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Chen L, Yang D, Yusufu Y, Liu H, Liu M, Lin Y, Luo Y, He Q, Chen M, Zeng Z, Zhang N, Wang Y. Trans-Arterial Embolization for Liver Metastases of Gastroenteropancreatic Neuroendocrine Tumors: Response Indicates Survival Benefit? Cancers (Basel) 2025; 17:309. [PMID: 39858091 PMCID: PMC11763690 DOI: 10.3390/cancers17020309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2024] [Revised: 01/11/2025] [Accepted: 01/13/2025] [Indexed: 01/27/2025] Open
Abstract
OBJECTIVE To determine the impact of trans-arterial embolization (TAE) on overall survival (OS) in patients with liver metastases from gastroenteropancreatic neuroendocrine tumors (LM-GEP-NETs) and to identify factors that may influence tumor response to TAE treatment. METHODS This study included patients with histologically and radiologically confirmed LM-GEP-NETs who received TAE treatment at The First Affiliated Hospital, Sun Yat-sen University, between November 2016 and January 2023. Imaging responses were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) criteria. Tumor response was defined as complete or partial remission. RESULTS In total, 267 patients with LM-GEP-NETs were included. Patients with liver tumor burdens <25%, 25-50%, and ≥50% had progressively worse OS (p < 0.005). According to the RECIST criteria, 65.9% of patients exhibited tumor responses. Using the mRECIST criteria, 77.5% of patients showed tumor responses. Survival analyses with log-rank tests indicated that patients with tumor responses assessed using either the RECIST or mRECIST criteria had significantly better OS (p = 0.015 and p = 0.023, respectively). Further logistic regression analyses showed that early TAE (within 4 months after diagnosis of liver metastases) was associated with tumor responses assessed using RECIST or mRECIST. These results were further verified using propensity score matching and inverse probability treatment weighting adjusted datasets. CONCLUSIONS A higher liver tumor burden was associated with poorer OS in patients with LM-GEP-NETs. Tumor response after TAE indicates survival benefits. Early TAE (within 4 months of diagnosis) was associated with better treatment responses.
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Affiliation(s)
- Luohai Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; (L.C.); (Y.Y.); (M.L.); (M.C.); (Z.Z.)
| | - Dequan Yang
- Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; (D.Y.); (H.L.)
| | - Yueriguli Yusufu
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; (L.C.); (Y.Y.); (M.L.); (M.C.); (Z.Z.)
| | - Haikuan Liu
- Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; (D.Y.); (H.L.)
| | - Man Liu
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; (L.C.); (Y.Y.); (M.L.); (M.C.); (Z.Z.)
| | - Yuan Lin
- Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China;
| | - Yanji Luo
- Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China;
| | - Qiao He
- Department of Nuclear Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China;
| | - Minhu Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; (L.C.); (Y.Y.); (M.L.); (M.C.); (Z.Z.)
| | - Zhirong Zeng
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; (L.C.); (Y.Y.); (M.L.); (M.C.); (Z.Z.)
| | - Ning Zhang
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; (L.C.); (Y.Y.); (M.L.); (M.C.); (Z.Z.)
| | - Yu Wang
- Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; (D.Y.); (H.L.)
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Ammann M, Adjei Antwi SK, Gudmundsdottir H, Hackl H, Santol J, Guillot BE, Pappalettera G, Thiels CA, Warner SG, Truty MJ, Kendrick ML, Smoot RL, Nagorney DM, Cleary SP, Halfdanarson TR, Starlinger PP. Surgical and oncologic outcomes for liver resections of cystic neuroendocrine tumor liver metastasis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109464. [PMID: 39580261 DOI: 10.1016/j.ejso.2024.109464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 10/23/2024] [Accepted: 11/13/2024] [Indexed: 11/25/2024]
Abstract
BACKGROUND Cystic neuroendocrine tumor liver metastases (NETLM) are rare and dynamics in the liquid compartment often misinterpreted as rapid progression, affecting selection for liver resection candidates. This study retrospectively evaluates surgical and oncologic outcomes in patients with cystic versus solid NETLM from small bowel and pancreatic primaries. METHODS Between 2000 and 2020, 12 patients with cystic NETLM were identified among 464 patients who underwent >90 % tumor cytoreduction debulking hepatectomy at the Mayo Clinic. Tumor and patient characteristics, as well as surgical and oncologic outcomes, were compared with the total cohort of patients with solid NETLM, including a propensity-matched cohort. RESULTS Patients with cystic NETLM were similar in age (55.4 vs. 59.7 years; p = 0.113) and sex (58 % vs. 51 % men; p = 0.772) to those with solid NETLM. Synchronous metastases (92 % vs. 77 %; p = 0.314), bilobar distribution (83 % vs. 79 %; p = 1.000), lesion numbers (p = 0.547), Ki67 % expression (p = 0.311), and extrahepatic lesions (8 % vs. 18 %; p = 0.702) were similar. Cystic metastases were larger (7.3 vs. 3.8 cm; p < 0.001). Surgical risk did not differ, with major morbidity (25 % vs. 22 %; p = 0.729) and mortality (0 % vs. <2 %; p = 1.000). Median overall survival (OS) was 13.8 vs. 10.6 years (p = 0.513), and hepatic-progression-free survival (PFS) was 0.71 vs. 1.78 years (p = 0.507). Matched cohorts showed no significant difference in OS (13.80 vs. 8.57; p = 0.316) or hepatic-PFS (0.71 vs. 1.33; p = 0.620). CONCLUSION Surgical risk and long-term outcomes do not significantly differ between cystic and solid NETLMs. Given excellent long-term survival rates with >90 % cytoreduction, radical debulking is advised for both phenotypes when clinically feasible.
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Affiliation(s)
- Markus Ammann
- Department of Surgery, Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA; Department of Surgery, State Hospital Wiener Neustadt, Wiener Neustadt, Austria
| | - Stella K Adjei Antwi
- Department of Surgery, Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA; Department of Surgery, University Milano-Bicocca, Minao, Italy
| | - Hallbera Gudmundsdottir
- Department of Surgery, Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA; Division of Health Care Delivery Research, Robert D. and Patricia E. Kern Center for Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
| | - Hubert Hackl
- Institute of Bioinformatics, Biocenter, Medical University of Innsbruck, Innsbruck, Austria
| | - Jonas Santol
- Department of Surgery, Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA; Department of Surgery, HPB Center, Vienna Health Network, Clinic Favoriten and Sigmund Freud Private University, Vienna, Austria
| | - Benedetto E Guillot
- Department of Surgery, Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA
| | - Giulia Pappalettera
- Department of Surgery, Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA
| | - Cornelius A Thiels
- Department of Surgery, Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA
| | - Susanne G Warner
- Department of Surgery, Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA
| | - Mark J Truty
- Department of Surgery, Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA
| | - Michael L Kendrick
- Department of Surgery, Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA
| | - Rory L Smoot
- Department of Surgery, Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA
| | - David M Nagorney
- Department of Surgery, Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA
| | - Sean P Cleary
- Department of Surgery, Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA; Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Canada
| | | | - Patrick P Starlinger
- Department of Surgery, Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA.
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Gujarathi R, Tobias J, Abou Azar S, Keutgen XM, Liao CY. Peptide Receptor Radionuclide Therapy versus Capecitabine/Temozolomide for the Treatment of Metastatic Pancreatic Neuroendocrine Tumors. Cancers (Basel) 2024; 16:2993. [PMID: 39272851 PMCID: PMC11394401 DOI: 10.3390/cancers16172993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 08/16/2024] [Accepted: 08/26/2024] [Indexed: 09/15/2024] Open
Abstract
Background: Peptide Receptor Radionuclide Therapy (PRRT), a form of Radioligand Therapy (RLT), and Capecitabine/Temozolomide (CAPTEM) are cornerstones of systemic therapy for metastatic pancreatic neuroendocrine tumors (PNETs). Data regarding comparative efficacy are lacking. Herein, we compare the efficacy of PRRT vs. CAPTEM as second-line/beyond regimens and treatment sequencing. Methods: Clinicopathologic, radiographic, and genomic data were captured for metastatic PNETs seen in our multi-disciplinary NET clinic between 2013 and 2023. The primary outcome was progression-free survival (PFS) after progression on a previous line of systemic therapy. The secondary outcomes were objective response rate (ORR), time to response (TTR), and overall survival (OS). Results: Fifty-nine cases were included. PFS was similar in the PRRT (n = 29) and CAPTEM (n = 30) groups (PRRT = 21.90 months vs. CAPTEM = 20.03 months; HR 0.99; p = 0.97). On subgroup analysis, PRRT had longer PFS in cases without extrahepatic metastases (26.47 months vs. 17.67 months; p = 0.03) and cases with a mutation in the MEN1, DAXX, and/or ATRX genes (28.43 months vs. 18.67 months; p = 0.03). PRRT had reduced PFS in patients with grade 3 disease (7.83 months vs. 16.33 months; p = 0.02). ORR did not vary significantly (34.78% vs. 40.91%; p = 0.67). CAPTEM responders showed shorter TTR (6.03 months vs. 11.15 months; p = 0.03). In patients who received both, OS did not vary based on the sequence (HR 1.20; p = 0.75). Conclusions: PFS, ORR, and OS are similar when using PRRT vs. CAPTEM as second-line-and-beyond therapy for patients with metastatic PNETs. However, patients with MEN1, DAXX, and/or ATRX mutations or without extrahepatic metastases might better benefit from PRRT and patients with grade 3 disease from CAPTEM. Candidates for surgical debulking or with tumor-induced symptoms may benefit from initial treatment with CAPTEM due to shorter TTR.
