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Background: The association of complement with the progression of acute T cell mediated rejection (ATCMR) is not well understood. We investigated the production of complement components and the expression of complement regulatory proteins (Cregs) in acute T-cell mediated rejection using rat and human renal allografts. Methods: We prepared rat allograft and syngeneic graft models of renal transplantation. The expression of Complement components and Cregs was assessed in the rat grafts using quantitative real-time PCR (qRT-PCR) and immunofluorescent staining. We also administered anti-Crry and anti-CD59 antibodies to the rat allograft model. Further, we assessed the relationship between the expression of membrane cofactor protein (MCP) by immunohistochemical staining in human renal grafts and their clinical course. Results: qRT-PCR results showed that the expression of Cregs, CD59 and rodent-specific complement regulator complement receptor 1-related gene/protein-y (Crry), was diminished in the rat allograft model especially on day 5 after transplantation in comparison with the syngeneic model. In contrast, the expression of complement components and receptors: C3, C3a receptor, C5a receptor, Factor B, C9, C1q, was increased, but not the expression of C4 and C5, indicating a possible activation of the alternative pathway. When anti-Crry and anti-CD59 mAbs were administered to the allograft, the survival period for each group was shortened. In the human ATCMR cases, the group with higher MCP expression in the grafts showed improved serum creatinine levels after the ATCMR treatment as well as a better 5-year graft survival rate. Conclusions: We conclude that the expression of Cregs in allografts is connected with ATCMR. Our results suggest that controlling complement activation in renal grafts can be a new strategy for the treatment of ATCMR. [ABSTRACT FROM AUTHOR]

Introduction: Image-defined risk factors (IDRFs) have been propounded for predicting the surgical risks associated with localized neuroblastoma (NB) since 2009. In 2011, a new guideline (NG) for assessing IDRFs was published. According to the NG, the situation in which "the tumor is only in contact with renal vessels," should be considered to be "IDRF-present." Previously, this situation was diagnosed as "IDRF absent." In this study, we evaluated the IDRFs in localized NB patients to clarify the predictive capability of IDRFs for surgical complications, as well as the usefulness of the NG. Materials andMethods: A total of 107 localized patients with NB were included in this study. The enhanced computed tomography and magnetic resonance images from the time of their diagnoses were evaluated by a single radiologist. We also analyzed the association of clinical factors, including the IDRFs (before and after applying the NG), with surgical complications.Results: Of the 107 patients, 33 and 74 patients were diagnosed as IDRF-present (OP group), and IDRF-absent (ON group) before the NG, respectively. According to the NG, there were 76 and 31 patients who were classified as IDRF-present (NP group) and IDRF absent (NN group), respectively. Thus, 43 (40%) patients in the ON group were reassigned to the NP group after the NG. Surgical complications were observed in 17 of 82 patients who underwent surgical resection. Of the patients who underwent secondary operations, surgical complication rates were 55% in the OP group and 44% in the NP group. According to a univariate analysis, non-INSS 1, IDRFs before and after the NG and secondary operations were significantly associated with surgical complications. In a multivariate analysis, non-INSS 1 status and IDRFs after the NG were significantly associated with surgical complications. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We herein report the rare case of a 4-year-5-month-old boy who presented with primary renal neuroblastoma. The patient developed repeated lung and liver metastatic recurrences, but, following a combination of chemotherapy, radiation therapy and aggressive surgical resection, the patient is now in remission. To investigate the pathogenesis of lung metastasis, immunohistochemistry was performed for matrix metalloproteinase-9 and -14 (MMP-9 and MMP-14), molecular markers of invasion, metastasis and angiogenesis in neuroblastoma. In the present case, MMP-9 expression was not observed, but MMP-14 expression was detected in the primary lesion and was more highly expressed in the metastatic lesion compared with the primary one. Given the MMP-14 staining in other cases, expression of MMP-14 may be associated with the aggressiveness of the tumor. This suggests that selected clones with high MMP-14 expression in the primary tumor might metastasize and form MMP-14-rich lesions. [ABSTRACT FROM AUTHOR]

