respectively, whereas IOS (lid so at HH in 4 cases and POST in 2. Conclusion. Preoperative 3D-MRCP and VIES accurately depict biliary morphology, allowing concrete operative planning in pediatric CC patients, complementing IOC and IOS. (Surgery 2011;149:569-75.)

To evaluate the usefulness of multi-detector row computed tomography (MDCT) in the postoperative long-term follow-up of biliary atresia (BA) patients for detection of esophagogastric varices due to portal hypertension and intrahepatic bile duct (IHBD) dilatations. Well-developed esophagogastric varices can cause unexpected life-threatening rupture and contribute to the progression of hepatopulmonary vascular diseases. Dilated IHBDs can trigger cholangitis. After corrective surgery, 29 BA patients (median age 14 years, range 6 months to 27 years) with suspected long-term sequelae underwent 16-slice MDCT. Esophagogastric varices and IHBD dilatations were evaluated using reconstructed images. Detection rates for esophagogastric varices were compared between MDCT and endoscopic findings. Differences in detection rates for IHBD dilatations between MDCT and ultrasonography (US) were also investigated. Detection rates for esophageal varices did not differ significantly between MDCT and endoscopy, while three cases positive only on MDCT, including one with hepatopulmonary syndrome, showed conspicuous peri-esophageal varices deep in the esophageal wall. MDCT showed a significantly higher detection rate than endoscopy (p = 0.03) for gastric fundal varices. MDCT with the maximum intensity projection disclosed IHBD dilatations in 17 postoperative BA cases, 15 out of which had past history of cholangitis, while US detected them in 6 cases (p = 0.003). In addition, MDCT was more advantageous for detecting IHBD dilatations, particularly those located in the posterior lobe. Among postoperative BA patients, compared to endoscopy, MDCT had comparable and superior detection rates for esophageal and gastric fundal varices, respectively. MDCT also precisely demonstrated the location and extent of IHBD dilatations. In long-term follow-up of BA patients, MDCT can help determine follow-up strategies.

Purpose Fetal stabilization (FS) is a way to decrease stresses to the fetus during the perinatal period to control persistent pulmonary hypertension in neonates (PPHN). Although FS in congenital diaphragmatic hernia (CDH) patients has been reported, the effect of FS has not been evaluated sufficiently. The present study retrospectively evaluated influences of FS on the postnatal status of CDH patients. Methods Twenty-three cases of prenatally diagnosed CDH which were treated after birth in our institution from April 1998 to March 2010 were reviewed. From April 1998 to May 2007, FS was performed by administration of fentanyl and midazolam to the mother before subsequent cesarean section (FS group, n = 10). Beginning from June 2007, FS was discontinued (non-FS, n = 13). Results At the first postnatal estimation, flow pattern of the ductus arteriosus had no difference between two groups. The oxygenation index of the FS group was significantly higher than that in the non-FS group (p = 0.045). Only the non-FS group had correlations between estimated standardized lung volume (% lung volume) and alveolar-arterial oxygen tension difference (p = 0.022), and between % lung volume and the oxygenation index (p = 0.0037). Conclusion During the period immediately after birth, FS had no obvious therapeutic effect on PPHN, and had a negative impact on respiratory status.

Cerebral aneurysms arising from fenestration of the horizontal (A(1)) segment in the anterior cerebral artery (ACA) are very rare. In this paper, we report our case, discuss radiological features, and review previous cases. A 70-year-old male was referred to our hospital presenting with memory disturbance. His unruptured cerebral aneurysm in the A(1) segment was incidentally found by magnetic resonance angiography (MRA). Three dimensional computed tomographic angiography (3D-CTA) demonstrated this aneurysm arising from fenestration of the A(1) segment. Surgical neck clipping was performed via the pterional approach, while sacrificing one pair of the A(1) segment. The patient's post operative course was uneventful. Only 14 cases with an aneurysm arising from fenestration of the A(1) segment have been reported previously. In the present case, 3D-CTA was very useful for finding out where the aneurysm arose from, and we also had to be careful about perforating arteries from the A(1) segment during the surgery.

Pancreaticobiliary maljunction (PBM) is defined as a congenital anomaly in which the main pancreatic and common bile ducts are joined outside the duodenal wall and forms the long common channel. Although PBM and pancreas divisum are congenital anomalies causing pancreatitides, distinct data about the incidence of pancreas divisum in pediatric PBM has not been reported to date. The present study was designed to reveal the incidence and clinical features of pancreas divisum in cases of PBM. The configurations of pancreatic ducts of 78 pediatric cases of PBM were assessed by endoscopic retrograde cholangiopancreatography (ERCP) and/or intraoperative cholangiopancreatography. Additional cannulation of the minor papilla was performed when the entire length of the main pancreatic duct was not detected with cannulation of the major papilla alone. Clear pancreatography was obtained in 71 cases out of 78 cases of PBM. Abnormal fusion of the pancreatic duct was detected in 1 case (1.4%) with complete pancreas divisum. This case was asymptomatic preoperatively and for 10 years postoperatively. Pancreas divisum exists in 1.4% of PBM. Although pancreas divisum is one of the pathogenesis of pancreatitis in PBM, is rarely associated with PBM and not always causes pancreatitis.

