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Jeph S, Gupta S, Yedururi S, Daoud TE, Stanietzky N, Morani AC. Liver Imaging in Gastroenteropancreatic Neuroendocrine Neoplasms. J Comput Assist Tomogr 2024; 48:577-587. [PMID: 38438332 DOI: 10.1097/rct.0000000000001576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2024]
Abstract
ABSTRACT The incidence of neuroendocrine neoplasms (NENs) has gradually increased over the past few decades with the majority of patients presenting with metastases on initial presentation. The liver is the most common site of initial metastatic disease, and the presence of liver metastasis is an independent prognostic factor associated with a negative outcome. Because NENs are heterogenous neoplasms with variable differentiation, grading, and risk of grade transformation over time, accurate diagnosis and management of neuroendocrine liver lesions are both important and challenging. This is particularly so with the multiple liver-directed treatment options available. In this review article, we discuss the diagnosis, treatment, and response evaluation of NEN liver metastases.
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Affiliation(s)
- Sunil Jeph
- From the Department of Radiology, Penn State University, Hershey, PA
| | - Shiva Gupta
- Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Sireesha Yedururi
- Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Taher E Daoud
- Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Nir Stanietzky
- Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Ajaykumar C Morani
- Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX
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Murakami M, Hirahata K, Fujimori N, Yamamoto T, Oda Y, Kozono S, Ueda K, Ito T, Nakamura M, Ogawa Y. Two cases of pancreatic neuroendocrine tumors with ectopic ACTH syndrome during their disease course. Clin J Gastroenterol 2024; 17:363-370. [PMID: 38244178 DOI: 10.1007/s12328-023-01908-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 12/08/2023] [Indexed: 01/22/2024]
Abstract
Pancreatic neuroendocrine tumors (PanNETs) are rare malignant tumors that occur in the pancreas. They are divided into functioning and non-functioning tumors based on the presence or absence of their specific hormonal hyper-expression symptoms. Adrenocorticotropic hormone (ACTH)-producing PanNETs are rare, functional tumors, and their clinical characteristics and outcomes have not been well reported.Here, we report the cases of two patients with PanNETs who presented with ectopic ACTH syndrome (EAS) during the course of their disease. Case 1 involved a non-functioning PanNET at the time of surgery. During treatment for recurrent liver metastases, the patient presented with EAS and tumor-associated hypercalcemia, probably due to ACTH and parathyroid hormone-related peptide (PTHrP) production from the liver tumor. Case 2 was a gastrinoma, and similar to Case 1, this patient presented with EAS during the treatment of recurrent liver metastases.It is not uncommon for patients with PanNETs to have multiple hormones and develop secondary hormone secretion during their disease course, although tumor phenotypes differ between primary and metastatic sites. In patients with functioning PanNETs, symptom control with anti-hormonal therapy is essential, in addition to anti-tumor therapy, especially for EAS, which is an endocrine emergency disease that requires prompt diagnosis and treatment.
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Affiliation(s)
- Masatoshi Murakami
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Keisuke Hirahata
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Nao Fujimori
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
| | - Takeo Yamamoto
- Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshinao Oda
- Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shingo Kozono
- Department of Surgery, Kitakyushu Municipal Medical Center, Kitakyushu, Japan
| | - Keijiro Ueda
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Testuhide Ito
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, Fukuoka, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, International University of Health and Welfare, Fukuoka, Japan
| | - Masafumi Nakamura
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshihiro Ogawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
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Nanno Y, Toyama H, Ueshima E, Sofue K, Matsumoto I, Ishida J, Urade T, Fukushima K, Gon H, Tsugawa D, Komatsu S, Kuramitsu K, Goto T, Asari S, Yanagimoto H, Kido M, Ajiki T, Fukumoto T. Transarterial chemoembolization for liver metastases of a pancreatic neuroendocrine neoplasm: a single-center experience. Surg Today 2023; 53:1396-1400. [PMID: 37355500 DOI: 10.1007/s00595-023-02714-9] [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: 01/13/2023] [Accepted: 05/16/2023] [Indexed: 06/26/2023]
Abstract
Transarterial chemoembolization (TACE) is performed for pancreatic neuroendocrine tumor (PanNEN) liver metastases; however, the safety and efficacy of TACE procedures, especially for patients who have undergone previous pancreatic surgery, have not been established. We reviewed 48 TACE procedures (1-6 procedures/patient) performed on 11 patients with PanNEN liver metastases, including 16 TACE procedures (4-6 procedures/patient) for 3 patients with a history of biliary-enteric anastomosis. The overall tumor objective response rate was 94%. The incidence of Clavien‒Dindo grade ≥ 2 complications was 1/16 (6%) and 1/32 (3%), and the median time to untreatable progression was 31 (14-41) and 27 (2-60) months among patients with and without a history of biliary-enteric anastomosis, respectively. Although validation is needed in future studies, our experiences have shown that TACE treatment is a viable treatment option for PanNEN liver metastases, even after biliary-enteric anastomosis with experienced teams and careful patient follow-up.
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Affiliation(s)
- Yoshihide Nanno
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Hirochika Toyama
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
| | - Eisuke Ueshima
- Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Keitaro Sofue
- Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Ippei Matsumoto
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Jun Ishida
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Takeshi Urade
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Kenji Fukushima
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Hidetoshi Gon
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Daisuke Tsugawa
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Shohei Komatsu
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Kaori Kuramitsu
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Tadahiro Goto
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Sadaki Asari
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Hiroaki Yanagimoto
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Masahiro Kido
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Tetsuo Ajiki
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Takumi Fukumoto
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
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Clift AK, Drymousis P, von Roon A, Humphries A, Goldin R, Bomanji J, Leaman S, Wasan H, Habib N, Frilling A. Management of Small Bowel Neuroendocrine Tumours: 10 Years' Experience at a Tertiary Referral Centre. Cancers (Basel) 2023; 15:4438. [PMID: 37760408 PMCID: PMC10526159 DOI: 10.3390/cancers15184438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 08/24/2023] [Accepted: 09/01/2023] [Indexed: 09/29/2023] Open
Abstract
BACKGROUND Neuroendocrine tumours (NET) arising from the small bowel are clinically challenging and are often diagnosed at advanced stages. Disease control with surgery alone can be demanding. Multimodal treatment concepts integrating surgery and non-surgical modalities could be of benefit. METHOD Retrospective review of consecutive adult patients with SB NET treated at Imperial College Healthcare NHS Trust between 1 January 2010 and 31 December 2019. Data regarding clinicopathological characteristics, treatments, and disease trajectory were extracted and summarised. Overall and progression/recurrence-free survival were estimated at 5 and 10 years. RESULTS 154 patients were identified, with a median age of 64 years (range 33-87); 135/154 (87.7%) had stage III/IV disease at diagnosis. Surgery was used in 125 individuals (81.2%), typically with either segmental small bowel resection (60.8%) or right hemicolectomy (33.6%) and mesenteric lymphadenectomy for the primary tumour. Systemic and/or liver-directed therapies were used in 126 (81.8%); 60 (47.6%) had more than one line of non-surgical treatment. Median follow-up was 67.2 months (range 3.1-310.4); overall survival at 5 and 10 years was 91.0% (95% CI: 84.9-94.7%) and 82.5% (95% CI: 72.9-88.9%), respectively. Imaging-based median progression-free survival was 42.7 months (95% CI: 24.7 to 72.4); 5-year progression-free survival was 63.4% (95% CI: 55.0-70.6%); 10-year progression-free survival was 18.7% (95% CI: 12.4-26.1). Nineteen patients (12.3%) reached 10 years follow-up without disease recurrence and therefore were considered cured. CONCLUSIONS Most patients with SB NET present in a metastasised stage. Multimodal treatment concepts may be associated with excellent clinical outcomes. Future work should explore optimal approaches to treatment sequencing and patient selection.
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Affiliation(s)
- Ashley K. Clift
- Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0HS, UK; (A.K.C.)
- CRUK Oxford Centre, Department of Oncology, University of Oxford, Oxford OX1 2JD, UK
| | - Panagiotis Drymousis
- Department of Surgery, Ealing Hospital, London North West University Healthcare NHS Trust, London HA1 3UJ, UK
| | - Alexander von Roon
- Department of Surgery, University College London Hospitals NHS Foundation Trust London, London NW1 2BU, UK
| | - Adam Humphries
- Department of Gastroenterology, St Mark’s Hospital, London North West University Health Care NHS Trust, London HA1 3UJ, UK
| | - Robert Goldin
- Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0HS, UK; (A.K.C.)
| | - Jamshed Bomanji
- Department of Nuclear Medicine, University College London Hospitals NHS Foundation Trust London, London NW1 2BU, UK
| | - Sydney Leaman
- MRC Centre for Neurodevelopmental Disorders, King’s College London, London SE1 8WA, UK
| | - Harpreet Wasan
- Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0HS, UK; (A.K.C.)
| | - Nagy Habib
- Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0HS, UK; (A.K.C.)
| | - Andrea Frilling
- Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0HS, UK; (A.K.C.)