Purpose: Necrotizing enterocolitis (NEC) is a devastating inflammatory disease of preterm infants that may depend on overexpression of toll-like receptor-4 (TLR4) in the immature intestine. Surfactant protein (SP)-D is a member of the collectin family and plays an important role in innate immunity, particularly in the airways. Although SP-D also exists in the intestines, little is known about its function. This study investigated whether SP-D can attenuate the inflammatory response of TLR4-overexpressing embryonal intestinal cells.Methods: All experimental procedures were performed using the human intestinal cell line INT407 originally derived from human embryonal intestines. Platelet-activating factor (PAF), reported to be elevated in NEC patients, was used to induce TLR4 overexpression in the human embryonal intestinal cell line INT407. TLR4 expression was measured using quantitative real-time PCR. Inflammatory responses to PAF (5 µM), the TLR4 agonist lipopolysaccharide (LPS, 100 ng/ml), PAF + LPS, and PAF + LPS following SP-D pretreatment (20 µg/ml) were assessed by enzyme-linked immunosorbent assay (ELISA) of interleukin-8 (IL-8) release (in pg/ml).Results: Expression of TLR4 mRNA (mean ± SD) was upregulated by PAF (369 % ± 28 %, p < 0.001). Stimulation with PAF + LPS resulted in higher IL-8 release (1959.3 ± 52.3) than control (141.2 ± 12.4), LPS (167.3 ± 65.8), or PAF (1527.2 ± 129.4) treatment (p < 0.05). Release in response to PAF + LPS (1590.1 ± 319.3) was attenuated by SP-D pretreatment (1161.6 ± 131.6; p < 0.05).Conclusion: SP-D attenuates LPS-induced IL-8 production in TLR4-overexpressing intestinal cells, suggesting that SP-D may have a protective effect in the development of NEC in preterm infants. [ABSTRACT FROM AUTHOR]

Several questions and answers related to pediatric surgery is presented including indications and timing for laparoscopic pyloromyotomy, similarity between surgical technique and complication rate of laparoscopic pyloromyotomy, and indications for laparoscopic fundoplication.

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. [ABSTRACT FROM AUTHOR]

Background Xenotransplantation is considered to be one of the most attractive strategies for overcoming the worldwide shortage of organs. However, many obstructions need to be overcome before it will achieve clinical use in patients. One such obstacle is the development of an effective immunosuppressive strategy. We previously reported that myeloid-derived suppressor cells (MDSCs), a heterogeneous population of progenitor and immature myeloid cells, suppress xenogenic CTL-mediated cytotoxicity. Because of their heterogeneous nature, MDSC can function via several suppressive mechanisms that disrupt both innate and adaptive immunity. Since macrophages play a pivotal role in the rejection of a xenograft, in this study, we evaluated the suppressive effects of MDSC against macrophage-mediated xenogenic rejection. Materials and methods To evaluate the effect of monocyte-derived MDSCs on xenogenic immune reactions, a CFSE(carboxyfluorescein diacetate, succinimidyl ester)assay was employed to assess cytotoxicity. Results While, in the absence of activation, primed MDSCs had no detectable effect on macrophage-induced cytotoxicity against SEC cells, LPS-activated MDSCs were found to significantly suppress xenogenic cytotoxicity. A CFSE cytotoxicity assay revealed that MDSCs significantly suppressed macrophage-induced cytotoxicity. Furthermore, an indoleamine 2,3 dioxygenase (IDO) inhibitor, 1-methyl tryptophan (1-MT), abolished the MDSC-induced suppression of macrophage-mediated xeno-rejection, indicating that MDSCs may suppress macrophage-mediated cytotoxicity in an IDO-dependent manner. Conclusion These findings indicate that MDSCs have great potential for immunosuppressing macrophage-mediated xeno-rejection. [ABSTRACT FROM AUTHOR]

