Recent advances in the in vitro characterization of human adult enteric neural progenitor cells have opened new possibilities for cell-based therapies in gastrointestinal motility disorders. However, ...whether these cells are able to integrate within an in vivo gut environment is still unclear. In this study, we transplanted neural progenitor-containing neurosphere-like bodies (NLBs) in a mouse model of hypoganglionosis and analyzed cellular integration of NLB-derived cell types and functional improvement. NLBs were propagated from postnatal and adult human gut tissues. Cells were characterized by immunohistochemistry, quantitative PCR and subtelomere fluorescence in situ hybridization (FISH). For in vivo evaluation, the plexus of murine colon was damaged by the application of cationic surfactant benzalkonium chloride which was followed by the transplantation of NLBs in a fibrin matrix. After 4 weeks, grafted human cells were visualized by combined in situ hybridization (Alu) and immunohistochemistry (PGP9.5, GFAP, SMA). In addition, we determined nitric oxide synthase (NOS)-positive neurons and measured hypertrophic effects in the ENS and musculature. Contractility of treated guts was assessed in organ bath after electrical field stimulation. NLBs could be reproducibly generated without any signs of chromosomal alterations using subtelomere FISH. NLB-derived cells integrated within the host tissue and showed expected differentiated phenotypes i.e. enteric neurons, glia and smooth muscle-like cells following in vivo transplantation. Our data suggest biological effects of the transplanted NLB cells on tissue contractility, although robust statistical results could not be obtained due to the small sample size. Further, it is unclear, which of the NLB cell types including neural progenitors have direct restoring effects or, alternatively may act via 'bystander' mechanisms in vivo. Our findings provide further evidence that NLB transplantation can be considered as feasible tool to improve ENS function in a variety of gastrointestinal disorders.
Tissue ACE phenotyping in lung cancer Danilov, Sergei M; Metzger, Roman; Klieser, Eckhard ...
PloS one,
12/2019, Volume:
14, Issue:
12
Journal Article
Peer reviewed
Open access
Pulmonary vascular endothelium is the main metabolic site for Angiotensin I-Converting Enzyme (ACE)-mediated degradation of several biologically-active peptides (angiotensin I, bradykinin, ...hemo-regulatory peptide Ac-SDKP). Primary lung cancer growth and lung cancer metastases decrease lung vascularity reflected by dramatic decreases in both lung and serum ACE activity. We performed precise ACE phenotyping in tissues from subjects with lung cancer.
ACE phenotyping included: 1) ACE immunohistochemistry with specific and well-characterized monoclonal antibodies (mAbs) to ACE; 2) ACE activity measurement with two ACE substrates (HHL, ZPHL); 3) calculation of ACE substrates hydrolysis ratio (ZPHL/HHL ratio); 4) the pattern of mAbs binding to 17 different ACE epitopes to detect changes in ACE conformation induced by tumor growth (conformational ACE fingerprint).
ACE immunostaining was dramatically decreased in lung cancer tissues confirmed by a 3-fold decrease in ACE activity. The conformational fingerprint of ACE from tumor lung tissues differed from normal lung (6/17 mAbs) and reflected primarily higher ACE sialylation. The increase in ZPHL/HHL ratio in lung cancer tissues was consistent with greater conformational changes of ACE. Limited analysis of the conformational ACE fingerprint in normal lung tissue and lung cancer tissue form the same patient suggested a remote effect of tumor tissue on ACE conformation and/or on "field cancerization" in a morphologically-normal lung tissues.
Local conformation of ACE is significantly altered in tumor lung tissues and may be detected by conformational fingerprinting of human ACE.
During embryonic development, the trachea emerges from an area of the foregut, which is often referred to as "anterior" or "common" foregut tube or simply foregut. To explain this process of ...differentiation, four competing models exist to date. The outgrowth and watershed models propose a foregut that remains constant in length. In the outgrowth model, the trachea buds off and elongates from the foregut, while in the watershed model, a mesenchymal wedge splits the growing foregut into the trachea and esophagus. In contrast, the septation model proposes a cranial splitting and thus a shortening of the "common" foregut tube into the trachea and esophagus by an emerging septum. Finally, the splitting and extension model describes an interaction of cranial splitting of the foregut and simultaneous caudal tracheal and esophageal growth.
