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Academic Center for Hepato-Pancreato-Biliary diseases

Last updated: 69 days ago.

The primary aim of this ACE is to be a world-wide leading center for HPB diseases in the three pillars of academic medicine: patient care, research, and teaching. Patient care involves expert multidisciplinary decision making as well as innovative diagnostic and therapeutic modalities. Research involves both epidemiological, translational and clinical research. Education involves teaching knowledge, judgment, and skills covering the complete spectrum from medical students to specialists.

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ACE research activities

The focus of research of the ACE is both epidemiological, translational and clinical research. 

Translational studies involve close collaborations between clinicians and scientists, for example: organoids of biliary tumors for personalized treatment, genomics of chronic HBV infection, and the innate immune response in viral hepatitis. 

Clinical research includes the initiation of several international registries (e.g. for PBC and pancreatic cysts), multi-center phase II trials (e.g. LAPC) and nation-wide phase III trials (e.g. PREOPANC and APEC).

Most of the studies in our ACE are multidisciplinary, for example pancreatitis studies (e.g. APEC trial) comparing endoscopic with surgical management, and oncological studies (e.g. PREOPANC trial) comparing combinations of surgery and systemic treatment. Future multidisciplinary phase 3 trials include PUMP trial and the PREOPANC-2 trial. Typically, each PhD student is supervised by professors of two or more disciplines.

The ACE has many long-term international collaborations, including: Johns Hopkins University (surveillance of patients at risk for pancreatic cancer, prognostic models for cholangiocarcinoma), Mayo Clinic (PSC, NASH, and liver transplantation), Memorial Sloan Kettering Cancer Center (cholangiocarcinoma and regional chemotherapy) and a world-wide registry for pancreatic cysts. The department of Hepatology at the Erasmus MC and the Toronto Centre for Liver Disease in Toronto, Canada, are collaborating on viral hepatitis, cholestatic liver disease and liver transplantation. In addition, the Erasmus MC participates in a international network on cholangiocarcinoma and liver adenomas (EURACAN).

Type of collaborations of the ACE

The ACE has many long-term international collaborations, including: Johns Hopkins University (surveillance of patients at risk for pancreatic cancer; prognostic models for cholangiocarcinoma), Mayo Clinic (PSC, NASH, and liver transplantation), Memorial Sloan Kettering Cancer Center (cholangiocarcinoma and regional chemotherapy), and a world-wide registry for pancreatic cysts.

ACE contribution to educational programs

Education within this ACE involves teaching knowledge, judgment and skills. The ACE contributes to education for all degrees: BA, MSc, PhD, medical specialization (AIOS), sub-specialization (clinical fellows), nurse practitioners and physician assistants. The liver transplantation fellowship program is accredited by the UEMS (European Union of Medical Specialist), the HPB program is scheduled for European accreditation this year. We offer competitive international fellowships, including a 6-months fellowship for advanced endoscopic skills (ERCP and EUS), a 4-month fellowship for liver transplantation and ultrasound of the liver and a two-year surgical fellowship for HPB and transplantation. Fellows come from all over the world including UK, Italy, Poland, Georgia, Turkey and Japan. Several postgraduate courses are organized by the ACE for an international audience, for example the basic course in liver transplantation and the annual Liver Day. We have a close collaboration with the International Organisation for Professionals (IASGO).

Each year we organize the minor “Organ transplantation” for medical students from the EUR and LUMC and for students of clinical Technology EUR (TU Delft) and of Biomedical Sciences (Leiden University). This minor includes all aspects of transplantation of Heart, Lung and Kidney transplantation and (multi-organ) donation, such as, organ failure, surgical techniques, machine perfusion and preservation, immunology, ethical and psychological aspects of transplantation and donation. Furthermore, we offer the minor students to join a transplant clinic or laboratory in foreign countries like Italy, the UK, Spain, Poland, Germany and France for 2 weeks. 

Evaluations including SETQ and audits allow for continuous improvement of our teaching programs. Moreover, we develop novel educational programs. For example, we developed and validated a novel teaching model to ensure safe training in ERCP.

ACE patient care activities

Most interventions within the ACE are not offered outside academic hospitals, including: liver transplantation, complex interventional endoscopy, management of hilar cholangiocarcinoma, management of benign and malignent liver tumors and liver resection in cirrhotic patients.

