Early diagnosis and treatment of gastrointestinal neuroendocrine tumors

Shen,Hong; Yu,Zhuo; Zhao,Jing; Li,Xiu‑Zhen; Pan,Wen‑Sheng

doi:10.3892/ol.2016.5062

Early diagnosis and treatment of gastrointestinal neuroendocrine tumors

Authors:
- Hong Shen
- Zhuo Yu
- Jing Zhao
- Xiu‑Zhen Li
- Wen‑Sheng Pan
View Affiliations

Affiliations: Department of Medical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China, Department of Pathology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China, Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
Published online on: August 29, 2016 https://doi.org/10.3892/ol.2016.5062
Pages: 3385-3392

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present retrospective analysis on the macroscopic appearance and pathological characteristics of gastrointestinal neuroendocrine tumors (NETs) was to investigate methods for their early diagnosis and treatment. A total of 78 patients were divided into submucosal NET and deeper invasion NET groups, according to the depth of tumor invasion exhibited by the patients. The clinicopathological characteristics and survival time of the NET patients were analyzed and compared. The pathological characteristics of the submucosal NETs group were investigated according to the diameter of the tumor (≤5.0 mm, 5.1‑10.0 mm or >10.0 mm). The depth of invasion at diagnosis was observed to significantly correlate with histopathological classification, diameter of the tumor, macroscopic appearance, growth pattern, lymphatic‑vascular involvement, lymph node (LN) metastasis and distant metastasis. In the submucosal NETs group, high‑grade tumors with lymphatic or venule invasion and distant metastasis were associated with an increased risk of nodal metastases. In patients with minute tumors (≤5.0 mm), no lymphatic‑vascular involvement, LN or distant metastasis was observed. By contrast, patients with tumors measuring 5.1‑10.0 mm in diameter exhibited high lymphatic-vascular involvement and LN metastasis rates (46.2 and 30.8%, respectively). Survival time was significantly longer in patients with submucosal NETs compared with deeper invasion NETs and in patients with NET G1 and NET G2 compared with NEC. The results of the present study indicate that gastrointestinal submucosal NETs are closely associated with a slightly elevated macroscopic type, low‑grade tumors and a small diameter. These features may contribute to early diagnosis of gastrointestinal NETs. Therefore, a tumor diameter of <5.0 mm, with slightly elevated macroscopic appearance may indicate an absolute requirement for endoscopic resection, while tumors measuring 5.1‑10.0 mm in diameter must be considered carefully.

