Ultrasound for the evaluation of the urethra in pediatric patients.

Urethral lesions in pediatric patients can be visualized using ultrasonography. Therefore, sonographers and physicians should be familiar with the technique.

Recovery of bowel function after transperitoneal or retroperitoneal laparoscopic pyeloplasty. A multi-center study.

AIM: To document the recovery of bowel function (BF) in children after transperitoneal (TP) or retroperitoneal (RP) laparoscopic pyeloplasty. METHODS: Data were obtained retrospectively from four centers between 2008 and 2019 for TP (n = 51) and RP (n = 58). Each surgeon chose which technique to perform. RESULTS: Subject demographics were not significantly different. Differences in operative times were not significant (RP: 241 min versus TP: 225 min). Mean duration/requirement for postoperative epidural/intravenous analgesia were not significantly different (TP: 1.4 days versus RP: 1.3 days) and (TP: 66.7% versus RP: 67.2%), respectively. Postoperative nasogastric (NG) intubation was more common in RP (TP: 19.6% versus RP: 44.8%; p < .05). NG aspiration (TP: 0.15 mL/kg/hr versus RP: 0.16 mL/kg/hr), nausea (TP: 31.4% versus RP: 17.2%), and vomiting (TP: 19.6% versus RP: 15.5%) were not significantly different. There were no perioperative complications (including ileus). Abdominal distention was problematic in one case per group (TP: 2.0% versus RP: 1.7%). Times for oral liquid (TP: 0.69 day versus RP: 0.83 day), solid food (TP: 0.88 day versus RP 1.07 days), and the first bowel movement (TP: 2.86 days versus RP: 2.79 days), were not significantly different. CONCLUSIONS: BF recovery would appear to be consistent, independent of technique.

Therapeutic potential of mature adipocyte-derived dedifferentiated fat cells for inflammatory bowel disease.

PURPOSE: Our previous studies demonstrated that mature adipocyte-derived dedifferentiated fat (DFAT) cells possess similar multipotency as mesenchymal stem cells. Here, we examined the immunoregulatory potential of DFAT cells in vitro and the therapeutic effect of DFAT cell transplantation in a mouse inflammatory bowel disease (IBD) model. METHODS: The effect of DFAT cell co-culture on T cell proliferation and expression of immunosuppression-related genes in DFAT cells were evaluated. To create IBD, CD4+CD45RBhigh T cells were intraperitoneally injected into SCID mice. One week later, DFAT cells (1 × 105, DFAT group) or saline (Control group) were intraperitoneally injected. Subsequently bodyweight was measured every week and IBD clinical and histological scores were evaluated at 5 weeks after T cell administration. RESULTS: The T cell proliferation was inhibited by co-cultured DFAT cells in a cell density-dependent manner. Gene expression of TRAIL, IDO1, and NOS2 in DFAT cells was upregulated by TNFα stimulation. DFAT group improved IBD-associated weight loss, IBD clinical and histological scores compared to Control group. CONCLUSION: DFAT cells possess immunoregulatory potential and the cell transplantation promoted recovery from colon damage and improved clinical symptoms in the IBD model. DFAT cells could play an important role in the treatment of IBD.

Obliterative cholangiopathy in acquired cystic biliary atresia type III after cyst perforation: a case report.

