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Kawaguchi Y, De Bellis M, Panettieri E, Duwe G, Vauthey JN. Debate: Improvements in Systemic Therapies for Liver Metastases Will Increase the Role of Locoregional Treatments. Hematol Oncol Clin North Am 2025; 39:207-220. [PMID: 39510674 DOI: 10.1016/j.hoc.2024.08.009] [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] [Indexed: 11/15/2024]
Abstract
The benefit of resection of liver metastases depends on primary diseases. Neuroendocrine tumors are associated with favorable prognosis after resection of liver metastases. Gastric cancer has worse tumor biology, and resection of gastric liver metastases should be performed in selected patients. A multidisciplinary approach is well established for colorectal liver metastases (CLMs). Resection remains the only curative treatment of CLM. Chemotherapy and molecular-targeted therapy have improved survival in unresectable metastatic colorectal cancer. Understanding of the following two strategies, conversion therapy and two-stage hepatectomy, are important to make this patient group to be candidates for curative-intent surgery.
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Affiliation(s)
- Yoshikuni Kawaguchi
- Department of Surgical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA; Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
| | - Mario De Bellis
- Department of Surgical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA
| | - Elena Panettieri
- Department of Surgical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA
| | - Gregor Duwe
- Department of Surgical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
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2
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Tran CG, Sherman SK, Chandrasekharan C, Howe JR. Surgical Management of Neuroendocrine Tumor Liver Metastases. Hematol Oncol Clin North Am 2025; 39:37-53. [PMID: 39510676 DOI: 10.1016/j.hoc.2024.08.001] [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] [Indexed: 11/15/2024]
Abstract
Patients with neuroendocrine tumor liver metastases (NETLMs) may develop carcinoid syndrome, carcinoid heart disease, or other symptoms from overproduction of hormones. Hepatic resection and cytoreduction is the most direct treatment of NETLMs in eligible patients, and cytoreduction improves symptoms, may reduce the sequelae of carcinoid syndrome, and extends survival. Parenchymal-sparing procedures, such as ablation and enucleation, should be considered during cytoreduction to maximize treatment of multifocal tumors while preserving healthy liver tissue. For patients with large hepatic tumor burdens, high-grade disease, or comorbidities precluding surgery, liver-directed and systemic therapies can be used to palliate symptoms and improve progression-free survival.
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Affiliation(s)
- Catherine G Tran
- Department of Surgery, Division of Colorectal Surgery, University of Minnesota, Minneapolis, MN
| | - Scott K Sherman
- Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA
| | | | - James R Howe
- Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA.
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3
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Kenney LM, Hughes M. Surgical Management of Gastroenteropancreatic Neuroendocrine Tumors. Cancers (Basel) 2025; 17:377. [PMID: 39941746 PMCID: PMC11816225 DOI: 10.3390/cancers17030377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2024] [Revised: 01/17/2025] [Accepted: 01/22/2025] [Indexed: 02/16/2025] Open
Abstract
BACKGROUND/OBJECTIVES Neuroendocrine tumors (NETs) are heterogeneous malignancies arising from enterochromaffin cells that can arise from the gastrointestinal (GI) tract and pancreas. Surgical management is the cornerstone of treatment, with the optimal approach tailored by tumor grade, size, location, and presence of metastasis. This review discusses the current strategies for the surgical management of NETs of the gastroenteropancreatic tract. METHODS A review of the available literature was conducted to evaluate surgical approaches to NETs. Consensus guidelines were incorporated to synthesize evidence-based recommendations. RESULTS For gastric NETs, surgical approach depends on Rindi Classification, WHO grade, and tumor size, with endoscopic approaches favored for smaller and low-grade lesions. Small bowel NETs can be multifocal and thus often require a surgical approach with careful evaluation of the entire intestine. Pancreatic NETs are categorized as functional or non-functional, with enucleation or formal resection strategies based on size, location, functional status, and risk of malignancy. Colorectal NETs are primarily treated with transanal localized or formal surgical resection, depending on lesion size and depth of invasion or presence of lymph node involvement. Appendiceal NETs are either treated with appendectomy or right hemicolectomy, depending on the size, location, and invasiveness of the lesions. For metastatic NETs, cytoreduction, liver transplantation, and targeted therapies offer symptom relief and possible survival benefits. CONCLUSIONS Surgical resection provides curative potential for localized NETs and symptom control in metastatic cases. Future research is essential to refine guidelines for intermediate-risk lesions and multifocal tumors, ensuring optimal outcomes for patients with gastroenteropancreatic NETs.
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Affiliation(s)
- Lisa M. Kenney
- Department of Surgery, Eastern Virginia Medical School, Macon and Joan Brock Virginia Health Sciences at Old Dominion University, 825 Fairfax Avenue, Suite 610, Norfolk, VA 23507, USA;
| | - Marybeth Hughes
- Department of Surgery, Division of Surgical Oncology, Eastern Virginia Medical School, Macon and Joan Brock Virginia Health Sciences at Old Dominion University, 825 Fairfax Avenue, Suite 610, Norfolk, VA 23507, USA
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Hounschell CA, Higginbotham S, Al-Kasspooles M, Selby LV. Gastroenteropancreatic Neuroendocrine Tumor with Peritoneal Metastasis: A Review of Current Management. Cancers (Basel) 2024; 16:3472. [PMID: 39456565 PMCID: PMC11506451 DOI: 10.3390/cancers16203472] [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: 09/18/2024] [Revised: 10/07/2024] [Accepted: 10/10/2024] [Indexed: 10/28/2024] Open
Abstract
Peritoneal metastasis in gastroenteropancreatic neuroendocrine tumors poses a significant clinical challenge, with limited data guiding management strategies. We review the existing literature on surgical and systemic treatment modalities for peritoneal metastasis from gastroenteropancreatic neuroendocrine tumors. Surgical interventions, including cytoreductive surgery, have shown promise in improving symptom control and overall survival-particularly in cases in which 70% cytoreduction can be achieved. Hyperthermic intraperitoneal chemotherapy remains controversial due to a paucity of high-level evidence and a lack of consensus for routine use. The use of systemic therapy in the setting of peritoneal metastasis from gastroenteropancreatic neuroendocrine tumors is extrapolated from high-quality evidence for its use in the setting of the solid organ metastasis of this disease. The use of somatostatin analogs for symptom control and some antiproliferative effects is supported by large clinical trials. Additional strong evidence exists for the use of interferon-alpha, everolimus, and sunitinib, particularly in pancreatic neuroendocrine tumors. Cytotoxic chemotherapy and peptide receptor radionuclide therapy may be used in select cases, though as an emerging treatment modality, the optimal sequence of peptide receptor radionuclide therapy within the existing algorithms is unknown. Significant gaps in understanding and standardized management exist, particularly for those patients presenting with peritoneal metastasis, and targeted research to optimize outcomes in this population is needed.
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Affiliation(s)
- Corey A. Hounschell
- Department of Surgery, University of Kansas Medical Center, Kansas City, KS 66103, USA; (C.A.H.); (M.A.-K.)
| | | | - Mazin Al-Kasspooles
- Department of Surgery, University of Kansas Medical Center, Kansas City, KS 66103, USA; (C.A.H.); (M.A.-K.)
| | - Luke V. Selby
- Department of Surgery, University of Kansas Medical Center, Kansas City, KS 66103, USA; (C.A.H.); (M.A.-K.)
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Maurer E, Bartsch DK. [Local resection of small intestine neuroendocrine neoplasms (SI-NEN) : Current principles]. CHIRURGIE (HEIDELBERG, GERMANY) 2024; 95:818-824. [PMID: 38771340 DOI: 10.1007/s00104-024-02102-0] [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: 04/24/2024] [Indexed: 05/22/2024]
Abstract
BACKGROUND Neuroendocrine tumors of the small bowel (small intestine neuroendocrine neoplasms, SI-NEN) are the most frequent tumors of the small intestine and approximately 30-40% are still surgically treatable with curative intent at the time of diagnosis. Certain surgical principles must be followed for optimal oncological outcomes and good postoperative quality of life. METHODS Based on international guidelines and own experiences, the locoregional surgical treatment of SI-NENs is presented. RESULTS Locoregional SI-NENs should always be resected if technically feasible, as only this approach can achieve a long-term cure and even small primary tumors (< 10 mm) often already show lymphatic metastasis. The resectability of SI-NENs and their difficulty depend on the extent of lymphatic metastasis, which should be assessed based on preoperative imaging of the extent around the superior mesenteric artery. Currently, the surgical gold standard for SI-NENs is open surgery with bidigital palpation of the entire small intestine followed by primary tumor resection via small bowel segment resection, right hemicolectomy or ileocecal resection and vessel-sparing, and therefore organ-preserving lymphadenectomy (≥ 8 lymph nodes). The guidelines consider that laparoscopic or robotic approaches are justified only for early stages of SI-NENs. CONCLUSION Guideline-compliant surgical treatment of locoregional SI-NEN enables recurrence-free long-term survival with good quality of life.
