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6. Upregulation of the histone γ-H2AX correlates with worse patient survival and basal-like subtype in pancreatic ductal adenocarcinoma.

Author

Knipper, Karl, Hussein, Yussra, Simon, Adrian Georg, Fretter, Caroline, Damanakis, Alexander I., Zhao, Yue, Bruns, Christiane J., Schmidt, Thomas, Popp, Felix C., Quaas, Alexander, Lyu, Su Ir, Heise, Michael, Marusch, Frank, Siech, Marco, Mosa, Tawfik, Schniewind, Bodo, Tepel, Jürgen, Hartwig, Werner, Prinz, Christoph, and Rau, Bettina M.

Abstract

Purpose: Patients with pancreatic ductal adenocarcinoma (PDAC) have yet to experience significant benefits from targeted therapy. Olaparib is currently the only active substance in BRCA-mutated PDACs that successfully influences the DNA repair of carcinoma cells. H2AX belongs to the histone family and is known as a part of the DNA repair system. The inhibition of γ-H2AX could lead to the inhibition of mitotically active tumor cells. Therefore, we aimed to evaluate the predictive value of the γ-H2AX in patients with PDAC. Methods: All included patients (n = 311) received a pancreatic resection with curative intention in one of our PANCALYZE study centers. Subsequently, they were enrolled in a standardized follow-up protocol. Immunohistochemical stainings for γ-H2AX were conducted on tissue microarrays. Results: Patients exhibiting high levels of γ-H2AX expression experience more frequent R1 resections, indicating advanced tumor stages in this subgroup. Additionally, patients with high γ-H2AX expression demonstrated significantly poorer survival compared to those with low expression (median OS: 15 vs. 25 months, p < 0.001). In multivariate analyses, high γ-H2AX expression could be identified as an independent risk factor for worse patient survival. Moreover, high γ-H2AX expression could be more frequently observed in the more aggressive basal-like subtype. Conclusion: γ-H2AX can be characterized as a predictive biomarker for poorer patient survival. Consequently, upcoming clinical trials focused on the efficacy of targeted therapies influencing the DNA repair system and radiotherapy should evaluate γ-H2AX as a potential biomarker for therapy response. Furthermore, γ-H2AX may serve as a viable target for treatment in the future. [ABSTRACT FROM AUTHOR]

Published
2024
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7. 3rd St. Gallen EORTC Gastrointestinal Cancer Conference: Consensus recommendations on controversial issues in the primary treatment of pancreatic cancer

Author

Lutz, Manfred P., Zalcberg, John R., Ducreux, Michel, Aust, Daniela, Bruno, Marco J., Büchler, Markus W., Delpero, Jean-Robert, Gloor, Beat, Glynne-Jones, Rob, Hartwig, Werner, Huguet, Florence, Laurent-Puig, Pierre, Lordick, Florian, Maisonneuve, Patrick, Mayerle, Julia, Martignoni, Marc, Neoptolemos, John, Rhim, Andrew D., Schmied, Bruno M., Seufferlein, Thomas, Werner, Jens, van Laethem, Jean-Luc, and Otto, Florian

Published
2017
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8. Pancreatic anastomosis after pancreatoduodenectomy: A position statement by the International Study Group of Pancreatic Surgery (ISGPS)

Author

Shrikhande, Shailesh V., Sivasanker, Masillamany, Vollmer, Charles M., Friess, Helmut, Besselink, Marc G., Fingerhut, Abe, Yeo, Charles J., Fernandez-delCastillo, Carlos, Dervenis, Christos, Halloran, Christoper, Gouma, Dirk J., Radenkovic, Dejan, Asbun, Horacio J., Neoptolemos, John P., Izbicki, Jakob R., Lillemoe, Keith D., Conlon, Kevin C., Fernandez-Cruz, Laureano, Montorsi, Marco, Bockhorn, Max, Adham, Mustapha, Charnley, Richard, Carter, Ross, Hackert, Thilo, Hartwig, Werner, Miao, Yi, Sarr, Michael, Bassi, Claudio, and Büchler, Markus W.

