Abstract
There are vast differences in terminology, classification and grading of gastrointestinal neuroendocrine tumours (NETs); mostly the organ or tissue of origin is considered for nomenclature and grading. GI-NETs are relatively rare, accounting for approximately 0.5 % of all human cancers. Embryologically NETs are divided into three categories as described by William and Sandler: foregut carcinoids (lung, stomach, duodenum, upper jejenum and pancreas), midgut carcinoids (lower jejenum, ileum, appendix, caecum) and hindgut carcinoids (colon and rectum). GI-NETs are those arising at the oesophagus, stomach, bile ducts and gall bladder, duodenum, jejunum, appendix, colon and rectum. Oesophageal NETs are extremely rare. Gastric NETs are divided into four groups based on clinicopathological features as type 1, type 2, type 3 and type 4. This classification has also prognostic and management implications. Primary duodenal NETs account for less than 2 % of all gastrointestinal NETs. They are relatively benign lesions with slow growth pattern and low metastatic potential. The ileum and appendix are the most common sites of NETs in the West, while colorectal NETs are relatively more common in the East. As for the classification, management also depends on the primary site, grade and the stage of the disease. In localised disease, surgery is the mainstay of treatment. In symptomatic cases, somatostatin analogues are effective. Liver-directed therapies and systemic cytotoxic drugs and targeted agents can be used in selected cases.
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References
Yao JC, Hassan M, Phan A et al (2008) 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
Modlin IM, Oberg K, Chung DC et al (2008) Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol 9:61–72
Crocetti E, Paci E (2003) Malignant carcinoids in the USA, SEER 1992–1999. An epidemiological study with 6830 cases. Eur J Cancer Prev 12:191–194
Taal BG, Visser O (2004) Epidemiology of neuroendocrine tumours. Neuroendocrinology 80(Suppl 1):3–7
Karpathakis A, Caplin M, Thirlwell C (2012) Hitting the target: where do molecularly targeted therapies fit in the treatment scheduling of neuroendocrine tumours? Endocr Relat Cancer 19:R73–R92
Oberg K (2012) Neuroendocrine tumors of the digestive tract: impact of new classifications and new agents on therapeutic approaches. Curr Opin Oncol 24:433–440
Steinmuller T, Kianmanesh R, Falconi M et al (2008) Consensus guidelines for the management of patients with liver metastases from digestive (neuro)endocrine tumors: foregut, midgut, hindgut, and unknown primary. Neuroendocrinology 87:47–62
Williams ED, Sandler M (1963) The classification of carcinoid tumours. Lancet 1:238–239
Kloppel G, Rindi G, Anlauf M et al (2007) Site-specific biology and pathology of gastroenteropancreatic neuroendocrine tumors. Virchows Arch 451(Suppl 1):S9–S27
Brenner S, Heimlich H, Widman M (1969) Carcinoid of esophagus. N Y State J Med 69:1337–1339
Ready AR, Soul JO, Newman J et al (1989) Malignant carcinoid tumour of the oesophagus. Thorax 44:594–596
Li QL, Zhang YQ, Chen WF et al (2012) Endoscopic submucosal dissection for foregut neuroendocrine tumors: an initial study. World J Gastroenterol 18:5799–5806
Lindberg GM, Molberg KH, Vuitch MF et al (1997) Atypical carcinoid of the esophagus: a case report and review of the literature. Cancer 79:1476–1481
Chen WF, Zhou PH, Li QL et al (2012) Clinical impact of endoscopic submucosal dissection for gastric neuroendocrine tumors: a retrospective study from mainland China. ScientificWorldJournal 2012:869769
Jianu CS, Lange OJ, Viset T et al (2012) Gastric neuroendocrine carcinoma after long-term use of proton pump inhibitor. Scand J Gastroenterol 47:64–67
Bordi C (1999) Gastric carcinoids. Ital J Gastroenterol Hepatol 31(Suppl 2):S94–S97
Li TT, Qiu F, Qian ZR et al (2014) Classification, clinicopathologic features and treatment of gastric neuroendocrine tumors. World J Gastroenterol 20:118–125