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Affiliation(s)
- Elisabeth Maurer
- Klinik für Visceral‑, Thorax- und Gefäßchirurgie, Philipps-Universität Marburg, Baldingerstraße, 35043, Marburg, Deutschland.
| | - Detlef K Bartsch
- Klinik für Visceral‑, Thorax- und Gefäßchirurgie, Philipps-Universität Marburg, Baldingerstraße, 35043, Marburg, Deutschland
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Sharma A, Muralitharan M, Ramage J, Clement D, Menon K, Srinivasan P, Elmasry M, Reed N, Seager M, Srirajaskanthan R. Current Management of Neuroendocrine Tumour Liver Metastases. Curr Oncol Rep 2024; 26:1070-1084. [PMID: 38869667 PMCID: PMC11416395 DOI: 10.1007/s11912-024-01559-w] [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] [Accepted: 05/22/2024] [Indexed: 06/14/2024]
Abstract
PURPOSE OF REVIEW This article aims to illustrate the current state of investigations and management of liver metastases in patients with Neuroendocrine Neoplasms. Neuroendocrine tumours (NETs) are rising in incidence globally and have become the second most prevalent gastrointestinal malignancy in UK and USA. Frequently, patients have metastatic disease at time of presentation. The liver is the most common site of metastases for gastro-enteropancreatic NETs. Characterisation of liver metastases with imaging is important to ensure disease is not under-staged. RECENT FINDINGS Magnetic resonance imaging and positron emission tomography are now becoming standard of care for imaging liver metastases. There is an increasing armamentarium of therapies available for management of NETs and loco-regional therapy for liver metastases. The data supporting surgical and loco-regional therapy is reviewed with focus on role of liver transplantation. It is important to use appropriate imaging and classification of NET liver metastases. It is key that decisions regarding approach to treatment is undertaken in a multidisciplinary team and that individualised approaches are considered for management of patients with metastatic NETs.
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Affiliation(s)
- Aditya Sharma
- Department of Gastroenterology, King's College Hospital, SE5 9RS, London, U.K
| | | | - John Ramage
- Neuroendocrine Tumour Unit, Institute of Liver Studies, King's College Hospital, SE5 9RS, London, U.K
| | - Dominique Clement
- Department of Gastroenterology, King's College Hospital, SE5 9RS, London, U.K
- Neuroendocrine Tumour Unit, Institute of Liver Studies, King's College Hospital, SE5 9RS, London, U.K
| | - Krishna Menon
- Institute of Liver Studies, King's College Hospital, SE5 9RS, London, U.K
| | - Parthi Srinivasan
- Institute of Liver Studies, King's College Hospital, SE5 9RS, London, U.K
| | - Mohamed Elmasry
- Institute of Liver Studies, King's College Hospital, SE5 9RS, London, U.K
| | - Nick Reed
- Department of Oncology, Beatson Centre, G12 0YN, Glasgow, U.K
| | - Matthew Seager
- Department of Radiology, King's College Hospital, SE5 9RS, London, U.K
| | - Rajaventhan Srirajaskanthan
- Department of Gastroenterology, King's College Hospital, SE5 9RS, London, U.K..
- Neuroendocrine Tumour Unit, Institute of Liver Studies, King's College Hospital, SE5 9RS, London, U.K..
- Neuroendocrine Tumour Unit Institute of liver studies, King's College Hospital, SE5 9RS, London, U.K..
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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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8
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Kartik A, Armstrong VL, Stucky CC, Wasif N, Fong ZV. Contemporary Approaches to the Surgical Management of Pancreatic Neuroendocrine Tumors. Cancers (Basel) 2024; 16:1501. [PMID: 38672582 PMCID: PMC11048062 DOI: 10.3390/cancers16081501] [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: 02/20/2024] [Revised: 04/04/2024] [Accepted: 04/10/2024] [Indexed: 04/28/2024] Open
Abstract
The incidence of pancreatic neuroendocrine tumors (PNETs) is on the rise primarily due to the increasing use of cross-sectional imaging. Most of these incidentally detected lesions are non-functional PNETs with a small proportion of lesions being hormone-secreting, functional neoplasms. With recent advances in surgical approaches and systemic therapies, the management of PNETs have undergone a paradigm shift towards a more individualized approach. In this manuscript, we review the histologic classification and diagnostic approaches to both functional and non-functional PNETs. Additionally, we detail multidisciplinary approaches and surgical considerations tailored to the tumor's biology, location, and functionality based on recent evidence. We also discuss the complexities of metastatic disease, exploring liver-directed therapies and the evolving landscape of minimally invasive surgical techniques.
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Affiliation(s)
| | | | | | | | - Zhi Ven Fong
- Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, Mayo Clinic Arizona, Phoenix, AZ 85054, USA
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9
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Van Den Heede K, van Beek DJ, Van Slycke S, Borel Rinkes I, Norlén O, Stålberg P, Nordenström E. Surgery for advanced neuroendocrine tumours of the small bowel: recommendations based on a consensus meeting of the European Society of Endocrine Surgeons (ESES). Br J Surg 2024; 111:znae082. [PMID: 38626261 DOI: 10.1093/bjs/znae082] [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: 11/10/2023] [Revised: 02/19/2024] [Accepted: 03/04/2024] [Indexed: 04/18/2024]
Abstract
BACKGROUND Small bowel neuroendocrine tumours often present with locally advanced or metastatic disease. The aim of this paper is to provide evidence-based recommendations regarding (controversial) topics in the surgical management of advanced small bowel neuroendocrine tumours. METHODS A working group of experts was formed by the European Society of Endocrine Surgeons. The group addressed 11 clinically relevant questions regarding surgery for advanced disease, including the benefit of primary tumour resection, the role of cytoreduction, the extent of lymph node clearance, and the management of an unknown primary tumour. A systematic literature search was performed in MEDLINE to identify papers addressing the research questions. Final recommendations were presented and voted upon by European Society of Endocrine Surgeons members at the European Society of Endocrine Surgeons Conference in Mainz in 2023. RESULTS The literature review yielded 1223 papers, of which 84 were included. There were no randomized controlled trials to address any of the research questions and therefore conclusions were based on the available case series, cohort studies, and systematic reviews/meta-analyses of the available non-randomized studies. The proposed recommendations were scored by 38-51 members and rated 'strongly agree' or 'agree' by 64-96% of participants. CONCLUSION This paper provides recommendations based on the best available evidence and expert opinion on the surgical management of locally advanced and metastatic small bowel neuroendocrine tumours.
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Affiliation(s)
- Klaas Van Den Heede
- Department of General and Endocrine Surgery, Onze-Lieve-Vrouw (OLV) Hospital Aalst-Asse-Ninove, Aalst, Belgium
| | - Dirk-Jan van Beek
- Department of Endocrine Surgical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Sam Van Slycke
- Department of General and Endocrine Surgery, Onze-Lieve-Vrouw (OLV) Hospital Aalst-Asse-Ninove, Aalst, Belgium
- Department of General Surgery, AZ Damiaan, Ostend, Belgium
- Department of Head and Skin, University Hospital Ghent, Ghent, Belgium
| | - Inne Borel Rinkes
- Department of Endocrine Surgical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Olov Norlén
- Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden
| | - Peter Stålberg
- Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden
| | - Erik Nordenström
- Department of Surgery, Skåne University Hospital, Lund, Sweden
- Department of Clinical Sciences, Lund University, Lund, Sweden
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Chi Y, Jiang L, Shi S, He S, Bai C, Cao D, Cai J, Chen Q, Chen X, Deng Y, Du S, Huang Z, Huo L, Ji Y, Li J, Lou W, Luo J, Shi X, Song L, Sun B, Tan H, Wang F, Wang X, Wei Z, Wu W, Xiu D, Xu J, Xue H, Yang Y, Yin F, Yu J, Yuan C, Zhang Y, Zhou W, Zhao D, Zhao H. Chinese expert consensus on multidisciplinary diagnosis and treatment of pancreatic neuroendocrine liver metastases. JOURNAL OF PANCREATOLOGY 2023; 6:139-150. [DOI: 10.1097/jp9.0000000000000141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025] Open
Abstract
Many management strategies are available for pancreatic neuroendocrine neoplasms with liver metastases. However, a lack of biological, molecular, and genomic information and an absence of data from rigorous trials limit the validity of these strategies. This review presents the viewpoints from an international conference consisting of several expert working groups. The working groups reviewed a series of questions of particular interest to clinicians taking care of patients with pancreatic neuroendocrine neoplasms with liver metastases by reviewing the existing management strategies and literature, evaluating the evidence on which management decisions were based, developing internationally acceptable recommendations for clinical practice, and making recommendations for clinical and research endeavors. The review for each question will be followed by recommendations from the panel.