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Affiliation(s)
- Rushabh Gujarathi
- Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA
| | - Joseph Tobias
- Section of Endocrine Surgery, Department of Surgery, University of Chicago, Chicago, IL 60637, USA
| | - Sara Abou Azar
- Section of Endocrine Surgery, Department of Surgery, University of Chicago, Chicago, IL 60637, USA
| | - Xavier M Keutgen
- Section of Endocrine Surgery, Department of Surgery, University of Chicago, Chicago, IL 60637, USA
| | - Chih-Yi Liao
- Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA
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Ammann M, Gudmundsdottir H, Hackl H, Antwi SKA, Santol J, Habermann EB, Thiels CA, Warner SG, Truty MJ, Kendrick ML, Smoot RL, Nagorney DM, Cleary SP, Halfdanarson TR, Starlinger PP. Neuroendocrine Tumors of Unknown Primary in the Setting of Cytoreductive Hepatectomy. Ann Surg Oncol 2024; 31:4931-4941. [PMID: 38717544 DOI: 10.1245/s10434-024-15374-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 04/09/2024] [Indexed: 07/13/2024]
Abstract
BACKGROUND Surgical cytoreduction for neuroendocrine tumor liver metastasis (NETLM) consistently shows positive long-term outcomes. Despite reservations in guidelines for surgery when the primary tumor is unidentified (UP-NET), this study compared the surgical and oncologic long-term outcomes between patients with these rare cases undergoing cytoreductive surgery and patients who had liver resection for known primaries. METHODS The study identified 32 unknown primary liver metastases (UP-NETLM) in 522 retrospectively evaluated patients who underwent resection of well-differentiated NETLM between January 2000 and December 2020. Tumor and patient characteristics were compared with those in 490 cases of liver metastasis from small intestinal (SI-NETLM) or pancreatic (pNETLM) primaries. Survival analysis was performed to highlight long-term outcome differences. Surgical outcomes were compared between liver resections alone and simultaneous primary resections to assess surgical risk distinctions. RESULTS The UP-NET patients had fewer NETLMs (p = 0.004), which on the average were larger than SI-NETLMs or pNETLMs (p = 0.002). Expression of Ki-67 was balanced among the groups. Major hepatectomy was performed more often in the UP-NETLM group (p = 0.017). The 10-year survival rate of 53% for UP-NETLM was comparable with that for SI-NETML (58%; p = 0.463) and pNETLMs (47%; p = 0.497). The median hepatic progression-free survival was 26 months for the UP-NETLM patients and 25 months for the SI-NETLM patients compared to 12 months for the pNETLM patients (p < 0.001). Perioperative mortality was lower than 2%, and severe postoperative morbidity occurred in 21%, similarly distributed among all the groups. CONCLUSION The surgical risk and long-term outcomes for the UP-NETLM patients were comparable with those for other NETLM cases, affirming the validity of equally aggressive surgical cytoreduction as a therapeutic option in carefully selected cases.
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Affiliation(s)
- Markus Ammann
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
- Department of Surgery, State Hospital Wiener Neustadt, Wiener Neustadt, Austria
| | - Hallbera Gudmundsdottir
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
- Division of Health Care Delivery Research, Robert D. and Patricia E. Kern Center for Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
| | - Hubert Hackl
- Institute of Bioinformatics, Biocenter, Medical University of Innsbruck, Innsbruck, Austria
| | - Stella K Adjei Antwi
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
- Department of Surgery, University Milano-Bicocca, Minao, Italy
| | - Jonas Santol
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
- Department of Surgery, HPB Center, Vienna Health Network, Clinic Favoriten and Sigmund Freud Private University, Vienna, Austria
| | - Elizabeth B Habermann
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
- Division of Health Care Delivery Research, Robert D. and Patricia E. Kern Center for Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
| | - Cornelius A Thiels
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Susanne G Warner
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Mark J Truty
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Michael L Kendrick
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Rory L Smoot
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - David M Nagorney
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Sean P Cleary
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
- Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Canada
| | | | - Patrick P Starlinger
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA.
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Butz F, Dukaczewska A, Jann H, Dobrindt EM, Reinhard L, Lurje G, Pratschke J, Goretzki PE, Schöning W, Mogl MT. Surgical Approach to Liver Metastases in GEP-NET in a Tertiary Reference Center. Cancers (Basel) 2023; 15:cancers15072048. [PMID: 37046708 PMCID: PMC10093386 DOI: 10.3390/cancers15072048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 03/07/2023] [Accepted: 03/28/2023] [Indexed: 04/03/2023] Open
Abstract
Indications for liver resection in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NET) vary from liver resection with curative intent to tumor debulking or tissue sampling for histopathological characterization. With increasing expertise, the number of minimally invasive liver surgeries (MILS) in GEP-NET patients has increased. However, the influence on the oncological outcome has hardly been described. The clinicopathological data of patients who underwent liver resection for hepatic metastases of GEP-NET at the Department of Surgery, Charité—Universitätsmedizin Berlin, were analyzed. Propensity score matching (PSM) was performed to compare MILS with open liver surgery (OLS). In total, 22 patients underwent liver surgery with curative intent, and 30 debulking surgeries were analyzed. Disease-free survival (DFS) was longer than progression-free survival (PFS) (10 vs. 24 months), whereas overall survival (OS) did not differ significantly (p = 0.588). Thirty-nine (75%) liver resections were performed as OLS, and thirteen (25%) as MILS. After PSM, a shorter length of hospital stay was found for the MILS group (14 vs. 10 d, p = 0.034), while neither DFS/PFS nor OS differed significantly. Both curative intended and cytoreductive resection of hepatic GEP-NET metastases achieved excellent outcomes. MILS led to a reduced length of hospital, while preserving a good oncological outcome.
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Affiliation(s)
- Frederike Butz
- Department of Surgery, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, 10117 Berlin, Germany
- Correspondence:
| | - Agata Dukaczewska
- Department of Surgery, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, 10117 Berlin, Germany
| | - Henning Jann
- Department of Gastroenterology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, 10117 Berlin, Germany
| | - Eva Maria Dobrindt
- Department of Surgery, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, 10117 Berlin, Germany
| | - Lisa Reinhard
- Department of Surgery, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, 10117 Berlin, Germany
| | - Georg Lurje
- Department of Surgery, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, 10117 Berlin, Germany
| | - Johann Pratschke
- Department of Surgery, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, 10117 Berlin, Germany
| | - Peter E. Goretzki
- Department of Surgery, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, 10117 Berlin, Germany
| | - Wenzel Schöning
- Department of Surgery, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, 10117 Berlin, Germany
| | - Martina T. Mogl
- Department of Surgery, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, 10117 Berlin, Germany
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Mohamed A, Wu S, Hamid M, Mahipal A, Cjakrabarti S, Bajor D, Selfridge JE, Asa SL. Management of Appendix Neuroendocrine Neoplasms: Insights on the Current Guidelines. Cancers (Basel) 2022; 15:295. [PMID: 36612291 PMCID: PMC9818268 DOI: 10.3390/cancers15010295] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 12/19/2022] [Accepted: 12/26/2022] [Indexed: 01/03/2023] Open
Abstract
Appendiceal neuroendocrine neoplasms (ANENs) usually present as incidental findings at the time of appendectomy for acute appendicitis. They are rare, accounting for only 0.5-1% of intestinal neoplasms; they are found in 0.3-0.9% of all appendectomy specimens. They are usually sporadic tumors. There are several histological types including well-differentiated neuroendocrine tumors (NETs), poorly differentiated neuroendocrine carcinomas (NECs), and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs). Histologic differentiation and the grade of well-differentiated NETs correlate with clinical behavior and prognosis. Management varies based on differentiation, aggressiveness, and metastatic potential. There is debate about the optimal surgical management for localized appendiceal NETs that are impacted by many factors including the tumor size, the extent of mesoappendiceal spread, lymphovascular invasion and perineural involvement. In addition, the data to guide therapy in metastatic disease are limited due to the paucity of these tumors. Here, we review the current advances in the management of ANENs within the context of a multidisciplinary approach to these tumors.
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Affiliation(s)
- Amr Mohamed
- Division of Hematology and Medical Oncology, UH Seidman Cancer Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - Sulin Wu
- Department of Internal Medicine, UH Seidman Cancer Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
- Department of Medical Genetics, Center for Human Genetics, Case Western Reserve University, Cleveland, OH 44106, USA
| | - Mohamed Hamid
- Department of Stem Cell Biology and Regenerative Medicine, City of Hope Beckman Research Institute, Duarte, CA 91010, USA
| | - Amit Mahipal
- Division of Hematology and Medical Oncology, UH Seidman Cancer Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - Sakti Cjakrabarti
- Division of Hematology and Medical Oncology, UH Seidman Cancer Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - David Bajor
- Division of Hematology and Medical Oncology, UH Seidman Cancer Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - J. Eva Selfridge
- Division of Hematology and Medical Oncology, UH Seidman Cancer Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - Sylvia L. Asa
- Department of Pathology, UH Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA
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Nadalin S, Peters M, Königsrainer A. [Liver metastases of neuroendocrine tumors]. CHIRURGIE (HEIDELBERG, GERMANY) 2022; 93:659-666. [PMID: 35713676 DOI: 10.1007/s00104-022-01656-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 05/02/2022] [Indexed: 06/15/2023]
Abstract
Neuroendocrine liver metastases (NELM) are very heterogeneous with respect to the clinical presentation and the prognosis. The treatment of NELMs requires a multidisciplinary approach and patients with NELM should be referred to a specialized center. When possible, the resection of NELMs provides the best long-term results. The general selection criteria for liver resection include an acceptable general physical condition for a large liver operation, tumors with a favorable differentiation grade 1 or 2, a lack of extrahepatic lesions, a sufficient residual liver volume and the possibility to resect at least 70% of the metastases. Supplementary treatment, including simultaneous liver ablation, are generally safe and can increase the number of patients who can be considered for surgery. For patients with resectable NELM, the resection of the primary tumor is recommended either in a 2-stage or combined procedure. In selected patients with nonresectable NELM a liver transplantation can be carried out, which can be associated with excellent long-term results.
