Skip to main content
Top

25-07-2017 | Neuroendocrine tumors | Article

Neuroendocrine Liver Metastasis: Prognostic Implications of Primary Tumor Site on Patients Undergoing Curative Intent Liver Surgery

Journal: Journal of Gastrointestinal Surgery

Authors: Gaya Spolverato, MD, Fabio Bagante, MD, Luca Aldrighetti, MD, George Poultsides, MD, Todd W. Bauer, MD, Ryan C. Field, MD, Hugo P. Marques, MD, Matthew Weiss, MD, Shishir K. Maithel, MD, Timothy M. Pawlik, MD, MPH, PhD

Publisher: Springer US

Abstract

Background

Neuroendocrine tumors typically arise from pancreatic (PNET) vs. gastrointestinal or thoracic origins (non-PNET). The impact of primary tumor site on long-term prognosis following resection of neuroendocrine liver metastasis (NELM) remains poorly defined. The objective of the current study was to define the association of primary tumor location on prognosis of patients undergoing curative intent liver resection for NELM.

Methods

Between 1990 and 2014, 421 patients who underwent resection of NELM were identified from a multi-institutional database. Clinicopathological characteristics, operative details, and outcomes were stratified and analyzed by location of the primary tumor (PNET vs. non-PNET). A propensity score-matched analysis was utilized to assess the impact of primary tumor location on long-term survival.

Results

Among the 421 patients, 197 (46.8%) patients had NELM from a PNET primary while 224 (53.2%) had a non-PNET primary (small bowel, n = 145; rectal, n = 10; bronchial, n = 22; other, n = 47). There were no differences in tumor burden and tumor site, while presence of extrahepatic disease was more common among patients with non-PNET NELM (extrahepatic disease, PNET NELM, n = 11 27.5% vs. non-PNET NELM, n = 29 72.5%; p = 0.010). Patients with PNET NELM were more likely to have non-functional disease compared with patients who had non-PNET NELM (non-functional, PNET NELM, n = 117 54.9% vs. non-PNET NELM, n = 96 45.1%; p = 0.011). On the final pathological specimen of the resected NELM, patients with PNET NELM were more likely to have a moderately differentiated tumor (59.3%), while patients with non-PNET NELM were more likely to have a poorly differentiated tumor (67.8%) (p = 0.005). Patients with PNET NELM had a worse 5-year DFS and 5-year OS compared with patients who had non-PNET NELM (DFS, PNET 36.2% vs. non-PNET 55.2%; p = 0.001 and OS, PNET 79.5% vs. non-PNET 83.4%; p = 0.008). After propensity score matching, both 5-year DFS and 5-year OS of the PNET and non-PNET groups were comparable (DFS, PNET 46.2% vs. non-PNET 55.9%; p = 0.22 and OS, PNET 81.5% vs. non-PNET 84.3%; p = 0.19).

