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1. ASO Visual Abstract: Nationwide Use and Outcome of Surgery for Locally Advanced Pancreatic Cancer Following Induction Chemotherapy

Author

Stoop, Thomas F., Seelen, Leonard W. F., van’t Land, Freek R., Lutchman, Kishan R. D., van Dieren, Susan, Lips, Daan J., van der Harst, Erwin, Kazemier, Geert, Patijn, Gijs A., de Hingh, Ignace H., Wijsman, Jan H., Erdmann, Joris I., Festen, Sebastiaan, Groot Koerkamp, Bas, Mieog, J. Sven D., Dulk, Marcel den, Stommel, Martijn W. J., Busch, Olivier R., de Wilde, Roeland F., de Meijer, Vincent E., Riele, Wouter te, Molenaar, I. Quintus, van Eijck, Casper H. J., van Santvoort, Hjalmar C., and Besselink, Marc G.

Published
2024
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2. Outcomes of liver surgery: A decade of mandatory nationwide auditing in the Netherlands

Author

Patijn, Gijs A., Torrenga, Hans, van Heek, N. Tjarda, Oosterling, Steven J., de Graaff, Michelle R., Klaase, Joost M., Dulk, Marcel den, Buis, C.I., Derksen, Wouter J.M., Hagendoorn, Jeroen, Leclercq, Wouter K.G., Liem, Mike S.L., Hartgrink, Henk H., Swijnenburg, Rutger-Jan, Vermaas, M., Belt, Eric J. Th, Bosscha, Koop, Verhoef, Cees, Olde Damink, Steven, Kuhlmann, Koert, Marsman, H.M., Ayez, Ninos, van Duijvendijk, Peter, van den Boezem, Peter, Manusama, Eric R., Grünhagen, Dirk J., and Kok, Niels F.M.

Published
2024
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3. Association of modified textbook outcome and overall survival after surgery for colorectal liver metastases: A nationwide analysis

Author

Manusama, Hans Torrenga E., van Heek, Tjarda N., Oosterling, S.J., Voigt, Kelly R., de Graaff, Michelle R., Verhoef, Cornelis, Kazemier, Geert, Swijneburg, Rutger J., Mieog, J.Sven D., Derksen, Wouter J.M., Buis, Carlijn I., Gobardhan, Paul D., Dulk, Marcel den, van Dam, Ronald M., Liem, Mike S.L., Leclercq, Wouter K.G., Bosscha, Koop, Belt, Eric J.T., Vermaas, Maarten, Kok, Niels F.M., Patijn, Gijs A., Marsman, H.M., van den Boezem, Peter B., Klaase, Joost M., and Grünhagen, Dirk J.

Published
2024
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4. Survival of patients with colorectal liver metastases treated with and without preoperative chemotherapy: Nationwide propensity score-matched study

Author

Buis, Carlijn I., Hagendoorn, Jeroen, Derksen, Wouter J.M., Torrenga, Hans, Manusama, Eric, Tjarda van Heek, N., Oosterling, Steven J., Bosscha, Koop, Braat, Andries E., Hoogwater, Frederik J.H., Consten, Esther C.J., van der Leij, Christiaan, Burgmans, Mark C., Liem, Mike S.L., Belt, Eric J.Th, Patijn, Gijs A., de Graaff, Michelle.R., Klaase, Joost M., van Dam, Ronald M., Kuhlmann, Koert F.D., Kazemier, Geert, Swijnenburg, Rutger-Jan, Elfrink, Arthur K.E., Verhoef, Cees, Mieog, J.Sven, van den Boezem, Peter B., Gobardhan, Paul, Rijken, Arjen M., Lips, Daan J., Leclercq, Wouter G.K., Marsman, Hendrik A., van Duijvendijk, Peter, van der Hoeven, Joost A.B., Vermaas, Maarten, Dulk, Marcel den, Grünhagen, Dirk J., and Kok, Niels F.M.