Background. Treating functional gastrointestinal disorders is extremely difficult. We herein report the effect of the oral administration of Ninjinto (NJT, ginseng decoction), a traditional Japanese Kampo medicine, on chronic intestinal failure. Patients and Methods. Seven patients with chronic intestinal failure treated with NJT were evaluated in this study. The primary diseases included chronic intestinal pseudoobstruction (CIPO: n=4), short bowel syndrome (SBS: n=2), and intestinal atresia n=1. All patients orally received NJT extract granules at a dose of 0.3 g/kg BW per day. The treatment outcomes were then assessed according to the patients’ symptoms and consecutive abdominal X-ray findings. Results. The targeted symptoms were abdominal distension in four patients, diarrhea in three patients, and frequent hospitalization due to infections in two patients. An improvement in the symptoms was observed in six of the seven patients, whereas one patient with SBS did not show any improvement. An improvement in an abdominal roentgenogram was observed in the four patients with remarkably dilated bowel loops due to CIPO. Conclusions. NJT may be effective in controlling functional gastrointestinal disorders associated with chronic intestinal failure. The use of Kampo medicine in the field of pediatric surgery may help to improve the quality of life in children suffering from such conditions. [ABSTRACT FROM AUTHOR]

Background Surgical intestinal disorders, such as necrotizing enterocolitis ( NEC), focal intestinal perforation ( FIP), and meconium-related ileus ( MRI), are serious morbidities in very low-birthweight infants ( VLBWI). The aim of this study was to compare the composite outcomes of death or neurodevelopmental impairment ( NDI) in VLBWI with surgical intestinal disorders and assess independent risk factors for death and NDI at 18 months of corrected age. Methods A retrospective matched-cohort study was conducted at 11 institutes. We included VLBWI who had undergone laparotomy for NEC, FIP, and MRI. Two control subjects were chosen for every surgical patient and matched for gestational age and birthweight to form the comparison group. Death and neurodevelopmental outcome at 18 months of corrected age were evaluated. Results The number of infants in the NEC, FIP, MRI, and control groups was 44, 47, 42, and 261, respectively. In-hospital mortality was higher in infants with NEC and MRI relative to those in the control group ( P < 0.001). The incidence rate for NDI at 18 months of corrected age was higher in infants with MRI relative to those in the control group ( P = 0.021). On logistic regression analysis, low gestational age, male sex, small for gestational age, intraventricular hemorrhage, and MRI were associated with increased risk of death or NDI at 18 months of corrected age. Conclusions NEC and MRI were associated with in-hospital mortality, and MRI was associated with NDI or death at 18 months of corrected age. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) are defined as a small population of cancer cells with the properties of high self-renewal, differentiation, and tumor-initiating functions. Recent studies have demonstrated that aldehyde dehydrogenase 1 (ALDH1) is a marker for CSCs in adult cancers. Although CSCs have been identified in some different types of pediatric solid tumors, there have been no studies regarding the efficacy of ALDH1 as a marker for CSCs. Therefore, in order to elucidate whether ALDH1 can be used as a marker for CSCs of pediatric sarcoma, we examined the characteristics of a population of cells with a high ALDH1 activity (ALDH1high cells) in rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children. We used the human embryonal RMS (eRMS) cell lines RD and KYM-1, and sorted the cells into two subpopulations of ALDH1high cells and cells with a low ALDH1 activity (ALDH1low cells). Consequently, we found that the ALDH1high cells comprised 3.9% and 8.2% of the total cell population, respectively, and showed a higher capacity for self-renewal and tumor formation than the ALDH1low cells. With regard to chemoresistance, the survival rate of the ALDH1high cells was found to be higher than that of the ALDH1low cells following treatment with chemotherapeutic agents for RMS. Furthermore, the ALDH1high cells exhibited a higher degree of pluripotency and gene expression of Sox2, which is one of the stem cell markers. Taken together, the ALDH1high cells possessed characteristics of CSCs, including colony formation, chemoresistance, differentiation and tumor initiation abilities. These results suggest that ALDH1 is a potentially useful marker of CSCs in eRMS. [ABSTRACT FROM AUTHOR]