Background/Purpose: It has previously been shown that neuroblastomas with favorable prognosis often express a high level of nerve growth factor receptor trkA. We performed an expression analysis of trkA in 106 NB samples based on the quantitative real-time polymerase chain reaction (PCR) and reevaluated the prognostic power of trkA. Materials and methods: A total of 106 primary tumors from NB patients treated from 1988 to 2009 were analyzed. MYCN was amplified in 13 cases. TaqMan probe method was used for quantitative PCR. Primers and probes were designed to detect trkA I and trkA II, but not the oncogenic splice variant trkA III. Results: Expression analysis by real-time PCR revealed a wide range of expression levels of trkA within neuroblastoma tissues. Extremely low levels of trkA that were undetectable by semiquantitative PCR were able to be quantified by this method. trkA was predominantly expressed in tumors with favorable outcome. Further analysis of trkA expression was performed in a cohort excluding mass-screened neuroblastomas. Strikingly, multivariate analysis containing age, MYCN status, and trkA expression identified trkA as the only variable that independently predicts the prognosis of the 44 patients who presented clinically. Conclusion: High-resolution expression analysis targeting trkA and trkA II may add more statistical power on trkA as a biological marker. (C) 2010 Elsevier Inc. All rights reserved.

Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive vascular neoplasm that mainly occurs during childhood. Although KHE may involve various organs, involvement of the choledochus has not been reported. We report a case of KHE in a 5-month-old male infant. The patient was admitted with icterus and acholic stool. Contrast computed tomography revealed a vascular tumor in the hepatic portal region causing biliary obstruction. Excision of the extrahepatic duct and hepatoportoenterostomy were performed successfully, and he has been well during 3 years of postoperative follow-up. (C) 2010 Elsevier Inc. All rights reserved.

Noninvasive evaluation of organ redox states provides invaluable information in many clinical settings. We evaluated a newly developed reduction/oxidation-sensitive green fluorescent protein (roGFP) probe that reports cellular redox potentials and their dynamic changes in live cells. On hypoxia/reoxygenation (H/R) of AML12 liver cells, roGFP indicated mild reduction during hypoxia, but immediate transient oxidation after reoxygenation. The roGFP probe confirmed the antioxidative effects of N-acetylcysteine, catalase, redox factor-1, and Mn-SOD/CuZn-SOD against H/R-induced cellular oxidative stress (OS). In a mouse liver ischemia/reperfusion (I/R) model, roGFP transduced by using an adenoviral vector revealed immediate reduction of the liver under ischemia, and two distinct peaks of OS: (a) early, observed within 60 min after reperfusion, similar to the in vitro study; and (b) later, at 24 h. The early peak levels paralleled the ischemic time up to 75 min and the postischemic liver injury (sGOT/GPT/LDH) in the later phase (6 and 24 h after I/R). The roGFP probe successfully indicated postischemic OS of the liver in living mice, accurately predicting postischemic liver injury. This probe may represent an effective OS marker indicating organ redox states and also predicting the damage/function. Antioxid. Redox Signal. 11, 2563-2572.

A boy with a history of esophageal atresia repair received an esophagoesophagostomy at 14 months for a severe refractory anastomotic stricture, which had already required repeated balloon dilation with intralesional dexamethasone injection. Anastomotic leakage and stricture was again evident after the second surgery, and the patient underwent five procedures of balloon dilations with intralesional dexamethasone injection. Dysphagia was persistent and the patient required dilation every 2-3 weeks. After the sixth dilation, the patient was given 1 mg/kg per day of dexamethasone i.v. for 3 days. Dexamethasone i.v. was tapered during the following 3 days and finished at day 6. A week later, endoscopic findings showed an apparent improvement in the stricture. Another dilation was followed by 1 mg/kg per day dexamethasone i.v. for 7 days, and 0.75 kg/mg per day oral dexamethasone for another 7 days. The stricture improved completely and the anastomosis was patent after the second dilation. The patient is doing well without dysphagia and has not required additional dilation for over 18 months after the last dilation. Balloon dilation in combination with systemic dexamethasone administration may be an effective treatment that could substitute invasive techniques including surgical manipulation for severe refractory strictures.