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Ito T, Ueda K, Fujimori N, Jensen RT. Clinical Manifestation of Endocrine Tumors of the Pancreas. THE PANCREAS 2023:791-798. [DOI: 10.1002/9781119876007.ch102] [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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Akabane M, Kobayashi Y, Kinowaki K, Okubo S, Shindoh J, Hashimoto M. Primary hepatic neuroendocrine neoplasm diagnosed by somatostatin receptor scintigraphy: A case report. World J Clin Cases 2022; 10:2222-2228. [PMID: 35321183 PMCID: PMC8895177 DOI: 10.12998/wjcc.v10.i7.2222] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Revised: 07/15/2021] [Accepted: 01/22/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Primary hepatic neuroendocrine neoplasm (NEN) is a rare condition, and it is difficult to differentiate between primary and metastatic hepatic NENs. Herein, we report a case of primary hepatic NEN that initially mimicked a hemangioma but showed a gradual increase in size on long-term careful observation. CASE SUMMARY A 47-year-old woman was incidentally diagnosed with a 12-mm liver mass, suspected to be a hemangioma. Since then, regular follow-up had been carried out. Ten years later, she was referred to our institute due to the tumor (located in segment 4) having increased to 20 mm. Several imaging studies depicted no apparent extrahepatic lesion. Positron emission tomography (PET)/computed tomography exhibited significant accumulation in the mass lesion, which made us consider the possibility of malignancy. Left hepatectomy was performed. The histopathological diagnosis was neuroendocrine tumor grade 2, with somatostatin receptor 2a/5 positivity. Postoperative somatostatin receptor scintigraphy (SRS) showed no other site, leading to the diagnosis of NEN of primary hepatic origin. The gradual growth of the hepatic NEN over 10 years suggested that it was likely to be a primary liver tumor. CONCLUSION In this case, positivity on PET and postoperative SRS may have helped determine whether the tumor was primary or metastatic.
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Affiliation(s)
- Miho Akabane
- Division of Hepatobiliary-pancreatic Surgery, Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo 105-8470, Japan
| | - Yuta Kobayashi
- Division of Hepatobiliary-pancreatic Surgery, Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo 105-8470, Japan
| | - Keiichi Kinowaki
- Department of Diagnostic Pathology, Toranomon Hospital, Tokyo 105-8470, Japan
| | - Satoshi Okubo
- Division of Hepatobiliary-pancreatic Surgery, Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo 105-8470, Japan
| | - Junichi Shindoh
- Division of Hepatobiliary-pancreatic Surgery, Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo 105-8470, Japan
| | - Masaji Hashimoto
- Division of Hepatobiliary-pancreatic Surgery, Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo 105-8470, Japan
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Inaba Y, Hijioka S, Iwama I, Asai T, Miyamura H, Chatani S, Hasegawa T, Murata S, Kato M, Sato Y, Yamaura H, Onaya H, Shimizu J, Hara K. Clinical usefulness of Somatostatin Receptor Scintigraphy in the Diagnosis of Neuroendocrine Neoplasms. ASIA OCEANIA JOURNAL OF NUCLEAR MEDICINE & BIOLOGY 2022; 10:1-13. [PMID: 35083344 PMCID: PMC8742849 DOI: 10.22038/aojnmb.2021.56254.1390] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 04/03/2021] [Accepted: 05/11/2021] [Indexed: 12/13/2022]
Abstract
OBJECTIVES We investigated the detectability of somatostatin receptor scintigraphy (SRS) for neuroendocrine neoplasms (NEN). METHODS From January 2016 to October 2020, 125 SRS examinations using indium-111 pentetreotide performed for patients with NEN lesions were retrospectively evaluated. The detection rate of NEN lesions was determined according to histopathological classification by primary site and by organ. RESULTS At least one NEN lesion was detected in 73% (91/125) with a positive Krenning score of ≥2 in SRS. The detection of abdominal NENs (gastrointestinal tract, 38; pancreas, 62; and others, 14) was 89% (49/55) for neuroendocrine tumor (NET)-grade (G) 1, 78% (32/41) for NET-G2, 66% (2/3) for NET-G3, 31% (4/13) for neuroendocrine carcinoma (NEC), 100% (1/1) for mixed neuroendocrine-non-neuroendocrine neoplasm, and 0% (0/1) for non-classified NEN. That of thoracic NENs was 33% (2/6) for typical carcinoid tumor and 40% (2/5) for atypical carcinoid tumor. For a total of 226 organ lesions, hepatic lesions were 76% (58/76); pancreatic lesions, 61% (31/51); lymph node lesions, 77% (27/35); bone lesions, 83% (20/24); duodenal lesions, 82% (9/11); and other lesions, 41% (11/27). CONCLUSION The detectability of SRS for NEN in Japan was verified at a center, and its usefulness was confirmed.
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Affiliation(s)
- Yoshitaka Inaba
- Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan
| | - Susumu Hijioka
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan
| | - Isanori Iwama
- Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan
| | - Tsubasa Asai
- Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan
| | - Hiroki Miyamura
- Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan
| | - Shohei Chatani
- Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan
| | - Takaaki Hasegawa
- Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan
| | - Shinichi Murata
- Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan
| | - Mina Kato
- Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan
| | - Yozo Sato
- Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan
| | - Hidekazu Yamaura
- Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan
| | - Hiroaki Onaya
- Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan
| | - Junichi Shimizu
- Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan
| | - Kazuo Hara
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan
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Marchese U, Gaillard M, Pellat A, Tzedakis S, Abou Ali E, Dohan A, Barat M, Soyer P, Fuks D, Coriat R. Multimodal Management of Grade 1 and 2 Pancreatic Neuroendocrine Tumors. Cancers (Basel) 2022; 14:433. [PMID: 35053593 PMCID: PMC8773540 DOI: 10.3390/cancers14020433] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 01/11/2022] [Accepted: 01/13/2022] [Indexed: 12/13/2022] Open
Abstract
Pancreatic neuroendocrine tumors (p-NETs) are rare tumors with a recent growing incidence. In the 2017 WHO classification, p-NETs are classified into well-differentiated (i.e., p-NETs grade 1 to 3) and poorly differentiated neuroendocrine carcinomas (i.e., p-NECs). P-NETs G1 and G2 are often non-functioning tumors, of which the prognosis depends on the metastatic status. In the localized setting, p-NETs should be surgically managed, as no benefit for adjuvant chemotherapy has been demonstrated. Parenchymal sparing resection, including both duodenum and pancreas, are safe procedures in selected patients with reduced endocrine and exocrine long-term dysfunction. When the p-NET is benign or borderline malignant, this surgical option is associated with low rates of severe postoperative morbidity and in-hospital mortality. This narrative review offers comments, tips, and tricks from reviewing the available literature on these different options in order to clarify their indications. We also sum up the overall current data on p-NETs G1 and G2 management.
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Affiliation(s)
- Ugo Marchese
- Department of Digestive, Hepatobiliary and Pancreatic Surgery, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (M.G.); (S.T.); (D.F.)
| | - Martin Gaillard
- Department of Digestive, Hepatobiliary and Pancreatic Surgery, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (M.G.); (S.T.); (D.F.)
| | - Anna Pellat
- Gastroenterology and Digestive Oncology Unit, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (A.P.); (E.A.A.); (R.C.)
| | - Stylianos Tzedakis
- Department of Digestive, Hepatobiliary and Pancreatic Surgery, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (M.G.); (S.T.); (D.F.)
| | - Einas Abou Ali
- Gastroenterology and Digestive Oncology Unit, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (A.P.); (E.A.A.); (R.C.)
| | - Anthony Dohan
- Department of Radiology, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (A.D.); (M.B.); (P.S.)
| | - Maxime Barat
- Department of Radiology, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (A.D.); (M.B.); (P.S.)
| | - Philippe Soyer
- Department of Radiology, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (A.D.); (M.B.); (P.S.)
| | - David Fuks
- Department of Digestive, Hepatobiliary and Pancreatic Surgery, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (M.G.); (S.T.); (D.F.)
| | - Romain Coriat
- Gastroenterology and Digestive Oncology Unit, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (A.P.); (E.A.A.); (R.C.)
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Effraimidis G, Knigge U, Rossing M, Oturai P, Rasmussen ÅK, Feldt-Rasmussen U. Multiple endocrine neoplasia type 1 (MEN-1) and neuroendocrine neoplasms (NENs). Semin Cancer Biol 2021; 79:141-162. [PMID: 33905872 DOI: 10.1016/j.semcancer.2021.04.011] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 01/03/2021] [Accepted: 04/16/2021] [Indexed: 12/14/2022]
Abstract
Neuroendocrine neoplasms (NENs) are relatively rare neoplasms with 6.4-times increasing age-adjusted annual incidence during the last four decades. NENs arise from neuroendocrine cells, which release hormones in response to neuronal stimuli and they are distributed into organs and tissues. The presentation and biological behaviour of the NENs are highly heterogeneous, depending on the organ. The increased incidence is mainly due to increased awareness and improved detection methods both in the majority of sporadic NENs (non-inherited), but also the inherited groups of neoplasms appearing in at least ten genetic syndromes. The most important one is multiple endocrine neoplasia type 1 (MEN-1), caused by mutations in the tumour suppressor gene MEN1. MEN-1 has been associated with different tumour manifestations of NENs e.g. pancreas, gastrointestinal tract, lungs, thymus and pituitary. Pancreatic NENs tend to be less aggressive when arising in the setting of MEN-1 compared to sporadic pancreatic NENs. There have been very important improvements over the past years in both genotyping, genetic counselling and family screening, introduction and validation of various relevant biomarkers, as well as newer imaging modalities. Alongside this development, both medical, surgical and radionuclide treatments have also advanced and improved morbidity, quality of life and mortality in many of these patients. Despite this progress, there is still space for improving insight into the genetic and epigenetic factors in relation to the biological mechanisms determining NENs as part of MEN-1. This review gives a comprehensive update of current evidence for co-occurrence, diagnosis and treatment of MEN-1 and neuroendocrine neoplasms and highlight the important progress now finding its way to international guidelines in order to improve the global management of these patients.
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Affiliation(s)
- Grigoris Effraimidis
- ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Medical Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Ulrich Knigge
- ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Medical Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Surgery and Transplantation, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Maria Rossing
- Centre for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Peter Oturai
- Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Åse Krogh Rasmussen
- ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Medical Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Ulla Feldt-Rasmussen
- ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Medical Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Denmark; Institute of Clinical Medicine, Faculty of Health Sciences, Copenhagen University, Denmark.