Background Xenotransplantation is an appealing alternative to human allotransplantation because of a worldwide shortage of organs. One of the obstacles for xenografts is cellular rejection by the innate immune system, comprised of NK cells, monocytes, and macrophages. In this study the inhibitory function of HLA-G1, a MHC Ib molecule, on macrophage-mediated cytotoxicity was examined. Furthermore, this study also evaluates the suppressive effect of cytokine production by macrophages. Methods The expression of inhibitory receptors that interact with HLA-G1, immunoglobulin-like transcript 2 (ILT2), ILT4 and KIR2DL4 (CD158d) on in vitro generated macrophages were examined by flow cytometry. Complementary DNA (cDNA) of HLA-G1, HLA-E and human β2-microglobulin (hβ2m) were prepared and transfected into swine endothelial cells (SECs). The expression of the transgenic genes was evaluated by flow cytometry, and macrophage-mediated SEC cytolysis was assessed using the macrophages. Results In vitro generated macrophages expressed not only ILT2 and ILT4 but CD158d as well. The transgenic HLA-G1 on SECs indicated significant suppression in macrophage-mediated cytotoxicity, which was equivalent to that of transgenic HLA-E. Furthermore, the results on real time PCR and ELISA revealed that transgenic HLA-G1 induces the anti-inflammatory cytokines, such as IL-10 and TGF-β, and suppresses iNOS mRNA expression, indicating that transgenic HLA-G1 has suppressive effects in a broad range of transplant rejection. Conclusion These results indicate that generating HLA-G1 transgenic pigs can protect porcine grafts from macrophage-mediated cytotoxicity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Object: The purpose of this study is to evaluate the outcome of our therapeutic strategy for antenatally diagnosed congenital diaphragmatic hernia (ADCDH). Methods: We treated 61 cases of ADCDH according to our strategy. Prostaglandin E1 was required to be maintained the patency of the ductus arteriosus (PDA) in 39 cases (Group I) while it was not administered in 22 cases (Group II). Left ventricular end-diastolic dimension (LVDD) and Tei index were measured with echocardiography on days 0, 2, and 7 after birth. Radical surgery was performed on all cases by day 2. Results: On day 0, Group I showed smaller LVDD and Tei index than those in Group II. Between day 0 and day 2, these parameters increased significantly in Group I, but not in Group II. On day 7, no significant difference in these parameters was observed between the two groups. Five patients died of cardiac and respiratory failure, resulting in a survival rate of 92 %. Conclusion: Our therapeutic strategy improves the clinical outcome of ADCDH. This can be attributed to two factors: earlier surgery resulting in improved LV function. The latter attenuates pulmonary hypertension and maintains PDA with a consequent decrease in right ventricular afterload to compensate for the low cardiac output resulting from PDA. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to clarify the outcome of patients with cardiovascular malformation ( CVM) among those with congenital diaphragmatic hernia ( CDH) who are indicated for the Fontan procedure. Methods The subjects included 76 CDH patients with CVM recruited from a national survey of 614 CDH patients. The outcomes were evaluated between two groups divided according to indication for the Fontan procedure. Patients with functional univentricular disease were considered to be candidates for the Fontan procedure. Results Sixteen (21.1%) of the 76 patients were candidates for the Fontan procedure, accounting for 2.6% of all 614 patients with CDH. None of these patients, however, underwent the Fontan procedure. Among the 16 patients, the absence of obstruction of the left ventricular outflow tract ( LVOTO) was significantly associated with better 90 day survival (71.4%, 5/7, for those without LVOTO vs 0.0%, 0/9, for those with LVOTO, P = 0.0007). After excluding 22 patients with chromosomal and/or genetic abnormalities or syndromes, the 90 day survival rate was significantly better in neonates without than with indication for the Fontan procedure (62.5%, 25/40 vs 28.6%, 4/14, P = 0.0271). Conclusions Patients with indications for the Fontan procedure are rare, and the outcome of patients with LVOTO among those with CDH is especially poor. [ABSTRACT FROM AUTHOR]

