Preview

Experimental and Clinical Gastroenterology

Advanced search

DIARRHEA AS A CLINICAL MARKER OF NEUROENDOCRINE TUMORS

Abstract

Neuroendocrine tumors (NET) are a rare, but dangerous disease, and often have malignant character. The frequency is about 35 cases at 100.000 population, with 2-5 new cases on 100.000 people a year. The majority of NET produce the active substances in various degree influencing exocrine function and motility of the gastrointestinal tract (GIT). The frequent clinical manifestation of NET is diarrhea. It is necessary to carry out a differential diagnosis of NET in patients with the persistent not stopped diarrhea and/or ulcer damage of a GIT. The purposes of treatment of NET are the elimination of primary tumor (and its metastasizes - if they are) and normalization of a hormonal background that leads to a regress of clinical symptoms. The randomized controlled studies PROMID and CLARINET with a high degree of substantiality have shown symptomatic improvement and significant anti-proliferative effect of somatostatin analogs in the treatment of NET. In the CLARINET study, the lanreotide Autogel was effective at a wide range of patients with highly - and moderate differentiated NET (Ki-67 <10%), including with primary tumor in a small intestine and pancreas, with a primary tumor of unknown localization, and with metastatic damage of a liver. Now somatostatin analogs are considered as the first line of drug treatment of patients with highly - and moderate differentiated NET of digestive tract regardless of the extent of metastatic damage of a liver.

About the Author

I. A. Ilovayskaya
Moscow Regional Research and Clinical Institute («MONIKI»); A.I.Yevdokimov Moscow State University of Medicine and Dentistry
Russian Federation


References

1. Rossana B, Silvia R, Mariangela T, et al. Gastrointestinal neuroendocrine tumors: Searching the optimal treatment strategy - A literature review.// Crit Rev Oncol Hematol. 2016 Feb; 98: 264-274

2. Кузьминов А.Е., Полозкова С. А., Орел Н. Ф., Горбунова В. А. Нейроэндокринные опухоли.// Эффективная фармакотерапия. 2012, № 34, С. 44-48

3. van der Zwan J.M, Trama A, Otter R, Larrañaga N, Tavilla A, Marcos-Gragera R, Dei Tos A.P, Baudin E, Poston G, Links T, RARECARE W.G. Rare neuroendocrine tumours: results of the surveillance of rare cancers in Europe project. Eur J Cancer. 2013 Jul; 49(11):2565-78

4. Yao J.C, Hassan M, Phan A, Dagohoy C, Leary C, Mares J.E, Abdalla E.K, Fleming J.B, Vauthey J.N, Rashid A, Evans D.B. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008 Jun 20; 26(18):3063-72.

5. Sandvik O.M, Søreide K, Gudlaugsson E, Kvaløy J.T, Søreide J.A Epidemiology and classification of gastroenteropancreatic neuroendocrine neoplasms using current coding criteria. Br J Surg. 2016 Feb; 103(3):226-32.

6. Scherübl H, Streller B, Stabenow R, Herbst H, Höpfner M, Schwertner C, Steinberg J, Eick J, Ring W, Tiwari K, Zappe S.M Clinically detected gastroenteropancreatic neuroendocrine tumors are on the rise: epidemiological changes in Germany. World J Gastroenterol. 2013 Dec 21; 19(47):9012-9.

7. Tsai H.J, Wu C.C, Tsai CR, Lin S.F, Chen L.T, Chang J.S. The epidemiology of neuroendocrine tumors in Taiwan: a nation-wide cancer registry-based study. PLoS One. 2013; 8(4): e62487.

8. Chauhan A, Yu Q, Ray N, Farooqui Z, Huang B, Durbin E.B, Tucker T, Evers M, Arnold S, Anthony LB. Global burden of neuroendocrine tumors and changing incidence in Kentucky. Oncotarget. 2018 Apr 10;9(27):19245-19254. doi: 10.18632/oncotarget.24983.