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Affiliation(s)
- Yihebali Chi
- Department of Medical Oncology, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Liming Jiang
- Department of Diagnostic Radiology, National Cancer Center Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Susheng Shi
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shun He
- Department of Endoscopy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chunmei Bai
- Department of Medical Oncology, Peking Union Medical College Hospital, Beijing, China
| | - Dan Cao
- Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Jianqiang Cai
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qichen Chen
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiao Chen
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yiqiao Deng
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shunda Du
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhen Huang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Li Huo
- Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yuan Ji
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jie Li
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China
| | - Wenhui Lou
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jie Luo
- Department of Pathology, China-Japan Friendship Hospital, Beijing, China
| | - Xueying Shi
- Department of Pathology, Peking University Third Hospital, School of Basic Medical Science, Peking University Health Science Center, Beijing, China
| | - Lijie Song
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Bei Sun
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Huangying Tan
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing, China
| | - Feng Wang
- Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Xuan Wang
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhewen Wei
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wenming Wu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Dianrong Xiu
- Department of General Surgery, Peking University Third Hospital, Beijing, China
| | - Jianming Xu
- Department of Gastrointestinal Oncology, The Fifth Medical Center of the PLA General Hospital, Beijing, China
| | - Huadan Xue
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yi Yang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fei Yin
- Department of Gastroenterology, Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Jiangyuan Yu
- Department of Nuclear Medicine, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital & Institute, Beijing, China
| | - Chunhui Yuan
- Department of General Surgery, Peking University Third Hospital, Beijing, China
| | - Yefan Zhang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weixun Zhou
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Dongbing Zhao
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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11
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Rosowicz A, Bangla VG, Johnson JW, Olson L, Chen J, Divino CM. Surgery Improves Patient-Reported Outcomes in Patients with Intestinal and Pancreatic NETs: A Prospective Analysis. Ann Surg Oncol 2023; 30:6777-6785. [PMID: 37349613 DOI: 10.1245/s10434-023-13729-4] [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: 01/25/2023] [Accepted: 05/23/2023] [Indexed: 06/24/2023]
Abstract
BACKGROUND Incorporation of patient-reported outcomes such as health-related quality of life has become increasingly important in the management of chronic diseases such as cancer. In this prospective study, we examined the effect of surgical resection on quality of life in patients with intestinal and pancreatic neuroendocrine tumors (NETs). METHODS Thirty-two patients underwent NET resection at our institution from January 2020 to January 2022. All patients completed the 12-item short-form quality-of-life survey prior to surgery, as well as at the 3-, 6-, and 12-month postoperative time points. The presence and severity of specific carcinoid syndrome symptoms (diarrhea, flushing, and abdominal pain) were also recorded during pre- and postoperative appointments. RESULTS Patients experienced significant increases in both mental and physical health after surgery. Mental health scores significantly increased at all three time points (baseline: 51.33; 3-month: 53.17, p = 0.02; 6-month: 57.20, p < 0.001; 12-month: 57.34, p = 0.002), and physical health scores increased at 6 and 12 months (baseline: 50.39; 6-month: 53.16, p = 0.04; 12-month: 55.02, p = 0.003). Younger patients benefited more in terms of physical health, while older patients had more significant increases in mental health. Patients with metastatic disease, larger primary tumors, and those receiving medical therapy had lower baseline quality-of-life scores and greater improvements after surgery. The vast majority of patients in this study also experienced alleviation of carcinoid syndrome symptoms. CONCLUSIONS In addition to prolonging survival, resection of intestinal and pancreatic NETs leads to significantly improved patient-reported quality of life.
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Affiliation(s)
| | - Venu G Bangla
- Department of Surgery, General Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | - Laura Olson
- Department of Surgery, General Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jenny Chen
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Celia M Divino
- Department of Surgery, General Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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12
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Howe JR. Metastatic small bowel neuroendocrine tumours: surgical management of the primary. Br J Surg 2023; 110:1293-1295. [PMID: 37566464 DOI: 10.1093/bjs/znad247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Revised: 07/17/2023] [Accepted: 07/18/2023] [Indexed: 08/13/2023]
Affiliation(s)
- James R Howe
- Surgical Oncology and Endocrine Surgery, Roy J. and Lucille A. Carver University of Iowa College of Medicine, Iowa City, Iowa, USA
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13
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Ruff SM, Thompson DA, Lad NL, Anantha S, DePeralta DK, Weiss MJ, Deutsch GB. Surgical debulking is associated with improved survival for patients with neuroendocrine liver metastases of unknown primary. HPB (Oxford) 2023; 25:1074-1082. [PMID: 37258312 DOI: 10.1016/j.hpb.2023.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Revised: 03/27/2023] [Accepted: 05/05/2023] [Indexed: 06/02/2023]
Abstract
BACKGROUND Resection of neuroendocrine tumors (NET) with surgical debulking of liver metastasis (NETLM) is associated with improved survival. In patients with an unknown primary (UP-NETLM), the effects of debulking remains unclear. METHODS The National Cancer Database (2004-2016) was queried for patients with small intestine (SI) and pancreas (P) NETLMs. If the liver was listed as the primary site, the patient's disease was classified as UP-NETLM. RESULTS Patients with UP-NETLM, SI-NETLM, and P-NETLM who were managed non-operatively demonstrated a significant difference in 5-year overall survival (OS) (21.5% vs. 39.2% vs. 17.1%; p < 0.0001). OS in patients who underwent debulking was higher (63.7% vs. 73.2% vs. 54.2%). Patients with UP-NETLMs who underwent debulking had similar OS to patient with SI-NETLM (p = 0.051), but significantly higher OS, depending on tumor differentiation, compared to patients with P-NETLMs. If well-differentiated, surgery for UP-NETLMs was associated with a higher rate of OS (p = 0.009), while no difference was observed if moderately (p = 0.209) or poorly/undifferentiated (p = 0.633). P-NETLMs were associated with worse OS (p < 0.001) on multivariate analysis. DISCUSSION Debulking in patients with UP-NETLMs was associated with similar OS compared to patients with SI-NETLMs and better or similar OS compared to patient with P-NETLMs.
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Affiliation(s)
- Samantha M Ruff
- Department of General Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, 270-05 76th Ave, Queens, NY, 11040, United States
| | - Dane A Thompson
- Department of General Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, 270-05 76th Ave, Queens, NY, 11040, United States
| | - Neha L Lad
- Northwell Health Cancer Institute, 1111 Marcus Ave, New Hyde Park, NY 11042, United States
| | - Sandeep Anantha
- Northwell Health Cancer Institute, 1111 Marcus Ave, New Hyde Park, NY 11042, United States
| | - Danielle K DePeralta
- Northwell Health Cancer Institute, 1111 Marcus Ave, New Hyde Park, NY 11042, United States
| | - Matthew J Weiss
- Northwell Health Cancer Institute, 1111 Marcus Ave, New Hyde Park, NY 11042, United States
| | - Gary B Deutsch
- Northwell Health Cancer Institute, 1111 Marcus Ave, New Hyde Park, NY 11042, United States.
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14
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Chetcuti Zammit S, Sidhu R. Small bowel neuroendocrine tumours - casting the net wide. Curr Opin Gastroenterol 2023; 39:200-210. [PMID: 37144538 DOI: 10.1097/mog.0000000000000917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/06/2023]
Abstract
PURPOSE OF REVIEW Our aim is to provide an overview of small bowel neuroendocrine tumours (NETs), clinical presentation, diagnosis algorithm and management options. We also highlight the latest evidence on management and suggest areas for future research. RECENT FINDINGS Dodecanetetraacetic acid (DOTATATE) scan can detect NETs with an improved sensitivity than when compared with an Octreotide scan. It is complimentary to small bowel endoscopy that provides mucosal views and allows the delineation of small lesions undetectable on imaging. Surgical resection is the best management modality even in metastatic disease. Prognosis can be improved with the administration of somatostatin analogues and Evarolimus as second-line therapies. SUMMARY NETs are heterogenous tumours affecting most commonly the distal small bowel as single or multiple lesions. Their secretary behaviour can lead to symptoms, most commonly diarrhoea and weight loss. Metastases to the liver are associated with carcinoid syndrome.
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Affiliation(s)
| | - Reena Sidhu
- Academic Department of Gastroenterology, Royal Hallamshire Hospital, Department of Infection, Immunity and Cardiovascular Diseases, University of Sheffield, Sheffield, UK
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15
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Mahuron KM, Singh G. Defining a New Classification System for the Surgical Management of Neuroendocrine Tumor Liver Metastases. J Clin Med 2023; 12:jcm12072456. [PMID: 37048539 PMCID: PMC10095340 DOI: 10.3390/jcm12072456] [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: 01/23/2023] [Revised: 03/16/2023] [Accepted: 03/18/2023] [Indexed: 04/14/2023] Open
Abstract
Although rarely curative, hepatic cytoreduction of neuroendocrine tumor liver metastases (NETLM) is associated with improved symptom control and prolonged survival. Preoperative 68Ga DOTATATE and gadoxetic acid-enhanced liver MRI can improve characterization of hepatic disease extent to improve surgical clearance, and resection of the primary tumor is associated with improved survival regardless of whether the liver metastases are treated. As parenchymal-sparing surgical techniques and the lowering of the debulking threshold have expanded the numbers of eligible NETLM patients for hepatic cytoreduction, we propose a new classification system to help guide surgical management. A multimodal approach that includes surgery, liver-directed therapies, and systemic therapies has improved outcomes and increased longevity for patients with well-differentiated metastatic NET.
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Affiliation(s)
- Kelly M Mahuron
- Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA
| | - Gagandeep Singh
- Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA
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16
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Sinnamon AJ, Luo E, Xu A, Zhu S, Denbo JW, Fleming JB, Anaya DA. Simultaneous Hepatic and Visceral Resection: Preoperative Risk Stratification and Implications on Return to Intended Oncologic Therapy. Ann Surg Oncol 2023; 30:1772-1783. [PMID: 36418800 DOI: 10.1245/s10434-022-12834-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 11/01/2022] [Indexed: 11/25/2022]
Abstract
PURPOSE Sequence of therapies for synchronous liver metastasis (LM) is complex, with data supporting individualized approaches, although no guiding tools are currently available. We assessed the impact of simultaneous hepatic and visceral resections (SHVR) on textbook outcome (TO) and return to intended oncologic therapy (RIOT), and provide risk-stratification tools to guide individualized decision making and counseling. METHODS Patients with synchronous LM undergoing hepatectomy ± SHVR were included (2015-2021). Primary and secondary outcomes were TO and RIOT (days), respectively. Using multivariable modeling, a risk score for TO was developed. Decision tree analysis using recursive partitioning was performed for hierarchical risk stratification. The associations between SHVR, TO, and RIOT were examined. RESULTS Among 533 patients identified, 124 underwent SHVR. TO overall was 71.7%; 79.2% in the non-SHVR group and 46.8% in the SHVR group (p < 0.001). SHVR was the strongest predictor of non-TO (right colon/small bowel: odds ratio [OR] 4.63, 95% confidence interval [CI] 2.65-8.08; left colon/rectum: OR 6.09, 95% CI 2.59-14.3; stomach/pancreas: OR 6.69, 95% CI 1.46-30.7; multivisceral: OR 10.9, 95% CI 3.03-39.5). A composite score was developed yielding three risk strata for TO (score 0-2: 89% vs. score 3-5: 67% vs. score ≥ 6: 37%; p < 0.001). Decision tree analysis was congruent, identifying SHVR as the most important determinant of TO. In patients with colorectal LM, SHVR was associated with delayed time to RIOT (p = 0.004); the risk-stratification tool for TO was equally predictive of RIOT (p < 0.01). CONCLUSIONS SHVR is associated with reduced likelihood of TO and in turn delayed RIOT. As SHVR is increasingly performed in order to consolidate cancer care, patient selection considering these different outcomes is critical.