View Figures

View References

1	Modlin IM, Lye KD and Kidd M: A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 97:934–959. 2003. View Article : Google Scholar : PubMed/NCBI
2	Pape UF, Berndt U, Müller-Nordhorn J, Böhmig M, Roll S, Koch M, Willich SN and Wiedenmann B: Prognostic factors of long-term outcome in gastroenteropancreatic neuroendocrine tumours. Endocr Relat Cancer. 15:1083–1097. 2008. View Article : Google Scholar : PubMed/NCBI
3	Hauso O, Gustafsson BI, Kidd M, Waldum HL, Drozdov I, Chan AK and Modlin IM: Neuroendocrine tumor epidemiology: Contrasting Norway and North America. Cancer. 113:2655–2664. 2008. View Article : Google Scholar : PubMed/NCBI
4	Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, Abdalla EK, Fleming JB, Vauthey JN, Rashid A and Evans DB: One hundred years after ‘carcinoid’: Epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 26:3063–3072. 2008. View Article : Google Scholar : PubMed/NCBI
5	Berge T and Linell F: Carcinoid tumours. Frequency in a defined population during a 12-year period. Acta Pathol Microbiol Scand A. 84:322–330. 1976.PubMed/NCBI
6	Oberg K and Eriksson B: Endocrine tumours of the pancreas. Best Pract Res Clin Gastroenterol. 19:753–781. 2005. View Article : Google Scholar : PubMed/NCBI
7	Modlin IM, Oberg K, Chung DC, Jensen RT, de Herder WW, Thakker RV, Caplin M, Fave G Delle, Kaltsas GA, Krenning EP, et al: Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol. 9:61–72. 2008. View Article : Google Scholar : PubMed/NCBI
8	Scherübl H, Cadiot G, Jensen RT, Rösch T, Stölzel U and Klöppel G: Neuroendocrine tumors of the stomach (gastric carcinoids) are on the rise: Small tumors, small problems? Endoscopy. 42:664–671. 2010. View Article : Google Scholar : PubMed/NCBI
9	Scherübl H: Rectal carcinoids are on the rise: Early detection by screening endoscopy. Endoscopy. 41:162–165. 2009. View Article : Google Scholar : PubMed/NCBI
10	Scherübl H, Jensen RT, Cadiot G, Stölzel U and Klöppel G: Neuroendocrine tumors of the small bowels are on the rise: Early aspects and management. World J Gastrointest Endosc. 2:325–334. 2010. View Article : Google Scholar : PubMed/NCBI
11	Strosberg J, Gardner N and Kvols L: Survival and prognostic factor analysis of 146 metastatic neuroendocrine tumors of the mid-gut. Neuroendocrinology. 89:471–476. 2009. View Article : Google Scholar : PubMed/NCBI
12	Zar N, Garmo H, Holmberg L, Rastad J and Hellman P: Long-term survival of patients with small intestinal carcinoid tumors. World J Surg. 28:1163–1168. 2004. View Article : Google Scholar : PubMed/NCBI
13	Scherübl H, Jensen RT, Cadiot G, Stölzel U and Klöppel G: Management of early gastrointestinal neuroendocrine neoplasms. World J Gastrointest Endosc. 3:133–139. 2011. View Article : Google Scholar : PubMed/NCBI
14	Kulke MH, Benson AB III, Bergsland E, Berlin JD, Blaszkowsky LS, Choti MA, Clark OH, Doherty GM, Eason J, Emerson L, et al: Neuroendocrine tumors. J Natl Compr Canc Netw. 10:724–764. 2012.PubMed/NCBI
15	Zhou FR, Huang LY and Wu CR: Endoscopic mucosal resection for rectal carcinoids under micro-probe ultrasound guidance. World J Gastroenterol. 19:2555–2559. 2013. View Article : Google Scholar : PubMed/NCBI
16	Yamaguchi N, Isomoto H, Nishiyama H, Fukuda E, Ishii H, Nakamura T, Ohnita K, Hayashi T, Kohno S, Nakao K and Shikuwa S: Endoscopic submucosal dissection for rectal carcinoid tumors. Surg Endosc. 24:504–508. 2010. View Article : Google Scholar : PubMed/NCBI
17	Participants in the Paris Workshop, . The Paris endoscopic classification of superficial neoplastic lesions: Esophagus, stomach, and colon: November 30 to December 1, 2002. Gastrointest Endosc. 58(Suppl 6): S3–S43. 2003.PubMed/NCBI
18	Endoscopic Classification Review Group, . Update on the Paris classification of superficial neoplastic lesions in the digestive tract. Endoscopy. 37:570–578. 2005. View Article : Google Scholar : PubMed/NCBI
19	Borrmann R: Tumors of the stomach and duodenumHandbook of Special Pathological Anatomy and Histology: Digestive Tract. Borchardt H, Borrmann R, Christeller E, Dietrich A, Fischer W, Von Gierke E, Hauser G, Kaiserling C, Koch M, Koch W, et al: 4. 1st. Springer Vienna; Berlin: pp. 8651926, (In German).