The ACE is recognized by the Netherlands Federation of University Hospitals (NFU) as a center of expertise for a nearly all rare HPB diseases, including: hepatocellular adenoma, cholangiocarcinoma, hepatocellular carcinoma, hereditary chronic pancreatitis, recurrent acute pancreatitis, autoimmune pancreatitis and congenital pancreatic cysts. Further increase in patient volume for these rare diseases is reassured by the new regional cancer network (EMBRAZE).
Transmural multidisciplinary clinical pathways have been implemented to reassure effective and efficient patient care. Value-based health care programs are near completion for cholangiocarcinoma, liver tumors and liver transplantation. Moreover, the ACE played a central role in the development of several national guidelines (e.g. pancreatic cancer), international guidelines (e.g. benign liver tumors) and nationwide clinical audits (e.g. pancreatic resection).
The ACE has contributed significantly to innovations in patient care, including: interventional endoscopy for pancreatic necrosis, management of pancreatic cysts and imaging in the modern operating roomand Ytrium treatment of malignant liver tumors.

Societal Relevance to Research, Education and Patient Care

Involvement in public health is exemplified by the international leading role in surveillance of individuals at high-risk for pancreatic cancer, and patients with pancreatic cysts, both in collaboration with the ACE Prevention. Moreover, members of the ACE co-authored the appraisal on early detection of pancreatic cancer of the Dutch Cancer Society. The ACE has developed curricula for all levels of training, for example, an HPB and liver transplantation curriculum for medical students that covers the same diseases as the ACE. The ACE continuous to innovate education, for example, with the recent development of a teaching model for ERCP and a robotic HPB surgery training program that is being developed.

The ACE wrote educational material for patients that is available on the website of the Dutch Cancer Society: kanker.nl. The ACE has played a leading role in both the development of national guidelines (e.g. pancreatic cancer, hepatocellular carcinoma, liver transplantation, organ donation after euthanasia and viral hepatitis) and international guidelines (e.g. chronic pancreatitis and liver adenoma). Moreover, the ACE has authored and edited many medical textbooks and is also highly visible in the lay press and media (e.g. in the past few months Volkskrant, NRC and RTL Late Night). Also, the ACE actively participates in the organization of the Erasmus Liver Day, held yearly in Rotterdam, NL.

Viability of Research, Education and Patient Care

Knowledge sharing is a key part of daily practice within the ACE: for example, between consultants and residents in clinic or in the OR, or between disciplines in the many weekly multidisciplinary meetings within the ACE. Several PhD students were trained during their curriculum at collaborating international leading centers.

The ACE is represented at all international meetings by PhD students presenting their original work and by consultants invited as lecturers or moderators. Many publications are the result of international collaborations involving both original research and consensus guidelines. To improve the quality of our work we focus on governance and leadership skills of our various units in our ACE, this in close collaboration with our network. A bibliometric network analysis is currently not available. However, the list of ten key publications in the next section demonstrates that the ACE participates in the international top.