Anorectal malformations encompass a broad spectrum of congenital defects and are related to the development of the genital tubercle, including the cloacal plate and urorectal septum. To explore the cellular and molecular basis of anorectal malformations oils, we analyzed the pathogenetic process using two mouse models: Danforth&apos;s short tail (Sd) and all-trans retinoic acid (ATRA)-treated mice. Embryologically, the cloacal plate may be divided into distal and proximal parts, with the distal part subdivided into ventral and dorsal parts. In the two Mouse models. anorectal malformations occur due to improper development of the proximal part of the cloacal plate. At 10.5 days postcoitus (CIPC). in Sd homozygotes, there was a lack of Shh expression only in the cloacal plate and the endoderm around the cloacal plate. In addition, Wnt5a was not expressed in the mesoderm adjacent to the cloacal plate in the two Mouse models. and Axin2. which is regulated by Wnt signaling, was not expressed in the dorsal part of the cloacal plate at 12.5 dpc. Based oil these results, we suggest that Wnt5a, which is downstream of Shh signaling, and Axin2 affect the development of the proximal part of the cloacal plate. (Pediatr Res 66: 149-154, 2009)

A rare case of gastric duplication of childhood is reported. A 1-month-old boy underwent pyloromyotomy for infantile hypertrophic pyloric stenosis. At laparotomy, a protruding lesion was identified in the anterior wall of the pylorus. The pylorus was hypertrophic as indicated preoperatively, and a normal pyloromyotomy was performed. Wedge biopsy of the protruding lesion revealed an intestinal structure, and gastric duplication was diagnosed. The child remained asymptomatic thereafter, but considering the risk of the duplication becoming symptomatic, a second laparotomy was performed at I year of age. The duplication cyst shared part of the wall with the pylorus, and the cyst was removed by cystectomy, leaving the pyloric muscle intact. The cyst was found to be communicating with the pancreatic duct. The child is doing well without any symptoms as of 18 months after second laparotomy. To the best of our knowledge, this is the youngest case of gastroduodenal duplication with pancreatic duct communication yet reported. (c) 2008 Published by Elsevier Inc.

Background: Pancreatitis associated with pancreaticobiliary maljunction (PBM) is commonly treated nonoperatively before surgery. It is, however, sometimes uncontrollable, and little has been reported about the management. Methods: Focusing on the preoperative management, we reviewed clinical courses of 4 PBM cases (ages 1 to 7 years old). Each had pancreatitis that was totally resistant to medical treatment and was applied endoscopic sphincterotomy (ES). Results: The first case underwent percutaneous transhepatic catheter drainage (PTCD) primarily. In spite of daily lavage using the drainage tube for a week, plugs located in the common channel were not removed, and clinical findings were not improved. Therefore, ES followed by removal of protein plugs was performed to improve pancreatitis dramatically. Through this experience, 3 subsequent cases with refractory pancreatitis all underwent successful ES primarily soon after the medical treatments turned out to be ineffective. In all 4 cases, protein plugs were impacted in common channels, and ES could successfully remove the plugs that were impossible to remove by using PTCD. Improved preoperative pancreaticobiliary decompression by ES shortens the duration of recalcitrant acute pancreatitis associated with PBM allowing for a subsequent safe operation. Conclusions: Endoscopic sphincterotomy is one of the useful preoperative managements for refractory pancreatitis associated with PBM. (C) 2008 Elsevier Inc. All rights reserved.

Background/Aims:Ischemia/reperfusion damage to the liver remains a serious concern in many clinical situations. Major mechanisms for this certainly include oxidative stress. Methods:The effects of ablating the p66 isoform of ShcA (p66(shc)) on hypoxia/reoxygenation (H/R)-induced oxidative stress and cell injury in hepatocytes were investigated. Results: Immediately after reoxygenation, AML12 cells were clearly under oxidative stress; many cells underwent apoptosis. However, knockdown of p66(shc) by specific RNAi markedly decreased cellular oxidative stress and H/R-induced apoptosis, as well as conferring resistance to H2O2 insult. These data suggest that prevention of apoptosis conferred by ablation of p66(shc) results from changed ROS-scavenging, but not inhibition of ROS generation. These data were also confirmed in fibroblasts from p66(shc) knockout mice. Anti-oxidant molecules, such as MnSOD and Ref-1 and the anti-apoptotic molecule Bcl-xL were up-regulated, and pro-apoptotic FLICE was down-regulated, by ablation of p66. Interestingly, catalase expression was not affected in p66(shc)-knockdown-AML12 cells although it is a major target in other cell types. Conclusions: Our findings suggest that in hepatocytes, ablation of p66 A, is cytoprotective against H/R-induced oxidative stress, with MnSOD and Ref-1 playing critical roles, and with up-regulation of Bcl-xL and down-regulation of FLICE contributing jointly to preventing cells from undergoing oxidant-induced apoptosis. (C) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

