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1. Superiority of Step-up Approach vs Open Necrosectomy in Long-term Follow-up of Patients With Necrotizing Pancreatitis

Author

Hollemans, Robbert A., Bakker, Olaf J., Boermeester, Marja A., Bollen, Thomas L., Bosscha, Koop, Bruno, Marco J., Buskens, Erik, Dejong, Cornelis H., van Duijvendijk, Peter, van Eijck, Casper H., Fockens, Paul, van Goor, Harry, van Grevenstein, Wilhelmina M., van der Harst, Erwin, Heisterkamp, Joos, Hesselink, Eric J., Hofker, Sijbrand, Houdijk, Alexander P., Karsten, Tom, Kruyt, Philip M., van Laarhoven, Cornelis J., Laméris, Johan S., van Leeuwen, Maarten S., Manusama, Eric R., Molenaar, I. Quintus, Nieuwenhuijs, Vincent B., van Ramshorst, Bert, Roos, Daphne, Rosman, Camiel, Schaapherder, Alexander F., van der Schelling, George P., Timmer, Robin, Verdonk, Robert C., de Wit, Ralph J., Gooszen, Hein G., Besselink, Marc G., and van Santvoort, Hjalmar C.

Published
2019
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2. Endoscopic Versus Surgical Step-Up Approach for Infected Necrotizing Pancreatitis (ExTENSION): Long-term Follow-up of a Randomized Trial

Author

Onnekink, Anke M., primary, Boxhoorn, Lotte, additional, Timmerhuis, Hester C., additional, Bac, Simon T., additional, Besselink, Marc G., additional, Boermeester, Marja A., additional, Bollen, Thomas L., additional, Bosscha, Koop, additional, Bouwense, Stefan A.W., additional, Bruno, Marco J., additional, van Brunschot, Sandra, additional, Cappendijk, Vincent C., additional, Consten, Esther C.J., additional, Dejong, Cornelis H., additional, Dijkgraaf, Marcel G.W., additional, van Eijck, Casper H.J., additional, Erkelens, Willemien G., additional, van Goor, Harry, additional, van Grinsven, Janneke, additional, Haveman, Jan-Willem, additional, van Hooft, Jeanin E., additional, Jansen, Jeroen M., additional, van Lienden, Krijn P., additional, Meijssen, Maarten A.C., additional, Nieuwenhuijs, Vincent B., additional, Poley, Jan-Werner, additional, Quispel, Rutger, additional, de Ridder, Rogier J., additional, Römkens, Tessa E.H., additional, van Santvoort, Hjalmar C., additional, Scheepers, Joris J., additional, Schwartz, Matthijs P., additional, Seerden, Tom, additional, Spanier, Marcel B.W., additional, Straathof, Jan Willem A., additional, Timmer, Robin, additional, Venneman, Niels G., additional, Verdonk, Robert C., additional, Vleggaar, Frank P., additional, van Wanrooij, Roy L., additional, Witteman, Ben J.M., additional, Fockens, Paul, additional, and Voermans, Rogier P., additional

Published
2022
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3. Superiority of Step-up Approach vs Open Necrosectomy in Long-term Follow-up of Patients With Necrotizing Pancreatitis

Author

Cornelis H. C. Dejong, Joos Heisterkamp, Erik Buskens, Philip M Kruyt, Maarten S. van Leeuwen, Robbert A. Hollemans, Marja A. Boermeester, Ralph J. de Wit, Camiel Rosman, Wilhelmina M U van Grevenstein, Sijbrand Hofker, Eric R. Manusama, I. Quintus Molenaar, Vincent B. Nieuwenhuijs, Daphne Roos, George P. van der Schelling, Marco J. Bruno, Marc G. Besselink, Koop Bosscha, Peter van Duijvendijk, Johan S. Laméris, Cornelis J. H. M. van Laarhoven, Robert C. Verdonk, Thomas L. Bollen, Paul Fockens, Olaf J. Bakker, Hein G. Gooszen, Harry van Goor, Alexander P. Houdijk, Alexander F. Schaapherder, Erwin van der Harst, Hjalmar C. van Santvoort, Robin Timmer, Tom M. Karsten, Casper H.J. van Eijck, Eric J. Hesselink, Bert van Ramshorst, Surgery, MUMC+: MA Heelkunde (9), RS: NUTRIM - R2 - Liver and digestive health, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Value, Affordability and Sustainability (VALUE), Methods in Medicines evaluation & Outcomes research (M2O), Gastroenterology & Hepatology, APH - Methodology, AII - Infectious diseases, AGEM - Digestive immunity, Gastroenterology and Hepatology, and AGEM - Re-generation and cancer of the digestive system

