Center of Expertise for Neuroendocrine Neoplasms

THE CENTER

The Center of Expertise for Neuroendocrine Tumors (EKPA-LAIKO NET Center) is part of the Endocrinology Unit of the 1^st Department of Propaedeutic and Internal Medicine of the Medical School of National and Kapodistrian University of Athens, Greece. The Center is located at General Hospital of Athens Laiko (G.H.A.).

The EKPA-LAIKO NET Center consists of a multidisciplinary team of several subspecialties dealing with patients harbouring a wide spectrum of neuroendocrine diseases such as:

• Neuroendocrine Tumors (Carcinoids) of the stomach, duodenum, small and large bowel, rectum, pancreas, appendix and lung
• Functioning (carcinoid syndrome, insulinoma, gastrinoma, vipoma) and non-functioning neuroendocrine tumors
• Multiple Endocrine Neoplasia Type 1 (MEN 1) and other familial syndromes such as neurofibromatosis type 1, Von Hippel Lindau (VHL), MEN 2, Familial Isolated Pituitary Adenomas (FIPA), familial pheochromocytoma and paraganglioma

The EKPA-LAIKO NET Center successfully applied as a European Neuroendocrine Tumor Society (ENETS) Center of Excellence (CoE) in 2016 and was certified in March 2017 following external assessment. Overall, more than 1000 patients with neuroendocrine tumors (NET) are followed in the department. More than 100 new patients with gastro-entero-pancreatic NET (GEP-NET) are seen in the center per year while the number of new patients increases constantly by 10-20% annually.

Lead and coordinator of the EKPA-LAIKO NET Center is Professor Gregory Kaltsas who is also a member of the ENETS advisory board and participates in the preparation and development of international guidelines regarding patients with NETs. Responsible for the control to adhere the existing guidelines is Professor Gregory Kaltsas.

The Center has the required infrastructure which includes signed contracts among all relevant disciplines as per ENETS requirements, including the main partners (Endocrinology, Surgery, Oncology, Gastroenterology, Nuclear Medicine, Radiology and Histopathology). Secondary partners include Cardiology, Nutrition Service, Psychological Services and others. All partners have more than 5 years of experience in the field of NET and  follow standard operation procedures (SOP) as per ENETS requirements (see Neuroendocrinology 2012, Standards of Care in NET released in ENETS Consensus conference in Palma, Mallorca).

The EKPA-LAIKO NET Center participates in national and international trials on NET patients and has published multiple original research and review papers in international medical journals. In addition, is in close collaboration with other ENETS centers.

What are Neuroendocrine Neoplasms (NENs)

NENs are relatively rare and heterogenous neoplasms that develop mostly in the gastrointestinal (stomach, pancreas, bowel) and respiratory (lungs) system but can be found virtually in every tissue of the human body. All NENs are considered as potentially malignant albeit the majority (70-80%) is of lower malignant potential compared to other cancers as even in the presence of metastatic disease their evolution is slower and outcomes are better compared to other cancers.  

NENs are derived from neuroendocrine cells that belong to the diffuse endocrine system that have common links with the nervous and endocrine system and are characterized by their ability to synthesize and secrete compounds that when are bioactive can cause distinct clinical syndromes (such NENs are called functioning and can cause the carcinoid and other syndromes).

Epidemiology

NENs are considered to be relatively rare affecting approximately 1/2000 inhabitants. However, during the last decades their overall prevalence has substantially increased although it is believed that a significant number still remains underdiagnosed. This is probably related to the absence or presence of non-specific symptoms related to NENs as the majority are non-functioning and thus not related to a secretory syndrome. Furthermore, related symptoms can be extremely common and non-specific, encountered in many diseases with increased prevalence such as gastritis, peptic ulcer, irritable bowel syndrome, asthma, disorders of glucose metabolism, menopause and others.  For a subset of NENs (functioning NENs), approximately 20%, symptoms may be relatively specific leading to their prompt diagnosis.

NENs can be diagnosed at any age but are mostly present in the 5-6 decade of life and may develop along with other endocrine neoplasms in the context of familial syndromes that are associated with specific chromosomal abnormalities (such as Multiple Endocrine Neoplasia Syndrome 1 and others).

Common Clinical Presentation

Functioning NENs can be diagnosed because of the presence of a secretory syndrome such as in the case of carcinoid syndrome (diarrhea, flushing episodes, rashes, cramps, dyspnea and heart valvular problems). Pancreatic NENs can cause symptoms secondary to the secretion of insulin, gastrin and other hormones causing hypoglycemia and peptic ulcer disease.