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10
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Niederle B, Selberherr A, Bartsch DK, Brandi ML, Doherty GM, Falconi M, Goudet P, Halfdanarson TR, Ito T, Jensen RT, Larghi A, Lee L, Öberg K, Pavel M, Perren A, Sadowski SM, Tonelli F, Triponez F, Valk GD, O'Toole D, Scott-Coombes D, Thakker RV, Thompson GB, Treglia G, Wiedenmann B. Multiple Endocrine Neoplasia Type 1 and the Pancreas: Diagnosis and Treatment of Functioning and Non-Functioning Pancreatic and Duodenal Neuroendocrine Neoplasia within the MEN1 Syndrome - An International Consensus Statement. Neuroendocrinology 2021; 111:609-630. [PMID: 32971521 DOI: 10.1159/000511791] [Citation(s) in RCA: 73] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Accepted: 09/18/2020] [Indexed: 11/19/2022]
Abstract
The better understanding of the biological behavior of multiple endocrine neoplasia type 1 (MEN1) organ manifestations and the increase in clinical experience warrant a revision of previously published guidelines. Duodenopancreatic neuroendocrine neoplasias (DP-NENs) are still the second most common manifestation in MEN1 and, besides NENs of the thymus, remain a leading cause of death. DP-NENs are thus of main interest in the effort to reevaluate recommendations for their diagnosis and treatment. Especially over the last 2 years, more clinical experience has documented the follow-up of treated and untreated (natural-course) DP-NENs. It was the aim of the international consortium of experts in endocrinology, genetics, radiology, surgery, gastroenterology, and oncology to systematically review the literature and to present a consensus statement based on the highest levels of evidence. Reviewing the literature published over the past decade, the focus was on the diagnosis of F- and NF-DP-NENs within the MEN1 syndrome in an effort to further standardize and improve treatment and follow-up, as well as to establish a "logbook" for the diagnosis and treatment of DP-NENs. This shall help further reduce complications and improve long-term treatment results in these rare tumors. The following international consensus statement builds upon the previously published guidelines of 2001 and 2012 and attempts to supplement the recommendations issued by various national and international societies.
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Affiliation(s)
- Bruno Niederle
- Department of Surgery, Medical University of Vienna, Vienna, Austria,
| | | | - Detlef K Bartsch
- Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Marburg, Germany
| | - Maria L Brandi
- Firmo Lab, Fondazione F.I.R.M.O. and University Florence, Florence, Italy
| | - Gerard M Doherty
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Massimo Falconi
- Pancreatic Surgery, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy
| | - Pierre Goudet
- Service de Chirurgie Viscérale et Endocrinienne, Centre Hospitalier Universitaire François Mitterand, Dijon, France
| | | | - Tetsuhide Ito
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital and Department of Gastroenterology, Graduate School of Medical Sciences, International University of Health and Welfare, Sawara-ku, Fukuoka, Japan
| | - Robert T Jensen
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Alberto Larghi
- Digestive Endoscopy Unit, Fondazione Policlinico A. Gemelli IRCCS and Center for Endoscopic Research, Therapeutics and Training, Catholic University, Rome, Italy
| | - Lingaku Lee
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Kjell Öberg
- Endocrine Oncology, Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden
| | - Marianne Pavel
- Endocrinology and Diabetology, Department of Medicine 1, University Clinic of Erlangen, Erlangen, Germany
| | - Aurel Perren
- Institute of Pathology, University of Bern, Bern, Switzerland
| | - Samira M Sadowski
- Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Francesco Tonelli
- Department of Surgery and Translational Medicine, University of Florence, Florence, Italy
| | - Frédéric Triponez
- Thoracic and Endocrine Surgery, University Hospital of Geneva, Geneva, Switzerland
| | - Gerlof D Valk
- Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Dermot O'Toole
- Department of Clinical Medicine, St. James's Hospital and St Vincent's University Hospital and Trinity College, Dublin, Ireland
| | - David Scott-Coombes
- Department of Endocrine Surgery, University Hospital of Wales, Cardiff, United Kingdom
| | - Rajesh V Thakker
- Academic Endocrine Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, United Kingdom
| | - Geoffrey B Thompson
- Section of Endocrine Surgery, Department of Gastroenterologic and General Surgery, Mayo Clinic, Rochester, Minnesota, USA
| | - Giorgio Treglia
- Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | - Bertram Wiedenmann
- Department of Gastroenterology and Hepatology, Campus Virchow-Klinikum and Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany
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11
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Xiang JX, Zhang XF, Weiss M, Aldrighetti L, Poultsides GA, Bauer TW, Fields RC, Maithel SK, Marques HP, Pawlik TM. Multi-institutional Development and External Validation of a Nomogram Predicting Recurrence After Curative Liver Resection for Neuroendocrine Liver Metastasis. Ann Surg Oncol 2020; 27:3717-3726. [PMID: 32436187 DOI: 10.1245/s10434-020-08620-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2020] [Indexed: 04/06/2025]
Abstract
OBJECTIVES To establish and externally validate a novel nomogram to predict recurrence of patients undergoing curative liver resection for neuroendocrine liver metastasis (NELM). METHODS A total of 279 patients who underwent curative liver resection for NELM identified from an international multicenter database were utilized to develop a nomogram to predict recurrence; 98 cases from two different institutions were used to externally validate the nomogram. RESULTS Among 279 patients in the development cohort, median age was 57 years, and 50.5% were male. On multivariate analysis, primary tumor location (pancreatic vs nonpancreatic, HR 2.1, p = 0.004), tumor grade (Ref. well, moderate HR 1.9, p = 0.022; poor HR 1.6, p = 0.238), lymph node metastasis (positive vs negative, HR 2.6, p = 0.002), and extent of resection (major vs parenchymal-sparing resection, HR 0.3, p = 0.001) were independently associated with recurrence-free survival. The beta coefficients from the final multivariable model were utilized to develop a nomogram. The nomogram demonstrated good ability to predict risk of recurrence (training cohort, C-index 0.754; validation cohort, C-index 0.748). The calibrated nomogram predicted recurrence-free survival that closely corresponded to actual recurrence. Decision curve analysis demonstrated that the nomogram had a good net benefit for most of the threshold probabilities, especially between 20 and 60%, in both development and validation cohorts. CONCLUSIONS The externally validated novel nomogram predicted 3- and 5-year recurrence-free survival among patients with NELM. Prediction of individual recurrence risk may help guide personalized estimates of prognosis, as well as surveillance protocols and consideration of adjuvant therapies.
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Affiliation(s)
- Jun-Xi Xiang
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xu-Feng Zhang
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Health Services Management and Policy, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Matthew Weiss
- Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Luca Aldrighetti
- Department of Surgery, Scientific Institute San Raffaele, Vita-Salute San Raffaele University, Milan, Italy
| | | | - Todd W Bauer
- Department of Surgery, University of Virginia, Charlottesville, VA, USA
| | - Ryan C Fields
- Department of Surgery, School of Medicine, Washington University, St. Louis, MO, USA
| | | | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - Timothy M Pawlik
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Health Services Management and Policy, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
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12
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Tsilimigras DI, Xiang JX, Zhang XF, Pawlik TM. ASO Author Reflections: A Nomogram to Predict Recurrence after Curative-Intent Resection for Neuroendocrine Liver Metastasis. Ann Surg Oncol 2020; 27:3727-3728. [PMID: 32440717 DOI: 10.1245/s10434-020-08622-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Indexed: 11/18/2022]
Affiliation(s)
- Diamantis I Tsilimigras
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH, USA
| | - Jun-Xi Xiang
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xu-Feng Zhang
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH, USA
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH, USA.
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13
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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: 22] [Impact Index Per Article: 4.4] [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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14
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Masui T, Nagai K, Anazawa T, Kasai Y, Sato A, Nakano K, Uchida Y, Yogo A, Kawaguchi Y, Takaori K, Uemoto S. Risk factors for short recurrence-free survival after resection of pancreatic neuroendocrine tumor (PanNET) liver metastases: which patients should undergo resection? Scand J Gastroenterol 2020; 55:479-484. [PMID: 32223573 DOI: 10.1080/00365521.2020.1743352] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Background: In the treatment of metastatic pancreatic neuroendocrine tumors (PanNETs), surgical resection is the first choice if curative resection is expected. However, most patients develop recurrence after resection of liver metastasis. Because one of the benefits of resection is to gain a tumor-free period for the patients, it is important to identify which patients achieve longer recurrence-free survival (RFS) by resection. In this study, the clinicopathological factors associated with RFS after resection of metastatic PanNETs in the liver were evaluated to identify the patient group that is suitable for resection.Methods: Consecutively diagnosed patients with PanNET liver metastasis with resection at our hospital from January 2000 to July 2019 were evaluated. A total of 26 metastatic PanNET patients with primary liver resections were evaluated. The median follow-up time was 48.3 months.Results: There were 18 NET recurrences of the total 26 resections, with a median RFS of 17.9 months. Independent risk factors for short RFS were a high Ki67 index (p = .009) and the number of resected tumors (p = .045). When the cut-off value for the Ki67 index was 5.0% and that for the number of resected tumors was 6, Ki67 > 5.0% tumors had shorter RFS (4.9 months vs. 38.2 months p = .006), and patients with tumors > = 7 tumors had shorter RFS (4.7 months vs. 27.5 months p = .001).Conclusions: These findings indicate that good candidates for resection of metastatic tumors of PanNETs could be patients with low Ki67 tumors and a small number of metastatic tumors.