Published
2017
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9. Definition and classification of chyle leak after pancreatic operation: A consensus statement by the International Study Group on Pancreatic Surgery

Author

Besselink, Marc G., van Rijssen, L. Bengt, Bassi, Claudio, Dervenis, Christos, Montorsi, Marco, Adham, Mustapha, Asbun, Horacio J., Bockhorn, Maximillian, Strobel, Oliver, Büchler, Markus W., Busch, Olivier R., Charnley, Richard M., Conlon, Kevin C., Fernández-Cruz, Laureano, Fingerhut, Abe, Friess, Helmut, Izbicki, Jakob R., Lillemoe, Keith D., Neoptolemos, John P., Sarr, Michael G., Shrikhande, Shailesh V., Sitarz, Robert, Vollmer, Charles M., Yeo, Charles J., Hartwig, Werner, Wolfgang, Christopher L., and Gouma, Dirk J.

Published
2017
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15. Contributors

Author

Abou-Alfa, Ghassan K., primary, Abou Khalil, Jad, additional, Addeo, Pietro, additional, Adsay, N. Volkan, additional, Agarwal, Anil Kumar, additional, Alemi, Farzad, additional, Allen, Peter J., additional, Al-Mukhtar, Ahmed, additional, Aloia, Thomas A., additional, Andersen, Jesper B., additional, Anderson, Christopher D., additional, Arslan-Carlon, Vittoria, additional, Asbun, Horacio J., additional, Aussilhou, Béatrice, additional, Awad, Joseph, additional, Azoulay, Daniel, additional, Bachellier, Philippe, additional, Baker, Talia B., additional, Bamboat, Zubin M., additional, Barkun, Jeffrey Stewart, additional, Bassi, Claudio, additional, Basturk, Olca, additional, Beard, Rachel E., additional, Bedossa, Pierre, additional, Belghiti, Jacques, additional, Bellorin-Marin, Omar, additional, Besselink, Marc G.H., additional, Bilchik, Anton J., additional, Blumgart, Leslie H., additional, Boas, Franz Edward, additional, Brody, Lynn A., additional, Brown, Karen T., additional, Bruix, Jordi, additional, Bruno, David A., additional, Brunt, Elizabeth M., additional, Burns, Justin M., additional, Butturini, Giovanni, additional, Caicedo, Juan Carlos, additional, Callery, Mark P., additional, Calvino, Abdul Saied, additional, Carpenter, Danielle H., additional, Carter, C. Ross, additional, Cauchy, François, additional, Chan, Chung Yip, additional, Chan, See Ching, additional, Chapman, William C., additional, Cherqui, Daniel, additional, Cho, Clifford S., additional, Chung, Jin Wook, additional, Clanton, Jesse, additional, Clary, Bryan Marshall, additional, Cleary, Sean Patrick, additional, Collins, Kelly M., additional, Conneely, John Barry, additional, Connell, Louise C., additional, Corvera, Carlos U., additional, Costa, Guido, additional, Covey, Anne M., additional, Crippin, Jeffrey S., additional, Croome, Kristopher P., additional, Dabbous, Hany, additional, D'Angelica, Michael I., additional, Darcy, Michael D., additional, Davis, Jeremy L., additional, de Jonge, Jeroen, additional, DeMatteo, Ronald P., additional, DePeralta, Danielle K., additional, Desai, Niraj M., additional, de Santibañes, Eduardo, additional, de Santibañes, Martin, additional, Dickson, Euan J., additional, DiMaio, Christopher John, additional, Do, Richard Kinh Gian, additional, Dokmak, Safi, additional, Donati, Marcello, additional, Doyle, M.B. Majella, additional, Dudeja, Vikas, additional, Dunphy, Mark, additional, Earl, Truman M., additional, Ebata, Tomoki, additional, Dika, Imane El, additional, El-Gohary, Yousef, additional, Endo, Itaru, additional, Enestvedt, C. Kristian, additional, Espat, N. Joseph, additional, Ethun, Cecilia G., additional, Fan, Sheung Tat, additional, Fanta, Paul T., additional, Farges, Olivier, additional, Ferrone, Cristina R., additional, Fields, Ryan C., additional, Fischer, Mary, additional, Fisher, Sarah B., additional, Flaherty, Devin C., additional, Fong, Yuman, additional, Friedman, Scott L., additional, Gabr, Ahmed, additional, Galloway, John R., additional, Geller, David A., additional, Gerdes, Hans, additional, Gerst, Scott R., additional, Gittes, George K., additional, Glorioso, Jaime, additional, Gluskin, Jill S., additional, Goh, Brian K.P., additional, Gonzalez, Stevan A., additional, Goodman, Karyn A., additional, Gores, Gregory J., additional, Gotuzzo, Eduardo H., additional, Gouma, Dirk J., additional, Greig, Paul D., additional, Griffin, James F., additional, Halloran, Christopher M., additional, Halpern, Neil A., additional, Hammill, Chet W., additional, Hansen, Paul D., additional, Harding, James J., additional, M. Harrison, Ewen, additional, Hartwig, Werner, additional, Hasegawa, Kiyoshi, additional, Hechtman, Jaclyn F., additional, Heimbach, Julie K., additional, Helton, William S., additional, Hemming, Alan W., additional, Henderson, J. Michael, additional, Hirshberg, Asher, additional, Howe, James R., additional, Hughes, Christopher B., additional, Iacobuzio-Donahue, Christine, additional, Jarnagin, William R., additional, Jenkins, Roger L., additional, Jutric, Zeljka, additional, Kahlert, Christoph, additional, Kallini, Joseph Ralph, additional, Kangrga, Ivan, additional, Karanicolas, Paul