Abstract
Presence of liver metastases in neuroendocrine tumors is a major factor altering both quality of life and prognosis. Surgery is recognized as the sole curative treatment. When it is not possible, radiological directed therapies are crucial, particularly in liver metastases from the small bowel. Thermal ablative therapies as radiofrequency ablation and microwave are alternative treatments alone or in combination with surgery. Hepatic artery embolization or chemoembolization, as radioembolization, has been shown to have good clinical, biochemical, and morphological responses when liver burden does not permit ablative therapies. However, technical issues are multiple and there is no randomized study to compare their efficacy. The choice of management depends on liver burden and metastases pattern, but also on origin of the primary tumor, tumor differentiation, and tumor proliferative activity. These patients should benefit of a multidisciplinary management to limit morbidity and mortality.
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Frilling A, Sotiropoulos GC, Li J, Kornasiewicz O, Plockinger U (2010) Multimodal management of neuroendocrine liver metastases. HPB (Oxford) 12(6):361–379. doi:10.1111/j.1477-2574.2010.00175.x
Auernhammer CJ, Goke B (2011) Therapeutic strategies for advanced neuroendocrine carcinomas of jejunum/ileum and pancreatic origin. Gut 60(7):1009–1021. doi:10.1136/gut.2009.204453
Godwin JD 2nd (1975) Carcinoid tumors. An analysis of 2,837 cases. Cancer 36(2):560–569
Zeitels J, Naunheim K, Kaplan EL, Straus F 2nd (1982) Carcinoid tumors: a 37-year experience. Arch Surg 117(5):732–737
McDermott EW, Guduric B, Brennan MF (1994) Prognostic variables in patients with gastrointestinal carcinoid tumours. Br J Surg 81(7):1007–1009
Kianmanesh R, Sauvanet A, Hentic O, Couvelard A, Levy P, Vilgrain V, Ruszniewski P, Belghiti J (2008) Two-step surgery for synchronous bilobar liver metastases from digestive endocrine tumors: a safe approach for radical resection. Ann Surg 247(4):659–665. doi:10.1097/SLA.0b013e31816a7061
Elias D, Lasser P, Ducreux M, Duvillard P, Ouellet JF, Dromain C, Schlumberger M, Pocard M, Boige V, Miquel C, Baudin E (2003) Liver resection (and associated extrahepatic resections) for metastatic well-differentiated endocrine tumors: a 15-year single center prospective study. Surgery 133(4):375–382. doi:10.1067/msy.2003.114
Chamberlain RS, Canes D, Brown KT, Saltz L, Jarnagin W, Fong Y, Blumgart LH (2000) Hepatic neuroendocrine metastases: does intervention alter outcomes? J Am Coll Surg 190(4):432–445
Dromain C, de Baere T, Lumbroso J, Caillet H, Laplanche A, Boige V, Ducreux M, Duvillard P, Elias D, Schlumberger M, Sigal R, Baudin E (2005) Detection of liver metastases from endocrine tumors: a prospective comparison of somatostatin receptor scintigraphy, computed tomography, and magnetic resonance imaging. J Clin Oncol 23(1):70–78. doi:10.1200/JCO.2005.01.013
Elias D, Lefevre JH, Duvillard P, Goere D, Dromain C, Dumont F, Baudin E (2010) Hepatic metastases from neuroendocrine tumors with a “thin slice” pathological examination: they are many more than you think. Ann Surg 251(2):307–310. doi:10.1097/SLA.0b013e3181bdf8cf
Marrache F, Vullierme MP, Roy C, El Assoued Y, Couvelard A, O’Toole D, Mitry E, Hentic O, Hammel P, Levy P, Ravaud P, Rougier P, Ruszniewski P (2007) Arterial phase enhancement and body mass index are predictors of response to chemoembolisation for liver metastases of endocrine tumours. Br J Cancer 96(1):49–55. doi:10.1038/sj.bjc.6603526