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Affiliation(s)
- S Nadalin
- Klinik für Allgemeine, Viszeral- Und Transplantationschirurgie, Universitätsklinikum Tübingen, Hoppe-Seyler-Straße 3, 72076, Tübingen, Deutschland.
| | - M Peters
- Klinik für Allgemeine, Viszeral- Und Transplantationschirurgie, Universitätsklinikum Tübingen, Hoppe-Seyler-Straße 3, 72076, Tübingen, Deutschland
| | - A Königsrainer
- Klinik für Allgemeine, Viszeral- Und Transplantationschirurgie, Universitätsklinikum Tübingen, Hoppe-Seyler-Straße 3, 72076, Tübingen, Deutschland
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8
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Perioperative Carcinoid Crisis: A Systematic Review and Meta-Analysis. Cancers (Basel) 2022; 14:cancers14122966. [PMID: 35740631 PMCID: PMC9221110 DOI: 10.3390/cancers14122966] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 06/06/2022] [Accepted: 06/13/2022] [Indexed: 01/05/2023] Open
Abstract
Simple Summary Intraoperative carcinoid crisis (CC) is thought to be a potentially lethal complication for patients with neuroendocrine tumors (NET). Though perioperative octreotide is often recommended for prevention, recent NET society guidelines raised concerns regarding limited data supporting the use of perioperative octreotide to prevent CC. The aim of our meta-analysis was to evaluate the existing evidence characterizing CC and the efficacy of prophylactic octreotide. We found that CC occurs frequently in patients having midgut NETs surgery, specifically those with NET liver metastasis, and is associated with worse postoperative outcomes. Our findings did not show a decreased risk in CC with prophylactic octreotide and questioned the advantage of routine prophylactic octreotide. Abstract Background: Surgery is the only curative option for patients with neuroendocrine tumors (NET) and is also indicated for debulking of liver metastasis. Intraoperative carcinoid crisis (CC) is thought to be a potentially lethal complication. Though perioperative octreotide is often recommended for prevention, recent NET society guidelines raised concerns regarding limited data supporting its use. We sought to evaluate existing evidence characterizing CC and evaluating the efficacy of prophylactic octreotide. Methods: A systematic review was performed on studies including patients having surgery for well-differentiated NET and/or NET liver metastasis (2000–2021), and reporting data on the incidence, risk factors, or prognosis of CC, and/or use of prophylactic octreotide. Meta-analysis was performed using random-effects models. Results: Eight studies met inclusion criteria (n = 943 operations). The pooled incidence of CC was 19% (95% CI [0.06–0.36]). Liver metastasis (odds ratio 2.85 [1.49–5.47]) and gender (male 0.58 [0.34–0.99]) were the only significant risk factors. The occurrence of CC was associated with increased risk of major postoperative complications (2.12 [1.03–4.35]). The use of prophylactic octreotide was not associated with decreased risk of CC (0.73 [0.32–1.66]). Notably, there was no standard prophylactic octreotide strategy used. Conclusions: Intraoperative carcinoid crisis is a common complication occurring in up to 20% of patients with midgut NET and/or liver metastasis undergoing surgery. Prophylactic octreotide may not provide an efficient way to prevent this complication. Future studies should focus on prospective evaluation of well-defined prophylactic protocols using a standardized definition for CC.
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Hamad A, Underhill J, Ansari A, Thayaparan V, Cloyd JM, Li Y, Pawlik TM, Tsung A, Abushahin L, Ejaz A. Surgical treatment of hepatic oligometastatic pancreatic ductal adenocarcinoma: An analysis of the National Cancer Database. Surgery 2022; 171:1464-1470. [PMID: 35115154 DOI: 10.1016/j.surg.2021.12.029] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 11/11/2021] [Accepted: 12/29/2021] [Indexed: 12/26/2022]
Abstract
BACKGROUND Patients with liver-only metastatic pancreatic adenocarcinoma have traditionally been offered palliative chemotherapy alone. Recent studies have explored the role of surgical resection among patients with limited metastatic disease. National practice patterns and the impact of surgery among these patients remains unknown. METHODS The National Cancer Database was queried for all patients with pancreatic adenocarcinoma between 2010 and 2015. The primary outcome was overall survival from the time of diagnosis. Patients with liver-only metastatic disease were included. Univariable and multivariable logistic regression models were constructed to determine the association of patient, hospital, and regional factors with receipt of surgical resection. A propensity score-matched cohort (1:1) was generated by matching patient- and tumor-related factors (age, sex, race, comorbidity burden, primary tumor site, primary tumor size) among patients with liver-only stage IV pancreatic adenocarcinoma who received chemotherapy alone compared to those who received chemotherapy and underwent pancreatectomy and liver metastatectomy. RESULTS Among 312,426 patients who met the study criteria, one half (n = 140,043, 50.4%) had stage IV disease; metastatic sites included bone (n = 5493, 3.1%), brain (n = 620, 0.4%), lung (n = 16,580, 9.5%), and liver (n = 62,444, 35.7%). Patients with stage IV disease were more likely to be younger (odds ratio: 1.10, 95% confidence interval: 1.0-1.2; P = .03) and have poorly (odds ratio: 2.1, 95% confidence interval: 1.8-2.5; P < .001) or undifferentiated (odds ratio: 3.1, 95% confidence interval: 2.3-4.1; P < .001) tumors. Among stage IV patients with liver-only disease (n = 47,785, 14.9%), 891 patients (1.9%) underwent pancreatic resection. Patients who underwent resection were more likely to be younger (odds ratio 1.4, 95% confidence interval: 1.0-1.8; P = .03) and treated at an academic/research center (odds ratio 2.1, 95% confidence interval: 1.2-3.5; P = .006). Median overall survival among patients who underwent resection was 10.74 months versus 3.4 months among patients who did not undergo resection. After controlling for patient and disease-related factors, patients who underwent surgical resection had a lower risk of death versus patients who did not undergo surgery (hazard ratio: 0.5, 95% confidence interval: 0.4-0.6; P < .001). After propensity score matching, patients who received multimodality treatment for liver-only metastatic pancreatic adenocarcinoma (surgery, chemotherapy) had a longer median overall survival (15.6 months vs 8.1 months) compared to those who received chemotherapy alone (P < .001). CONCLUSION This study suggests that pancreatic resection in patients with liver metastases, in combination with chemotherapy and/or chemoradiation, may be associated with improved survival in well-selected patients. However, attempts at an aggressive surgical approach for patients with liver-only stage IV pancreatic adenocarcinoma patients should only be performed only under a well-designed prospective clinical trial.
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Affiliation(s)
- Ahmad Hamad
- Division of Surgical Oncology, The Ohio State University, Columbus, OH. http://www.twitter.com/ahmadhamad4
| | - Jennifer Underhill
- Division of Surgical Oncology, The Ohio State University, Columbus, OH. http://www.twitter.com/Jenn_Underhill
| | - Aliya Ansari
- Division of Surgical Oncology, The Ohio State University, Columbus, OH
| | - Varna Thayaparan
- Division of Surgical Oncology, The Ohio State University, Columbus, OH
| | - Jordan M Cloyd
- Division of Surgical Oncology, The Ohio State University, Columbus, OH. http://www.twitter.com/jcloydmd
| | - Yaming Li
- Division of Surgical Oncology, The Ohio State University, Columbus, OH
| | - Timothy M Pawlik
- Division of Surgical Oncology, The Ohio State University, Columbus, OH. http://www.twitter.com/timpawlik
| | - Allan Tsung
- Division of Surgical Oncology, The Ohio State University, Columbus, OH. http://www.twitter.com/allantsung
| | - Laith Abushahin
- Division of Medical Oncology, The Ohio State University, Columbus, OH
| | - Aslam Ejaz
- Division of Surgical Oncology, The Ohio State University, Columbus, OH.
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10
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Mogl MT, Öllinger R, Jann H, Gebauer B, Fehrenbach U, Amthauer H, Wetz C, Schmelzle M, Raschzok N, Krenzien F, Goretzki PE, Pratschke J, Schoening W. Differenzierte Therapiestrategie bei Lebermetastasen gastro-entero-pankreatischer Neuroendokriner Neoplasien. Zentralbl Chir 2022; 147:270-280. [DOI: 10.1055/a-1830-8442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
ZusammenfassungNeuroendokrine Neoplasien (NEN) bilden eine heterogene Gruppe maligner Tumoren, die überwiegend dem gastro-entero-pankreatischen System (GEP) zuzuordnen sind. Hierbei sind Dünndarm und
Pankreas die häufigsten Organe für Primärtumoren, die Leber stellt den dominanten Metastasierungsort dar. Da viele Patient*innen lange asymptomatisch bleiben, führen oftmals zufällig
diagnostizierte Lebermetastasen oder ein Ileus zur Diagnose. Die einzige kurative Therapieoption stellt die komplette Entfernung von Primarius und Metastasen dar. Besonders im Falle der
metastasierten Erkrankung sollten die vorhandenen Therapieoptionen immer im interdisziplinären Tumorboard mit Spezialisten*innen aus Gastroenterologie, (Leber-)Chirurgie, Radiologie,
Nuklearmedizin, Radiotherapie, Pathologie und Endokrinologie evaluiert werden. Durch die Kombination der verschiedenen Therapieverfahren kann auch für Patient*innen mit fortgeschrittener
Erkrankung eine jahrelange Prognose bei guter Lebensqualität erreicht werden. Wichtig für die Therapieentscheidung sind neben patientenindividuellen Faktoren der Differenzierungsgrad des
Tumors, dessen hormonelle Sekretion, das Metastasierungsmuster und der Erkrankungsverlauf. Die Behandlung von Lebermetastasen umfasst neben den unterschiedlichen chirurgischen Strategien die
lokal-ablativen radiologischen und nuklearmedizinischen Verfahren, die als Ergänzung zu den systemischen Therapien zur Verfügung stehen.
