Abstract
Neuroendocrine neoplasms (NENs) of the gastrointestinal (GI) tract are a heterogeneous group of tumors originating from neuroendocrine cells distributed throughout the gut and frequently presenting with correlated hypersecretory syndromes, especially in metastatic diseases. Gut-derived NENs have been classified according to their embryological origin into tumors of the foregut (bronchi, stomach, pancreas, gallbladder, duodenum), midgut (duodenum, ileum, appendix, right colon), and hindgut (left colon, rectum).
The incidence of NENs diagnosed has increased in the last years, with GI primary tumors representing the majority of diagnosis. NENs may occur as part of complex familial endocrine cancer syndromes such as multiple endocrine neoplasia type 1 (MEN 1), multiple endocrine neoplasia type 2 (MEN 2), neurofibromatosis type 1, Von Hippel–Lindau syndrome, and Carney’s complex, although the majority occurs as sporadic isolated tumors.
The management of NENs of the GI tract in the setting of locoregional disease consists of different therapeutic approaches, in particular medical treatment and endoscopic procedures, and it varies greatly depending on the site of origin.
In patients with gastric NENs (gNENs), the approach depends on the clinical presentation of the tumor, classified in three types. Type 1 gNENs are associated with hypergastrinemia and chronic atrophic gastritis; the frequency of metastasis is low. Type 2 gNENs occur in patients with hypergastrinemia due to Zollinger-Ellison syndrome in combination with MEN 1. Type 3 gNENs are sporadic and have a more malignant course, frequently presenting with metastasis at the time of diagnosis.
Duodenal NENs are rare (less than 2% of all GI-NENs), and gastrinomas are the most frequent type of tumors originating in this site.
Rectal NENs are commonly small and generally low to intermediate grade (G1–2), whereas colonic NENs are often aggressive, poorly differentiated, and higher grade (G3).
Bibliography
Burkitt MD, Pritchard DM (2006) Review article: pathogenesis and management of gastric carcinoid tumours. Aliment Pharmacol Ther 24(9):1305–1320
Rindi G, Luinetti O, Cornaggia M, Capella C, Solcia E (1993) Three subtypes of gastric argyrophil carcinoid and the gastric neuroendocrine carcinoma: a clinicopathologic study. Gastroenterology 104(4):994–1006
Waldum HL, Sandvik AK, Idle JR (1998) Gastrin is the most important factor in ECL tumorigenesis. Gastroenterology 114(5):1113–1115
Lehy T, Roucayrol AM, Mignon M (2000) Histomorphological characteristics of gastric mucosa in patients with Zollinger-Ellison syndrome or autoimmune gastric atrophy: role of gastrin and atrophying gastritis. Microsc Res Tech 48(6):327–338
Borch K, Ahren B, Ahlman H, Falkmer S, Granerus G, Grimelius L (2005) Gastric carcinoids: biologic behavior and prognosis after differentiated treatment in relation to type. Ann Surg 242(1):64–73
Borch K, Renvall H, Liedberg G (1985) Gastric endocrine cell hyperplasia and carcinoid tumors in pernicious anemia. Gastroenterology 88(3):638–648
Rindi G, Azzoni C, La Rosa S, Klersy C, Paolotti D, Rappel S, Stolte M, Capella C, Bordi C, Solcia E (1999) ECL cell tumor and poorly differentiated endocrine carcinoma of the stomach: prognostic evaluation by pathological analysis. Gastroenterology 116(3):532–542
Hosokawa O, Kaizaki Y, Hattori M, Douden K, Hayashi H, Morishita M, Ohta K (2005) Long-term follow up of patients with multiple gastric carcinoids associated with type A gastritis. Gastric Cancer (Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association) 8(1):42–46
Rindi G et al (2006) TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch 449:395–401
Campana D, Nori F, Pezzilli R, Piscitelli L, Santini D, Brocchi E, Corinaldesi R, Tomassetti P (2008) Gastric endocrine tumors type I: treatment with long-acting somatostatin analogs. Endocr Relat Cancer 15(1):337–342