Non-functioning NENs are not related to a secretory syndrome and are associated with non-specific symptoms such as abdominal pain, nausea, loss of appetite and loss of weight.

In some cases, NENs are asymptomatic and are diagnosed during imaging studies for other purposes.

Diagnosis

In the majority of NENs, besides functioning ones, the diagnosis is made with a relative delay mainly due to the absence of specific symptoms and the slow growth of the NEN.

When the diagnosis is made at the initial stages of NEN development these neoplasms are of relatively small size usually localized and the prognosis is the most optimal. However, in their majority NENs are diagnosed relatively late when the disease has already spread to nearby (usually lymph node) or distant tissues (usually the liver). Although in such cases complete cure of the patients’ is not feasible patients can exhibit a protracted course maintaining a good quality of life with the use of different therapeutic approaches.

Blood tests

Blood tests give us information on general blood count, biochemistry profile, calcium, fasting gut hormones, chromogranin A, ACTH, cortisol, calcitonin, pituitary hormone screen and oncology markers.

Urine tests

A number of NENs secrete substances that are excreted in the urine such a 5-hyroxy-indoloacetic-acid (from serotonin metabolism) particularly those derived from the small bowel and have developed metastases to the liver. You will be asked to collect all your urine produced within 24 hours and at the same time to avoid consuming foods and drinks that may affect the measurement such as chocolates, bananas, vanilla, tomatoes and drinking coffee and alcohol.

Endoscopies

Inspection of the upper (stomach, duodenum) and lower (large bowel, rectum and lower small bowel) gastrointestinal tract with gastroscopy and colonoscopy or their modifications. Occasionally, an endoscopic ultrasound is needed to identify the precise size and depth of bowel wall invasion from the NEN in lesions of the stomach and duodenum and identify or confirm pancreatic lesions. The investigation allows biopsy taking to verify the diagnosis further histologically. A camera can also be used to identify small bowel lesions not visible to advanced endoscopy. 

Radiology- Nuclear Medicine

The localization of a NEN is best undertaken through computerized tomography (CT) or magnetic resonance imaging (MRI) for lung and abdominal (upper or lower) lesions. MRI is superior to CT to identify liver lesions using specific sequences. Radionuclear imaging with ¹¹¹In-labelled octreotide or more recent with ⁶⁸Gallium-DOTATATE PET/CT is used to detect the presence of somatostatin receptors that are found in the majority of NETs as their presence can predict prognosis and affect therapeutic decisions. Recently ¹⁸FDG-PET is also used to identify lesions that they have a higher proliferative capacity and can thus herald a more aggressive course.

Biopsy

This method allows access to a sample of the NEN either in the form of cell blocks or tissue components. It can be done either during endoscopic procedures or following biopsies in lesions of either the primary neoplasm or a metastatic deposit through a specific needle and/or during radiological procedures (endoscopy, ultrasound, CT). The patient is explicitly described the procedure and gives his consent; all such procedures should be undertaken in centers and by operators with relevant experience. 

Patients with NENs of the small bowel should also undergo an echogram of the heart to identify potential valvular lesions.

Treatment

Ideally decisions for the management of patients with NENs should be taken in the context of a (Multidisciplinary Team, MDT). The MDT is formed by physicians with specialties relevant to the management of patients with NENs. Each patient has a specific therapeutic plan that depends on the tissue of origin of the NEN, stage of the disease and grade and considers the performance characteristics of the patient (condition of overall health).  It is important that the patient is informed and participates in decision making.

During the course of your disease you may come across with the following specialties

Endocrinologists

Gastroenterologists

Surgeons

Oncologists

Radiologists, Interventional Radiologist

Nuclear Medicine Physicians

Histopathologists

Cardiologists

Dieticians, Nurses, Pain management teams

Surgical resection

If the NEN is of well-differentiation and lies in a specific anatomic area (localized disease) or there is limited spread to nearby or other areas (mostly to the liver) surgery is the treatment of choice and the best option of obtaining a ‘cure’. If following surgery, the lesion(s) are completely excised, in the majority of cases no further treatment is administered and the patient is followed up at regular intervals to identify potential early recurrences. In cases of extensive disease, surgery may still be utilized particularly in the presence of a difficult to control secretory syndrome in order to reduce the tumor load or in the presence of local compressing symptoms (such as bowel obstruction, jaundice) in order to debulk part of the tumor and ameliorate symptoms. In such cases there is still residual tumor tissue.

