0000000000211044
AUTHOR
Daniel Drescher
Common variants in the HLA-DQ region confer susceptibility to idiopathic achalasia
Idiopathic achalasia is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus(1,2). This ultimately leads to massive dilatation and an irreversibly impaired megaesophagus. We performed a genetic association study in 1,068 achalasia cases and 4,242 controls and fine-mapped a strong MHC association signal by imputing classical HLA haplotypes and amino acid polymorphisms. An eight-residue insertion at position 227-234 in the cytoplasmic tail of HLA-DQ beta 1 (encoded by HLA-DQB1*05:03 and HLA-DQB1*06:01) confers the strongest risk for achalasia (P = 1.73 x 10(-19)). In addition, two amino acid substitutions in the. extracellular …
Die operative Therapie einer segmentalen, primären intestinalen Lymphangiektasie des Jejunums mit ausgeprägtem Chylaskos
Primary intestinal lymphangiectasia (PIL) is a protein-losing, exsudative gastroenteropathy causing lymphatic obstruction. Diagnosis depends on clinical examination and histological findings. Conservative treatment modalities include a low-fat diet and enteral nutritional therapy in order to reduce enteric protein loss and to improve fat metabolism. Other treatment options consist of administration of antiplasmin or octreotide to lower lymph flow and secretion. We report on a 58-year-old patient who underwent exploratory laparotomy due to a worsening physical status, recurrent chylaskos and leg oedema under conservative dietary therapy. Intraoperative findings showed a typical PIL of the je…
Coexpression of receptor-tyrosine-kinases in gastric adenocarcinoma-a rationale for a molecular targeting strategy?
AIM: To define the (co-)expression pattern of target receptor-tyrosine-kinases (RTK) in human gastric adenocarcinoma. METHODS: The (co-)expression pattern of VEGFR1-3, PDGFRα/β and EGFR1 was analyzed by RT-PCR in 51 human gastric adenocarcinomas. In addition, IHC staining was applied for confirmation of expression and analysis of RTK localisation. RESULTS: The majority of samples revealed a VEGFR1 (98%), VEGFR2 (80%), VEGFR3 (67%), PDGFRα (82%) and PDGFRβ (82%) expression, whereas only 62% exhibited an EGFR1 expression. 78% of cancers expressed at least four out of six RTKs. While VEGFR1-3 and PDGFRα revealed a predominantly cytoplasmatic staining in tumor cells, accompanied by an additiona…
Model of Wound Healing for Esophagogastric Anastomoses in Rats
<b><i>Background:</i></b> Anastomotic leakage after esophageal surgery is a significant cause of morbidity and mortality. Postoperative leakage of esophagogastric anastomosis has been reported in 2–30% of surgical patient, resulting in an increased need for reoperation and a high risk of subsequent esophageal stricture formation and fistula. So far, experimental investigations on major factors influencing the healing of esophageal anastomoses, e.g. neovascularization and collagen deposition, have been hindered by the lack of a functional rodent model. <b><i>Methods:</i></b> We developed a novel technique of gastric tube formation followed by e…
Murine genetic deficiency of neuronal nitric oxide synthase (nNOS-/-) and interstitial cells of Cajal (W/Wv): Implications for achalasia?
Background and aim Nitric oxide (NO) is an important inhibitory mediator of esophageal function, and its lack leads to typical features of achalasia. In contrast, the role of intramuscular interstitial cells of Cajal (ICC-IM) and vasoactive intestinal peptide (VIP) in lower esophageal sphincter (LES) function is still controversial. Therefore, we examined the function and morphology of the LES in vivo in NO-deficient (nNOS(-/-) ), ICC-IM-deficient (W/W(v) )-, and wild-type (WT) mice. Methods Esophageal manometry was performed with a micro-sized transducer catheter to quantify LES pressure, swallow evoked LES relaxation, and esophageal body motility. The LES morphology was examined by semiqu…
Co-expression of receptor tyrosine kinases in esophageal adenocarcinoma and squamous cell cancer.
This study aimed to define the co-expression pattern of target receptor tyrosine kinases (RTKs) in human esophageal adenocarcinoma and squamous cell cancer. The co-expression pattern of vascular endothelial growth factor receptor (VEGFR)1-3, platelet-derived growth factor receptor (PDGFR)alpha/beta and epidermal growth factor receptor 1 (EGFR1) was analyzed by RT-PCR in 50 human esophageal cancers (35 adenocarcinomas and 15 squamous cell cancers). In addition, IHC staining was applied for the confirmation of the expression and analysis of RTK localisation. The adenocarcinoma samples revealed VEGFR1 (97%), VEGFR2 (94%), VEGFR3 (77%), PDGFRalpha (91%), PDGFRbeta (85%) and EGFR1 (97%) expressi…
Impact of Minimally Invasive Surgery in the Spectrum of Current Achalasia Treatment Options
Minimally invasive Heller myotomy has evolved the “gold standard” procedure for achalasia in the spectrum of current treatment options. The laparoscopic technique has proved superior to the thoracoscopic approach due to improved visualization of the esophagogastric junction. Operative controversies most recently include the length of the myotomy, especially of its fundic part, with respect to the balance between postoperative persistent dysphagia and development of gastroesophageal reflux, as well as the type of the added antireflux procedure. Perioperative mortality should approach 0%, and favorable long-term results can be achieved in > 90%.
PDGFRa/β expression correlates with the metastatic behavior of human colorectal cancer: A possible rationale for a molecular targeting strategy
As new multi-target tyrosine kinase inhibitors are emerging in the therapy of various malignancies, our aim was to define the co-expression pattern of receptor-tyrosine-kinase platelet-derived growth factor receptors alpha and beta (PDGFRalpha/beta) in human colorectal cancer. The co-expression pattern of PDGFRalpha/beta was analyzed by RT-PCR in 99 histologically confirmed human colorectal carcinomas and five colorectal cancer cell lines. In addition, immunohistochemical (IHC) staining was applied for confirmation of expression and analysis of receptor tyrosine kinase (RTK) localisation. The colorectal cancer cell lines that were analysed revealed varying expression intensities of PDGFRalp…
Does expression of receptor tyrosine kinases in gastric adenocarcinoma correlate with clinicopathological parameters?
Introduction: The prognosis for patients with gastric cancer depends on the stage of the disease. Radical surgery and lymph node dissection represent the only curative intent and are the standard therapeutic option for patients with limited disease. As new multi-targeted receptor tyrosine kinase inhibitors (RTK) are ermerging in the therapy of diverse malignomas, our aim was to analyze the relevance of the targeted receptor tyrosine kinases on local growth, lymphatic dissemination and overall survival in gastric adenocarcinoma. Methods: The (co-)expression pattern of VEGFR1, VEGFR2, VEGFR3, PDGFRα, PDGFRβ and EGFR1 was analyzed by RT-PCR in 56 consecutive samples of human gastric adenocarci…