Lucas M. Wessel
Heidelberg University
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Featured researches published by Lucas M. Wessel.
Neonatology | 2010
Kitty G. Snoek; Irwin Reiss; Anne Greenough; Irma Capolupo; Berndt Urlesberger; Lucas M. Wessel; Laurent Storme; Jan Deprest; Thomas Schaible; Arno van Heijst; Dick Tibboel
In 2010, the congenital diaphragmatic hernia (CDH) EURO Consortium published a standardized neonatal treatment protocol. Five years later, the number of participating centers has been raised from 13 to 22. In this article the relevant literature is updated, and consensus has been reached between the members of the CDH EURO Consortium. Key updated recommendations are: (1) planned delivery after a gestational age of 39 weeks in a high-volume tertiary center; (2) neuromuscular blocking agents to be avoided during initial treatment in the delivery room; (3) adapt treatment to reach a preductal saturation of between 80 and 95% and postductal saturation >70%; (4) target PaCO2 to be between 50 and 70 mm Hg; (5) conventional mechanical ventilation to be the optimal initial ventilation strategy, and (6) intravenous sildenafil to be considered in CDH patients with severe pulmonary hypertension. This article represents the current opinion of all consortium members in Europe for the optimal neonatal treatment of CDH.
Neonatology | 2010
Kitty G. Snoek; Irwin Reiss; Anne Greenough; Irma Capolupo; Berndt Urlesberger; Lucas M. Wessel; Laurent Storme; Jan Deprest; Thomas Schaible; Arno van Heijst; Dick Tibboel; Karel Allegaert; Anne Debeer; Richard Keijzer; Alexandra Benachi; P. Tissieres; Florian Kipfmueller; T. Schaible; Cormac Breatnach; Neil Patel; E. Leva; F. Ciralli; Pietro Bagolan; Andrea Dotta; Francesco Morini; A. Di Pede; Ragnhild Emblem; K. Ertesvag; M. Migdal; A. Piotrowski
Congenital diaphragmatic hernia (CDH) is associated with high mortality and morbidity. To date, there are no standardized protocols for the treatment of infants with this anomaly. However, protocols based on the literature and expert opinion might improve outcome. This paper is a consensus statement from the CDH EURO Consortium prepared with the aim of achieving standardized postnatal treatment in European countries. During a consensus meeting between high-volume centers with expertise in the treatment of CDH in Europe (CDH EURO Consortium), the most recent literature on CDH was discussed. Thereafter, 5 experts graded the studies according to the Scottish Intercollegiate Guidelines Network (SIGN) Criteria. Differences in opinion were discussed until full consensus was reached. The final consensus statement, therefore, represents the opinion of all consortium members. Multicenter randomized controlled trials on CDH are lacking. Use of a standardized protocol, however, may contribute to more valid comparisons of patient data in multicenter studies and identification of areas for further research.
Annals of Surgery | 2016
Kitty G. Snoek; Irma Capolupo; Joost van Rosmalen; Lieke de Jongste-van den Hout; Sanne Vijfhuize; Anne Greenough; Rene Wijnen; Dick Tibboel; Irwin Reiss; Alessandra Di Pede; Andrea Dotta; Pietro Bagolan; Ulrike Kraemer; Carla Pinto; Maria Gorett Silva; Joana Saldanha; Prashanth Bhat; Vadivelam Murthy; Arno van Heijst; Thomas Schaible; Lucas M. Wessel; Karel Allegaert; Anne Debeer
Objectives:To determine the optimal initial ventilation mode in congenital diaphragmatic hernia. Background:Congenital diaphragmatic hernia is a life-threatening anomaly with significant mortality and morbidity. The maldeveloped lungs have a high susceptibility for oxygen and ventilation damage resulting in a high incidence of bronchopulmonary dysplasia (BPD) and chronic respiratory morbidity. Methods:An international, multicenter study (NTR 1310), the VICI-trial was performed in prenatally diagnosed congenital diaphragmatic hernia infants (n = 171) born between November 2008 and December 2013, who were randomized for initial ventilation strategy. Results:Ninety-one (53.2%) patients initially received conventional mechanical ventilation and 80 (46.8%) high-frequency oscillation. Forty-one patients (45.1%) randomized to conventional mechanical ventilation died/ had BPD compared with 43 patients (53.8%) in the high-frequency oscillation group. An odds ratio of 0.62 [95% confidence interval (95% CI) 0.25–1.55] (P = 0.31) for death/BPD for conventional mechanical ventilation vs high-frequency oscillation was demonstrated, after adjustment for center, head-lung ratio, side of the defect, and liver position. Patients initially ventilated by conventional mechanical ventilation were ventilated for fewer days (P = 0.03), less often needed extracorporeal membrane oxygenation support (P = 0.007), inhaled nitric oxide (P = 0.045), sildenafil (P = 0.004), had a shorter duration of vasoactive drugs (P = 0.02), and less often failed treatment (P = 0.01) as compared with infants initially ventilated by high-frequency oscillation. Conclusions:Our results show no statistically significant difference in the combined outcome of mortality or BPD between the 2 ventilation groups in prenatally diagnosed congenital diaphragmatic hernia infants. Other outcomes, including shorter ventilation time and lesser need of extracorporeal membrane oxygenation, favored conventional ventilation.
