Reviews in Endocrine and Metabolic Disorders

, Volume 18, Issue 4, pp 373–378 | Cite as

Neuroendocrine neoplasms – still a challenge despite major advances in clinical care with the development of specialized guidelines

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The term ‘neuroendocrine neoplasms’ (NEN) covers a wide range of tumors originating from neuroendocrine cells in various organs. Heterogeneity and rarity of NEN have hampered early diagnosis and standardized treatment for years, with many physicians being unaware of the clinical relevance of NEN. Although expanding knowledge of the molecular characteristics of neuroendocrine cells resulted in new diagnostic and therapeutic possibilities, their integration into management algorithms is still ongoing. Furthermore, availability of diagnostic and therapeutic tools varies considerably in different regions of the world.

Confronted with the very specific challenges of NEN, various groups and professional societies developed guidelines to standardize the approach to this fascinating but life-threating disease. Especially the European Neuroendocrine Tumor Society (ENETS) has continuously updated their recommendations, starting 2004 with a summary paper [1], but later developing highly subtype-specific guidelines recognizing the great differences between the various forms of NEN. These guidelines focused on functioning and non-functioning pancreatic NEN ([2, 3, 4, 5], revised 2012 [6, 7] and 2016 [8]), gastric and duodenal NEN ([9, 10], revised 2012 [11] and 2016 [12]), jejunal-ileal NEN ([13], revised 2016 [14]), NEN of the appendix ([15], revised 2012 [16] and 2016 [17]), on colorectal NEN ([18], revised 2012 [19] and 2016 [20]), and most recently on pulmonary NEN [21]. Separate guidelines covered metastases from NEN ([22], revised 2012 [23] and 2016 [24]), with a special focus on brain, cardiac and ovarian metastases ([25], bone and lung metastases [26], and on peritoneal carcinomatosis [27]. The importance of adequate grading was acknowledged with specific guidelines for poorly-differentiated NEN [28, 29], and subsequently with guidelines separately for high-grade neuroendocrine tumors and neuroendocrine carcinomas [30]. To allow for a more standardized approach to NEN, ENETS also published consensus proposals on the TNM classification of foregut [31] and midgut/hindgut NEN [32]. In addition, ENETS recognized the need for standards of care when applying various diagnostic and therapeutic techniques, and therefore published specific recommendations on the morphological diagnosis ([33], updated 2017 [34]) and the endocrine evaluation ([35], updated 2017 [36]) of NEN, tumor localization by ultrasound, CT and MRI, and nuclear imaging ([37, 38], updated 2017 [39]), and evaluation of cardiac disease [40]. Standards of therapy were published for surgery [41], with specific recommendations for pre- and perioperative therapy ([42], updated 2017 [43]), for biotherapy ([44], updated 2017 [45]), for peptide receptor radionuclide therapy (PRRT) ([46], updated 2017 [47]), for chemotherapy ([48], updated 2017 [49], and for follow-up ([50], updated 2017 [51]).

Another European Society, the European Society for Medical Oncology (ESMO), published their clinical practice guidelines on NEN ([52, 53], updated 2012 [54, 55] and 2016 [56]) from a slightly different perspective. Furthermore, societies from several countries issued guidelines, e.g. the North American Neuroendocrine Tumor Society [57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68], the Polish Network of Neuroendocrine Tumours ([69, 70, 71, 72, 73], updated 2017 [74, 75, 76, 77, 78]), the Nordic Neuroendocrine Tumor Group [79, 80, 81, 82], the Canadian National Expert Group [54], the Spanish Society of Medical Oncology [83, 84, 85], the Brazilian Gastrointestinal Tumour Group [86], and the UK and Ireland Neuroendocrine Tumor Society [87, 88]. Although this list is certainly not complete, it allows recognition of region-specific differences in the handling of NEN, but also underscores the ongoing difficulties in managing patients with NEN.

This and a subsequent issue of REVIEWS IN ENDOCRINE AND METABOLIC DISORDERS are devoted to practical aspects in the current management of neuroendocrine neoplasms, written from individual experts in their specific field to assist clinicians involved in the daily care of NEN who may be somehow overwhelmed by the large number of published guidelines.