Elias D, Goere D, Leroux G, Dromain C, Leboulleux S, de Baere T, Ducreux M, Baudin E (2009) Combined liver surgery and RFA for patients with gastroenteropancreatic endocrine tumors presenting with more than 15 metastases to the liver. Eur J Surg Oncol 35(10):1092–1097. doi:10.1016/j.ejso.2009.02.017
Akyildiz HY, Mitchell J, Milas M, Siperstein A, Berber E (2010) Laparoscopic radiofrequency thermal ablation of neuroendocrine hepatic metastases: long-term follow-up. Surgery 148(6):1288–1293. doi:10.1016/j.surg.2010.09.014, discussion 1293
Mulier S, Ni Y, Jamart J, Ruers T, Marchal G, Michel L (2005) Local recurrence after hepatic radiofrequency coagulation: multivariate meta-analysis and review of contributing factors. Ann Surg 242(2):158–171
Berber E, Siperstein AE (2007) Perioperative outcome after laparoscopic radiofrequency ablation of liver tumors: an analysis of 521 cases. Surg Endosc 21(4):613–618. doi:10.1007/s00464-006-9139-y
Mazzaglia PJ, Berber E, Milas M, Siperstein AE (2007) Laparoscopic radiofrequency ablation of neuroendocrine liver metastases: a 10-year experience evaluating predictors of survival. Surgery 142(1):10–19. doi:10.1016/j.surg.2007.01.036
Martin RC, Scoggins CR, McMasters KM (2010) Safety and efficacy of microwave ablation of hepatic tumors: a prospective review of a 5-year experience. Ann Surg Oncol 17(1):171–178. doi:10.1245/s10434-009-0686-z
Shapiro RS, Shafir M, Sung M, Warner R, Glajchen N (1998) Cryotherapy of metastatic carcinoid tumors. Abdom Imaging 23(3):314–317
Bilchik AJ, Sarantou T, Foshag LJ, Giuliano AE, Ramming KP (1997) Cryosurgical palliation of metastatic neuroendocrine tumors resistant to conventional therapy. Surgery 122(6):1040–1047, discussion 1047–1048
Seifert JK, Cozzi PJ, Morris DL (1998) Cryotherapy for neuroendocrine liver metastases. Semin Surg Oncol 14(2):175–183. doi:10.1002/(SICI)1098-2388(199803)14:2<175::AID-SSU10>3.0.CO;2-2
Kennedy AS, Dezarn WA, McNeillie P, Coldwell D, Nutting C, Carter D, Murthy R, Rose S, Warner RR, Liu D, Palmedo H, Overton C, Jones B, Salem R (2008) Radioembolization for unresectable neuroendocrine hepatic metastases using resin 90Y-microspheres: early results in 148 patients. Am J Clin Oncol 31(3):271–279. doi:10.1097/COC.0b013e31815e4557
King J, Quinn R, Glenn DM, Janssen J, Tong D, Liaw W, Morris DL (2008) Radioembolization with selective internal radiation microspheres for neuroendocrine liver metastases. Cancer 113(5):921–929. doi:10.1002/cncr.23685
Rhee TK, Lewandowski RJ, Liu DM, Mulcahy MF, Takahashi G, Hansen PD, Benson AB 3rd, Kennedy AS, Omary RA, Salem R (2008) 90Y Radioembolization for metastatic neuroendocrine liver tumors: preliminary results from a multi-institutional experience. Ann Surg 247(6):1029–1035. doi:10.1097/SLA.0b013e3181728a45
Cao CQ, Yan TD, Bester L, Liauw W, Morris DL (2010) Radioembolization with yttrium microspheres for neuroendocrine tumour liver metastases. Br J Surg 97(4):537–543. doi:10.1002/bjs.6931
Kalinowski M, Dressler M, Konig A, El-Sheik M, Rinke A, Hoffken H, Gress TM, Arnold R, Klose KJ, Wagner HJ (2009) Selective internal radiotherapy with Yttrium-90 microspheres for hepatic metastatic neuroendocrine tumors: a prospective single center study. Digestion 79(3):137–142. doi:10.1159/000209849