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Affiliation(s)
| | | | | | - Yosuke Kasai
- Department of Surgery, Kyoto University, Kyoto, Japan
| | - Asahi Sato
- Department of Surgery, Kyoto University, Kyoto, Japan
| | - Kenzo Nakano
- Department of Surgery, Kyoto University, Kyoto, Japan
| | | | - Akitada Yogo
- Department of Surgery, Kyoto University, Kyoto, Japan
| | | | | | - Shinji Uemoto
- Department of Surgery, Kyoto University, Kyoto, Japan
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15
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Spolverato G, Bagante F, Tsilimigras DI, Pawlik TM. Liver transplantation in patients with liver metastases from neuroendocrine tumors. MINERVA CHIR 2019; 74:399-406. [PMID: 31280548 DOI: 10.23736/s0026-4733.19.08119-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The prevalence of metastatic disease in neuroendocrine tumors (NETs) is very high (60-80%) and cancer-related death among these patients is generally due to metastatic disease. Numerous treatment options for cure and disease control have been investigated for patients with neuroendocrine liver metastases (NELM). Despite the success of liver directed therapy on slowing tumor progression and palliating symptoms, the chance of being cured by liver resection is 40-50% and only roughly 20% of patients have potentially resectable disease. As such, there has been interest in liver transplantation (LT) as a potentially curative option for patients with unresectable disease. Several criteria have been proposed in order to balance long-term outcomes of patients with NELM and the problem of organ shortage including the Milan-NET criteria, the UNOS criteria and the ENETS guidelines. In the most representative studies, recurrence rate after LT has ranged from 30% to 60% with a 5-year OS ranging from 50% to 97%. This large variability is due to the retrospective nature of the studies available, which used different inclusion criteria. As such, outcomes and the prognostic factors associated with LT for NELM warrant further investigation.
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Affiliation(s)
- Gaya Spolverato
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy
| | - Fabio Bagante
- Department of Surgery, University of Verona, Verona, Italy
| | | | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA -
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16
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Liver metastases of neuroendocrine tumors: is it possible to diagnose different histologic subtypes depending on multiphasic CT features? Abdom Radiol (NY) 2019; 44:2147-2155. [PMID: 30863999 DOI: 10.1007/s00261-019-01963-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
PURPOSE To assess and compare the multiphasic computed tomography (CT) features of neuroendocrine tumor (NET) liver metastases and to investigate the possibility to predict the histologic subtype of the primary tumor. MATERIALS AND METHODS Between January 2013 and December 2017 patients with biopsy proven NET with at least one liver metastasis who underwent multiphasic CT were enrolled in this study. All cases were acquired using a standardized multiphasic liver CT protocol, arterial, portal, and hepatic venous phases were obtained. Images were retrospectively analyzed in consensus by two abdominal radiologists blinded to clinical data and histologic subtype. The size, number, and location of lesions were noted. Enhancement patterns of each lesion on arterial, portal, and hepatic venous phases were assessed. For quantitative analysis, CT attenuation of tumors, liver parenchyma, and aorta were measured using a circular region of interest (ROI) on arterial, portal, and hepatic venous phases for reflecting the blood supply of the tumor. Tumor-to-aorta and tumor-to-liver ratio were calculated in all three phases. Differences between subtypes of NET liver metastases were studied using ROC analysis of clustered data. RESULTS A total of 255 neuroendocrine tumor liver metastases divided into 101 (39.6%) pancreatic, 60 (23.5%) gastroenteric and 94 (36.8%) lung NET liver metastases were analyzed. Contrast enhancement of lesions was homogeneous in 78% of patients (n = 199), which was significantly more frequent in patients with pancreatic group than in those with gastroenteric origin (n = 90, 89.1% vs. n = 28, 46.7%; p < 0.001). Gastroenteric NET metastases frequently showed heterogeneous enhancement, which was significantly higher than in the other two groups (50% vs. 3% and 2%). With respect to the location of the primary tumor, the difference in enhancement patterns of the liver lesions was statistically significant (p < 0.001). Pancreatic NET metastases were mostly hyperdense on arterial images and isodense on portal and hepatic venous phase images (79.2%, n = 80). Gastroenteric NET metastases were mostly hyperdense on arterial phase images and hypodense on portal and hepatic venous phase images (n = 28, 46.7%). The most frequent pattern for lung NET metastases was hypoattenuation on all three phase images (n = 44, 46.8%). ROC analysis of clustered data revealed statistically significant differences between pancreatic NET liver metastases, gastroenteric NET liver metastases, and lung NET liver metastases in terms of tumor-to-aorta (T-A) ratio and tumor-to-liver (T-L) ratio (p < 0.001). CONCLUSION We observed statistically significant differences in multiphasic CT features (enhancement pattern, T-A ratio, and T-L ratio) between histologic subtypes of NET liver metastases. As the difference in histological subtypes of NET liver metastases results in a different prognosis and different management strategy, these CT features might help to identify the primary tumor when it is not known to ensure accurate tumor staging and to provide optimal treatment.
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Fung AK, Chong CC. Surgical strategy for neuroendocrine liver metastases. SURGICAL PRACTICE 2019. [DOI: 10.1111/1744-1633.12364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- Andrew Kai‐Yip Fung
- Department of SurgeryThe Chinese University of Hong Kong, Prince of Wales Hospital Hong Kong
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18
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Li G, Tian ML, Bing YT, Tao LY, Wang HY, Jiang B, Yuan CH, Xiu DR. Clinicopathological features and prognosis factors for survival in elderly patients with pancreatic neuroendocrine tumor: A STROBE-compliant article. Medicine (Baltimore) 2019; 98:e14576. [PMID: 30882623 PMCID: PMC6426577 DOI: 10.1097/md.0000000000014576] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
To investigate the features and prognosis of the elderly patients with pancreatic neuroendocrine tumor (pNET).The patients diagnosed with pNETs between 2004 and 2014 were identified from the Surveillance Epidemiology and End Results database. The ethical approval was waived because the present study was analysis of the data from Surveillance Epidemiology and End Results database.A total of 4608 patients with "one primary only" histologically pNETs were confirmed and 653 were older than 75 years. Cancer-specific survival (CSS) and overall survival (OS) were examined. The elderly patients (≥75 years) have disadvantage in CSS and OS compared with younger cohort. Multivariate logistic regression revealed that the elderly patients have increased poorly differentiated composition, and decreased proportion of Black patients, receipt of surgery, married status, and number of removed lymph node. Multivariate Cox regression analysis demonstrated worse differentiation. Patients of T3-4 and M1 stage were associated with poor CSS, while patients of being female, tumor locating at pancreatic body/tail, receipt of surgery, and being married were associated with better CSS in the elderly patients. Meanwhile, patients with higher histological grade and M1 stage have poor OS, while patients with the characteristics of female, being married, tumor location at pancreatic body/tail and tumor surgery have better OS. Distant metastatic elderly patients underwent primary site surgery had better CSS and OS than the patients without surgery.The elderly patients have increased possibility of poorly differentiated tumor, and decreased proportion of Black patients, surgery of primary site, number of removed lymph node and married status. Worse differentiation and tumor metastasis were independent risk factors for both CSS and OS, while primary tumor located in body/tail of pancreas, female patients, surgery of tumor primary site, and being married were protective factors.
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19
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Xiang JX, Zhang XF, Weiss M, Aldrighetti L, Poultsides GA, Bauer TW, Fields RC, Maithel SK, Marques HP, Pawlik TM. Early recurrence of well-differentiated (G1) neuroendocrine liver metastasis after curative-intent surgery: Risk factors and outcome. J Surg Oncol 2018; 118:1096-1104. [PMID: 30261105 DOI: 10.1002/jso.25246] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2018] [Accepted: 08/28/2018] [Indexed: 01/05/2023]
Abstract
BACKGROUND The objective of the current study was to identify the risk of early vs late recurrence of well-differentiated (G1) neuroendocrine liver metastasis (NELM) after curative-intent resection. METHODS Patients who underwent curative-intent resection for well-differentiated NELM were identified from a multi-institutional database. Clinicopathological details, as well as the long-term overall (OS) and recurrence free survival (RFS) were obtained and compared. The optimal cutoff value to differentiate early and late recurrence was determined to be 1 year based on trend curve analysis. RESULTS Among the 548 patients undergoing curative resection for NELM, 162 patients had a well-differentiated NELM. After a median follow-up of 69 months, 59 (36.4%) patients had tumor recurrence; 23 (39.0%) patients recurred within 1 year (early recurrence) after surgery, while 36 (61.0%) recurred after 1 year (late recurrence). Early recurrence was associated with worse outcome vs late recurrence (5-year OS, 72.4% vs 92.0%; P = 0.020) and no recurrence (5-year OS, 72.4% vs 100.0%; P < 0.001). In addition, postrecurrence survival was worse within 36 months after recurrence among patients who recurred early compared with patients who recurred late (survival after recurrence at 36 months: early recurrence, 71.6% vs late recurrence, 91.4%; P = 0.047), although survival was comparable at 60 months (early recurrence, 71.6% vs late recurrence, 70.0%; P = 0.304). On multivariable analysis, nonfunctional neuroendocrine tumors (hazard ratio [HR], 4.4; 95% confidence interval [CI], 1.2-16.7; P = 0.029) and lymph node metastasis (HR, 3.6; 95% CI, 1.1-11.1; P = 0.028) were independent risk factors for early recurrence, whereas lymph node metastasis (HR, 3.0; 95% CI, 1.2-7.8; P = 0.020) and R1 resection (HR, 3.9; 95% CI, 1.4-10.5; P = 0.008) were independently associated with late recurrence. CONCLUSIONS Roughly, one-third of patients with well-differentiated NELM experienced a recurrence following curative-intent surgery. Among patients who recurred, two out of five patients recurred within 1 year after surgery. Early recurrence of well-differentiated NELM was associated with the hormone functional status and lymph node metastasis.