Published
2023
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7. Hospital variation and outcomes of simultaneous resection of primary colorectal tumour and liver metastases: a population-based study

Author

Manusama, Eric R., Bosscha, Koop, Belt, Eric J.T., Vermaas, Maarten, Consten, Esther C.J., van Heek, N.T., Oosterling, Steven J., Besselink, Marc G.H., de Boer, Marieke T., Braat, Andries E., DeJong, Cornelis H.C., Hagendoorn, Jeroen, Molenaar, I.Q., Patijn, Gijs A., Marsman, Hendrik A., Hoogwater, Frederik J.H., Krul, Myrtle F., Elfrink, Arthur K.E., Buis, Carlijn I., Swijnenburg, Rutger-Jan, te Riele, Wouter W., Verhoef, Cornelis, Gobardhan, Paul D., Dulk, Marcel den, Liem, Mike S.L., Tanis, Pieter J., Mieog, J.S.D., van den Boezem, Peter B., Leclercq, Wouter K.G., Nieuwenhuijs, Vincent B., Gerhards, Michael F., Klaase, Joost M., Grünhagen, Dirk J., Kok, Niels F.M., and Kuhlmann, Koert F.D.

Published
2022
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8. Outcomes of liver surgery: A decade of mandatory nationwide auditing in the Netherlands

Author

de Graaff, Michelle R., primary, Klaase, Joost M., additional, Dulk, Marcel den, additional, Buis, C.I., additional, Derksen, Wouter J.M., additional, Hagendoorn, Jeroen, additional, Leclercq, Wouter K.G., additional, Liem, Mike S.L., additional, Hartgrink, Henk H., additional, Swijnenburg, Rutger-Jan, additional, Vermaas, M., additional, Belt, Eric J. Th, additional, Bosscha, Koop, additional, Verhoef, Cees, additional, Olde Damink, Steven, additional, Kuhlmann, Koert, additional, Marsman, H.M., additional, Ayez, Ninos, additional, van Duijvendijk, Peter, additional, van den Boezem, Peter, additional, Manusama, Eric R., additional, Grünhagen, Dirk J., additional, Kok, Niels F.M., additional, Patijn, Gijs A., additional, Torrenga, Hans, additional, van Heek, N. Tjarda, additional, and Oosterling, Steven J., additional

Published
2024
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9. Association of modified textbook outcome and overall survival after surgery for colorectal liver metastases: A nationwide analysis

Author

Voigt, Kelly R., primary, de Graaff, Michelle R., additional, Verhoef, Cornelis, additional, Kazemier, Geert, additional, Swijneburg, Rutger J., additional, Mieog, J.Sven D., additional, Derksen, Wouter J.M., additional, Buis, Carlijn I., additional, Gobardhan, Paul D., additional, Dulk, Marcel den, additional, van Dam, RonaldM., additional, Liem, Mike S.L., additional, Leclercq, Wouter K.G., additional, Bosscha, Koop, additional, Belt, Eric J.T., additional, Vermaas, Maarten, additional, Kok, Niels F.M., additional, Patijn, Gijs A., additional, Marsman, H.M., additional, van den Boezem, Peter B., additional, Klaase, Joost M., additional, Grünhagen, Dirk J., additional, Manusama, Hans Torrenga E., additional, van Heek, Tjarda N., additional, and Oosterling, S.J., additional

Published
2024
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11. Impact of nationwide implementation of best practices in pancreatic cancer care (PACAP-1): a stepped-wedge cluster randomised controlled trial