BACKGROUND: In biliary atresia, the disease process of obliterative cholangiopathy may begin in the perinatal period; however, no chronological evidence exists on how the cholangiopathy progresses to biliary obliteration. This is the first acquired case with the final diagnosis of type III cystic biliary atresia with an extrahepatic biliary cyst which showed the progression of obliterative cholangiopathy in chronological order after birth. CASE PRESENTATION: An 81-day-old girl presented with acute abdominal distress due to bilious peritonitis caused by biliary cyst perforation, for which she underwent emergency biliary drainage. Postoperative images showed a dilated common bile duct and hepatic ducts bilaterally, with flow of the contrast medium to the duodenum through the dilated common bile duct. Biochemistry of the bile collected during and after the operation revealed elevated levels of pancreatic enzymes in the bile from the gallbladder. The patient was diagnosed as having a congenital choledochal cyst and underwent laparotomy at 120 days of age which revealed that she had pancreaticobiliary maljunction. The biliary cyst was resected at the narrow portion just above the junction with the main pancreatic duct. During dissection up to the hepatic hilum, we found that the hilar hepatic ducts were bilaterally replaced by fibrous tissue and were obstructed, leading to a diagnosis of type III a1, µ biliary atresia. The fibrous tissue was excised, and hepatic portoenterostomy was performed according to the Kasai procedure. The patient's postoperative course was uneventful and the jaundice resolved within 1 month. She has had normal liver function tests with no episode of cholangitis for 3 years after discharge. CONCLUSIONS: We demonstrated the process of acquired type III biliary atresia in a patient with cystic biliary atresia and biliary cyst perforation. To the best of our knowledge, this is the first case of acquired cystic biliary atresia showing chronological progression of the course of obliterative cholangiopathy, providing a better understanding of the development of type III biliary atresia as an acquired disease.

Timing and outcome of stoma closure in very low birth weight infants with surgical intestinal disorders.

PURPOSE: Very low birth weight infants (VLBWIs) are at risk of surgical intestinal disorders including necrotizing enterocolitis (NEC), focal intestinal perforation (FIP), and meconium-related ileus (MRI). We conducted this study to verify whether the timing of stoma closure and that of enteral nutrition establishment after stoma closure in VLBWIs differ among the most common disorders. METHODS: A retrospective multicenter study was conducted at 11 institutes. We reviewed the timing of stoma closure and enteral nutrition establishment in VLBWIs who underwent stoma creation for intestinal disorders. RESULTS: We reviewed the medical records of 73 infants: 21 with NEC, 24 with FIP, and 25 with MRI. The postnatal age at stoma closure was 107 (28-359) days for NEC, 97 (25-302) days for FIP, and 101 (15-264) days for MRI (p = 0.793), and the postnatal age at establishment of enteral nutrition was 129 (42-381) days for NEC, 117 (41-325) days for FIP, and 128 (25-308) days for MRI (p = 0.855). The body weights at stoma closure were 1768 (620-3869) g for NEC, 1669 (1100-3040) g for FIP, and 1632 (940-3776) g (p = 0.614) for MRI. There were no significant differences among the three groups. CONCLUSIONS: The present study revealed that the time and body weights at stoma closure and the postoperative restoration of bowel function in VLBWIs did not differ among the three diseases.

Risk factors for surgical intestinal disorders in VLBW infants: Case-control study.

BACKGROUND: Very low-birthweight (VLBW) infants (VLBWI) are at increased risk for surgical intestinal disorders including necrotizing enterocolitis (NEC), focal intestinal perforation (FIP) and meconium-related ileus (MRI). The aim of this study was to identify disease-specific risk factors for surgical intestinal disorders in VLBWI. METHODS: A retrospective multicenter case-control study was conducted at 11 institutes. We reviewed VLBWI who underwent laparotomy for intestinal disorders including perforation and intractable bowel obstruction. The surgical disorders were classified into four categories (NEC, FIP, MRI, others) based on the macroscopic findings at operation. In order to identify risk factors, two matched controls for each subject were chosen based on gestational age and birthweight. OR and 95%CI were calculated using a conditional logistic regression model and a multivariate model. RESULTS: A total of 150 cases (NEC, n = 44; FIP, n = 47; MRI, n = 42; others, n = 17) and 293 controls were identified. The cases and controls were similar in terms of gestational age and birthweight (cases/controls, 26.7 ± 2.5/26.5 ± 2.6 weeks; 790 ± 256/795 ± 257 g). On multivariate modeling, disease-specific risk factors were as follows: female (OR, 0.23; 95%CI: 0.06-0.89), respiratory distress syndrome (OR, 35.7; 95%CI: 2.48-514) and patent ductus arteriosus (OR, 10.9; 95%CI: 1.51-79.3) for NEC; outborn delivery (OR, 5.47; 95%CI: 1.48-20.2) for FIP; and twin pregnancy (OR, 4.25; 95%CI: 1.06-17.1), PROM (OR, 6.85; 95%CI: 1.33-35.4) and maternal steroid (OR, 0.23; 95%CI: 0.07-0.79) for MRI. CONCLUSIONS: Different risk factors were identified for NEC, FIP and MRI, suggesting that each disease has a different etiology, and that different strategies are required to prevent these diseases.

