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Choledochal malformation (CM) is a rare disease that can lead to malignancy and potential long-term sequelae despite surgical resection. There is no long-term follow-up data on patients after CM resection in Germany. We aimed to determine the long-term outcome of our patients with a duration of follow-up >10 years and focused on long-term sequelae and health-related quality of life (HRQOL).

Survival rates of patients with visceral congenital malformations have increased considerably. However, long-term morbidity in these patients is high. In the last decades, these circumstances have led to a shift in goals of caretakers and researchers with a new focus on patients’ perspectives and long-term morbidity. Health-related quality of life (HrQoL) is the most commonly used patient-reported outcome measure to assess the impact of chronic symptoms on patients’ everyday lives. Most pediatric surgical conditions can cause a significantly decreased HrQoL in affected patients compared to the healthy population. In order to guarantee life-long care and to minimize the impact on HrQoL a regular interdisciplinary follow-up is obligatory. The period of transition from child-centered to adult-oriented medicine represents a critical phase in the long-term care of these complex patients. This scoping review aims to summarize relevant pediatric surgical conditions focusing on long-term-morbidity and HrQoL assessment in order to demonstrate the necessity for a well-structured and standardized transition for pediatric surgical patients.

Living donor liver transplantation (LDLT) is regularly performed in small-sized infants. Computed tomography (CT)-based donor liver volumetry is used to estimate the graft size. The aim of our study was to assess the results of CT liver volumetry and their impact on the clinical outcome after LDLT in extremely small-sized infants.

Introduction The nitrofen model of congenital diaphragmatic hernia (CDH) creates a Bochdalek-type diaphragmatic defect and has been widely used to investigate the pathogenesis of CDH. However, the exact pathogenesis of the diaphragmatic defect in this model is still poorly understood. Chicken ovalbumin upstream promotor-transcription factor II (COUP-TFII) is expressed in the embryonic pleuroperitoneal folds (PPF) in the early stage of development and in the diaphragm in the late days of gestation. COUP-TFII is known to be a strong repressor of the retinoid signaling pathway (RSP), which plays an important role in diaphragm development. Furthermore, it has been recently shown that COUP-TFII is upregulated during early gestation in the nitrofen-induced hypoplastic lung. We designed this study to investigate the hypothesis that COUP-TFII gene expression is upregulated during early diaphragmatic development in the PPF.Material and Methods Timed pregnant rats were exposed to either olive oil (Control) or nitrofen (CDH) on day 9 of gestation (D9). Fetuses were sacrificed on D13, D18 or D21. The PPF was dissected from D13 fetuses using laser capture microdissection. Diaphragms were dissected from D18 and D21 fetuses under the dissection microscope. The relative mRNA expression levels of COUP-TFII were determined using real-time PCR. Immunohistochemistry was performed to evaluate diaphragmatic protein expression and the distribution of COUP-TFII.Results On D13, gene expression levels of COUP-TFII in the PPF were significantly increased in the CDH group (82.93 ± 11.85) compared to Controls (46.22 ± 8.09; p < 0.05), whereas there were no differences at later time points. The immunoreactivity of diaphragmatic COUP-TFII was markedly increased in the PPF in the CDH group compared to Controls on D13. No difference in immunoreactivity was observed on D18 and D21.Conclusion Upregulation of COUP-II gene expression in the PPF may contribute to the diaphragmatic defect in the nitrofen CDH model by inhibiting the RSP. [ABSTRACT FROM AUTHOR]

Introduction: The nitrofen model of Congenital Diaphragmatic Hernia (CDH) displays a diaphragmatic defect of the Bochdalek-type and has been widely used to investigate the pathogenesis of CDH. However, the exact pathomechanism of the diaphragmatic defect is still poorly understood. Fibroblast growth factor (FGF) receptorlike 1 (FGFRL1), a member of the FGF receptor family, plays a key role in physiological diaphragmatic development. FGFRL1 is expressed in the fetal diaphragm at low levels in early gestation and its expression steadily increases, becoming most pronounced in later gestational stages. It has been reported that FGFRL1 homozygous null mice have thin, partially amuscular diaphragms and die at birth due to respiratory failure. The aim of this study was to investigate the hypothesis that FGFRL1 gene expression in the diaphragm is downregulated during the later gestational stages in the nitrofen CDH model. Material and Methods: Timed pregnant rats were exposed to either olive oil or 100 mg nitrofen on day 9 of gestation (D9). Cesarean section was performed on D18 or D21. Fetal diaphragms (n = 40) were micro-dissected and divided into CDH group and controls. Total RNA was extracted from the diaphragms and the mRNA levels of FGFRL1 were determined using real-time PCR. Immunohistochemistry was performed to evaluate diaphragmatic protein expression of FGFRL1. Student ' s t-test and Mann-Whitney test were used, where appropriate. Statistical significance was considered for p < 0.05. Results: Relative mRNA expression levels of FGFRL1 were significantly decreased in the CDH group compared to controls on D18 (3.63±1.65 vs. 6.04±3.12, p <0.05) and D21 (1.36±1.01 vs. 2.57±1.34, p <0.05). Immunoreactivity of FGFRL1 was markedly decreased in the diaphragms of the CDH group compared to controls on D18 and D21. Conclusion: Our data provide strong evidence that downregulation of the FGFRL1 gene during the late stages of gestation may contribute to the development of the diaphragmatic defect in nitrofen-induced CDH. [ABSTRACT FROM AUTHOR]