Plockinger U (2007) Diagnosis and treatment of gastric neuroendocrine tumours. Wien Klin Wochenschr 119:570–572
Kidd M, Siddique ZL, Drozdov I et al (2010) The CCK(2) receptor antagonist, YF476, inhibits Mastomys ECL cell hyperplasia and gastric carcinoid tumor development. Regul Pept 162:52–60
Fossmark R, Sordal O, Jianu CS et al (2012) Treatment of gastric carcinoids type 1 with the gastrin receptor antagonist netazepide (YF476) results in regression of tumours and normalisation of serum chromogranin A. Aliment Pharmacol Ther 36:1067–1075
Ravizza D, Fiori G, Trovato C et al (2007) Long-term endoscopic and clinical follow-up of untreated type 1 gastric neuroendocrine tumours. Dig Liver Dis 39:537–543
Hosoya Y, Fujii T, Nagai H et al (1999) A case of multiple gastric carcinoids associated with multiple endocrine neoplasia type 1 without hypergastrinemia. Gastrointest Endosc 50:692–695
Debelenko LV, Emmert-Buck MR, Zhuang Z et al (1997) The multiple endocrine neoplasia type I gene locus is involved in the pathogenesis of type II gastric carcinoids. Gastroenterology 113:773–781
Tomassetti P, Migliori M, Caletti GC et al (2000) Treatment of type II gastric carcinoid tumors with somatostatin analogues. N Engl J Med 343:551–554
Hosoya Y, Nagai H, Koinuma K et al (2003) A case of aggressive neuroendocrine carcinoma of the stomach. Gastric Cancer 6:55–59
Kloppel G, Clemens A (1996) The biological relevance of gastric neuroendocrine tumors. Yale J Biol Med 69:69–74
Bordi C, Falchetti A, Azzoni C et al (1997) Aggressive forms of gastric neuroendocrine tumors in multiple endocrine neoplasia type I. Am J Surg Pathol 21:1075–1082
Rindi G, Kloppel G (2004) Endocrine tumors of the gut and pancreas tumor biology and classification. Neuroendocrinology 80(Suppl 1):12–15
Scherubl H, Cadiot G, Jensen RT et al (2010) Neuroendocrine tumors of the stomach (gastric carcinoids) are on the rise: small tumors, small problems? Endoscopy 42:664–671
Namikawa T, Oki T, Kitagawa H et al (2013) Neuroendocrine carcinoma of the stomach: clinicopathological and immunohistochemical evaluation. Med Mol Morphol 46:34–40
Klimstra DS, Modlin IR, Coppola D et al (2010) The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas 39:707–712
Nikou GC, Toubanakis C, Moulakakis KG et al (2011) Carcinoid tumors of the duodenum and the ampulla of Vater: current diagnostic and therapeutic approach in a series of 8 patients. Case series. Int J Surg 9:248–253
Capella C, Riva C, Rindi G et al (1990) Endocrine tumors of the duodenum and upper jejunum. A study of 33 cases with clinico-pathological characteristics and hormone content. Hepatogastroenterology 37:247–252
Mullen JT, Wang H, Yao JC et al (2005) Carcinoid tumors of the duodenum. Surgery 138:971–977; discussion 977–978
Soga J (2003) Endocrinocarcinomas (carcinoids and their variants) of the duodenum. An evaluation of 927 cases. J Exp Clin Cancer Res 22:349–363
Pipeleers-Marichal M, Somers G, Willems G et al (1990) Gastrinomas in the duodenums of patients with multiple endocrine neoplasia type 1 and the Zollinger-Ellison syndrome. N Engl J Med 322:723–727
Pipeleers-Marichal M, Donow C, Heitz PU et al (1993) Pathologic aspects of gastrinomas in patients with Zollinger-Ellison syndrome with and without multiple endocrine neoplasia type I. World J Surg 17:481–488
Kolby L, Nilsson O, Ahlman H (2004) Gastroduodenal endocrine tumours. Scand J Surg 93:317–323
Park MI (2013) Endoscopic treatment for early foregut neuroendocrine tumors. Clin Endosc 46:450–455
Zyromski NJ, Kendrick ML, Nagorney DM et al (2001) Duodenal carcinoid tumors: how aggressive should we be? J Gastrointest Surg 5:588–593
Burke AP, Sobin LH, Federspiel BH et al (1990) Carcinoid tumors of the duodenum. A clinicopathologic study of 99 cases. Arch Pathol Lab Med 114:700–704
Eltawil KM, Gustafsson BI, Kidd M et al (2010) Neuroendocrine tumors of the gallbladder: an evaluation and reassessment of management strategy. J Clin Gastroenterol 44:687–695
Yamamoto M, Nakajo S, Miyoshi N et al (1989) Endocrine cell carcinoma (carcinoid) of the gallbladder. Am J Surg Pathol 13:292–302