Key and relevant publications of the last five years

  • Evolving trends in machine perfusion for liver transplantation - Authors Dutkowski P., Guarrera J.V., de Jonge J., Martins P.N., Porte R.J., Clavien P.A. - Gastroenterology - 10.1053/j.gastro.2018.12.037
  • Dutch Pancreatic Cancer Group. Laparoscopic versus open pancreatoduodenectomy for pancreatic or periampullary tumours (LEOPARD-2): a multicentre, patient-blinded, randomised controlled phase 2/3 trial - Bas Groot Koerkamp collaborator - Lancet Gastroenterol Hepatol 2019 Mar;4(3):199-207
  • Reduction of immunosuppressive tumor microenvironment in cholangiocarcinoma by ex vivo targeting immune checkpoint molecules - Authors: Zhou, G., Sprengers, D., Mancham, S., Erkens, R., Boor, P.P.C., van Beek, A.A., Doukas, M., Noordam, L., Campos Carrascosa, L., de Ruiter, V., van Leeuwen, R.W.F., Polak, W.G., de Jonge, J., Groot Koerkamp, B., van Rosmalen, B., van Gulik, T.M., Verheij, J., IJzermans, J.N.M., Bruno, M.J., Kwekkeboom, J. - Journal of Hepatology - 10.1016/j.jhep.2019.05.026
  • Growth of hepaotcellular adenoma during pregnancy: a prospective study - Authors: Gaspersz, M.P., Klompenhouwer, A.J., Broker, M.E.E., Thomeer, M.G.J., van Aalten, S.M., Steegers, E., Terkivatan, T., de Koning, H., de Man, R.A., IJzermans, J.N.M. - Journal of Hepatology - 10.1016/j.jhep.2019.09.0
  • Reply to "Detection and analysis of circulating epithelial cells in liquid biopsies from patients withliver disease: implications for transplant chimerism - Authors: Roos, F.J.M., IJzermans, J.N.M., van der Laan, L.J.W. - Gastroenterology. 2019 May;156(6):1932-1933. doi: 10.1053/j.gastro.2018.12.047
  • Hepatic angiomyolipoma: an international multicenter analysis on diagnosis, management and outcome - Klompenhouwer A.J., Dwarkasing R.S., Doukas M., Pellegrino S., Vilgrain V., Paradis V., Soubrane O., Beane J.D., Geller D.A., Nalesnik M.A., Tripke V., Lang H., Schmelzle M., Pratschke J., Schöning W., Beal E., Sun S., Pawlik, T.M., de Man, R.A., IJzermans, J.N.M. - HPB (Oxford). 2020 Apr;22(4):622-629. doi: 10.1016/j.hpb.2019.09.004
  • Neoadjuvant FOLFIRINOX in Patients With Borderline Resectable Pancreatic Cancer: A Systematic Review and Patient-Level Meta-Analysis - Janssen Q.P., Buettner S., Suker M., Beumer B.R., Addeo P., Bachellier P., Bahary N., Bekaii-Saab T., Bali M.A., Besselink M.G., Boone B.A., Chau I., Clarke S., Dillhoff M., El-Rayes B.F., Frakes J.M., Grose D., Hosein P.J., Jamieson N.B., Javed A.A., Khan K., Kim K.P., Kim S.C., Kim S.S., Ko A.H., Lacy J., Margonis G.A., McCarter M.D., McKay C.J., Mellon E.A., Moorcraft S.Y., Okada KI., Paniccia A., Parikh P.J., Peters N.A., Rabl H., Samra J., Tinchon C., van Tienhoven G., van Veldhuisen E., Wang-Gillam A., Weiss M.J., Wilmink J.W., Yamaue H., Homs M.Y.V., van Eijck C.H.J., Katz M.H.G., Groot Koerkamp B. - J Natl Cancer Inst. 2019 Aug 1;111(8):782-794
  • Large-Scale Production of LGR5-Positive Bipotential Human Liver Stem Cells - Schneeberger K., Sánchez-Romero N., Ye S., van Steenbeek F.G., Oosterhoff L.A., Pla Palacin I., Chen C., van Wolferen M.E., van Tienderen G., Lieshout R., Colemonts-Vroninks H., Schene I., Hoekstra R., Verstegen M.M.A., van der Laan L.J.W., Penning L.C., Fuchs S.A., Clevers H., De Kock J., Baptista P.M., Spee B. - Hepatology. 2020 Jul;72(1):257-270
  • Coffee and herbal tea consumption is associated with lower liver stiffness in the general population: The Rotterdam study. Authors: Alferink LJM, Fittipaldi J, Kiefte-de Jong JC, Taimr P, Hansen BE, Metselaar HJ, et al. J Hepatol. 2017;67(2):339-48.
  • To target or not to target viral antigens in HBV related HCC? Authors: Buschow SI, Sprengers D, Woltman AM. J Hepatol. 2015;62(6):1449-50.
  • Ursodeoxycholic acid therapy and liver transplant-free survival in patients with primary biliary cholangitis. Authors: Harms MH, van Buuren HR, Corpechot C, Thorburn D, Janssen HLA, Lindor KD, et al. J Hepatol. 2019;71(2):357-65.
  • Counter-regulation of rejection activity against human liver grafts by donor PD-L1 and recipient PD-1 interaction. Authors: Shi XL, Mancham S, Hansen BE, de Knegt RJ, de Jonge J, van der Laan LJ, et al. J Hepatol. 2016;64(6):1274-82.
  • Risk of cirrhosis-related complications in patients with advanced fibrosis following hepatitis C virus eradication. Authors: van der Meer AJ, Feld JJ, Hofer H, Almasio PL, Calvaruso V, Fernandez-Rodriguez CM, et al. J Hepatol. 2017;66(3):485-93.
  • Corrigendum to "MicroRNA profiles in graft preservation solution are predictive of ischemic-type biliary lesions after liver transplantation". Authors: Verhoeven CJ, Selten JW, Roest HP, Farid WRR, de Ruiter PE, Hansen BE, et al. [J Hepatol 2013; 59:1231-1238]. J Hepatol. 2017.
  • Reduction of immunosuppressive tumor microenvironment in cholangiocarcinoma by ex vivo targeting immune checkpoint molecules. Authors: Zhou G, Sprengers D, Mancham S, Erkens R, Boor PPC, van Beek AA, et al. J Hepatol. 2019;71(4):753-62.
  • Number needed to treat with ursodeoxycholic acid therapy to prevent liver transplantation or death in primary biliary cholangitis. Authors: Harms MH, de Veer RC, Lammers WJ, Corpechot C, Thorburn D, Janssen HLA, et al. Gut. 2020;69(8):1502-9.
  • The Yield and Safety of Screening Colonoscopy in Patients Evaluated for Liver Transplantation. Authors: Oey RC, van Tilburg L, Erler NS, Metselaar HJ, Spaander MCW, van Buuren HR, et al. Hepatology. 2019;69(6):2598-607.
  • Reliable prediction of clinical outcome in patients with chronic HCV infection and compensated advanced hepatic fibrosis: a validated model using objective and readily available clinical parameters. Authors: van der Meer AJ, Hansen BE, Fattovich G, Feld JJ, Wedemeyer H, Dufour JF, et al. Gut. 2015;64(2):322-31