J., additional, Katz, Seth S., additional, Katz, Steven C., additional, Kelly, Kaitlyn J., additional, Kemeny, Nancy E., additional, Kennedy, Eugene P., additional, Khalili, Korosh, additional, Khan, Adeel S., additional, Khan, Saboor, additional, Kim, Heung Bae, additional, Kingham, T. Peter, additional, Kirk, Allan D., additional, S. Klimstra, David, additional, Kluger, Michael, additional, Knechtle, Stuart J., additional, Koea, Jonathan B., additional, Kokudo, Norihiro, additional, Koliogiannis, Dionysios, additional, Kooby, David A., additional, Korenblat, Kevin, additional, Krebs, Simone, additional, LaQuaglia, Michael J., additional, LaQuaglia, Michael P., additional, LaRusso, Nicholas F., additional, Laurent, Alexis, additional, Lazaridis, Konstantinos N., additional, Leal, Julie N., additional, Lee, Eliza J., additional, Lee, Major Kenneth, additional, Lee, Ser Yee, additional, Lencioni, Riccardo, additional, Liccioni, Alexandre, additional, Lidsky, Michael E., additional, Lin, Chung-Wei, additional, Linehan, David C., additional, Lopez-Solis, Roberto Carlos, additional, Lowell, Jeffrey A., additional, Madoff, David C., additional, Maggi, Jason, additional, Maithel, Shishir K., additional, Majeed, Ali W., additional, Malfertheiner, Peter, additional, Malleo, Giuseppe, additional, Mao, Shennen A., additional, Marchegiani, Giovanni, additional, Marcos, Luis A., additional, Markmann, James F., additional, Marsh, J. Wallis, additional, Martin, Robert C.G., additional, Matsuyama, Ryusei, additional, Matter, Matthias S., additional, Mattera, Francisco Juan, additional, Maxwell, Jessica E., additional, Mazza, Oscar M., additional, McGilvray, Ian D., additional, McKay, Colin J., additional, McWeeney, Doireann M., additional, Melendez, Jose, additional, Mendelsohn, Robin B., additional, Miller, George, additional, Mönkemüller, Klaus E., additional, Mori, Ryutaro, additional, Moutinho, Vitor, additional, Nagino, Masato, additional, Nagorney, David M., additional, Nagula, Satish, additional, Nakeeb, Attila, additional, Nedredal, Geir I., additional, Neoptolemos, John P., additional, Neuberger, James, additional, Nyberg, Scott L., additional, O'Connor, Rachel, additional, O'Grady, John G., additional, Oldfield, Frances E., additional, Oldhafer, Karl J., additional, Olthoff, Kim M., additional, Orloff, Susan L., additional, Paniccia, Alessandro, additional, Paradis, Valérie, additional, Parks, Rowan W., additional, Pascal, Gérard, additional, Pastores, Stephen M., additional, Pawlik, Timothy M., additional, Pillarisetty, Venu G., additional, Pingpank, James Francis, additional, Pinson, C. Wright, additional, Pitt, Henry Anthony, additional, Pomposelli, James J., additional, Procopio, Fabio, additional, Pucci, Michael J., additional, Qadan, Motaz, additional, Rajkomar, Kheman, additional, Reddy, Srinevas K., additional, Reig, Maria E., additional, Reza, Joseph Arturo, additional, Roberts, John Paul, additional, Robson, Piera Marie Cote, additional, Rocha, Flavio G., additional, Roll, Garrett Richard, additional, Ronnekleiv-Kelly, Sean M., additional, Rosemurgy, Alexander S., additional, Rosen, Charles B., additional, Saldinger, Pierre F., additional, Salem, Riad, additional, Salem, Suhail Bakr, additional, Salvia, Roberto, additional, Sandroussi, Charbel, additional, Sanford, Dominic E., additional, Scatton, Olivier, additional, Schattner, Mark Andrew, additional, Schecter, William Palmer, additional, Schoellhammer, Hans Francis, additional, Schulick, Richard D., additional, Schwartz, Lawrence H., additional, Shah, Kevin N., additional, Shepherd, Ross W., additional, Shimada, Hiroshi, additional, Shimoda, Masafumi, additional, Shindoh, Junichi, additional, Shokouh-Amiri, Hosein, additional, Sicklick, Jason K., additional, Siegelbaum, Robert H., additional, Singh, Gagandeep, additional, Smoot, Rory L., additional, Solomon, Stephen B., additional, Soubrane, Olivier, additional, Spinelli, Nicholas, additional, Stauffer, John A., additional, Stewart, Lygia, additional, Strand, Matthew S., additional, Tabibian, James H., additional, Torzilli, Guido, additional, Trotter, James F., additional, Turcotte, Simon, additional, Turmelle, Yumirle P., additional, Tzimas, Demetrios J., additional, Van Gulik, Thomas, additional, Vannucci, Andrea, additional, Vauthey, Jean-Nicolas, additional, Vetter, Diana, additional, Vilgrain, Valérie, additional, Villamil, Alejandra Maria, additional, Voigt, Louis P., additional, Vollmer, Charles M., additional, Wands, Jack R., additional, Wattacheril, Julia, additional, Weber, Sharon Marie, additional, Weiss, Matthew J., additional, Weitz, Jürgen, additional, Werner, Jens, additional, Winner, Megan, additional, Wong, John, additional, Yang, Dennis, additional, Yarmohammadi, Hooman, additional, Yeo, Charles J., additional, Yeo, Theresa Pluth, additional, Yoon, Chang Jin, additional, Yopp, Adam, additional, Young, D. Owen, additional, Zhao, Kai, additional, Zibari, Gazi B., additional, and Zogopoulos, George, additional