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Affiliation(s)
- Martina T. Mogl
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow-Klinikum, Charité Universitätsmedizin Berlin, Berlin, Deutschland
| | - Robert Öllinger
- Europäisches Metastasenzentrum Charité, Charité Universitätsmedizin-Berlin, Berlin, Deutschland
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow-Klinikum, Charité Universitätsmedizin Berlin, Berlin, Deutschland
| | - Henning Jann
- Medizinische Klinik für Hepatologie und Gastroenterologie, Charité Universitätsmedizin Berlin, Berlin, Deutschland
| | - Bernhard Gebauer
- Klinik für Radiologie, Charité Universitätsmedizin Berlin, Berlin, Deutschland
| | - Uli Fehrenbach
- Klinik für Radiologie, Charité Universitätsmedizin Berlin, Berlin, Deutschland
| | - Holger Amthauer
- Klinik für Nuklearmedizin, Charité Universitätsmedizin Berlin, Berlin, Deutschland
| | - Christoph Wetz
- Klinik für Nuklearmedizin, Charité Universitätsmedizin Berlin, Berlin, Deutschland
| | - Moritz Schmelzle
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow-Klinikum, Charité Universitätsmedizin Berlin, Berlin, Deutschland
| | - Nathanael Raschzok
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow-Klinikum, Charité Universitätsmedizin Berlin, Berlin, Deutschland
| | - Felix Krenzien
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow-Klinikum, Charité Universitätsmedizin Berlin, Berlin, Deutschland
| | - Peter E. Goretzki
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow-Klinikum, Charité Universitätsmedizin Berlin, Berlin, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow-Klinikum, Charité Universitätsmedizin Berlin, Berlin, Deutschland
| | - Wenzel Schoening
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow-Klinikum, Charité Universitätsmedizin Berlin, Berlin, Deutschland
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11
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Que QY, Zhang LC, Bao JQ, Ling SB, Xu X. Role of surgical treatments in high-grade or advanced gastroenteropancreatic neuroendocrine neoplasms. World J Gastrointest Surg 2022; 14:397-408. [PMID: 35734618 PMCID: PMC9160682 DOI: 10.4240/wjgs.v14.i5.397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 01/19/2022] [Accepted: 04/09/2022] [Indexed: 02/06/2023] Open
Abstract
Over the last 40 years, the incidence and prevalence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have continued to increase. Compared to other epithelial neoplasms in the same organ, GEP-NENs exhibit indolent biological behavior, resulting in more chances to undergo surgery. However, the role of surgery in high-grade or advanced GEP-NENs is still controversial. Surgery is associated with survival improvement of well-differentiated high-grade GEP-NENs, whereas poorly differentiated GEP-NENs that may benefit from resection require careful selection based on Ki67 and other tissue biomarkers. Additionally, surgery also plays an important role in locally advanced and metastatic disease. For locally advanced GEP-NENs, isolated major vascular involvement is no longer an absolute contraindication. In the setting of metastatic GEP-NENs, radical intended surgery is recommended for patients with low-grade and resectable metastases. For unresectable metastatic disease, a variety of surgical approaches, including cytoreduction of liver metastasis, liver transplantation, and surgery after neoadjuvant treatment, show survival benefits. Primary tumor resection in GEP-NENs with unresectable metastatic disease is associated with symptom control, prolonged survival, and improved sensitivity toward systemic therapies. Although there is no established neoadjuvant or adjuvant strategy, increasing attention has been given to this emerging research area. Some studies have reported that neoadjuvant therapy effectively reduces tumor burden, improves the effectiveness of subsequent surgery, and decreases surgical complications.
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Affiliation(s)
- Qing-Yang Que
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou 310006, Zhejiang Province, China
- Zhejiang University Cancer Center, Hangzhou 310006, Zhejiang Province, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310006, Zhejiang Province, China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| | - Lin-Cheng Zhang
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou 310006, Zhejiang Province, China
- Zhejiang University Cancer Center, Hangzhou 310006, Zhejiang Province, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310006, Zhejiang Province, China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| | - Jia-Qi Bao
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou 310006, Zhejiang Province, China
- Zhejiang University Cancer Center, Hangzhou 310006, Zhejiang Province, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310006, Zhejiang Province, China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| | - Sun-Bin Ling
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou 310006, Zhejiang Province, China
- Zhejiang University Cancer Center, Hangzhou 310006, Zhejiang Province, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310006, Zhejiang Province, China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| | - Xiao Xu
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou 310006, Zhejiang Province, China
- Zhejiang University Cancer Center, Hangzhou 310006, Zhejiang Province, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310006, Zhejiang Province, China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
- Institute of Organ Transplantation, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
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12
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Kulkarni R, Kabir I, Hodson J, Raza S, Shah T, Pandanaboyana S, Dasari BVM. Impact of the extent of resection of neuroendocrine tumor liver metastases on survival: A systematic review and meta-analysis. Ann Hepatobiliary Pancreat Surg 2022; 26:31-39. [PMID: 34980681 PMCID: PMC8901984 DOI: 10.14701/ahbps.21-101] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 09/11/2021] [Accepted: 09/14/2021] [Indexed: 11/17/2022] Open
Abstract
In patients with neuroendocrine tumors with liver metastases (NETLMs), complete resection of both the primary and liver metastases is a potentially curative option. When complete resection is not possible, debulking of the tumour burden has been proposed to prolong survival. The objective of this systematic review was to evaluate the effect of curative surgery (R0-R1) and debulking surgery (R2) on overall survival (OS) in NETLMs. For the subgroup of R2 resections, outcomes were compared by the degree of hepatic debulking (≥ 90% or ≥ 70%). A systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines using PubMed, Medline, CINAHL, Cochrane, and Embase databases. Hazard ratios (HRs) were estimated for each study and pooled using a random-effects inverse-variance meta-analysis model. Of 538 articles retrieved, 11 studies (1,729 patients) reported comparisons between curative and debulking surgeries. After pooling these studies, OS was found to be significantly shorter in debulking resections, with an HR of 3.49 (95% confidence interval, 2.70–4.51; p < 0.001). Five studies (654 patients) compared outcomes between ≥ 90% and ≥ 70% hepatic debulking approaches. Whilst these studies reported a tendency for OS and progression-free survival to be shorter in those with a lower degree of debulking, they did not report sufficient data for this to be assessed in a formal meta-analysis. In patients with NETLM, OS following surgical resection is the best to achieve R0-R1 resection. There is also evidence for a progressive reduction in survival benefit with lesser debulking of tumour load.
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Affiliation(s)
- Rugved Kulkarni
- Department of HPB and Liver Transplantation, Queen Elizabeth Hospital, Birmingham, United Kingdom
| | - Irfan Kabir
- Department of HPB and Liver Transplantation, Queen Elizabeth Hospital, Birmingham, United Kingdom
| | - James Hodson
- Institute of Translational Medicine, Queen Elizabeth Hospital, Birmingham, United Kingdom
| | - Syed Raza
- Department of HPB and Liver Transplantation, Queen Elizabeth Hospital, Birmingham, United Kingdom
| | - Tahir Shah
- Department of Neuroendocrine Medicine and Hepatology, Queen Elizabeth Hospital, Birmingham, United Kingdom
| | - Sanjay Pandanaboyana
- HPB and Liver Transplant Unit, Newcastle University, Newcastle Upon Tyne, United Kingdom
| | - Bobby V M Dasari
- Department of HPB and Liver Transplantation, Queen Elizabeth Hospital, Birmingham, United Kingdom
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13
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Nagel I, Herrmann K, Lahner H, Rischpler C, Weber F. Combined medical therapy, nuclear medicine therapy and other therapies in metastatic neuroendocrine tumor. Nucl Med Mol Imaging 2022. [DOI: 10.1016/b978-0-12-822960-6.00156-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
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14
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Resection of Primary Gastrointestinal Neuroendocrine Tumor Among Patients with Non-Resected Metastases Is Associated with Improved Survival: A SEER-Medicare Analysis. J Gastrointest Surg 2021; 25:2368-2376. [PMID: 33403563 DOI: 10.1007/s11605-020-04898-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 12/19/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND The objective of this study was to analyze whether primary tumor resection (PTR) among patients with stage IV gastrointestinal neuroendocrine tumor (GI-NET) and unresected metastases was associated with improved outcomes. METHODS Patients diagnosed with stage IV GI-NETs were identified in the linked SEER-Medicare database from 2004 to 2015. Overall survival (OS) of patients who did versus did not undergo PTR was examined using bivariate and multivariable cox regression analysis as well as propensity score matching (PSM). RESULTS Among 2219 patients with metastatic GI-NETs, 632 (28.5%) underwent PTR, whereas 1587 (71.5%) did not. The majority of individuals had a NET in the pancreas (n = 969, 43.6%); the most common site of metastatic disease was the liver (n = 1064, 47.9%). Patients with stage IV small intestinal NETs most frequently underwent PTR (62.6%) followed by individuals with colon NETs (56.5%). After adjusting for all competing factors, PTR remained independently associated with improved OS (HR = 0.65, 95% CI: 0.56-0.76). Following PSM (n = 236 per group), patients who underwent PTR had improved OS (median OS: 1.3 years vs 0.8 years, p = 0.016). While PTR of NETs originating from stomach, small intestine, colon, and pancreas was associated with improved OS, PTR of rectal NET did not yield a survival benefit. CONCLUSION Primary GI-NET resection was associated with a survival benefit among individuals presenting with metastatic GI-NET with unresected metastases. Resection of primary GI-NET among patients with stage IV disease and unresected metastases should only be performed in selected cases following multi-disciplinary evaluation.
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15
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Sakaray Y, Abuji K, Chatterjee D, Irrinki S. Giant retroperitoneal lymph node-an uncommon presentation of duodenal neuroendocrine tumour. BMJ Case Rep 2021; 14:14/7/e243048. [PMID: 34290018 DOI: 10.1136/bcr-2021-243048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Primary retroperitoneal neuroendocrine tumours (NETs) are extremely rare, and many a times, these are metastatic lesions with known or unknown primary location, most commonly arising from the stomach, duodenum, small intestine and rectum. NETs arising from the duodenum are more commonly seen in the first part of the duodenum followed by the second part. The incidence is increasing because of easy accessibility to endoscopies and cross-sectional imaging. In NETs, lymph node (LN) metastasis occurs commonly when the tumour size is more than 2 cm. In contrast, LN metastasis occurs even with subcentimetric lesions, especially the ampullary variant of NETs. A patient presented to us with mild abdominal pain and found to have retroduodenal mass. On evaluation found to be a metastatic LN deposit of NET with the primary arising from the first part and supra-ampullary part of duodenum.
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Affiliation(s)
- Yashwant Sakaray
- General Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Kishore Abuji
- General Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Debajyoti Chatterjee
- Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Santhosh Irrinki
- General Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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16
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Abstract
The latest WHO classification cleanly divides gastrointestinal neuroendocrine neoplasms into neuroendocrine tumor (NET; well-differentiated, any grade) and neuroendocrine carcinoma (NEC; poorly differentiated, high-grade by definition), along with mixed neuroendocrine-non-neuroendocrine neoplasms. NECs are always aggressive, with multiple mutations; they are treated with chemotherapy. NETs have widely different presentations, behavior, and management depending on site of origin. Esophageal examples are vanishingly rare. Most gastric and appendiceal tumors are indolent, as are many colonic and rectal tumors. The duodenum is home to some unusual variants of NET, and jejunal/ileal NETs frequently metastasize, which impacts their staging and clinical management.
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Affiliation(s)
- Raul S Gonzalez
- Department of Pathology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA; Harvard Medical School, Boston, MA, USA.