Somatostatin analogs

These agents are the cornerstone of treatment for the majority of well differentiated NENs and functioning NENs. They are administered as monthly injections and cause reduction of the secretory component of the NEN and thus amelioration of the related symptoms, such as the carcinoid syndrome, whereas they can cause stabilization of the disease for a considerable period of time although reduction of the tumor load is not usually seen.

Molecular targeted therapies

The most commonly used compounds are everolimus (afinitor) και sunitinib (sutent) although many more are under development and are been evaluated in phase III trials. These compounds act by inhibiting several molecular pathways that are activated in NENs and can control the disease for a significant period of time. They are usually associated with a variety of different adverse effects however the majority of patients can tolerate treatment with only a small minority discontinuing these agents.

Chemotherapy

Occasionally, when tumor load is considerable and/or in the presence of relatively rapid growth of the neoplasm a number of different chemotherapeutic agents can be used considering patients’ characteristics. There are several different schemes that can be administered either by mouth without the need of admission to the hospital and are not associated with the known chemotherapy related side effects such as hair loss and nausea although they may need specific monitoring of the patient.

Interferon

Interferon stimulates the immune system to fight cancer and may be effective, especially in combination with somatostatin analogues. Its use has been restricted due to significant adverse events.

Treatment with radiopeptides (Peptide Receptor Radiotherapy, PRRT)

This form of treatment is based in the administration of radio-labelled compounds that are attached to a chelator and the whole complex to a somatostatin analog that binds selectively to the surface of the NENs harboring somatostatin receptors. As a result, following intravenous administration these compounds bind and can be internalized to the NEN leading to cellular damage without affecting nearby healthy tissues. PRRT has been shown to be efficacious in many different NENs leading to a significant number of them in substantial reduction and disease control for a prolonged period. The radioactivity administered does not cause side effects whereas the patients do not have to be admitted to hospital but receive their treatment as outpatients.

Liver embolization

Liver embolization, that is, cutting off the blood supply to tumours in the liver with or without the addition of chemotherapy (chemoembolization), is useful for patients who have predominantly liver disease.

Thermal ablation

Thermal ablation such as radio-frequency ablation, i.e. probes that “burn” away the tumours, may be useful in patients who have a small number of liver tumours.

Liver transplantation

Rarely, liver transplantation is considered in patients who have disease confined to the liver and have had investigations to fully exclude disease outside the liver. Even so, other criteria will need to be met and the concern is of recurrence of disease after liver transplant.

The Centre personnel work in close contact with numerous Departments of LAIKO G.H.A. as well as Departments of other hospitals and Private Diagnostic Centers.

LAIKO General Hospital of Athens

• 1^st Department of General Surgery, (Scientific Supervisor: Professor Ev. Felekouras)
• 2^nd Department of General Surgery, (Scientific supervisor: Assoc. Professor G. Sotiropoulos)
• Gastroenterology Unit, Department of Pathophysiology, (Scientific supervisor: Assoc. Professor S. Sougioultzis)
• 1^st Department of Pathology, (Scientific Supervisor: Professor St. Theocharis)
• Department of Biochemistry, (Scientific Supervisor: Professor Aggeliki Papapanagiotou)
• Department of Cardiology, (Scientific Supervisor: Dr. G. Anastasiadis)
• Department of Nuclear Medicine, (Scientific Supervisor: Dr. An.Velidaki)
• Department of Radiology and Invasive Radiology, (Scientific Supervisor: Dr. C. Vergadis)
• Division of Clinical Dieticians, (Scientific Supervisor: Dr. L. Poulia)

Evangelismos Hospital

• Department of Pathology, (Scientific Supervisor: Dr. D. Rontogianni)

 ATΤIKOΝ General Hospital of Athens

• Department of Nuclear Medicine, (Scientific Supervisor: Prof. S. Chatzhioannou)
• 4^th Department of Internal Medicine, (Scientific Supervisor: Dr. A. Koumarianou). Dr Koumarianou is also currently a member of the Advisory Board of ENETS

General Hospital of Athens Gennimatas

• Department of Gastroenterology, (Scientific Supervisor: Dr. I. Karoumpalis)

 Army Share Fund Hospital (NIMTS)