Published
2017
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17. Cytokeratin 6 identifies basal-like subtypes of pancreatic ductal adenocarcinoma with decreased survival.

Author

Lyu, Su Ir, Krey, Thaddaeus, Damanakis, Alexander I., Zhao, Yue, Bruns, Christiane J., Schmidt, Thomas, Popp, Felix C., Quaas, Alexander, Knipper, Karl, the PANCALYZE Study Group, Heise, Michael, Marusch, Frank, Siech, Marco, Mosa, Tawfik, Schniewind, Bodo, Tepel, Jürgen, Hartwig, Werner, Prinz, Christoph, Rau, Bettina M., and Niedergethmann, Marco

Subjects
PANCREATIC duct, KERATIN, IMMUNOSTAINING, ADENOCARCINOMA, PERIOSTIN, PANCREATIC intraepithelial neoplasia
Abstract

Purpose: Rising incidence of pancreatic ductal adenocarcinoma (PDAC) bind with insufficient therapy options showcases a great medical challenge. Further biomarkers are required to identify patients, who will benefit from more aggressive therapy. Methods: 320 patients were included by the PANCALYZE study group. Cytokeratin 6 (CK6) immunohistochemical staining as a putative marker for the basal-like subtype of PDAC was performed. The correlation between CK6 expression patterns and survival data, as well as various markers of the (inflammatory) tumor microenvironment, were analyzed. Results: We divided the study population based on the expression pattern of CK6. Patients with a high CK6 tumor expression had a significantly shorter survival (p = 0.013), confirmed in a multivariate cox regression model. CK6-expression is an independent marker for a decreased overall survival (HR = 1.655, 95% CI 1.158–2.365, p = 0.006). In addition, the CK6-positive tumors showed significantly less plasma cell infiltration and more cancer-associated fibroblasts (CAFs) expressing Periostin and SMA. Conclusions: CK6 could be considered as an independent biomarker for a shorter overall survival. CK6 is a clinically easily accessible biomarker for the identification of the basal-like subtype of PDAC. Therefore, it could be taken into consideration in deciding for the more aggressive therapy regimes. Prospectively, studies addressing the chemosensitive characteristics of this subtype are required. [ABSTRACT FROM AUTHOR]