Subjects
0301 basic medicine, Time Factors, GUIDELINES, law.invention, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], 0302 clinical medicine, Quality of life, Randomized controlled trial, Interquartile range, law, Recurrence, QUALITY-OF-LIFE, Minimally Invasive, Clinical endpoint, Digestive System Surgical Procedures, Pancreatic Surgery, Pain, Postoperative, Pancreatitis, Acute Necrotizing, NECROSIS, Gastroenterology, Health Care Costs, Progression-Free Survival, Survival Rate, FECAL ELASTASE-1, Drainage, 030211 gastroenterology & hepatology, Reoperation, medicine.medical_specialty, SF-36, CLASSIFICATION, Infected Necrosis, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, EQ-5D, Internal medicine, medicine, Journal Article, MANAGEMENT, Humans, Incisional Hernia, Pancreas, Hepatology, business.industry, medicine.disease, Surgery, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], 030104 developmental biology, STATES, Quality of Life, Pancreatitis, Exocrine Pancreatic Insufficiency, business, SF-36 HEALTH SURVEY, Follow-Up Studies
Abstract

BACKGROUND & AIMS: In a 2010 randomized trial (the PANTER trial), a surgical step-up approach for infected necrotizing pancreatitis was found to reduce the composite endpoint of death or major complications compared with open necrosectomy; 35% of patients were successfully treated with simple catheter drainage only. There is concern, however, that minimally invasive treatment increases the need for reinterventions for residual peripancreatic necrotic collections and other complications during the long term. We therefore performed a long-term follow-up study. METHODS: We reevaluated all the 73 patients (of the 88 patients randomly assigned to groups) who were still alive after the index admission, at a mean 86 months (+/- 11 months) of follow-up. We collected data on all clinical and health care resource utilization endpoints through this follow-up period. The primary endpoint was death or major complications (the same as for the PANTER trial). We also measured exocrine insufficiency, quality of life (using the Short Form-36 and EuroQol 5 dimensions forms), and Izbicki pain scores. RESULTS: From index admission to long-term follow-up, 19 patients (44%) died or had major complications in the step-up group compared with 33 patients (73%) in the open-necrosectomy group (P = .005). Significantly lower proportions of patients in the step-up group had incisional hernias (23% vs 53%; P = .004), pancreatic exocrine insufficiency (29% vs 56%; P = .03), or endocrine insufficiency (40% vs 64%; P = .05). There were no significant differences between groups in proportions of patients requiring additional drainage procedures (11% vs 13%; P = .99) or pancreatic surgery (11% vs 5%; P = .43), or in recurrent acute pancreatitis, chronic pancreatitis, Izbicki pain scores, or medical costs. Quality of life increased during follow-up without a significant difference between groups. CONCLUSIONS: In an analysis of long-term outcomes of trial participants, we found the step-up approach for necrotizing pancreatitis to be superior to open necrosectomy, without increased risk of reinterventions.

Published
2019

4. Sa283 ENDOSCOPIC VERSUS SURGICAL STEP-UP APPROACH FOR INFECTED NECROTIZING PANCREATITIS: LONG-TERM FOLLOW-UP OF A MULTICENTER RANDOMIZED CONTROLLED TRIAL (EXTENSION)

