CME Topic

Carcinoid Tumors of the Gastrointestinal Tract

Authors: Vishal Ghevariya MD, Anju Malieckal MD, Nehal Ghevariya MD, Mohammed Mazumder MD, Sury Anand MD

Abstract

Abstract:The gastrointestinal tract is the largest neuroendocrine system in the body. Carcinoid tumors are amine precursor uptake decarboxylase (APUD) omas that arise from enterochromaffin cells throughout the gut. These tumors secrete discrete bioactive substances producing characteristic immunohistochemical patterns. Most tumors are asymptomatic and detected at late stages. Hepatic metastases are commonly responsible for carcinoid syndrome. The small bowel is the most common location of carcinoids. Computed tomography scan and magnetic resonance imaging are useful in the detection of these tumors. The measurement of bioactive amines is the initial diagnostic test. Various treatment options, including somatostatin analogs, interferon, chemotherapy, surgery, hepatic artery chemoembolization, and surgery have emerged in the past two decades. However, the incidence and prevalence of carcinoid tumors has increased, while mean survival time has not changed significantly. The lack of standardized classification, federal support, and an incomplete understanding of the complications of this disease are some of the impediments to progress in treatment.

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References

References1. Modlin IM, Kidd M, Latich I, et al. Current status of gastrointestinal carcinoids. Gastroenterology 2005;128:1717–1751.ModlinIM]]KiddM]]LatichI&etal;Current status of gastrointestinal carcinoids.Gastroenterology20051281717-17512. Williams ED, Sandler M. The classification of carcinoid tumours. Lancet 1963;1:238–239.WilliamsED]]SandlerMThe classification of carcinoid tumours.Lancet19631238-2393. Kytölä S, Nord B, Elder EE, et al. Alterations of the SDHD gene locus in midgut carcinoids, Merkel cell carcinomas, pheochromocytomas, and abdominal paragangliomas. Genes Chromosomes Cancer 2002;34:325–332.KytöläS]]NordB]]ElderEE&etal;Alterations of the SDHD gene locus in midgut carcinoids, Merkel cell carcinomas, pheochromocytomas, and abdominal paragangliomas.Genes Chromosomes Cancer200234325-3324. Rindi G, Klöppel G, Couvelard A, et al. TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch 2007;451:757–762.RindiG]]KlöppelG]]CouvelardA&etal;TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system.Virchows Arch2007451757-7625. Landry CS, Brock G, Scoggins CR, et al. A proposed staging system for small bowel carcinoid tumors based on an analysis of 6,380 patients. Am J Surg 2008;196:896–903.LandryCS]]BrockG]]ScogginsCR&etal;A proposed staging system for small bowel carcinoid tumors based on an analysis of 6,380 patients.Am J Surg2008196896-9036. Yao J, Hassan CM, Phan A, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in United States. J Clin Oncol 2008;26:3063–3072.YaoJ]]HassanCM]]PhanA&etal;One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in United States.J Clin Oncol2008263063-30727. Maggard MA, O’Connell JB. Updated population-based review of carcinoid tumors. Ann Surg 2004;240:117–122.MaggardMA]]O’ConnellJBUpdated population-based review of carcinoid tumors.Ann Surg2004240117-1228. Toumpanakis CG, Caplin ME. Molecular genetics of gastroenteropancreatic neuroendocrine tumors. Am J Gastroenterol 