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Significance of preoperative C-reactive protein as a parameter of the perioperative course and long-term prognosis in squamous cell carcinoma and adenocarcinoma of the oesophagus

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World Journal of Gastroenterology 2006年第23期12卷 3746-3750页

作者： Ines Gockel Kathrin Dirksen Claudia M Messow theodor junginger Department of General and Abdominal Surgery Johannes Gutenberg-UniversityMainzGermany Institute of Biostatistics and Documentation Johannes Gutenberg-UniversityMainzGermany

AIM： C-reactive protein （CRP） is an acute-phase reactant and a known indicator of the malignant potential of the tumour. The aim of this study was to investigate the significance of preoperative CRP as a parameter of the perioperative course and long-term prognosis in patients with squamous cell carcinoma and aclenocarcinoma of the oesophagus. METHODS： Serum CRP was determined preoperatively in 291 of 371 patients undergoing oesophagectomy for cancer from December 1989 to March 2004. Median patient age was 59 （28-79） year, 82.5% of patients were males. Squamous cell carcinoma was diagnosed in 151 （51.9%） and aclenocarcinoma in 122 patients. Transhiatal oesophagectomy was clone in 151 （51.9%） patients and 134 （46.0%） patients underwent the abclominothoracic procedure. RESULTS： In 127 （43.6%） patients the preoperative serum CRP concentration was within the normal range （〈 5 mg/clL）, elevated CRP levels were measured in 164 （56.4%） patients. Tumour extension （P 〈 0.0005） and the number of lymph nodes affected by metastatic spread （P = 0.015） were significantly increased in the group with elevated CRP levels. Among the perioperative parameters both the number of blood transfusions （P = 0.006） and the general complication rate （P = 0.002） were higher in patients with elevated preoperative CRP levels. The long-term survival rate of 13.6 （0-109.8） mo was poorer in the group with elevated CRP levels compared to 18.9 （0-155.4） mo in the group with normal CRP levels （log-rank test： P = 0.107）. Multivariateanalysis with backward variables selection identified preoperative CRP as an independent prognostic factor of the long-term prognosis in patients with oesophageal carcinoma, with a hazard ratio of 1.182 （95% confidence interval： 1.030-1.356）. CONCLUSION： The preoperative serum CRP-level is an easily determined independent prognostic marker in patients with squamous cell carcinoma and adenocarcinoma of the oesophagus.

关键词： Preoperative C-reactive protein Perioperativecourse Long-term prognosis Squamous cell carcinoma Aclenocarcinoma Oesophagus

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Reduction of ischemia reperfusion injury after liver resection and hepatic inflow occlusion by α-lipoic acid in humans

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World Journal of Gastroenterology 2006年第42期12卷 6812-6817页

作者： Fritz Dünschede Kirsten Erbes Achim Kircher Stefanie Westermann Joachim Seifert Arno Schad Kempski Oliver Alexandra K Kiemer junginger theodor Department of General and Abdominal Surgery University hospital Mainz Germany Institute for Pathology University hospital Mainz Germany Institute for Neurosurgical Pathophysiology University hospital Mainz Germany Department of Pharmacy Pharmaceutical Biology Saarland University Germany

AIM： To evaluate the protective effects of preconditioning by α-lipoic acid （LA） in patients undergoing hepatic resection under inflow occlusion of the liver. METHODS： Twenty-four patients undergoing liver resection for various reasons either received 600 mg LA or NaCI 15 min before transection performed under inflow occlusion of the liver. Blood samples and liver wedge biopsy samples were obtained after opening of the abdomen immediately after inflow occlusion of the liver, and 30 min after the end of inflow occlusion of the liver. RESULTS： Serum levels of aspartate transferase and alanine transferase were reduced at all time points in patients who received LA in comparison to those who received NaCL. This was accompanied by reduced histomorphological features of oncosis. We observed TUNEL-positive hepatocytes in the livers of the untreated patients, especially after 30 min of ischemia. LA attenuated this increase of TUNEL-positive hepatocytes. Under preconditioning with LA, ATP content was significantly enhanced after 30 min of ischemia and after 30 min of reperfusion. CONCLUSION： This is the first report on the potential for LA reducing ischemia/reperfusion injury （IRI） of the liver in humans who were undergoing liver surgery. Beside its simple and rapid application, side effects did not occur. LA might therefore represent a new strategy against hepatic IRI in humans.