Published
2023
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20. Applicability of the surgical risk calculator by the American College of Surgeons in the setting of German patients undergoing complete pancreatectomy: multicentre study using data from the StuDoQ|Pancreas registry.

Author

Höhn, Philipp, Runde, Fabian, Luu, Andreas Minh, Fahlbusch, Tim, Fein, Daniel, Klinger, Carsten, Uhl, Waldemar, Belyaev, Orlin, Gutt, Carsten, Köninger, Jörg, Schnitzbauer, Andreas, Schafmayer, Clemens, Farkas, Stefan, Hartwig, Werner, Torge Mees, Sören, Klammer, Frank, Glanemann, Matthias, Ghadimi, Michael, Anthuber, Matthias, and Reißfelder, Christoph

Subjects
GERMANS, PANCREATECTOMY, CALCULATORS, GASTRIC emptying, SURGEONS, KIDNEY failure
Abstract

Introduction: Surgical risk calculators can estimate risk probabilities for postoperative outcomes utilizing patient-specific risk factors. They provide meaningful information for obtaining informed consent. The aim of the present paper was to evaluate the predictive value of the surgical risk calculators by the American College of Surgeons in German patients undergoing total pancreatectomy. Methods: Data for patients who underwent total pancreatectomy between 2014 and 2018 were acquired from the Study, Documentation, and Quality Center of the German Society for General and Visceral Surgery. Risk factors were entered manually into the surgical risk calculators and calculated risks were compared with actual outcomes. Results: Of the 408 patients analysed, predicted risk was higher in patients with complications except for the prediction of re-admission (P = 0.127), delayed gastric emptying (P = 0.243), and thrombosis (P = 0.256). In contrast, classification of patients into below, above, or average risk by the surgical risk calculators only produced meaningful results for discharge to nursing facility (P < 0.001), renal failure (P = 0.003), pneumonia (P = 0.001), serious complications, and overall morbidity (both P < 0.001). Assessment of discrimination and calibration showed poor results (scaled Brier scores 8.46 per cent or less). Conclusion: Overall surgical risk calculator performance was poor. This finding promotes the development of a specific surgical risk calculator applicable to the German healthcare system. We evaluated the Surgical Risk Calculator of the American College of Surgeons in a national, multicentre collective of patients undergoing total pancreatectomy. Overall performance was poor, but results are probably biased by input data. Whether the Surgical Risk Calculator is applicable to an external cohort remains unclear. [ABSTRACT FROM AUTHOR]

Published
2023
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24. Additional file 1 of Outcomes and risks in palliative pancreatic surgery: an analysis of the German StuDoQ|Pancreas registry

Author

Hofmann, Felix O., Miksch, Rainer C., Weniger, Maximilian, Keck, Tobias, Anthuber, Matthias, Witzigmann, Helmut, Nuessler, Natascha C., Reissfelder, Christoph, Köninger, Jörg, Ghadimi, Michael, Bartsch, Detlef K., Hartwig, Werner, Angele, Martin K., D’Haese, Jan G., and Werner, Jens

Abstract

Additional file 1: Table S1. Software. Fig S1. Missingness and Missingness Patterns. Fig S2. Box-and-whisker plots of imputed values. Fig S3. Density plot of imputed values. Fig S4. Strip plot of imputed values. Fig S5. Mean and standard deviation of imputed values.