Author

Augustinus, Simone, primary, Mackay, Tara M., additional, Latenstein, Anouk E.J., additional, van der Geest, Lydia G., additional, Bogte, Auke, additional, Bonsing, Bert A., additional, Bos, Hendrik, additional, Bosscha, Koop, additional, Borsens, Lodewijk A.A., additional, Cirkel, Geert A., additional, Hol, Lieke, additional, Busch, Olivier R.C., additional, Creemers, Geert-Jan, additional, Curvers, Wouter L., additional, Derks, Sarah, additional, Dulk, Marcel den, additional, van Dieren, Susan, additional, van Driel, Lydi M.J.W., additional, Festen, Sebastiaan, additional, van Geenen, Erwin J.M., additional, de Groot, Derk-Jan A., additional, de Groot, Jan-Willem B., additional, Koerkamp, Bas Groot, additional, Mohammad, Nadia Haj, additional, Haberkorn, Brigitte C.M., additional, Haver, Joyce T., additional, van der Harst, Erwin, additional, Hemmink, G.J. Maarten, additional, de Hingh, Ignace H., additional, Hoge, Chantal, additional, Homs, Marjolein Y.V., additional, Inderson, Akin, additional, Jacobs, Maarten A.J.M., additional, Kerver, Emile D., additional, Liem, Mike S.L., additional, Los, Maartje, additional, Lubbinge, Hans, additional, Luelmo, Saskia A.C., additional, de Meijer, Vincent E., additional, Mekenkamp, Leonie, additional, Molenaar, I. Quintus, additional, Patijn, Gijs A., additional, Quispel, Rutger, additional, Römkens, Tessa E.H., additional, van Santvoort, Hjalmar C., additional, Schreinemakers, Jennifer M.J., additional, Schut, Heidi, additional, Seerden, Tom, additional, Stommel, Martijn W.J., additional, Venneman, Niels G., additional, Verdonk, Robert C., additional, Verheij, Joanne, additional, van Vilsteren, Frederike G.I., additional, de Vos-Geelen, Judith, additional, Vulink, Annelie, additional, Wientjes, Caroline A., additional, Wit, Fennie, additional, Wessels, Frank J., additional, Zonderhuis, Babs, additional, Henri van Werkhoven, C., additional, van Hooft, Jeanin E., additional, van Eijck, Casper H.J., additional, Wilmink, Johanna W., additional, van Laarhoven, Hanneke W.M., additional, and Besselink, Marc G., additional

Published
2023
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12. Survival of patients with colorectal liver metastases treated with and without preoperative chemotherapy: Nationwide propensity score-matched study

Author

de Graaff, Michelle.R., primary, Klaase, Joost M., additional, van Dam, Ronald M., additional, Kuhlmann, Koert F.D., additional, Kazemier, Geert, additional, Swijnenburg, Rutger-Jan, additional, Elfrink, Arthur K.E., additional, Verhoef, Cees, additional, Mieog, J.Sven, additional, van den Boezem, Peter B., additional, Gobardhan, Paul, additional, Rijken, Arjen M., additional, Lips, Daan J., additional, Leclercq, Wouter G.K., additional, Marsman, Hendrik A., additional, van Duijvendijk, Peter, additional, van der Hoeven, Joost A.B., additional, Vermaas, Maarten, additional, Dulk, Marcel den, additional, Grünhagen, Dirk J., additional, Kok, Niels F.M., additional, Buis, Carlijn I., additional, Hagendoorn, Jeroen, additional, Derksen, Wouter J.M., additional, Torrenga, Hans, additional, Manusama, Eric, additional, Tjarda van Heek, N., additional, Oosterling, Steven J., additional, Bosscha, Koop, additional, Braat, Andries E., additional, Hoogwater, Frederik J.H., additional, Consten, Esther C.J., additional, van der Leij, Christiaan, additional, Burgmans, Mark C., additional, Liem, Mike S.L., additional, Belt, Eric J.Th, additional, and Patijn, Gijs A., additional

Published
2023
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13. Predictive genetic biomarkers for the development of peritoneal metastases in colorectal cancer