Campana D, Ravizza D, Ferolla P, Faggiano A, Grimaldi F, Albertelli M, Berretti D, Castellani D, Cacciari G, Fazio N, Colao A, Ferone D, Tomassetti P (2016) Clinical management of patients with gastric neuroendocrine neoplasms associated with chronic atrophic gastritis: a retrospective, multicentre study. Endocrine 51(1):131–139
Manfredi S, Pagenault M, de Lajarte-Thirouard AS, Bretagne JF (2007) Type 1 and 2 gastric carcinoid tumors: long-term follow-up of the efficacy of treatment with a slow-release somatostatin analogue. Eur J Gastroenterol Hepatol 19(11):1021–1025
Grozinsky-Glasberg S, Kaltsas G, Gur C, Gal E, Thomas D, Fichman S, Alexandraki K, Barak D, Glaser B, Shimon I, Gross DJ (2008) Long-acting somatostatin analogues are an effective treatment for type 1 gastric carcinoid tumours. European Journal of Endocrinology/European Federation of Endocrine Societies 159(4):475–482
Jianu CS, Fossmark R, Syversen U, Hauso O, Fykse V, Waldum HL (2011) Five-year follow-up of patients treated for 1 year with octreotide long-acting release for enterochromaffin-like cell carcinoids. Scand J Gastroenterol 46(4):456–463
Peracchi M, Gebbia C, Basilisco G, Quatrini M, Tarantino C, Vescarelli C, Massironi S, Conte D (2005) Plasma chromogranin A in patients with autoimmune chronic atrophic gastritis, enterochromaffin-like cell lesions and gastric carcinoids. European Journal of Endocrinology/European Federation of Endocrine Societies. 152(3):443–448
Rappel S, Altendorf-Hofmann A, Stolte M (1995) Prognosis of gastric carcinoid tumours. Digestion 56(6):455–462
Hori K, Fukui H, Imura J, Kojima T, Fujita M, Kawamata H, Chiba T, Fujimori T (2000) Benign gastric carcinoid tumor with hypergastrinemia followed up for 12 years. Gastric Cancer (Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association) 3(3):161–164
Ravizza D, Fiori G, Trovato C, Fazio N, Bonomo G, Luca F, Bodei L, Pelosi G, Tamayo D, Crosta C (2007) Long-term endoscopic and clinical follow-up of untreated type 1 gastric neuroendocrine tumours. Dig Liver Dis 39(6):537–543
Merola E, Sbrozzi-Vanni A, Panzuto F, D'Ambra G, Di Giulio E, Pilozzi E, Capurso G, Lahner E, Bordi C, Annibale B, Delle FG (2012) Type I gastric carcinoids: a prospective study on endoscopic management and recurrence rate. Neuroendocrinology 95(3):207–213
Uygun A, Kadayifci A, Polat Z, Yilmaz K, Gunal A, Demir H, Bagci S (2014) Long-term results of endoscopic resection for type I gastric neuroendocrine tumors. J Surg Oncol 109(2):71–74
Ozao-Choy J, Buch K, Strauchen JA, Warner RR, Divino CM (2010) Laparoscopic antrectomy for the treatment of type I gastric carcinoid tumors. J Surg Res 162(1):22–25
Basuroy R, Srirajaskanthan R, Prachalias A, Quaglia A, Ramage JK (2014) Review article: the investigation and management of gastric neuroendocrine tumours. Aliment Pharmacol Ther 39(10):1071–1084
Delle Fave G, O'Toole D, Sundin A, Taal B, Ferolla P, Ramage JK, Ferone D, Ito T, Weber W, Zheng-Pei Z, De Herder WW, Pascher A, Ruszniewski P (2016) ENETS consensus guidelines update for Gastroduodenal neuroendocrine neoplasms. Neuroendocrinology 103(2):119–124
Lahner E, Esposito G, Pilozzi E, Galli G, Corleto VD, Di Giulio E, Annibale B (2015) Gastric cancer in patients with type I gastric carcinoids. Gastric Cancer (Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association) 18(3):564–570
Vannella L, Lahner E, Annibale B (2012) Risk for gastric neoplasias in patients with chronic atrophic gastritis: a critical reappraisal. World J Gastroenterol 18(12):1279–1285
Grozinsky-Glasberg S, Thomas D, Strosberg JR, Pape UF, Felder S, Tsolakis AV, Alexandraki KI, Fraenkel M, Saiegh L, Reissman P, Kaltsas G, Gross DJ (2013) Metastatic type 1 gastric carcinoid: a real threat or just a myth? World J Gastroenterol 19(46):8687–8695
Fykse V, Sandvik AK, Qvigstad G, Falkmer SE, Syversen U, Waldum HL (2004) Treatment of ECL cell carcinoids with octreotide LAR. Scand J Gastroenterol 39(7):621–628
