Neuroendocrine carcinoma (NEC) of the esophagus and the stomach is aggressive. The purpose of this study was to determine the optimal therapeutic strategy.
Both clinicopathological factors and treatment results were examined in 34 patients with immunohistochemically diagnosed NEC of the upper gastrointestinal tract (esophagus 22; stomach 12).
Twenty-nine tumors showed protruding and localized type, like submucosal tumor. Esophagectomy and gastrectomy were performed in six and eight patients, respectively. Among the six patients with esophageal NEC, three with node metastasis developed recurrence within seven months, while the other three (pT1bN0) had no recurrence. Regarding gastric NEC, three patients with pT3N1 or 2 tumor received adjuvant chemotherapy and achieved a 5-year survival. However, the other five experienced recurrence after gastrectomy. Systemic chemotherapy was performed as the main treatment for 18 patients with advanced NEC. The median survival was 10 months after initial chemotherapy. No marked differences in the response were recognized between the 14 cases with esophageal NEC and the 4 with gastric NEC. The median survival was 14.3 and 5.3 months for the 11 effective and 7 non-effective patients, respectively.
A macroscopically unique appearance, like submucosal tumor, suggests the possibility of NEC. Esophagectomy is an effective treatment option for limited-stage NEC without node metastasis, while gastrectomy followed by adjuvant chemotherapy may be effective for NEC even with node metastasis when R0 resection can be achieved. Systemic chemotherapy is relatively effective for advanced NEC, although early progression frequently develops.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Egashira A, Morita M, Kumagai R et al (2017) Neuroendocrine carcinoma of the esophagus: clinicopathological and immunohistochemical features of 14 cases. PLoS ONE 12:e0173501. https://doi.org/10.1371/journal.pone.0173501
Xie JW, Lu J, Lin JX et al (2017) Different long-term oncologic outcomes after radical surgical resection for neuroendocrine carcinoma and adenocarcinoma of the stomach. Oncotarget 8:57495–57504. https://doi.org/10.18632/oncotarget.15488
International Agency of Research on Cancer, WHO (2019) WHO classification of tumors, Digestive system tumors, 5th edn. International Agency of Research on Cancer, Lyon, France
Morita M, Saeki H, Nakaji YU et al (2016) Conversion to neuroendocrine carcinoma from squamous cell carcinoma of the esophagus after definitive chemoradiotherapy. Anticancer Res 36:4045–4049
Deng Y, Chen X, Ye Y et al (2016) Histological characterisation and prognostic evaluation of 62 gastric neuroendocrine carcinomas. Contemp Oncol (Pozn) 20:311–319. https://doi.org/10.5114/wo.2016.61852
Cai W, Ge W, Yuan Y et al (2019) A 10-year population-based study of the differences between NECs and carcinomas of the esophagus in terms of clinicopathology and survival. J Cancer 10:1520–1527. https://doi.org/10.7150/jca.29483
Xie JW, Lu J, Wang JB et al (2018) Prognostic factors for survival after curative resection of gastric mixed adenoneuroendocrine carcinoma: a series of 80 patients. BMC Cancer 18:1021. https://doi.org/10.1186/s12885-018-4943-z
Japan Neuroendocrine Tumor Society (2019) Clinical practice guidelines for gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) 2019, Kanehara & Co., Ltd, Tokyo (in Japanese)
International Agency for Research on Cancer WHO (2017) Digestive system tumors/TNM classification of malignant tumours, 8th edn. Wiley Blackwell, Chidhester
Vos B, Rozema T, Miller RC et al (2011) Small cell carcinoma of the esophagus: a multicentre Rare Cancer Network study. Dis Esophagus 24:258–264. https://doi.org/10.1111/j.1442-2050.2010.01133.x
Nishikura K, Watanabe H, Iwafuchi M et al (2003) Carcinogenesis of gastric endocrine cell carcinoma: analysis of histopathology and p53 gene alteration. Gastric Cancer 6:203–209. https://doi.org/10.1007/s10120-003-0249-0
van der Veen A, Seesing MFJ, Wijnhoven BPL et al (2018) Management of resectable esophageal and gastric (mixed adeno)neuroendocrine carcinoma: a nationwide cohort study. Eur J Surg Oncol 44:1955–1962. https://doi.org/10.1016/j.ejso.2018.07.058