Purpose: The precise mechanism of pulmonary hypoplasia (HP) associated with congenital diaphragmatic hernia (CDH) remains unclear. Insulin- like growth factors (IGFs) play an essential role in fetal lung development through IGF receptors (IGFRs) by regulating cellular proliferation, differentiation and survival. It has been reported that the expression of genes involved in IGF-IGFR signaling is altered in the nitrofen-induced hypoplastic lung during the later stages of lung development. IGF-binding proteins (IGFBPs) control bioavailability, activity and disruption of IGFs through the high affinity IGFBP/IGF complexes. IGFBP-4 is a key inhibitor of IGF-IGFR signalingmediated cell proliferation. It has been revealed that cell proliferation in fetal lung fibroblasts is inhibited by increased IGFBP-4 production. We hypothesized that IGFBP-4 gene expression is increased during the later stages of lung development in the nitrofen-induced CDH lung. Methods: Pregnant Sprague-Dawley rats were exposed to either olive oil or nitrofen on day 9 (D9) of gestation. Fetuses were harvested by cesarean section on D18 and D21. Fetal lungs were divided into 3 groups: control, nitrofen without CDH [CDH(-)] and nitrofen with CDH [CDH( + )] (n = 24 at each time point). Relative mRNA levels of IGFBP-4 were determined using real-time RT-PCR. Immunohistochemistry was performed to evaluate the protein expression of IGFBP-4. Results: The relative expression levels of IGFBP- 4 mRNA were significantly increased in CDH(-) and CDH(+) groups on D18 and D21 compared to controls. Immunohistochemistry showed increased IGFBP-4 expression in mesenchymal compartments on D18 and D21 in hypoplastic lungs compared to controls. Conclusion: Overexpression of pulmonary IGFBP-4 during the later stages of lung development may contribute to pulmonary hypoplasia in the nitrofen-induced CDH model by inhibiting IGF-mediated cell proliferation. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary hypoplasia is a primary cause of high morbidity and mortality in neonates with Congenital Diaphragmatic Hernia (CDH). However, the precise pathogenesis of PH associated with CDH is still not clearly understood. It has been recently reported that lung Kruppel-like factor (LKLF), a member of the Kruppel-like factor family of transcription factors, is predominantly expressed in lungs and plays an important role in lung morphogenesis and functional maturation. It has been reported that homozygous deletion of LKLF gene in mice results in reduced lung morphogenesis. It is further reported that chimeric mice derived from LKLF-/- embryonic stem cells exhibit delayed lung development especially in the later gestational stages. We therefore designed this study to test the hypothesis that the LKLF gene is down-regulated during later stages of lung development in nitrofen-induced hypoplastic lungs. Material and Methods: Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetal lungs were harvested on D15, D18, and D21 and divided into 3 groups:control, nitrofen without CDH(CDH( - )) and nitrofen with CDH(CDH(+)) (n = 24 for each group). Realtime RT-PCR analysis was performed to investigate pulmonary gene expression levels of LKLF. Differences between the 3 groups at each time point were tested statistically and significance was accepted at p < 0.05. Immunohistochemistry was also performed to evaluate LKLF protein expression and distribution. Results: The relative mRNA expression levels of LKLF on D18 and D21 were significantly decreased (p < 0.01) in CDH( - ) and CDH( + ) groups compared to controls. The gene expression levels of LKLF on D15 did not differ significantly between the nitrofen group and controls. Immunohistochemical study showed strong LKLF immunoreactivity on D18 and D21 in nitrofeninduced hypoplastic lung compared to controls, whereas no difference was seen on D15. Conclusions: Our results provide evidence for the first time that LKLF is down-regulated in the later stages of lung development in nitrofen- induced hypoplastic lungs. These data suggest that the down-regulation of LKLF during this critical period of lung morphogenesis may impair lung development and maturation, resulting in pulmonary hypoplasia in the nitrofen CDH model. [ABSTRACT FROM AUTHOR]

