Liver Resection for Gastroenteropancreatic Neuroendocrine Tumors with Extrahepatic Disease
Abstract
:1. Introduction
2. Materials and Methods
2.1. Data
2.2. Patients
2.3. Data Variables
2.4. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Díez, M.; Teulé, A.; Salazar, R. Gastroenteropancreatic neuroendocrine tumors: Diagnosis and treatment. Ann. Gastroenterol. 2013, 26, 29–36. [Google Scholar]
- Xu, Z.; Wang, L.; Dai, S.; Chen, M.; Li, F.; Sun, J.; Luo, F. Epidemiologic Trends of and Factors Associated with Overall Survival for Patients with Gastroenteropancreatic Neuroendocrine Tumors in the United States. JAMA Netw. Open 2021, 4, e2124750. [Google Scholar] [CrossRef] [PubMed]
- Yao, J.C.; Hassan, M.; Phan, A.; Dagohoy, C.; Leary, C.; Mares, J.E.; Abdalla, E.K.; Fleming, J.B.; Vauthey, J.N.; Rashid, A.; et al. One hundred years after “carcinoid”: Epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J. Clin. Oncol. 2008, 26, 3063–3072. [Google Scholar] [CrossRef] [PubMed]
- Maxwell, J.E.; Sherman, S.K.; O’Dorisio, T.M.; Bellizzi, A.M.; Howe, J.R. Liver-directed surgery of neuroendocrine metastases: What is the optimal strategy? Surgery 2016, 159, 320–335. [Google Scholar] [CrossRef]
- Riihimäki, M.; Hemminki, A.; Sundquist, K.; Sundquist, J.; Hemminki, K. The epidemiology of metastases in neuroendocrine tumors. Int. J. Cancer 2016, 139, 2679–2686. [Google Scholar] [CrossRef] [PubMed]
- Mayo, S.C.; de Jong, M.C.; Bloomston, M.; Pulitano, C.; Clary, B.M.; Reddy, S.K.; Clark Gamblin, T.; Celinski, S.A.; Kooby, D.A.; Staley, C.A.; et al. Surgery versus intra-arterial therapy for neuroendocrine liver metastasis: A multicenter international analysis. Ann. Surg. Oncol. 2011, 18, 3657–3665. [Google Scholar] [CrossRef]
- Mahuron, K.M.; Singh, G. Defining a New Classification System for the Surgical Management of Neuroendocrine Tumor Liver Metastases. J. Clin. Med. 2023, 12, 2456. [Google Scholar] [CrossRef]
- Howe, J.R.; Cardona, K.; Fraker, D.L.; Kebebew, E.; Untch, B.R.; Wang, Y.Z.; Law, C.H.; Liu, E.H.; Kim, M.K.; Menda, Y.; et al. The Surgical Management of Small Bowel Neuroendocrine Tumors: Consensus Guidelines of the North American Neuroendocrine Tumor Society. Pancreas 2017, 46, 715–731. [Google Scholar] [CrossRef]
- Howe, J.R.; Merchant, N.B.; Conrad, C.; Keutgen, X.M.; Hallet, J.; Drebin, J.A.; Minter, R.M.; Lairmore, T.C.; Tseng, J.F.; Zeh, H.J.; et al. The North American Neuroendocrine Tumor Society Consensus Paper on the Surgical Management of Pancreatic Neuroendocrine Tumors. Pancreas 2020, 49, 1–33. [Google Scholar] [CrossRef]
- Kennedy, A.; Bester, L.; Salem, R.; Sharma, R.A.; Parks, R.W.; Ruszniewski, P. Role of hepatic intra-arterial therapies in metastatic neuroendocrine tumours (NET): Guidelines from the NET-Liver-Metastases Consensus Conference. HPB 2015, 17, 29–37. [Google Scholar] [CrossRef]
- Jia, Z.; Wang, W. Yttrium-90 radioembolization for unresectable metastatic neuroendocrine liver tumor: A systematic review. Eur. J. Radiol. 2018, 100, 23–29. [Google Scholar] [CrossRef] [PubMed]
- Tai, E.; Kennedy, S.; Farrell, A.; Jaberi, A.; Kachura, J.; Beecroft, R. Comparison of transarterial bland and chemoembolization for neuroendocrine tumours: A systematic review and meta-analysis. Curr. Oncol. 2020, 27, 537–546. [Google Scholar] [CrossRef]