Author

Onnekink, Anke M., primary, Boxhoorn, Lotte, additional, Bac, Simon, additional, Timmerhuis, Hester C., additional, Besselink, Marc G., additional, Boermeester, Marja A., additional, Bollen, Thomas, additional, Bosscha, Koop, additional, Bouwense, Stefan A., additional, Bruno, Marco J., additional, Van Brunschot, Sandra, additional, Cappendijk, Vincent C., additional, Consten, Esther, additional, Dejong, Cornelis H., additional, Dijkgraaf, Marcel, additional, Van Eijck, Casper H., additional, Erkelens, G. Willemien, additional, van Goor, Harry, additional, van Grevenstein, Helma, additional, van Grinsven, Janneke, additional, Haveman, Jan illem, additional, Hofker, Sijbrand H., additional, Jansen, Jeroen M., additional, van Lienden, Krijn P., additional, Meijssen, Maarten, additional, Wanrooij, Roy V., additional, Nieuwenhuijs, Vincent B., additional, Poley, Jan-Werner, additional, Quispel, Rutger, additional, De Ridder, Rogier, additional, Romkens, Tessa, additional, Van Santvoort, Hjalmar C., additional, Scheepers, Joris J., additional, Schwartz, Matthijs P., additional, Seerden, Tom, additional, Spanier, Marcel, additional, Straathof, Jan Willem, additional, Timmer, Robin, additional, Venneman, Niels G., additional, Verdonk, Robert C., additional, Vleggaar, Frank P., additional, Witteman, Ben, additional, Fockens, Paul, additional, and Voermans, Rogier P., additional

Published
2021
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5. Fr289 POSTPONED OR IMMEDIATE DRAINAGE OF INFECTED NECROTIZING PANCREATITIS (POINTER): A MULTICENTER RANDOMIZED TRIAL

Author

Boxhoorn, Lotte, primary, van Dijk, Sven M., additional, van Grinsven, Janneke, additional, Verdonk, Robert C., additional, Boermeester, Marja A., additional, Bollen, Thomas, additional, Bouwense, Stefan A., additional, Bruno, Marco J., additional, Cappendijk, Vincent C., additional, Dejong, Cornelis H., additional, Duijvendijk, Peter V., additional, Van Eijck, Casper H., additional, Fockens, Paul, additional, Francken, Michiel F.G., additional, van Goor, Harry, additional, Hadithi, Muhammed, additional, Hallensleben, Nora D., additional, Haveman, Jan illem, additional, Jacobs, Maarten, additional, Jansen, Jeroen M., additional, Kop, Marnix P.M., additional, van Lienden, Krijn P., additional, Manusama, Eric R., additional, Mieog, J.S., additional, Molenaar, Quintus, additional, Nieuwenhuijs, Vincent B., additional, Poen, A.C., additional, Poley, Jan-Werner, additional, van de Poll, Marcel, additional, Quispel, Rutger, additional, Romkens, Tessa E.H, additional, Schwartz, Matthijs P., additional, Seerden, Tom, additional, Stommel, Martijn W.J., additional, Straathof, Jan Willem, additional, Timmerhuis, Hester C., additional, Venneman, Niels G., additional, Voermans, Rogier P., additional, Van De Vrie, W, additional, Witteman, Ben, additional, Dijkgraaf, Marcel G., additional, Van Santvoort, Hjalmar C., additional, and Besselink, Marc G., additional

Published
2021
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6. Fr289 POSTPONED OR IMMEDIATE DRAINAGE OF INFECTED NECROTIZING PANCREATITIS (POINTER): A MULTICENTER RANDOMIZED TRIAL

Author

Jan-Werner Poley, Niels G. Venneman, Michiel F. G. Francken, Janneke van Grinsven, Rogier P. Voermans, Muhammed Hadithi, Tom C.J. Seerden, Rutger Quispel, Nora D L Hallensleben, Casper H.J. van Eijck, Marja A. Boermeester, Hjalmar C. van Santvoort, Cornelis H. C. Dejong, Lotte Boxhoorn, Thomas L. Bollen, Maarten A J M Jacobs, Marc G. Besselink, Marco J. Bruno, Marcel C. G. van de Poll, Ben J.M. Witteman, Stefan A.W. Bouwense, Robert C. Verdonk, Jeroen M. Jansen, Marcel G. W. Dijkgraaf, Krijn P. van Lienden, Eric R. Manusama, Paul Fockens, Matthijs P. Schwartz, Sven M. van Dijk, W van de Vrie, Marnix P. M. Kop, Peter van Duijvendijk, Quintus Molenaar, Hester C. Timmerhuis, Jan Willem A Straathof, Harry van Goor, Vincent B. Nieuwenhuijs, Vincent C. Cappendijk, J.S.D. Mieog, Martijn W J Stommel, Jan illem Haveman, Alexander C. Poen, and Tessa E H Römkens