Albores-Saavedra J, Nadji M, Henson DE et al (1986) Intestinal metaplasia of the gallbladder: a morphologic and immunocytochemical study. Hum Pathol 17:614–620
Sasatomi E, Nalesnik MA, Marsh JW (2013) Neuroendocrine carcinoma of the extrahepatic bile duct: case report and literature review. World J Gastroenterol 19:4616–4623
Pape UF, Perren A, Niederle B et al (2012) ENETS Consensus Guidelines for the management of patients with neuroendocrine neoplasms from the jejuno-ileum and the appendix including goblet cell carcinomas. Neuroendocrinology 95:135–156
Strosberg J (2012) Neuroendocrine tumours of the small intestine. Best Pract Res Clin Gastroenterol 26:755–773
Ahmed A, Turner G, King B et al (2009) Midgut neuroendocrine tumours with liver metastases: results of the UKINETS study. Endocr Relat Cancer 16:885–894
Helland SK, Prosch AM, Viste A (2006) Carcinoid tumours in the gastrointestinal tract–a population-based study from Western Norway. Scand J Surg 95:158–161
Plockinger U, Rindi G, Arnold R et al (2004) Guidelines for the diagnosis and treatment of neuroendocrine gastrointestinal tumours. A consensus statement on behalf of the European Neuroendocrine Tumour Society (ENETS). Neuroendocrinology 80:394–424
Strosberg JR, Weber JM, Feldman M et al (2013) Prognostic validity of the American Joint Committee on Cancer staging classification for midgut neuroendocrine tumors. J Clin Oncol 31:420–425
Maggard MA, O’Connell JB, Ko CY (2004) Updated population-based review of carcinoid tumors. Ann Surg 240:117–122
Tomioka K, Fukoe Y, Lee Y et al (2013) Primary neuroendocrine carcinoma of the appendix: a case report and review of the literature. Anticancer Res 33:2635–2638
Grozinsky-Glasberg S, Alexandraki KI, Barak D et al (2013) Current size criteria for the management of neuroendocrine tumors of the appendix: are they valid? Clinical experience and review of the literature. Neuroendocrinology 98:31–37
Holt N, Gronbaek H (2013) Goblet cell carcinoids of the appendix. ScientificWorldJournal 2013:543696
Lawrence B, Gustafsson BI, Chan A et al (2011) The epidemiology of gastroenteropancreatic neuroendocrine tumors. Endocrinol Metab Clin North Am 40:1–18, vii
Modlin IM, Lye KD, Kidd M (2003) A 5-decade analysis of 13,715 carcinoid tumors. Cancer 97:934–959
Ramage JK, Goretzki PE, Manfredi R et al (2008) Consensus guidelines for the management of patients with digestive neuroendocrine tumours: well-differentiated colon and rectum tumour/carcinoma. Neuroendocrinology 87:31–39
West NE, Wise PE, Herline AJ et al (2007) Carcinoid tumors are 15 times more common in patients with Crohn’s disease. Inflamm Bowel Dis 13:1129–1134
Boudreaux JP, Klimstra DS, Hassan MM et al (2010) The NANETS consensus guideline for the diagnosis and management of neuroendocrine tumors: well-differentiated neuroendocrine tumors of the Jejunum, Ileum, Appendix, and Cecum. Pancreas 39:753–766
Mandair D, Caplin ME (2012) Colonic and rectal NET’s. Best Pract Res Clin Gastroenterol 26:775–789
Caplin M, Sundin A, Nillson O et al (2012) ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms: colorectal neuroendocrine neoplasms. Neuroendocrinology 95:88–97
Tsikitis VL, Wertheim BC, Guerrero MA (2012) Trends of incidence and survival of gastrointestinal neuroendocrine tumors in the United States: a seer analysis. J Cancer 3:292–302
Ito T, Sasano H, Tanaka M et al (2010) Epidemiological study of gastroenteropancreatic neuroendocrine tumors in Japan. J Gastroenterol 45:234–243
Yoon SN, Yu CS, Shin US et al (2010) Clinicopathological characteristics of rectal carcinoids. Int J Colorectal Dis 25:1087–1092
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Esin, E., Telli, T.A., Yalcin, S. (2015). Overview of Gastrointestinal Neuroendocrine Tumours. In: Yalcin, S., Öberg, K. (eds) Neuroendocrine Tumours. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-45215-8_11
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DOI: https://doi.org/10.1007/978-3-662-45215-8_11
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