Published
2022
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38. Definition of a standard lymphadenectomy in surgery for pancreatic ductal adenocarcinoma: A consensus statement by the International Study Group on Pancreatic Surgery (ISGPS)

Author

Tol, Johanna A.M.G., Gouma, Dirk J., Bassi, Claudio, Dervenis, Christos, Montorsi, Marco, Adham, Mustapha, Andrén-Sandberg, Ake, Asbun, Horacio J., Bockhorn, Maximilian, Büchler, Markus W., Conlon, Kevin C., Fernández-Cruz, Laureano, Fingerhut, Abe, Friess, Helmut, Hartwig, Werner, Izbicki, Jakob R., Lillemoe, Keith D., Milicevic, Miroslav N., Neoptolemos, John P., Shrikhande, Shailesh V., Vollmer, Charles M., Yeo, Charles J., and Charnley, Richard M.

Published
2014
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39. Extended pancreatectomy in pancreatic ductal adenocarcinoma: Definition and consensus of the International Study Group for Pancreatic Surgery (ISGPS)

Author

Hartwig, Werner, Vollmer, Charles M., Fingerhut, Abe, Yeo, Charles J., Neoptolemos, John P., Adham, Mustapha, Andrén-Sandberg, Åke, Asbun, Horacio J., Bassi, Claudio, Bockhorn, Max, Charnley, Richard, Conlon, Kevin C., Dervenis, Christos, Fernandez-Cruz, Laureano, Friess, Helmut, Gouma, Dirk J., Imrie, Clem W., Lillemoe, Keith D., Milićević, Miroslav N., Montorsi, Marco, Shrikhande, Shailesh V., Vashist, Yogesh K., Izbicki, Jakob R., and Büchler, Markus W.

Published
2014
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41. Borderline resectable pancreatic cancer: A consensus statement by the International Study Group of Pancreatic Surgery (ISGPS)

Author

Bockhorn, Maximilian, Uzunoglu, Faik G., Adham, Mustapha, Imrie, Clem, Milicevic, Miroslav, Sandberg, Aken A., Asbun, Horacio J., Bassi, Claudio, Büchler, Markus, Charnley, Richard M., Conlon, Kevin, Cruz, Laureano Fernandez, Dervenis, Christos, Fingerhutt, Abe, Friess, Helmut, Gouma, Dirk J., Hartwig, Werner, Lillemoe, Keith D., Montorsi, Marco, Neoptolemos, John P., Shrikhande, Shailesh V., Takaori, Kyoichi, Traverso, William, Vashist, Yogesh K., Vollmer, Charles, Yeo, Charles J., and Izbicki, Jakob R.

Published
2014
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42. When to perform a pancreatoduodenectomy in the absence of positive histology? A consensus statement by the International Study Group of Pancreatic Surgery

Author

Asbun, Horacio J., Conlon, Kevin, Fernandez-Cruz, Laureano, Friess, Helmut, Shrikhande, Shailesh V., Adham, Mustapha, Bassi, Claudio, Bockhorn, Maximilian, Büchler, Markus, Charnley, Richard M., Dervenis, Christos, Fingerhutt, Abe, Gouma, Dirk J., Hartwig, Werner, Imrie, Clem, Izbicki, Jakob R., Lillemoe, Keith D., Milicevic, Miroslav, Montorsi, Marco, Neoptolemos, John P., Sandberg, Aken A., Sarr, Michael, Vollmer, Charles, Yeo, Charles J., and Traverso, William L.

Published
2014
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46. Interaction of complement and leukocytes in severe acute pancreatitis: potential for therapeutic intervention

Author

Hartwig, Werner, Klafs, Martina, Kirschfink, Michael, Hackert, Thilo, Schneider, Lutz, Gebhard, Martha-Maria, Buchler, Markus W., and Werner, Jens

Subjects
Enterocolitis, Neonatal necrotizing -- Research, Enterocolitis, Pseudomembranous -- Research, Complement deficiency (Immunology) -- Research, Lung diseases -- Health aspects, Lung diseases -- Research, Lung diseases -- Care and treatment, Leukocyte disorders -- Research, Rats -- Physiological aspects, Rats -- Research, Rattus -- Physiological aspects, Rattus -- Research, Biological sciences
Abstract