Author

Heuvelings, Danique J.I., primary, Wintjens, Anne G.W.E, additional, Moonen, Laura, additional, Engelen, Sanne M.E., additional, Iersel, Liselot B. Valkenburg - van, additional, Dulk, Marcel Den, additional, Beckervordersandforth, Jan, additional, Thijssen, Sharon G.M., additional, Leunissen, Daphne J.G., additional, Stassen, Laurents P.S., additional, Keszthelyi, Daniel, additional, de Hingh, Ignace H.J.T., additional, Mujagic, Zlatan, additional, Speel, Ernst-Jan M., additional, and Bouvy, Nicole D., additional

Published
2023
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15. Computer-aided decision support and 3D modelling in pancreatic cancer surgery

Author

Rasenberg, Diederik, primary, Ramaekers, Mark, additional, Jacobs, Igor, additional, Pluyter, Jon, additional, Geurts, Luc, additional, Nederend, Joost, additional, de Hingh, Ignace, additional, Bonsing, Bert, additional, Vahrmeijer, Alexander, additional, van der Harst, Erwin, additional, Dulk, Marcel den, additional, van Dam, Ronald, additional, Koerkamp, Bas Groot, additional, Surgery Group, Amsterdam UMC., additional, Riele, Wouter te, additional, Reinhard, Rinze, additional, Jansen, Frank Willem, additional, Dankelman, Jenny, additional, Mieog, Sven, additional, and Luyer, Misha, additional

Published
2023
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19. Surgical Outcome After Pancreatoduodenectomy for Duodenal Adenocarcinoma Compared with Other Periampullary Cancers: A Nationwide Audit Study

Author

Bakker, J.K. de, Suurmeijer, J.A., Toennaer, J.G.J., Bonsing, B.A., Busch, O.R., Eijck, C.H.J. van, Hingh, I.H.J.T. de, Meijer, V.E. de, Molenaar, I.Q., Santvoort, H.C. van, Stommel, M.W.J., Festen, S., Harst, E, Patijn, G., Lips, D.J., Dulk, Marcel den, Bosscha, K., Besselink, M.G., and Kazemier, G.

Subjects
Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], All institutes and research themes of the Radboud University Medical Center
Abstract

Contains fulltext : 291512.pdf (Publisher’s version ) (Open Access) BACKGROUND: Surgical outcome after pancreatoduodenectomy for duodenal adenocarcinoma could differ from pancreatoduodenectomy for other cancers, but large multicenter series are lacking. This study aimed to determine surgical outcome in patients after pancreatoduodenectomy for duodenal adenocarcinoma, compared with other periampullary cancers, in a nationwide multicenter cohort. METHODS: After pancreatoduodenectomy for cancer between 2014 and 2019, consecutive patients were included from the nationwide, mandatory Dutch Pancreatic Cancer Audit. Patients were stratified by diagnosis. Baseline, treatment characteristics, and postoperative outcome were compared between groups. The association between diagnosis and major complications (Clavien-Dindo grade III or higher) was assessed via multivariable regression analysis. RESULTS: Overall, 3113 patients, after pancreatoduodenectomy for cancer, were included in this study: 264 (8.5%) patients with duodenal adenocarcinomas and 2849 (91.5%) with other cancers. After pancreatoduodenectomy for duodenal adenocarcinoma, patients had higher rates of major complications (42.8% vs. 28.6%; p

Published
2023

20. ASO Visual Abstract: Surgical Outcome After Pancreatoduodenectomy for Duodenal Adenocarcinoma Compared with Other Periampullary Cancers-A Nationwide Audit Study

Author

Bakker, J.K. de, Annelie Suurmeijer, J., Toennaer, J.G.J., Bonsing, B.A., Busch, O.R., Eijck, C.H.J. van, Hingh, I.H.J.T. de, Meijer, V.E. de, Quintus Molenaar, I., Santvoort, H.C. van, Stommel, M.W.J., Festen, S., Harst, E.V., Patijn, G., Lips, D.J., Dulk, Marcel den, Bosscha, K., Besselink, M.G., and Kazemier, G.

