Experimentally Induced Biliary Atresia by Means of Rotavirus-Infection Is Directly Linked to Severe Damage of the Microvasculature in the Extrahepatic Bile Duct.

Vascular damage has been reported to contribute to atresia formation in several diseases including biliary atresia. This study focused on the extrahepatic biliary plexus in experimental biliary atresia. Newborn BALB/cAnNCrl-pups were infected with rhesus rotavirus within 24 hr after birth to induce experimental biliary atresia. The extrahepatic biliary plexus was examined by confocal microscopy on whole-mount preparations, scored by three independent researchers, and further evaluated at the subcellular level with transmission electron microscopy. Imaging results revealed a progressive destruction of the extrahepatic biliary vascular plexus in the course of experimental biliary atresia induced by rotavirus infection. Endothelial cell damage was already visible as cell swelling and necrosis in the first days after infection and a damaged microcirculation that rapidly deteriorated with progression of obliterative cholangiopathy, was observed in the infected mice as early as 72 hr after birth. In experimental biliary atresia, the destruction of the extrahepatic biliary vascular plexus starts already in the first days postinfection and clearly precedes the morphological symptoms of atresia. The deterioration of the vascular bed architecture continues with disease progression. Therefore, we conclude that the (ultra)structural changes in the extrahepatic biliary microvasculature occurring before the visible onset of atresia has a predictive diagnostic value and this impairment in blood supply to the extrahepatic bile duct may be an important contributing factor to the pathogenesis of acquired biliary atresia. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. Anat Rec, 302:818-824, 2019. © 2018 Wiley Periodicals, Inc.

Trace metal release after minimally-invasive repair of pectus excavatum.

BACKGROUND: Several studies have shown a high incidence of metal allergy after minimally-invasive repair of pectus excavatum (MIRPE). We postulated that MIRPE is associated with a significant release of trace metal ions, possibly causing the allergic symptoms. METHODS: We evaluated the concentration with chromium, cobalt and nickel in blood, urine and tissue in patients prior to MIRPE and in patients who underwent an explantation of the stainless-steel bar(s) after three years. RESULTS: Our study group consisted of 20 patients (mean age 19 years) who had bar explantation and our control group included 20 patients (mean age 16 years) prior to MIRPE. At the time of bar removal we detected significantly elevated concentrations of chromium and nickel in the tissue compared to patients prior to the procedure (p<0,001). We also found a significant increase in the levels of chromium in urine and nickel in blood in patients three years post MIRPE (p<0,001). Four patients temporarily developed symptoms of metal allergy, all had elevated metal values in blood and urine at explantation. CONCLUSIONS: Minimally-invasive repair of pectus excavatum can lead to a significant trace metal exposure.

MicroRNA-146a-mediated downregulation of IRAK1 protects mouse and human small intestine against ischemia/reperfusion injury.

Intestinal ischemia/reperfusion (I/R) injury causes inflammation and tissue damage and is associated with high morbidity and mortality. Uncontrolled activation of the innate immune system through toll-like receptors (Tlr) plays a key role in I/R-mediated tissue damage but the underlying mechanisms have not been fully resolved. Here, we identify post-transcriptional upregulation of the essential Tlr signalling molecule interleukin 1 receptor-associated kinase (Irak) 1 as the causative mechanism for post-ischemic immune hyper-responsiveness of intestinal epithelial cells. Increased Irak1 protein levels enhanced epithelial ligand responsiveness, chemokine secretion, apoptosis and mucosal barrier disruption in an experimental intestinal I/R model using wild-type, Irak1(-/-) and Tlr4(-/-) mice and ischemic human intestinal tissue. Irak1 accumulation under hypoxic conditions was associated with reduced K48 ubiquitination and enhanced Senp1-mediated deSUMOylation of Irak1. Importantly, administration of microRNA (miR)-146a or induction of miR-146a by the phytochemical diindolylmethane controlled Irak1 upregulation and prevented immune hyper-responsiveness in mouse and human tissue. These findings indicate that Irak1 accumulation triggers I/R-induced epithelial immune hyper-responsiveness and suggest that the induction of miR-146a offers a promising strategy to prevent I/R tissue injury.

LigaSure in laparoscopic transperitoneal heminephroureterectomy in children: a comparative study.