We report herein a case of prenatally detected neonatal adrenocortical tumor (ACT). The patient was ail otherwise healthy newborn girl. No signs of Beckwith-Wiedemann syndrome were identified, and her family medical history did not suggest predisposition to cancer. Computed tomography and ultrasonography after birth revealed a round solid tumor 40 mm in diameter in the right suprarenal area. The precise diagnosis of ACT was unexpectedly obtained based on results from the Japanese neonatal mass screening program. Blood 17-hydroxyprogesterone is routinely measured as a part of this program for early detection of congenital adrenal hyperplasia in Japan. Abnormally elevated level of 17-hydroxyprogesterone was reported in the patient and, thus, led to the diagnosis of ACT. Surgical resection was safely performed with perioperative steroid replacement. Adrenocortical tumors are extremely rare in childhood, particularly in the neonatal period. some or these tumors secrete abnormally high levels of cortisol, suppressing function of the contralateral adrenal gland and, thus, leading to life-threatening postoperative adrenal insufficiency. Scheduled steroid replacement enables safe perioperative management in such cases. Adrenocortical tumor should always be considered among the differential diagnoses for neonatal suprarenal mass because precise diagnosis will enable the physician to develop appropriate treatment strategies. (c) 2008 Elsevier Inc, All rights reserved.

Background. Pancreaticobiliary mallunction (PBM), which firequently accompanies choledochal dilation., is a high, risk factor for biliary tract (gallbladder bile duct) carcinoma because of the continuous rejlux of pancreatic juice into the biliary tract. The aim of this study was to clarify the preferable operative age in PBM patients fir the prevention of biliary tract carcinogenesis, with reference to the dilation types of bile ducts. Methods. There were 165 PBM patients in total studied, including 92 pediatric patients (&lt;= 15 y) (cystic, 63; spindle-like, 29; nondilation, 0) and 73 adult patients (&gt; 15 gamma) (cystic, 45; spindle-like, 18; nondilalion, 10) who underwent operative excision of extrahepatic bile ducts or cholecyslectomy. We investigated incidence by age of biliary tract malignancies and the risk according to types of dilation. Results. In the pediatric group, no carcinoma case could be found preoperatively or postoperatively (mean follow-up period, 11.7y). In the adult group, bile duct carcinomas could be detected in 6 cases of a cystic type (6 of 45; 13.3%) (3 Preoperative, 3 postoperative). Among the bile duct. carcinoma cases, the youngest patient was a 21-year-old woman who had undergone excision of an extrahepatic bile duct, 3 years previously. Gallbladder carcinomas were detected in 16 patients: 3 of 45 cystic (6.7%), 6 of 18 spindle-like (33.3 %), and 8 of 10 nandilatian (80.0%), in whom the youngest patient was a 41-yearold woman with a spindle-like type. Conclusions. To prevent biliary tract carcinogenesis in PBM patients, cyslic-dilated choledochus should be excised in childhood, before the development to a precanceraus stage. In spindle-like and nondilation. types, cholecyslect.onn, is absolutely necessary in early adulthood, before age 40.

Background/Purpose: There are various treatment strategies for gastroesophageal varices in children. We studied the therapeutic value of endoscopic variceal clipping (EVC) and ligation (EVL). Methods: Four hundred ninety-nine endoscopic examinations performed between 1991 and 2005 were retrospectively analyzed. F2 and F3 varices with red color signs on follow-up endoscopy were treated with prophylactic EVC. In variceal rupture cases, EVC and EVL were used in combination. Results: Eighty-two prophylactic EVCs were done, and variceal progression was prevented in 89.9%. However, some patients had persistent red color signs and required frequent EVC. Ten emergent procedures were done for variceal rupture, and, in 4 cases, EVL was used to arrest massive variceal bleeding. Five patients developed bleeding during follow-up cause by rupture of gastric fundal varices, which probably had been aggravated by prior treatment for esophageal varices. Conclusions: The control of gastroesophageal varices by routine EVC was satisfactory. However, ruptures during follow-up suggested the importance of controlling gastric fundal varices. Endoscopic variceal ligation is a simple, effective, and safe treatment tool, particularly for ruptured varices. However, it is difficult to treat gastric fundal varices with EVL; this disadvantage of EVIL can be overcome by the concomitant use of EVC. (c) 2006 Elsevier Inc. All rights reserved.

The prognosis for children with malignant solid tumors has improved dramatically in Japan. During the last two decades, various groups have conducted sequential studies of the treatment of children with neuroblastoma, Wilms' tumor, and hepatoblastoma. Most institutes participated in nonrandomized trials designed to evaluate the safety and efficacy of combination chemotherapy, surgery, and radiotherapy in each group study and treated children with these tumors The results are reviewed and areas for future investigation are identified.