Journal of Pediatric Surgery | 1998
Steffan Loff; Karl-Ludwig Waag; B. Kränzlin; D. Zovko; A. Dzakovic; Iwgo Jester; Hartmut Wirth; Lucas M. Wessel
BACKGROUND/PURPOSE Currently, the reason for hepatobiliary dysfunction associated with long-term total parenteral nutrition (TPN) is much debated and still unclear. No agreement can be achieved about whether bacteriotoxins and sepsis, enteral starvation, consequences of abdominal operations, or the TPN solution itself is the real cause for the disease. Animal models were criticized for their short period of TPN and their failure to demonstrate cholestasis and bile duct proliferation. The aim of this study was to establish an animal model for long-term TPN in which the same alterations of the hepatobiliary system as observed in humans could be produced. METHODS In this model, rabbits could be kept for the first time under continuous TPN for 4 weeks. Three serial liver biopsy sections were taken operatively from each animal and biochemical analyses were performed four times. A control group of enterally fed rabbits underwent exactly the same procedure in respect to operations and handling, so that differences in macroscopical, biochemical, and histological changes between both groups could be attributed exclusively to TPN. RESULTS Only in the TPN group gallbladder distension developed in all animals after 1 week. After 3 and 4 weeks, viscous dark bile, sludge and stones, a slight rise in direct bilirubin, and a decline in plasma albumin and alkaline phosphatase was noted. In both groups liver biopsy results showed a similar degree of mild portal inflammation and single-cell necrosis at equivalent time points. These changes could be caused by antiseptics, antibiotics, anesthesia, and operations. Although mild to moderate proliferative changes and no hydropic degeneration developed in the control group during the same time, the TPN group generated marked proliferative and degenerative changes. We noted as early as 1 week after starting TPN a severe hydropic degeneration in 90% of the animals. Fibrosis and bile duct proliferation increased from a slight degree after 1 week up to a moderate to severe degree after 3 and 4 weeks, respectively. CONCLUSIONS The hepatobiliary alterations associated with TPN in children, which cannot be separated clinically from consequences of multiple other factors, can almost identically be reproduced in our rabbit model as a clear consequence of TPN. Furthermore, the hydropic degeneration of the liver cells begins in zone 3 and is an early predominant feature of hepatobiliary dysfunction in rabbits and infants. It must be rated as a response to a direct cytotoxic effect on the liver cell.
Journal of Pediatric Surgery | 2011
Susanne Maier; Katrin Zahn; Lucas M. Wessel; Thomas Schaible; Joachim Brade; Konrad Reinshagen
OBJECTIVE Congenital diaphragmatic hernia (CDH) is known to be a predisposing factor in gastroesophageal reflux (GER) leading to pulmonary and nutritional problems. The aim of this prospective, randomized, patient-blinded study was to evaluate the benefit of antireflux surgery at the time of CDH repair. METHODS From 2003 to 2009, 79 neonates with left-sided CDH were included. Forty-three had regular hernia closure. Thirty-six patients additionally had fundoplication at hernia repair. Follow-up was at 6, 12, and 24 months after birth with a standardized questionnaire and a thorax radiograph. Patients with clinical signs for GER were evaluated with upper gastrointestinal series and 24-hour pH-metry. RESULTS Seventy-nine of 263 patients participated in this prospective trial. Survival rate was 88.61%. The GER symptoms were almost significantly more frequent in the group without concomitant fundoplication at the age of 6 months. At 24 months, the difference between both groups was not significant anymore. Development of body weight in the first 2 years of life was similar in both groups. No complications related to initial antireflux surgery were noted. CONCLUSION Patients profit from fundoplication at CDH repair only within the first year of life. At the present point of this study, simultaneous fundoplication at the time of primary CDH repair cannot be recommended as a standard procedure in all patients with left-sided CDH.
