Original Article
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World J Gastroenterol. Dec 21, 2013; 19(47): 9012-9019
Published online Dec 21, 2013. doi: 10.3748/wjg.v19.i47.9012
Clinically detected gastroenteropancreatic neuroendocrine tumors are on the rise: Epidemiological changes in Germany
Hans Scherübl, Brigitte Streller, Roland Stabenow, Hermann Herbst, Michael Höpfner, Christoph Schwertner, Joachim Steinberg, Jan Eick, Wanda Ring, Krishna Tiwari, Sören M Zappe
Hans Scherübl, Christoph Schwertner, Joachim Steinberg, Jan Eick, Wanda Ring, Krishna Tiwari, Klinik für Gastroenterologie, GI Onkologie und Infektiologie, Vivantes Klinikum Am Urban, 10967 Berlin, Germany
Brigitte Streller, Roland Stabenow, Gemeinsames Krebsregister der Länder Berlin, Brandenburg, Mecklenburg-Vorpommern, Sachsen-Anhalt und der Freistaaten Sachsen und Thüringen (GKR), 10967 Berlin, Germany
Hermann Herbst, Institut für Pathologie, Vivantes Netzwerk für Gesundheit GmbH, 10967 Berlin, Germany
Michael Höpfner, Institut für Physiologie, Charité-Universitätsmedizin, 10117 Berlin, Germany
Sören M Zappe, Charité-Universitätsmedizin Berlin, HNO-Klinik, Campus Virchow Klinikum, 13353 Berlin, Germany
Author contributions: Scherübl H analyzed data and wrote the paper; Streller B and Stabenow R performed research; Herbst H, Höpfner M, Schwertner C, Steinberg J, Eick J, Ring W and Tiwari K analyzed data; Zappa S performed research and wrote the paper.
Correspondence to: Dr. Hans Scherübl, Professor, Klinik für Gastroenterologie, GI Onkologie und Infektiologie, Vivantes Klinikum Am Urban, Akademisches Lehrkrankenhaus der Charité Dieffenbachstrasse 1, 10967 Berlin, Germany. hans.scheruebl@vivantes.de
Telephone: +49-301-30225201 Fax: +49-301-30225205
Received: February 25, 2013
Revised: July 17, 2013
Accepted: September 16, 2013
Published online: December 21, 2013

AIM: To study the epidemiologic changes of gastroenteropancreatic neuroendocrine tumors (GEP-NET) in Germany, we analyzed two time periods 1976-1988 and 1998-2006.

METHODS: We evaluated epidemiological data of GEP-NET from the former East German National Cancer Registry (DDR Krebsregister, 1976-1988) and its successor, the Joint Cancer Registry (GKR, 1998-2006), which was founded after German reunification. Due to a particularly substantial database the epidemiological data from the federal states of Mecklenburg-Western Pomerania, Saxony, Brandenburg and Thuringia, covering a population of more than 10.8 million people, were analyzed. Survival probabilities were calculated using life table analysis. In addition, GEP-NET patients were evaluated for one or more second (non-GEP-NET) primary malignancies.

RESULTS: A total of 2821 GEP neuroendocrine neoplasms were identified in the two registries. The overall incidence increased significantly between 1976 and 2006 from 0.31 (per 100.000 inhabitants per year) to 2.27 for men and from 0.57 to 2.38 for women. In the later period studied (2004-2006), the small intestine was the most common site. Neuroendocrine (NE) neoplasms of the small intestine showed the largest absolute increase in incidence, while rectal NE neoplasms exhibited the greatest relative increase. Only the incidence of appendiceal NET in women showed little change between 1976 and 2006. Overall survival of patients varied for sex, tumor site and the two periods studied but improved significantly over time. Interestingly, about 20% of the GEP-NET patients developed one or more second malignancies. Their most common location was the gastrointestinal tract. GEP-NET patients without second malignancies fared better than those with one or more of them.

CONCLUSION: The number of detected GEP-NET increased about 5-fold in Germany between 1976 and 2006. At the same time, their anatomic distribution changed, and the survival of GEP-NET patients improved significantly. Second malignancies are common and influence the overall survival of GEP-NET patients. Thus, GEP-NET warrant our attention as well as intensive research on their tumorigenesis.

Keywords: Neuroendocrine, Tumor, Epidemiology, Gastrinoma, Insulinoma, Endoscopy, German history, Reunification, Second malignancy

Core tip: Modern endoscopic and radiological tumor imaging have been implicated in the rise of the incidence of detected neuroendocrine tumors (NET) in Western countries. The particularities of German history, which resulted in two German states with two different health care systems from 1949-1989, allowed to study the epidemiological changes of NET in Germany on the background of two health care systems in 1949-1989. The number of detected gastroenteropancreatic-NET increased about 5-fold between 1976 and 2006. Most likely, the general availability of endoscopy after German reunification contributed to the major rise in frequency of detected rectal, gastric and duodenal NET in the new federal states of reunified Germany.