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17
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Hishida T, Masai K, Kaseda K, Asakura K, Asamura H. Debulking surgery for malignant tumors: the current status, evidence and future perspectives. Jpn J Clin Oncol 2021; 51:1349-1362. [PMID: 34254145 DOI: 10.1093/jjco/hyab107] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 06/22/2021] [Indexed: 11/14/2022] Open
Abstract
Debulking surgery, also called cytoreductive surgery, is a resection of the tumor as much as possible and an intended incomplete resection for unresectable malignant tumors. Since the most important principle in surgical oncology is complete R0 resection, debulking surgery goes against the basic principle and obscures the concept of operability. However, debulking surgery has been advocated for various types of advanced malignant tumors, including gynecological cancers, urological cancers, gastrointestinal cancers, breast cancers and other malignancies, with or without adjuvant therapy. Positive data from randomized trials have been shown in subsets of ovarian cancer, renal cell carcinoma, colorectal cancer and breast cancer. However, recent trials for renal cell carcinoma, colorectal cancer and breast cancer have tended to show controversial results, mainly according to the survival improvement of nonsurgical systemic therapy alone. On the other hand, debulking surgery still has a therapeutic role for slow-growing and borderline malignant tumors, such as pseudomyxoma peritonei and thymomas. The recent understanding of tumor heterogeneity and clonal evolution responsible for malignancy and drug resistance indicates that select patients may obtain prolonged survival by the synergistic effect of debulking surgery and novel systemic therapy. This review aimed to describe the current status and evidence of debulking surgery in a cross-organ manner and to discuss future perspectives in the current era with advances in systemic therapy.
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Affiliation(s)
| | | | | | | | - Hisao Asamura
- Division of Thoracic Surgery, Department of Surgery, Keio University School of Medicine, Tokyo, Japan
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18
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Tang LH. Pancreatic Neuroendocrine Neoplasms: Landscape and Horizon. Arch Pathol Lab Med 2021; 144:816-828. [PMID: 32298138 DOI: 10.5858/arpa.2019-0654-ra] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/12/2020] [Indexed: 11/06/2022]
Abstract
CONTEXT.— Since the initial description of pancreatic endocrine physiology and the recognition of islet cell tumors in the 1800s, there have been noteworthy advances in the pathobiology of pancreatic neuroendocrine neoplasms (PanNENs), and definition of the important distinction between well-differentiated neuroendocrine tumor (PanNET) and poorly differentiated neuroendocrine carcinoma (PanNEC). The evolving knowledge has resulted in a continuous update in terminology, classification, and grading system for this group of neoplasms. Pancreatic neuroendocrine tumors associated with hereditary conditions have been linked to unique molecular and genetic events, and sporadic PanNETs have specific gene signatures. Based on accumulative experience and knowledge, therapeutic strategies have been defined for this group of neoplasms. OBJECTIVE.— To review the evolution and description of the pathologic-genomic evolution of PanNENs, and to facilitate accurate pathologic interpretation for the corresponding clinical management. DATA SOURCES.— Literature review of published studies and author's own work. CONCLUSIONS.— Evolving experience and knowledge have established subtypes of pancreatic neuroendocrine neoplasms, based on their genotype and phenotype. Accurate pathologic interpretation of the specific neoplasm has significant implications for therapy and prognosis.
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Affiliation(s)
- Laura H Tang
- From the Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York
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19
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Aoki T, Kubota K, Kiritani S, Arita J, Morizane C, Masui T, Kudo A, Komoto I, Hatano E, Ito T, Osamura RY, Unno M, Uemoto S, Kokudo N. Survey of surgical resections for neuroendocrine liver metastases: A project study of the Japan Neuroendocrine Tumor Society (JNETS). JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2021; 28:489-497. [PMID: 33792204 DOI: 10.1002/jhbp.956] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 03/07/2021] [Accepted: 03/09/2021] [Indexed: 01/30/2023]
Abstract
BACKGROUND/PURPOSE Hepatic resection is considered the treatment of choice for neuroendocrine liver metastases (NELM). However, the safety and efficacy of resection have not been fully evaluated using a large cohort. The aim of the present study was to collect real-world data regarding hepatic resections for NELM. METHODS A retrospective, multicenter survey was conducted. The background characteristics of patients undergoing an initial hepatic resection for NELM, the operative details, pathological findings, and patient outcomes were investigated. RESULTS A total of 222 patients were enrolled from 30 institutions. The primary tumor site was the pancreas in 58.6%, and the presentation of NELM was synchronous in 63.1% of the cases. Concomitant resection of the primary tumor and liver metastases was performed for 66.4% of the synchronous metastases, and the 90-day morbidity and mortality rates were 12.6% and 0.9%, respectively. The operations resulted in R2 resections in 26.1% of the cases, and 83.4% of the patients experienced recurrence after R0/1 resections. However, the patients were treated using multiple modalities after R2 resection or recurrence, and the overall survival rate was relatively favorable, with 5-year and 10-year survival rates of 70.2%, and 43.4%, respectively. Univariable and multivariable analyses identified the tumor grading (G3) of the primary tumor as a significant prognostic factor for both the recurrence-free and overall survivals. CONCLUSIONS The present data confirmed the safety of the surgical resection of NELM. Although recurrences were frequent, the survival outcomes after resection were favorable when a multi-disciplinary treatment approach was used.
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Affiliation(s)
- Taku Aoki
- Second Department of Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Keiichi Kubota
- Second Department of Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Sho Kiritani
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Junichi Arita
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Chigusa Morizane
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Toshihiko Masui
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Atsushi Kudo
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Izumi Komoto
- Department of Surgery, Kansai Electric Power Hospital, Osaka, Japan
| | - Etsuro Hatano
- Department of Gastroenterological Surgery, Hyogo College of Medicine, Hyogo, Japan
| | - Tetsuhide Ito
- Neuroendocrine Tumor Center, Fukuoka Sanno Hospital, International University of Health and Welfare, Fukuoka, Japan
| | - Robert Y Osamura
- Division of Diagnostic Pathology, Nippon Koukan Hospital, Kanagawa, Japan.,Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Michiaki Unno
- Department of Surgery, Tohoku University School of Medicine, Miyagi, Japan
| | - Shinji Uemoto
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Norihiro Kokudo
- Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
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20
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Abstract
Liver metastases are commonly detected in a range of malignancies including colorectal cancer (CRC), pancreatic cancer, melanoma, lung cancer and breast cancer, although CRC is the most common primary cancer that metastasizes to the liver. Interactions between tumour cells and the tumour microenvironment play an important part in the engraftment, survival and progression of the metastases. Various cells including liver sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, parenchymal hepatocytes, dendritic cells, resident natural killer cells as well as other immune cells such as monocytes, macrophages and neutrophils are implicated in promoting and sustaining metastases in the liver. Four key phases (microvascular, pre-angiogenic, angiogenic and growth phases) have been identified in the process of liver metastasis. Imaging modalities such as ultrasonography, CT, MRI and PET scans are typically used for the diagnosis of liver metastases. Surgical resection remains the main potentially curative treatment among patients with resectable liver metastases. The role of liver transplantation in the management of liver metastasis remains controversial. Systemic therapies, newer biologic agents (for example, bevacizumab and cetuximab) and immunotherapeutic agents have revolutionized the treatment options for liver metastases. Moving forward, incorporation of genetic tests can provide more accurate information to guide clinical decision-making and predict prognosis among patients with liver metastases.
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Fernandes MR, Ghezzi CLA, Grezzana-Filho TJM, Feier FH, Leipnitz I, Chedid AD, Cerski CTS, Chedid MF, Kruel CRP. Giant hepatic extra-gastrointestinal stromal tumor treated with cytoreductive surgery and adjuvant systemic therapy: A case report and review of literature. World J Gastrointest Surg 2021; 13:315-322. [PMID: 33796218 PMCID: PMC7992998 DOI: 10.4240/wjgs.v13.i3.315] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 12/17/2020] [Accepted: 03/08/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Primary extra-gastrointestinal stromal tumors (E-GIST) of the liver are rare. The clinical presentation may range from asymptomatic to bleeding or manifestations of mass effect. Oncologic surgery followed by adjuvant therapy with imatinib is the standard of care. However, under specific circumstances, a cytoreductive approach may represent a therapeutic option. We describe herein the case of an 84-year-old woman who presented with a tender, protruding epigastric mass. Abdominal computed tomography scan revealed a large, heterogeneous mass located across segments III, IV, V, and VIII of the liver. The initial approach was transarterial embolization of the tumor, which elicited no appreciable response. Considering the large size and central location of the tumor and the advanced age of the patient, non-anatomic complete resection was indicated. Due to substantial intraoperative bleeding and hemodynamic instability, only a near-complete resection could be achieved. Histopathology and immunohistochemical staining confirmed the diagnosis of primary E-GIST of the liver. Considering the risk/benefit ratio for therapeutic options, debulking surgery may represent a strategy to control pain and prolong survival.
CASE SUMMARY Here, we present a case report of a patient diagnosed with E-GIST primary of the liver, which was indicated a cytoreductive surgery and adjuvant therapy with imatinib.
CONCLUSION E-GIST primary of the liver is a rare conditional, the treatment is with systemic therapy and total resection surgery. However, a cytoreductive surgery will be necessary when a complete resection is no possible.
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Affiliation(s)
- Michel Ribeiro Fernandes
- Department of Gastrointestinal Surgery and Transplantation, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, RS, Brazil
| | | | - Tomaz JM Grezzana-Filho
- Department of Gastrointestinal Surgery and Transplantation, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, RS, Brazil
| | - Flávia Heinz Feier
- Department of Gastrointestinal Surgery and Transplantation, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, RS, Brazil
| | - Ian Leipnitz
- Department of Gastrointestinal Surgery and Transplantation, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, RS, Brazil
| | - Aljamir Duarte Chedid
- Department of Gastrointestinal Surgery and Transplantation, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, RS, Brazil
| | | | - Marcio Fernandes Chedid
- Department of Gastrointestinal Surgery and Transplantation, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, RS, Brazil
| | - Cléber Rosito Pinto Kruel
- Department of Gastrointestinal Surgery and Transplantation, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, RS, Brazil
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22
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Machairas N, Daskalakis K, Felekouras E, Alexandraki KI, Kaltsas G, Sotiropoulos GC. Currently available treatment options for neuroendocrine liver metastases. Ann Gastroenterol 2021; 34:130-141. [PMID: 33654350 PMCID: PMC7903580 DOI: 10.20524/aog.2021.0574] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Accepted: 09/10/2020] [Indexed: 12/16/2022] Open
Abstract
Neuroendocrine neoplasms (NEN) are frequently characterized by a high propensity for metastasis to the liver, which appears to be a dominant site of distant-stage disease, affecting quality of life and overall survival. Liver surgery with the intention to cure is the treatment of choice for resectable neuroendocrine liver metastases (NELM), aiming to potentially prolong survival and ameliorate hormonal symptoms refractory to medical control. Surgical resection is indicated for patients with NELM from well-differentiated NEN, while its feasibility and complexity are largely dictated by the degree of liver involvement. As a result of advances in surgical techniques over the past decades, complex 1- and 2-stage, or repeat liver resections are performed safely and effectively by experienced surgeons. Furthermore, liver transplantation for the treatment of NELM should be anchored in a multimodal and multidisciplinary therapeutic strategy and restricted only to highly selected individual cases. A broad spectrum of interventional radiology treatments for NELM have recently been available, with expanding indications that are more applicable, as they are less limited by patient- and tumor-related parameters, being therefore important adjuncts or alternatives to surgery. Overall, liver-targeted treatment modalities may precede the administration of systemic molecular targeted agents and chemotherapy for patients with liver-dominant metastatic disease; these appear to be a crucial component of multimodal management of patients with NEN. In the present review, we discuss surgical and non-surgical liver-targeted treatment approaches for NELM, each complementing the other, with a view to assisting physicians in optimizing multimodal NEN patient care.
