Cancer cell invasion takes place at the cancer-host interface and is a prerequisite for distant metastasis. The relationships between current biological and clinical concepts such as cell migration modes, tumour budding and epithelial-mesenchymal transition (EMT) remains unclear in several aspects, especially for the 'real' situation in human cancer. We developed a novel method that provides exact three-dimensional (3D) information on both microscopic morphology and gene expression, over a virtually unlimited spatial range, by reconstruction from serial immunostained tissue slices. Quantitative 3D assessment of tumour budding at the cancer-host interface in human pancreatic, colorectal, lung and breast adenocarcinoma suggests collective cell migration as the mechanism of cancer cell invasion, while single cancer cell migration seems to be virtually absent. Budding tumour cells display a shift towards spindle-like as well as a rounded morphology. This is associated with decreased E-cadherin staining intensity and a shift from membranous to cytoplasmic staining, as well as increased nuclear ZEB1 expression.
Our study identifies clinically relevant risk factors for postpancreatectomy hemorrhage and mortality. Interventional treatment of extraluminal hemorrhage is successful in about half of the cases and if unsuccessful constitutes a valuable adjunct to operative hemostasis. Based on our observations, we propose a treatment scheme for PPH. Risk factor analysis suggests appropriate patient selection especially for extended resections and pancreatogastrostomy for reconstruction in pancreatoduodenectomy.
Background: Fundamental experimental research into intestinal anastomotic healing in rodent models will gain increasing interest in the future. Methods: The aim of this study was to describe our 5-year experience with a standardized experimental setup of small and large bowel anastomoses in a rodent model and present a basic set of assessment tools investigating anastomotic healing. Anastomotic technique, perioperative complications such as anastomotic insufficiency (AI) and obstructive ileus were in the focus. Results: During different studies with varying study patterns, 167 rat small bowel anastomoses and 120 colonic anastomoses were performed. Overall mortality was 3.6% in small bowel and 2.5% in colonic anastomoses, AI occurred in 2.9 and 4%, respectively. A postoperative obstructive ileus was seen in 3/167 small bowel anastomoses and none in the colonic group. Conclusion: When performing experimental intestinal anastomoses in a standardized operative setting and critically considering special perioperative issues, the incidence of relevant complications can be maintained at an adequately low level.
Background: Anastomotic leakage is a major factor for morbidity in colorectal surgery. Anastomotic reinforcement with biological or synthetic materials has been claimed to be useful in preventing anastomotic leakage. Methods: We evaluated a non-cross-linked collagenous matrix Bio-Gide® (BG) for sealing colonic anastomoses in a rodent model. The animals were investigated for 4, 30 and 90 days. Macroscopic examination, histological examination and measurement of bursting pressure were performed. The anastomotic stricture rate was evaluated by radiographic contrast enema. Results: Microscopically anastomoses sealed by BG showed impaired anastomotic healing. Blood vessel ingrowth and collagen deposition were decreased without reaching significance after 4 days. The anastomotic bursting pressure was significantly decreased (p = 0.0454) in the early phase of healing. Anastomotic neovascularization was significantly decreased compared to the control group after 30 (p = 0.0058) and 90 days (p = 0.0275). Although no difference in anastomotic stricture rate was evident, the rate of intra-abdominal adhesions was significantly increased after 30 (p = 0.0124) and 90 days (p = 0.0281). Conclusion: BG failed to improve colonic anastomotic healing. Early anastomotic healing was impaired if anastomoses were reinforced with BG. BG did not affect the anastomotic stricture rate for up to 3 months; nevertheless, intra-abdominal adhesions were increased.
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