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204. Well-differenitated duodenal tumor/carcinoma(excluding gastrinomas)

Author

Jensen, R., Rindi, G., Arnold, R., Lopes, J., Brandi, M., Bechstein, W., Christ, E., Taal, B., Knigge, U., Ahlman, H., Kwekkeboom, D., O'Toole, D., Cadiot, G., Caplin, M., Chung, D., Couvelard, A., Herder, W. D., Fave, G. D., Eriksson, B., Falchetti, A., Falconi, Massimo, Ferone, D., Goretzki, P., Gross, D., Hochhauser, D., Hyrdel, R., Kaltsas, G., Keleştimur, F., Kianmanesh, R., Knapp, W., Komminoth, P., Körner, M., Kos Kudła, B., Kvols, L., Lewington, V., Manfredi, Riccardo, Mcnicol, A., Mitry, E., Niederle, B., Nikou, G., Nilsson, O., Öberg, K., O'Connor, J., Pauwels, S., Pape, U., Pavel, M., Perren, A., Plöckinger, U., Ramage, J., Ricke, J., Ruszniewski, P., Salazar, R., Sauvanet, A., Scarpa, Aldo, Scoazec, J., Garcia, M. S., Steinmüller, T., Sundin, A., Cutsem, E. V., Vullierme, M., Wiedenmann, B., Wildi, S., Yao, J., Zgliczynski, S., Radiology & Nuclear Medicine, R., Jensen, G., Rindi, R., Arnold, J., Lope, M., Brandi, W., Bechstein, E., Christ, B., Taal, U., Knigge, H., Ahlman, D., Kwekkeboom, D., O'Toole, G., Cadiot, M., Caplin, D., Chung, A., Couvelard, W. D., Herder, G. D., Fave, B., Eriksson, A., Falchetti, Falconi, Massimo, D., Ferone, P., Goretzki, D., Gro, D., Hochhauser, R., Hyrdel, G., Kaltsa, F., Keleştimur, R., Kianmanesh, W., Knapp, P., Komminoth, M., Körner, B., Kos Kudła, L., Kvol, V., Lewington, R., Manfredi, A., Mcnicol, E., Mitry, B., Niederle, G., Nikou, O., Nilsson, K., Öberg, J., O'Connor, S., Pauwel, U., Pape, M., Pavel, A., Perren, U., Plöckinger, J., Ramage, J., Ricke, P., Ruszniewski, R., Salazar, A., Sauvanet, A., Scarpa, J., Scoazec, M. S., Garcia, T., Steinmüller, A., Sundin, E. V., Cutsem, M., Vullierme, B., Wiedenmann, S., Wildi, J., Yao, and S., Zgliczynski

Subjects
ENDOCRINE GASTROENTEROPANCREATIC TUMORS, medicine.medical_specialty, Somatostatin receptor scintigraphy, Endocrine and Autonomic Systems, business.industry, Endocrinology, Diabetes and Metabolism, General surgery, Carcinoma, ZOLLINGER-ELLISON-SYNDROME, Well differentiated, Cellular and Molecular Neuroscience, Endocrinology, Duodenal Neoplasms, Internal medicine, Duodenal Tumor, Cancer centre, medicine, AMPULLARY CARCINOID-TUMORS, Humans, ZOLLINGER-ELLISON-SYNDROME, SOMATOSTATIN RECEPTOR SCINTIGRAPHY, ENDOCRINE GASTROENTEROPANCREATIC TUMORS, AMPULLARY CARCINOID-TUMORS, business, SOMATOSTATIN RECEPTOR SCINTIGRAPHY
Abstract