In a series of studies, using an identical rat intestinal transplantation model, we evaluated the effects of several drugs. FK-506 caused a significant attenuation in the proliferation of allogeneic CD4+ T cells and IFN-γ secreting effector functions. FYT720 resulted in a marked reduction in the numbers of lymphocytes, associated with a reduction of T cell recruitment, in grafts. An anti-MAdCAM antibody was next reported to significantly down-regulate CD4+ T cell infiltration in intestinal grafts by blocking the adhesion molecule, and could be useful as an induction therapy. Concerning TAK-779, this CCR5 and CXCR3 antagonist diminished the number of graft-infiltrating cells by suppressing the expression of their receptors in the graft. As a result, it reduced the total number of recipient T cells involved in graft rejection. As the next step, we focused on the participation of monocytes/ macrophages in this field. PQA-18 has been the focus of a novel immunosuppressant that attenuates not only the production of various cytokines, such as IL-2 & TNF-α, on T cells, but the differentiation of macrophages by inhibiting PAK2 as well. In this report, we summarize our previous studies not only regarding the above drugs, but on an anti-complement drug and a JAK inhibitor as well. • FTY720 resulted in a significant reduction in lymphocyte count in grafts. • Anti-MAdCAM-1 treatment for the graft down-regulated the infiltration of CD4+ cells. • TAK-779 diminished the number of graft-infiltrating cells. • PQA-18 suppresses not only MLR but macrophage differentiation/polarization as well. [ABSTRACT FROM AUTHOR]

We report a case of successful magnetic compression anastomosis ( MCA) for obstructed cyst-jejunostomy in a young woman who had undergone surgery for type 1 biliary atresia ( BA) on day 78 of life. A 16-year-old girl was admitted with obstructive jaundice. Jaundice resolved with percutaneous trans-hepatic cholangiodrainage ( PTCD) but contrast medium injected from the PTCD tube did not flow through the anastomosis. Magnets were placed on each side of the anastomosis, in the cyst and the jejunum, to compress the partition. On postoperative day ( POD) 6, the anastomosis was recanalized and the PTCD tube placed trans-anastomotically until POD 245. The patient remained free from jaundice after removal of the PTCD tube. MCA can be a useful and less invasive procedure for treating biliary tract anastomotic obstruction in patients with BA. [ABSTRACT FROM AUTHOR]

Background Congenital diaphragmatic hernia is associated with cardiovascular malformation. Many prognostic factors have been identified for isolated congenital diaphragmatic hernia; however, reports of concurrent congenital diaphragmatic hernia and cardiovascular malformation in infants are limited. This study evaluated congenital diaphragmatic hernia associated with cardiovascular malformation in infants. Factors associated with prognosis for patients were also identified. Methods This retrospective cohort study was based on a Japanese survey of congenital diaphragmatic hernia patients between 2006 and 2010. Frequency and outcome of cardiovascular malformation among infants with congenital diaphragmatic hernia were examined. Severity of congenital diaphragmatic hernia and cardiovascular malformation were compared as predictors of mortality and morbidity. Results Cardiovascular malformation was identified in 76 (12.3%) of 614 infants with congenital diaphragmatic hernia. Mild cardiovascular malformation was detected in 19 (33.9%) and severe cardiovascular malformation in 37 (66.1%). Their overall survival rate at discharge was 46.4%, and the survival rate without morbidity was 23.2%. Mortality and morbidity at discharge were more strongly associated with severity of cardiovascular malformation (adjusted OR 7.69, 95% CI 1.96-30.27; adjusted OR 7.93, 95% CI 1.76−35.79, respectively) than with severity of congenital diaphragmatic hernia. Conclusions The prognosis for infants with both congenital diaphragmatic hernia and cardiovascular malformation remains poor. Severity of cardiovascular malformation is a more important predictive factor for mortality and morbidity than severity of congenital diaphragmatic hernia. [ABSTRACT FROM AUTHOR]

