The Pancreas Professor

You are still working hard in your 80s – what are your plans for the future and how long do you plan to go on working?
 

I consider it a great privilege to be able to do scientific and diagnostic work at my age, both physically and practically (instead of organizationally). Because sustained mental work demands good physical condition, my plans for the future are based on a reasonably stable state of health.

Fortunately, I am able to continue ongoing projects – many of which I undertake in collaboration with Atsuko Kasajima at the University Hospital Rechts der Isar in Munich. Together, we have the opportunity to carry out morphomolecular studies on pancreatic neuroendocrine tumors, funded by the German Research Foundation (DFG) and the European Neuroendocrine Tumor Society (ENETS). 

Our primary research goal is to advance the morphomolecular subtyping of pancreatic neuroendocrine tumors in order to gain insight into the enormous heterogeneity of these tumors. In this regard, we have made significant progress over the last two years in linking the phenotype and genotype of pancreatic neuroendocrine neoplasms. We will continue to work on this important research project, and I will be involved as long as my health permits.

How would you summarize your contribution to the understanding of the pathogenesis of pancreatic neoplasms, both endocrine and exocrine?
 

The insights that I was able to gain from investigations of the heterogeneity of pancreatic neuroendocrine tumors have contributed greatly to the advancement of the clinicopathological classification of these tumors – and thus to the development of the WHO classification – in the last two decades. On the one hand, it was possible to map the diversity of neuroendocrine pancreatic tumors and, in this context, also of neuroendocrine extra-pancreatic tumors. On the other hand, it was possible to gain access to the tumor’s diagnostic individuality that plays an extraordinary role in treatment.

In the case of exocrine pancreatic tumors, which have also occupied me over the years, the focus was on the description of new entities and, in particular, on the characterization of precursor lesions for ductal adenocarcinoma, which is clinically the most important and most common pancreatic tumor. I am particularly proud that I was able to contribute to the molecular pathogenesis of pancreatic cancer and to the understanding of the importance of KRAS mutation as one of the most important driver mutations for the development of this tumor.

Which aspect of your work has given you the most personal satisfaction?
 

The work in which I described the pathology of new pancreatic diseases immediately comes to mind. I was fascinated when I first saw the changes in the beta cells of the pancreas in newborns suffering from persistent hyperinsulinemic hypoglycemia. They reflected reactive changes of receptor disease and not of a neoplastic event, as was often discussed at the time. 

Similarly exciting was my observation and long-standing description of a tumor that was practically unknown at the time, which is now called solid-pseudopapillary neoplasm, and which ultimately carries the secret of its origin and nature within it. Furthermore, I am intrigued by the fact that, in multiple endocrine neoplasia type 1 in the pancreas, each individual tumor produces its own pancreatic hormone – and probably its genetic profile – and grows individually in the pancreas as if it were a model disease for tumor heterogeneity. 

Additionally, the descriptions of new hereditary pancreatic endocrine tumor diseases, such as glucagon cell hyperplasia and neoplasia and MAFA-related insulinomatosis, have been of great interest to me, as they have provided new insights into the development of pancreatic neuroendocrine tumors. 

Finally, I would also like to mention two non-neoplastic diseases of the pancreas – alcoholic pancreatitis and autoimmune pancreatitis – in whose pathogenesis and differentiation from other forms of pancreatitis I was able to play a fundamental role.

What was your involvement in the classification of pancreatic tumors?
 

As a member of the international group of pancreatic tumor specialists, I have been involved in the development of the classification of exocrine pancreatic tumors since 1996 and of endocrine pancreatic tumors since 2000.

The discussions on the classification were always very stimulating and enjoyable for me, and there were only very few situations in which it was difficult to reach a consensus. I have fond memories of working under the direction of Paul Kleihues and later Hiroko Ohgaki, together with Juan Rosai, Ricardo Lloyd, and Bob Osamura, as editor of the 4th edition of the WHO Classification of Endocrine Tumors in 2017.

What were your major achievements while directing the pathology departments in Brussels, Belgium and Kiel, Germany?
 

On reflection, I think my greatest achievements in both institutes were to spark an interest in research questions in my colleagues and to encourage them to engage in creative work. I did this by pointing out that, as pathologists, they were already doing translation research every day, whether they liked it or not.

What did it mean to you to be invited to present the Simeonidis lecture this year?
 

Being invited to give the Simeonidis Lecture at the ECP 2024 Annual Meeting in Florence was both a great task and a great honor for me. It gave me the unique opportunity to combine the developments in the subtyping of neuroendocrine pancreatic tumors – in which I was involved in the past – with the latest current findings that I had worked on with my colleagues and collaborators.

What advice do you have for those following in your footsteps?
 

Focus on one or two important questions and never lose sight of them in the face of life's daily demands. Enjoy what you do and enjoy thinking, even if it is hard work. Set yourself a goal, even if you think it is beyond your abilities.