a Digestive Diseases Branch, NIDDK, NIH, Bethesda, Md. , USA; b Dipartimento di Patologia e Medicina di Laboratorio, Universita di Parma, Parma , Italy; c Division of Gastroenterology and Endocrinology, Department of Internal Medicine, Philipps University, Marburg , Germany; d Department of Pathology, IPATIMUP Hospital, Porto , Portugal; e Dipartimento di Fisiopatologia Clinica, Universita di Firenze, Firenze , Italy; f Department of Surgery, Johann-Wolfgang-Goethe-Universitat, Frankfurt , Germany; g E. Christ, Department of Endocrinology, Inselspital, Bern , Switzerland; h Department of Oncology, Netherlands Cancer Centre, Amsterdam , The Netherlands; i Department of Surgery, Rigshospitalet Blegdamsvej Hospital, Copenhagen , Denmark; j Department of Surgery, Gothenburg University, Gothenburg , Sweden; k Department of Nuclear Medicine, Erasmus Medical Center, Rotterdam , The Netherlands; l Service de Gastroenterologie-Pancreatologie, Pole des Maladies de l’Appareil Digestif, Hopital Beaujon, Clichy , France

Published
2006

205. Well-differentiated pancreatic tumor/carcinoma: Insulinoma

Author

Herder, W. D., Niederle, B., Scoazec, J., Pauwels, S., Klöppel, G., Falconi, Massimo, Kwekkeboom, D., Öberg, K., Eriksson, B., Wiedenmann, B., Rindi, G., O'Toole, D., Ferone, D., Ahlman, H., Arnold, R., Bechstein, W., Cadiot, G., Caplin, M., Christ, E., Chung, D., Couvelard, A., Fave, G. D., Falchetti, A., Goretzki, P., Gross, D., Hochhauser, D., Hyrdel, R., Jensen, R., Kaltsas, G., Keleştimur, F., Kianmanesh, R., Knapp, W., Knigge, U., Komminoth, P., Körner, M., Kos Kudła, B., Kvols, L., Lewington, V., Lopes, J., Manfredi, Riccardo, Mcnicol, A., Mitry, E., Nikou, G., Nilsson, O., O'Connor, J., Pape, U., Pavel, M., Perren, A., Plöckinger, U., Ramage, J., Ricke, J., Ruszniewski, P., Salazar, R., Sauvanet, A., Scarpa, Aldo, Garcia, M. S., Steinmüller, T., Sundin, A., Taal, B., Cutsem, E. V., Vullierme, M., Wildi, S., Yao, J., Zgliczyñski, S., W. W., de Herder, B., Niederle, J., Scoazec, S., Pauwel, G., Kloppel, Falconi, Massimo, D. J., Kwekkeboom, K., Oberg, B., Eriksson, B., Wiedenmann, G., Rindi, D., O'Toole, D., Ferone, F. C., Conference, E. N., Tumor Society, Internal Medicine, and Gastroenterology & Hepatology

Subjects
medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Intraoperative ultrasound, Carcinoma pancreas, Cellular and Molecular Neuroscience, Endocrinology, OCTREOTIDE, Internal medicine, medicine, ENDOSCOPIC ULTRASOUND, Humans, Carcinoma, Insulinoma, Pancreatic Neoplasms, Pancreas Carcinoma, Somatostatin receptor scintigraphy, SLET-CELL TUMORS, Endocrine and Autonomic Systems, business.industry, General surgery, HYPERINSULINEMIC HYPOGLYCEMIA, LOCALIZATION, University hospital, Well differentiated, SLET-CELL TUMORS, SOMATOSTATIN RECEPTOR SCINTIGRAPHY, NEUROENDOCRINE TUMORS, HYPERINSULINEMIC HYPOGLYCEMIA, INTRAOPERATIVE ULTRASOUND, ENDOSCOPIC ULTRASOUND, ENDOCRINE TUMORS, LOCALIZATION, OCTREOTIDE, MRI, ENDOCRINE TUMORS, INTRAOPERATIVE ULTRASOUND, business, SOMATOSTATIN RECEPTOR SCINTIGRAPHY, NEUROENDOCRINE TUMORS, MRI
Abstract