Conclusion

PNET patients more often present with non-functional NELM and moderately differentiated tumors. On propensity-matched analysis, factors such as extrahepatic disease and tumor grade, but not primary tumor location, were associated with prognosis of patients undergoing curative intent liver surgery for NELM.
Literature
1.
Farley HA, Pommier RF. Treatment of Neuroendocrine Liver Metastases. Surgical oncology clinics of North America. Jan 2016;25(1):217–225.
2.
Spolverato G, Bagante F, Wagner D, et al. Quality of life after treatment of neuroendocrine liver metastasis. J Surg Res. Sep 2015;198(1):155–164.
3.
Chamberlain RS, Canes D, Brown KT, et al. Hepatic neuroendocrine metastases: does intervention alter outcomes? Journal of the American College of Surgeons. Apr 2000;190(4):432–445.
4.
Thompson GB, van Heerden JA, Grant CS, Carney JA, Ilstrup DM. Islet cell carcinomas of the pancreas: a twenty-year experience. Surgery. Dec 1988;104(6):1011–1017.
5.
Chen H, Hardacre JM, Uzar A, Cameron JL, Choti MA. Isolated liver metastases from neuroendocrine tumors: does resection prolong survival? Journal of the American College of Surgeons. Jul 1998;187(1):88–92; discussion 92–83.
6.
Sarmiento JM, Heywood G, Rubin J, Ilstrup DM, Nagorney DM, Que FG. Surgical treatment of neuroendocrine metastases to the liver: a plea for resection to increase survival. Journal of the American College of Surgeons. Jul 2003;197(1):29–37.
7.
Knox CD, Anderson CD, Lamps LW, Adkins RB, Pinson CW. Long-term survival after resection for primary hepatic carcinoid tumor. Annals of surgical oncology. Dec 2003;10(10):1171–1175.
8.
Osborne DA, Zervos EE, Strosberg J, et al. Improved outcome with cytoreduction versus embolization for symptomatic hepatic metastases of carcinoid and neuroendocrine tumors. Ann Surg Oncol. Apr 2006;13(4):572–581.
9.
Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. Feb 15 2003;97(4):934–959.
10.
Saxena A, Chua TC, Sarkar A, et al. Progression and survival results after radical hepatic metastasectomy of indolent advanced neuroendocrine neoplasms (NENs) supports an aggressive surgical approach. Surgery. Feb 2011;149(2):209–220.
11.
Pape UF, Berndt U, Muller-Nordhorn J, et al. Prognostic factors of long-term outcome in gastroenteropancreatic neuroendocrine tumours. Endocrine-related cancer. Dec 2008;15(4):1083–1097.
12.
Frilling A, Modlin IM, Kidd M, et al. Recommendations for management of patients with neuroendocrine liver metastases. The lancet oncology. Jan 2014;15(1):e8–21.
13.
Rindi G, D'Adda T, Froio E, Fellegara G, Bordi C. Prognostic factors in gastrointestinal endocrine tumors. Endocrine pathology. Fall 2007;18(3):145–149.
14.
McDermott EW, Guduric B, Brennan MF. Prognostic variables in patients with gastrointestinal carcinoid tumours. The British journal of surgery. Jul 1994;81(7):1007–1009.
15.
Mayo SC, de Jong MC, Bloomston M, et al. Surgery versus intra-arterial therapy for neuroendocrine liver metastasis: a multicenter international analysis. Annals of surgical oncology. Dec 2011;18(13):3657–3665.
16.
Mayo SC, Herman JM, Cosgrove D, et al. Emerging approaches in the management of patients with neuroendocrine liver metastasis: role of liver-directed and systemic therapies. Journal of the American College of Surgeons. Jan 2013;216(1):123–134.
17.
Spolverato G, Vitale A, Ejaz A, et al. Net health benefit of hepatic resection versus intraarterial therapies for neuroendocrine liver metastases: A Markov decision model. Surgery. Aug 2015;158(2):339–348.
18.
Bagante F, Spolverato G, Merath K, et al. Neuroendocrine liver metastasis: The chance to be cured after liver surgery. Journal of surgical oncology. Feb 01 2017.
19.
Mayo SC, de Jong MC, Pulitano C, et al. Surgical management of hepatic neuroendocrine tumor metastasis: results from an international multi-institutional analysis. Annals of surgical oncology. Dec 2010;17(12):3129–3136.
20.
Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S. The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas. Aug 2010;39(6):707–712.
21.
Couinaud C. Liver anatomy: portal (and suprahepatic) or biliary segmentation. Digestive surgery. 1999;16(6):459–467.
22.
Spolverato G, Pawlik TM. Liver-directed therapies: surgical approaches, alone and in combination with other interventions. American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting. 2014:101–110.
23.
Harrell FE, Jr, Lee KL, Mark DB. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Statistics in medicine. Feb 28 1996;15(4):361–387.
24.
Saxena A, Chua TC, Perera M, Chu F, Morris DL. Surgical resection of hepatic metastases from neuroendocrine neoplasms: a systematic review. Surgical oncology. Sep 2012;21(3):e131–141.
25.
Cho CS, Labow DM, Tang L, et al. Histologic grade is correlated with outcome after resection of hepatic neuroendocrine neoplasms. Cancer. Jul 01 2008;113(1):126–134.
26.
Glazer ES, Tseng JF, Al-Refaie W, et al. Long-term survival after surgical management of neuroendocrine hepatic metastases. HPB : the official journal of the International Hepato Pancreato Biliary Association. Aug 2010;12(6):427–433.
27.
Elias D, Lasser P, Ducreux M, et al. Liver resection (and associated extrahepatic resections) for metastatic well-differentiated endocrine tumors: a 15-year single center prospective study. Surgery. Apr 2003;133(4):375–382.