The important cell cycle regulatory gene p15[SUPNK4b] has been shown to be inactivated in acute myeloid leukemia and myelodysplastic syndrome. Little is known about the expression and epigenetic modification of this gene in chronic myelomonocytic leukemia (CMML) that belongs to the myelo-dysplastic/myeloproliferative disorders (MDS/MPD) with a high proportion of blastic transformation. Analysis of bone marrow trephines in a series of 33 CMML cases showed an aberrant p15&[SUPINK4b] gene methylation in up to 58% of cases. Methylation was analyzed employing different methylation-specific PCR and genomic sequencing protocols. It turned out to be spread over a broad area of the 5′ region and exhibited substantial heterogeneity between cases and even in individual patients. The degree of aberrant methylation was correlated with a reduced mRNA as well as reduced protein expression, and was associated with a higher expression of DNA methyltransferase DNMT 3A. We conclude that aberrant gene methylation is a frequent event in CMML that might contribute to the pathogenesis of this MDS/MPD. [ABSTRACT FROM AUTHOR]

Background:  Esophageal atresia (EA) is a rare disease requiring surgical repair, usually within the first days of life. Patients with EA require intensive postoperative care and often have comorbidities. There is a lack of data on the costs incurred by patients with EA during the first year of life., Methods:  Anonymized claims data were provided by the Techniker Krankenkasse (∼10.8 million clients). Data were extracted for patients who had an inpatient diagnosis of EA (International Classification of Diseases [ICD]: Q39.0 or Q39.1) and a reconstruction of the esophageal passage in case of atresia (Operationen-und Prozedurenschlüssel [German version of ICPM, International Classification of Procedures in Medicine; OPS] 5-428.0 to 5-428.7, 5-316.1 or 5-431.0) during their first hospital stay. All patients were in their first year of life at initial hospitalization (2016-2020) and were followed up for 1 year. Costs, length of hospital stay, and duration of mechanical ventilation and differentiated OPS services were analyzed using descriptive statistics. Multiple linear regression was used to analyze the determinants of hospital costs., Results:  A total of 119 patients with EA were included (55.5% male). The mean cost of the 1-year observation period was €89,736 ± 97,419 (range €12,755-640,154). The increasing costs of the initial hospitalization led to a disproportionate increase in the costs of the 1-year observation period. The presence of an associated malformation combined with surgical complications was associated with almost five-fold higher costs than in patients without an associated malformation and an uncomplicated course (€193,103 ± 157,507 vs. €39,846 ± 33,473). The mean duration of mechanical ventilation was 23.2 ± 43.1 days and the mean length of hospital stay was 80.3 ± 77.2 days., Conclusion:  To our knowledge, this is the first study to investigate the costs of EA patients in the first year of life. The presence of an associated malformation combined with surgical complications was associated with almost five-fold higher costs than in patients without an associated malformation and an uncomplicated course., Competing Interests: None declared., (Thieme. All rights reserved.)

Aim of the Study:  Esophageal atresia (EA) is associated with impaired motor development, cardiopulmonary function, and physical activity (PA). Despite missing scientific evidence, this fact is often attributed to associated congenital heart disease (CHD). The aim of this study was to investigate PA in EA patients without CHD compared with CHD patients and healthy controls., Methods:  In this multicenter study, EA patients aged 6 through 17 years were included. Moderate-to-vigorous PA (MVPA, minutes per week) was assessed using the standardized and validated questionnaire Motorik-Modul Physical Activity Questionnaire. EA patients were randomly matched 1:4 for gender and age with patients with CHD ( n  = 1,262) and healthy controls ( n  = 6,233). Patients born with both EA and CHD were excluded. Means and 95% confidence intervals (95% CIs) were calculated. To identify associated factors, Spearman's correlation was performed., Main Results:  Overall, 69 EA patients were matched with 276 CHD patients and 276 controls (57% male, 43% female, mean age 10,3 years, 95% CI: 9.5-11.1). Mean MVPA was reduced in EA (492 minutes, 95% CI: 387-598) and CHD patients (463 minutes, 95% CI: 416-511) compared with controls (613 minutes, 95% CI: 548-679). In subgroup analysis, MVPA was reduced further in females and older age groups with EA and CHD. For EA patients, there was no statistical association between Gross type, current symptoms, surgical approaches, and MVPA., Conclusion:  Isolated EA and CHD were associated with reduced PA, especially in females and teenagers. To avoid additional morbidity associated with sedentary behavior, PA should be promoted during follow-up., Competing Interests: None declared., (Thieme. All rights reserved.)