Subjects
medicine.medical_specialty, Hepatology, Randomized controlled trial, law, business.industry, Pointer (computer programming), Gastroenterology, Medicine, Drainage, business, Necrotizing pancreatitis, law.invention, Surgery
Published
2021

7. Sa283 ENDOSCOPIC VERSUS SURGICAL STEP-UP APPROACH FOR INFECTED NECROTIZING PANCREATITIS: LONG-TERM FOLLOW-UP OF A MULTICENTER RANDOMIZED CONTROLLED TRIAL (EXTENSION)

Author

Stefan A.W. Bouwense, Marcel Spanier, Maarten Meijssen, Niels G. Venneman, Matthijs P. Schwartz, Koop Bosscha, Roy L.J. van Wanrooij, Jan illem Haveman, Robin Timmer, Jan Willem A Straathof, Frank P. Vleggaar, Janneke van Grinsven, Helma M.U. van Grevenstein, Thomas L. Bollen, Jeroen M. Jansen, Marja A. Boermeester, Robert C. Verdonk, Joris J. Scheepers, Sijbrand Hofker, Rogier de Ridder, Cornelis H. C. Dejong, Tom C.J. Seerden, Rogier P. Voermans, Esther C. J. Consten, Lotte Boxhoorn, Hjalmar C. van Santvoort, Jan-Werner Poley, Marco J. Bruno, Marc G. Besselink, Tessa E H Römkens, Hester C. Timmerhuis, Sandra van Brunschot, Simon Bac, Rutger Quispel, Vincent B. Nieuwenhuijs, Ben J.M. Witteman, Casper H.J. van Eijck, Harry van Goor, Marcel G. W. Dijkgraaf, Vincent C. Cappendijk, Krijn P. van Lienden, Paul Fockens, Anke M. Onnekink, and G. Willemien Erkelens

Subjects
medicine.medical_specialty, Hepatology, Randomized controlled trial, business.industry, law, Long term follow up, Gastroenterology, Medicine, business, Necrotizing pancreatitis, law.invention, Surgery
Published
2021

8. The Value of a 24/7 Online Nationwide Multidisciplinary Expert Panel for Acute Necrotizing Pancreatitis

Author

Nicolien J. Schepers, Harry van Goor, Marc G. Besselink, Stefan A.W. Bouwense, Sandra van Brunschot, Marco J. Bruno, Casper H.J. van Eijck, Maarten S. van Leeuwen, Olaf J. Bakker, Marja A. Boermeester, Hjalmar C. van Santvoort, Krijn P. van Lienden, Paul Fockens, Robin Timmer, Janneke van Grinsven, Vincent B. Nieuwenhuijs, Jan-Werner Poley, H. Sijbrand Hofker, Hein G. Gooszen, Alexander F. Schaapherder, Cornelis H. C. Dejong, Johan S. Laméris, Benthe Doeve, Thomas L. Bollen, Vincent C. Cappendijk, Jan Willem Haveman, Gastroenterology & Hepatology, Other departments, APH - Methodology, Surgery, Gastroenterology and Hepatology, Radiology and Nuclear Medicine, and Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
Acute necrotizing pancreatitis, Adult, Male, medicine.medical_specialty, Health Services Accessibility, 03 medical and health sciences, 0302 clinical medicine, Multidisciplinary approach, Predictive Value of Tests, Risk Factors, medicine, Humans, Cooperative Behavior, Intensive care medicine, Aged, Netherlands, Patient Care Team, Internet, Hepatology, business.industry, Delivery of Health Care, Integrated, Pancreatitis, Acute Necrotizing, Remote Consultation, Gastroenterology, Middle Aged, Prognosis, Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10], Early Diagnosis, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Interdisciplinary Communication, business, Value (mathematics), Program Evaluation
Abstract

Contains fulltext : 175667.pdf (Publisher’s version ) (Closed access)

Published
2017

9. Mo1407 The Value of a 24/7 Online Nationwide Multidisciplinary Expert Panel for Necrotizing Pancreatitis: A 5-Years' Experience