Subjects
Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], All institutes and research themes of the Radboud University Medical Center, Center for Biblical and Theological Studies (CBTS)
Abstract

Contains fulltext : 291514.pdf (Publisher’s version ) (Closed access) 01 april 2023

Published
2023

21. Hospital variation and outcomes of simultaneous resection of primary colorectal tumour and liver metastases: a population-based study

Author

Krul, Myrtle F., primary, Elfrink, Arthur K.E., additional, Buis, Carlijn I., additional, Swijnenburg, Rutger-Jan, additional, te Riele, Wouter W., additional, Verhoef, Cornelis, additional, Gobardhan, Paul D., additional, Dulk, Marcel den, additional, Liem, Mike S.L., additional, Tanis, Pieter J., additional, Mieog, J.S.D., additional, van den Boezem, Peter B., additional, Leclercq, Wouter K.G., additional, Nieuwenhuijs, Vincent B., additional, Gerhards, Michael F., additional, Klaase, Joost M., additional, Grünhagen, Dirk J., additional, Kok, Niels F.M., additional, Kuhlmann, Koert F.D., additional, Manusama, Eric R., additional, Bosscha, Koop, additional, Belt, Eric J.T., additional, Vermaas, Maarten, additional, Consten, Esther C.J., additional, van Heek, N.T., additional, Oosterling, Steven J., additional, Besselink, Marc G.H., additional, de Boer, Marieke T., additional, Braat, Andries E., additional, DeJong, Cornelis H.C., additional, Hagendoorn, Jeroen, additional, Molenaar, I.Q., additional, Patijn, Gijs A., additional, Marsman, Hendrik A., additional, and Hoogwater, Frederik J.H., additional

Published
2022
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22. Implementation and first results of a mandatory, nationwide audit on liver surgery

Author

van der Werf, Leonie R., Kok, Niels F. M., Buis, Carlijn I., Grünhagen, Dirk J., Hoogwater, Frederik J. H., Swijnenburg, Rutger Jan, Dulk, Marcel den, Dejong, Kees C. H. C., Klaase, Joost M., de Boer, Marieke T., Besselink, Marc G. H., van Gullik, Thomas M., Hagendoorn, Jeroen, van Hillegersberg, Richard, Liem, Mike S. L., Molenaar, I. Quintus, Patijn, Gijs A., Porte, Robert J., te Riele, Wouter W., van Santvoort, Hjalmar C., Verhoef, Kees, Burgmans, Marc C., van Delden, Otto M., van der Leij, Christiaan, Meijerink, Martijn R., Moelker, Adriaan, Prevoo, Warner, Surgery, AGEM - Digestive immunity, AGEM - Re-generation and cancer of the digestive system, CCA - Cancer Treatment and Quality of Life, Radiology and Nuclear Medicine, ACS - Amsterdam Cardiovascular Sciences, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Other Research, MUMC+: MA Heelkunde (9), RS: NUTRIM - R2 - Liver and digestive health, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, CCA - Cancer Treatment and quality of life, Radiology and nuclear medicine, Groningen Institute for Organ Transplantation (GIOT), and Value, Affordability and Sustainability (VALUE)

Subjects
Male, Liver surgery, medicine.medical_specialty, RESECTION, ENHANCED RECOVERY, MEDLINE, Audit, 030230 surgery, Liver resections, MORBIDITY, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Hepatectomy, Humans, Medicine, Registries, Neoplasm Metastasis, Aged, Netherlands, Quality Indicators, Health Care, Retrospective Studies, Clinical Audit, Hepatology, business.industry, General surgery, Liver Neoplasms, Gastroenterology, Outcome measures, Retrospective cohort study, CHEMOTHERAPY, Middle Aged, CANCER, METASTASES, Population Surveillance, 030220 oncology & carcinogenesis, Female, Colorectal Neoplasms, business, Complication, Follow-Up Studies
Abstract