PLOS ONE | 2013
Cornelia Irene Hagl; Sabine Heumüller-Klug; Elvira Wink; Lucas M. Wessel; Karl-Herbert Schäfer
Stem cell therapies seem to be an appropriate tool for the treatment of a variety of diseases, especially when a substantial cell loss leads to a severe clinical impact. This is the case in most neuronal cell losses. Unfortunately, adequate neural stem cell sources are hard to find and current alternatives, such as induced programmed stem cells, still have incalculable risks. Evidence of neurogenesis in the adult human enteric nervous system brought up a new perspective. In humans the appendix harbors enteric neuronal tissue and is an ideal location where the presence of neural stem cells is combined with a minimal invasive accessibility. In this study appendices from adults and children were investigated concerning their neural stem cell potential. From each appendix tissue samples were collected, and processed for immunohistochemistry or enteric neural progenitor cell generation. Free-floating enteric neurospheres (EnNS’s) could be generated after 6 days in vitro. EnNS’s were either used for transplantation into rat brain slices or differentiation experiments. Both transplanted spheres and control cultures developed an intricate network with glia, neurons and interconnecting fibers, as seen in primary enteric cultures before. Neuronal, glial and neural stem cell markers could be identified both in vitro and in vivo by immunostaining. The study underlines the potential of the enteric nervous system as an autologous neural stem cell source. Using the appendix as a potential target opens up a new perspective that might lead to a relatively unproblematic harvest of neural stem cells.
Pediatric Surgery International | 1999
S. Loff; B. Kränzlin; M. Moghadam; A. Dzakovic; Lucas M. Wessel; W. Back; S. Hosie; H. Wirth; Karl-Ludwig Waag
Abstract We analyzed clinical, biochemical, and histo- logic parameters of ten infants with parenteral nutrition-induced hepatobiliary dysfunction. The data were compared with the results of a rabbit model. All infants were born prematurely with low birth weight. Their clinical diagnoses were necrotizing enterocolitis (6), gastroschisis (1), intrauterine volvulus (1), and lung hypoplasia (2). All required total (TPN) or partial parenteral nutrition for at least 8 weeks. All had repeated episodes of infections or sepsis. A rise in bilirubin and aminotransferase levels occurred after a minimum of 5 weeks; peak bilirubin levels ranged from 4 to 14 mg% and aminotransferases from 40 to 140 IU/l. One child later developed gallstones. Liver biopsies after 1 to 24 months showed fibrosis, bile-duct proliferation, cholestasis, and hydropic degeneration. All of the above-mentioned clinical factors have been accused of causing the observed biochemical and histologic changes. In our rabbit model we were able to produce almost identical symptoms by TPN alone: gallbladder distension, sludge, and stones developed after 1–4 weeks of TPN as well as uncharacteristic changes in aminotransferases and bilirubin after 4 weeks. Liver histology revealed severe hydropic degeneration of zone 3 as early as 1 week after beginning TPN. A rise of fibrosis and bile-duct proliferation after 1 to 4 weeks of infusion was statistically significant. Cholestasis, as was observed in the infants, could not be detected. In our model, all alterations observed could be attributed exclusively to TPN. We therefore assume that TPN was the true cause of the dysfunction. In a second experimental series infusions were reduced to 80% PN and free access to lab chow. These animals produced normal feces, indicating physiologic enteral stimulation. They developed the same degenerative and proliferative histologic changes, whereas gallbladder distension, sludge, and stones were not noted. We conclude that: (1) The TPN solution itself is responsible for the histologic changes in the liver, which is supported by the fact that hydropic degeneration of zone 3 is typical of a direct toxic effect; and (2) Complete enteral starvation with an absence of enteral stimulation causes disease of the lower biliary tract.
BMC Musculoskeletal Disorders | 2011
Marion Rapp; Daniel Svoboda; Lucas M. Wessel; Martin M. Kaiser
BackgroundThe different treatment strategies for bone cysts in children are often associated with persistence and high recurrence rates of the lesions. The safety and clinical outcomes of a combined mechanical and biological treatment with elastic intramedullary nailing, artificial bone substitute and autologous platelet rich plasma are evaluated.MethodsFrom 02/07 to 01/09 we offered all children with bone cysts the treatment combination of elastic intramedullary nailing (ESIN), artificial bone substitute (Orthoss®) and autologous platelet rich plasma, concentrated by the Gravitational Platelet Separation (GPS®) - System. All patients were reviewed radiologically for one year following the removal of the intramedullary nailing, which was possible because of cyst obliteration.ResultsA cohort of 12 children (4 girls, 8 boys) was recruited. The mean patient age was 11.4 years (range 7-15 years). The bone defects (ten humeral, two femoral) included eight juvenile and four aneurysmal bone cysts. Five patients suffered from persistent cysts following earlier unsuccessful treatment of humeral bone cyst after pathologic fracture; the other seven presented with acute pathologic fractures. No peri- or postoperative complications occurred. The radiographic findings showed a total resolution of the cysts in ten cases (Capanna Grade 1); in two cases a small residual cyst remained (Capanna Grade 2). The intramedullary nails were removed six to twelve months (mean 7.7) after the operation; in one case, a fourteen year old boy (Capanna Grade 2), required a further application of GPS® and Orthoss® to reach a total resolution of the cyst. At follow-up (20-41 months, mean 31.8 months) all patients showed very good functional results and had returned to sporting activity. No refracture occurred, no further procedure was necessary.ConclusionsThe combination of elastic intramedullary nailing, artificial bone substitute and autologous platelet rich plasma (GPS®) enhances the treatment of bone cysts in children, with no resulting complications.