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Affiliation(s)
- Nikolaos Machairas
- 2nd Department of Propaedeutic Surgery (Nikolaos Machairas, Georgios C. Sotiropoulos)
| | - Kosmas Daskalakis
- 1st Department of Propaedeutic Internal Medicine (Kosmas Daskalakis, Krystallenia I. Alexandraki, Gregory Kaltsas)
| | - Evangelos Felekouras
- 1st Department of Surgery (Evangelos Felekouras), National and Kapodistrian University of Athens, Medical School, Athens, Greece
| | - Krystallenia I Alexandraki
- 1st Department of Propaedeutic Internal Medicine (Kosmas Daskalakis, Krystallenia I. Alexandraki, Gregory Kaltsas)
| | - Gregory Kaltsas
- 1st Department of Propaedeutic Internal Medicine (Kosmas Daskalakis, Krystallenia I. Alexandraki, Gregory Kaltsas)
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23
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Benhaim L, Faron M, Hadoux J, Gelli M, Sourrouille I, Burtin P, Honoré C, Malka D, Leboulleux S, Ducreux M, Scoazec JY, Goere D, Baudin E. Long-Term Results after Surgical Resection of Peritoneal Metastasis from Neuroendocrine Tumors. Neuroendocrinology 2021; 111:599-608. [PMID: 32512564 DOI: 10.1159/000509220] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Accepted: 06/08/2020] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Peritoneal metastases from neuroendocrine tumors are associated with a bad prognosis. The objective of our study was to evaluate whether surgical resection could lead to prolonged survival in selected patients. This survival was compared to that of patients operated for liver metastasis. METHODS From our prospectively maintained database we included 88 patients who underwent the complete resection of peritoneal and/or liver metastasis between January 1995 and December 2016 in Gustave-Roussy. Three resection groups were compared: peritoneal metastasis alone, liver metastasis alone, and the combined resection of liver and peritoneal metastases. RESULTS The median peritoneal cancer index was 10 in the peritoneal group and 11 in the peritoneal + liver group. The 5-year overall survival was 81% (60-100) in the peritoneal group compared to 78% (65.2-92.8) in the liver group, and 72% (58.7-89.7) in the peritoneal + liver group (p = 0.71). The 3-year disease-free survival reached 26.9% (16.1-45.1) in the liver group, 12.5% (2.3-68.2) in the peritoneal group, and 32.4% (19.9-52.6) in the combined liver + peritoneal group (p = 0.45). In the univariate analysis, the prognosis factors for a longer survival were: small bowel primary tumor origin, low preoperative chromogranin A level, and tumor grade ≤1. CONCLUSION Despite a high recurrence rate, long-term overall survival can be achieved after the resection of peritoneal metastasis in selected patients. This survival is comparable to that of patients operated for liver metastasis only. Surgery should stand as a standard treatment for peritoneal metastases in patients with resectable disease.
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Affiliation(s)
- Léonor Benhaim
- Department of Surgical Oncology, Gustave-Roussy Cancer Campus, Villejuif, France,
| | - Matthieu Faron
- Department of Surgical Oncology, Gustave-Roussy Cancer Campus, Villejuif, France
- Department of Biostatistics and Epidemiology, INSERM Unit 1018 CESP, Oncostat Team, Gustave-Roussy Cancer Campus, Villejuif, France
| | - Julien Hadoux
- Department of Nuclear Medicine, Gustave Roussy Cancer Campus, Villejuif, France
| | - Maximiliano Gelli
- Department of Surgical Oncology, Gustave-Roussy Cancer Campus, Villejuif, France
| | - Isabelle Sourrouille
- Department of Surgical Oncology, Gustave-Roussy Cancer Campus, Villejuif, France
| | - Pascal Burtin
- Department of Gastro-enterology, Gustave-Roussy Cancer Campus, Villejuif, France
| | - Charles Honoré
- Department of Surgical Oncology, Gustave-Roussy Cancer Campus, Villejuif, France
| | - David Malka
- Department of Gastro-enterology, Gustave-Roussy Cancer Campus, Villejuif, France
| | - Sophie Leboulleux
- Department of Nuclear Medicine, Gustave Roussy Cancer Campus, Villejuif, France
| | - Michel Ducreux
- Department of Gastro-enterology, Gustave-Roussy Cancer Campus, Villejuif, France
| | - Jean-Yves Scoazec
- Department of Nuclear Medicine, Gustave Roussy Cancer Campus, Villejuif, France
| | - Diane Goere
- Department of Surgical Oncology, Gustave-Roussy Cancer Campus, Villejuif, France
| | - Eric Baudin
- Department of Nuclear Medicine, Gustave Roussy Cancer Campus, Villejuif, France
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24
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Pickens RC, Sulzer JK, Passeri MJ, Murphy K, Vrochides D, Martinie JB, Baker EH, Ocuin LM, McKillop IH, Iannitti DA. Operative Microwave Ablation for the Multimodal Treatment of Neuroendocrine Liver Metastases. J Laparoendosc Adv Surg Tech A 2020; 31:917-925. [PMID: 33296283 DOI: 10.1089/lap.2020.0558] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Background and Purpose: Operative microwave ablation (MWA) is a safe modality for treating hepatic tumors. The aim of this study is to present our 10-year, single-center experience of operative MWA for neuroendocrine liver metastases (NLM). Methods: A single-institution retrospective review of patients who underwent operative MWA for NLM was performed (2008-2018). Demographics, primary tumor site, operative approach, combined surgical operations, and carcinoid symptoms were recorded. Clinical outcomes for major complications, readmission, and mortality were analyzed 30 days postoperatively. Postablation imaging was evaluated for incomplete ablation/missed lesions, and surveillance imaging reviewed for local, regional, and metastatic recurrence. Results: Of the 50 patients (166 targeted lesions) who received MWA for NLM, 41 (82%) were treated with a minimally invasive approach, and 22 (44%) underwent MWA concomitant with hepatectomy and/or primary tumor resection. Within the study cohort 70% of patients were treated with curative intent with a 77% (27/35) success rate. Carcinoid symptoms were reported in 40% (20/50) of patients preoperatively, and MWA treatment improved symptoms in 19/20 patients. Incomplete ablation occurred in 1/166 treated lesions. Recurrence-free survival at 1 and 5 years was 86% and 28%, respectively. Overall survival at 1 and 5 years was 94% and 70%, respectively (median follow-up 32 months, range 0-116 months). Conclusion: Operative MWA is a versatile modality, which can be safe and effectively performed alone or combined with hepatectomy for NLM, preferably using a minimally invasive approach, to achieve symptom control and possibly improve survival.
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Affiliation(s)
- Ryan C Pickens
- Division of Hepato-Pancreato-Biliary Surgery, Department of Surgery, Carolinas Medical Center, Atrium Health, Charlotte, North Carolina, USA
| | - Jesse K Sulzer
- Division of Hepato-Pancreato-Biliary Surgery, Department of Surgery, Carolinas Medical Center, Atrium Health, Charlotte, North Carolina, USA
| | - Michael J Passeri
- Division of Hepato-Pancreato-Biliary Surgery, Department of Surgery, Carolinas Medical Center, Atrium Health, Charlotte, North Carolina, USA
| | - Keith Murphy
- Carolinas Center for Surgical Outcomes Science, Carolinas Medical Center, Atrium Health, Charlotte, North Carolina, USA
| | - Dionisios Vrochides
- Division of Hepato-Pancreato-Biliary Surgery, Department of Surgery, Carolinas Medical Center, Atrium Health, Charlotte, North Carolina, USA
| | - John B Martinie
- Division of Hepato-Pancreato-Biliary Surgery, Department of Surgery, Carolinas Medical Center, Atrium Health, Charlotte, North Carolina, USA
| | - Erin H Baker
- Division of Hepato-Pancreato-Biliary Surgery, Department of Surgery, Carolinas Medical Center, Atrium Health, Charlotte, North Carolina, USA
| | - Lee M Ocuin
- Division of Hepato-Pancreato-Biliary Surgery, Department of Surgery, Carolinas Medical Center, Atrium Health, Charlotte, North Carolina, USA
| | - Iain H McKillop
- Division of Hepato-Pancreato-Biliary Surgery, Department of Surgery, Carolinas Medical Center, Atrium Health, Charlotte, North Carolina, USA
| | - David A Iannitti
- Division of Hepato-Pancreato-Biliary Surgery, Department of Surgery, Carolinas Medical Center, Atrium Health, Charlotte, North Carolina, USA
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Cloyd JM, Ejaz A, Konda B, Makary MS, Pawlik TM. Neuroendocrine liver metastases: a contemporary review of treatment strategies. Hepatobiliary Surg Nutr 2020; 9:440-451. [PMID: 32832495 PMCID: PMC7423566 DOI: 10.21037/hbsn.2020.04.02] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Accepted: 03/31/2020] [Indexed: 12/12/2022]
Abstract
Well-differentiated neuroendocrine tumors (NETs) are globally increasing in prevalence and the liver is the most common site of metastasis. Neuroendocrine liver metastases (NELM) are heterogeneous in clinical presentation and prognosis. Fortunately, recent advances in diagnostic techniques and therapeutic strategies have improved the multidisciplinary management of this challenging condition. When feasible, surgical resection of NELM offers the best long-term outcomes. General indications for hepatic resection include performance status acceptable for major liver surgery, grade 1 or 2 tumors, absence of extrahepatic disease, adequate size and function of future liver remnant, and feasibility of resecting >90% of metastases. Adjunct therapies including concomitant liver ablation are generally safe when used appropriately and may expand the number of patients eligible for surgery. Among patients with synchronous resectable NELM, resection of the primary either in a staged or combined fashion is recommended. For patients who are not surgical candidates, liver-directed therapies such as transarterial embolization, chemoembolization, and radioembolization can provide locoregional control and improve symptoms of carcinoid syndrome. Multiple systemic therapy options also exist for patients with advanced or progressive disease. Ongoing research efforts are needed to identify novel biomarkers that will define the optimal indications for and sequencing of treatments to be delivered in a personalized fashion.