Author

Jan Willem Haveman, Stefan A.W. Bouwense, Maarten S. van Leeuwen, Vincent B. Nieuwenhuijs, Hein G. Gooszen, Alexander F. Schaapherder, Benthe Doeve, Olaf J. Bakker, Hjalmar C. van Santvoort, Robin Timmer, Marc G. Besselink, Sandra van Brunschot, Marco J. Bruno, Johan S. Laméris, Marja A. Boermeester, Thomas L. Bollen, Jan-Werner Poley, Sijbrand Hofker, Cornelis H. C. Dejong, Janneke van Grinsven, Krijn P. van Lienden, Casper H.J. van Eijck, Paul Fockens, Nicolien J. Schepers, Harry van Goor, and Vincent C. Cappendijk

Subjects
medicine.medical_specialty, Hepatology, Multidisciplinary approach, business.industry, Gastroenterology, medicine, Necrotizing pancreatitis, Intensive care medicine, business, Value (mathematics)
Published
2016

13. Altered glutamine metabolism in rat portal drained viscera and hindquarter during hyperammonemia

Author

Peter B. Soeters, Margitta T. Kampman, Nicolaas E. P. Deutz, and Cornelis H. C. Dejong

Subjects
Blood Glucose, Male, medicine.medical_specialty, Glutamine, Portacaval, Ischemia, Glutamic Acid, Biology, Ammonia production, Glutamates, Ammonia, Internal medicine, medicine, Animals, Urea, Lactic Acid, Amino Acids, Intestinal Mucosa, chemistry.chemical_classification, Analysis of Variance, Hepatology, Portacaval Shunt, Surgical, Muscles, Gastroenterology, Rats, Inbred Strains, Hyperammonemia, Metabolism, medicine.disease, Pathophysiology, Hindlimb, Rats, Amino acid, Viscera, Endocrinology, Liver, chemistry, Regional Blood Flow, Lactates, Muscle Contraction
Abstract

In normal rats, muscle is the major glutamine releasing organ and gut is the major glutamine consuming organ. It has been suggested that enhanced muscle ammonia detoxification and gut ammonia production occurs during liver insufficiency-induced hyperammonemia. Therefore, ammonia and amino acid fluxes across portal-drained viscera and hindquarter, and muscle concentrations were measured in portacaval shunted and acute liver ischemia rats. Arterial ammonia and most amino acids were increased after portacaval shunting and increased progressively during liver ischemia, but net hindquarter ammonia uptake was not observed. Net hindquarter glutamine efflux was increased during portacaval shunting, but it decreased during liver ischemia, while muscle glutamine concentrations increased. The comparable net portal drained viscera glutamine uptake in normal and portacaval shunted rats changed during liver ischemia from net uptake to release, coinciding with release of most other amino acids. These results cast doubt on the ammonia detoxifying role of muscle during acute liver ischemia-induced hyperammonemia in the rat. The portal drained viscera glutamine release during severe hyperammonemia could be due to intestinal damage.

Published
1992

19. A Conservative and Minimally Invasive Approach to Necrotizing Pancreatitis Improves Outcome

Author

van Santvoort, Hjalmar C., primary, Bakker, Olaf J., additional, Bollen, Thomas L., additional, Besselink, Marc G., additional, Ahmed Ali, Usama, additional, Schrijver, A. Marjolein, additional, Boermeester, Marja A., additional, van Goor, Harry, additional, Dejong, Cornelis H., additional, van Eijck, Casper H., additional, van Ramshorst, Bert, additional, Schaapherder, Alexander F., additional, van der Harst, Erwin, additional, Hofker, Sijbrand, additional, Nieuwenhuijs, Vincent B., additional, Brink, Menno A., additional, Kruyt, Philip M., additional, Manusama, Eric R., additional, van der Schelling, George P., additional, Karsten, Tom, additional, Hesselink, Eric J., additional, van Laarhoven, Cornelis J., additional, Rosman, Camiel, additional, Bosscha, Koop, additional, de Wit, Ralph J., additional, Houdijk, Alexander P., additional, Cuesta, Miguel A., additional, Wahab, Peter J., additional, and Gooszen, Hein G., additional

Published
2011
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24. S1758 Loss of the Guardians at the Intestinal Barrier: Paneth Cell Apoptosis as a New Phenomenon in Human Intestinal Ischemia-Induced Bacterial Translocation

Author

Grootjans, Joep, primary, Hodin, Caroline, additional, de Haan, Jacco-Juri, additional, Lenaerts, Kaatje, additional, Hadfoune, M'hamed, additional, Derikx, Joep, additional, de Bruine, Adriaan P., additional, van Dam, Ronald, additional, Dejong, Cornelis H., additional, and Buurman, Wim, additional