World Journal of Gastroenterology | 2015
Sabine Heumüller-Klug; Carsten Sticht; Karin Kaiser; Elvira Wink; Cornelia Irene Hagl; Lucas M. Wessel; Karl-Herbert Schäfer
AIM To characterize the influence of location, species and treatment upon RNA degradation in tissue samples from the gastrointestinal tract. METHODS The intestinal samples were stored in different medium for different times under varying conditions: different species (human and rat), varying temperature (storage on crushed ice or room temperature), time point of dissection of the submucous-mucous layer from the smooth muscle (before or after storage), different rinsing methods (rinsing with Medium, PBS, RNALater or without rinsing at all) and different regions of the gut (proximal and distal small intestine, caecum, colon and rectum). The total RNA from different parts of the gut (rat: proximal and distal small intestine, caecum, colon and rectum, human: colon and rectum) and individual gut layers (muscle and submucosal/mucosal) was extracted. The quality of the RNA was assessed by micro capillary electrophoresis. The RNA quality was expressed by the RNA integrity number which is calculated from the relative height and area of the 18 S and 28 S RNA peaks. From rat distal small intestine qPCR was performed for neuronal and glial markers. RESULTS RNA obtained from smooth muscle tissue is much longer stable than those from submucosal/mucosal tissue. At RT muscle RNA degrades after one day, on ice it is stable at least three days. Cleaning and separation of gut layers before storage and use of RNALater, maintains the stability of muscle RNA at RT for much longer periods. Different parts of the gut show varying degradation periods. RNA obtained from the submucosal/mucosal layer always showed a much worse amplification rate than RNA from muscle tissue. In general RNA harvested from rat tissue, either smooth muscle layer or submucosal/mucosal layer is much longer stable than RNA from human gut tissue, and RNA obtained from smooth muscle tissue shows an increased stability compared to RNA from submucosal/mucosal tissue. At RT muscle RNA degrades after one day, while the stability on ice lasts at least three days. Cleaning and separation of gut layers before storage and use of RNALater, maintains the stability of muscle RNA at RT for much longer periods. Different parts of the gut show varying degradation periods. The RNA from muscle and submucosal/mucosal tissue of the proximal small intestine degrades much faster than the RNA of distal small intestine, caecum or colon with rectum. RNA obtained from the submucosal/mucosal layer always showed a much more reduced amplification rate than RNA from muscle tissue [β-Tubulin III for muscle quantification cycle (Cp): 22.07 ± 0.25, for β-Tubulin III submucosal/mucosal Cp: 27.42 ± 0.19]. CONCLUSION Degradation of intestinal mRNA depends on preparation and storage conditions of the tissue. Cooling, rinsing and separating of intestinal tissue reduce the degradation of mRNA.
Pediatric Surgery International | 2012
Cornelia Irene Hagl; Sabine Heumüller; Markus Klotz; Ulrike Subotic; Lucas M. Wessel; Karl-Herbert Schäfer
Background and aimsThe transplantation of neural crest derived stem cells (NCSC’s) is a potent alternative for the treatment of Hirschsprung’s disease (HSCR). Cells to be transplanted should find an appropriate microenvironment to survive and differentiate. To investigate the quality of this microenvironment, effects of HSCR-smooth-muscle-protein extracts upon NCSC’s were studied in vitro.MethodsPostnatal human gut from children undergoing colonic resection due to HSCR was divided in segments. Smooth muscle was dissected and homogenized. Glial-cell-line-derived-neurotrophic-factor (GDNF) concentration was measured in the homogenates from the individual segment using ELISA. NCSC’s were exposed to protein extracts derived from ganglionic and aganglionic HSCR segments, and their effect upon neurite outgrowth, survival and branching was evaluated.ResultsThe amount of the factors varied considerably between the proximal and distal segments, and also from patient to patient. While extracts from proximal segments tended to have more prominent effects, all HSCR-muscle-protein extracts increased neuronal survival and network formation.ConclusionMuscle protein from aganglionic bowel supports the survival and outgrowth of NCSC’s and is so an appropriate target for neural stem cell treatment.