a Department of Internal Medicine, Section of Endocrinology, Erasmus MC, Rotterdam, The Netherlands; b Division of General Surgery, Department of Surgery, Medical University of Vienna, Vienna , Austria; c Hospices Civils de Lyon, Hopital Edouard-Herriot Service Central d‘Anatomie et Cytologie Pathologiques, Lyon , France; d Centre de Medecine Nucleaire, Universite Catholique de Louvain, Brussels , Belgium; e Department of Pathology, University of Kiel, Kiel , Germany; f B Unit of Surgery, Department of Surgery, University of Verona, Verona , Italy; g Department of Nuclear Medicine, Erasmus MC, Rotterdam , The Netherlands; h Department of Endocrine Oncology, University Hospital, Uppsala , Sweden; i Department of Internal Medicine, Division of Hepatology and Gastroenterology, Interdisciplinary Center of Metabolism and Endocrinology, Charite, Campus Virchow Hospital, University for Medicine Berlin, Berlin , Germany; j Service de Gastroenterologie-Pancreatologie, Pole des Maladies de l‘Appareil Digestif, Hopital Beaujon, Clichy , France; k Department of Pathology and Laboratory Medicine, Universita degli Studi, Parma, Italy; l Department of Endocrinology, Genoa University, Genoa , Italy

Published
2006

211. Renal Function Outcomes With Tacrolimus QD After De Novo Liver Transplantation for Different Primary Diseases: Ad Hoc Analysis From The DIAMOND Randomized, Controlled Trial.

Author

Bechstein, W., primary, Truneĉka, P., additional, Klempnauer, J., additional, Pirenne, J., additional, Bennet, W., additional, Zhao, A., additional, Isoniemi, H., additional, Kamar, N., additional, Settmacher, U., additional, Brown, M., additional, Undre, N., additional, and Tisone, G., additional

Published
2014
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212. The European Liver Transplant Registry (ELTR): Improved Survival Outcomes in De Novo Liver Transplantation With Tacrolimus Prolonged Release (ADVAGRAF).

Author

Adam, R., primary, Karam, V., additional, Delvart, V., additional, Trunecka, P., additional, Samuel, D., additional, Bechstein, W., additional, Nemec, P., additional, Tisone, G., additional, Klempnauer, J., additional, Rossi, M., additional, Rummo, O., additional, Belghiti, J., additional, Krawczyk, M., additional, Pratschke, J., additional, Kollmar, O., additional, Boudjema, K., additional, Colledan, M., additional, Ericzon, B., additional, Mantion, G., additional, Baccarani, U., additional, Neuhaus, P., additional, Paul, A., additional, Bachellier, P., additional, Zamboni, F., additional, and Muiesan, P., additional

Published
2014
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213. Renal Function Outcomes With Tacrolimus QD After De Novo Liver Transplantation for Different Baseline eGFR: Ad Hoc Analysis From the DIAMOND Randomized Controlled Trial.

Author

Tisone, G., primary, Klempnauer, J., additional, Bechstein, W., additional, Pirenne, J., additional, Friman, S., additional, Zhao, A., additional, Isoniemi, H., additional, Rostaing, L., additional, Settmacher, U., additional, Brown, M., additional, Undre, N., additional, and Trunecka, P., additional

Published
2014
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215. Reperfusion of the Transplanted Liver: Heterogeneous Techniques in European Transplantation Centres

Author

Manzini, G., Houben, P., Kremer, M., Bechstein, W. O., Becker, T., Berlakovich, G. A., Friess, H., Guba, M., Hohenberger, W., Jonas, S., Kalff, J. C., Klar, E., Klempnauer, J., Lerut, J., Lippert, H., Lorf, T., Nadalin, S., Nashan, B., Neuhaus, P., Paul, A., Pirenne, J., Ringers, J., Rogiers, X., Schilling, M. K., Senninger, N., Settmacher, U., Stippel, D. L., Tscheliessnigg, K., van Lanschot, J. J., Ysbaert, D., Binder, H., Buechler, M. W., Schemmer, P., Manzini, G., Houben, P., Kremer, M., Bechstein, W. O., Becker, T., Berlakovich, G. A., Friess, H., Guba, M., Hohenberger, W., Jonas, S., Kalff, J. C., Klar, E., Klempnauer, J., Lerut, J., Lippert, H., Lorf, T., Nadalin, S., Nashan, B., Neuhaus, P., Paul, A., Pirenne, J., Ringers, J., Rogiers, X., Schilling, M. K., Senninger, N., Settmacher, U., Stippel, D. L., Tscheliessnigg, K., van Lanschot, J. J., Ysbaert, D., Binder, H., Buechler, M. W., and Schemmer, P.