PhD theses of the last five years

  • W.L. Lammers. Predicting outcome in primary biliary cirrhosis. Promotor: H.L.A. Janssen. Copromotors: H.R. van Buuren, B.E. Hansen. November 2015.
  • X. Shi. New insights in immune regulation after liver transplantation. Promotor: H.J. Metselaar. Copromotor: J. Kwekkeboom. March 2016.
  • C.J. Verhoeven. Biomarkers to assess graft quality in liver transplantation. Promotors: H.J. Metselaar, J.N.M. IJzermans. Copromotor: L.J.W. van der Laan. October 2016
  • R. de Groen. Understanding the innate immune response in viral hepatitis: interferons and NK cells. Promotors: H.J. Metselaar, A. Boonstra. October 2017.
  • A.J. Klompenhouwer. Benign liver tumors: from diagnosis to prognosis. Promotors: J.N.M. IJzermans, R.A. de Man. October 2019.
  • K. Sideras. The immune system in pancreatic cancer: innocent bystander or effect modulator? Promotors: M.J. Bruno, S. Sleijfer. April 2017
  • G. Zhou. Regulation of intra-tumoral T cell immunity inliver cancer. Promotor: M.J. Bruno. Copromotor: J. Kwekkeboom. July 2018.
  • I. Konings. Surveillance of individuals at high risk for developing pancreatic cancer. Promotor: M.J. Bruno. December 2018.
  • P.A. van Riet. Feasibility and clinical application of EUS-guided fine needle aspiration and biopsy. Promotor: M.J. Bruno. Copromotor: D.J. Cahen. November 2019.
  • N.A. van Huizen. Collagen in colorectal cancer: a mass spectrometry analysis. Promotors: J.N.M. IJzermans, P.A.E. Sillevis Smitt. Copromotor: T.M. Luider. January 2020
  • S. Levolger. Skeletal Muscle Wasting: clinical implications and experimental treatment. Promotor: J.N.M. IJzermans. Copromotor: R.W.F. de Bruin. November 2019.
  • M.P. Gaspersz. Perihilar Cholangiocarcinoma: improving prognostication and palliative treatment. Promotor: J.N.M. IJzermans. Copromotor: B. Groot Koerkamp. April 2019.
  • M. Kalisvaart. Assessment of graft quality and postoperative complications in liver transplantation. Promotor: J.N.M. IJzermans. Copromotor: J. de Jonge. December 2018.
  • S. Buttner. Personalized Hepatobiliary Cancer Treatment. Promotors: J.N.M. IJzermans, T.M. Pawlik. Copromotor: B. Groot Koerkamp. June 2018.
  • J. Fest. The role of inflammationin cancer and mortality. Promotors: C.H.J. van Eijck, B.H.C. Stricker. Copromotor: T.R. Ruiter. November 2019
  • M. Suker. Locally advanced pancreatic cancer: beyond the borders. Promotor: C.H.J. van Eijck. Copromotor: B. Groot Koerkamp. September 2019.
  • E.E. Vietsch. Circulating biomarkers in cancer progression and treatment. Promotors: C.H.J. van Eijck, A. Wellstein. December 2018.
  • C.G. Genç. Recurrence and survival of pancreatic neuroendocrine tumors. Promotor: C.H.J. van Eijck. Copromotor: E.J.M. Nieveen van Dijkum. December 2018.

Non-scientific publications related to the ACE

  • 27th November 2015, Convention Center "De Doelen", Rotterdam, NL. Patientsday about Liver diseases: "A .. liver: repair or replace?"
  • 29th November 2019, Convention Center "De Doelen", Rotterdam, NL. Patients day about Liver diseases: ‘Surviving a livere disease'

Principal coordinator(s)

  • J.N.M. IJzermans

Leading investigator(s)

  • M.J. Bruno
  • J. de Jonge
  • R.A. de Man
  • B. Groot Koerkamp
  • J.N.M. IJzermans
  • H.J. Metselaar
  • M.P. Peppelenbosch
  • W.G. Polak
  • J.W. Poley
  • M.G.J. Thomeer
  • L.J.W. van der Laan
  • C.H.J. van Eijck

Collaborating investigator(s)

  • P.A. Boonstra
  • F.A.L.M. Eskens
  • L.H. Graven
  • M.Y.V. Homs
  • M.G.M. Hunink
  • A.M. Mendez Romero
  • F.E.J.A. Willemsen