Here we examine the development of the undifferentiated foregut by micro computed tomography, which allows precise measurements.
Our results show that this area of the foregut transforms into the larynx, a process, which is independent from tracheal and esophageal development.
These observations are only consistent with the outgrowth model.
Purpose: To describe a minimally invasive technique with primary closure and strong suture connection that is feasible in cases of larger, most common type B defects of congenital diaphragmatic ...hernia (CDH). Background: The thoracoscopic approach (TA) is a favorable technique for the repair of CDH and is still evolving globally. A common issue is finding the optimal suture technique for secure closure in order to prevent recurrences. Whether a defect can be closed only by sutures or by using a patch depends on the size of CDH, the presence of a muscular rim along the inner thoracic surface and finally on the surgeon’s experience. From a geometrical point of view, the challenge is to transform the circular defect into a line, without tension, with a strong compound and preferably without additional material. To address this, we apply a setting of the sutures in a “T-shape” and a way to lead the sutures around the rib bones in order to increase stability. This method allows for the primary closure of CDHs and also applies to larger defects. Cases: We present seven newborns with posterolateral CDH on the left side. The defects were solely repaired by TA and by the suturing technique described in detail.
Pancreatic trauma in children is rare; therefore, both scientific knowledge and clinical experience regarding its management are limited. Abdominal sonography and subsequent computed tomography (CT) ...imaging are the diagnostic mainstay after severe abdominal trauma in many pediatric trauma centers. However, the diagnosis of pancreatic injury is missed on the initial imaging in approximately one third of cases, with even higher numbers in young children. While conservative treatment is preferred in low-grade injuries, surgical interventions may be indicated in more severe injuries. We present a case series including four patients with high-grade pancreatic injury. Two patients were treated surgically with open laparotomy and primary suture of the head of the pancreas and pancreatico-enterostomy, one patient underwent endoscopic stenting of the pancreatic duct and one received conservative management including observation and secondary endoscopic treatment. We want to emphasize the fact that using a minimally invasive approach can be a feasible option in high-grade pancreatic injury in selected cases. Therefore, we advocate the necessity of fully staffed and equipped high-level pediatric trauma centers.
(1) Background: Accessory liver lobes are a rare finding and only a few case reports of accessory liver lobes in abdominal wall defects have been reported so far. In the case of a congenital wall ...defect including liver parenchyma, there is still an ongoing debate on the definition of the abdominal wall defect and best care practice. Even though congenital abdominal wall defects are frequently diagnosed in prenatal screenings, controversy on the underlying etiology, embryology and underlying anatomy remains. Prenatal distinction between omphalocele and hernia into the cord cannot always be obtained; however, due to its clinical relevance for postnatal management and counseling of parents, accurate diagnosis is essential. (2) Case Presentation: We describe the uncommon postnatal finding of a pediculated accessory liver lobe with gallbladder in a preterm with umbilical cord hernia, which was prenatally diagnosed as omphalocele. Postnatal examination revealed an amniotic sac with a diameter of six and a small abdominal wall defect of three centimeters in diameter. Postnatal management included resection of the accessory liver lobe and gallbladder and closure of the defect. (3) Results and (4) Conclusions: Throughout the literature, the distinction between umbilical cord hernia and omphalocele has been variable. This has led to confusion and difficulties regarding postnatal treatment options. In order to achieve an accurate prenatal and/or postnatal diagnosis, the morphological differences and clinical manifestation of umbilical cord hernia and omphalocele need to be assessed. Further embryological studies are warranted to understand the underlying embryological pathology of omphalocele and umbilical cord hernia and offer appropriate treatment. In consideration of possibly severe complications in the case of the torsion of a pedunculated accessory liver lobe, we strongly recommend primary removal once pre- or intraoperative identification has been made.
