Browsing by Author "Schuler, P."

Background: Intravital microscopy allows direct visualization of the hepatic microvasculature. We report on a novel application of this technique using a chamber model that simulates the conditions of pneumoperitoneum. Methods: For this purpose, we designed a peritoneal cavity chamber for rats. In the present study, we evaluated the technical procedure without any induction of increased intraabdominal pressure to assess undisturbed hepatic microcirculation. Intravital microscopy of the liver was performed in 12 rats. Animals that underwent the same operative procedure without the chamber served as controls (n = 12). Results: Hepatic sinusoidal perfusion rate, leukocyte endothelial cell interaction, and bile flow showed no significant differences between the groups. Operating time was longer in the chamber group. Conclusion: The peritoneal cavity chamber is an attractive approach for the study of hepatic microvascular, cellular, and molecular mechanisms that are important to our understanding of the potential harmful effects of laparoscopy on hepatic circulation and liver function.

Background and aims. The impact of laparoscopy on tumor progression is still unclear. This study investigated the effect of CO2 pneumoperitoneum on the intra-abdominal growth of human colon carcinoma independently of the effect of the immune system. Methods. SCID mice underwent either median laparotomy or laparoscopy. Human colon carcinoma cells were implanted into the upper abdomen. The control group was not operated on following cell injection. Tumor growth and the protein expression pattern of proliferation marker Ki67, cell-cell adhesion molecules E-cadherin, alpha- and beta-catenin, and cell-extracellular matrix adhesion molecules CD44 v5 and v6 in tumor tissue were analyzed on postoperative day 14. Results. Total tumor volume in the laparoscopy group significantly exceeded that in the laparotomy group. Immunohistochemistry revealed reduced expression of alpha-catenin and elevated expression on beta-catenin and CD44 v5 in the tumor tissue of the laparoscopy group. Conclusion. The expression pattern of proteins associated with tumor progression and the increase in tumor growth suggest an increased risk of laparoscopy at least for the growth of advanced human colon carcinoma.

Background: To date, the effects of increased abdominal pressure, as given during carbon dioxide (CO2) pneumoperitoneum, on hepatic microcirculation and biliary excretion are unknown. Methods: Using a custom-made peritoneal cavity chamber, we performed intravital microscopy of the left liver lobe under conditions of CO) pneumoperitoneum in a rat model. In addition, biliary excretion was assessed. Results: The establishment of a CO2 pneumoperitoneum of 4 or 8 mmHg resulted in sinusoidal perfusion failure that was more pronounced in the periportal regions than in the midzonal and pericentral regions of the liver acinus. Biliary excretion was considerably reduced at an intraabdominal pressure of 8 mmHg. Leukocyte-endothelial cell interactions increased significantly in both hepatic sinusoids and postsinusoidal venules. Conclusion: Alterations in hepatic microcirculation and liver function must be taken into consideration in any kind of laparoscopic surgery and may be of particular clinical relevance in patients with liver pathology.

Background: The purpose of this study was to review surgical experience with gastrointestinal stromal tumours (GISTs) at a single tertiary university hospital, and to identify morphological and genetic prognostic markers of tumour progression. Methods: Forty-eight GISTs from 39 patients were reviewed retrospectively. The prognostic significance of DNA copy number changes, measured by comparative genomic hybridization (CGH), and morphological markers in low-risk and high-risk tumours were investigated. Results: Significantly more patients died from disease after incomplete tumour resection than after complete primary resection (P = 0020). Tumour size of 5 cm or greater, mitotic count of 2 or more, and proliferative activity greater than 10 per cent were significantly associated with a shorter recurrence-free survival (P = 0020, P = 0001 and P = 0.002 respectively). Patients with low-risk tumours had a significantly better outcome than those with high-risk GISTs, both in terms of overall and recurrence-free survival (P less than or equal to 0.001). CGH performed on 16 tumours revealed fewer DNA sequence copy number changes in low-risk than in high-risk GISTs. Non-progressive GISTs contained significantly fewer genetic alterations than recurrent or metastatic tumours (P < 0.001). Only tumours with more than five changes showed disease progression. Conclusion: Complete surgical resection is the most important means of cure for GISTs. DNA copy number changes are related to the behaviour of these tumours and may serve as additional prognostic markers.

Although the significance of tumour site for estimating malignant potential in gastrointestinal stromal tumours (GISTs) has recently been recognized, site-specific genetic patterns have not to date been defined. This study examined 52 e-kit-positive primary GISTs (with a mean follow-up of 42.3 months in 51 cases) from three different locations (35 gastric, 12 small intestinal, and five colorectal) using comparative genomic hybridization (CGH). In general, tumour site correlated with key prognostic factors, including tumour size, mitotic rate, proliferative activity, and probable malignant potential. Furthermore, several DNA copy number changes showed a site-dependent pattern. These included losses at 14q (gastric 83%, intestinal 35%; p = 0.001), losses at 22q (gastric 46%, intestinal 82%; p = 0.02), losses at 1p (gastric 23%, intestinal 88%; p = 1 x 10(-5)), losses at 15q (gastric 14%, intestinal 59%; p = 0.002), losses at 9q (gastric 14%, intestinal 53%; p = 0.006), and gains at 5p (gastric 11%, intestinal 53%; p = 0.002). These data demonstrate strong site-dependent genetic heterogeneity in GISTs that may form a basis for subclassification. Prognostic evaluation of DNA copy number changes identified losses at 9q as a site-independent prognostic marker associated with shorter disease-free survival (p = 0.03) and overall survival (p = 0.002). Furthermore, 9q loss also appeared to carry prognostic value in predicting overall survival for patients with advanced or progressive GISTs (p = 0.003). Copyright (C) 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley Sons, Ltd.