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Affiliation(s)
- Jun-Xi Xiang
- Department of Hepatobiliary Surgery, Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xu-Feng Zhang
- Department of Hepatobiliary Surgery, Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Department of Surgery, Wexner Medical Center, The Ohio State University, Columbus, Ohio
| | - Matthew Weiss
- Department of Surgery, Johns Hopkins Hospital, Baltimore, Maryland
| | - Luca Aldrighetti
- Department of Surgery, Scientific Institute San Raffaele, Vita-Salute San Raffaele University, Milan, Italy
| | | | - Todd W Bauer
- Department of Surgery, University of Virginia, Charlottesville, Virginia
| | - Ryan C Fields
- Department of Surgery, Washington University, School of Medicine, St Louis, Missouri
| | | | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - Timothy M Pawlik
- Department of Surgery, Wexner Medical Center, The Ohio State University, Columbus, Ohio
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20
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Yu X, Gu J, Wu H, Fu D, Li J, Jin C. Resection of Liver Metastases: A Treatment Provides a Long-Term Survival Benefit for Patients with Advanced Pancreatic Neuroendocrine Tumors: A Systematic Review and Meta-Analysis. JOURNAL OF ONCOLOGY 2018; 2018:6273947. [PMID: 30538745 PMCID: PMC6261248 DOI: 10.1155/2018/6273947] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Accepted: 10/24/2018] [Indexed: 02/07/2023]
Abstract
PURPOSE Nonsurgical therapies, including biotherapy, chemotherapy, and liver-directed therapy, provided a limit survival benefit for PNET patients with hepatic metastases. With the development of liver resection technique, there was a controversy on whether to perform a liver resection for these patients. METHODS A computerized search was made of the Medline/PubMed, EMbase, Cochrane Library, and SinoMed (CBM) before March 2018. A meta-analysis was performed to investigate the differences in the efficacy of liver resection and nonliver resection treatments based on the evaluation of morbidity, 30-day mortality, symptom relief rate, and 1-, 3-, and 5-year survival. Two investigators reviewed all included articles and extracted the data of them. The meta-analysis was performed via Review Manager 5.3 software. RESULTS A total of 13 cohort studies with 1524 patients were included in this meta-analysis. Compared with the nonliver resection group, liver resection group had a longer 1-, 3-, and 5-year survival time and a higher symptom relief with an acceptable mortality and morbidity. CONCLUSIONS Liver resection is a safe treatment and could significantly prolong the long-term prognosis for highly selected patients with resectable liver metastases from PNET. Further randomized, controlled trials are needed.
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Affiliation(s)
- Xinzhe Yu
- Department of Thoracic Surgery, Fudan University Shanghai Cancer Center. 270 Dong-An Rd, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jichun Gu
- Pancreatic Surgery Department, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China
| | - Haoxuan Wu
- Department of Thoracic Surgery, Fudan University Shanghai Cancer Center. 270 Dong-An Rd, Shanghai 200032, China
| | - Deliang Fu
- Pancreatic Surgery Department, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China
| | - Ji Li
- Pancreatic Surgery Department, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China
| | - Chen Jin
- Pancreatic Surgery Department, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China
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21
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Frilling A, Clift AK. Surgical Approaches to the Management of Neuroendocrine Liver Metastases. Endocrinol Metab Clin North Am 2018; 47:627-643. [PMID: 30098720 DOI: 10.1016/j.ecl.2018.04.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Surgical approaches to hepatic metastases occupy an important role in the management of patients with neuroendocrine neoplasms and may have curative or palliative intentions. Resection of hepatic disease with curative intent is the only modality offering potential cure for patients with liver metastases; however, only a minority of patients are eligible. Regardless of resection margin, disease recurrence almost invariably occurs and novel adjuvant/neoadjuvant therapies are mandated to be included within multimodal treatment concepts. Liver transplantation in meticulously selected patients may be associated with excellent outcomes, but unfortunately demands on donated organs limit the wider utilization of this approach.
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Affiliation(s)
- Andrea Frilling
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0HS, UK.
| | - Ashley Kieran Clift
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0HS, UK
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Iodine quantification to distinguish hepatic neuroendocrine tumor metastasis from hepatocellular carcinoma at dual-source dual-energy liver CT. Eur J Radiol 2018; 105:20-24. [PMID: 30017280 DOI: 10.1016/j.ejrad.2018.05.019] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2018] [Revised: 04/20/2018] [Accepted: 05/15/2018] [Indexed: 02/07/2023]
Abstract
PURPOSE To investigate the value of third-generation dual-source dual-energy computed tomography (DECT) iodine quantification to distinguish hepatic neuroendocrine tumor (NET) metastasis from hepatocellular carcinoma (HCC) in non-cirrhotic liver parenchyma. MATERIAL AND METHODS Forty-six patients (mean age, 64.9 ± 10.1 years; 28 male and 18 female) with either hepatic NET metastasis or HCC, who had undergone liver DECT, were included in this retrospective study. For each lesion, arterial-phase attenuation values and DECT quantitative parameters, including iodine uptake, fat fraction, normalized iodine uptake (NIU), and lesion-to-liver-parenchyma ratio (LPR) were evaluated. Available cumulative data from histopathology, MRI, PET/CT, or interval imaging follow-up served as the reference standard for all liver lesions. In addition, the diagnostic accuracy of contrast-enhanced and material decomposition analysis for the differentiation of hepatic NET metastasis and HCC was assessed using receiver operating characteristics (ROC) curve analysis. RESULTS Hepatic NET metastasis and HCC showed significant differences in arterial attenuation (P = 0.003), iodine uptake (P < 0.001), NIU (P < 0.001), and LPR (P = 0.003). No significant differences were found for unenhanced attenuation and fat fraction values (P = 0.686 and P = 0.892, respectively). NIU showed superior sensitivity (100%; iodine uptake, 71%), while both iodine uptake and NIU revealed superior specificity (100% and 90%, respectively) compared to LPR (sensitivity, 96%; specificity, 80%) and arterial attenuation analysis (sensitivity, 79%; specificity, 80%) (P ≤ 0.016). CONCLUSION Third-generation DECT with assessment of iodine uptake improves the differentiation of hepatic NET metastasis and HCC in non-cirrhotic liver, with NIU showing the strongest diagnostic performance.
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23
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Hasegawa S, Kobayashi N, Tokuhisa M, Goto A, Takano S, Takada Y, Kaneta T, Mori R, Matsuyama R, Endo I, Yamanaka S, Nakajima A, Inoue T, Ichikawa Y. Clinical Usefulness of Somatostatin Receptor Scintigraphy in Japanese Patients with Gastroenteropancreatic Neuroendocrine Tumors. Digestion 2018; 96:13-20. [PMID: 28609761 DOI: 10.1159/000470838] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Accepted: 03/10/2017] [Indexed: 02/04/2023]
Abstract
BACKGROUND/AIMS Somatostatin receptor (SSTR) scintigraphy (SRS) is the standard imaging modality for evaluation of gastroenteropancreatic neuroendocrine tumor (GEP-NET) in Western countries. However, this modality was not approved in Japan until recently. The purpose of this study was to evaluate the clinical efficacy of SRS for detecting GEP-NET in Japanese patients. METHODS Japanese patients with advanced GEP-NET were enrolled and evaluated by the SRS and CT. We also compared SRS and immunohistochemical expression of SSTR type 2a (SSTR2a). RESULTS We enrolled 16 patients and the primary sites were the pancreas in 9, the stomach in 1, the small intestine in 2, the colon in 3, and unknown in 1. SRS showed positive findings in 3 (100%) of grade 1 (G1) and in 12 (92.3%) of grade 2 (G2) lesions. In the liver, SRS and CT detected lesions in 13 and 14 cases, respectively. The concordance rate of SSTR2a expression with SRS findings was 93.8% in the whole body and 92.9% in the liver. CONCLUSIONS SRS could detect almost all of G1 and G2. SRS could be useful to detect lesions, with a high concordance rate with CT and pathological findings. We confirmed that SRS is a useful and reliable modality for Japanese patients.
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Affiliation(s)
- Sho Hasegawa
- Oncology Division, Yokohama City University Hospital, Yokohama, Japan
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Sposito C, Droz Dit Busset M, Citterio D, Bongini M, Mazzaferro V. The place of liver transplantation in the treatment of hepatic metastases from neuroendocrine tumors: Pros and cons. Rev Endocr Metab Disord 2017; 18:473-483. [PMID: 29359266 DOI: 10.1007/s11154-017-9439-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Liver metastases occur in nearly half of NET patients (MNETs) and heavily affect prognosis, with 5-yr. OS around 19-38%. Although it is difficult to show outcome differences for available treatments, due to the long course of disease, surgery for MNETs remains the most effective option in terms of survival and symptom control. Since MNETs frequently present as an oligo-metastatic, liver-limited disease, unresectable in 80% of cases, liver transplantation (LT) has emerged as a potential curative treatment. Nevertheless, experience with LT for MNETs is limited and burdened by highly heterogeneous outcomes and significant recurrence rate, mostly explained by the variability of selection criteria. Several prognostic factors have been identified: extended surgery on primary tumor associated to LT, elderly patients, pancreatic primary (pNET), extensive liver involvement, poorly differentiated tumors, high Ki67 levels and short wait time to LT. A proper patients' selection based on these data (Milan NET criteria) allows a significant survival advantage over non-transplant strategies, with excellent outcomes in recent series (69-97.2% 5-yr. OS) as opposed to patients undergoing non-surgical treatments (34-50.9%). Evidence indicates LT as the best option for selected patients with MNETs. The use of organs for MNETs is therefore justified.