Outcome in VLBW infants with surgical intestinal disorder at 18 months of corrected age.

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.

Evaluation of the efficacy of incision and drainage versus hainosankyuto treatment for perianal abscess in infants: a multicenter study.

PURPOSE: We retrospectively compared the short-term outcomes between incision and drainage (ID) and hainosankyuto (TJ-122, Tsumura & Co, Tokyo, Japan) treatment for perianal abscess (PA) in infants. METHODS: We retrospectively examined 48 consecutive patients (median age 129 days; range 19-330 days) who presented with PA over a 3 year period. Group 1 comprised 26 patients who were treated with ID at presentation, and Group 2 comprised 22 patients who were treated with oral TJ-122 at presentation; oral treatment was continued until the disappearance of purulent discharge and resolution of induration at the abscess site. RESULTS: PAs were identified in all 48 patients at presentation. The median duration of follow-up was 26 months (range 13-40 months). At presentation, there were no differences in the gender, age, birth weight, duration of symptoms, skin erosion or prevalence of diarrhea between the two groups. Purulent discharge resolved within a median period of 26 days (range 7-42 days) in Group 2, but persisted for 40 days (range 4-196 days) in Group 1. The induration resolved within a median period of 39 days (range 7-91 days) in Group 2, but persisted for 70 days (range 4-308 days) in Group 1 (p = 0.04). CONCLUSIONS: TJ-122 treatment was more beneficial than ID in treating PA in infants.

Identification of aberrant methylation regions in neuroblastoma by screening of tissue-specific differentially methylated regions.

BACKGROUND: The identification of tissue-specific differentially methylated regions (tDMRs) is key to our understanding of mammalian development. Research has indicated that tDMRs are aberrantly methylated in cancer and may affect the oncogenic process. PROCEDURE: We used the MassARRAY EpiTYPER system to determine the quantitative methylation levels of seven neuroblastomas (NBs) and two control adrenal medullas at 12 conserved tDMRs. A second sample set of 19 NBs was also analyzed. Statistical analysis was carried out to determine the relationship of the quantitative methylation levels to other prognostic factors in these sample sets. RESULTS: Screening of 12 tDMRs revealed 2 genomic regions (SLC16A5 and ZNF206) with frequent aberrant methylation patterns in NB. The methylation levels of SLC16A5 and ZNF206 were low compared to the control adrenal medullas. The SLC16A5 methylation level (cut-off point, 13.25%) was associated with age at diagnosis, disease stage, and Shimada classification but not with MYCN amplification. The ZNF206 methylation level (cut-off point, 68.80%) was associated with all of the prognostic factors analyzed. Although the methylation levels at these regions did not reach statistical significance in their association with prognosis in mono-variant analysis, patients with both hypomethylation of SLC16A5 and hypermethylation of ZNF206 had a significantly prolonged event-free survival, when these two variables were analyzed together. CONCLUSIONS: We demonstrated that two tDMRs frequently displayed altered methylation patterns in the NB genome, suggesting their distinct involvement in NB development/differentiation. The combined analysis of these two regions could serve as a diagnostic biomarker for poor clinical outcome.

[Clinical features of solid malignant tumors in childhood].