Background: The Dutch Hepato Biliary Audit (DHBA) was initiated in 2013 to assess the national quality of liver surgery. This study aimed to describe the initiation and implementation of this audit along with an overview of the results and future perspectives.Methods: Registry of patients undergoing liver surgery for all primary and secondary liver tumors in the DHBA is mandatory. Weekly, benchmarked information on process and outcome measures is reported to surgical teams. In this study, the first results of patients with colorectal liver metastases were presented, including results of data verification.Results: Between 2014 and 2017, 6241 procedures were registered, including 4261 (68%) resections for colorectal liver metastases. For minor- and major liver resections for colorectal liver metastases, the median [interquartile range] hospital stay was 6 [4-8] and 8 [6-12] days, respectively. A postoperative complicated course (complication leading to >14 days of hospital stay, reintervention or death) occurred in 26% and 43% and the 30-day/in-hospital mortality was 1% and 4%, respectively. The completeness of data was 97%. In 3.6% of patients, a complicated postoperative course was erroneously omitted.Conclusion: Nationwide implementation of the DHBA has been successful. This was the first step in creating a complete evaluation of the quality of liver surgery.

Published
2019

23. ASO Author Reflections: Nationwide Experience on Locally Advanced Pancreatic Cancer Surgery After Induction Chemotherapy in the Netherlands: A Stepping Stone for the PREOPANC-4 Trial.

Author

Stoop, Thomas F., Seelen, Leonard W. F., van 't Land, Freek R., van Eijck, Casper H. J., van Santvoort, Hjalmar C., Besselink, Marc G., for the Dutch Pancreatic Cancer Group, Lips, Daan J., van der Harst, Erwin, Kazemier, Geert, Patijn, Gijs A., de Hingh, Ignace H., Wijsman, Jan H., Erdmann, Joris I., Festen, Sebastiaan, Groot Koerkamp, Bas, Mieog, J. Sven D., Dulk, Marcel den, Stommel, Martijn W. J., and Busch, Olivier R.

Published
2024
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24. Perioperative and long-term Outcome of en-bloc arterial resection in pancreatic surgery

Author

Wiltberger, Georg, primary, Dulk, Marcel den, additional, Bednarsch, Jan, additional, Czigany, Zoltan, additional, Lang, Sven A., additional, Andert, Anne, additional, Lamberzt, Andreas, additional, Heij, Lara R., additional, de Vos-Geelen, Judith, additional, Stommel, Martijn W.J., additional, van Dam, Ronald M., additional, Dejong, Cornelis, additional, Ulmer, Florian, additional, and Neumann, Ulf Peter, additional

Published
2021
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26. Multicenter Observational Study of Adhesion Formation After Open-and Laparoscopic Surgery for Colorectal Cancer.

Author

Stommel, Martijn W. J., ten Broek, Richard P. G., Strik, Chema, Slooter, Gerrit D., Verhoef, Cornelis, Grünhagen, Dirk J., van Duijvendijk, Peter, Bemelmans, Marc H. A., Dulk, Marcel den, Sietses, Colin, van Heek, Tjarda N. T., van den Boezem, Peter B., de Wilt, Johannes H. W., and van Goor, Harry

Abstract

Objective: The aim of this study was to compare adhesion formation after laparoscopic and open colorectal cancer resection. Summary of Background Data: After colorectal surgery, most patients develop adhesions, with a high burden of complications. Laparoscopy seems to reduce adhesion formation, but evidence is poor. Trials comparing open- and laparoscopic colorectal surgery have never assessed adhesion formation. Methods: Data on adhesions were gathered during resection of colorectal liver metastases. Incidence of adhesions adjacent to the original incision was compared between patients with previous laparoscopic- and open colorectal resection. Secondary outcomes were incidence of any adhesions, extent and severity of adhesions, and morbidity related to adhesions or adhesiolysis. Results: Between March 2013 and December 2015, 151 patients were included. Ninety patients (59.6%) underwent open colorectal resection and 61 patients (40.4%) received laparoscopic colorectal resection. Adhesions to the incision were present in 78.9% after open and 37.7% after laparoscopic resection (P < 0.001). The incidence of abdominal wall adhesions and of any adhesion was significantly higher after open resection; the incidence of visceral adhesions did not significantly differ. The extent of abdominal wall and visceral adhesions and the median highest Zühlke score at the incision were significantly higher after open resection. There were no differences in incidence of small bowel obstruction during the interval between the colorectal and liver operations, the incidence of serious adverse events, and length of stay after liver surgery. Conclusion: Laparoscopic colorectal cancer resection is associated with a lower incidence, extent, and severity of adhesions to parietal surfaces. Laparoscopy does not reduce the incidence of visceral adhesions. [ABSTRACT FROM AUTHOR]