Massironi S, Zilli A, Fanetti I, Ciafardini C, Conte D, Peracchi M (2015) Intermittent treatment of recurrent type-1 gastric carcinoids with somatostatin analogues in patients with chronic autoimmune atrophic gastritis. Dig Liver Dis 47(11):978–983
Thomas D, Tsolakis AV, Grozinsky-Glasberg S, Fraenkel M, Alexandraki K, Sougioultzis S, Gross DJ, Kaltsas G (2013) Long-term follow-up of a large series of patients with type 1 gastric carcinoid tumors: data from a multicenter study. European Journal of Endocrinology/European Federation of Endocrine Societies 168(2):185–193
Oberg K (2012) Biotherapies for GEP-NETs. Best Pract Res Clin Gastroenterol 26(6):833–841
Moore AR, Boyce M, Steele IA, Campbell F, Varro A, Pritchard DM (2013) Netazepide, a gastrin receptor antagonist, normalises tumour biomarkers and causes regression of type 1 gastric neuroendocrine tumours in a nonrandomised trial of patients with chronic atrophic gastritis. PLoS One 8(10):e76462
Fossmark R, Sordal O, Jianu CS, Qvigstad G, Nordrum IS, Boyce M, Waldum HL (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(11–12):1067–1075
Kantsevoy SV, Adler DG, Conway JD, Diehl DL, Farraye FA, Kwon R, Mamula P, Rodriguez S, Shah RJ, Wong Kee Song LM, Tierney WM (2008) Endoscopic mucosal resection and endoscopic submucosal dissection. Gastrointest Endosc 68(1):11–18
Yamamoto H, Kawata H, Sunada K, Sasaki A, Nakazawa K, Miyata T, Sekine Y, Yano T, Satoh K, Ido K, Sugano K (2003) Successful en-bloc resection of large superficial tumors in the stomach and colon using sodium hyaluronate and small-caliber-tip transparent hood. Endoscopy 35(8):690–694
Ono H, Kondo H, Gotoda T, Shirao K, Yamaguchi H, Saito D, Hosokawa K, Shimoda T, Yoshida S (2001) Endoscopic mucosal resection for treatment of early gastric cancer. Gut 48(2):225–229
Rosch T, Sarbia M, Schumacher B, Deinert K, Frimberger E, Toermer T, Stolte M, Neuhaus H (2004) Attempted endoscopic en bloc resection of mucosal and submucosal tumors using insulated-tip knives: a pilot series. Endoscopy 36(9):788–801
Gotoda T, Kondo H, Ono H, Saito Y, Yamaguchi H, Saito D, Yokota T (1999) A new endoscopic mucosal resection procedure using an insulation-tipped electrosurgical knife for rectal flat lesions: report of two cases. Gastrointest Endosc 50(4):560–563
Kim HH, Kim GH, Kim JH, Choi MG, Song GA, Kim SE (2014) The efficacy of endoscopic submucosal dissection of type I gastric carcinoid tumors compared with conventional endoscopic mucosal resection. Gastroenterol Res Pract 2014:253860
Tomassetti P, Migliori M, Caletti GC, Fusaroli P, Corinaldesi R, Gullo L (2000) Treatment of type II gastric carcinoid tumors with somatostatin analogues. N Engl J Med 343(8):551–554
Meko JB, Norton JA (1995) Management of patients with Zollinger-Ellison syndrome. Annu Rev Med 46:395–411
Yao JC, Fazio N, Singh S, Buzzoni R, Carnaghi C, Wolin E, Tomasek J, Raderer M, Lahner H, Voi M, Pacaud LB, Rouyrre N, Sachs C, Valle JW, Delle Fave G, Van Cutsem E, Tesselaar M, Shimada Y, Oh DY, Strosberg J, Kulke MH, Pavel ME (2016) Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet 387(10022):968–977
Sorbye H, Welin S, Langer SW, Vestermark LW, Holt N, Osterlund P, Dueland S, Hofsli E, Guren MG, Ohrling K, Birkemeyer E, Thiis-Evensen E, Biagini M, Gronbaek H, Soveri LM, Olsen IH, Federspiel B, Assmus J, Janson ET, Knigge U (2013) Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study. Annals of Oncology (Official Journal of the European Society for Medical Oncology/ESMO) 24(1):152–160
Nikou GC, Toubanakis C, Moulakakis KG, Pavlatos S, Kosmidis C, Mallas E, Safioleas P, Sakorafas GH, Safioleas MC (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 (London, England) 9(3):248–253
Pipeleers-Marichal M, Donow C, Heitz PU, Kloppel G (1993) Pathologic aspects of gastrinomas in patients with Zollinger-Ellison syndrome with and without multiple endocrine neoplasia type I. World J Surg 17(4):481–488