Published
2012

217. A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma

Author

Schnitzbauer, A, Zuelke, C, Graeb, C, Rochon, J, Bilbao, I, Burra, P, de Jong, K, Duvoux, C, Kneteman, N, Adam, R, Bechstein, W, Becker, T, Beckebaum, S, Chazouilleres, O, Cillo, U, Colledan, M, Fandrich, F, Gugenheim, J, Hauss, J, Heise, M, Hidalgo, E, Jamieson, N, Konigsrainer, A, Lamby, P, Lerut, J, Makisalo, H, Margreiter, R, Mazzaferro, V, Mutzbauer, I, Otto, G, Pageaux, G, Pinna, A, Pirenne, J, Rizell, M, Rossi, G, Rostaing, L, Roy, A, Turrion, V, Schmidt, J, Troisi, R, van Hoek, B, Valente, U, Wolf, P, Wolters, H, Mirza, D, Scholz, T, Steininger, R, Soderdahl, G, Strasser, S, Jauch, K, Neuhaus, P, Schlitt, H, Geissler, E, Schnitzbauer AA, Zuelke C, Graeb C, Rochon J, Bilbao I, Burra P, de Jong KP, Duvoux C, Kneteman NM, Adam R, Bechstein WO, Becker T, Beckebaum S, Chazouilleres O, Cillo U, Colledan M, Fandrich F, Gugenheim J, Hauss JP, Heise M, Hidalgo E, Jamieson N, Konigsrainer A, Lamby PE, Lerut JP, Makisalo H, Margreiter R, Mazzaferro V, Mutzbauer I, Otto G, Pageaux GP, Pinna AD, Pirenne J, Rizell M, Rossi G, Rostaing L, Roy A, Turrion VS, Schmidt J, Troisi RI, van Hoek B, Valente U, Wolf P, Wolters H, Mirza DF, Scholz T, Steininger R, Soderdahl G, Strasser SI, Jauch KW, Neuhaus P, Schlitt HJ, Geissler EK, Schnitzbauer, A, Zuelke, C, Graeb, C, Rochon, J, Bilbao, I, Burra, P, de Jong, K, Duvoux, C, Kneteman, N, Adam, R, Bechstein, W, Becker, T, Beckebaum, S, Chazouilleres, O, Cillo, U, Colledan, M, Fandrich, F, Gugenheim, J, Hauss, J, Heise, M, Hidalgo, E, Jamieson, N, Konigsrainer, A, Lamby, P, Lerut, J, Makisalo, H, Margreiter, R, Mazzaferro, V, Mutzbauer, I, Otto, G, Pageaux, G, Pinna, A, Pirenne, J, Rizell, M, Rossi, G, Rostaing, L, Roy, A, Turrion, V, Schmidt, J, Troisi, R, van Hoek, B, Valente, U, Wolf, P, Wolters, H, Mirza, D, Scholz, T, Steininger, R, Soderdahl, G, Strasser, S, Jauch, K, Neuhaus, P, Schlitt, H, Geissler, E, Schnitzbauer AA, Zuelke C, Graeb C, Rochon J, Bilbao I, Burra P, de Jong KP, Duvoux C, Kneteman NM, Adam R, Bechstein WO, Becker T, Beckebaum S, Chazouilleres O, Cillo U, Colledan M, Fandrich F, Gugenheim J, Hauss JP, Heise M, Hidalgo E, Jamieson N, Konigsrainer A, Lamby PE, Lerut JP, Makisalo H, Margreiter R, Mazzaferro V, Mutzbauer I, Otto G, Pageaux GP, Pinna AD, Pirenne J, Rizell M, Rossi G, Rostaing L, Roy A, Turrion VS, Schmidt J, Troisi RI, van Hoek B, Valente U, Wolf P, Wolters H, Mirza DF, Scholz T, Steininger R, Soderdahl G, Strasser SI, Jauch KW, Neuhaus P, Schlitt HJ, and Geissler EK