Background During the last decade, new supportive modalities and new therapeutic strategies to treat congenital diaphragmatic hernia ( CDH) have been introduced. In Japan, the large number of hospitals prevents centralizing infants with CDH in tertiary centers. The aim of this study was to evaluate the correlations between the number of CDH patients, survival rates, and the current strategies employed to treat CDH at the individual hospitals. Methods Eighty-three hospitals with 674 CDH cases were analyzed using questionnaires. We classified the hospitals into three groups according to the number of CDH patients treated: Group 1 ( G1; more than 21 patients), Group 2 ( G2; 11-20 patients), and Group 3 ( G3; fewer than 10 patients). Results The median number of CDH patients in G1, G2, and G3 were 28, 14, and 4, respectively. The overall survival rate was 74.5%. When only the isolated CDH cases with a prenatal diagnosis were included, the overall survival rate was 79.3%. The survival rate of isolated CDH cases with a prenatal diagnosis was significantly higher in G1 than that in G2 or G3 (87.2% vs 75.2% vs 74.3%; P < 0.001). There were no differences in perinatal therapeutic strategies among the three groups. Conclusions We concluded that it might therefore be important to centralize infants with CDH, especially those with isolated CDH with a prenatal diagnosis, to tertiary centers in Japan in order to improve the survival rates. [ABSTRACT FROM AUTHOR]

Background: A nationwide survey on neonatal surgery conducted by the Japanese Society of Pediatric Surgeons has demonstrated that the mortality of neonatal intestinal perforation has risen over the past 15 years. The incidence of intestinal perforation in extremely low-birthweight (ELBW) neonates has been increasing as more ELBW neonates survive and as the live-birth rate of ELBW has increased. In contrast to necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP), the pathogenesis of meconium-related ileus, defined as functional bowel obstruction characterized by delayed meconium excretion and microcolon, remains unclarified. Methods: The histology of 13 ELBW neonates with intestinal perforation secondary to meconium-related ileus was reviewed, and the radiology of 33 cases of meconium-related ileus diagnosed on contrast enema was reviewed. Specimens obtained from 16 ELBW neonates without gastrointestinal disease served as age-matched controls for histological assessment. Results: The size of the ganglion cell nucleus in meconium-related ileus and in control subjects was 47.3 ± 22.0 µm2 and 37.8 ± 11.6 µm2, respectively, which was not significantly different. In all cases of meconium-related ileus, contrast enema demonstrated a microcolon or small-sized colon, with a gradual caliber change in the ileum and filling defects due to meconium in the ileum or colon, showing not-identical locations of caliber changes and filling defects. Conclusion: Morphological immaturity of ganglia was not suggested to be the pathogenesis of meconium-related ileus. Impaction of inspissated meconium is not the cause of obstruction, but the result of excessive water absorption in the hypoperistaltic bowel before birth, although the underlying mechanism responsible for the fetal hypoperistalsis remains unclear. [ABSTRACT FROM AUTHOR]

Rikkunshito (TJ-43), a herbal medicine consisting of eight herbs, is used to treat chronic dyspepsia. Studies have shown that TJ-43 improves human gastric emptying. This study investigated the effects of TJ-43 on the clinical symptoms and esophageal acid exposure in children with symptomatic gastroesophageal reflux (GER). Eight children, aged from 2 months to 15 years (median age 4 years), were studied. Six of them had neurological impairment. TJ-43 (0.3 g/kg/day) was given orally or via nasogastric tubes in three divided doses before meals for 7 days. Their symptoms were frequent emesis in four, nausea in two, and hematemesis and stridor in one each. Twenty-four-hour esophageal pH monitoring was conducted using multichannel pH electrodes located at the distal esophagus (P1) and 10 cm proximal to P1 (P2). The clinical symptoms and esophageal pH were compared before and after TJ-43 therapy for 1 week. The frequency of emesis decreased in three patients. Other symptoms, including nausea, hematemesis, and stridor, were relieved in the remaining patients. Measured at the distal pH electrode, the percentage time of esophageal pH < 4.0 and the mean duration of reflux decreased significantly (P < 0.05). However, the number of acid reflux per hour did not change significantly, and no pH parameters measured at the proximal electrode differed significantly. The short-term administration of TJ-43 relieved symptoms and reduced the distal esophageal acid exposure through improved esophageal acid clearance. [ABSTRACT FROM AUTHOR]