2008;103:729–732.ToumpanakisCG]]CaplinMEMolecular genetics of gastroenteropancreatic neuroendocrine tumors.Am J Gastroenterol2008103729-7329. Maton PN. The carcinoid syndrome. JAMA 1988;260:1602–1605.MatonPNThe carcinoid syndrome.JAMA19882601602-160510. Törnebrandt K, Nobin A, Ericsson M, et al. Circulation, respiration and serotonin levels in carcinoid patients during neurolept anaesthesia. Anaesthesia 1983;38:957–967.TörnebrandtK]]NobinA]]EricssonM&etal;Circulation, respiration and serotonin levels in carcinoid patients during neurolept anaesthesia.Anaesthesia198338957-96711. Marsh HM, Martin JK Jr, Kvols LK, et al. Carcinoid crisis during anesthesia: successful treatment with a somatostatin analogue. Anesthesiology 1987;66:89–91.MarshHM]]MartinJKJr]]KvolsLK&etal;Carcinoid crisis during anesthesia: successful treatment with a somatostatin analogue.Anesthesiology19876689-9112. Strobe L, D’Hondt E, Ramboer C, et al. Ileal carcinoid tumors and intestinal ischemia. Hepatogastroenterology 1994;41:499–502.StrobeL]]D’HondtE]]RamboerC&etal;Ileal carcinoid tumors and intestinal ischemia.Hepatogastroenterology199441499-50213. Eckhauser FE, Argenta LC, Strodel WE, et al. Mesenteric angiopathy, intestinal gangrene, and midgut carcinoids. Surgery 1981;90:720–728.EckhauserFE]]ArgentaLC]]StrodelWE&etal;Mesenteric angiopathy, intestinal gangrene, and midgut carcinoids.Surgery198190720-72814. Bivens CH, Marecek RL, Feldman JM. Peyronie’s disease—a presenting complaint of the carcinoid syndrome. N Engl J Med 1973;289:844–845.BivensCH]]MarecekRL]]FeldmanJMPeyronie’s disease—a presenting complaint of the carcinoid syndrome.N Engl J Med1973289844-84515. Kidd M, Hinoue T, Eick G, et al. Global expression analysis of ECL cells in Mastomys natalensis gastric mucosa identifies alterations in the AP-1 pathway induced by gastrin-mediated transformation. Physiol Genomics 2004;20:131–142.KiddM]]HinoueT]]EickG&etal;Global expression analysis of ECL cells in Mastomys natalensis gastric mucosa identifies alterations in the AP-1 pathway induced by gastrin-mediated transformation.Physiol Genomics200420131-14216. Modlin IM, Shapiro MD, Kidd M. Carcinoid tumor and fibrosis: a relation with little explanation. Am J Gastroenterol 2004;99:1–13.ModlinIM]]ShapiroMD]]KiddMCarcinoid tumor and fibrosis: a relation with little explanation.Am J Gastroenterol2004991-1317. Ohrvall U, Eriksson B, Juhlin C, et al. Method for dissection of mesenteric metastases in mid-gut carcinoid tumors. World J Surg 2000;24:1402–1408.OhrvallU]]ErikssonB]]JuhlinC&etal;Method for dissection of mesenteric metastases in mid-gut carcinoid tumors.World J Surg2000241402-140818. Swain CP, Tavill AS, Neale G. Studies of tryptophan and albumin metabolism in a patient with carcinoid syndrome, pellagra, and hypoproteinemia. Gastroenterology 1976;71:484–489.SwainCP]]TavillAS]]NealeGStudies of tryptophan and albumin metabolism in a patient with carcinoid syndrome, pellagra, and hypoproteinemia.Gastroenterology197671484-48919. Wareing TH, Sawyers JL. Carcinoids and the carcinoid syndrome. Am J Surg 1983;145:769–772.WareingTH]]SawyersJLCarcinoids and the carcinoid syndrome.Am J Surg1983145769-77220. Morin LJ, Zuerner RT. Retroperitoneal fibrosis and carcinoid tumor. JAMA 1971;216:1647–1648.MorinLJ]]ZuernerRTRetroperitoneal fibrosis and carcinoid tumor.JAMA19712161647-164821. Melmon