Guido Rindi and his co-authors start with their perspective on histology of NEN in their paper CYTO-HISTOLOGY IN NET: WHAT IS NECESSARY TODAY AND WHAT IS THE FUTURE? [89]. Matthias M. Weber and co-authors discuss the endocrine evaluation of functioning NEN in their paper HORMONE SECRETING GASTRO-ENTERO-PANCREATIC NEUROENDOCRINE NEOPLASIAS (GEP-NEN): WHEN TO CONSIDER, HOW TO DIAGNOSE? [90]. Javier G. Castillo and co-authors give us some insight on diagnostic evaluation of carcinoid heart disease in their paper ECHOCARDIOGRAPHY IN FUNCTIONAL MIDGUT NEUROENDOCRINE TUMORS: WHEN AND HOW OFTEN? [91]. As localization of the primary tumor in patients with proven NEN is sometimes difficult, Gregory A. Kaltsas and his group present an overview on the MANAGEMENT OF NEUROENDOCRINE TUMORS OF UNKNOWN PRIMARY [92]. With many guidelines initially focusing in NEN of the gastrointestinal tract, pulmonary NEN were somehow neglected, but Robert A. Ramirez and co-authors update us on the MANAGEMENT OF PULMONARY NEUROENDOCRINE TUMORS [93]. Moving to new aspects of treatment, Ernst von Dobschuetz and co-authors answer the question IS THERE ANY ROLE FOR MINIMALLY INVASIVE SURGERY IN NET? [94]. With the frequent occurrence of liver metastases, Philippe Ruszniewski and co-authors present their view on LIVER TRANSARTERIAL EMBOLIZATIONS IN METASTATIC NEUROENDOCRINE TUMORS [95], and Vincenzo Mazzaferro and co-authors discuss THE PLACE OF LIVER TRANSPLANTATION IN THE TREATMENT OF HEPATIC METASTASES FROM NEUROENDOCRINE TUMORS: PROS AND CONS [96]. Although the low proliferation rate in the majority of NEN and the possibility of specific treatments such as biotherapy and PRRT leaves a somehow smaller role for chemotherapy, certain types of NEN may require such an approach, and therefore Ashley Grossman and co-authors answer the question CHEMOTHERAPY IN NETs: WHEN AND HOW [97]. As NEN may occur as part of multiple endocrine neoplasia syndromes with important consequences for the patient and family members, Triona O’Shea and Maralyn Druce discuss WHEN SHOULD GENETIC TESTING BE PERFORMED IN PATIENTS WITH NEUROENDOCRINE TUMOURS? [98]. Finally, it is less known, that Merkel cell carcinoma is a skin cancer with a neuroendocrine phenotype, and Claus Garbe and co-authors enlighten us on similarities and differences in their article MERKEL CELL CARCINOMA: EPIDEMIOLOGY, PATHOGENESIS, DIAGNOSIS AND THERAPY [99].

We hope that this first part of 2 issues of this journal devoted to the management of NEN will provide you with the most up-to-date information on key areas in the management of NEN. We are thankful to our colleagues across the world for summarizing their vast experience, and look forward to give you further insight into this orphan disease form which still poses a major challenge to the caring physician.

Notes

Compliance with ethical standards

Conflict of interest

Prof. Stephan Petersenn declares that he has received fees for serving as a consultant on advisory boards for Ipsen and Novartis, and for presenting at workshops organized by Ipsen, Novartis, and Pfizer. He has no conflict of interest related to this article.

Prof. Christian A. Koch declares that he has received fees for serving as a consultant on the Advisory Board of Novartis. He has no conflict of interest related to this article.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.ENDOC Center for Endocrine TumorsHamburgGermany
  2. 2.Medicover Oldenburg MVZOldenburgGermany
  3. 3.Department of Medicine IIITechnical University of DresdenDresdenGermany
  4. 4.University of LouisvilleLouisvilleUSA

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