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Affiliation(s)
- Andrew J Sinnamon
- Section of Hepatobiliary Tumors, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. .,University of South Florida Morsani College of Medicine, Tampa, FL, USA.
| | - Eric Luo
- University of South Florida Morsani College of Medicine, Tampa, FL, USA
| | - Aileen Xu
- University of South Florida Morsani College of Medicine, Tampa, FL, USA
| | - Sarah Zhu
- Section of Hepatobiliary Tumors, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Jason W Denbo
- Section of Hepatobiliary Tumors, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Jason B Fleming
- Section of Hepatobiliary Tumors, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Daniel A Anaya
- Section of Hepatobiliary Tumors, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
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Abstract
Neuroendocrine tumors (NETs) represent a heterogeneous group of tumors, with variable presentation based on the location of origin and degree of metastatic spread. There are no randomized control trials to guide surgical management; however, surgery remains the mainstay of treatment for most gastroenteropancreatic NETs based on retrospective studies. Metastatic disease is common at the time of presentation, particularly in the liver. There is a role for cytoreduction for improvement of both symptoms and survival. Robust prospective randomized data exists to support the use of medical therapies to improve progression-free and overall survival in patients with advanced, metastatic, and unresectable NETs.
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18
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Surgery, Liver Directed Therapy and Peptide Receptor Radionuclide Therapy for Pancreatic Neuroendocrine Tumor Liver Metastases. Cancers (Basel) 2022; 14:cancers14205103. [PMID: 36291892 PMCID: PMC9599940 DOI: 10.3390/cancers14205103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 09/19/2022] [Accepted: 10/12/2022] [Indexed: 11/16/2022] Open
Abstract
Pancreatic neuroendocrine tumors (PNETs) are described by the World Health Organization (WHO) classification by grade (1–3) and degree of differentiation. Grade 1 and 2; well differentiated PNETs are often characterized as relatively “indolent” tumors for which locoregional therapies have been shown to be effective for palliation of symptom control and prolongation of survival even in the setting of advanced disease. The treatment of liver metastases includes surgical and non-surgical modalities with varying degrees of invasiveness; efficacy; and risk. Most of these modalities have not been prospectively compared. This paper reviews literature that has been published on treatment of pancreatic neuroendocrine liver metastases using surgery; liver directed embolization and peptide receptor radionuclide therapy (PRRT). Surgery is associated with the longest survival in patients with resectable disease burden. Liver-directed (hepatic artery) therapies can sometimes convert patients with borderline disease into candidates for surgery. Among the three embolization modalities; the preponderance of data suggests chemoembolization offers superior radiographic response compared to bland embolization and radioembolization; but all have similar survival. PRRT was initially approved as salvage therapy in patients with advanced disease that was not amenable to resection or embolization; though the role of PRRT is evolving rapidly
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19
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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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20
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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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21
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Deguelte S, Metoudi A, Rhaiem R, Hoeffel C, Brixi H, Cadiot G, Kianmanesh R. Small Intestinal Neuroendocrine Neoplasm: Factors Associated with the Development of Local Tumor-Related Symptoms. Neuroendocrinology 2022; 112:252-262. [PMID: 33853084 DOI: 10.1159/000516514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 04/12/2021] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Clinical presentations of small intestinal neuroendocrine neoplasms (SiNENs) can range from asymptomatic to life-threatening complications. Other than primary tumor(s), mesenteric mass (MM) can provide local tumor-related (LTR) symptoms. Although some expert centers propose routine primary resection to avoid complications in stage IV patients, some guidelines suggest avoiding primary tumor resection unless in the presence of symptoms. This study was aimed to identify factors associated with the presence or development of LTR symptoms. METHODS From 2012 to 2019, SiNEN patients with appropriate initial morphological imaging were included. All initial imaging was reviewed. Associations between factors and LTR symptoms were assessed by logistic regression. RESULTS Among 144 SiNEN patients, 66 met the inclusion criteria. Multivariate analysis identified on initial morphological imaging (i) any visible primary tumor (p < 0.01) and (ii) MM contact ≥180° with the superior mesenteric vessels (p ≤ 0.02), as independent factors associated with LTR symptoms in the whole study population as well as in the subgroup of primary resected patients. Among the 14 (21%) patients with both factors on initial cross-sectional conventional imaging, 12 (18%) were straightaway symptomatic at diagnosis and the remaining became symptomatic during the follow-up. All asymptomatic patients, without upfront surgery and without any predictive factor 16/18 (89%), stayed asymptomatic during the 2.7-year median follow-up. The absence of association between these 2 factors yielded a sensitivity of 100%, a specificity of 62%, and a negative predictive value of 100% for the occurrence of LTR symptoms. CONCLUSION The presence of any visible primary tumor and/or MM superior mesenteric vessels contact ≥180° at initial cross-sectional imaging are 2 easily identifiable factors, which can help physicians for the decision-making regarding timing and type of surgery for SiNENs. Larger multicenter studies should endorse these results.
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Affiliation(s)
- Sophie Deguelte
- Department of Endocrine, Digestive and Oncological Surgery, Robert Debré University-Hospital, Reims, France
- Faculty of Medicine, EA 3797, University of Reims Champagne-Ardenne, Reims, France
| | - Alicia Metoudi
- Department of Endocrine, Digestive and Oncological Surgery, Robert Debré University-Hospital, Reims, France
| | - Rami Rhaiem
- Department of Endocrine, Digestive and Oncological Surgery, Robert Debré University-Hospital, Reims, France
| | - Chirstine Hoeffel
- Department of Radiology, Robert Debré University-Hospital, Reims, France
- Reims Medical School, University of Reims Champagne Ardennes, Reims, France
| | - Hedia Brixi
- Department of Hepato-Gastro-Enterology, Robert Debré University-Hospital, Reims, France
| | - Guillaume Cadiot
- Reims Medical School, University of Reims Champagne Ardennes, Reims, France
- Department of Hepato-Gastro-Enterology, Robert Debré University-Hospital, Reims, France
| | - Reza Kianmanesh
- Department of Endocrine, Digestive and Oncological Surgery, Robert Debré University-Hospital, Reims, France
- Reims Medical School, University of Reims Champagne Ardennes, Reims, France
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Frey S, Mirallié E, Le Bras M, Regenet N. What Are the Place and Modalities of Surgical Management for Pancreatic Neuroendocrine Neoplasms? A Narrative Review. Cancers (Basel) 2021; 13:5954. [PMID: 34885063 PMCID: PMC8656750 DOI: 10.3390/cancers13235954] [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] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 11/23/2021] [Accepted: 11/24/2021] [Indexed: 12/14/2022] Open
Abstract
Pancreatic neuroendocrine neoplasms (panNENs) are a heterogeneous group of tumors derived from cells with neuroendocrine differentiation. They are considered malignant by default. However, their outcomes are variable depending on their presentation in the onset of hereditary syndromes, hormonal secretion, grading, and extension. Therefore, although surgical treatment has long been suggested as the only treatment of pancreatic neuroendocrine neoplasms, its modalities are an evolving landscape. For selected patients (small, localized, non-functional panNENs), a "wait and see" strategy is suggested, as it is in the setting of multiple neuroendocrine neoplasia type 1, but the accurate size cut-off remains to be established. Parenchyma-sparring pancreatectomy, aiming to limit pancreatic insufficiency, are also emerging procedures, which place beyond the treatment of insulinomas and small non-functional panNENs (in association with lymph node picking) remains to be clarified. Furthermore, giving the fact that the liver is generally the only metastatic site, surgery keeps a place of choice alongside medical therapies in the treatment of metastatic disease, but its modalities and extensions are still a matter of debate. This narrative review aims to describe the current recommended surgical management for pancreatic NENs and controversies in light of the actual recommendations and recent literature.
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Affiliation(s)
- Samuel Frey
- Université de Nantes, Quai de Tourville, 44000 Nantes, France; (S.F.); (E.M.)
- L’institut du Thorax, Université de Nantes, CNRS, INSERM, CHU de Nantes, 44000 Nantes, France
- Chirurgie Cancérologique, Digestive et Endocrinienne, Institut des Maladies de l’Appareil Digestif, CHU de Nantes, 44000 Nantes, France
| | - Eric Mirallié
- Université de Nantes, Quai de Tourville, 44000 Nantes, France; (S.F.); (E.M.)