BACKGROUND: This study was conducted to evaluate the feasibility of using the LigaSure vessel sealing system (Valleylab, Boulder, CO) in laparoscopic transperitoneal vs. open retroperitoneal heminephroureterectomy in children. MATERIALS AND METHODS: Seven consecutive patients with impaired renal duplex systems underwent laparoscopic heminephroureterectomies using LigaSure between April 2003 and April 2005. The operative time, complications, and hospital stay were analyzed prospectively. The data of 7 consecutive patients who had undergone open retroperitoneal heminephroureterectomy from 2001 to 2003 were analyzed for comparison purposes. The mean ages, underlying disease, and location of the affected kidney pole were not significantly different between these groups. RESULTS: There were no intraoperative complications during laparoscopic heminephroureterectomy and all procedures were completed laparoscopically. The mean operative time of 144 minutes (range, 90-210 minutes) for laparoscopic heminephroureterectomy was somewhat longer than in open heminephroureterectomy-mean time 110 minutes (range, 60-165 minutes) (P = 0.5). Complications of open retroperitoneal heminephroureterectomy included bleeding of the surface of the remaining kidney pole in one patient, requiring extensive hemostatic suturing. Postoperative recovery was uneventful in all laparoscopic procedures, whereas intermittent retention of urine was noticed in one patient undergoing the open procedure. CONCLUSION: Laparoscopic heminephroureterectomy using LigaSure is feasible in children and has a similar operative time compared to conventional heminephroureterectomy.

Exposure to carbon dioxide and helium reduces in vitro proliferation of pediatric tumor cells.

BACKGROUND: Minimally invasive techniques are increasingly applied to children with malignant tumors. We showed previously that CO(2) used for pneumoperitoneum modulates the function of macrophages and polymorphonuclear cells via direct effects and via acidification. Numerous in vitro and small animal model studies also confirmed an alteration of the behavior of several types of adult tumor cells by CO(2). The impact of CO(2) and other gases used for pneumoperitoneum on the behavior of various pediatric tumors has not yet been determined. METHODS: Cell lines of neuroblastoma (IMR 32, SK-N-SH, Sy5y), lymphoma (Daudi), hepatoblastoma (Huh 6), hepatocellular carcinoma (Hep G2), and rhabdomyosarcoma (Te 671) were incubated for 2 h. Incubation was performed with 100% CO(2), 100% helium, and 5% CO(2) as control. Cell proliferation was determined by the MTT-assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] by actively growing cells to produce a blue formazan product. The MTT-assay was performed before, directly after incubation, and daily for 4 days. Vitality of the cells was determined by trypan blue. The extracellular pH during incubation was measured during gas exposition every 10 min using Bayer Rapid Lab 855. RESULTS: CO(2) for 2 h significantly decreased the proliferation of neuroblastoma, lymphoma, hepatoblastoma, and hepatocellular carcinoma cells. This decrease persisted over 4 days in neuroblastoma, lymphoma, and hepatocellular carcinoma cells. The CO(2) had no impact on hepatoblastoma and rhabdomyosarcoma cells. Helium had a similar effect on neuroblastoma cells. After 4 days, a significant decrease of cell activity was found in two neuroblastoma cell lines and in hepatoblastoma cells. Helium had no effect on lymphoma and hepatocellular carcinoma cells. The extracellular pH was 6.2 during incubation with CO(2), and 7.6 during incubation with helium. CONCLUSION: CO(2) and helium may affect the proliferation of some pediatric tumor cell lines in vitro. However, some of these effects and the impact on the extracellular pH are differential. The role of pH modulation, hypoxia and direct effects of gases remain to be investigated before a general recommendation on the use of minimally invasive techniques in pediatric oncology can be given.

Complications of the minimally invasive repair of pectus excavatum.

BACKGROUND: Minimally invasive repair of pectus excavatum (MIRPE) has become widely popular since its introduction in the late 1990s by Nuss. We describe 1 unusual complication after MIRPE and 1 life-threatening bleeding during removal of the pectus bar. METHODS: We report the cases of 2 patients in a single institution, more than 100 MIRPE procedures performed so far, and review of literature. CASES: A 14-year-old girl presented 6 months after MIRPE in another institution. During removal of the pectus bar, a massive hemorrhage from both chest wounds occurred, requiring emergency sternotomy. Arrosion of a pulmonary vessel close to the metal bar had led to the bleeding. The second case was a bilateral sternoclavicular dislocation after MIRPE, which has not caused symptoms so far, in a 13-year-old girl. CONCLUSIONS: Numerous operative and postoperative complications after MIRPE are feasible. This is the first report of a life-threatening bleeding during removal of the pectus bar. Minimally invasive repair of pectus excavatum procedure and removal of the pectus bar should only occur in specialized institutions with wide experience in thoracic surgery.