关键词： Liver ischemia Pringle manoeuvre Pharmacological pre-treatment Liver preconditioning Apoptosis Adenosine triphosphate

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Protective effects of ischemic preconditioning and application of lipoic acid prior to 90 min of hepatic ischemia in a rat model

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World Journal of Gastroenterology 2007年第27期13卷 3692-3698页

作者： Friedrich Duenschede Kirsten Erbes Nina Riegler Patrick Ewald Achim Kircher Stefanie Westermann Arno Schad Imke Miesmer Simon Albrecht-Schck Ines Gockel Alexandra K Kiemer theodor junginger Department of General and Abdominal Surgery University hospital Mainz Langenbeckstr.1 D-55131 Mainz Germany Institute for Pathology University hospital Mainz Germany Department of Pharmacy Pharmaceutical Biology Saarland University 66123 Saarbrücken Germany

AIM： To compare different preconditioning strategies to protect the liver from ischemia/reperfusion injury focusing on the expression of pro- and anti-apoptotic proteins. Interventions comprised different modes of ischemic preconditioning （IP） as well as pharmacologic pretreatment by α-lipoic acid （LA）. METHODS： Several groups of rats were compared： sham operated animals, non-pretreated animals （nt）, animals receiving IP （10 rain of ischemia by clamping of the portal triad and 10 min of reperfusion） prior to sustained ischemia, animals receiving selective ischemic preconditioning （IPsel, 10 min of ischemia by selective clamping of the ischemic lobe and 10 rain of reperfusion） prior to sustained ichemia, and animals receiving 500 1μmol α-LA injected i.v. 15 min prior to the induction of 90 min of selective ischemia. RESULTS： Cellular damage was decreased only in the LA group. TUNEL-positive hepatocytes as well as necrotic hepatocyte injury were also decreased only by LA（19 ± 2 vs 10 ± 1, P〈 0.05 and 29 ± 5 vs 12 ± 1, P 〈 0.05）. Whereas caspase 3- activities in liver tissue were unchanged, caspase 9- activity in liver tissue was decreased only by LA pretreatment （3.1 ± 0.3 vs 1.8 ± 0.2, P 〈 0.05）. Survival rate as the endpoint of liver function was increased after IP and LA pretreatment but not after IPsel. Levels of lipid peroxidation （LPO） in liver tissue were decreased in the IP as well as in the LA group compared to the nt group. Determination of pro- and anti-apoptotic proteins showed a shift towards anti-apoptotic proteins by LA. In contrast, both our IP strategies failed to influence apototic cell death. CONCLUSION： IP, consisting of 10 min of ischemia and 10 min of reperfusion, ischemia/reperfusion injury protects only partly against of the liver prior to 90 min of selective ischemia. IPsel did not influence ischemic tolerance of the liver. LA improved tolerance to ischemia, possibly by downregulation of pro-apoptotic Bax.

关键词： Warm liver ischemia Liver preconditioning Apoptosis Lipid peroxidation Pharmacological preconditioning

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Coexpression of receptor-tyrosine-kinases in gastric adenocarcinoma-a rationale for a molecular targeting strategy?

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World Journal of Gastroenterology 2007年第26期13卷 3605-3609页

作者： Daniel Drescher Markus Moehler Ines Gockel Kirsten Frerichs Annett Müller Friedrich Dünschede Thomas Borschitz Stefan Biesterfeld Martin Holtmann Thomas Wehler Andreas Teufel Kerstin Herzer Thomas Fischer Martin R Berger theodor junginger Peter R Galle Carl C Schimanski Department of General and Abdominal Surgery Johannes Gutenberg University of Mainz MainzGermany First Department of Internal Medicine Johannes Gutenberg University of Mainz MainzGermany Institute of Pathology Johannes Gutenberg University of MainzMainzGermany Third Department of Internal Medicine Johannes Gutenberg University of Mainz MainzGermany Unit of toxicology and chemotherapy German Cancer Research CenterGermany

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, PDGFR（α/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 additional nuclear staining for VEGFR3, EGFR1 was almost exclusively detected on the membrane of tumor cells. PDGFRβ was restricted to stromal pericytes, which also depicted a PDGFRα expression. CONCLUSION： Our results reveal a high rate ofreceptor-tyrosine-kinases coexpression in gastric adenocarcinoma and might therefore encourage an application of multiple-target RTK-inhibitors within a combination therapy.

关键词： VEGFR EGFR PDGFR Cancer Adeno-carcinoma Gastric Stomach

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