• Department of Gastroenterology, (Scientific Supervisor: Dr. E. Vlachou)

 Foundation of Medical-Biological Research of the Academy of Athens

• Department of PET/CT,(Scientific Supervisor: Prof. S. Chatzhioannou)

Diagnostic Centers in the Private Sector-Athens

• Department of CT/MRI, BIOIATRIKI Diagnostic Center, Peristeri, Athens (Scientific supervisor Dr. D. Kolomodi)

LAIKO General Hospital of Athens is part of the National Health System (NHS) that hosts several Departments of the Medical School of the National and Kapodistrian University of Athens. It operates under the supervision of the Ministry of Health lead by a Chief Executive and a Deputy. The operational delivery is organized through groups of clinical specialties required to adhere to the organisational policies and procedures that include business continuity policies and operational plans.

The hospital provides 24hours on-call duties every 4 days and daily from 08.00-14.30 thereby providing availability for continuous admission to hospital for patients with NETs in need for acute or scheduled inpatient care.

The EKPA-LAIKO NET Center provides a defined infrastructure including an organizational management structure naming main partners and core partners, secondary partners, supportive care partners, referring and affiliated partners in a given interdisciplinary cooperation and communication structure.

Data of patients are collected in the hospital –based patients’ database in line with the existing National and European Patient Registry guidelines.

All departments that participate in the Center follow standard operating procedures (Standard Operating Procedures-SOPs) according to guidelines by ΕNETS.

The specialized personnel consists of:

• Gregory Kaltsas, Professor of Internal Medicine and Endocrinology, who is the Lead and Coordinator of the Center and the Head of the Endocrinology Unit
• Eva Kassi, Associate Professor of Biochemistry and Molecular Endocrinology
• Marina Tsoli, Endocrinologist, Academic Scholar Fellow
• Elli Anagnostou, Endocrinologist, Academic Scholar Fellow
• Aggeliki Karapanagioti, secretarial office
• Maria Lekakou, secretarial office

The organization of the Center also includes all relevant medical specialties according to prerequisites from the ENETS including Endocrinology, Surgery, Oncology, Gastroenterology, Nuclear Medicine, Radiology and Histopathology as well as secondary specialties such as Cardiology, Nutrition Service, Psychological Services and others.

1^st assessment of out-patient care

Patients can make an appointment for the out-patient clinic using:

• Hospital appointments contact number: 1535
• Center secretary contact number: 2107462217
• E-mail:  endopf@gmail.com

SPECIALIZED OUT-PATIENT CLINIC	Day	Time	Place	Treating Physicians
Out-patient clinic of Neuroendocrine Oncology	Monday	1000-1400	16 Sevastoupoleos str. (LAIKO Specialized Outpatient Clinics) 5th floor	Gregory Kaltsas, Marina Tsoli, Elli Anagnostou
Out-patient clinic of Neuroendocrine Oncology	Wednesday	830-1400	16 Sevastoupoleos str. (LAIKO Specialized Outpatient Clinics) 5th floor	Gregory Kaltsas, Marina Tsoli, Elli Anagnostou
Out-patient clinic of Neuroendocrine Oncology	Friday	1000-1430	16 Sevastoupoleos str. (LAIKO Specialized Outpatient Clinics) 5th floor	Gregory Kaltsas, Marina Tsoli, Elli Anagnostou

DIAGNOSTIC APPROACH

The EKPA-LAIKO NET Center has access to all the required standard and technologically advanced diagnostic facilities provided either by the General Hospital of Athens (G.H.A.) Laiko or the other collaborators of the Centre.

Diagnostic work-up consists mainly of blood and urine laboratory tests, imaging studies (X-rays, ultrasound, computed tomography, magnetic resonance tomography, bone scintigraphy, somatostatin receptor scintigraphy) and occasionally, invasive procedures such as endoscopic ultrasound or liver biopsy.

Further testing that may be required include reviewing of pathology samples (including immunohistochemical evaluation for general and hormonal neuroendocrine markers and somatostatin receptors), functional imaging including ⁶⁸Gallium-DOTATATE -PET/CT and ¹⁸FDG-PET/CT and genetic (molecular) testing.

In addition, in some cases it is performed, in collaboration with the ENETS Center of Excellence Royal Free of London, genetic testing (NETest) that according to recent studies helps to estimate the activity of the disease and the probability of response to specific treatment modalities. This test is available only in specific medical departments globally and is considered to be the future gold-standard method for the diagnosis and follow-up of patients with NETs.