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Affiliation(s)
- Carlo Sposito
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Via Venezian 1, 20133, Milan, Italy
| | - Michele Droz Dit Busset
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Via Venezian 1, 20133, Milan, Italy
| | - Davide Citterio
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Via Venezian 1, 20133, Milan, Italy
| | - Marco Bongini
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Via Venezian 1, 20133, Milan, Italy
| | - Vincenzo Mazzaferro
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Via Venezian 1, 20133, Milan, Italy.
- University of Milan, Milan, Italy.
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25
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Masui T, Sato A, Nakano K, Uchida Y, Yogo A, Anazawa T, Nagai K, Kawaguchi Y, Takaori K, Uemoto S. Comparison of Recurrence Between Pancreatic and Duodenal Neuroendocrine Neoplasms After Curative Resection: A Single-Institution Analysis. Ann Surg Oncol 2017; 25:528-534. [PMID: 29164413 DOI: 10.1245/s10434-017-6260-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2017] [Indexed: 01/15/2023]
Abstract
BACKGROUND The primary site of a neuroendocrine neoplasms (NEN) around the head of the pancreas is sometimes difficult to assess before resection, and the characteristics of the primary site around this region have not been elucidated for recurrence after curative resection. In this study, the clinicopathologic characteristics of pancreatic NEN (PanNEN) and duodenal NEN (DuNEN) were evaluated, and the risk factors as well as the recurrence types after resection were investigated. METHODS Consecutively diagnosed NEN patients at the authors' hospital from January 2000 to July 2016 were evaluated in this study. For 117 PanNEN patients and 31 non-ampullary DuNEN patients, R0 resection was achieved. The median follow-up period was 8.1 years. RESULTS In this study, 27 PanNEN patients (23.1%) had recurrences, with a median disease-free survival (DFS) of 133 months, whereas 11 DuNEN patients (35.5%) had recurrences, with a median DFS of 156 months. The PanNEN patients tended to have primary recurrence in the liver (85.2%), followed by lymph nodes (11.1%). The independent risk factors for short DFS were lymph node metastasis at resection (p = 0.001) and microvascular invasion (p = 0.048). In contrast, the DuNEN patients were likely to have lymph node metastasis (81.8%). The independent risk factors for short DFS were lymph node metastasis at resection (p = 0.003) and large diameter (p = 0.013). CONCLUSIONS Most initial recurrences of PanNEN occurred in the liver, whereas those of DuNEN appeared in lymph nodes, suggesting that proper diagnosis of the primary site and appropriate imaging methods for surveillance after resection are necessary.
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Affiliation(s)
- Toshihiko Masui
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan.
| | - Asahi Sato
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Kenzo Nakano
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Yuichiro Uchida
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Akitada Yogo
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Takayuki Anazawa
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Kazuyuki Nagai
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Yoshiya Kawaguchi
- Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan
| | - Kyoichi Takaori
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Shinji Uemoto
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
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Almond L, Hodson J, Ford S, Gourevitch D, Roberts K, Shah T, Isaac J, Desai A. Role of palliative resection of the primary tumour in advanced pancreatic and small intestinal neuroendocrine tumours: A systematic review and meta-analysis. Eur J Surg Oncol 2017; 43:1808-1815. [DOI: 10.1016/j.ejso.2017.05.016] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Revised: 05/02/2017] [Accepted: 05/15/2017] [Indexed: 01/22/2023] Open
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Tao L, Xiu D, Sadula A, Ye C, Chen Q, Wang H, Zhang Z, Zhang L, Tao M, Yuan C. Surgical resection of primary tumor improves survival of pancreatic neuroendocrine tumor with liver metastases. Oncotarget 2017; 8:79785-79792. [PMID: 29108359 PMCID: PMC5668092 DOI: 10.18632/oncotarget.19523] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2017] [Accepted: 07/13/2017] [Indexed: 02/07/2023] Open
Abstract
This study investigates survival of patients diagnosed with pancreatic neuroendocrine tumor with liver metastases based on local treatment on the primary tumor. Patients diagnosed with stage IV PNET between 2010 and 2014 were identified from the Surveillance Epidemiology and End Results database. Cancer-Specific Survival and Overall Survival were examined. A total of 191 patients with pancreatic neuroendocrine tumor with liver metastases were included in this analysis. There were 47 patients (24.6%) who received surgical resection and 144 (75.4%) who did not. Patients with N1 stage was more likely to be treated with surgical resection. The results showed that surgical resection of primary tumor was associated with Cancer-Specific Survival (p = 0.028) and Overall Survival (p = 0.025) benefit. Not receiving surgery, being unmarried and N1 stage are factors associated with poor survival. This study reveals that local treatment on the primary benefits both Cancer-Specific Survival and Overall Survival in PNET patients with LM. This may be suggestive for the management on this patient population.
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Affiliation(s)
- Lianyuan Tao
- Department of General Surgery, Peking University Third Hospital, Beijing 100191, China
| | - Dianrong Xiu
- Department of General Surgery, Peking University Third Hospital, Beijing 100191, China
| | - Abuduhaibaier Sadula
- Department of General Surgery, Peking University Third Hospital, Beijing 100191, China
| | - Chen Ye
- Department of General Surgery, Peking University Third Hospital, Beijing 100191, China
| | - Qing Chen
- Department of General Surgery, Peking University Third Hospital, Beijing 100191, China
| | - Hanyan Wang
- Department of General Surgery, Peking University Third Hospital, Beijing 100191, China
| | - Zhipeng Zhang
- Department of General Surgery, Peking University Third Hospital, Beijing 100191, China
| | - Lingfu Zhang
- Department of General Surgery, Peking University Third Hospital, Beijing 100191, China
| | - Ming Tao
- Department of General Surgery, Peking University Third Hospital, Beijing 100191, China
| | - Chunhui Yuan
- Department of General Surgery, Peking University Third Hospital, Beijing 100191, China
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Management Options for Advanced Low or Intermediate Grade Gastroenteropancreatic Neuroendocrine Tumors: Review of Recent Literature. Int J Surg Oncol 2017; 2017:6424812. [PMID: 28593056 PMCID: PMC5448049 DOI: 10.1155/2017/6424812] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2017] [Revised: 04/13/2017] [Accepted: 04/26/2017] [Indexed: 02/06/2023] Open
Abstract
Our understanding of the biology, genetics, and natural history of neuroendocrine tumors (NETs) of the gastrointestinal tract and pancreas has improved considerably in the last several decades and the spectrum of available therapeutic options is rapidly expanding. The management of patients with metastatic low or intermediate grade NETs has been revolutionized by the development of new treatment strategies such as molecular targeting therapies with everolimus and sunitinib, somatostatin analogs, tryptophan hydroxylase inhibitors, and peptide receptor radionuclide therapy that can be used alone or as a multimodal approach with or without surgery. To further define and clarify the utility, appropriateness, and the sequence of the growing list of available therapies for this patient population will require more high level evidence; however, data from well-designed randomized phase III clinical trials is rapidly accumulating that will further stimulate development of new management strategies. It is therefore important to thoroughly review emerging evidence and report major findings in frequent updates, which will expand our knowledge and contribute to a better understanding, characterization, and management of advanced NETs.
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Cavalcoli F, Rausa E, Conte D, Nicolini AF, Massironi S. Is there still a role for the hepatic locoregional treatment of metastatic neuroendocrine tumors in the era of systemic targeted therapies? World J Gastroenterol 2017; 23:2640-2650. [PMID: 28487601 PMCID: PMC5403743 DOI: 10.3748/wjg.v23.i15.2640] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2017] [Revised: 03/11/2017] [Accepted: 03/20/2017] [Indexed: 02/06/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) frequently present with distant metastases at the time of diagnosis and the liver is the most frequent site of spreading. The early identification of metastatic disease represents a major prognostic factor for GEP-NENs patients. Radical surgical resection, which is feasible for a minority of patients, is considered the only curative option, while the best management for patients with unresectable liver metastases is still being debated. In the last few years, a number of locoregional and systemic treatments has become available for GEP-NEN patients metastatic to the liver. However, to date only a few prospective studies have compared those therapies and the optimal management option is based on clinical judgement. Additionally, locoregional treatments appear feasible and safe for disease control for patients with limited liver involvement and effective in symptoms control for patients with diffuse liver metastases. Considering the lack of randomized controlled trials comparing the locoregional treatments of liver metastatic NEN patients, clinical judgment remains key to set the most appropriate therapeutic pathway. Prospective data may ultimately lead to more personalized and optimized treatments. The present review analyzes all the locoregional therapy modalities (i.e., surgery, ablative treatments and transarterial approach) and aims to provide clinicians with a useful algorithm to best treat GEP-NEN patients metastatic to the liver.