- Chirurgie Cancérologique, Digestive et Endocrinienne, Institut des Maladies de l’Appareil Digestif, CHU de Nantes, 44000 Nantes, France
| | - Maëlle Le Bras
- Endocrinologie, Diabétologie et Nutrition, L’institut du Thorax, CHU Nantes, 44000 Nantes, France;
| | - Nicolas Regenet
- Chirurgie Cancérologique, Digestive et Endocrinienne, Institut des Maladies de l’Appareil Digestif, CHU de Nantes, 44000 Nantes, France
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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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25
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Abstract
Small bowel neuroendocrine tumors (SBNETS) are slow-growing neoplasms with a noted propensity toward metastasis and comparatively favorable prognosis. The presentation of SBNETs is varied, although abdominal pain and obstructive symptoms are the most common presenting symptoms. In patients with metastases, hypersecretion of serotonin and other bioactive amines results in diarrhea, flushing, valvular heart disease, and bronchospasm, termed carcinoid syndrome. The treatment of SBNETs is multimodal and includes surgery, liver-directed therapy, somatostatin analogues, targeted therapy, and peptide receptor radionuclide therapy.
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Tran CG, Sherman SK, Howe JR. The Landmark Series: Management of Small Bowel Neuroendocrine Tumors. Ann Surg Oncol 2021; 28:2741-2751. [PMID: 33452604 DOI: 10.1245/s10434-020-09566-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Accepted: 12/20/2020] [Indexed: 12/12/2022]
Abstract
Surgical resection is the foundation for treatment of small bowel neuroendocrine tumors (SBNETs). Guidelines for surgical management of SBNETs rely on retrospective data, which suggest that primary tumor resection and cytoreduction improve symptoms, prevent future complications, and lengthen survival. In advanced NETs, improvement in progression-free survival has been reported in large, randomized, controlled trials of various medical treatments, including somatostatin analogues, targeted therapy, and peptide receptor radionuclide therapy. This review discusses important studies influencing the management of SBNETs and the limitations of current evidence regarding surgical interventions for SBNETs.
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Affiliation(s)
- Catherine G Tran
- Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA
| | - Scott K Sherman
- Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA
| | - James R Howe
- Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
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Tran CG, Sherman SK, Chandrasekharan C, Howe JR. Surgical Management of Neuroendocrine Tumor Liver Metastases. Surg Oncol Clin N Am 2021; 30:39-55. [PMID: 33220808 PMCID: PMC7739028 DOI: 10.1016/j.soc.2020.08.001] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Patients with neuroendocrine tumor liver metastases (NETLMs) may develop carcinoid syndrome, carcinoid heart disease, or other symptoms from overproduction of hormones. Hepatic resection and cytoreduction is the most direct treatment of NETLMs in eligible patients, and cytoreduction improves symptoms, may reduce the sequelae of carcinoid syndrome, and extends survival. Parenchymal-sparing procedures, such as ablation and enucleation, should be considered during cytoreduction to maximize treatment of multifocal tumors while preserving healthy liver tissue. For patients with large hepatic tumor burdens, high-grade disease, or comorbidities precluding surgery, liver-directed and systemic therapies can be used to palliate symptoms and improve progression-free survival.
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Affiliation(s)
- Catherine G Tran
- Department of Surgery, University of Iowa Hospitals & Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA
| | - Scott K Sherman
- Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA
| | - Chandrikha Chandrasekharan
- Department of Internal Medicine, Division of Hematology, Oncology and Blood and Marrow Transplantation, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA
| | - James R Howe
- Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA.
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Keutgen XM, Vaghaiwalla TM. Surgical Evaluation of Appendiceal Neuroendocrine Tumors. NEUROENDOCRINE TUMORS 2021:191-206. [DOI: 10.1007/978-3-030-62241-1_12] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Goldmann A, Clerici T. Small Intestine NETs. ENDOCRINE SURGERY COMPREHENSIVE BOARD EXAM GUIDE 2021:711-745. [DOI: 10.1007/978-3-030-84737-1_29] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Kawaguchi Y, De Bellis M, Panettieri E, Duwe G, Vauthey JN. Debate: Improvements in Systemic Therapies for Liver Metastases Will Increase the Role of Locoregional Treatments. Surg Oncol Clin N Am 2021; 30:205-218. [PMID: 33220806 PMCID: PMC7709757 DOI: 10.1016/j.soc.2020.08.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The benefit of resection of liver metastases depends on primary diseases. Neuroendocrine tumors are associated with favorable prognosis after resection of liver metastases. Gastric cancer has worse tumor biology, and resection of gastric liver metastases should be performed in selected patients. A multidisciplinary approach is well established for colorectal liver metastases (CLMs). Resection remains the only curative treatment of CLM. Chemotherapy and molecular-targeted therapy have improved survival in unresectable metastatic colorectal cancer. Understanding of the following two strategies, conversion therapy and two-stage hepatectomy, are important to make this patient group to be candidates for curative-intent surgery.
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Affiliation(s)
- Yoshikuni Kawaguchi
- Department of Surgical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA; Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
| | - Mario De Bellis
- Department of Surgical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA
| | - Elena Panettieri
- Department of Surgical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA
| | - Gregor Duwe
- Department of Surgical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
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Abstract
BACKGROUND Neuroendocrine tumors are becoming increasingly prevalent, with many patients presenting with or developing metastatic disease to the liver. METHODS In this landmark series paper, we highlight the critical studies that have defined the surgical management of neuroendocrine tumor liver metastases, as well as several randomized control trials which have investigated strategies for systemic control of metastatic disease. RESULTS Liver-directed surgical approaches and locally ablative procedures are recommended for patients with limited, resectable, and in some cases, nonresectable tumor burden. Angiographic liver-directed techniques, such as transarterial embolization, chemoembolization, and radioembolization, offer another approach for management in patients with liver-predominant disease. Peptide receptor radionuclide therapy is a promising therapy for patients with hepatic and/or extrahepatic metastases. Various systemic medical therapies are also available as adjunct or definitive therapy for patients with metastatic disease. CONCLUSIONS This article reviews current data regarding management of neuroendocrine liver metastases and highlights areas for future study.
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Affiliation(s)
- Alexandra Gangi
- Division of Surgical Oncology, Department of Surgery, Cedars Sinai Medical Center, 8700 Beverly Blvd; AC 1049, Los Angeles, CA 90048
| | - James R. Howe
- Surgical Oncology and Endocrine Surgery, University of Iowa Carver College of Medicine, 4644 JCP, 200 Hawkins Drive, University of Hospitals and Clinics, Iowa City, IA, 52242
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Koea J. Management of Locally Advanced and Unresectable Small Bowel Neuroendocrine Tumours. World J Surg 2020; 45:219-224. [PMID: 32860138 DOI: 10.1007/s00268-020-05740-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/07/2020] [Indexed: 10/23/2022]
Abstract
Three subtypes of small bowel neuroendocrine tumours (SBNETs) have been described: Type A: SBNET with resectable mesenteric disease that does not involve the mesenteric root; Type B: "Borderline resectable" SBNET presenting with mesenteric nodal metastases and fibrosis adjacent but not encasing the main trunk of the superior mesenteric artery (SMA) and superior mesenteric vein (SMV); and Type C: "Locally advanced or irresectable" SBNET where tumour deposits and fibrosis encase the SMA and SMV. Type C SBNETs are rare and constitute around 5% of patients in reported series, although this may underestimate the prevalence. In these patients, almost all will present with symptoms of intestinal ischemia or obstruction and symptom management should be a primary main focus of treatment. All patients should be carefully staged with cross-sectional imaging and 68 Ga-dotate positron emission tomography, and discussed at a dedicated neuroendocrine tumour multidisciplinary meeting. Expert surgical review should always be sought as experienced centers have a high rate of successful resection of primary tumours and mesenteric disease. If resection is not feasible, surgical bypass should be considered in patients with a discrete and symptomatic point of obstruction. Non-operative management should emphasize symptomatic treatment with somatostatin analogs, nutritional advice and support and palliative care. Successful neoadjuvant approaches utilizing peptide radionucleide receptor therapy and systemic chemotherapy with everolimus or temazolamide/capecitabine have not been reported.
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Affiliation(s)
- Jonathan Koea
- The Department of Surgery, North Shore Hospital, Private Bag 93503, Takapuna, Auckland, 0620, New Zealand.
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Role of Primary Tumor Resection for Metastatic Small Bowel Neuroendocrine Tumors. World J Surg 2020; 45:213-218. [PMID: 32797281 DOI: 10.1007/s00268-020-05727-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/31/2020] [Indexed: 12/21/2022]
Abstract
While small bowel resection is well established as standard of care for curative-intent management of localized and loco-regional small bowel neuroendocrine tumors (SB-NETs), resection of the primary tumor in the setting of metastatic disease is debated. This review addresses the role of primary tumor resection for stage IV well-differentiated grade 1 and 2 SB-NETs. While survival benefits have been reported for primary tumor resection in the setting of metastatic disease, these studies are limited by selection bias and thus controversial. The main clinical benefits of primary tumor resection for stage IV disease involve the prevention of potentially debilitating complications associated with mesenteric fibrosis, including intestinal obstruction, mesenteric ischemia and angina, venous congestion, malabsorption, and malnutrition. Patients with metastases undergoing initial resection of the primary SB-NETs appear to have fewer episodes of care and re-intervention for loco-regional complications than those who do not undergo resection. As recommended by the NANETS and ENETS guidelines, resection of the primary tumor for stage IV SB-NETs should be strongly considered to avoid future loco-regional complications and potentially to improve survival. All patients with stage IV SB-NETs should be assessed by a surgeon experienced in the management of NETs to consider surgical therapies, including resection of the primary tumor despite metastatic disease.