Abstract

Background: The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC.Methods/Design: The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 21/2 -year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating.Discussion: If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to p

Published
2010

218. Randomized trial of surgery versus surgery followed by adjuvant hepatic arterial infusion with 5-fluorouracil and folinic acid for liver metastases of colorectal cancer. German Cooperative on Liver Metastases (Arbeitsgruppe Lebermetastasen)

Author

Lorenz, M, Müller, H H, Schramm, H, Gassel, H J, Rau, H G, Ridwelski, K, Hauss, J, Stieger, R, Jauch, K W, Bechstein, W O, and Encke, A

Subjects
Research Article
Abstract

OBJECTIVE: To determine the impact of adjuvant hepatic arterial infusion (HAI) on survival relative to resection alone in patients with radical resection of colorectal liver metastases. SUMMARY BACKGROUND DATA: Nearly 40% to 50% of all patients with colorectal carcinoma develop liver metastases. Curative resection results in a 5-year survival rate of 25% to 30%. Intrahepatic recurrence occurs after a median of 9 to 12 months in up to 60% of patients. The authors hypothesized that adjuvant intraarterial infusion of 5-fluorouracil (5-FU) might decrease the rate of intrahepatic recurrence and improve survival in patients with radical resection of colorectal liver metastases. METHODS: Between April 5, 1991, and December 31, 1996, patients with colorectal liver metastases from 26 hospitals were stratified by the number of metastases and the site of the primary tumor and randomized to resection of the liver metastases followed by adjuvant HAI of 5-FU (1000 mg/m2 per day for 5 days as a continuous 24-hour infusion) plus folinic acid (200 mg/m2 per day for 5 days as a short infusion), or liver resection only. RESULTS: The first planned intention-to-treat interim analysis after inclusion of 226 patients and 91 events (deaths) showed a median survival of 34.5 months for patients with adjuvant therapy versus 40.8 months for control patients. The median time to progression was 14.2 months for the chemotherapy group versus 13.7 months for the control group. Grade 3 and 4 toxicities (World Health Organization), mainly stomatitis (57.6%) and nausea (55.4%), occurred in 25.6% of cycles and 62.9% of patients. CONCLUSION: According to this planned interim analysis, adjuvant HAI, when used in this dose and schedule in patients with resection of colorectal liver metastases, reduced the risk of death at best by 15%, but at worst the risk of death was doubled. Thus, the chance of detecting an expected 50% improvement in survival by the use of HAI was only 5%. Patient accrual was therefore terminated.