- Deyo, R.A.; Cherkin, D.C.; Ciol, M.A. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J. Clin. Epidemiol. 1992, 45, 613–619. [Google Scholar] [CrossRef]
- Basturk, O.; Tang, L.; Hruban, R.H.; Adsay, V.; Yang, Z.; Krasinskas, A.M.; Vakiani, E.; La Rosa, S.; Jang, K.-T.; Frankel, W.L.; et al. Poorly Differentiated Neuroendocrine Carcinomas of the Pancreas: A Clinicopathologic Analysis of 44 Cases. Am. J. Surg. Pathol. 2014, 38, 437–447. [Google Scholar] [CrossRef] [PubMed]
- Tran, C.G.; Sherman, S.K.; Chandrasekharan, C.; Howe, J.R. Surgical Management of Neuroendocrine Tumor Liver Metastases. Surg. Oncol. Clin. N. Am. 2021, 30, 39–55. [Google Scholar] [CrossRef] [PubMed]
- Mayo, S.C.; de Jong, M.C.; Pulitano, C.; Clary, B.M.; Reddy, S.K.; Gamblin, T.C.; Celinksi, S.A.; Kooby, D.A.; Staley, C.A.; Stokes, J.B.; et al. Surgical management of hepatic neuroendocrine tumor metastasis: Results from an international multi-institutional analysis. Ann. Surg. Oncol. 2010, 17, 3129–3136. [Google Scholar] [CrossRef]
- Saxena, A.; Chua, T.C.; Chu, F.; Al-Zahrani, A.; Morris, D.L. Optimizing the surgical effort in patients with advanced neuroendocrine neoplasm hepatic metastases: A critical analysis of 40 patients treated by hepatic resection and cryoablation. Am. J. Clin. Oncol. 2012, 35, 439–445. [Google Scholar] [CrossRef] [PubMed]
- Lewis, M.A.; Hobday, T.J. Treatment of neuroendocrine tumor liver metastases. Int. J. Hepatol. 2012, 2012, 973946. [Google Scholar] [CrossRef]
- Elias, D.; Lasser, P.; Ducreux, M.; Duvillard, P.; Ouellet, J.F.; Dromain, C.; Schlumberger, M.; Pocard, M.; Boige, V.; Miquel, C.; et al. Liver resection (and associated extrahepatic resections) for metastatic well-differentiated endocrine tumors: A 15-year single center prospective study. Surgery 2003, 133, 375–382. [Google Scholar] [CrossRef]
- Ho, A.S.; Picus, J.; Darcy, M.D.; Tan, B.; Gould, J.E.; Pilgram, T.K.; Brown, D.B. Long-term outcome after chemoembolization and embolization of hepatic metastatic lesions from neuroendocrine tumors. AJR Am. J. Roentgenol. 2007, 188, 1201–1207. [Google Scholar] [CrossRef]
- Chauhan, A.; Del Rivero, J.; Ramirez, R.A.; Soares, H.P.; Li, D. Treatment Sequencing Strategies in Advanced Neuroendocrine Tumors: A Review. Cancers 2022, 14, 5248. [Google Scholar] [CrossRef]
- Kennedy, K.R.; Turner, J.H.; MacDonald, W.B.G.; Claringbold, P.G.; Boardman, G.; Ransom, D.T. Long-term survival and toxicity in patients with neuroendocrine tumors treated with. Cancer 2022, 128, 2182–2192. [Google Scholar] [CrossRef] [PubMed]
- Arrivi, G.; Verrico, M.; Roberto, M.; Barchiesi, G.; Faggiano, A.; Marchetti, P.; Mazzuca, F.; Tomao, S. Capecitabine and Temozolomide (CAPTEM) in Advanced Neuroendocrine Neoplasms (NENs): A Systematic Review and Pooled Analysis. Cancer Manag. Res. 2022, 14, 3507–3523. [Google Scholar] [CrossRef] [PubMed]
- Stueven, A.K.; Kayser, A.; Wetz, C.; Amthauer, H.; Wree, A.; Tacke, F.; Wiedenmann, B.; Roderburg, C.; Jann, H. Somatostatin Analogues in the Treatment of Neuroendocrine Tumors: Past, Present and Future. Int. J. Mol. Sci. 2019, 20, 3049. [Google Scholar] [CrossRef]