Saxena A, Chua TC, Bester L, Kokandi A, Morris DL (2010) Factors predicting response and survival after yttrium-90 radioembolization of unresectable neuroendocrine tumor liver metastases: a critical appraisal of 48 cases. Ann Surg 251(5):910–916. doi:10.1097/SLA.0b013e3181d3d24a
Rajekar H, Bogammana K, Stubbs RS (2011) Selective internal radiation therapy for gastrointestinal neuroendocrine tumour liver metastases: a new and effective modality for treatment. Int J Hepatol 2011:404916. doi:10.4061/2011/404916
Steward MJ, Warbey VS, Malhotra A, Caplin ME, Buscombe JR, Yu D (2008) Neuroendocrine tumors: role of interventional radiology in therapy. Radiographics 28(4):1131–1145. doi:10.1148/rg.284075170
Dominguez S, Denys A, Madeira I, Hammel P, Vilgrain V, Menu Y, Bernades P, Ruszniewski P (2000) Hepatic arterial chemoembolization with streptozotocin in patients with metastatic digestive endocrine tumours. Eur J Gastroenterol Hepatol 12(2):151–157
Granberg D, Eriksson LG, Welin S, Kindmark H, Janson ET, Skogseid B, Oberg K, Eriksson B, Nyman R (2007) Liver embolization with trisacryl gelatin microspheres (embosphere) in patients with neuroendocrine tumors. Acta Radiol 48(2):180–185. doi:10.1080/02841850601080440
Therasse E, Breittmayer F, Roche A, De Baere T, Indushekar S, Ducreux M, Lasser P, Elias D, Rougier P (1993) Transcatheter chemoembolization of progressive carcinoid liver metastasis. Radiology 189(2):541–547
Carrasco CH, Charnsangavej C, Ajani J, Samaan NA, Richli W, Wallace S (1986) The carcinoid syndrome: palliation by hepatic artery embolization. AJR Am J Roentgenol 147(1):149–154
Kress O, Wagner HJ, Wied M, Klose KJ, Arnold R, Alfke H (2003) Transarterial chemoembolization of advanced liver metastases of neuroendocrine tumors–a retrospective single-center analysis. Digestion 68(2–3):94–101. doi:10.1159/000074522
Kim YH, Ajani JA, Carrasco CH, Dumas P, Richli W, Lawrence D, Chuang V, Wallace S (1999) Selective hepatic arterial chemoembolization for liver metastases in patients with carcinoid tumor or islet cell carcinoma. Cancer Invest 17(7):474–478
Eriksson BK, Larsson EG, Skogseid BM, Lofberg AM, Lorelius LE, Oberg KE (1998) Liver embolizations of patients with malignant neuroendocrine gastrointestinal tumors. Cancer 83(11):2293–2301. doi:10.1002/(SICI)1097-0142(19981201)83:11<2293::AID-CNCR8>3.0.CO;2-E
Pitt SC, Knuth J, Keily JM, McDermott JC, Weber SM, Chen H, Rilling WS, Quebbeman EJ, Agarwal DM, Pitt HA (2008) Hepatic neuroendocrine metastases: chemo- or bland embolization? J Gastrointest Surg 12(11):1951–1960. doi:10.1007/s11605-008-0640-6
Maire F, Lombard-Bohas C, O’Toole D, Vullierme MP, Rebours V, Couvelard A, Pelletier A-L, Zappa M, Pilleul F, Hentic O, Hammel P, Ruszniewski P (2012) Hepatic arterial embolization versus chemoembolization in the treatment of liver metastases of well-differentiated midgut endocrine tumors. A prospective randomized study. Neuroendocrinology (in press)
Ruutiainen AT, Soulen MC, Tuite CM, Clark TW, Mondschein JI, Stavropoulos SW, Trerotola SO (2007) Chemoembolization and bland embolization of neuroendocrine tumor metastases to the liver. J Vasc Interv Radiol 18(7):847–855. doi:10.1016/j.jvir.2007.04.018
Gupta S, Johnson MM, Murthy R, Ahrar K, Wallace MJ, Madoff DC, McRae SE, Hicks ME, Rao S, Vauthey JN, Ajani JA, Yao JC (2005) Hepatic arterial embolization and chemoembolization for the treatment of patients with metastatic neuroendocrine tumors: variables affecting response rates and survival. Cancer 104(8):1590–1602. doi:10.1002/cncr.21389