We report a case of a two-yr-old boy with hepatoblastoma resectable only by total hepatectomy including the vena cava. Successful LTx was performed with a living donor segment without vena cava reconstruction. The tumor was located in the bilateral lobe, surrounding the IVC. In spite of the high-dose chemotherapy, the tumor did not become resectable. LTx was performed using left lateral segment after removal of the IVC combined with total hepatectomy. Because the collaterals were well developed, the patient tolerated the procedure well. The serum AFP level decreased from 186 699 to 8 ng/mL in 11 months after LTx without local recurrence or distant metastasis. [ABSTRACT FROM AUTHOR]

Background/purpose: The authors compared the clinical outcome between laparoscopically assisted endorectal pull-through (EPT) with an extraanal approach (EA) and conventional abdominal approach (AB) in Hirschsprung's disease (HD), and found that the former approach was less invasive and can provide a better clinical outcome. Recently, they introduced transanal approach (TA) without laparoscopical assistance and compared the clinical outcomes of these three approaches.Methods: In the period between 1990 and 1997, 20 cases of HD underwent EPT with AB (Group A), between 1998 and 2001, 21 cases underwent EPT with EA (Group E), and between 2004 and 2005, eight cases underwent EPT with TA (Group T). There was no difference in age and weight distribution among three groups. Clinical outcome was assessed 3 years after surgery.Results: The operation time in Groups A, E and T was comparable (4.9 +/- 0.8, 5.2 +/- 0.8 and 4.3 +/- 0.8 h), whereas blood loss (98 +/- 52, 36 +/- 30 and 36 +/- 30 ml) and the incidence of postoperative complications requiring surgical intervention (25, 0 and 0%) was significantly lower in Groups E and T compared with Group A. The incidence of postoperative enteritis (25, 29 and 13%) was lower in Group T compared with Groups A and E. In Group E, two cases had persistent constipation, which required anorectal myotomy. Voluntary defecation (>once/2 days) was comparable among the groups (70, 87 and 88%). Soiling (small amount of involuntary passage of stool) was significantly less frequent in Groups E and T (45, 14 and 0%).Conclusion: EPT with perineal approaches is less invasive and can provide a better clinical outcome than EPT with AB in terms of postoperative soiling. Compared with EA and TA, EA tended to develop stagnant enteritis or residual constipation. [ABSTRACT FROM AUTHOR]

PQA-18 (Prenylated quinolinecarboxylic acid-18) has been reported to be a novel immunosuppressant that attenuates the production of various cytokines, and the differentiation of macrophages by inhibiting PAK2. In this study, we investigated the function of this drug mainly on macrophages using a rat small intestinal transplant model. Male Dark Agouti (DA) and Lewis rats (LEW), 7–9 weeks of age, were used as donor and recipient, respectively. Approximately 15 cm intestinal grafts were heterotopically transplanted to the recipient rats. The recipient rat was treated with PQA-18 (4 mg/kg/day) by intraperitoneal injection (ip) from postoperative day 1 for 2 weeks. The in vivo effects of this drug were evaluated based on changes in body weight, and the population of each type of blood cell. Mixed lymphocyte reaction (MLR) was also assessed, using the T cells from intestinal mesenteric lymph nodes (MLN) of the grafts on POD6. Total cells from MLN and graft Payer's patch (PP) were next collected on POD6, and the number of infiltrated macrophages was determined. While the survival time was 7.0 ± 0.77 days for the control group (n = 9), that for the PQA-18 group was 10.7 ± 1.26 days (n = 10) (p <.001). Histological examinations showed a relatively clear difference in the grafts for both groups. In addition, the MLR response was significantly lower in recipients treated with PQA-18, suggesting PQA-18 well suppressed the T cells. Moreover, while a significant increase of both MHC class II and CD11b/c positive cells, estimated as differentiated/polarized macrophages, in MLN & PP was observed in the control group, PQA-18-administration significantly suppressed the differentiation of macrophages in the MLN & PP. PQA-18 significantly prolonged the survival of the rats with intestinal grafts, and also suppressed the infiltration of lymphocytes, and macrophages to the grafts. • A novel immunosuppressant that attenuates the differentiation of macrophages by inhibiting PAK2. • A significant improvement of rat intestinal graft survival by PQA-18. • PQA-18 has no observable nephrotoxicity. [ABSTRACT FROM AUTHOR]