Published
2018
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27. Survival of elderly rectal cancer patients not improved: Analysis of population based data on the impact of TME surgery

Author

Rutten, Harm, primary, Dulk, Marcel den, additional, Lemmens, Valery, additional, Nieuwenhuijzen, Grard, additional, Krijnen, Pieta, additional, Jansen-Landheer, Marlies, additional, van de Poll Franse, Lonneke, additional, Coebergh, Jan-Willen, additional, Martijn, Hendrik, additional, Marijnen, Corrie, additional, and van de Velde, Cock, additional

Published
2007
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30. Morphometry of interstitial fibrosis

Author

Heer, Emile De, Sijpkens, Yvo W. J., Verkade, Martijn, Dulk, Marcel den, Langers, Alexandra, Schutrups, Jan, Bruijn, Jan Anthonie, and Es, Leendert A. van

Abstract

Several clinical studies have confirmed that histomorphometric changes in the tubulointerstitial compartment contain the best correlating parameters to predict the development of progressive renal insufficiency. The process of interstitial fibrosis is accompanied by an influx of inflammatory cells, up-regulation of fibrogenic cytokines such as transforming growth factor-β and basic fibroblast growth factor, transient down-modulation of their antagonists, generation and proliferation of myofibroblasts, and finally, by accumulation of interstitial collagens and proteoglycans. A careful morphometric analysis of interstitial fibrosis requires sensitive parameters through which the severity can be quantified and by which the progression into renal insufficiency can be predicted. We have addressed these issues by morphometric analysis of both human biopsies and by refining existing experimental models in the rat. Morphometric analysis was performed using a Zeiss microscope equipped with a full colour 3CCD camera and KS-400 image analysis software from Zeiss-Kontron. For studies with human material, biopsies were examined from patients with various renal diseases including patients with chronic allotransplant dysfunction. The development of interstitial fibrosis was correlated with clinical parameters. In experimental models, we analysed the interstitial composition and eventual glomerular alterations in rats with bovine serum albumin (BSA)-induced protein overload nephropathy and with human IgG-induced chronic serum sickness nephritics. Finally, we adapted and refined the model of ureter obstruction-induced interstitial fibrosis in the rat. For this purpose, custom-made titanium clips (S&T, Neuhaus, Switzerland) were implanted around the ureter in the abdomen of rats to obstruct the ureter without causing necrosis. The clips were removed at various time points after obstruction of the ureter (1-14 days). The subsequent remodelling of the interstitium was studied thereafter, in order to establish whether uraemia-induced interstitial fibrosis remains reversible at all times. In rat models, we have found that both protein overload-induced and serum sickness-induced interstitial fibrosis are accompanied by the development of focal and segmental glomerulosclerosis. Only in the ureter obstruction model did selective interstitial fibrosis develop, and remained reversible at all times studied. For the reliable assessment of interstitial fibrosis we have found that the best correlating parameters of interstitial fibrosis with renal function were: (i) the ratio of protein accumulation of TGF-β-1 and its antagonist decorin; (ii) interstitial expression of smooth muscle α-actin; and (iii) accumulation of interstitial collagens (as determined by immunoperoxidase and by Sirius red staining).

Published
2000

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