Neuroendocrine tumors of the appendix

The aim. The aim of our study was to analyze the available data from literature sources concerning the issues of epidemiology, pathology, clinic, diagnosis, and features of surgical treatment of neuroendocrine tumors of the vermiform process.
Materials and methods. We conducted a retrospective analysis of foreign and domestic literature sources that contain upto-date information about the state of the problem of neuroendocrine tumors of the vermiform process
Results. Appendicular neuroendocrine tumors (ANEO) account for up to 16.7% of all neuroendocrine tumors of the gastrointestinal tract. In 54% of cases, ANEO show themselves for the fi rst time with a picture of an acute abdomen that resembles that of acute appendicitis. The main method of treatment is surgical. So far, there are no clinical guidelines that specify clear criteria for performing an appendectomy or right-sided hemicolectomy. Although gastrointestinal neuroendocrine tumors are less sensitive to it, there is evidence of a good response to temozolomide therapy (CAPTEM scheme: temozolomide+capecitabine). Octreotide can also be eff ective, especially in the group of functionally active ANIOS. The 5-year survival rate of patients with ANEO is 94% for tumors up to 1 cm in diameter, 70.5% for tumors larger than 2 cm, and 33.7% for distant metastases at the time of diagnosis.
Conclusion. Treatment of patients with ANEO gives rise to the following confl ict situation: on the one hand, the risk of recurrence of the disease in the long term is quite low, but if it occurs, it signifi cantly worsens the prognosis and, consequently, signifi cantly affects the overall survival. We emphasize the need to further study the biological properties of ANIO, the importance of generalizing all available data, which is possible only with close international contact of scientists around the world.

1. Трифанов В.С., Кит О. И., Колесников Е. Н. и соавт. Клинико-иммуногистохимический анализ нейроэндокринных опухолей поджелудочной железы // Современные проблемы науки и образования. – 2019, № 3. http://science-education.ru/ru/article/view?id=28865 Trifanov V. S., Kit O. I., Kolesnikov E. N. i soavt. Klinikoimmunogistoximicheskij analiz nejroe`ndokrinny`x opuxolej podzheludochnoj zhelezy` [Clinical and immunohistochemical analysis of neuroendocrine pancreatic tumors]. Sovremenny`e problemy` nauki i obrazovaniya – Modern problems of science and education, 2019, no. 3. Available at: http://science-education.ru/ru/article/view?id=28865

2. Кит О. И. Нейроэндокринные, клинические и морфологические аспекты рака желудка, Новочеркасск: Издательство «Лик», 2014, 224 с. Kit O. I. Nejroe`ndokrinny`e, klinicheskie i morfologicheskie aspekty` raka zheludka [Neuroendocrine, clinical and morphological aspects of gastric cancer]. Novocherkassk, «Lik» Publ., 2014. 224 p.

3. Тимошкина Н.Н., Водолажский Д. И., Ефимова И. Ю. и соавт. Исследование CpG-метилирования промоторных участков генов APC, CDH13, MLH1, MGMT, P16, RASSF1A при метастазирующем раке толстой кишки // Известия высших учебных заведений. Северо-Кавказский регион. Естественные науки, 2017, № 3–2 (195–2), С. 111–117. Timoshkina N. N., Vodolazhskij D. I., Efimova I. Yu. i soavt. Issledovanie CpG-metilirovaniya promotorny`x uchastkov genov APC, CDH13, MLH1, MGMT, P16, RASSF1A pri metastaziruyushhem rake tolstoj kishki [Investigation of CpG-methylation of promoter sites of APC, CDH13, MLH1, MGMT, P16, and RASSF1A genes in metastatic colon cancer]. Izvestiya vy`sshix uchebny`x zavedenij. Severo-Kavkazskij region. Estestvenny`e nauki – News of higher educational institutions. North Caucasus region. Natural science, 2017, no. 3–2(195–2), pp. 111–117.

4. Кит О. И., Водолажский Д. И., Двадненко К. В. и соавт. Аберрантное метилирование промоторных участков генов APC, CDH13 и MGMT у больных колоректальным раком // Сибирский онкологический журнал, 2016, T. 15, № 2, С. 48–55. Kit O. I., Vodolazhskij D. I., Dvadnenko K. V. i soavt. Aberrantnoe metilirovanie promotorny`x uchastkov genov APC, CDH13 i MGMT u bol`ny`x kolorektal`ny`m rakom [Aberrant methylation of promoter sites of APC, CDH13 and MGMT genes in colorectal cancer patients]. Sibirskij onkologicheskij zhurnal – Siberian journal of Oncology, 2016, vol. 15, no. 2, pp. 48–55.

5. Белобородов В.А., Пинский С. Б., Батороев Ю. К., Дворниченко В. В. Нейроэндокринные опухоли желудочно-кишечного тракта. Нейроэндокринные опухоли червеобразного отростка // Сибирский медицинский журнал, 2014, № 8, С. 10–14. Beloborodov V. A., Pinskij S. B., Batoroev Yu.K., Dvornichenko V. V. Nejroe`ndokrinny`e opuxoli zheludochno-kishechnogo trakta. Nejroe`ndokrinny`e opuxoli cherveobraznogo otrostka [Neuroendocrine tumors of the gastrointestinal tract. Neuroendocrine tumors of the Appendix]. Sibirskij medicinskij zhurnal – Siberian journal of Oncology, 2014, no. 8, pp. 10–14.