TREATMENT AND FOLLOW UP

Treatment and coordination of follow-up is provided via the respective specialties coordinated by the NET MDT based on ENETS guidelines, local expertise and availability. All collaborators follow standard operating procedures (SOPs) that are based on ENETS guidelines.

The therapeutic management of patients with NET includes surgical resection, medical treatment with long-acting somatostatin analogues and other options (molecular targeted agents and chemotherapy), peptide receptor radiotherapy (PRRT), as well as debulking techniques such as radiofrequency ablation and embolization/chemoembolization. In some instances, combination of various treatment options may be required.

Surgical treatment is provided at two General Surgery Departments (1^st and 2^nd) of Laiko General Hospital by experienced surgeons that are members of the multidisciplinary team. Radiofrequency ablation and trans-arterial embolization (± chemotherapy) in the liver are performed in the department of interventional radiology at Laiko General Hospital. Treatment with chemotherapy or PRRT is provided at Attiko General Hospital which is part of EKPA-LAIKO NET Center.

Secretarial office:

176 Michalakopoulou street, 11527, Goudi, Athens

Tel: 2107462217

E-mail: endopf@gmail.com  

LAIKO General Hospital of Athens:

17 Agiou Thoma street, 11527, Goudi, Athens

Tel: 2132060800, 1535 (for appointments)