Ho AS, Picus J, Darcy MD, Tan B, Gould JE, Pilgram TK, Brown DB (2007) Long-term outcome after chemoembolization and embolization of hepatic metastatic lesions from neuroendocrine tumors. AJR Am J Roentgenol 188(5):1201–1207. doi:10.2214/AJR.06.0933
Strosberg JR, Choi J, Cantor AB, Kvols LK (2006) Selective hepatic artery embolization for treatment of patients with metastatic carcinoid and pancreatic endocrine tumors. Cancer Control 13(1):72–78
Lammer J, Malagari K, Vogl T, Pilleul F, Denys A, Watkinson A, Pitton M, Sergent G, Pfammatter T, Terraz S, Benhamou Y, Avajon Y, Gruenberger T, Pomoni M, Langenberger H, Schuchmann M, Dumortier J, Mueller C, Chevallier P, Lencioni R (2010) Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Intervent Radiol 33(1):41–52. doi:10.1007/s00270-009-9711-7
de Baere T, Deschamps F, Teriitheau C, Rao P, Conengrapht K, Schlumberger M, Leboulleux S, Baudin E, Hechellhammer L (2008) Transarterial chemoembolization of liver metastases from well differentiated gastroenteropancreatic endocrine tumors with doxorubicin-eluting beads: preliminary results. J Vasc Interv Radiol 19(6):855–861. doi:10.1016/j.jvir.2008.01.030
Gaur SK, Friese JL, Sadow CA, Ayyagari R, Binkert CA, Schenker MP, Kulke M, Baum R (2011) Hepatic arterial chemoembolization using drug-eluting beads in gastrointestinal neuroendocrine tumor metastatic to the liver. Cardiovasc Intervent Radiol 34(3):566–572. doi:10.1007/s00270-011-0122-1
Guiu B, Deschamps F, Aho S, Munck F, Dromain C, Boige V, Malka D, Leboulleux S, Ducreux M, Schlumberger M, Baudin E, de Baere T (2012) Liver/biliary injuries following chemoembolisation of endocrine tumours and hepatocellular carcinoma: lipiodol vs. drug-eluting beads. J Hepatol 56(3):609–617. doi:10.1016/j.jhep.2011.09.012
Roche A, Girish BV, de Baere T, Ducreux M, Elias D, Laplanche A, Boige V, Schlumberger M, Ruffle P, Baudin E (2004) Prognostic factors for chemoembolization in liver metastasis from endocrine tumors. Hepatogastroenterology 51(60):1751–1756
Roche A, Girish BV, de Baere T, Baudin E, Boige V, Elias D, Lasser P, Schlumberger M, Ducreux M (2003) Trans-catheter arterial chemoembolization as first-line treatment for hepatic metastases from endocrine tumors. Eur Radiol 13(1):136–140. doi:10.1007/s00330-002-1558-0
Brown KT, Koh BY, Brody LA, Getrajdman GI, Susman J, Fong Y, Blumgart LH (1999) Particle embolization of hepatic neuroendocrine metastases for control of pain and hormonal symptoms. J Vasc Interv Radiol 10(4):397–403
Varker KA, Martin EW, Klemanski D, Palmer B, Shah MH, Bloomston M (2007) Repeat transarterial chemoembolization (TACE) for progressive hepatic carcinoid metastases provides results similar to first TACE. J Gastrointest Surg 11(12):1680–1685. doi:10.1007/s11605-007-0235-7
Ruszniewski P, Rougier P, Roche A, Legmann P, Sibert A, Hochlaf S, Ychou M, Mignon M (1993) Hepatic arterial chemoembolization in patients with liver metastases of endocrine tumors. A prospective phase II study in 24 patients. Cancer 71(8):2624–2630
Hoffmann RT, Paprottka P, Jakobs TF, Trumm CG, Reiser MF (2011) Arterial therapies of non-colorectal cancer metastases to the liver (from chemoembolization to radioembolization). Abdom Imaging 36(6):671–676. doi:10.1007/s00261-011-9753-6