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Surgery and Perioperative Management in Small Intestinal Neuroendocrine Tumors. J Clin Med 2020; 9:jcm9072319. [PMID: 32708330 PMCID: PMC7408509 DOI: 10.3390/jcm9072319] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 07/14/2020] [Accepted: 07/16/2020] [Indexed: 12/19/2022] Open
Abstract
Small-intestinal neuroendocrine tumors (SI-NETs) are the most prevalent small bowel neoplasms with an increasing frequency. In the multimodal management of SI-NETs, surgery plays a key role, either in curative intent, even if R0 resection is feasible in only 20% of patients due to advanced stage at diagnosis, or palliative intent. Surgeons must be informed about the specific surgical management of SI-NETs according to their hormonal secretion, their usual dissemination at the time of diagnosis and the need for bowel-preserving surgery to avoid short bowel syndrome. The aim of this paper is to review the surgical indications and techniques, and perioperative and postoperative management of SI-NETs.
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Sartori S, Bianchi L, Di Vece F, Tombesi P. Liver-directed therapies for liver metastases from neuroendocrine neoplasms: Can laser ablation play any role? World J Gastroenterol 2020; 26:3118-3125. [PMID: 32684730 PMCID: PMC7336329 DOI: 10.3748/wjg.v26.i23.3118] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Revised: 06/12/2020] [Accepted: 06/15/2020] [Indexed: 02/06/2023] Open
Abstract
Aggressive cytoreduction can prolong survival in patients with unresectable liver metastases (LM) from neuroendocrine neoplasms (NEN), and minimally invasive, liver-directed therapies are gaining increasing interest. Catheter-based treatments are used in disseminated disease, whereas ablation techniques are usually indicated when the number of LM is limited. Although radiofrequency ablation (RFA) is by far the most used ablative technique, the goal of this opinion review is to explore the potential role of laser ablation (LA) in the treatment of LM from NEN. LA uses thinner needles than RFA, and this is an advantage when the tumors are in at-risk locations. Moreover, the multi-fiber technique enables the use of one to four laser fibers at once, and each fiber provides an almost spherical thermal lesion of 12-15 mm in diameter. Such a characteristic enables to tailor the size of each thermal lesion to the size of each tumor, sparing the liver parenchyma more than any other liver-directed therapy, and allowing for repeated treatments with low risk of liver failure. A recent retrospective study reporting the largest series of LM treated with LA documents both safety and effectiveness of LA, that can play a useful role in the multimodality approach to LM from NEN.
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Affiliation(s)
- Sergio Sartori
- Department of Internal Medicine, Section of Interventional Ultrasound, St. Anna Hospital, Ferrara 44100, Italy
| | - Lara Bianchi
- Department of Internal Medicine, Section of Interventional Ultrasound, St. Anna Hospital, Ferrara 44100, Italy
| | - Francesca Di Vece
- Department of Internal Medicine, Section of Interventional Ultrasound, St. Anna Hospital, Ferrara 44100, Italy
| | - Paola Tombesi
- Department of Internal Medicine, Section of Interventional Ultrasound, St. Anna Hospital, Ferrara 44100, Italy
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The Chicago Consensus on peritoneal surface malignancies: Management of neuroendocrine tumors. Cancer 2020; 126:2561-2565. [PMID: 32282069 DOI: 10.1002/cncr.32865] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2019] [Accepted: 08/14/2019] [Indexed: 11/07/2022]
Abstract
The Chicago Consensus Working Group provides multidisciplinary recommendations for the management of neuroendocrine tumors specifically related to the management of peritoneal surface malignancy. These guidelines are developed with input from leading experts, including surgical oncologists, medical oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness in the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence.
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Affiliation(s)
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- Chicago Consensus Working Group, Chicago, Illinois
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37
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Gangi A, Manguso N, Gong J, Crystal JS, Paski SC, Hendifar AE, Tuli R. Midgut Neuroendocrine Tumors with Liver-only Metastases: Benefit of Primary Tumor Resection. Ann Surg Oncol 2020; 27:4525-4532. [PMID: 32394299 DOI: 10.1245/s10434-020-08510-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND Management of metastatic midgut neuroendocrine tumors (MNET) remains controversial. The benefits of resecting the primary tumor are not clear and advocated only for select patients. This study aimed to determine whether resection of the primary MNET in patients with untreated liver-only metastases has an impact on survival. METHODS This retrospective study reviewed data of the National Cancer Database from 2004 to 2015 for patients with liver-only metastatic MNETs and compared those who received resection of their primary MNET with those who did not. Patient demographics, tumor characteristics, and clinical outcomes were compared between the groups. The primary outcome was overall survival (OS) after adjustment for patient, demographic, and tumor-related factors. RESULTS The study identified 1952 patients with a median age of 63 years (range, 18-90 years). The median primary tumor size was 2.4 cm (range, 0.1-20 cm). Of these patients, 1295 (66%) underwent resection of the primary tumor and 667 (34%) did not. The patients who underwent resection were younger (median age, 63 vs 65 years; p < 0.001) and had smaller primary tumors (median, 2.3 vs 3.0 cm; p < 0.001). The patients with clinical T1 or T2 tumors were significantly less likely to undergo resection than those with stage T3 or T4 tumors (58.5% vs 89.7%; p < 0.001). The median follow-up period was 43 months (range, 1-83 months). In the entire cohort, 483 deaths occurred, with a 5-year OS of 61%. The 5-year OS rate was 49% for the patients who underwent resection and 66% for those who did not (p < 0.001). When the patients were grouped according to T stage, no OS difference between resection and no resection for stages T1 (p = 0.07) and T2 (p = 0.40) was identified. However, the 5-year OS rate was significantly better for the resected patient cohort with T3 (67.5% vs 37.2%; p < 0.001) or T4 (59.8% vs 21.5%; p < 0.001) tumors. CONCLUSIONS The patients with treatment-naïve liver-only metastatic MNET had improved OS when the primary tumor was resected, particularly those with clinical stage T3 or T4 tumors. These patients may benefit from surgical resection of their primary tumor.
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Affiliation(s)
- Alexandra Gangi
- Division of Surgical Oncology, Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
| | - Nicholas Manguso
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Jun Gong
- Department of Gastrointestinal Malignancies, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Jessica S Crystal
- Division of Surgical Oncology, Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Shirley C Paski
- Department of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Andrew E Hendifar
- Department of Gastrointestinal Malignancies, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Richard Tuli
- Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.,Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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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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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: 8] [Impact Index Per Article: 1.6] [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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The Chicago Consensus on Peritoneal Surface Malignancies: Management of Neuroendocrine Tumors. Ann Surg Oncol 2020; 27:1788-1792. [PMID: 32285274 DOI: 10.1245/s10434-020-08321-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Indexed: 12/21/2022]
Abstract
The Chicago Consensus Working Group provides multidisciplinary recommendations for the management of neuroendocrine tumors specifically related to the management of peritoneal surface malignancy. These guidelines are developed with input from leading experts including surgical oncologists, medical oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness in the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence.
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Resection of the Primary Gastrointestinal Neuroendocrine Tumor Improves Survival With or Without Liver Treatment. Ann Surg 2020; 270:1131-1137. [PMID: 29746336 DOI: 10.1097/sla.0000000000002809] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
OBJECTIVE The aim of this study was to determine outcomes of primary tumor resection in metastatic neuroendocrine tumors across all primary tumor sites. BACKGROUND Primary tumor resection (PTR) may offer a survival benefit in metastatic gastrointestinal neuroendocrine tumors (GI-NETs); however, few studies have examined the effect of primary site and grade on resection and survival. METHODS This is a retrospective study of patients with metastatic GI-NETs at presentation between 2005 and 2011 using the California Cancer Registry (CCR) dataset merged with California Office of Statewide Health Planning and Development (OSHPD) inpatient longitudinal database. Primary outcome was overall survival (OS). Univariate and multivariate (MV) analyses were performed using the Pearson Chi-squared tests and Cox proportional hazard, respectively. OS was estimated using the Kaplan-Meier method and log-rank test. RESULTS A total of 854 patients with GI-NET metastases on presentation underwent 392 PTRs. Liver metastases occurred in 430 patients; 240 received liver treatment(s). PTR improved OS in patients with untreated metastases (median survival 10 vs 38 months, P < 0.001). On MV analysis adjusted for demographics, tumor stage, grade, chemotherapy use, Charlson comorbidity index, primary tumor location, or treatment of liver metastases, PTR with/without liver treatment improved OS in comparison to no treatment [hazard ratio (HR) 0.50, P < 0.001 and 0.39, P < 0.001, respectively]. PTR offered a survival benefit across all grades (low-grade, HR 0.38, P = 0.002 and high-grade, HR 0.62, P = 0.025) CONCLUSION:: PTR in GI-NET is associated with a better survival, with or without liver treatment, irrespective of grade. This study supports the resection of the primary tumor in patients with metastatic GI-NETs, independent of liver treatment.