Published
2010
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25. 475n Minimally Invasive Step-up Approach Versus Open Necrosectomy in Necrotizing Pancreatitis: A Randomized Controlled Multicenter Trial

Author

van Santvoort, Hjalmar C., primary, Bakker, Olaf J., additional, Besselink, Marc G., additional, Hofker, Hendrik S., additional, Boermeester, Marja A., additional, Dejong, Cornelis H., additional, van Goor, Harry, additional, Schaapherder, Alexander F., additional, van Eijck, Casper H., additional, and Bollen, Thomas L., additional

Published
2010
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32. Disruption of Endoplasmic Reticulum Homeostasis in Human Intestine in Response to Ischemia/Reperfusion: Novel Insight From Genome-Wide Transcript Profiling

Author

Cornelis H. C. Dejong, Joep P. M. Derikx, Erik A.L. Biessen, Ronald M. van Dam, Kaatje Lenaerts, Marco Manca, Joep Grootjans, Bas Boonen, and Wim A. Buurman

Subjects
Hepatology, Human intestine, Endoplasmic reticulum, Gastroenterology, Ischemia, medicine, Transcript profiling, Biology, medicine.disease, Genome, Homeostasis, Cell biology
Published
2011

33. Level of Activation of the Unfolded Protein Response Correlates With Paneth Cell Apoptosis in Human Small Intestine Exposed to Ischemia/Reperfusion

Author

Ronald M. van Dam, Caroline M. Hodin, Cornelis H. C. Dejong, Wim A. Buurman, Kasper M.A. Rouschop, Jacco J de Haan, Joep P. M. Derikx, Fons Verheyen, Joep Grootjans, Kaatje Lenaerts, Academic Medical Center, RS: NUTRIM - R2 - Gut-liver homeostasis, Genetica & Celbiologie, RS: CARIM School for Cardiovascular Diseases, RS: GROW - School for Oncology and Reproduction, Surgery, and Radiotherapie

Subjects
EXPRESSION, XBP1, Inflammation, Biology, digestive system, Ischemic Damage, ENDOPLASMIC-RETICULUM STRESS, medicine, REPERFUSION, PERMEABILITY, Hepatology, ATF6, Endoplasmic reticulum, Inflammatory Bowel Disease, Gastroenterology, HEMORRHAGIC-SHOCK, Molecular biology, DYSFUNCTION, ISCHEMIA, ALPHA, medicine.anatomical_structure, DDIT3, Apoptosis, Intestinal Microbiota, DEFENSINS, Paneth cell, Unfolded protein response, Tumor necrosis factor alpha, medicine.symptom, INFLAMMATORY-BOWEL-DISEASE
Abstract

BACKGROUND & AIMS: In the intestine, Paneth cells participate in the innate immune response. Their highly secretory function makes them susceptible to environmental conditions that cause endoplasmic reticulum (ER) stress. We investigated whether intestinal ischemia/reperfusion (I/R) induces ER stress, thereby activating the unfolded protein response (UPR), and whether excessive UPR activation affects Paneth cells. In addition, we investigated the consequences of Paneth cell compromise during physical barrier damage. METHODS: Jejunal I/R was studied using a human experimental model (n = 30 patients). Activation of the UPR was assessed using immunofluorescence for binding protein and quantitative polymerase chain reaction analyses for C/EBP homologous protein (CHOP), growth arrest and DNA-damage inducible protein 34 (GADD34), and X-box binding protein 1 (XBP1) splicing. Paneth cell apoptosis was assessed by double staining for lysozyme and M30. Male Sprague-Dawley rats underwent either intestinal I/R to investigate UPR activation and Paneth cell apoptosis, or hemorrhagic shock with or without intraperitoneal administration of dithizone, to study consequences of Paneth cell compromise during physical intestinal damage. In these animals, bacterial translocation and circulating tumor necrosis factor-alpha and interleukin-6 levels were assessed. RESULTS: In jejunum samples from humans and rats, I/R activated the UPR and resulted in Paneth cell apoptosis. Apoptotic Paneth cells showed signs of ER stress, and Paneth cell apoptosis correlated with the extent of ER stress. Apoptotic Paneth cells were shed into the crypt lumen, significantly lowering their numbers. In rats, Paneth cell compromise increased bacterial translocation and inflammation during physical intestinal damage. CONCLUSIONS: ER stress-induced Paneth cell apoptosis contributes to intestinal I/R-induced bacterial translocation and systemic inflammation.