Published
1998

219. Diagnostik und Therapie des hepatozellulären Karzinoms

Author

Greten, T., additional, Malek, N., additional, Schmidt, S., additional, Arends, J., additional, Bartenstein, P., additional, Bechstein, W., additional, Bernatik, T., additional, Bitzer, M., additional, Chavan, A., additional, Dollinger, M., additional, Domagk, D., additional, Drognitz, O., additional, Düx, M., additional, Farkas, S., additional, Folprecht, G., additional, Galle, P., additional, Geißler, M., additional, Gerken, G., additional, Habermehl, D., additional, Helmberger, T., additional, Herfarth, K., additional, Hoffmann, R., additional, Holtmann, M., additional, Huppert, P., additional, Jakobs, T., additional, Keller, M., additional, Klempnauer, J., additional, Kolligs, F., additional, Körber, J., additional, Lang, H., additional, Lehner, F., additional, Lordick, F., additional, Lubienski, A., additional, Manns, M., additional, Mahnken, A., additional, Möhler, M., additional, Mönch, C., additional, Neuhaus, P., additional, Niederau, C., additional, Ocker, M., additional, Otto, G., additional, Pereira, P., additional, Pott, G., additional, Riemer, J., additional, Ringe, K., additional, Ritterbusch, U., additional, Rummeny, E., additional, Schirmacher, P., additional, Schlitt, H., additional, Schlottmann, K., additional, Schmitz, V., additional, Schuler, A., additional, Schulze-Bergkamen, H., additional, von Schweinitz, D., additional, Seehofer, D., additional, Sitter, H., additional, Straßburg, C., additional, Stroszczynski, C., additional, Strobel, D., additional, Tannapfel, A., additional, Trojan, J., additional, van Thiel, I., additional, Vogel, A., additional, Wacker, F., additional, Wedemeyer, H., additional, Wege, H., additional, Weinmann, A., additional, Wittekind, C., additional, Wörmann, B., additional, and Zech, C., additional

Published
2013
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223. Corticosteroid withdrawal in simultaneous pancreas-kidney transplantation: a 3-year report.

Author

UCL - MD/CHIR - Département de chirurgie, Malaise, Jacques, Nakache, R., Kahl, A., Bechstein, W., Langrehr, J., Uhl, I., Engelking, A., Neuhaus, P., VAN OPHEM, Dominique, Squifflet, Jean-Paul, UCL - MD/CHIR - Département de chirurgie, Malaise, Jacques, Nakache, R., Kahl, A., Bechstein, W., Langrehr, J., Uhl, I., Engelking, A., Neuhaus, P., VAN OPHEM, Dominique, and Squifflet, Jean-Paul

Abstract

Corticosteroids are an important element of immunosuppressive protocols, but their long-term use has detrimental effects on patient health, requiring eventual discontinuation. Herein, we present an evaluation of the safety and feasibility of corticosteroid withdrawal based on the findings of the Euro-SPK001 study. PATIENTS AND METHODS: In this prospective, multicenter study, 205 simultaneous pancreas-kidney (SPK) transplant recipients were randomized to immunosuppressive treatment with either tacrolimus and mycophenolate mofetil (MMF) (n = 103) or cyclosporine microemulsion (CsA-ME) and MMF (n = 102). All patients received concomitant rATG induction therapy, MMF, and short-term corticosteroids. RESULTS: Corticosteroid withdrawal was successful in the majority of in-study patients: 66% tacrolimus and 73% cyclosporin-ME. In-study patients selected for corticosteroid withdrawal experienced fewer pancreatic or kidney graft losses and fewer episodes of acute rejection compared with out-of-study patients or those continuing corticosteroid therapy. Acute rejection episodes occurred after corticosteroid withdrawal in two patients who had a previous rejection and in five patients who were rejection free before corticosteroid withdrawal. No rejection episodes were associated with graft loss or immediate serious consequences. Overall, corticosteroid withdrawal was achieved with an increase in both MMF and tacrolimus dosage. CONCLUSION: Corticosteroid withdrawal was successful in the majority of in-study patients. A long-term survey of corticosteroid withdrawal in SPK transplantation with multifactorial analyses is necessary to confirm these early results and to evaluate possible positive effects on glucose metabolism and hypertension.