The pathogenesis of pediatric malignant tumors is associated with congenital abnormalities. Oncogenes and antioncogenes are identified in some of these cases. Neuroblastoma arises from the adrenal medulla and sympathetic ganglia. Most neuroblastomas produce catecholamine. Urinary vanillylmandelic acid(VMA)and homovanillic acid(HVA), metabolites of catecholamine, are sensitive tumor markers. Risk stratification according to tumor stage and a combination of prognostic factors helps determine the appropriate therapeutic strategy in clinical settings. Nephroblastoma(Wilms tumor)is the most common pediatric renal tumor and is often accompanied by congenital anomalies. Surgical resection of the tumor and the involved kidney is the initial treatment recommendation in the US and Japan. Consecutive chemotherapy and radiotherapy are administered after surgical staging and a definite histopathological diagnosis. Prognosis is relatively good for most nephroblastoma cases with a favorable histology. In addition to nephroblastoma, clear cell sarcoma of the kidney, characterized by a tendency to metastasize to the bone, is a renal tumor with poor prognosis. Rhabdoid tumor of the kidney is another tumor type; however, its pathogenesis is still unknown and it is associated with extremely poor prognosis because of the lack of effective therapeutic measures. Hepatoblastoma is the most common malignant liver tumor. The serum alpha-fetoprotein level is the most effective tumor marker. Complete surgical resection of the involved liver lobe is the definitive approach for cure. Preoperative chemotherapy increases the possibility of complete surgical resection. High-risk patients have a poor prognosis.

Point-of-Care Ultrasound for Mimicker Lesions of Incarcerated Inguinal Hernia.

Inguinal hernia is the most common surgical disease in pediatric patients, and urgent intervention such as manual reduction is needed for incarcerated inguinal hernia. Torsion of undescended testes, inguinal herniated ovarian torsion, and purulent lymphadenitis are mimickers of this condition. If these mimicker lesions are misdiagnosed as incarcerated inguinal hernia, manual reduction usually fails, and edematous and erythematous changes may occur in these mimicker lesions due to manual reduction. For physicians in the emergency department, prompt decisions and familiarity with the sonographic appearance of different contents within an inguinal hernia are important to accurately diagnose these mimickers. In this case series, we present sonographic images of a typical case of incarcerated inguinal hernia (an 11-month-old male with right incarcerated inguinal hernia) and three cases of mimicker lesions (a 7-month-old female with herniated ovarian torsion, a 7-year-old boy with undescended testicular torsion, and a 2-month-old male with purulent lymphadenitis). The incidence of incarcerated inguinal hernia is reported to be higher in males (80%), on the right side (60%), and in infants and toddlers. This information is important for diagnosing mimicker lesions. In addition, to prevent manual reduction in mimicker diseases, point-of-care ultrasound before manual reduction in suspected cases of incarcerated inguinal hernia is important.

Prediction of testicular atrophy based on sonographic findings immediately after successful manual detorsion.

Purpose: To investigate and determine the sonographic findings obtained from manually distorted testes to predict testicular atrophy following manual detorsion. Materials and methods: Twenty-two patients who had been diagnosed with testicular torsion and undergone manual detorsion were included. These patients were classified according to the presence or absence of testicular atrophy. The duration of symptoms, presence or absence of hyperperfusion within the entire affected testis, and echogenicity (homogeneous or heterogeneous) within the affected testis were compared using the Mann-Whitney U-test or Fisher's exact test, as appropriate. Results: Testicular atrophy was detected in seven patients. There was a significant difference in the frequency of hyperperfusion within the entire affected testis (with atrophy [present/absent] vs. without atrophy [present/absent] = 0/7 vs. 8/7, P = 0.023) between patients with and without testicular atrophy. No significant differences in the duration of symptoms (with atrophy vs. without atrophy = 7 ± 3.3 h vs. 4.7 ± 3.6 h, P = 0.075) or frequency of echogenicity within the testis (with atrophy [heterogeneous/homogeneous] vs. without atrophy [heterogeneous/homogeneous] = 2/5 vs. 2/13, P = 0.565) were observed between the groups. Conclusions: This small cohort study suggests that the presence of hyperperfusion within the entire affected testis immediately after successful manual detorsion is useful in predicting the avoidance of testicular atrophy.