Relative publications of the last three years

1. Alexandraki KI, Kaltsatou M, Kyriakopoulos G, Mavroeidi V, Kostopoulou A, Atlan K, Theocharis S, Rindi G, Grossman AB, Grozinsky-Glasberg S, Kaltsas GA. Distinctive features of pancreatic neuroendocrine neoplasms exhibiting an increment in proliferative activity during the course of the disease. Endocrine. 2020 Nov 11. doi: 10.1007/s12020-020-02540-w.
2. Koumarianou A, Kaltsas G. Surufatinib – a novel oral agent for neuroendocrine tumours. Nat Rev Endocrinol. 2020 Oct 30. doi: 10.1038/s41574-020-00439-0.
3. Alexandraki KI, Kaltsas G, Grozinsky-Glasberg S, Oleinikov K, Kos-Kudła B, Kogut A, Srirajaskanthan R, Pizanias M, Poulia KA, Ferreira C, Weickert MO, Daskalakis K. The effect of prophylactic surgery in survival and HRQoL in appendiceal NEN. 2020 Oct;70(1):178-186. doi: 10.1007/s12020-020-02356-8.
4. Tsoli M, Dimitriadis GK, Androulakis II, Kaltsas G, Grossman A. Paraneoplastic Syndromes Related to Neuroendocrine Tumors. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dungan K, Grossman A, Hershman JM, Hofland HJ, Kaltsas G, Koch C, Kopp P, Korbonits M, McLachlan R, Morley JE, New M, Purnell J, Singer F, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–. 2020 Sep 26.
5. Tsoli M, Spei ME, Wallin G, Kaltsas G, Daskalakis K. Association of a Palliative Surgical Approach to Stage IV Pancreatic Neuroendocrine Neoplasms with Survival: A Systematic Review and Meta-Analysis. Cancers (Basel). 2020 Aug 11;12(8):2246. doi: 10.3390/cancers12082246.
6. Koumarianou A, Alexandraki KI, Wallin G, Kaltsas G, Daskalakis K. Pathogenesis and Clinical Management of Mesenteric Fibrosis in Small Intestinal Neuroendocine Neoplasms: A Systematic Review. J Clin Med. 2020 Jun 8;9(6):1777. doi: 10.3390/jcm9061777.
7. Koumarianou A, Pectasides D, Koliou GA, Dionysopoulos D, Kolomodi D, Poulios C, Skondra M, Sgouros J, Pentheroudakis G, Kaltsas G, Fountzilas G. Efficacy and Safety of First-Line Everolimus Therapy Alone or in Combination with Octreotide in Gastroenteropancreatic Neuroendocrine Tumors. A Hellenic Cooperative Oncology Group (HeCOG) Study. Biology (Basel). 2020 Mar 9;9(3). doi: 10.3390/biology9030051.
8. Daskalakis K, Alexandraki KI, Kloukina I, Kassi E, Felekouras E, Xingi E, Pagakis SN, Tsolakis AV, Andreakos E, Kaltsas G, Kambas K. Increased autophagy/mitophagy levels in primary tumours of patients with pancreatic neuroendocrine neoplasms. 2020 Feb 29. doi: 10.1007/s12020-020-02228-1.
9. Tsoli M, Alexandraki K, Xanthopoulos C, Kassi E, Kaltsas G. Medical Treatment of Gastrointestinal Neuroendocrine Neoplasms. Horm Metab Res. 2020 Feb 27. doi: 10.1055/a-1110-7251.
10. Öberg K, Califano A, Strosberg JR, Ma S, Pape U, Bodei L, Kaltsas G, Toumpanakis C, Goldenring JR, Frilling A, Paulson S. A meta-analysis of the accuracy of a neuroendocrine tumor mRNA genomic biomarker (NETest) in blood. Ann Oncol. 2020 Feb;31(2):202-212. doi: 10.1016/j.annonc.2019.11.003.
11. Alexandraki KI, Daskalakis K, Tsoli M, Grossman AB, Kaltsas GA. Endocrinological Toxicity Secondary to Treatment of Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs). Trends Endocrinol Metab. 2020 Mar;31(3):239-255. doi: 10.1016/j.tem.2019.11.003.
12. Hofland J, Kaltsas G, de Herder WW. Advances in the Diagnosis and Management of Well-Differentiated Neuroendocrine Neoplasms. Endocr Rev. 2020 Apr 1;41(2). doi: 10.1210/endrev/bnz004.
13. Daskalakis K, Alexandraki K, Kassi E, Tsoli M, Angelousi A, Ragkousi A, Kaltsas G. The risk of lymph node metastases and their impact on survival in patients with appendiceal neuroendocrine neoplasms: a systematic review and meta-analysis of adult and paediatric patients. Endocrine. 2020 Jan;67(1):20-34. doi: 10.1007/s12020-019-02072-y.
14. Chatzellis E, Daskalakis K, Angelousi A, Tsoli M, Alexandraki KI, Wachula E, Meirovitz A, Maimon O, Grozinsky-Glasberg S, Gross D, Kos-Kudła B, Koumarianou A, Kaltsas G. Authors’ Response to the Letter by Lamarca et al. Entitled “Temozolomide-Capecitabine Chemotherapy for Neuroendocrine Neoplasms: The Dilemma of Treatment Duration” Regarding “Activity and Safety of Standard and Prolonged Capecitabine/Temozolomide Administration in Patients with Advanced Neuroendocrine Neoplasms”. 2020;110(1-2):158-160. doi: 10.1159/000503999.