The authors present a neonatal case of allergic colitis, which manifested the difficulty of spontaneous defecation and irregular narrowing of distal rectum in contrast enema. Rectal suction biopsy showed positive acetylcholinesterase activity. These clinical, radiological and histological findings were indistinguishable from Hirschsprung's disease. Gastrointestinal symptoms were improved by the cessation of cow's milk formula. The present findings may impact on the less recognizable gastrointestinal manifestation of allergic colitis. [ABSTRACT FROM AUTHOR]

In the original publication, the fifth author name was erroneously published as 'Patmika Jiaravuthiasan'. The correct author name should read as, 'Patmika Jiaravuthisan'. The original article was corrected. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to investigate the natural history and associated predictors of musculoskeletal deformities in congenital diaphragmatic hernia (CDH) survivors. Methods A multicenter retrospective survey was conducted among CDH patients between January 2006 and December 2010 in Japan, and a follow-up survey was performed between September 2013 and October 2013. One hundred and eighty-two (79.8%) of the 228 patients were alive. An orthopedic survey of 159 survivors without severe coexisting congenital anomalies was subsequently carried out, and the rates of pectus excavatum (PE), scoliosis and chest asymmetry were evaluated. Results Scoliosis, PE and chest asymmetry were found in 20 (12.6%), 19 (11.9%) and 12 (7.5%) patients, respectively. In total, 44 patients (27.7%) developed orthopedic abnormalities. Reduction in the oxygenation index within 24 h after birth ( P = 0.044), large diaphragmatic defects ( P = 0.047) and patch repair ( P = 0.014) were predictive for scoliosis. In addition, Apgar score at 5 min was significantly lower in the patients who developed PE ( P = 0.034); and stomach herniation ( P = 0.004) and liver herniation ( P = 0.013) at prenatal diagnosis and large diaphragmatic defects ( P = 0.036) were predictive of chest asymmetry. Conclusions Approximately one-quarter of the survivors developed musculoskeletal abnormalities in the present survey of CDH patients. These data suggest that each musculoskeletal abnormality has its own specific predictors. [ABSTRACT FROM AUTHOR]

We report an exacerbation of congenital oesophageal stenosis caused by accidental ingestion of tape that had been placed on a postoperative scar of the right thumb. Treatment by tape fixation in infants with gastrointestinal disease should be carefully monitored. [ABSTRACT FROM AUTHOR]

Aim : To show the clinical, physiological and histological characteristics in GER with cow's milk intolerance Methods : Nine children with GERD tess than 6 years old who had at least recurrent vomiting as ther symptom were studied. Endoscopic and histologic diagnosis, gastric scintigraphy and 24 h-pH monitoring, blood tests were done. Results : All children had cow's milk intolerance clinically. Acid reflux in esophagus and delayed gastric emptying were shown. Duodenitis with histamine and substance P and mild esophagitis were present in these children. Conclusions : Duodenitis with chemical mediators secondary to cow's milk intolerance may play an important role for the cause of GER in children. [ABSTRACT FROM AUTHOR]