Donow C, Pipeleers-Marichal M, Schroder S, Stamm B, Heitz PU, Kloppel G (1991) Surgical pathology of gastrinoma. Site, size, multicentricity, association with multiple endocrine neoplasia type 1, and malignancy. Cancer 68(6):1329–1334
Karagiannis S, Eshagzaiy K, Duecker C, Feyerabend B, Mozdzanowski E, Faiss S (2009) Endoscopic resection with the cap technique of a carcinoid tumor in the duodenal bulb. Endoscopy 41(Suppl 2):E288–E289
Dalenback J, Havel G (2004) Local endoscopic removal of duodenal carcinoid tumors. Endoscopy 36(7):651–655
Tai WP, Yue H (2009) Endoscopic mucosa resection of a duodenum carcinoid tumor of 1.2 cm diameter: a case report. Med Oncol (Northwood, London, England) 26(3):319–321
Honda T, Yamamoto H, Osawa H, Yoshizawa M, Nakano H, Sunada K, Hanatsuka K, Sugano K (2009) Endoscopic submucosal dissection for superficial duodenal neoplasms. Digestive Endoscopy (Official Journal of the Japan Gastroenterological Endoscopy Society) 21(4):270–274
Matsumoto S, Miyatani H, Yoshida Y, Nokubi M (2011) Duodenal carcinoid tumors: 5 cases treated by endoscopic submucosal dissection. Gastrointest Endosc 74(5):1152–1156
De Palma GD, Masone S, Siciliano S, Maione F, Falleti J, Mansueto G, De Rosa G, Persico G (2010) Endocrine carcinoma of the major papilla: report of two cases and review of the literature. Surg Oncol 19(4):235–242
Crocetti E, Paci E (2003) Malignant carcinoids in the USA, SEER 1992-1999. An epidemiological study with 6830 cases. European Journal of Cancer Prevention (The Official Journal of the European Cancer Prevention Organisation (ECP)) 12(3):191–194
Anthony LB, Strosberg JR, Klimstra DS, Maples WJ, O'Dorisio TM, Warner RR, Wiseman GA, Benson AB 3rd, Pommier RF (2010) The NANETS consensus guidelines for the diagnosis and management of gastrointestinal neuroendocrine tumors (nets): well-differentiated nets of the distal colon and rectum. Pancreas 39(6):767–774
Jetmore AB, Ray JE, Gathright JB Jr, McMullen KM, Hicks TC, Timmcke AE (1992) Rectal carcinoids: the most frequent carcinoid tumor. Dis Colon Rectum 35(8):717–725
Soga J (1997) Carcinoids of the rectum: an evaluation of 1271 reported cases. Surg Today 27(2):112–119
Son HJ, Sohn DK, Hong CW, Han KS, Kim BC, Park JW, Choi HS, Chang HJ, Oh JH (2013) Factors associated with complete local excision of small rectal carcinoid tumor. Int J Color Dis 28(1):57–61
Park CH, Cheon JH, Kim JO, Shin JE, Jang BI, Shin SJ, Jeen YT, Lee SH, Ji JS, Han DS, Jung SA, Park DI, Baek IH, Kim SH, Chang DK (2011) Criteria for decision making after endoscopic resection of well-differentiated rectal carcinoids with regard to potential lymphatic spread. Endoscopy 43(9):790–795
Iishi H, Tatsuta M, Yano H, Narahara H, Iseki K, Ishiguro S (1996) More effective endoscopic resection with a two-channel colonoscope for carcinoid tumors of the rectum. Dis Colon Rectum 39(12):1438–1439
Boskoski I, Volkanovska A, Tringali A, Bove V, Familiari P, Perri V, Costamagna G (2013) Endoscopic resection for gastrointestinal neuroendocrine tumors. Expert Rev Gastroenterol Hepatol 7(6):559–569
Zhao ZF, Zhang N, Ma SR, Yang Z, Han X, Zhao YF, Gao F, Gong ZJ, Yang L (2012) A comparative study on endoscopy treatment in rectal carcinoid tumors. Surg Laparosc Endosc Percutan Tech 22(3):260–263
Kim KM, Eo SJ, Shim SG, Choi JH, Min BH, Lee JH, Chang DK, Kim YH, Rhee PL, Kim JJ, Rhee JC, Kim JY (2013) Treatment outcomes according to endoscopic treatment modalities for rectal carcinoid tumors. Clin Res Hepatol Gastroenterol 37(3):275–282
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Campana, D. et al. (2018). Therapy for Locoregional Disease: Stomach/Duodenum, Colon/Rectum. In: Colao, A., Faggiano, A., de Herder, W. (eds) Neuroendocrine Tumors in Real Life. Springer, Cham. https://doi.org/10.1007/978-3-319-59024-0_16
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