15. Tsolakis AV, Ragkousi A, Vujasinovic M, Kaltsas G, Daskalakis K. Gastric neuroendocrine neoplasms type 1: A systematic review and meta-analysis. World J Gastroenterol. 2019 Sep 21;25(35):5376-5387. doi: 10.3748/wjg.v25.i35.5376.
16. Daskalakis K, Tsoli M, Alexandraki KI, Angelousi A, Chatzellis E, Tsolakis AV, Karoumpalis I, Kolomodi D, Kassi E, Kaltsas G. Magnetic Resonance Imaging or Endoscopic Ultrasonography for Detection and Surveillance of Pancreatic Neuroendocrine Neoplasms in Patients with Multiple Endocrine Neoplasia Type 1? Horm Metab Res. 2019 Sep;51(9):580-585. doi: 10.1055/a-0931-7005.
17. Angelousi A, Koffas A, Grozinsky-Glasberg S, Gertner J, Kassi E, Alexandraki K, Caplin ME, Kaltsas G, Toumpanakis C. Diagnostic and Management Challenges in Vasoactive Intestinal Peptide Secreting Tumors: A Series of 15 Patients. 2019 Aug;48(7):934-942. doi: 10.1097/MPA.0000000000001347.
18. Daskalakis K, Tsoli M, Karapanagioti A, Chrysochoou M, Thomas D, Sougioultzis S, Karoumpalis I, Kaltsas GA, Alexandraki KI. Recurrence and metastatic potential in Type 1 gastric neuroendocrine neoplasms. Clin Endocrinol (Oxf). 2019 Oct;91(4):534-543. doi: 10.1111/cen.14055.
19. Chatzellis E, Angelousi A, Daskalakis K, Tsoli M, Alexandraki KI, Wachuła E, Meirovitz A, Maimon O, Grozinsky-Glasberg S, Gross D, Kos-Kudła B, Koumarianou A, Kaltsas G. Activity and Safety of Standard and Prolonged Capecitabine/Temozolomide Administration in Patients with Advanced Neuroendocrine Neoplasms. 2019;109(4):333-345. doi: 10.1159/000500135.
20. Daskalakis K, Tsoli M, Angelousi A, Kassi E, Alexandraki KI, Kolomodi D, Kaltsas G, Koumarianou A. Anti-tumour activity of everolimus and sunitinib in neuroendocrine neoplasms. Endocr Connect. 2019 Jun;8(6):641-653. doi: 10.1530/EC-19-0134.
21. Alexandraki KI, Tsoli M, Kyriakopoulos G, Angelousi A, Nikolopoulos G, Kolomodi D, Kaltsas GA. Current concepts in the diagnosis and management of neuroendocrine neoplasms of unknown primary origin. Minerva Endocrinol. 2019 Dec;44(4):378-386. doi: 10.23736/S0391-1977.19.03012-8.
22. Angelousi A, Kassi E, Ansari-Nasiri N, Randeva H, Kaltsas G, Chrousos G. Clock genes and cancer development in particular in endocrine tissues. Endocr Relat Cancer. 2019 Jun;26(6):R305-R317. doi: 10.1530/ERC-19-0094.
23. Tsoli M, Chatzellis E, Koumarianou A, Kolomodi D, Kaltsas G. Current best practice in the management of neuroendocrine tumors. Ther Adv Endocrinol Metab. 2018 Oct 31;10:2042018818804698. doi:10.1177/2042018818804698.
24. Daskalakis K, Tsoli M, Srirajaskanthan R, Chatzellis E, Alexandraki K, Angelousi A, Pizanias M, Randeva H, Kaltsas G, Weickert MO. Lung Metastases in Patients with Well-Differentiated Gastroenteropancreatic Neuroendocrine Neoplasms: An Appraisal of the Validity of Thoracic Imaging Surveillance. 2019;108(4):308-316. doi: 10.1159/000497183.
25. Alexandraki KI, Pizanias M, Uri I, Thomas D, Page T, Kolomodi D, Low CS, Adesanya O, Tsoli M, Gross DJ, Randeva H, Srirajaskanthan R, Grozinsky-Glasberg S, Kaltsas G, Weickert MO. The prognosis and management of neuroendocrine neoplasms-related metastatic bone disease: lessons from clinical practice. 2019 Jun;64(3):690-701. doi: 10.1007/s12020-019-01838-8.
26. Jensen RT, Bodei L, Capdevila J, Couvelard A, Falconi M, Glasberg S, Kloppel G, Lamberts S, Peeters M, Rindi G, Rinke A, Rothmund M, Sundin A, Welin S, Fazio N; The ENETS 2016 Munich Advisory Board Participants; ENETS 2016 Munich Advisory Board Participants. Unmet Needs in Functional and Nonfunctional Pancreatic Neuroendocrine Neoplasms. 2019;108(1):26-36. doi: 10.1159/000494258.
27. Daskalakis K, Chatzelis E, Tsoli M, Papadopoulou-Marketou N, Dimitriadis GK, Tsolakis AV, Kaltsas G. Endocrine paraneoplastic syndromes in patients with neuroendocrine neoplasms. 2019 May;64(2):384-392. doi: 10.1007/s12020-018-1773-3.