KL, Sjoerdsma A, Mason DT. Distinctive clinical and therapeutic aspects of the syndrome associated with bronchial carcinoid tumors. Am J Med 1965;39:568–581.MelmonKL]]SjoerdsmaA]]MasonDTDistinctive clinical and therapeutic aspects of the syndrome associated with bronchial carcinoid tumors.Am J Med196539568-58122. Feldman JM. Urinary serotonin in the diagnosis of carcinoid tumors. Clin Chem 1986;32:840–844.FeldmanJMUrinary serotonin in the diagnosis of carcinoid tumors.Clin Chem198632840-84423. Tormey WP, Fitzgerald RJ. The clinical and laboratory correlates of an increased urinary 5-hydroxyindoleacetic acid. Postgrad Med J 1995;71:542–545.TormeyWP]]FitzgeraldRJThe clinical and laboratory correlates of an increased urinary 5-hydroxyindoleacetic acid.Postgrad Med J199571542-54524. Janson ET, Holmberg L, Stridsberg M, et al. Carcinoid tumors: analysis of prognostic factors and survival in 301 patients from a referral center. Ann Oncol 1997;8:685–690.JansonET]]HolmbergL]]StridsbergM&etal;Carcinoid tumors: analysis of prognostic factors and survival in 301 patients from a referral center.Ann Oncol19978685-69025. Eriksson B, Oberg K. Peptide hormones as tumor markers in neuroendocrine gastrointestinal tumors. Acta Oncol 1991;30:477–483.ErikssonB]]ObergKPeptide hormones as tumor markers in neuroendocrine gastrointestinal tumors.Acta Oncol199130477-48326. Krenning EP, Kooij PP, Bakker WH, et al. Radiotherapy with a radiolabeled somatostatin analogue, [111In/DTPA-D-Phe1]-octreotide. A case history. Ann N Y Acad Sci 1994;733:496–506.KrenningEP]]KooijPP]]BakkerWH&etal;Radiotherapy with a radiolabeled somatostatin analogue, [111In/DTPA-D-Phe1]-octreotide. A case history.Ann N Y Acad Sci1994733496-50627. Lebtahi R, Le Cloirec J, Houzard C, et al. Detection of neuroendocrine tumors:99mTc-P829 scintigraphy compared with 111In-pentetreotide scintigraphy. J Nucl Med 2002;43:889–895.LebtahiR]]Le CloirecJ]]HouzardC&etal;Detection of neuroendocrine tumors:99mTc-P829 scintigraphy compared with 111In-pentetreotide scintigraphy.J Nucl Med200243889-89528. Zuetenhorst JM, Hoefnageli CA, Boot H, et al. Evaluation of (111)In-pentetreotide, (131)I-MIBG and bone scintigraphy in the detection and clinical management of bone metastases in carcinoid disease. Nucl med Commun 2002;23:735–741.ZuetenhorstJM]]HoefnageliCA]]BootH&etal;Evaluation of (111)In-pentetreotide, (131)I-MIBG and bone scintigraphy in the detection and clinical management of bone metastases in carcinoid disease.Nucl med Commun200223735-74129. Hoegerle S, Altehoefer C, Ghanem N, et al. Whole-body 18Fdopa PET for detection of gastrointestinal carcinoid tumors. Radiology 2001;220:373–380.HoegerleS]]AltehoeferC]]GhanemN&etal;Whole-body 18Fdopa PET for detection of gastrointestinal carcinoid tumors.Radiology2001220373-38030. Modlin IM, Tang LH. Approaches to the diagnosis of gut neuroendocrine tumors: the last word (today). Gastroenterology 1997;112:583–590.ModlinIM]]TangLHApproaches to the diagnosis of gut neuroendocrine tumors: the last word (today).Gastroenterology1997112583-59031. Hellman P, Lundström T, Ohrvall U, et al. Effect of surgery on the outcome of midgut carcinoid disease with lymph node and liver metastases. World J Surg 2002;26:991–997.HellmanP]]LundströmT]]OhrvallU&etal;Effect of surgery on the outcome of midgut carcinoid disease with lymph node and liver