- Fazio, N.; Kulke, M.; Rosbrook, B.; Fernandez, K.; Raymond, E. Updated Efficacy and Safety Outcomes for Patients with Well-Differentiated Pancreatic Neuroendocrine Tumors Treated with Sunitinib. Target. Oncol. 2021, 16, 27–35. [Google Scholar] [CrossRef] [PubMed]
- Yao, J.C.; Pavel, M.; Lombard-Bohas, C.; Van Cutsem, E.; Voi, M.; Brandt, U.; He, W.; Chen, D.; Capdevila, J.; de Vries, E.G.E.; et al. Everolimus for the Treatment of Advanced Pancreatic Neuroendocrine Tumors: Overall Survival and Circulating Biomarkers From the Randomized, Phase III RADIANT-3 Study. J. Clin. Oncol. 2016, 34, 3906–3913. [Google Scholar] [CrossRef] [PubMed]
- Dasari, A.; Shen, C.; Halperin, D.; Zhao, B.; Zhou, S.; Xu, Y.; Shih, T.; Yao, J.C. Trends in the Incidence, Prevalence, and Survival Outcomes in Patients with Neuroendocrine Tumors in the United States. JAMA Oncol. 2017, 3, 1335–1342. [Google Scholar] [CrossRef]
- Woltering, E.A.; Voros, B.A.; Beyer, D.T.; Wang, Y.Z.; Thiagarajan, R.; Ryan, P.; Wright, A.; Ramirez, R.A.; Ricks, M.J.; Boudreaux, J.P. Aggressive Surgical Approach to the Management of Neuroendocrine Tumors: A Report of 1,000 Surgical Cytoreductions by a Single Institution. J. Am. Coll. Surg. 2017, 224, 434–447. [Google Scholar] [CrossRef]
- Chan, D.L.; Dixon, M.; Law, C.H.L.; Koujanian, S.; Beyfuss, K.A.; Singh, S.; Myrehaug, S.; Hallet, J. Outcomes of Cytoreductive Surgery for Metastatic Low-Grade Neuroendocrine Tumors in the Setting of Extrahepatic Metastases. Ann. Surg. Oncol. 2018, 25, 1768–1774. [Google Scholar] [CrossRef]
- Limbach, K.E.; Mahuron, K.M.; Scott, A.T.; Ituarte, P.H.G.; Singh, G. Liver-Directed Therapy in Neuroendocrine Neoplasms Metastatic to Both Liver and Bone. J. Clin. Med. 2023, 12, 7646. [Google Scholar] [CrossRef]
- Limbach, K.E.; Pommier, R.F. Management of Metastatic GEPNETs. Surg. Oncol. Clin. N. Am. 2020, 29, 281–292. [Google Scholar] [CrossRef]
- Lewis, A.; Li, D.; Williams, J.; Singh, G. Pancreatic Neuroendocrine Tumors: State-of-the-Art Diagnosis and Management. Oncology 2017, 31, e1–e12. [Google Scholar]
- Ramage, J.K.; Ahmed, A.; Ardill, J.; Bax, N.; Breen, D.J.; Caplin, M.E.; Corrie, P.; Davar, J.; Davies, A.H.; Lewington, V.; et al. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). Gut 2012, 61, 6–32. [Google Scholar] [CrossRef] [PubMed]
- Fallows, M.; Samant, A.; Wilson, H.; Mirnezami, R. A Systematic Review of Surgical Management Strategies in the Treatment of Peritoneal Carcinomatosis of Neuroendocrine Origin. Curr. Oncol. 2023, 30, 6316–6329. [Google Scholar] [CrossRef] [PubMed]
- Leung, U.; Gönen, M.; Allen, P.J.; Kingham, T.P.; DeMatteo, R.P.; Jarnagin, W.R.; D’Angelica, M.I. Colorectal Cancer Liver Metastases and Concurrent Extrahepatic Disease Treated with Resection. Ann. Surg. 2017, 265, 158–165. [Google Scholar] [CrossRef]
- Adam, R.; Delvart, V.; Pascal, G.; Valeanu, A.; Castaing, D.; Azoulay, D.; Giacchetti, S.; Paule, B.; Kunstlinger, F.; Ghémard, O.; et al. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: A model to predict long-term survival. Ann. Surg. 2004, 240, 644–658. [Google Scholar] [CrossRef]
Variable † | Gastric n = 1045 | Pancreas n = 1795 | Small Bowel n = 2071 | Colon n = 870 | Rectum n = 3947 |
---|---|---|---|---|---|