de Baere T, Roche A, Amenabar JM, Lagrange C, Ducreux M, Rougier P, Elias D, Lasser P, Patriarche C (1996) Liver abscess formation after local treatment of liver tumors. Hepatology 23(6):1436–1440. doi:10.1002/hep. 510230620
Kim W, Clark TW, Baum RA, Soulen MC (2001) Risk factors for liver abscess formation after hepatic chemoembolization. J Vasc Interv Radiol 12(8):965–968
Wigmore SJ, Redhead DN, Thomson BN, Currie EJ, Parks RW, Madhavan KK, Garden OJ (2003) Postchemoembolisation syndrome–tumour necrosis or hepatocyte injury? Br J Cancer 89(8):1423–1427. doi:10.1038/sj.bjc.6601329
Pavel M, Baudin E, Couvelard A, Krenning E, Oberg K, Steinmuller T, Anlauf M, Wiedenmann B, Salazar R (2011) ENETS consensus guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary. Neuroendocrinology. doi:10.1159/000335597
Cadiot G (2010) Tumeurs endocrines digestives. Thésaurus National de cancérologie Digestive. Available via http://www.snfge.org/data/moduledocument/publication/5/1252.htm. 2010
Ajani JA, Carrasco CH, Charnsangavej C, Samaan NA, Levin B, Wallace S (1988) Islet cell tumors metastatic to the liver: effective palliation by sequential hepatic artery embolization. Ann Intern Med 108(3):340–344
Diamandidou E, Ajani JA, Yang DJ, Chuang VP, Brown CA, Carrasco HC, Lawrence DD, Wallace S (1998) Two-phase study of hepatic artery vascular occlusion with microencapsulated cisplatin in patients with liver metastases from neuroendocrine tumors. AJR Am J Roentgenol 170(2):339–344
Gupta S, Yao JC, Ahrar K, Wallace MJ, Morello FA, Madoff DC, Murthy R, Hicks ME, Ajani JA (2003) Hepatic artery embolization and chemoembolization for treatment of patients with metastatic carcinoid tumors: the M.D. Anderson experience. Cancer J 9(4):261–267
Loewe C, Schindl M, Cejna M, Niederle B, Lammer J, Thurnher S (2003) Permanent transarterial embolization of neuroendocrine metastases of the liver using cyanoacrylate and lipiodol: assessment of mid- and long-term results. AJR Am J Roentgenol 180(5):1379–1384
Osborne DA, Zervos EE, Strosberg J, Boe BA, Malafa M, Rosemurgy AS, Yeatman TJ, Carey L, Duhaine L, Kvols LK (2006) Improved outcome with cytoreduction versus embolization for symptomatic hepatic metastases of carcinoid and neuroendocrine tumors. Ann Surg Oncol 13(4):572–581. doi:10.1245/ASO.2006.03.071
Bloomston M, Al-Saif O, Klemanski D, Pinzone JJ, Martin EW, Palmer B, Guy G, Khabiri H, Ellison EC, Shah MH (2007) Hepatic artery chemoembolization in 122 patients with metastatic carcinoid tumor: lessons learned. J Gastrointest Surg 11(3):264–271. doi:10.1007/s11605-007-0089-z
Kamat PP, Gupta S, Ensor JE, Murthy R, Ahrar K, Madoff DC, Wallace MJ, Hicks ME (2008) Hepatic arterial embolization and chemoembolization in the management of patients with large-volume liver metastases. Cardiovasc Intervent Radiol 31(2):299–307. doi:10.1007/s00270-007-9186-3
Sward C, Johanson V, Nieveen van Dijkum E, Jansson S, Nilsson O, Wangberg B, Ahlman H, Kolby L (2009) Prolonged survival after hepatic artery embolization in patients with midgut carcinoid syndrome. Br J Surg 96(5):517–521. doi:10.1002/bjs.6587
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Zappa, M., Abdel-Rehim, M., Hentic, O. et al. Liver-directed therapies in liver metastases from neuroendocrine tumors of the gastrointestinal tract. Targ Oncol 7, 107–116 (2012). https://doi.org/10.1007/s11523-012-0219-8
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DOI: https://doi.org/10.1007/s11523-012-0219-8