The embryology of the diaphragm Mayer, Steffi, MD; Metzger, Roman, MD, PhD; Kluth, Dietrich, MD, PhD
Seminars in pediatric surgery,
08/2011, Volume:
20, Issue:
3
Journal Article
Peer reviewed
Despite the progress in prenatal diagnosis and intervention as well as postnatal therapeutic strategies, congenital diaphragmatic hernia (CDH) is still associated with a meaningful mortality because ...of the induced pulmonary hypoplasia. An essential key in understanding the pathogenesis of CDH is the underlying embryology, which has been neglected during the last decades. Likewise, the development of the normal diaphragm is still poorly understood. Obsolescent perceptions, mainly formed from histologic sections, are still propagated. In this review we present an atlas of scanning electron microscopy images that depict the normal and defective development of the diaphragm in the nitrofen rat model for CDH. Our findings suggest that the normal diaphragm mainly develops from the posthepatic mesenchymal plate. If the development of the posthepatic mesenchymal plate is impaired, a diaphragmatic defect occurs.
AIM：To investigate morphological changes of intestinal smooth muscle contractile fibres in small bowel atresia patients.METHODS：Resected small bowel specimens from small bowel atresia patients（n = ...12） were divided into three sections（proximal,atretic and distal）.Standard histology hematoxylin-eosin staining and enzyme immunohistochemistry was performed to visualize smooth muscle contractile markers-smooth muscle actin（SMA） and desmin using conventional paraffin sections of the proximal and distal bowel.Small bowel from agematched patients（n = 2） undergoing Meckel＇s diverticulum resection served as controls.RESULTS：The smooth muscle coat in the proximal bowel of small bowel atresia patients was thickened compared with control tissue,but the distal bowel was unchanged.Expression of smooth muscle contractile fibres SMA and desmin within the proximal bowel was slightly reduced compared with the distal bowel and control tissue.There were no major differences in the architecture of the smooth muscle within the proximal bowel and the distal bowel.The proximal and distal bowel in small bowel atresia patients revealed only minimal differences regarding smooth muscle morphology and the presence of smooth muscle contractile filament markers.CONCLUSION：Changes in smooth muscle contractile filaments do not appear to play a major role in postoperative motility disorders in small bowel atresia.
Intrauterine autoamputation of the ovary is an extremely rare diagnosis in the pediatric population. The current literature is limited to contradictory recommendations, while a standard management ...protocol for autoamputated adnexa secondary to intrauterine ovarian torsion is yet to be established. We report 2 cases of auto-amputation of the ovary, leading to a free-floating intra-abdominal cyst in the newborn. Laparoscopic management was successful in both cases.
Intestinal aganglionosis in children is a common cause of neonatal and infantile obstruction or ileus. Diagnosis is based on a histologically proven absence of enteric ganglion cells in deep biopsies ...of the gut wall. Therapeutic goal is a one-stage repair with a resection of the affected segment. The endorectal pull-through (ERP) can be performed entirely transanally in a lot of the cases. In patients with difficult preparation or a high aganglionosis ERP often needs to be assisted by laparoscopy or laparotomy. We present two cases with a technical modification performing a totally transanal pull-through colectomy without any trocars other than an umbilical camera trocar. The procedure starts with a classical endorectal technique. Usually, the transanal preparation is limited by reaching the colon descendens. A camera trocar is inserted and under laparoscopic vision the preparation is completed placing the instruments directly via the opened anus. After reaching the healthy colon segment, the pull-through is completed transanally. One of the main advantages of ERP is the sparing dissection. Our modification combines advantages of laparoscopy and ERP. The umbilical camera allows an excellent view while the instruments for dissection are used like with ERP without any further trocar or traction of the anal sphincter. The dispensation of any transanal trocar allows a higher grade of freedom in preparation and possibly a smaller trauma on the distal anal channel.
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