Maru DM, Khurana H, Rashid A et al (2008) Retrospective study of clinicopathologic features and prognosis of high-grade neuroendocrine carcinoma of the esophagus. Am J Surg Pathol 32:1404–1411. https://doi.org/10.1097/PAS.0b013e31816bf41f
Hong L, Zhang Y, Liu Z (2018) Neuroendocrine carcinoma of esophageal and gastric cardia: clinicopathologic and immunohistochemistry study of 80 cases. Oncotarget 9:10754–10764. https://doi.org/10.18632/oncotarget.23610
Chen MH, Kuo YJ, Yeh YC et al (2015) High neuroendocrine component is a factor for poor prognosis in gastrointestinal high-grade malignant mixed adenoneuroendocrine neoplasms. J Chin Med Assoc 78:454–459. https://doi.org/10.1016/j.jcma.2015.04.002
Deng HY, Ni PZ, Wang YC et al (2016) Neuroendocrine carcinoma of the esophagus: clinical characteristics and prognostic evaluation of 49 cases with surgical resection. J Thorac Dis 8:1250–1256. https://doi.org/10.21037/jtd.2016.04.21
Situ D, Lin Y, Long H et al (2013) Surgical treatment for limited-stage primary small cell cancer of the esophagus. Ann Thorac Surg 95:1057–1062. https://doi.org/10.1016/j.athoracsur.2012.11.014
Chen WW, Wang F, Chen S et al (2014) Detailed analysis of prognostic factors in primary esophageal small cell carcinoma. Ann Thorac Surg 97:1975–1981. https://doi.org/10.1016/j.athoracsur.2014.02.037
Xu L, Li Y, Liu X et al (2017) Treatment strategies and prognostic factors of limited-stage primary small cell carcinoma of the esophagus. J Thorac Oncol 12:1834–1844. https://doi.org/10.1016/j.jtho.2017.09.1966
Wong AT, Shao M, Rineer J et al (2017) Treatment and survival outcomes of small cell carcinoma of the esophagus: an analysis of the National Cancer Data Base. Dis Esophagus 30:1–5. https://doi.org/10.1111/dote.12487
Deng HY, Li G, Luo J et al (2018) The role of surgery in treating resectable limited disease of esophageal neuroendocrine carcinoma. World J Surg 42:2428–2436. https://doi.org/10.1007/s00268-018-4475-3
Kuo CH, Hsieh CC, Chan ML et al (2011) Small cell carcinoma of the esophagus: a report of 16 cases from a single institution and literature review. Ann Thorac Surg 91:373–378. https://doi.org/10.1016/j.athoracsur.2010.09.030
Meng MB, Zaorsky NG, Jiang C et al (2013) Radiotherapy and chemotherapy are associated with improved outcomes over surgery and chemotherapy in the management of limited-stage small cell esophageal carcinoma. Radiother Oncol 106:317–322. https://doi.org/10.1016/j.radonc.2013.01.008
Kubota T, Ohyama S, Hiki N et al (2012) Endocrine carcinoma of the stomach: clinicopathological analysis of 27 surgically treated cases in a single institute. Gastric Cancer 15:323–330. https://doi.org/10.1007/s10120-011-0122-5
Ishida M, Sekine S, Fukagawa T et al (2013) Neuroendocrine carcinoma of the stomach: morphologic and immunohistochemical characteristics and prognosis. Am J Surg Pathol 37:949–959. https://doi.org/10.1097/PAS.0b013e31828ff59d
Okita NT, Kato K, Takahari D et al (2011) Neuroendocrine tumors of the stomach: chemotherapy with cisplatin plus irinotecan is effective for gastric poorly-differentiated neuroendocrine carcinoma. Gastric Cancer 14:161–165. https://doi.org/10.1007/s10120-011-0025-5
Yamaguchi T, Machida N, Morizane C et al (2014) Multicenter retrospective analysis of systemic chemotherapy for advanced neuroendocrine carcinoma of the digestive system. Cancer Sci 105:1176–1181. https://doi.org/10.1111/cas.12473
We thank Brian Quinn for assisting with the preparation of the manuscript.
This work was supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sport, Science and Technology of Japan (Grant No. 18K08638) and the Fujii Setsuro Memorial Foundation.
Conflict of interest
The authors declare that they have no conflict of interest in association with the present study.
All procedures performed in this study involving human participants were in accordance with ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical statements.
Informed consent was obtained from individual participants in the study.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Morita, M., Taguchi, K., Kagawa, M. et al. Treatment strategies for neuroendocrine carcinoma of the upper digestive tract. Int J Clin Oncol (2020). https://doi.org/10.1007/s10147-020-01631-y
- Neuroendocrine carcinoma