metastases.World J Surg200226991-99732. Zimmer T, Ziegler K, Liehr RM, et al. Endosonography of neuroendocrine tumors of the stomach, duodenum, and pancreas. Ann N Y Acad Sci 1994;733:425–436.ZimmerT]]ZieglerK]]LiehrRM&etal;Endosonography of neuroendocrine tumors of the stomach, duodenum, and pancreas.Ann N Y Acad Sci1994733425-43633. Coates SW Jr, DeMarco DC. Metastatic carcinoid tumor discovered by capsule endoscopy and not detected by esophagogastroduodenoscopy. Dig Dis Sci 2004;49:639–641.CoatesSWJr]]DeMarcoDCMetastatic carcinoid tumor discovered by capsule endoscopy and not detected by esophagogastroduodenoscopy.Dig Dis Sci200449639-64134. Burke AP, Thomas RM, Elsayed AM, et al. Carcinoids of the jejunum and ileum: an immunohistochemical and clinicopathologic study of 167 cases. Cancer 1997;79:1086–1093.BurkeAP]]ThomasRM]]ElsayedAM&etal;Carcinoids of the jejunum and ileum: an immunohistochemical and clinicopathologic study of 167 cases.Cancer1997791086-109335. Nies C, Zielke A. Hasse C, et al. Carcinoid tumors of Meckel’s diverticula. Report of two cases and review of the literature. Dis colon Rectum 1992;35:589–596.NiesC]]ZielkeA]]HasseC&etal;Carcinoid tumors of Meckel’s diverticula. Report of two cases and review of the literature.Dis colon Rectum199235589-59636. Mani S, Modlin IM, Ballantyne G, et al. Carcinoids of the rectum. J Am Coll Surg 1994;179:231–248.ManiS]]ModlinIM]]BallantyneG&etal;Carcinoids of the rectum.J Am Coll Surg1994179231-24837. Spread C, Berkel H, Jewell L, et al. Colon carcinoid tumors. A population-based study. Dis Colon Rectum 1994;37:482–491.SpreadC]]BerkelH]]JewellL&etal;Colon carcinoid tumors. A population-based study.Dis Colon Rectum199437482-49138. Ready AR, Soul JO, Newman J, et al. Malignant carcinoid tumour of the oesophagus. Thorax 1989;44:594–596.ReadyAR]]SoulJO]]NewmanJ&etal;Malignant carcinoid tumour of the oesophagus.Thorax198944594-59639. Lindberg GM, Molberg KH, Vuitch MF, et al. Atypical carcinoid of the esophagus: a case reoport and review of the literature. Cancer 1997;79:1476–1481.LindbergGM]]MolbergKH]]VuitchMF&etal;Atypical carcinoid of the esophagus: a case reoport and review of the literature.Cancer1997791476-148140. Mehta DC, Warner RR, Parnes I, et al. An 18-year follow-up of primary hepatic carcinoid with carcinoid syndrome. J Clin Gastroenterol 1996;23:60–62.MehtaDC]]WarnerRR]]ParnesI&etal;An 18-year follow-up of primary hepatic carcinoid with carcinoid syndrome.J Clin Gastroenterol19962360-6241. Chamberlain RS, Blumgart LH. Carcinoid tumors of the extrahepatic bile duct. A rare cause of malignant biliary obstruction. Cancer 1999;86:1959–1965.ChamberlainRS]]BlumgartLHCarcinoid tumors of the extrahepatic bile duct. A rare cause of malignant biliary obstruction.Cancer1999861959-196542. Billimoria KY, Bentrem DJ, Wayne JD, et al. Small bowel cancer in the United States: changes in epidemiology, treatment, and survival over the last 20 years. Ann Surg 2009;249:63–71.BillimoriaKY]]BentremDJ]]WayneJD&etal;Small bowel cancer in the United States: changes in epidemiology, treatment, and survival over the last 20 years.Ann Surg200924963-7143. Yamamoto C, Aoyagi K, Suekane H, et al. Carcinoid tumors of the duodenum: report of three cases treated by endoscopic resection. Endoscopy 1997;29:218–221.YamamotoC]]AoyagiK]]SuekaneH&etal;Carcinoid tumors of the