Published
2011

35. 475n Minimally Invasive Step-up Approach Versus Open Necrosectomy in Necrotizing Pancreatitis: A Randomized Controlled Multicenter Trial

Author

Harry van Goor, Koop Bosscha, Casper H.J. van Eijck, Philip M Kruyt, Eric R. Manusama, Tom M. Karsten, Robin Timmer, Hjalmar C. van Santvoort, Eric J. Hesselink, Thomas L. Bollen, Vincent B. Nieuwenhuijs, Cornelis H. C. Dejong, H. S. Hofker, Marja A. Boermeester, Cees H. van Laarhoven, Olaf J. Bakker, Bert van Ramshorst, Hein G. Gooszen, Marc G. Besselink, Alexander F. Schaapherder, Erwin van der Harst, George P. van der Schelling, Camiel Rosman, and Erik Buskens

Subjects
medicine.medical_specialty, Hepatology, business.industry, Multicenter trial, Gastroenterology, Medicine, business, Necrotizing pancreatitis, Surgery
Published
2010

36. S1758 Loss of the Guardians at the Intestinal Barrier: Paneth Cell Apoptosis as a New Phenomenon in Human Intestinal Ischemia-Induced Bacterial Translocation

Author

Jacco-Juri de Haan, Adriaan P. de Bruïne, Ronald M. van Dam, Caroline M. Hodin, Joep Grootjans, Wim A. Buurman, Cornelis H. C. Dejong, Kaatje Lenaerts, Joep P. M. Derikx, and M'hamed Hadfoune

Subjects
medicine.anatomical_structure, Hepatology, Apoptosis, Intestinal ischemia, Paneth cell, Gastroenterology, medicine, Bacterial translocation, Biology, Cell biology
Published
2010

40. Effect of high-fat enteral nutrition on inflammation and gut barrier function in rats after hemorrhagic shock

Author

Misha D. P. Luyer, Anita Vreugdenhil, Cornelis H. C. Dejong, Jan Jacobs, M'hamed Hadfoune, Jan Greve, and Wim A. Buurman

Subjects
medicine.medical_specialty, Hepatology, Gut barrier, business.industry, Gastroenterology, Inflammation, Endocrinology, Parenteral nutrition, Internal medicine, Hemorrhagic shock, medicine, High fat, medicine.symptom, business, Function (biology)
Published
2003

44. Supplementation of Diet With Galacto-oligosaccharides Increases Bifidobacteria, but Not Insulin Sensitivity, in Obese Prediabetic Individuals.

Author

Canfora EE, van der Beek CM, Hermes GDA, Goossens GH, Jocken JWE, Holst JJ, van Eijk HM, Venema K, Smidt H, Zoetendal EG, Dejong CHC, Lenaerts K, and Blaak EE

Subjects
Acetic Acid analysis, Acute-Phase Proteins, Adiposity, Aged, Blood Glucose metabolism, Body Mass Index, Carrier Proteins blood, Cytokines blood, Dietary Supplements, Double-Blind Method, Energy Metabolism, Feces chemistry, Feces microbiology, Female, Gastrointestinal Microbiome, Humans, Incretins blood, Insulin blood, Male, Membrane Glycoproteins blood, Middle Aged, Obesity complications, Prediabetic State complications, Bifidobacterium, DNA, Bacterial analysis, Galactose administration & dosage, Insulin Resistance, Obesity metabolism, Oligosaccharides administration & dosage, Prediabetic State metabolism
Abstract