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Affiliation(s)
- Jordan M. Cloyd
- Departments of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Aslam Ejaz
- Departments of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Bhavana Konda
- Departments of Internal Medicine, The Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Mina S. Makary
- Departments of Radiology, The Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Timothy M. Pawlik
- Departments of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, USA
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26
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Cloyd JM, Wiseman JT, Pawlik TM. Surgical management of pancreatic neuroendocrine liver metastases. J Gastrointest Oncol 2020; 11:590-600. [PMID: 32655938 PMCID: PMC7340805 DOI: 10.21037/jgo.2019.11.02] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 11/13/2019] [Indexed: 12/12/2022] Open
Abstract
Pancreatic neuroendocrine tumors (PNET) are a heterogeneous group of neoplasms that vary in their clinical presentation, behavior and prognosis. The most common site of metastasis is the liver. Surgical resection of neuroendocrine liver metastases (NELM) is thought to afford the best long-term outcomes when feasible. Initial preoperative workup should include surveillance for carcinoid syndrome, screening for evidence of liver insufficiency, and performance of imaging specific to neuroendocrine tumors such as a somatostatin receptor positron emission tomography scan. Standard surgical principles apply to hepatic surgery for NELM, namely prioritizing low central venous pressure anesthesia, minimizing blood loss, knowledge of liver anatomy, generous use of intraoperative ultrasound, as well as safe parenchymal transection techniques and practices to avoid bile leakage. Knowledge of established prognostic factors may assist with patient selection, which is important for optimizing short- and long-term outcomes of hepatic resection. Adjunct therapies such as concomitant liver ablation are used frequently and are generally safe when used appropriately. For patients with synchronous resectable NELM, resection of the primary either in a staged or combined fashion is recommended. Primary tumor resection in the setting of unresectable metastatic disease is more controversial, however generally recommended if morbidity is acceptable. For patients who are not surgical candidates, due to either patient performance status or burden of liver disease, several liver-directed therapies such as transarterial embolization, chemoembolization, and radioembolization are available to assist with locoregional control, extend progression-free survival (PFS), and improve symptoms of carcinoid syndrome. Multiple systemic therapy options exist for patients with metastatic PNET which are often prioritized for those patients with advanced or progressive disease. A systematic approach in a multi-disciplinary setting is likely to result in the best long-term outcomes for patients with pancreatic NELM. Ongoing research is needed to determine the optimal patient selection for hepatic surgery as well as the ideal treatment sequencing for those patients with NELM.
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Affiliation(s)
- Jordan M Cloyd
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner, Columbus, OH, USA
| | - Jason T Wiseman
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner, Columbus, OH, USA
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner, Columbus, OH, USA
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27
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Ma ZY, Gong YF, Zhuang HK, Zhou ZX, Huang SZ, Zou YP, Huang BW, Sun ZH, Zhang CZ, Tang YQ, Hou BH. Pancreatic neuroendocrine tumors: A review of serum biomarkers, staging, and management. World J Gastroenterol 2020; 26:2305-2322. [PMID: 32476795 PMCID: PMC7243647 DOI: 10.3748/wjg.v26.i19.2305] [Citation(s) in RCA: 100] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Revised: 03/27/2020] [Accepted: 04/27/2020] [Indexed: 02/06/2023] Open
Abstract
Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of tumors with complicated treatment options that depend on pathological grading, clinical staging, and presence of symptoms related to hormonal secretion. With regard to diagnosis, remarkable advances have been made: Chromogranin A is recommended as a general marker for pNETs. But other new biomarker modalities, like circulating tumor cells, multiple transcript analysis, microRNA profile, and cytokines, should be clarified in future investigations before clinical application. Therefore, the currently available serum biomarkers are insufficient for diagnosis, but reasonably acceptable in evaluating the prognosis of and response to treatments during follow-up of pNETs. Surgical resection is still the only curative therapeutic option for localized pNETs. However, a debulking operation has also been proven to be effective for controlling the disease. As for drug therapy, steroids and somatostatin analogues are the first-line therapy for those with positive expression of somatostatin receptor, while everolimus and sunitinib represent important progress for the treatment of patients with advanced pNETs. Great progress has been achieved in the combination of systematic therapy with local control treatments. The optimal timing of local control intervention, planning of sequential therapies, and implementation of multidisciplinary care remain pending.
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Affiliation(s)
- Zu-Yi Ma
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
- Shantou University of Medical College, Shantou 515000, Guangdong Province, China
| | - Yuan-Feng Gong
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Hong-Kai Zhuang
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
- Shantou University of Medical College, Shantou 515000, Guangdong Province, China
| | - Zi-Xuan Zhou
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Shan-Zhou Huang
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Yi-Ping Zou
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
- Shantou University of Medical College, Shantou 515000, Guangdong Province, China
| | - Bo-Wen Huang
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Zhong-Hai Sun
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
- Shantou University of Medical College, Shantou 515000, Guangdong Province, China
| | - Chuan-Zhao Zhang
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Yun-Qiang Tang
- Department of Hepatobiliary Surgery, the Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510080, Guangdong Province, China
| | - Bao-Hua Hou
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
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Abstract
OPINION STATEMENT Pancreatic neuroendocrine neoplasms (PanNENs) are increasingly recognized entities, whose incidence has dramatically grown during the last two decades. Surgery plays a pivotal role in their management as it represents the only chance of cure. Since PanNENs display a wide range of aggressiveness, their surgical management needs to be tailored on tumor's and patient's characteristics. Currently, there are several open questions and burning issues in the field of PanNEN, such as the management of asymptomatic nonfunctioning pancreatic neuroendocrine tumors (NF-PanNET) ≤ 2 cm. An active surveillance of these small lesions has been demonstrated to be safe although the available evidences are only based on retrospective studies. On the other hand, formal pancreatic resection associated with lymphadenectomy represents the gold standard for patients with localized NF-PanNEN > 2 cm or NF-PanNEN ≤ 2 cm in the presence of symptoms, dilation of the main pancreatic duct or suspicion of nodal metastases. Surgery plays also an important role in the setting of metastatic disease. In particular, surgery is generally recommended in the presence of low-grade, resectable, metastatic disease, but several series have reported also a survival benefit of palliative primary tumor resection in patients with unresectable liver metastases. The role of surgery in PanNEN G3 is still controversial. Indeed, surgery is associated with an improved survival in patients with well-differentiated PanNET G3, whereas there is almost no survival benefit in case of poorly differentiated lesions.
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29
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Scoville SD, Xourafas D, Ejaz AM, Tsung A, Pawlik T, Cloyd JM. Contemporary indications for and outcomes of hepatic resection for neuroendocrine liver metastases. World J Gastrointest Surg 2020; 12:159-170. [PMID: 32426095 PMCID: PMC7215975 DOI: 10.4240/wjgs.v12.i4.159] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Revised: 02/21/2020] [Accepted: 03/05/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Although surgical resection is associated with the best long-term outcomes for neuroendocrine liver metastases (NELM), the current indications for and outcomes of surgery for NELM from a population perspective are not well understood.
AIM To determine the current indications for and outcomes of liver resection (LR) for NELM using a population-based cohort.
METHODS A retrospective review of the 2014-2017 American College of Surgeons National Surgical Quality Improvement Program and targeted hepatectomy databases was performed to identify patients who underwent LR for NELM. Perioperative characteristics and 30-d morbidity and mortality were analyzed.
RESULTS Among 669 patients who underwent LR for NELM, the median age was 60 (interquartile range: 51-67) and 51% were male. While the number of metastases resected ranged from 1 to 9, the most common (45%) number of tumors resected was one. The majority (68%) of patients had a largest tumor size of < 5 cm. Most patients underwent partial hepatectomy (71%) while fewer underwent a right or left hepatectomy or trisectionectomy. The majority of operations were open (82%) versus laparoscopic (17%) or robotic (1%). In addition, 30% of patients underwent intraoperative ablation while 45% had another concomitant operation including cholecystectomy (28.8%), bowel resection (20.2%), or partial pancreatectomy (3.4%). Overall 30-d morbidity and mortality was 29% and 1.3%, respectively. On multivariate analysis, American Society of Anesthesiologists class ≥ 3 [odds ratios (OR), OR = 2.089, 95% confidence intervals (CI): 1.197-3.645], open approach (OR = 1.867, 95%CI: 1.148-3.036), right hepatectomy (OR = 1.618, 95%CI: 1.014-2.582), and prolonged operative time of > 230 min (OR = 1.731, 95%CI: 1.168-2.565) were associated with higher 30-d morbidity while intraoperative ablation and concomitant procedures were not.
CONCLUSION LR for NELM was performed with relatively low postoperative morbidity and mortality. Concomitant procedures performed at the time of LR did not increase morbidity.