Published
2005

226. Reperfusion of the Transplanted Liver: Heterogeneous Techniques in European Transplantation Centres

Author

Manzini, G., primary, Houben, P., additional, Kremer, M., additional, Bechstein, W. O., additional, Becker, T., additional, Berlakovich, G. A., additional, Friess, H., additional, Guba, M., additional, Hohenberger, W., additional, Jonas, S., additional, Kalff, J. C., additional, Klar, E., additional, Klempnauer, J., additional, Lerut, J., additional, Lippert, H., additional, Lorf, T., additional, Nadalin, S., additional, Nashan, B., additional, Neuhaus, P., additional, Paul, A., additional, Pirenne, J., additional, Ringers, J., additional, Rogiers, X., additional, Schilling, M. K., additional, Senninger, N., additional, Settmacher, U., additional, Stippel, D. L., additional, Tscheliessnigg, K., additional, van Lanschot, J. J., additional, Ysbaert, D., additional, Binder, H., additional, Büchler, M. W., additional, and Schemmer, P., additional

Published
2012
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231. Die Bedeutung der toxischen Sauerstoffradikale beim Ischämie/Reperfusionsschaden nach Lebertransplantation in der Ratte

Author

Galle, P., Bechstein, W.-O., Lehmann, Thorsten, Galle, P., Bechstein, W.-O., and Lehmann, Thorsten

Abstract

Einleitung: Der Ischämie/Reperfusionsschaden (I/R) ist die wesentliche Ursache des frühen Transplantatversagens nach Lebertransplantation (LTx). Fettlebern sind dabei besonders betroffen. Freie Sauerstoffradikale spielen bei der Pathogenese eine zentrale Rolle. Die Morphologie der so versagenden Transplantatleber ist charakterisiert durch Entzündung, Nekrose und Apoptose. Endogene Radikalfänger wie die Superoxiddismutase (SOD), nicht aber exogen zugefuhrte, bauen freie Radikale ab. Das Ziel der vorgelegten Studien war es, im Modell der LTx von gesunden und verfetteten Lebern in der Ratte mittels adenoviralem Gentransfer von SOD den I/R zu vermindern, die Überlebensrate zu erhöhen und zugrunde liegende Mechanismen aufzuzeigen. Methoden: Bei Experimenten mit verfetteten Lebern wurde eine ausgeprägte Steatose der Spenderlebern durch Füttern einer Ethanol- und fettreichen Diät (Lieber-DiCarli) erzeugt. Explantierte Lebern wurden für 24 h konserviert und orthotop transplantiert. Einigen Spendern wurde 72 h vor Organentnahme Cu/Zn-SOD enthaltendes Adenovirus (Ad.SOD1) i.v. appliziert. Als Kontrollen dienten Fettlebern, welche mit dem Gen von b-Galaktosidase (Ad.lacZ) transfiziert wurden, oder aber gesunde Lebern. Untersuchungsparameter waren neben Transfektionsparametern die Transaminasen, histopathologische Morphologie, Überlebensraten, sowie die Aktivierung von Transkriptionsfaktoren und deren Kinasen. Freie Radikale wurden in der Galle mittels Elektronenspin-Resonanz-Spektroskopie nachgewiesen. In weiteren Experimenten wurden auch die mitochondriale und die extrazelluläre Isoform hinsichtlich ihrer protektiven Wirkung untersucht. Ebenso wurde die Auswirkung der freien Radikale auf die Regeneration nach Teillebertransplantation untersucht. Ergebnisse: 72 h nach Injektion von Ad.lacZ exprimierten etwa 80% aller Hepatozyten die b-Galaktosidase. In der Ad.SOD1 Gruppe war die Genexpression 3-fach, die Aktivität 12-fach erhöht. Im Vergleich zu den unbehandelten oder Ad.lacZ, Background: Oxygen-derived free radicals play a central role in pathomechanisms of reperfusion injury after organ transplantation, and fatty livers are particularly susceptible. Endogenous radical scavenger systems such as superoxide dismutase (SOD) degrade toxic radicals; however, SOD is degraded rapidly when given exogenously. Therefore, the hypothesis that treatment of the donor liver with an adenoviral vector encoding the Cu/Zn-SOD gene (Ad.SOD1), or the Mn-SOD gene or the ec-SOD gene would lead to permanent gene expression and therefore protect the organ against injury and increase survival in a rat model of liver transplantation including fatty livers was tested. Transplantation of reduced-size livers may lead to a hypermetabolic state and increased production of oxygen radicals. Since oxygen radicals may cause liver injury and impair liver regeneration, we tested the hypothesis that overexpression of superoxide dismutase (SOD) in reduced-size livers (RSL) would accelerate regeneration and reduce injury in a rat model of transplantation of RSL. Methods: Donors received chow diet (untreated), high-fat diet, or ethanol-containing high-fat diet. Some donors were infected with Ad-SOD1, while untreated grafts and livers infected with the indicator gene lacZ encoding bacterial b-galactosidase (Ad.lacZ) served as controls. Some livers were harvested 72 hours later, reduced to 45% of weight, and transplanted. After liver transplantation, SOD activity and protein expression in liver, survival, histopathology, release of transaminases, free radical adducts in bile and activation of NF-kB, IkB kinase (IKK), Jun-N-terminal kinase (JNK) and TNFa were evaluated. Moreover, in transplanted split-livers regeneration was evaluated by Brdu-staining, and measurement of cyclinD1 and p21. Results: Approximately 80% of hepatocytes expressed b-galactosidase 72h after injection of Ad-lacZ. Moreover, SOD1 gene expression and activity were increased 3- and 10-fold in the Ad-SOD1 group