Background & Aims: The gut microbiota affects host lipid and glucose metabolism, satiety, and chronic low-grade inflammation to contribute to obesity and type 2 diabetes. Fermentation end products, in particular the short-chain fatty acid (SCFA) acetate, are believed to be involved in these processes. We investigated the long-term effects of supplementation with galacto-oligosaccharides (GOS), an acetogenic fiber, on the composition of the human gut microbiota and human metabolism., Methods: We performed a double-blinded, placebo-controlled, parallel intervention study of 44 overweight or obese (body mass index, 28-40 kg/m 2 ) prediabetic men and women (ages, 45-70 y) from October 2014 through October 2015 in Maastricht, The Netherlands. The participants were assigned randomly to groups who ingested 15 g GOS or isocaloric placebo (maltodextrin) daily with their regular meals for 12 weeks. Before and after this period, we collected data on peripheral and adipose tissue insulin sensitivity, fecal microbiota composition, plasma and fecal SCFA, energy expenditure and substrate oxidation, body composition, and hormonal and inflammatory responses. The primary outcome was the effect of GOS on peripheral insulin sensitivity, measured by the hyperinsulinemic-euglycemic clamp method., Results: Supplementation of diets with GOS, but not placebo, increased the abundance of Bifidobacterium species in feces by 5-fold (P = .009; q = 0.144). Microbial richness or diversity in fecal samples were not affected. We did not observe any differences in fecal or fasting plasma SCFA concentrations or in systemic concentrations of gut-derived hormones, incretins, lipopolysaccharide-binding protein, or other markers of inflammation. In addition, no significant alterations in peripheral and adipose tissue insulin sensitivity, body composition, and energy and substrate metabolism were found., Conclusions: Twelve-week supplementation of GOS selectively increased fecal Bifidobacterium species abundance, but this did not produce significant changes in insulin sensitivity or related substrate and energy metabolism in overweight or obese prediabetic men and women. ClincialTrials.gov number, NCT02271776., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Published
2017
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45. Level of activation of the unfolded protein response correlates with Paneth cell apoptosis in human small intestine exposed to ischemia/reperfusion.

Author

Grootjans J, Hodin CM, de Haan JJ, Derikx JP, Rouschop KM, Verheyen FK, van Dam RM, Dejong CH, Buurman WA, and Lenaerts K

Subjects
Animals, Antigens, Differentiation analysis, Bacterial Translocation, Cell Cycle Proteins analysis, DNA-Binding Proteins analysis, Female, Humans, Interleukin-6 blood, Intestine, Small pathology, Male, Paneth Cells pathology, Protein Phosphatase 1, Proto-Oncogene Proteins analysis, Rats, Rats, Sprague-Dawley, Regulatory Factor X Transcription Factors, Reperfusion Injury pathology, Shock, Hemorrhagic pathology, Transcription Factor CHOP analysis, Transcription Factors analysis, Tumor Necrosis Factor-alpha blood, Up-Regulation, X-Box Binding Protein 1, Apoptosis, Intestine, Small metabolism, Paneth Cells metabolism, Reperfusion Injury metabolism, Unfolded Protein Response
Abstract

Background & Aims: In the intestine, Paneth cells participate in the innate immune response. Their highly secretory function makes them susceptible to environmental conditions that cause endoplasmic reticulum (ER) stress. We investigated whether intestinal ischemia/reperfusion (I/R) induces ER stress, thereby activating the unfolded protein response (UPR), and whether excessive UPR activation affects Paneth cells. In addition, we investigated the consequences of Paneth cell compromise during physical barrier damage., Methods: Jejunal I/R was studied using a human experimental model (n = 30 patients). Activation of the UPR was assessed using immunofluorescence for binding protein and quantitative polymerase chain reaction analyses for C/EBP homologous protein (CHOP), growth arrest and DNA-damage inducible protein 34 (GADD34), and X-box binding protein 1 (XBP1) splicing. Paneth cell apoptosis was assessed by double staining for lysozyme and M30. Male Sprague-Dawley rats underwent either intestinal I/R to investigate UPR activation and Paneth cell apoptosis, or hemorrhagic shock with or without intraperitoneal administration of dithizone, to study consequences of Paneth cell compromise during physical intestinal damage. In these animals, bacterial translocation and circulating tumor necrosis factor-α and interleukin-6 levels were assessed., Results: In jejunum samples from humans and rats, I/R activated the UPR and resulted in Paneth cell apoptosis. Apoptotic Paneth cells showed signs of ER stress, and Paneth cell apoptosis correlated with the extent of ER stress. Apoptotic Paneth cells were shed into the crypt lumen, significantly lowering their numbers. In rats, Paneth cell compromise increased bacterial translocation and inflammation during physical intestinal damage., Conclusions: ER stress-induced Paneth cell apoptosis contributes to intestinal I/R-induced bacterial translocation and systemic inflammation., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Published
2011
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