Liver Metastasis | 77 (7) | 713 (40) | 309 (15) | 215 (25) | 120 (3) |
Primary NET | |||||
Resection when LM | |||||
present | |||||
No | 65 (84) | 648 (91) | 119 (39) | 100 (47) | 69 (58) |
Yes | 12 (16) | 64 (9) | 189 (61) | 115 (53) | 51 (42) |
Liver resection | |||||
No | 72 (94) | 660 (93) | 242 (78) | 200 (93) | 112 (93) |
Yes | - § | 53 (7) | 67 (22) | 15 (7) | - § |
TACE or Y90 | |||||
No | 60 (78) | 585 (82) | 236 (76) | 182 (85) | 82 (68) |
Yes | 17 (22) | 128 (18) | 73 (24) | 33 (15) | 38 (32) |
Overall Survival | |||||
[months, median (95% CI)] | |||||
Without LM | NR (139-NR) | 52 (45–58) | 142 (133–146) | 154 (133-NR) | NR (NR-NR) |
With LM | 18 (9–26) | 22 (18–25) | 70 (52–80) | 9 (7–12) | 17 (12–27) |
Variable † | NETLM n = 1434 | NETLM and EHD without LDT n = 256 | NETLM and EHD with LDT n = 71 | p-Value |
---|---|---|---|---|
Age [years, median (range)] | 61 (14–92) | 62 (33–90) | 55 (27–79) | <0.001 |
Sex | 0.632 | |||
Male | 783 (55) | 138 (43) | 36 (51) | |
Race/ethnicity | 0.653 | |||
White | 634 (67) | 109 (68) | 47 (75) | |
Black | 85 (9) | - § | - | |
Hispanic | 153 (16) | 26 (16) | - | |
Asian/Pacific Islander | 77 (8) | 14 (9) | - | |
Comorbidities | 0.265 | |||
None | 1006 (70) | 129 (62) | 48 (73) | |
One | 276 (19) | 48 (23) | 11 (17) | |
≥Two | 152 (11) | 32 (15) | - | |
Primary NET site | 0.109 | |||
Stomach | 1353 (11) | 13 (5) | - | |
Pancreas | 2221 (18) | 109 (43) | 20 (28) | |
Small Bowel | 2498 (20) | 53 (21) | 24 (34) | |
Colon | 1068 (9) | 52 (20) | 13 (18) | |
Rectum | 5090 (42) | 29 (11) | - | |
Primary NET resection | 0.112 | |||
No | 1001 (70) | 167 (65) | 39 (55) | |
Yes | 431 (30) | 89 (35) | 32 (45) | |
Liver-directed therapy modality | ||||
Liver resection | 148 (10) | 23 (32) | ||
TACE | 270 (19) | 49 (69) | ||
Y90 | 54 (4) | - | ||
Concurrent EHD site ‡ | ||||
Any | 327 (23) | |||
Lung | 91 (28) | 78 (30) | 13 (18) | 0.043 |
Peritoneum | 159 (49) | 113 (44) | 46 (65) | 0.002 |
Bone | 120 (37) | 101 (39) | 19 (27) | 0.050 |
Brain | 19 (6) | 18 (7) | - | 0.073 |
Number of EHD sites ‡ | 0.424 | |||
0 | 1107 (77) | |||
1 | 274 (19) | 210 (82) | 64 (90) | |
≥2 | 53 (4) | 46 (18) | - | |
Any chemotherapy | <0.001 | |||
No | 830 (58) | 159 (62) | 28 (39) | |
Yes | 565 (39) | 95 (37) | 38 (54) | |
Overall Survival | 0.006 | |||
[months, median (95% CI)] | 26 (7–72) | 16 (6–52) | 27 (7–83) |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Mahuron, K.M.; Limbach, K.E.; Hernandez, M.C.; Ituarte, P.H.G.; Li, D.; Kessler, J.; Singh, G. Liver Resection for Gastroenteropancreatic Neuroendocrine Tumors with Extrahepatic Disease. J. Clin. Med. 2024, 13, 4983. https://doi.org/10.3390/jcm13174983
Mahuron KM, Limbach KE, Hernandez MC, Ituarte PHG, Li D, Kessler J, Singh G. Liver Resection for Gastroenteropancreatic Neuroendocrine Tumors with Extrahepatic Disease. Journal of Clinical Medicine. 2024; 13(17):4983. https://doi.org/10.3390/jcm13174983
Chicago/Turabian StyleMahuron, Kelly M., Kristen E. Limbach, Matthew C. Hernandez, Philip H. G. Ituarte, Daneng Li, Jonathan Kessler, and Gagandeep Singh. 2024. "Liver Resection for Gastroenteropancreatic Neuroendocrine Tumors with Extrahepatic Disease" Journal of Clinical Medicine 13, no. 17: 4983. https://doi.org/10.3390/jcm13174983