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30
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Ronot M, Cuccioli F, Dioguardi Burgio M, Vullierme MP, Hentic O, Ruszniewski P, d’Assignies G, Vilgrain V. Neuroendocrine liver metastases: Vascular patterns on triple-phase MDCT are indicative of primary tumour location. Eur J Radiol 2017; 89:156-162. [DOI: 10.1016/j.ejrad.2017.02.007] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Revised: 01/25/2017] [Accepted: 02/04/2017] [Indexed: 10/20/2022]
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Ito T, Hijioka S, Masui T, Kasajima A, Nakamoto Y, Kobayashi N, Komoto I, Hijioka M, Lee L, Igarashi H, Jensen RT, Imamura M. Advances in the diagnosis and treatment of pancreatic neuroendocrine neoplasms in Japan. J Gastroenterol 2017; 52:9-18. [PMID: 27539256 DOI: 10.1007/s00535-016-1250-9] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2016] [Accepted: 07/27/2016] [Indexed: 02/06/2023]
Abstract
Several new developments have occurred in the field of pancreatic neuroendocrine neoplasm (PNEN) recently in Japan. First, the utility of chromogranin A (CgA), useful for the diagnosis and monitoring of the treatment response of neuroendocrine neoplasm (NEN), has been demonstrated in Japan. For PNEN diagnosis and treatment, grading and correct histological diagnosis according to the WHO 2010 classification is important. Regarding the histological diagnosis, the advent of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has enabled correct pathological diagnosis and suitable treatment for the affected tissue. Furthermore, EUS-FNA has also facilitates the assessment of the presence or absence of gene mutations. In addition, patients who have a well-differentiated neuroendocrine tumor (NET) showing a Ki-67 index of higher than 20 % according to the WHO 2010 classification, have also been identified, and their responses to treatment were found to be different from those of patients with poorly differentiated neuroendocrine carcinoma (NEC). Therefore, the concept of NET G3 was proposed. Additionally, somatostatin receptor type 2 is expressed in several cases of NET, and somatostatin receptor scintigraphy (111In-octreoscan) has also been approved in Japan. This advancement will undoubtedly contribute to the localization diagnosis, the identification of remote metastasis, and assessments of the treatment responses of PNEN. Finally, regarding the treatment strategy for PNEN, the management of liver metastasis is important. The advent of novel molecular-targeted agents has dramatically improved the prognosis of advanced PNEN. Multimodality therapy that accounts for the tumor stage, degree of tumor differentiation, tumor volume, and speed of tumor growth is required.
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Affiliation(s)
- Tetsuhide Ito
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
| | - Susumu Hijioka
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Toshihiko Masui
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Atsuko Kasajima
- Department of Pathology, Tohoku University Hospital, Sendai, Japan
| | - Yuji Nakamoto
- Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Noritoshi Kobayashi
- Department of Oncology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan
| | - Izumi Komoto
- Department of Surgery, Kansai Electric Power Hospital, Osaka, Japan
| | - Masayuki Hijioka
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Lingaku Lee
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Hisato Igarashi
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Robert Thomas Jensen
- Digestive Diseases Branch, National Institutes of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Masayuki Imamura
- Neuroendocrine Tumor Center, Kansai Electric Power Hospital, Osaka, Japan
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Fairhurst K, Leopardi L, Satyadas T, Maddern G. The safety and effectiveness of liver resection for breast cancer liver metastases: A systematic review. Breast 2016; 30:175-184. [PMID: 27764727 DOI: 10.1016/j.breast.2016.09.011] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Revised: 08/11/2016] [Accepted: 09/15/2016] [Indexed: 02/08/2023] Open
Abstract
Breast cancer liver metastases have traditionally been considered incurable and any treatment given therefore palliative. Liver resections for breast cancer metastases are being performed, despite there being no robust evidence for which patients benefit. This review aims to determine the safety and effectiveness of liver resection for breast cancer metastases. A systematic literature review was performed and resulted in 33 papers being assembled for analysis. All papers were case series and data extracted was heterogeneous so a meta-analysis was not possible. Safety outcomes were mortality and morbidity (in hospital and 30-day). Effectiveness outcomes were local recurrence, re-hepatectomy, survival (months), 1-, 2-, 3-, 5- year overall survival rate (%), disease free survival (months) and 1-, 2-, 3-, 5- year disease free survival rate (%). Overall median figures were calculated using unweighted median data given in each paper. Results demonstrated that mortality was low across all studies with a median of 0% and a maximum of 5.9%. The median morbidity rate was 15%. Overall survival was a median of 35.1 months and a median 1-, 2-, 3- and 5-year survival of 84.55%, 71.4%, 52.85% and 33% respectively. Median disease free survival was 21.5 months with a 3- and 5-year median disease free survival of 36% and 18%. Whilst the results demonstrate seemingly satisfactory levels of overall survival and disease free survival, the data are of poor quality with multiple confounding variables and small study populations. Recommendations are for extensive pilot and feasibility work with the ultimate aim of conducting a large pragmatic randomised control trial to accurately determine which patients benefit from liver resection for breast cancer liver metastases.
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Affiliation(s)
- Katherine Fairhurst
- University of Adelaide Discipline of Surgery, The Queen Elizabeth Hospital, Woodville, Adelaide, South Australia, 5011, Australia.
| | - Lisa Leopardi
- University of Adelaide Discipline of Surgery, The Queen Elizabeth Hospital, Woodville, Adelaide, South Australia, 5011, Australia.
| | - Thomas Satyadas
- University of Adelaide Discipline of Surgery, The Queen Elizabeth Hospital, Woodville, Adelaide, South Australia, 5011, Australia.
| | - Guy Maddern
- University of Adelaide Discipline of Surgery, The Queen Elizabeth Hospital, Woodville, Adelaide, South Australia, 5011, Australia.
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Calin ML, Sadiq A, Arevalo G, Fuentes R, Flanders VL, Gupta N, Nasri B, Singh K. The First Case Report of Robotic Multivisceral Resection for Synchronous Liver Metastasis from Pancreatic Neuroendocrine Tumor: A Case Report and Literature Review. J Laparoendosc Adv Surg Tech A 2016; 26:816-824. [PMID: 27454160 DOI: 10.1089/lap.2016.0342] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
INTRODUCTION Surgery for liver metastases in pancreatic neuroendocrine tumor (PNET) improves overall survival rate. We present the first case report for robotic multivisceral resection of distal pancreas, spleen, and left liver for metastatic PNET. MATERIALS AND METHODS We present a case of 52-year-old female diagnosed with PNET in the pancreatic neck metastatic to the liver, responding to somatostatin and bland embolization, who underwent surgical debulking using da Vinci robotic platform. Intraoperative Doppler ultrasound was used to define the vascular distribution and tumor extension. The parenchymal liver transection was performed with vessel sealer. The distal pancreas and the spleen were approached medial to lateral and resected in an en-bloc fashion. The left liver inflow, outflow, and splenic artery and vein were transected with vascular stapler device. RESULTS Da Vinci robot-assisted multivisceral resection has been performed with good postoperative outcome. Operative time was 369 minutes and the estimated blood loss was 100 mL. The patient had a short hospital stay with quick recovery and good outcome at 5 months follow-up after the surgery. DISCUSSION Liver metastases in PNETs are considered an adverse factor. Aggressive surgical management is a mainstay. The laparoscopic approach to pancreatic or hepatic surgery is difficult in inexperienced hands with steep learning curve. The recent robotic system seems to overcome many limitations. This is the first case of robotic multivisceral resection for synchronous liver metastasis from PNET. Concurrent primary tumor resection with hepatectomy offers potential curative intention.
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Affiliation(s)
- Marius L Calin
- 1 Department of General Surgery, Saint Vincent Hospital Indianapolis , Indianapolis, Indiana
| | - Aziz Sadiq
- 1 Department of General Surgery, Saint Vincent Hospital Indianapolis , Indianapolis, Indiana
| | - Gabriel Arevalo
- 1 Department of General Surgery, Saint Vincent Hospital Indianapolis , Indianapolis, Indiana
| | - Rocio Fuentes
- 1 Department of General Surgery, Saint Vincent Hospital Indianapolis , Indianapolis, Indiana
| | - Vincent L Flanders
- 2 Department of Interventional Radiology, Saint Vincent Hospital Indianapolis , Indianapolis, Indiana
| | - Niraj Gupta
- 3 Department of Oncology, Saint Vincent Hospital Indianapolis , Indianapolis, Indiana
| | - Baongoc Nasri
- 4 Department of Surgery, Tokyo Metropolitan Matsuzawa Hospital , Tokyo, Japan
| | - Kirpal Singh
- 1 Department of General Surgery, Saint Vincent Hospital Indianapolis , Indianapolis, Indiana
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Singh S, Asa SL, Dey C, Kennecke H, Laidley D, Law C, Asmis T, Chan D, Ezzat S, Goodwin R, Mete O, Pasieka J, Rivera J, Wong R, Segelov E, Rayson D. Diagnosis and management of gastrointestinal neuroendocrine tumors: An evidence-based Canadian consensus. Cancer Treat Rev 2016; 47:32-45. [PMID: 27236421 DOI: 10.1016/j.ctrv.2016.05.003] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2016] [Accepted: 05/07/2016] [Indexed: 02/07/2023]
Abstract
The majority of neuroendocrine tumors originate in the digestive system and incidence is increasing within Canada and globally. Due to rapidly evolving evidence related to diagnosis and clinical management, updated guidance on the diagnosis and treatment of gastrointestinal neuroendocrine tumors (GI-NETs) are of clinical importance. Well-differentiated GI-NETs may exhibit indolent clinical behavior and are often metastatic at diagnosis. Some NET patients will develop secretory disease requiring symptom control to optimize quality of life and clinical outcomes. Optimal management of GI-NETs is in a multidisciplinary environment and is multimodal, requiring collaboration between medical, surgical, imaging and pathology specialties. Clinical application of advances in pathological classification and diagnostic technologies, along with evolving surgical, radiotherapeutic and medical therapies are critical to the advancement of patient care. We performed a systematic literature search to update our last set of published guidelines (2010) and identified new level 1 evidence for novel therapies, including telotristat etiprate (TELESTAR), lanreotide (CLARINET), everolimus (RADIANT-2; RADIANT-4) and peptide receptor radionuclide therapy (PRRT; NETTER-1). Integrating these data with the clinical knowledge of 16 multi-disciplinary experts, we devised consensus recommendations to guide state of the art clinical management of GI-NETs.