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Limbach KE, Pommier SJ, Dewey E, Leon E, Pommier RF. Neuroendocrine metastases to the ovaries are significantly associated with small bowel neuroendocrine tumors and carcinomatosis. Am J Surg 2020; 219:795-799. [PMID: 32145918 DOI: 10.1016/j.amjsurg.2020.02.040] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Revised: 02/16/2020] [Accepted: 02/17/2020] [Indexed: 11/15/2022]
Abstract
INTRODUCTION Neuroendocrine tumors (NETs) metastatic to the ovary are traditionally considered rare, but data are lacking. This study seeks to better characterize the prevalence and outcomes of patients with neuroendocrine ovarian metastases (NOM). METHODS Women with well-differentiated lung and gastroenteropancreatic NETs 2007-2017 were identified by medical record query. Clinicopathologic data were reviewed among patients with and without NOM. RESULTS Of 242 patients, 27 (11.2%) developed NOM. NOM developed in 24.8% of SBNET patients and 65.7% of patients with carcinomatosis and intact ovaries. 33.3% had associated small bowel obstructions; 11.1% had ureteral obstruction. NOM were not apparent on imaging in 29.6% nor visible intraoperatively in 8.3%. Five-year survival rate was 61.5%. Those who underwent oophorectomy had a lower rate of subsequent ureteral obstruction (p < 0.01). CONCLUSIONS NOM are more prevalent than previously reported and associated with significant morbidity. Empiric oophorectomy may be considered for SBNET patients and strongly advised in carcinomatosis.
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Affiliation(s)
- Kristen E Limbach
- Division of Surgical Oncology, Oregon Health & Science University, USA
| | - SuEllen J Pommier
- Division of Surgical Oncology, Oregon Health & Science University, USA
| | - Elizabeth Dewey
- Department of General Surgery, Oregon Health & Science University, USA
| | - Enrique Leon
- Division of Surgical Oncology, Oregon Health & Science University, USA
| | - Rodney F Pommier
- Division of Surgical Oncology, Oregon Health & Science University, USA.
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Adam R, Kitano Y, Abdelrafee A, Allard MA, Baba H. Debulking surgery for colorectal liver metastases: Foolish or chance? Surg Oncol 2020; 33:266-269. [PMID: 32561091 DOI: 10.1016/j.suronc.2020.02.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Accepted: 02/13/2020] [Indexed: 12/21/2022]
Abstract
Even with the recent advances of surgical techniques and systemic therapies, we are often facing patients with multinodular bilateral disease for whom neither R0 nor R1 resection appears possible to perform. For such extensive cases, the tumor debulking approaches might provide a survival benefit, provided that an objective tumor response is obtained with chemotherapy. Here, we review all the arguments which may defend this strategy and propose some recommendations.
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Affiliation(s)
- René Adam
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Saclay, Inserm U 935, Villejuif, France.
| | - Yuki Kitano
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Saclay, Inserm U 935, Villejuif, France; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Ahmed Abdelrafee
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Saclay, Inserm U 935, Villejuif, France; Gastrointestinal Surgery Center, Department of Surgery, Mansoura University, Egypt
| | - Marc-Antoine Allard
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Saclay, Inserm U 935, Villejuif, France
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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Howe JR, Merchant NB, Conrad C, Keutgen XM, Hallet J, Drebin JA, Minter RM, Lairmore TC, Tseng JF, Zeh HJ, Libutti SK, Singh G, Lee JE, Hope TA, Kim MK, Menda Y, Halfdanarson TR, Chan JA, Pommier RF. The North American Neuroendocrine Tumor Society Consensus Paper on the Surgical Management of Pancreatic Neuroendocrine Tumors. Pancreas 2020; 49:1-33. [PMID: 31856076 PMCID: PMC7029300 DOI: 10.1097/mpa.0000000000001454] [Citation(s) in RCA: 231] [Impact Index Per Article: 46.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This manuscript is the result of the North American Neuroendocrine Tumor Society consensus conference on the surgical management of pancreatic neuroendocrine tumors from July 19 to 20, 2018. The group reviewed a series of questions of specific interest to surgeons taking care of patients with pancreatic neuroendocrine tumors, and for each, the available literature was reviewed. What follows are these reviews for each question followed by recommendations of the panel.
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Affiliation(s)
- James R. Howe
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
| | | | - Claudius Conrad
- Department of Surgery, St. Elizabeth Medical Center, Tufts University School of Medicine, Boston, MA
| | | | - Julie Hallet
- Department of Surgery, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Canada
| | - Jeffrey A. Drebin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Rebecca M. Minter
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | | | | | - Herbert J. Zeh
- Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX
| | - Steven K. Libutti
- §§ Department of Surgery, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
| | - Gagandeep Singh
- Department of Surgery, City of Hope Comprehensive Cancer Center, Duarte, CA
| | - Jeffrey E. Lee
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Thomas A. Hope
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA
| | - Michelle K. Kim
- Department of Medicine, Mt. Sinai Medical Center, New York, NY
| | - Yusuf Menda
- Department of Radiology, University of Iowa Carver College of Medicine, Iowa City, IA
| | | | - Jennifer A. Chan
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Rodney F. Pommier
- Department of Surgery, Oregon Health & Sciences University, Portland, OR
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Crown A, Rocha FG, Raghu P, Lin B, Funk G, Alseidi A, Hubka M, Rosales J, Lee M, Kennecke H. Impact of initial imaging with gallium‐68 dotatate PET/CT on diagnosis and management of patients with neuroendocrine tumors. J Surg Oncol 2019; 121:480-485. [DOI: 10.1002/jso.25812] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Accepted: 12/01/2019] [Indexed: 12/14/2022]
Affiliation(s)
- Angelena Crown
- Department of General, Thoracic and Vascular SurgeryVirginia Mason Medical CenterSeattle Washington
| | - Flavio G. Rocha
- Department of General, Thoracic and Vascular SurgeryVirginia Mason Medical CenterSeattle Washington
| | - Preethi Raghu
- Department of RadiologyVirginia Mason Medical CenterSeattle WA
| | - Bruce Lin
- Department of Medical OncologyVirginia Mason Medical CenterSeattle WA
| | - Gayle Funk
- Department of Medical OncologyVirginia Mason Medical CenterSeattle WA
| | - Adnan Alseidi
- Department of General, Thoracic and Vascular SurgeryVirginia Mason Medical CenterSeattle Washington
| | - Misho Hubka
- Department of General, Thoracic and Vascular SurgeryVirginia Mason Medical CenterSeattle Washington
| | - Joseph Rosales
- Department of Medical OncologyVirginia Mason Medical CenterSeattle WA
| | - Marie Lee
- Department of RadiologyVirginia Mason Medical CenterSeattle WA
| | - Hagen Kennecke
- Department of Medical OncologyVirginia Mason Medical CenterSeattle WA
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46
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Guccione L, Gough K, Drosdowsky A, Fisher K, Price T, Pavlakis N, Khasraw M, Wyld D, Ransom D, Kong G, Rogers M, Leyden S, Leyden J, Michael M, Schofield P. Defining the Supportive Care Needs and Psychological Morbidity of Patients With Functioning Versus Nonfunctioning Neuroendocrine Tumors: Protocol for a Phase 1 Trial of a Nurse-Led Online and Phone-Based Intervention. JMIR Res Protoc 2019; 8:e14361. [PMID: 31793892 PMCID: PMC6918201 DOI: 10.2196/14361] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Revised: 08/28/2019] [Accepted: 08/30/2019] [Indexed: 01/12/2023] Open
Abstract
Background Online information resources and support have been demonstrated to positively influence the well-being of people diagnosed with cancer. This has been explored in past literature for more common cancers; however, for rare cancers, such as neuroendocrine tumors (NETs), there are little to no support or resources available. Despite relatively good prognoses, the quality of life (QoL) of patients with NETs is significantly lower compared with samples of mixed cancer patients and the general population. Patients with NETs also typically report unclear and difficult pathways of disease management and treatment, given the heterogeneity of the diagnosis. There is a vital need to improve the availability of disease-specific information for this patient group and provide supportive care that is tailored to the unique needs of the NET patient population. Objective This study described the protocol of a study aimed to better understand the outcomes and experiences of patients diagnosed with NETs and to develop and pilot test a nurse-led online and phone-based intervention that will provide tailored supportive care targeted to NET subgroups (functioning vs nonfunctioning). Methods This is a multisite cohort with 3 phases, incorporating both quantitative and qualitative data collection. Phase 1 is a mixed methods prospective cohort study of NET patients identifying differences in patient experiences and priority of needs between NET subgroups. Phase 2 utilizes results from phase 1 to develop an online and nurse-led phone-based intervention. Phase 3 is to pilot test and evaluate the intervention’s acceptability, appropriateness, and feasibility. Results Currently, the project is progressing through phase 1 and has completed recruitment. A total of 138 participants have been recruited to the study. To date, patient-reported outcome data from 123 participants at baseline and 87 participants at 6-month follow-up have been collected. Of these, qualitative data from semistructured interviews from 35 participants have also been obtained. Phase 2 and phase 3 of the project are yet to be completed. Conclusions Limited research for patients with NETs suggests that QoL and patient experiences are significantly impaired compared with the general population. Furthermore, past research has failed to delineate how the clinical variability between those with functioning and nonfunctioning NETs impacts patient supportive care needs. This study will improve on the availability of disease-specific information as well as informing the design of a nurse-led online and phone-based supportive care intervention tailored for the unique needs of the NET patient population. International Registered Report Identifier (IRRID) DERR1-10.2196/14361