28. Baudin E, Hayes AR, Scoazec JY, Filosso PL, Lim E, Kaltsas G, Frilling A, Chen J, Kos-Kudła B, Gorbunova V, Wiedenmann B, Nieveen van Dijkum E, Ćwikła JB, Falkerby J, Valle JW, Kulke MH, Caplin ME; ENETS 2016 Munich Advisory Board Participants; ENETS 2016 Munich Advisory Board Participants. Unmet Medical Needs in Pulmonary Neuroendocrine (Carcinoid) Neoplasms. 2019;108(1):7-17. doi: 10.1159/000493980..
29. Toumpanakis C, Fazio N, Tiensuu Janson E, Hörsch D, Pascher A, Reed N, O Apos Toole D, Nieveen van Dijkum E, Partelli S, Rinke A, Kos-Kudla B, Costa F, Pape UF, Grozinsky-Glasberg S, Scoazec JY; The ENETS 2016 Munich Advisory Board Participants; ENETS 2016 Munich Advisory Board Participants. Unmet Needs in Appendiceal Neuroendocrine Neoplasms. 2019;108(1):37-44. doi: 10.1159/000493894.
30. Ramage JK, Valle JW, Nieveen van Dijkum EJM, Sundin A, Pascher A, Couvelard A, Kloeppel G; the ENETS 2016 Munich Advisory Board Participants; ENETS 2016 Munich Advisory Board Participants. Colorectal Neuroendocrine Neoplasms: Areas of Unmet Need. 2019;108(1):45-53. doi: 10.1159/000493767..
31. Capdevila J, Bodei L, Davies P, Gorbounova V, Jensen RT, Knigge UP, Krejs GJ, Krenning E, O’Connor JM, Peeters M, Rindi G, Salazar R, Vullierme MP, Pavel ME; ENETS 2016 Munich Advisory Board Participants; ENETS 2016 Munich Advisory Board Participants. Unmet Medical Needs in Metastatic Lung and Digestive Neuroendocrine Neoplasms. 2019;108(1):18-25. doi: 10.1159/000493319.
32. Sorbye H, Baudin E, Borbath I, Caplin M, Chen J, Cwikla JB, Frilling A, Grossman A, Kaltsas G, Scarpa A, Welin S, Garcia-Carbonero R; ENETS 2016 Munich Advisory Board Participants. Unmet Needs in High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms (WHO G3). 2019;108(1):54-62. doi: 10.1159/000493318.
33. Daskalakis K, Kaltsas G, Öberg K, Tsolakis AV. Lung Carcinoids: Long-Term Surgical Results and the Lack of Prognostic Value of Somatostatin Receptors and Other Novel Immunohistochemical Markers. 2018;107(4):355-365. doi: 10.1159/000493944.
34. Grozinsky-Glasberg S, Alexandraki KI, Angelousi A, Chatzellis E, Sougioultzis S, Kaltsas G. Gastric Carcinoids. Endocrinol Metab Clin North Am. 2018 Sep;47(3):645-660. doi: 10.1016/j.ecl.2018.04.013.
35. Kyriakopoulos G, Mavroeidi V, Chatzellis E, Kaltsas GA, Alexandraki KI. Histopathological, immunohistochemical, genetic and molecular markers of neuroendocrine neoplasms. Ann Transl Med. 2018 Jun;6(12):252. doi: 10.21037/atm.2018.06.27.
36. Tsoukalas N, Baxevanos P, Aravantinou-Fatorou E, Tolia M, Galanopoulos M, Tsapakidis K, Kyrgias G, Toumpanakis C, Kaltsas G. Advances on systemic treatment for lung neuroendocrine neoplasms. Ann Transl Med. 2018 Apr;6(8):146. doi: 10.21037/atm.2018.04.03.
37. Kanakis GA, Grimelius L, Papaioannou D, Kaltsas G, Tsolakis AV. Can insulin-like growth factor 1 (IGF-1), IGF-1 receptor connective tissue growth factor and Ki-67 labelling index have a prognostic role in pulmonary carcinoids? 2018 Apr 27;9(32):22653-22664. doi: 10.18632/oncotarget.25203.
38. Robbins HL, Symington M, Mosterman B, Goodby J, Davies L, Dimitriadis GK, Kaltsas G, Randeva HS, Weickert MO. Supplementation of Vitamin D Deficiency in Patients with Neuroendocrine Tumors Using Over-the-Counter Vitamin D3 Preparations. Nutr Cancer. 2018 Jul;70(5):748-754. doi: 10.1080/01635581.2018.1470650.
39. Weickert MO, Kaltsas G, Hörsch D, Lapuerta P, Pavel M, Valle JW, Caplin ME, Bergsland E, Kunz PL, Anthony LB, Grande E, Öberg K, Welin S, Lombard-Bohas C, Ramage JK, Kittur A, Yang QM, Kulke MH. Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome. Clin Ther. 2018 Jun;40(6):952-962.e2. doi: 10.1016/j.clinthera.2018.04.006..
40. Grozinsky-Glasberg S, Kaltsas G, Kaltsatou M, Lev-Cohain N, Klimov A, Vergadis V, Uri I, Bloom AI, Gross DJ. Hepatic intra-arterial therapies in metastatic neuroendocrine tumors: lessons from clinical practice. 2018 Jun;60(3):499-509. doi: 10.1007/s12020-018-1537-0.