In acute pancreatitis, local as well as systemic organ complications are mediated by the activation of various inflammatory cascades. The role of complement in this setting is unclear. The aim of the present study was to determine the level of complement activation in experimental pancreatitis, to evaluate the interaction of complement and leukocyte-endothelium activation, and to assess the effects of complement inhibition by soluble complement receptor 1 (sCR1) in this setting. Necrotizing pancreatitis was induced in Wistar rats by the combination of intravenous cerulein and retrograde infusion of glycodeoxycholic acid into the biliopancreatic duct; edematous pancreatitis was induced by intravenous cemlein only. In control animals, a sham operation (midline laparotomy) was performed. Complement activation, leukocyte sequestration, and pancreatic as well as pulmonary injury were assessed in the presence/ absence of sCR1. Increased levels of C3a were found in necrotizing but not in edematous pancreatitis. When complement activation in necrotizing pancreatitis was blocked by sCR1, levels of C3a and total hemolytic activity (CH50) were decreased. Leukocyte-endothelial interaction, as assessed by intravital microscopy, and pancreatic as well as pulmonary organ injury (wet-to-dry weight ratio, MPO activity, and histology) were ameliorated by sCR1. As a result of the present study, necrotizing but not edematous pancreatitis is characterized by significant and early complement activation. Based on the interaction of complement and leukocytes, complement inhibition by sCR1 may be a valuable option in the treatment of leukocyte-associated organ injury in severe pancreatitis. necrotizing pancreatitis; complement activation; soluble complement receptor 1; leukocyte endothelial interaction; lung injury

Published
2006

47. Contributors

Author

Abou-Alfa, Ghassan K., primary, Adsay, N. Volkan, additional, Akhurst, Timothy, additional, Alemi, Farzad, additional, Allegra, David, additional, Allen, Peter J., additional, Anderson, Christopher D., additional, Aoki, Taku, additional, Arulraj, Ramakrishnan, additional, Auer, Rebecca Ann C., additional, Aussilhou, Béatrice, additional, Awad, Joseph, additional, Ball, Chad G., additional, Bamboat, Zubin M., additional, Bassi, Claudio, additional, Becker, Christoph D., additional, Bedossa, Pierre, additional, Belghiti, Jacques, additional, Belletrutti, Paul, additional, Bilchik, Anton J., additional, Blumgart, Leslie H., additional, Bornman, Philippus C., additional, Boutros, Cherif, additional, Brody, Jonathan R., additional, Brody, Lynn A., additional, Brouquet, Antoine, additional, Brown, Karen T., additional, Brugge, William R., additional, Bruix, Jordi, additional, Bruno, David A., additional, Brunt, Elizabeth M., additional, Büchler, Markus W., additional, Burns, Justin M., additional, Butturini, Giovanni, additional, Callery, Mark P., additional, Carr-Locke, David L., additional, Cha, Charles, additional, Chan, See Ching, additional, Chapman, William C., additional, Cherqui, Daniel, additional, Cho, Clifford S., additional, Chung, Jin Wook, additional, Clary, Bryan, additional, Cocieru, Andrei, additional, Contreras, Carlos M., additional, Conzen, Kendra D., additional, Corvera, Carlos U., additional, Covey, Anne M., additional, Crippin, Jeffrey S., additional, Dabbous, Hany, additional, D’Angelica, Michael I., additional, Darcy, Michael, additional, Davenport, Mark, additional, De Jonge, Jeroen, additional, DeMatteo, Ronald P., additional, Demetriou, Achilles A., additional, Desai, Niraj M., additional, De Santibañes, Eduardo, additional, Desser, Terry S., additional, Dhanireddy, Kiran K., additional, Dokmak, Safi, additional, Doyle, M.B. Majella, additional, Earl, Truman M., additional, Ebata, Tomoki, additional, El-Gohary, Yousef, additional, Epstein, Andrew S., additional, Espat, N. Joseph, additional, Fan, Sheung Tat, additional, Farges, Olivier, additional, Fernandez-Del Castillo, Carlos, additional, Ferrone, Cristina R., additional, Fischer, Mary, additional, Fisher, James E., additional, Fong, Yuman, additional, Forner, Alejandro, additional, Friedman, Scott L., additional, Fritz, Stefan, additional, Galloway, John R., additional, Gerdes, Hans, additional, Getrajdman, George, additional, Ghaneh, Paula, additional, Ghittoni, Giorgia, additional, Gittes, George, additional, Goodman, Karyn A., additional, Gores, Gregory J., additional, Gotuzzo, Eduardo, additional, Gouma, Dirk J., additional, Greig, Paul D., additional, Halloran, Christopher M., additional, Halpern, Neil A., additional, Hann, Lucy E., additional, Harrison, Ewen M., additional, Hartwig, Werner, additional, Heimbach, Julie K., additional, Helton, William S., additional, Hemming, Alan W., additional, Henderson, J. Michael, additional, Hessheimer, Amelia J., additional, Hirshberg, Asher, additional, Ho, Alice, additional, House, Michael G., additional, Hsieh, Chung-Bao, additional, Hsu, Kuo-Feng, additional, Iannitti, David A., additional, Imamura, Hiroshi, additional, Imrie, Clem W., additional, Jarnagin, William R., additional, Jenkins, Roger L., additional, Kahl, Stefan, additional, Kangrga, Ivan, additional, Kelly, Kaitlyn, additional, Kemeny, Nancy E., additional, Kennedy, Eugene P., additional, Kerlan Jr, Robert K., additional, Khan, Adeel S., additional, Khan, Saboor, additional, Kingham, T. Peter, additional, Kirk, Allan D., additional, Kitagawa, Yuichi, additional, Klimstra, David S., additional, Kluger, Michael D., additional, Knechtle, Stuart J., additional, Kneuertz, Peter J., additional, Koea, Jonathan, additional, Koffron, Alan J., additional, Kokudo, Norihiro, additional, Kooby, David A., additional, Korenblat, Kevin, additional, Krasny, Robert M., additional, Krige, Jake, additional, Kurtz, Robert C., additional, Landman, Matthew P., additional, La Quaglia, Michael P., additional, LaRusso, Nicholas F., additional, Lau, Kwan N., additional, Lazaridis, Konstantinos N., additional, Lerch, Markus M., additional, Lillegard, Joseph B., additional, Lillemoe, Keith D., additional, Linehan, David C., additional, Logan, Susan, additional, Loveday, Benjamin, additional, Lowell, Jeffrey A., additional, Madoff, David C., additional, Maithel, Shishir K., additional, Majeed, Ali W., additional, Makuuchi, Masatoshi, additional, Malfertheiner, Peter, additional, Mamlouk, Mark, additional, Marchegiani, Giovanni, additional, Marcos, Luis A., additional, Markmann, James F., additional, Marsh, J. 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Published
2012
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49. Membrane-bound ICAM-1 is upregulated by trypsin and contributes to leukocyte migration in acute pancreatitis