Quality control of photosystem II: FtsH hexamers are localized near photosystem II at grana for the swift repair of damage.

The reaction center-binding D1 protein of Photosystem II is oxidatively damaged by excessive visible light or moderate heat stress. The metalloprotease FtsH has been suggested as responsible for the degradation of the D1 protein. We have analyzed the distribution and subunit structures of FtsH in spinach thylakoids and various membrane fractions derived from the thylakoids using clear native polyacrylamide gel electrophoresis and Western blot analysis. FtsH was found not only in the stroma thylakoids but also in the Photosystem II-enriched grana membranes. Monomeric, dimeric, and hexameric FtsH proteases were present as major subunit structures in thylakoids, whereas only hexameric FtsH proteases were detected in Triton X-100-solubilized Photosystem II membranes. Importantly, among the membrane fractions examined, hexameric FtsH proteases were most abundant in the Photosystem II membranes. In accordance with this finding, D1 degradation took place in the Photosystem II membranes under light stress. Sucrose density gradient centrifugation analysis of thylakoids and the Photosystem II membranes solubilized with n-dodecyl-ß-d-maltoside and a chemical cross-linking study of thylakoids showed localization of FtsH near the Photosystem II light-harvesting chlorophyll-protein supercomplexes in the grana. These results suggest that part of the FtsH hexamers are juxtapositioned to PSII complexes in the grana in darkness, carrying out immediate degradation of the photodamaged D1 protein under light stress.

The clinical course in pediatric solid tumor patients with focal nodular hyperplasia of the liver.

BACKGROUND: Focal nodular hyperplasia (FNH) of the liver is a rare benign lesion that may be related to the vascular and hepatic damage induced by completion of tumor therapy and a reaction to localized vascular abnormality. The aim of this study was to analyze the clinical course in pediatric solid tumor patients with FNH. METHODS: We analyzed thirty-two patients with pediatric solid tumors who received multiagent chemotherapy (15 advanced neuroblastomas, 7 hepatoblastomas, 5 rhabdomyosarcomas, 2 nephroblastomas, 1 rhabdoid tumor of the kidney, 1 clear cell sarcoma of the kidney and 1 pancreatoblastoma). All of them had been previously treated at our hospital, and have been alive for over 3 years without recurrence. RESULTS: FNH lesions were discovered in three (9.4%) of 32 patients, and were neuroblastoma (NB) stage 4. All 3 patients received induction chemotherapy and high-dose alkylating agents, and developed grade 3 (National Cancer Institute Common Toxicity Criteria; NCI-CTC) liver dysfunction during completion of tumor therapy without veno-occlusive disease. Two of the 3 patients received the same induction chemotherapy and high doses of alkylating agents with total body irradiation for cytoreductive agents prior to peripheral blood cell transplantation. FNH lesions in both female patients who received estrogen replacement therapy after completion of tumor therapy have expanded and are increasing. CONCLUSION: FNH appears to be a late complication of iatrogenic disease in NB stage 4 patients. The therapeutic agents for NB stage 4 and estrogen replacement therapy should be considered as risk factors for the development of FNH.

Therapeutic strategies of meconium obstruction of the small bowel in very-low-birthweight neonates.