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Affiliation(s)
- Steven D Scoville
- Department of Surgery, Division of Surgical Oncology at The Ohio State University, James Cancer Center, Columbus, OH 43210, United States
- The Arthur G James Comprehensive Cancer Center and Solove Research Institute, The Ohio State University, Columbus, OH 43210, United States
| | - Dimitrios Xourafas
- Department of Surgery, Division of Surgical Oncology at The Ohio State University, James Cancer Center, Columbus, OH 43210, United States
- Department of Surgery, Harvard Medical School, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, United States
| | - Aslam M Ejaz
- Department of Surgery, Division of Surgical Oncology at The Ohio State University, James Cancer Center, Columbus, OH 43210, United States
- Department of Surgery, The Ohio State University, Columbus, OH 43210, United States
| | - Allan Tsung
- Department of Surgery, Division of Surgical Oncology at The Ohio State University, James Cancer Center, Columbus, OH 43210, United States
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Timothy Pawlik
- Department of Surgery, Division of Surgical Oncology at The Ohio State University, James Cancer Center, Columbus, OH 43210, United States
- Department of Surgery, The Ohio State University, Columbus, OH 43210, United States
| | - Jordan M Cloyd
- Department of Surgery, Division of Surgical Oncology at The Ohio State University, James Cancer Center, Columbus, OH 43210, United States
- Department of Surgery, The Ohio State University, Columbus, OH 43210, United States
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
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30
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Abstract
OBJECTIVES The combination chemotherapy regimen capecitabine/temozolomide (CAPTEM) is efficacious for metastatic well-differentiated pancreatic neuroendocrine tumors (PNETs), but its role in the neoadjuvant setting has not been established. METHODS The outcomes of all patients with locally advanced or resectable metastatic PNETs who were treated with neoadjuvant CAPTEM between 2009 and 2017 at 2 high-volume institutions were retrospectively reviewed. RESULTS Thirty patients with locally advanced PNET (n = 10) or pancreatic neuroendocrine hepatic metastases (n = 20) received neoadjuvant CAPTEM. Thirteen patients (43%) exhibited partial radiographic response (PR), 16 (54%) had stable disease, and 1 (3%) developed progressive disease. Twenty-six (87%) patients underwent resection (pancreatectomy [n = 12], combined pancreatectomy and liver resection [n = 8], or major hepatectomy alone [n = 6]); 3 (18%) declined surgery despite radiographic PR, and 1 (3%) underwent aborted pancreatoduodenectomy. Median primary tumor size was 5.5 cm, and median Ki-67 index was 3.5%. Rates of PR were similar across tumor grades (P = 0.24). At median follow-up of 49 months, median progression-free survival was 28.2 months and 5-year overall survival was 63%. CONCLUSIONS Neoadjuvant CAPTEM is associated with favorable radiographic objective response rates for locally advanced or metastatic PNET and may facilitate selection of patients appropriate for surgical resection.
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Kasai Y, Hirose K, Corvera CU, Kim GE, Hope TA, Shih BE, Harun N, Kim MO, Warren RS, Bergsland EK, Nakakura EK. Residual tumor volume discriminates prognosis after surgery for neuroendocrine liver metastasis. J Surg Oncol 2020; 121:330-336. [PMID: 31828813 DOI: 10.1002/jso.25811] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Accepted: 12/05/2019] [Indexed: 01/24/2023]
Abstract
BACKGROUND AND OBJECTIVES We developed objective measurements of preoperative and residual tumor volume, and debulking rate, to evaluate their prognostic value for neuroendocrine liver metastasis (NELM). METHODS Seventy-three patients who underwent surgery for NELM were analyzed retrospectively. Indices of preoperative and postoperative residual tumor volume (pre-volume index [VI] and post-VI) were calculated as the sum of the cubes of individual tumor diameters on preoperative and postoperative imaging, respectively. The debulking rate (%) was calculated as 100 - 100 × post-VI/pre-VI. The classification and regression trees method was used to classify pre-VI and post-VI. RESULTS Overall survival (OS) was discriminated by preoperative tumor volume (5-year OS rates, 87.8% for low pre-VI and 60.1% for high pre-VI; P = .037) and residual tumor volume (5-year OS rates, 88.1% for low post-VI and 24.8% for high post-VI; P < .001). In contrast, debulking rates of 100%, ≥90%, and <90% did not discriminate OS (5-year OS rates, 88.0%, 61.9%, and 58.9%, respectively, not significant). In multivariate analysis, residual tumor volume (high post-VI, hazard ratio, 6.40; 95% confidence interval, 1.45-32.3) was an independent prognostic factor for OS. CONCLUSIONS Objective measurement of tumor volume demonstrates that residual tumor volume is prognostic after surgery for NELM.
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Affiliation(s)
- Yosuke Kasai
- Department of Surgery, University of California, San Francisco, San Francisco, California.,UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California
| | - Kenzo Hirose
- Department of Surgery, University of California, San Francisco, San Francisco, California.,UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California
| | - Carlos U Corvera
- Department of Surgery, University of California, San Francisco, San Francisco, California.,UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California
| | - Grace E Kim
- UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California.,Department of Pathology, University of California, San Francisco, San Francisco, California
| | - Thomas A Hope
- UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California.,Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California
| | - Brandon E Shih
- UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California
| | - Nusrat Harun
- UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California
| | - Mi-Ok Kim
- UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California.,Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California
| | - Robert S Warren
- Department of Surgery, University of California, San Francisco, San Francisco, California.,UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California
| | - Emily K Bergsland
- UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California.,Department of Medicine, University of California, San Francisco, San Francisco, California
| | - Eric K Nakakura
- Department of Surgery, University of California, San Francisco, San Francisco, California.,UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California
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Tsilimigras DI, Squires MH, Cloyd JM, Pawlik TM. Treatment strategies for neuroendocrine liver metastases: an update. Expert Opin Orphan Drugs 2019. [DOI: 10.1080/21678707.2019.1651639] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Diamantis I. Tsilimigras
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Malcolm H. Squires
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Jordan M. Cloyd
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Timothy M. Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
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Zheng M, Li Y, Li T, Zhang L, Zhou L. Resection of the primary tumor improves survival in patients with gastro-entero-pancreatic neuroendocrine neoplasms with liver metastases: A SEER-based analysis. Cancer Med 2019; 8:5128-5136. [PMID: 31328428 PMCID: PMC6718577 DOI: 10.1002/cam4.2431] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Revised: 07/01/2019] [Accepted: 07/08/2019] [Indexed: 12/12/2022] Open
Abstract
Patients who suffer from gastro‐entero‐pancreatic neuroendocrine neoplasms (GEP‐NENs) often present with liver metastatic disease. The efficacy of primary tumor resection (PTR) for these patients remains controversial due to the relatively heterogeneous behavior of the primary tumor and the lack of clinical evidence. In this series, GEP‐NEN patients with liver metastases (LM) were selected from the Surveillance, Epidemiology, and End Results database between 2010 and 2015. A logistic regression model was used to analyze variables that were associated with PTR. A Cox proportional hazards model was used to identify independent prognostic risk factors. In total, 1547 patients were enrolled in our study, including 897 patients who underwent PTR. Resection of the primary tumor was associated with prolonged survival in all patients (5‐year overall survival (OS) rates: 57.0% vs 15.4%, P < .001), and improved 5‐year OS rates were observed in patients with gastric, small intestinal, colorectal, and pancreatic subtypes (39.7%, 73.3%, 24.6%, and 59.7%, respectively). On the multivariate analysis, PTR was an independent prognostic factor of prolonged OS (HR = 0.48, 95% CI: 0.39‐0.59, P < .001). Patients with a young age (≤60 years), small intestinal or colorectal NENs, a large primary tumor, lymph node (LN) metastases, and high tumor differentiation were more likely to undergo PTR. However, patients with colorectal NENs or a large primary tumor (≥4 cm) were at an increased risk of death independently in the PTR subgroup. The risk factors for OS also included old age, gastric tumor location, and poor differentiation. In conclusion, although PTR prolonged OS in all GEP‐NEN patients presenting with LM, surgical recipients should be considered carefully. Age, primary tumor site, size, and differentiation might help surgeons identify patients who could benefit from PTR.
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Affiliation(s)
- Mengzhen Zheng
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yan Li
- Xinxiang Medical University, Xinxiang, China
| | - Tong Li
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Lianfeng Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Lin Zhou
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Tsilimigras DI, Ntanasis-Stathopoulos I, Kostakis ID, Moris D, Schizas D, Cloyd JM, Pawlik TM. Is Resection of Primary Midgut Neuroendocrine Tumors in Patients with Unresectable Metastatic Liver Disease Justified? A Systematic Review and Meta-Analysis. J Gastrointest Surg 2019; 23:1044-1054. [PMID: 30671800 DOI: 10.1007/s11605-018-04094-9] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Accepted: 12/28/2018] [Indexed: 01/31/2023]
Abstract
INTRODUCTION Patients with midgut neuroendocrine tumors (MNETs) frequently present with metastatic disease at the time of diagnosis. Although combined resection of the primary MNET and liver metastases (NELM) is usually recommended for appropriate surgical candidates, primary tumor resection (PTR) in the setting of extensive, inoperable metastatic disease remains controversial. METHODS A systematic review was performed according to PRISMA guidelines utilizing Medline (PubMed), Embase, and Cochrane library-Cochrane Central Register of Controlled Trials (CENTRAL) databases until September 30, 2018. RESULTS Among patients with MNET and NELM, 1226 (68.4%; range, 35.5-85.1% per study) underwent PTR, whereas 567 (31.6%; range, 14.9-64.5%) patients did not. Median follow-up ranged from 55 to 90 months. Cytoreductive liver surgery was performed in approximately 15.7% (range, 0-34.8%) of patients. Pooled 5-year overall survival (OS) among the resected group was approximately 73.1% (range, 57-81%) versus 36.6% (range, 21-46%) for the non-resection group. For patients without liver debulking surgery, PTR remained associated with a decreased risk of death at 5 years compared with patients who did not have the primary tumor resected (HR 0.36, 95% CI 0.16 to 0.79, p = 0.01; I2 58%, p = 0.12). For patients undergoing PTR, 30-day postoperative mortality ranged from 1.43 to 2%. CONCLUSION PTR was safe with a low peri-operative risk of mortality and was associated with an improved OS for patients with MNET and unresectable NELM. Given the poor quality of evidence, however, strong evidenced-based recommendations cannot be made based on these retrospective single center-derived data. Future well-design randomized controlled trials will be critical in elucidating the optimal treatment strategies for patients with MNET and advanced metastatic disease.
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Affiliation(s)
- Diamantis I Tsilimigras
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
| | | | - Ioannis D Kostakis
- Department of Transplantation, Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Demetrios Moris
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - Dimitrios Schizas
- School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Jordan M Cloyd
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA. .,Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Oncology, Health Services Management and Policy, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite, Columbus, OH, 670, USA.
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Colquhoun SD. Neuroendocrine tumors with hepatic metastases: A review of evolving treatment options. LIVER RESEARCH 2018. [DOI: 10.1016/j.livres.2018.08.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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