Author

Hartwig, Werner, Werner, Jens, Warshaw, Andrew L., Antoniu, Bozena, Fernandez-del Castillo, Carlos, Gebhard, Martha-Maria, Uhl, Waldemar, and Buchler, Markus W.

Subjects
Pancreatitis -- Research, Biological sciences
Abstract

In acute pancreatitis, ICAM-1 is upregulated in various organs and contributes to the development of organ injury. To investigate the effects of pancreatic proteases on ICAM-I expression and their role in the early process of eukocyte migration, human umbilical vein endothelial cells (HUVECs) were incubated with serum subjected to limited trypsin digestion and Wistar rats were injected with trypsin. Significant upregulation of membrane-bound ICAM-1 was seen on HUVECs incubated with trypsinated serum. Likewise, soluble ICAM-1 increased in the supernatant of HUVECs. Changes of membrane-bound ICAM-I and soluble 1CAM-1 were maximal with high concentrations of trypsin. HUVECs incubated with TNF-[alpha] (positive control) showed similar changes. In the pancreas and lungs of animals infused with trypsin, ICAM-1 and leukocyte sequestration were increased compared with controls. Reflecting the relevance of protease-induced ICAM-1 expression in leukocyte migration, leukocyte-endothelium interaction, as assessed by intravital microscopy, was markedly increased by trypsin. Inhibition of ICAM-1 ameliorated these changes significantly. In conclusion, trypsinated serum induces the upregulation of both membrane-bound ICAM-1 on endothelial cells and soluble ICAM-1. These changes contribute to the early steps of leukocyte migration in acute pancreatitis. The role of soluble ICAM-1 remains to be investigated. adhesion molecules; endothelial cells; proteases; systemic inflammatory response syndrome

Published
2004

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