duodenum: report of three cases treated by endoscopic resection.Endoscopy199729218-22144. Stinner B, Kisker O, Zielke A, et al. Surgical management for carcinoid tumors of small bowel, appendix, colon, and rectum. World J Surg 1996;20:183–188.StinnerB]]KiskerO]]ZielkeA&etal;Surgical management for carcinoid tumors of small bowel, appendix, colon, and rectum.World J Surg199620183-18845. Söreide JA, van Heerden JA, Thompson GB, et al. Gastrointestinal carcinoid tumors: long-term prognosis for surgically treated patients. World J Surg 2000;24:1431–1436.SöreideJA]]van HeerdenJA]]ThompsonGB&etal;Gastrointestinal carcinoid tumors: long-term prognosis for surgically treated patients.World J Surg2000241431-143646. Moertel CG. Treatment of the carcinoid tumor and the malignant carcinoid syndrome. J Clin Oncol 1983;1:727–740.MoertelCGTreatment of the carcinoid tumor and the malignant carcinoid syndrome.J Clin Oncol19831727-74047. Moertel CG. Karnofsky memorial lecture. An odyssey in the land of small tumors. J Clin Oncol 1987;5:1502–1522.MoertelCGKarnofsky memorial lecture. An odyssey in the land of small tumors.J Clin Oncol198751502-152248. Kothari T, Mangla JC. Malignant tumors associated with carcinoid tumors of the gastrointestinal tract. J Clin Gastroenterol 1981;3:43–46.KothariT]]ManglaJCMalignant tumors associated with carcinoid tumors of the gastrointestinal tract.J Clin Gastroenterol1981343-4649. Sarmiento JM, Heywood G, Rubin J, et al. Surgical treatment of neuroendocrine metastases to the liver: a plea for resection to increase survival. J Am Coll Surg 2003;197:29–37.SarmientoJM]]HeywoodG]]RubinJ&etal;Surgical treatment of neuroendocrine metastases to the liver: a plea for resection to increase survival.J Am Coll Surg200319729-3750. Christante D, Pommier S, Givi B, et al. Hepatic artery chemoinfusion with chemoembolization for neuroendocrine cancer with progressive hepatic metastases despite octreotide therapy. Surgery 2008;144:885–893.ChristanteD]]PommierS]]GiviB&etal;Hepatic artery chemoinfusion with chemoembolization for neuroendocrine cancer with progressive hepatic metastases despite octreotide therapy.Surgery2008144885-89351. Schnirer II, Yao JC, Ajani JA. Carcinoid—a comprehensive review. Acta Oncol 2003;42:672–692.SchnirerII]]YaoJC]]AjaniJACarcinoid—a comprehensive review.Acta Oncol200342672-69252. Modlin IM, Kidd M, Drozdov I, et al. Pharmacothearpy of neuroendocrine cancers. Expert Opin Pharmacother 2008;9:2617–2626.ModlinIM]]KiddM]]DrozdovI&etal;Pharmacothearpy of neuroendocrine cancers.Expert Opin Pharmacother200892617-262653. Moertel CG, Martin JK, O’Connell MJ, et al. Phase II trials in the malignant carcinoid tumor and the carcinoid syndrome. Proc Am Soc Clin Oncol 1982;2:169.MoertelCG]]MartinJK]]O’ConnellMJ&etal;Phase II trials in the malignant carcinoid tumor and the carcinoid syndrome.Proc Am Soc Clin Oncol1982216954. Kulke MH, Kim H, Clark JW, et al. A phase II trial of gemcitabine for metastatic neuroendocrine tumors. Cancer 2004;101:934–939.KulkeMH]]KimH]]ClarkJW&etal;A phase II trial of gemcitabine for metastatic neuroendocrine tumors.Cancer2004101934-93955. Oberg K, Norheim I, Lundqvist G, et al. Cytotoxic treatment in patients with malignant carcinoid tumors. Response to streptozocin—alone or in combination with 5-FU. Acta Oncol 1987;26:429–432.ObergK]]NorheimI]]LundqvistG&etal;Cytotoxic treatment in patients with malignant carcinoid tumors. Response to streptozocin—alone or in combination with 5-FU.Acta Oncol198726429-43256. Oberg K, Kvols L, Caplin M, et al. Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. Ann Oncol 2004;15:966–973.ObergK]]KvolsL]]CaplinM&etal;Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system.Ann Oncol200415966-97357. Janson ET, Oberg K. Long-term management of the carcinoid syndrome: treatment with octreotide alone and in combination with alpha-interferon. Acta Oncol 1993;32:225–229.JansonET]]ObergKLong-term management of the carcinoid syndrome: treatment with octreotide alone and in combination with alpha-interferon.Acta Oncol199332225-22958. Otte A, Herrmann R. Heppeler A, et al. Yttrium-90 DOTATOC: first clinical results. Eur J Nucl Med 1999;26:1439–1447.OtteA]]HerrmannR]]HeppelerA&etal;Yttrium-90 DOTATOC: first clinical results.Eur J Nucl Med1999261439-144759. Virgolini I, Britton K, Buscombe J, et al. In- and Y-DOTA-lanreotide: results and implications of the MAURITIUS trial. Semin Nucl Med 2002;32:148–155.VirgoliniI]]BrittonK]]BuscombeJ&etal;In- and Y-DOTA-lanreotide: results and implications of the MAURITIUS trial.Semin Nucl Med200232148-15560. Horsch D, Prasad V, Baum P. Longterm outcome of peptide receptor radionuclide therapy (PRRT) in 454 patients with progressive neuroendocrine tumors using yttrium-90 and lutetium-177 labelled somatostatin receptor targeting peptides. J Clin Oncol 2008;26(suppl) (abstract 4517).61. Kwekkeboom DJ, de Herder WW, Kam BL, et al. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA0, Tyr3] octreotate: toxicity, efficacy and survival. J Clin Oncol 2008;26:2124–2130.KwekkeboomDJ]]de HerderWW]]KamBL&etal;Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA0, Tyr3] octreotate: toxicity, efficacy and survival.J Clin Oncol2008262124-213062. Le Treut YP, Delpero JR, Dousset B, et al. Results of liver transplantation in the treatment of metastatic neuroendocrine tumors. A 31-case French multicentric report. Ann Surg 1997;225:355–364.Le TreutYP]]DelperoJR]]DoussetB&etal;Results of liver transplantation in the treatment of metastatic neuroendocrine tumors. A 31-case French multicentric report.Ann Surg1997225355-36463. Sutcliffe R, Maguire D, Ramage J, et al. Management of neuroendocrine liver metastases. Am J Surg 2004;187:39–46.SutcliffeR]]MaguireD]]RamageJ&etal;Management of neuroendocrine liver metastases.Am J Surg200418739-4664. Yao J, Phan T, Chang D, et al. Phase II study of RAD001 (everolimus) and depot octreotide (Sandostatin LAR) in patients with advanced low-grade neuroendocrine carcinoma (abstract). J Clin Oncol 2007;25:198s.YaoJ]]PhanT]]ChangD&etal;Phase II study of RAD001 (everolimus) and depot octreotide (Sandostatin LAR) in patients with advanced low-grade neuroendocrine carcinoma (abstract).J Clin Oncol200725198s65. Pinchot SN, Holen K, Sippel RS, et al. Carcinoid tumors. Oncologist 2008;13:1255–1269.PinchotSN]]HolenK]]SippelRS&etal;Carcinoid tumors.Oncologist2008131255-126966. Modlin IM, Moss SF, Chung DC, et al. Priorities for improving the management of gastroenteropancreatic neuroendocrine tumors. J Natl Cancer Inst 2008;100:1282–1289.ModlinIM]]MossSF]]ChungDC&etal;Priorities for improving the management of gastroenteropancreatic neuroendocrine tumors.J Natl Cancer Inst20081001282-1289