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Affiliation(s)
- Lisa Guccione
- Department of Cancer Experiences Research, Peter MacCallum Cancer Center, Melbourne, Australia.,Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia
| | - Karla Gough
- Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia
| | - Allison Drosdowsky
- Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia
| | - Krista Fisher
- Department of Cancer Experiences Research, Peter MacCallum Cancer Center, Melbourne, Australia
| | - Timothy Price
- Haematology and Oncology, The Queen Elizabeth Hospital, South Australia, Australia
| | - Nick Pavlakis
- Department of Medical Oncology, Royal North Shore Hospital, New South Wales, Australia
| | - Mustafa Khasraw
- Department of Medical Oncology, Royal North Shore Hospital, New South Wales, Australia
| | - David Wyld
- Department of Medical Oncology, Royal Brisbane and Women's Hospital, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Australia
| | - David Ransom
- Medical Oncology, Fiona Stanley Hospital, Western Australia, Australia
| | - Grace Kong
- Department of Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Megan Rogers
- Upper Gastrointestinal Cancer Service, Peter MacCallum Cancer Centre, Melbourne, Australia
| | | | | | - Michael Michael
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Penelope Schofield
- Department of Cancer Experiences Research, Peter MacCallum Cancer Center, Melbourne, Australia.,Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia.,Department of Psychology and Iverson Health Innovation Research Institute, Swinburne University, Melbourne, Australia
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Wang YZ, Chauhan A, Ramirez RA, Beyer DT, Stevens MA, Woltering EA, Boudreaux JP, Anthony L. Does the addition of adjuvant intraoperative tumor bed chemotherapy during midgut neuroendocrine tumor debulking procedures benefit patients? J Gastrointest Oncol 2019; 10:928-934. [PMID: 31602331 DOI: 10.21037/jgo.2019.07.05] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Background Midgut neuroendocrine tumor (NET) patients are often diagnosed at advanced stages with extensive mesenteric nodal and hepatic metastasis. The only potentially curative treatment is surgical tumor eradication. Despite an aggressive resection, macro and microscopic residual disease still may remain in the resection bed. We hypothesize that the application of 5-fluorouracil (5-FU) within the tumor bed will help eliminate microscopic residual disease. Methods Records of 189 patients who underwent extensive cytoreductive surgeries during 2003-2012 for advanced, midgut NETs with extensive mesenteric lymphadenopathy were reviewed. Eighty-six patients (46%) who had 5-FU saturated gel foam strips secured into their mesenteric resection sites served as the study group and a matching 103 patients (54%) who did not have such an intra-operative chemotherapy served as controls. Survival from the time of diagnosis and post-operative complications between the two groups were compared. Results Mortality rates at 30, 60 and 90 days post-operatively were 4%, 0%, 0% versus 2%, 0%, 2% for study and control groups, respectively. Major complications (Grades III & IV) at the same intervals were 0, 0, 1 versus 2, 3, 2 for study and control groups, respectively. Median survival was 236 months versus 148 months for the study and control groups, respectively 24 (P=0.15). Conclusions Intraoperative tumor resection bed chemotherapy is a safe adjuvant without discernible toxicity. This procedure may provide survival benefits to midgut NET patients with extensive mesenteric lymphadenopathy undergoing extensive cytoreductive surgery. Further study in prospective trials must be conducted to determine definitive benefit to the NET patient.
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Affiliation(s)
- Yi-Zarn Wang
- Department of Surgery, Baylor University Medical Center, Dallas, TX, USA
| | - Aman Chauhan
- Division of Medical Oncology, University of Kentucky, Markey Cancer Center, Lexington, KY, USA
| | - Robert A Ramirez
- Department of Hematology and Oncology, Ochsner Medical Center, New Orleans, LA, USA
| | - David T Beyer
- Department of Surgery, Baylor University Medical Center, Dallas, TX, USA
| | - Melissa A Stevens
- Department of Surgery, Baylor University Medical Center, Dallas, TX, USA
| | - Eugene A Woltering
- Department of Surgery, Baylor University Medical Center, Dallas, TX, USA
| | - J Philip Boudreaux
- Department of Surgery, Baylor University Medical Center, Dallas, TX, USA
| | - Lowell Anthony
- Division of Medical Oncology, University of Kentucky, Markey Cancer Center, Lexington, KY, USA
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48
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Horwitz JK, Marin ML, Warner RRP, Lookstein RA, Divino CM. EndoVascular Occlusion and Tumor Excision (EVOTE): a Hybrid Approach to Small-Bowel Neuroendocrine Tumors with Mesenteric Metastases. J Gastrointest Surg 2019; 23:1911-1916. [PMID: 31090038 DOI: 10.1007/s11605-019-04232-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Accepted: 04/12/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND Mesenteric metastases from small-bowel neuroendocrine tumors (SBNETs) present a surgical challenge due to encasement of mesenteric vessels. In this study, we evaluate the feasibility and safety of a new, hybrid surgical approach to these mesenteric masses, EndoVascular Occlusion and Tumor Excision (EVOTE). METHODS From 2014 to 2018, 13 patients underwent the EVOTE procedure after being referred to our institution for primary SBNETs with "unresectable" mesenteric metastases. During stage 1 of the hybrid EVOTE procedure, angiographic evaluation of the mesenteric mass is performed. If adequate collateralization is demonstrated, the encased mesenteric vessel(s) is embolized. Mass excision is performed the following day during stage 2 of the EVOTE procedure. RESULTS Preoperative embolization was successful in 86% of cases; 2 cases were aborted for persistent abdominal pain following occlusion testing. Complete surgical excision of the mesenteric mass was achieved in 86% of cases. The 30-day overall morbidity and mortality rate was 29% and 0%, respectively. There was one local recurrence at 31.8 months post-op; this patient underwent a repeat EVOTE procedure with successful complete excision. DISCUSSION EVOTE represents a new technique that aids in preoperative planning and surgical resection of SBNETs with mesenteric metastases.
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Affiliation(s)
- Julian K Horwitz
- Department of Surgery, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA
| | - Michael L Marin
- Department of Surgery, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA
| | - Richard R P Warner
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Robert A Lookstein
- Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Celia M Divino
- Department of Surgery, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
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Percutaneous Laser Ablation of Liver Metastases from Neuroendocrine Neoplasm. A Retrospective Study for Safety and Effectiveness. Cardiovasc Intervent Radiol 2019; 42:1571-1578. [PMID: 31410534 DOI: 10.1007/s00270-019-02308-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Accepted: 08/05/2019] [Indexed: 12/16/2022]
Abstract
PURPOSE To retrospectively assess safety and efficacy of laser ablation (LA) of multiple liver metastases (LM) from neuroendocrine neoplasms (NEN). METHODS Twenty-one patients with NEN and at least 3 LM ≤ 4 cm in diameter underwent ultrasonography-guided LA. Up to seven LM were ablated in a single session; if the number of LM exceeded seven, the remaining LM were ablated in further LA sessions with a time interval of 3-4 weeks. LA was performed according to the multifiber technique. The patients underwent contrast-enhanced CT 1 month after LA, and were subsequently monitored every 3 months for the first 2 years and then every 6 months. RESULTS In total, 189 LM were treated in 21 patients (mean 9 ± 8.2, median 6) in 41 LA sessions (range 1-5). The diameter of LM ranged from 5 to 35 mm (median 19 mm, mean 17.9 ± 6.4 mm). One grade 4 complication occurred (0.53%): a bowel perforation managed by surgery. Technical efficacy was 100%, primary efficacy rate 94.7%, and secondary efficacy rate 100%. Complete relief of hormone-related symptoms was obtained in all the 13 symptomatic patients. Median follow-up was 39 months (range 12-99). 1-, 2-, 3-, and 5-year survival rates were 95%, 86%, 66%, and 40%, respectively. Overall survival resulted higher for patients with Ki-67 expression ≤ 7% than for those with Ki-67 > 7% (p = 0.0347). CONCLUSIONS LA is a promising and safe technique to treat LM from NEN. A longer follow-up should provide definitive information on the long-term efficacy of this liver-directed therapy. LEVEL OF EVIDENCE Retrospective study, local non-random sample, level 3.
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Plasma Pancreastatin Predicts the Outcome of Surgical Cytoreduction in Neuroendocrine Tumors of the Small Bowel. Pancreas 2019; 48:356-362. [PMID: 30768573 DOI: 10.1097/mpa.0000000000001263] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVES Elevated pancreastatin (PST) levels have been shown to be associated with poor prognosis in small bowel neuroendocrine tumors (NETs). We hypothesized that plasma PST levels that remain elevated following surgical cytoreduction portend a poor prognosis in well-differentiated small bowel NETs. METHODS Patients diagnosed with small bowel NETs who underwent surgical cytoreduction at our institution were identified. Demographics, histopathologic characteristics, and biochemical data were collected. Only patients who had serial preoperative PST (PreopPST) and postoperative PST (PostopPST) levels were included in this study. Patients were sorted into groups by PST level to assess their response to surgical cytoreduction (group 1, PreopPST/PostopPST normal; group 2, PreopPST elevated/PostopPST normal; group 3, PreopPST/PostopPST elevated). Survival rates were calculated from the date of surgery. RESULTS PreopPST and PostopPST levels were collected from 300 patients. Patients in groups 1 (n = 74) and 2 (n = 81) had a significant survival advantage compared with patients in group 3 (n = 145) (P < 0.0001). Kaplan-Meier 5- and 10-year survival rates were as follows: group 1: 93% and 82%; group 2: 91% and 65%; and group 3: 58% and 34%, respectively. CONCLUSIONS Serial monitoring of plasma PST is useful in predicting long-term survival following surgical cytoreduction and can be helpful to identify patients who have a poor prognosis.
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