Published
2004

233. 6010 POSTER DISCUSSION Radiofrequency Ablation Combined With Systemic Treatment Versus Systemic Treatment Alone in Patients With Non- Resectable Colorectal Liver Metastases: a Randomized EORTC Intergroup Phase II Study (EORTC 40004)

Author

Ruers, T., primary, Punt, C., additional, van Coevorden, F., additional, Ledermann, J., additional, Poston, G., additional, Bechstein, W., additional, Lentz, M., additional, Mauei^, M., additional, Lutz, M., additional, and Nordlinger, B., additional

Published
2011
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242. Final results of the EORTC intergroup randomized study 40004 (CLOCC) evaluating the benefit of radiofrequency ablation (RFA) combined with chemotherapy for unresectable colorectal liver metastases (CRC LM).

Author

Ruers, T., primary, Punt, C. J., additional, van Coevorden, F., additional, Borel Rinkes, I., additional, Ledermann, J. A., additional, Poston, G. J., additional, Bechstein, W., additional, Lentz, M., additional, Mauer, M., additional, and Nordlinger, B., additional

Published
2010
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243. Daily dosing of tacrolimus in patients treated with HIV-1 therapy containing a ritonavir-boosted protease inhibitor or raltegravir

Author

Bickel, M., primary, Anadol, E., additional, Vogel, M., additional, Hofmann, W. P., additional, von Hentig, N., additional, Kuetscher, J., additional, Kurowski, M., additional, Moench, C., additional, Lennemann, T., additional, Lutz, T., additional, Bechstein, W. O., additional, Brodt, H. R., additional, and Rockstroh, J., additional

Published
2010
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245. Resectability and agreement between surgeons: Review of CT and MR scan of the CELIM study: (Multicenter randomized trial of cetuximab/FOLFOX versus cetuximab/FOLFIRI in unresectable liver metastases

Author

Bechstein, W. O., primary, Lang, H., additional, Köhne, C., additional, Parisi, F., additional, Raab, H. R., additional, Frilling, A., additional, Konopke, R., additional, Weitz, J., additional, Stroszczynski, C., additional, and Folprecht, G., additional

Published
2009
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249. Radiofrequency ablation (RFA) combined with chemotherapy for unresectable colorectal liver metastases (CRC LM): Interim results of a randomised phase II study of the EORTC-NCRI CCSG-ALM Intergroup 40004 (CLOCC)

Author

Ruers, T., primary, van Coevorden, F., additional, Pierie, J., additional, Borel Rinkes, I., additional, Punt, C., additional, Ledermann, J., additional, Poston, G. J., additional, Bechstein, W., additional, Lentz, M., additional, Collette, L., additional, and Nordlinger, B., additional

Published
2008
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