BACKGROUND: Meconium obstruction without cystic fibrosis in low-birthweight neonates is a distinct clinical entity. We aimed to determine what therapeutic strategies work best in very-low-birthweight neonates with meconium obstruction of the small bowel under varied clinical conditions caused by the associated diseases of prematurity. METHODS: Medical records of very-low-birthweight neonates with meconium obstruction of the small bowel treated from 1998 to 2008 were retrospectively reviewed. Pre- and postnatal data, treatments, and clinical outcomes were assessed. RESULTS: Nine patients with perinatal complications were identified. Mean gestational age and birthweight were 26.9 weeks and 863 g, respectively. Abdominal distension developed from 1 to 7 days of life. Five patients were initially treated with Gastrografin enema, three of whom had successful outcomes. Two hemodynamically unstable patients failed to respond to Gastrografin treatment; they ultimately died of sepsis. The remaining four without Gastrografin treatment underwent enterostomy to resolve the obstructions with good results. CONCLUSIONS: Gastrografin and surgical treatments should be appropriately selected based on the underlying pathologies of meconium obstruction of the small bowel. Therapeutic Gastrografin enema is effective, safe and repeatable; however, it is not recommended for hemodynamically unstable patients. Surgical intervention is reserved for those who develop rapid abdominal distension that risks perforation.

Effect of combined treatment with FK506, FTY720, and ex vivo graft irradiation in rat small bowel transplantation: expression of mucosal addressin cell adhesion molecule-1.

We studied the effect of the combined treatment with FK506, FTY720, and ex vivo graft irradiation. Five groups of SBT animals were studied on days 3, 5, and 7 after operation (untreated, FK506, FTY720, FK506 + FTY720, FK506 + FTY720 + irradiation). Indirect immunoperoxidase staining was performed against CD4 and MAdCAM-1. The numbers of CD4 positive cells in allografts were also analyzed by flow cytometry. The graft survival was prolonged in all of the FK506- and FTY720-treated groups. SBT allografts treated by FK506 and FTY720 demonstrated less infiltration of CD4 positive cells, but the irradiation group did not show any effects on its expression. In FK506- and FTY720-treated groups, MAdCAM-1 expression on the HEVs in PPs was up-regulated, and its expression on the ECVs in the LP was down-regulated compared with other allograft groups. Irradiation did not show any effects on MAdCAM-1 expression on both HEVs in PPs and ECVs in LP. FK506 and FTY720 prevented the infiltration of CD4 positive cells, the down-regulation of MAdCAM-1 expression on HEVs in PPs, and the up-regulation of MAdCAM-1 expression on ECVs in LP during the early phase of SBT.

Usefulness of power Doppler ultrasonography and superparamagnetic iron oxide enhanced magnetic resonance imaging for diagnosis of focal nodular hyperplasia of the liver after treatment of neuroblastoma.

Focal nodular hyperplasia (FNH) of the liver is rare in children, and it is usually diagnosed through a biopsy of the liver or hepatectomy. The authors report a case of a 10-year-old girl with multiple focal nodular hyperplasia lesions of the liver after the completion of tumor therapy for advanced neuroblastoma, and review the usefulness of the combination of power Doppler ultrasonography (US) and superparamagnetic iron oxide (SPIO) enhanced magnetic resonance imaging (MRI) for the diagnosis of FNH without a biopsy of the liver or hepatectomy.

Intestinal Failure-Associated Liver Disease and Eicosapentaenoic Acid/Arachidonic Acid Ratio.

Intestinal failure-associated liver disease (IFALD) is a fatal complication of short bowel syndrome managed with parenteral nutrition. A clinical cohort study reported the usefulness of parenteral administration of fish-derived omega-3 fatty acids in improving IFALD; however, no biomarker has been developed as yet. The authors report the case of a preterm infant with IFALD complicated by extensive short bowel syndrome. Intravenous administration of omega-3 fatty acids were introduced using Omegaven®at the age of 4 mo for IFALD. The IFALD improved with an increase in Eicosapentaenoic acid (EPA)/ Arachidonic acid (AA) ratio (from 0.08 to 1.99) 7 d after the intravenous treatment. It is important to administer omega-3 fatty acids intravenously at an early stage for IFALD associated with extensive short bowel syndrome. A low EPA/AA ratio may be a serum marker of disease activity in IFALD.