9. Dasari A, Shen C, Halperin D, Zhao B, Zhou S, Xu Y, Shih T, Yao J.C. Trends in the Incidence, Prevalence, and Survival Outcomes in Patients with Neuroendocrine Tumors in the United States. JAMA Oncol. 2017 Oct 1; 3(10):1335-1342.

10. Klöppel G. Neuroendocrine Neoplasms: Dichotomy, Origin and Classifications. Visc Med. 2017 Oct;33(5):324-330. doi: 10.1159/000481390.

11. Klimstra D.S., Modlin I. R., Coppola D., Lloyd R. V., Suster S. The Pathologic Classification of Neuroendocrine Tumors. A review of Nomenclature, Grading, and Staging Systems.// Pancreas, 2010, 39: 707-712.3. Cives M, Strosberg J. An Update on Gastroenteropancreatic Neuroendocrine Tumors.// Oncology (Williston Park). 2014 Sep 15; 28 (9): 749-756.

12. Vinik A.I, Chaya C. Clinical Presentation and Diagnosis of Neuroendocrine Tumors.// Hematol Oncol Clin North Am. 2016 Feb; 30 (1): 21-48.

13. Halperin DM, Shen C, Dasari A, Xu Y, Chu Y, Zhou S, Shih YT, Yao JC. Frequency of carcinoid syndrome at neuroendocrine tumour diagnosis: a population-based study. Lancet Oncol. 2017 Apr; 18(4):525-534.

14. Boutzios G, Kaltsas G. Clinical Syndromes Related to Gastrointestinal Neuroendocrine Neoplasms. Front Horm Res. 2015;44:40-57. doi: 10.1159/000382053.

15. Эндокринология: национальное руководство / под ред. И. И. Дедова, Г. А. Мельниченко., 2е издание, перераб. и доп. М.: ГЭОТАР-Медиа, 2016. - 1112 с.

16. Dedov I. I., Melnichenko G. A. Endocrinology: national leadership. Moscow, Geotar-media Publ., 2016, 1112 p.

17. Pavel M, Baudin E, Couvelard A et al. Barcelona Consensus Conference participants. ENETS Consensus Guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary. Neuroendocrinology. 2012; 95 (2): 157-76.

18. Clancy T.E. Surgical Management of Pancreatic Neuroendocrine Tumors. Hematol Oncol Clin North Am. 2016 Feb; 30 (1): 103-18.

19. Demirkan B.H, Eriksson B. Systemic treatment of neuroendocrine tumors with hepatic metastases. Turk J Gastroenterol. 2012; 23 (5): 427-437.

20. Шпаков А. О. Соматостатиновые рецепторы и сопряженные с ними сигнальные каскады. Журнал эволюцонной биохимии и физиологии 2012 - Т. 48. - № 4. - С. 329-341.

21. Schally A.V. Oncological applications of somatostatin analogues.// Cancer Res 1988; 1: 6977-6985.

22. Modlin I.M, Kidd M, Drozdov I, Siddique Z.L, Gustafsson B.I. Pharmacotherapy of neuroendocrine cancers.// Expert Opin Pharmacother 2008; 9 (15): 2617-2626.

23. Modlin I.M, Pavel M, Kidd M, Gustafsson B.I. Review article: somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine (carcinoid) tumours.// Aliment Pharmacol Ther. 2010 Jan 15; 31 (2): 169-188.

24. Орлова Р.В., Новик А. В. Современные подходы лекарственного лечения генерализованных форм нейроэндокринных опухолей. Симптоматическая терапия синдромов при нейроэндокринных неоплазиях// Практическая онкология, 2005, Т. 6, № 4, С. 240-246.

25. Karakaxas D, Gazouli M, Liakakos T, et al. Pancreatic neuroendocrine tumors: current opinions on a rare, but potentially curable neoplasm.// Eur J Gastroenterol Hepatol. 2014; 26 (8): 826-35.

26. Rinke A, Muller H.H, Schade-Brittinger C, et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group.// J Clin Oncol, 2009; 27: 4656-4663.

