Over a period of 10 years, five children developed postoperative intussusception after intra-abdominal procedures at the Department of Pediatric Surgery of the Johannes Gutenberg University Mainz. Two appendectomies, one ileal resection for a Meckel's diverticulum, one operative procedure for Hirschsprung's disease plus intestinal neuronal dysplasia type B, and one hiatoplasty with jejunostomy preceded the intussusception. Three of the five children were older than 2 years. The clinical symptoms consisted primarily of abdominal distension, diffuse abdominal pain, bilious vomiting, and rectal bleeding in one case. Preoperative diagnosis was achieved in four cases by abdominal ultrasound. Plain abdominal radiographs demonstrated dilated loops of small intestine with air-fluid levels in four of the five cases. In the case without radiographic findings, the jejunojejunal intussusception was missed even by a bowel follow-through. The intussusceptions were ileocolic (3), ileoileal (1), and jejunojejunal (1). A hydrostatic procedure to reduce an ileocolic intussusception was not successful. Operative treatment of the intussusception was performed in three cases within 5 days, once at 32 days, and once 3 months after the primary operation, in all cases by laparatomy and simple manual reduction without intestinal resection. In contrast to idiopathic intussusception, noninvasive hydrostatic procedures are not indicated in postoperative intussusception, since protection of intestinal anastomoses from hydrostatic pressure and exclusion of other causes of postoperative ileus are mandatory.

Classical Hodgkin lymphoma (cHL) has a typical clinical manifestation, with dissemination involving functionally neighboring lymph nodes. The factors involved in the spread of lymphoma cells are poorly understood. Here we show that cHL cell lines migrate with higher rates compared with non-Hodgkin lymphoma cell lines. cHL cell migration, invasion and adhesion depend on autocrine WNT signaling as revealed by the inhibition of WNT secretion with the porcupine inhibitors Wnt-C59/IWP-2, but did not affect cell proliferation. While application of recombinant WNT5A or WNT5A overexpression stimulates HL cell migration, neither WNT10A, WNT10B nor WNT16 did so. Time-lapse studies revealed an amoeboid type of cell migration modulated by WNT5A. Reduced migration distances and velocity of cHL cells, as well as altered movement patterns, were observed using porcupine inhibitor or WNT5A antagonist. Knockdown of Frizzled5 and Dishevelled3 disrupted the WNT5A-mediated RHOA activation and cell migration. Overexpression of DVL3-K435M or inhibition of ROCK (Rho-associated protein kinase) by Y-27632/H1152P disrupted cHL cell migration. In addition to these mechanistic insights into the role of WNT5A in vitro, global gene expression data revealed an increased WNT5A expression in primary HL cells in comparison with normal B-cell subsets and other lymphomas. Furthermore, the activity of both porcupine and WNT5A in cHL cells had an impact on lymphoma development in the chick chorionallantoic membrane assay. Massive bleeding of these lymphomas was significantly reduced after inhibition of WNT secretion by Wnt-C59. Therefore, a model is proposed where WNT signaling has an important role in regulating tumor-promoting processes.

Objective: A subset of fetuses with sacrococcygeal teratomas (SCT) develops hydrops caused by high-output heart failure. Identification of fetuses at risk for hydrops is important because surgical intervention may reverse the pathophysiology of the disease. The aim of this study was to evaluate sonographic prognostic factors regarding tumor morphology and vascularity associated with the development of hydrops in utero. Methods: Over a 10-year period, we identified 7 fetuses with SCT diagnosed antenatally and managed at the University of Mainz. We retrospectively reviewed the charts of mothers and infants and recorded data on prenatal diagnosis, tumor size and localization, perinatal management, neonatal care, and fetal outcome. Results: The diagnosis of SCT was made in all cases by ultrasound. The median gestational age at the time of initial diagnosis was 23 weeks. In 3 cases, signs of fetal heart failure were detected by ultrasound. Pathological blood flow in the venous system was further noted in 2 cases. One fetus developed hydrops. The mean gestational age at delivery was 35 weeks, depending on the presence or absence of maternal or fetal complications. Six infants were delivered by cesarean section, and 1 by vaginal delivery. After fetal stabilization, surgery was performed in 5 of 7 cases. Inadequate ventilation secondary to prematurity was a contributing factor to death in 1 fetus. One fetal intrauterine death occurred at 27 weeks of gestation. Conclusion: Pregnancies with antenatally diagnosed fetal SCT necessitate frequent monitoring to ensure the detection of fetal/maternal complications by ultrasound and Doppler ultrasound. The most important prognostic criteria were cardiomegaly, fetal hydrops, and increased preload indexes of the fetal venous system as sign of fetal heart failure. Many studies show that the occurrence of pulsations in the umbilical vein of a hydropic fetus correlates with a poor fetal outcome. The decision on the optimal time of delivery should therefore be made by a multidisciplinary team of specialists.

The interaction between vascular endothelial cells (ECs) and cancer cells is of vital importance to understand tumor dissemination. A paradigmatic cancer to study cell-cell interactions is classical Hodgkin Lymphoma (cHL) due to its complex microenvironment.The role of the interplay between cHL and ECs remains poorly understood. Here, we identify canonical WNT pathway activity as important for the mutual interactions between cHL cells and EC.We demonstrate that local canonical WNT signaling activates cHL cell chemotaxis towards ECs, adhesion to EC layers and cell invasion using the Wnt-inhibitor Dickkopf, tankyrases and casein kinase inhibitors but also knock-down of the lymphocyte enhancer binding-factor 1 (LEF-1) and β-catenin in cHL cells. Furthermore, LEF-1 and β-catenin-regulated cHL secretome promoted EC migration, sprouting and vascular tube formation involving VEGF-A. Importantly, high VEGFA expression is associated with a worse overall survival of cHL patients.These findings strongly support the concept that WNTs might function as regulator of lymphoma dissemination by affecting cHL cell chemotaxis and promoting endothelial cell behavior and thus angiogenesis through paracrine interactions.

Studying medulloblastoma, the most common malignant paediatric brain tumour, requires simple yet realistic in vitro models. In this study, we optimised a robust, reliable, three-dimensional (3D) culture method for medulloblastoma able to recapitulate the spatial conformation, cell–cell and cell–matrix interactions that exist in vivo and in patient tumours. We show that, when grown under the same stem cell enriching conditions, SHH subgroup medulloblastoma cell lines established tight, highly reproducible 3D spheroids that could be maintained for weeks in culture and formed pathophysiological oxygen gradients. 3D spheroid culture also increased resistance to standard-of-care chemotherapeutic drugs compared to 2D monolayer culture. We exemplify how this model can enhance in vitro therapeutic screening approaches through dual-inhibitor studies and continual monitoring of drug response. Next, we investigated the initial stages of metastatic dissemination using brain-specific hyaluronan hydrogel matrices. RNA sequencing revealed downregulation of cell cycle genes and upregulation of cell movement genes and key fibronectin interactions in migrating cells. Analyses of these upregulated genes in patients showed that their expression correlated with early relapse and overall poor prognosis. Our 3D spheroid model is a significant improvement over current in vitro techniques, providing the medulloblastoma research community with a well-characterised and functionally relevant culture method.