20	Bosman FT, Carneiro F, Hruban RH and Theise ND: WHO Classification of Tumours of the Digestive System. 3. 4th. IARC Press; Lyon: 2010
21	Pape UF, Jann H, Müller-Nordhorn J, Bockelbrink A, Berndt U, Willich SN, Koch M, Röcken C, Rindi G and Wiedenmann B: Prognostic relevance of a novel TNM classification system for upper gastroenteropancreatic neuroendocrine tumors. Cancer. 113:256–265. 2008. View Article : Google Scholar : PubMed/NCBI
22	Garcia-Carbonero R, Capdevila J, Crespo-Herrero G, Díaz-Pérez JA, Martínez Del Prado MP, Orduña V Alonso, Sevilla-García I, Villabona-Artero C, Beguiristain-Gómez A, Llanos-Muñoz M, et al: Incidence, patterns of care and prognostic factors for outcome of gastroenteropancreatic neuroendocrine tumors (GEP-NETs): Results from the National Cancer Registry of Spain (RGETNE). Ann Oncol. 21:1794–1803. 2010. View Article : Google Scholar : PubMed/NCBI
23	Cho MY, Sohn JH, Jin SY, Kim H, Jung ES, Kim MJ, Kim KM, Kim WH, Kim JM, Kang YK, et al: Gastrointestinal Pathology Study Group of Korean Society of Pathologists: Proposal for a standardized pathology report of gastroenteropancreatic neuroendocrine tumors: Prognostic significance of pathological parameters. Korean J Pathol. 47:227–237. 2013. View Article : Google Scholar : PubMed/NCBI
24	Yoshino T, Shimoda T, Saito A, Nakanishi Y, Yusuke T, Shirasu T and Miura S: Macroscopic features and its clinical treatment of stomach type differentiated adenocarcinoma in early gastric cancer. Stomach and Intestines. 34:513–525. 1999.(In Japanese).
25	Japanese Gastric Cancer Association, . Japanese gastric cancer treatment guidelines 2010 (ver. 3). Gastric cancer. 14:113–123. 2011. View Article : Google Scholar : PubMed/NCBI
26	Thomas RM, Baybick JH, Elsayed AM and Sobin LH: Gastric carcinoids. An immunohistochemical and clinicopathologic study of 104 patients. Cancer. 73:2053–2058. 1994. View Article : Google Scholar : PubMed/NCBI
27	Soga J: Early-stage carcinoids of the gastrointestinal tract: An analysis of 1,914 reported cases. Cancer. 103:1587–1595. 2005. View Article : Google Scholar : PubMed/NCBI
28	Ramage JK, Ahmed A, Ardill J, Bax N, Breen DJ, Caplin ME, Corrie P, Davar J, Davies AH, Lewington V, et al: Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). Gut. 61:6–32. 2012. View Article : Google Scholar : PubMed/NCBI
29	Basuroy R, Srirajaskanthan R, Prachalias A, Quaglia A and Ramage JK: Review article: The investigation and management of gastric neuroendocrine tumours. Aliment Pharmacol Ther. 39:1071–1084. 2014. View Article : Google Scholar : PubMed/NCBI
30	Heo J, Jeon SW, Jung MK, Kim SK, Shin GY, Park SM, Ahn SY, Yoon WK, Kim M and Kwon YH: A tailored approach for endoscopic treatment of small rectal neuroendocrine tumor. Surg Endosc. 28:2931–2938. 2014. View Article : Google Scholar : PubMed/NCBI
31	Kwon YH, Jeon SW, Kim GH, Kim JI, Chung IK, Jee SR, Kim HU, Seo GS, Baik GH, Choi KD and Moon JS: Long-term follow up of endoscopic resection for type 3 gastric NET. World J Gastroenterol. 19:8703–8708. 2013. View Article : Google Scholar : PubMed/NCBI
32	Sano T, Sasako M, Kinoshita T and Maruyama K: Recurrence of early gastric cancer. Follow-up of 1475 patients and review of the Japanese literature. Cancer. 72:3174–3178. 1993. View Article : Google Scholar : PubMed/NCBI
33	Sung HY, Kim SW, Kang WK, Kim SY, Jung CK, Cho YK, Park JM, Lee IS, Choi MG and Chung IS: Long-term prognosis of an endoscopically treated rectal neuroendocrine tumor: 10-year experience in a single institution. Eur J Gastroenterol Hepatol. 24:978–983. 2012. View Article : Google Scholar : PubMed/NCBI
34	Yokoyama S, Takifuji K, Tani M, Kawai M, Naka T, Uchiyama K and Yamaue H: Endoscopic resection of duodenal bulb neuroendocrine tumor larger than 10 mm in diameter. BMC Gastroenterol. 11:672011. View Article : Google Scholar : PubMed/NCBI
35	Baek IH: Endoscopic submucosal dissection or conventional endoscopic mucosal resection is an effective and safe treatment for rectal carcinoid tumors: A retrospective study. J Laparoendosc Adv Surg Tech A. 20:329–331. 2010. View Article : Google Scholar : PubMed/NCBI