6. Pawa N., Clift A., Osmani H. et al. Surgical management of patients with neuroendocrine neoplasms of the appendix: appendectomy or more? Neuroendocrinology, 2018, vol. 106, no. 3, pp.242–251. doi: 10.1159/000478742

7. Davenport E., Courtney E., Benson-Cooper S. et al. Appendiceal neuroendocrine neoplasms in the era of laparoscopic appendicectomy. ANZ J Surg, 2014, vol. 84, no. 5, pp. 337–340. doi: 10.1111/ans.12495

8. Moris D., Tsilimigras D. Neuroendocrine Neoplasms of the Appendix: A Review of the Literature. Anticancer research, 2018, vol. 38, no.3, pp. 601–612. doi: 10.21873/anticanres.12264

9. Boudreaux P., Klimstra D., Hassan M. et al. WellDifferentiated Neuroendocrine Tumors of the Jejunum, Ileum, Appendix, and Cecum. The NANETS Consensus Guideline for the Diagnosis and Management of Neuroendocrine Tumors. Pancreas, 2010, vol. 39, no. 6, pp. 753–766. doi: 10.1097/MPA.0b013e3181ebb2a5

10. Wu H., Chintagumpala M., Hicks J. et al. Neuroendocrine Tumor of the Appendix in Children. J Pediatr Hematol Oncol, 2017, vol. 39, no. 2, pp. 97–102.

11. Eğin S., Kamalı G., Kamalı S. et al. Neuroendocrine tumor of the appendix: Twelve years of results from a single institution. Ulus Travma Acil Cerrahi Derg, 2019, vol. 25, no. 2, pp. 118–122. doi: 10.14744/tjtes.2019.38283

12. Pape U., Niederle B., Costa F. et al. ENETS Consensus Guidelines for Neuroendocrine Neoplasms of the Appendix (Excluding Goblet Cell Carcinomas) Neuroendocrinology, 2016, vol. 103, no. 2, pp. 144–152. doi: 10.1159/000443165

13. Morais C., Silva E., Brandão P. et al. Neuroendocrine tumor of the appendix – a case report and review of the literature. Journal of Surgical Case Reports, 2019, vol. 1, no. 3, pp. 1–4. doi: 10.1093/jscr/rjz086

14. Henderson L., Fehily C., Folaranmi S. et al. Management and outcome of neuroendocrine tumours of the appendix – a two centre UK experience. Journal of Pediatric Surgery, 2014, vol. 49, no. 10, pp. 1513–1517. doi: 10.1016/j.jpedsurg.2014.05.019

15. Lambert G., Lardy H., Martelli H. et al. Surgical Management of Neuroendocrine Tumors of the Appendix in Children and Adolescents: A Retrospective French Multicenter Study of 114 Cases. Pediatr Blood Cancer, 2016, vol. 63, № 1, pp. 598–603. doi: 10.1002/pbc.25823

16. Bednarczuk T., Bolanowski M., Zemczak A. et al. Neuroendocrine neoplasms of the small intestine and appendix, management guidelines (recommended by the Polish Network of Neuroendocrine Tumours). Endokrynologia Polska, 2017, vol. 68, no. 2, pp. 223–236. doi: 10.5603/EP.2017.0018

17. Carr N., Sobin L. Neuroendocrine tumors of the appendix. Seminars in Diagnostic Pathology, 2004, vol. 21, no.1, pp. 108–119. doi: 10.1053/j.semdp.2004.11.004

18. Dasari A., Shen C., Halperin D. et al. Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the united states. JAMA Oncol, 2017, vol. 3, no. 10, pp. 1335–1342. doi: 10.1001/jamaoncol.2017.0589

19. Hsu C., Rashid A., Xing Y. et al. Varying malignant potential of appendiceal neuroendocrine tumors: importance of histologic subtype. J Surg Oncol, 2013, vol. 107, no. 2, pp. 136–143. doi: 10.1002/jso.23205

20. Kim J.Y., Hong S. M. Recent updates on neuroendocrine tumors from the gastrointestinal and pancreatobiliary tracts. Arch Pathol Lab Med, 2016, vol. 140, no. 5, pp. 437–448. doi: 10.5858/arpa.2015-0314-RA

21. Clift A.K., Frilling A. Neuroendocrine, goblet cell and mixed adeno-neuroendocrine tumours of the appendix: updates, clinical applications and the future. Expert Rev Gastroenterol Hepatol, 2017, vol. 11, no. 3, pp. 237–247. doi: 10.1080/17474124.2017.1282314

22. Shaib W., Krishna K., Kim S. et al. Appendiceal neuroendocrine, goblet and signet-ring cell tumors: a spectrum of diseases with different patterns of presentation and outcome. Cancer Res Treat, 2016, vol. 48, no. 2, pp. 596–604. doi: 10.4143/crt.2015.029

23. Koumarianou A., Kaltsas G., Kulke M. et al.Temozolomide in advanced neuroendocrine neoplasms: pharmacological and clinical aspects. Neuroendocrinology, 2015, vol. 101, no. 4, pp. 274–288. doi: 10.1159/000430816

24. Nussbaum D., Speicher P., Gulack B. et al. Management of 1- to 2-cm carcinoid tumors of the appendix: Using the National Cancer Data Base to address controversies in general surgery. J Am Coll Surg, 2015, vol. 220, no.5, pp. 894–903. doi: 10.1016/j.jamcollsurg.2015.01.005