27. Caplin M.E, Pavel M, Ćwikła J.B, Phan A.T, Raderer M, Sedláčková E, Cadiot G, Wolin E.M, Capdevila J, Wall L, Rindi G, Langley A, Martinez S, Blumberg J, Ruszniewski P CLARINET Investigators. Lanreotide in metastatic enteropancreatic neuroendocrine tumors.// New Engl J Med, 2014; 371: 224-233. doi: 10.1056/NEJMoa1316158.

28. Buil-Bruna N, Dehez M, Manon A, Nguyen T.X, Trocóniz I.F. Establishing the Quantitative Relationship Between Lanreotide Autogel®, Chromogranin A, and Progression-Free Survival in Patients with Nonfunctioning Gastroenteropancreatic Neuroendocrine Tumors. AAPS J. 2016 May;18(3):703-12. doi: 10.1208/s12248-016-9884-3.

29. Caplin M.E, Pavel M, Ćwikła J.B, Phan A.T, Raderer M, Sedláčková E, Cadiot G, Wolin EM, Capdevila J, Wall L, Rindi G, Langley A, Martinez S, Gomez-Panzani E, Ruszniewski P CLARINET Investigators. Anti-tumour effects of lanreotide for pancreatic and intestinal neuroendocrine tumours: the CLARINET open-label extension study. Endocr Relat Cancer. 2016 Mar;23(3):191-9. doi: 10.1530/ERC-15-0490.

30. Wolin E.M, Pavel M, Cwikla J.B, Phan A.T, Raderer M, Sedlackova E. Final progression-free survival analyses for lanreotide autogel/depot 120 mg in metastatic enteropancreatic neuroendocrine tumors: the CLARINET extension study. J Clin Oncol. 2017, Vol. 35, no. 15_suppl: 4089-4089. DOI: 10.1200/JCO.2017.35.15_suppl.4089

31. Phan A.T, Caplin M.E, Pavel M.E, Cwikla J B, Raderer M, Sedláčková E, Cadiot G, Wolin E.M, Capdevila J, Wall L, Rindi G, Langley A, Gomez-Panzani E, Ruszniewski PB. Effects of lanreotide Depot/Autogel in pancreatic neuroendocrine tumors: a subgroup analysis from the CLARINET study. J Clin Oncol. 2015. Vol. 33, no. 3_suppl:233-233. DOI: 10.1200/jco.2015.33.3_suppl.233

32. Cwikla J.B, Wolin E.M, Pavel M, Phan A.T, Raderer M, Sedláčková E, Cadiot G, Capdevila J, Rindi G, Lombard-Bohas C, Liyanage N, Truong Thanh X-M, Ruszniewski P, Caplin M. Ann Oncol. 2017. Vol. 28, Issue suppl_5, https://doi.org/10.1093/annonc/mdx368.023

33. Massironi S, Conte D, Rossi RE. Somatostatin analogues in functioning gastroenteropancreatic neuroendocrine tumours: literature review, clinical recommendations and schedules.// Scand J Gastroenterol. 2016; 51 (5): 513-523.

34. Saif M.W. Lanreotide for the treatment of gastroenteropancreatic neuroendocrine tumors.// Expert Opin Pharmacother. 2016;17 (3): 443-456.

35. Kos-Kudła B. Treatment of neuroendocrine tumors: new recommendations based on the CLARINET study.// Contemp Oncol (Pozn). 2015;19 (5): 345-9.

36. Mehrvarz Sarshekeh A, Halperin D.M, Dasari A. Update on management of midgut neuroendocrine tumors. Int J Endocrine Oncol. 2016;3(2):175-189. doi:10.2217/ije-2015-0004.


Review

For citations:


Ilovayskaya I.A. DIARRHEA AS A CLINICAL MARKER OF NEUROENDOCRINE TUMORS. Experimental and Clinical Gastroenterology. 2018;(6):143-149. (In Russ.)

Views: 378


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1682-8658 (Print)