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Affiliation(s)
- Simron Singh
- Sunnybrook Health Sciences Centre, Department of Medicine, University of Toronto, 2075 Bayview Ave. Room T2-047, Toronto, Ontario M4N 3M5, Canada.
| | - Sylvia L Asa
- University Health Network, Department of Pathology, University of Toronto, Toronto, Ontario M5G 2C4, Canada.
| | - Chris Dey
- Sunnybrook Health Sciences Centre, Department of Medical Imaging, University of Toronto, 2075 Bayview Ave. Room MG-182, Toronto, Ontario M4N 3M5, Canada.
| | - Hagen Kennecke
- BC Cancer Agency, Division of Medical Oncology, University of British Columbia, 600 West 10th Avenue, Vancouver, BC V5Z 4E1, Canada.
| | - David Laidley
- St. Joseph's Health Care London, Division of Nuclear Medicine, University of Western Ontario, 268 Grosvenor Street, London, Ontario N6A 4V2, Canada.
| | - Calvin Law
- Sunnybrook Health Sciences Centre, Department of Surgery, University of Toronto, 2075 Bayview Ave. Room T2-001, Toronto, Ontario M4N 3M5, Canada.
| | - Timothy Asmis
- The Ottawa Hospital Cancer Centre, Division of Medical Oncology, University of Ottawa, 501 Smyth Road, Ottawa, Ontario K1H8L6, Canada.
| | - David Chan
- Sunnybrook Health Sciences Centre, Department of Medicine, University of Toronto, 2075 Bayview Ave. Room T2-047, Toronto, Ontario M4N 3M5, Canada.
| | - Shereen Ezzat
- Princess Margaret Cancer Centre, Departments of Medicine & Oncology, University of Toronto, 610 University Ave. Room 7-327, Toronto, Ontario M5G 2N2, Canada.
| | - Rachel Goodwin
- The Ottawa Hospital Research Institute, Department of Medical Oncology, University of Ottawa, 501 Smyth Road, Ottawa, Ontario K1H8L6, Canada.
| | - Ozgur Mete
- University Health Network, Department of Pathology, University of Toronto, Toronto, Ontario M5G 2C4, Canada.
| | - Janice Pasieka
- Tom Baker Cancer Center and Foothills Medical Centre, Departments of Surgery & Oncology, University of Calgary, 1403 29th Street NW, North Tower Floor 10, Calgary, Alberta T2N 2T9, Canada.
| | - Juan Rivera
- McGill University Health Centre - Glen Campus, Bloc C - C04.5190, 1001 Decarie Blvd, Montreal, QC H4A 3J1, Canada.
| | - Ralph Wong
- CancerCare Manitoba, St Boniface General Hospital, 407 Tache Avenue, Winnipeg, Manitoba R2H 2A6, Canada.
| | - Eva Segelov
- St Vincent's Clinical School, University of New South Wales, 438 Victoria St, Darlinghurst, NSW 2010, Australia.
| | - Daniel Rayson
- QEII Health Sciences Centre, Division of Medical Oncology, Dalhousie University, Suite 457A Bethune Building, 1276 South Park Street, Halifax, NS B3H 2Y9, Canada.
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Mohammadi H, Chuong MD, Moeslein FM, Sharma NK. Selective internal radiation therapy for the treatment of inoperable neuroendocrine tumor liver metastases. INTERNATIONAL JOURNAL OF ENDOCRINE ONCOLOGY 2016. [DOI: 10.2217/ije.15.33] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Neuroendocrine tumor liver metastases are commonly present at the time of neuroendocrine tumor diagnosis. Surgical resection is potentially curative and achieves the best long-term results but is not feasible in many patients. Angiographic liver-directed treatment modalities such as transarterial embolization, transarterial chemoembolization and selective internal radiotherapy using Yttrium-90 ([90]Y)-labeled microspheres have been shown to be effective treatments with liver predominant disease. Here, we review the management of neuroendocrine tumor liver metastases including selective internal radiotherapy.
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Affiliation(s)
- Homan Mohammadi
- School of Medicine & Health Sciences, The George Washington University, 2300 Eye Street NW Washington, DC 20006, USA
| | - Michael D Chuong
- Department of Radiation Oncology, University of Maryland, 22 South Greene Street, Baltimore, MD 21201, USA
| | - Fred M Moeslein
- Department of Diagnostic Radiology & Nuclear Medicine, University of Maryland, 22 South Greene Street, Baltimore, MD 21201, USA
| | - Navesh K Sharma
- Division of Radiation Oncology, Penn State Hershey Cancer Institute, 500 University Drive, Hershey, PA 17033, USA
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Role of Locoregional and Systemic Approaches for the Treatment of Patients with Metastatic Neuroendocrine Tumors. J Gastrointest Surg 2015; 19:2273-82. [PMID: 26341823 DOI: 10.1007/s11605-015-2931-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Accepted: 08/20/2015] [Indexed: 01/31/2023]
Abstract
Although gastroenteropancreatic neuroendocrine tumors are often perceived as being indolent tumors, more than half of the patients will harbor liver metastases at the time of diagnosis. Gastroenteropancreatic neuroendocrine tumors have the potential to be aggressive and resistant to therapy, making the integration of both locoregional and systemic therapy even more critical in the treatment of patients with locally advanced or metastatic lesions. Over the last several years, significant advancements have been made in the surgical treatment, liver-directed therapy, and medical management of gastroenteropancreatic neuroendocrine tumors. While surgical resection is the cornerstone of therapy, cytoreductive surgery, orthotopic liver transplantation, local ablation, and intra-arterial therapy all improve the prognosis of patients suffering with locally advanced or metastatic disease. In addition, great strides have been made in the medical management of gastroenteropancreatic neuroendocrine tumors, particularly with the evolution of novel molecular targeted therapy, such as everolimus and sunitinib. Hence, gastroenteropancreatic neuroendocrine tumor is becoming a disease process requiring more of a multi-disciplinary approach with the integration of both locoregional and systemic therapies for improved outcomes.
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Spolverato G, Vitale A, Ejaz A, Kim Y, Cosgrove D, Schlacter T, Geschwind JF, Pawlik TM. Net health benefit of hepatic resection versus intraarterial therapies for neuroendocrine liver metastases: A Markov decision model. Surgery 2015; 158:339-48. [DOI: 10.1016/j.surg.2015.03.033] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2014] [Revised: 03/03/2015] [Accepted: 03/04/2015] [Indexed: 12/16/2022]
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Quality of life after treatment of neuroendocrine liver metastasis. J Surg Res 2015; 198:155-64. [PMID: 26095419 DOI: 10.1016/j.jss.2015.05.048] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Revised: 05/15/2015] [Accepted: 05/22/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND A large subset of patients with neuroendocrine liver metastasis (NELM) is symptomatic at the time of presentation. In addition to improving survival, treatment of NELM seeks to provide palliation of symptoms. However, data on health-related quality of life (QoL) are uncommon. We sought to define patient-reported QoL after treatment of NELM. METHODS Patients who underwent treatment of NELM at Johns Hopkins Hospital between 1998 and 2013 and who were alive as of March 2014 were identified (n = 125). These patients were invited to complete a QoL survey designed using validated assessment tools, to assess their physical, mental, and general health before treatment, after the most recent treatment and at the time of the study. Clinicopathologic data were collected and correlated with QoL data. RESULTS The response rate was 68.0% (n = 85). Median patient age was 55 y and most were male (59.2%). Most patients had a pancreatic (24.7%) or a small bowel (37.7%) primary tumor; the overwhelming majority had multiple NELM (83.5%). Patient-reported symptoms before any treatment included diarrhea (41.1%), flushing (34.1%), fatigue (36.5%), and osteoarticular pain (18.8%). Initial treatment of NELM consisted of surgery in 55 patients (64.7%) and nonsurgical treatment in 30 patients (35.3%). Many patients reported an overall improvement in physical health and mental health. Specifically, the proportion of patients reporting diarrhea (before any treatment, 41.1% versus currently, 25.9%; P = 0.019) and flushing (before any treatment, 34.1% versus currently, 10.5%; P < 0.001) tended to decrease over time and a lower proportion of patients reported to be currently sad about being ill (before any treatment, 31.8% versus currently, 23.2%; P = 0.009). Patients with a very poor QoL at the time of the diagnosis were more likely to experience an improvement in QoL after treatment. Interestingly, there was no difference in the improvement in overall QoL whether the initial treatment for NELM was surgical or nonsurgical; however, a lower proportion of patients were dissatisfied with surgery versus nonsurgical therapy (5.4% versus 9.4%; P = 0.001). CONCLUSIONS Less than one-fourth of patients experienced a significant improvement in QoL after treatment of NELM. The patients who benefit the most of treatment were those who were more symptomatic before any treatment.
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Åkerström G, Norlén O, Edfeldt K, Crona J, Björklund P, Westin G, Hellman P, Stålberg P. A review on management discussions of small intestinal neuroendocrine tumors ‘midgut carcinoids’. INTERNATIONAL JOURNAL OF ENDOCRINE ONCOLOGY 2015. [DOI: 10.2217/ije.15.2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
European Neuroendocrine Tumor Society staging, together with the Ki67 grading system, has appeared as superior for classification of neuroendocrine tumors (NET). The management of small intestinal NET (SI-NET) has been overall controversial. Mesenteric metastases occur also with the smallest SI-NET, and the majority of patients risk to ultimately progress with liver metastases. 68Gallium (somatostatin receptor)/PET/CT has appeared as most sensitive for imaging, and fluorodeoxyglucose-PET is recommended to identify lesions with high proliferation. Our treatment policy for SI-NET is to initiate somatostatin analog treatment, and in order to prevent abdominal complications we recommend early intestinal resection for removal of primary tumors and clearance of lymph node metastases. Liver metastases are liberally treated by resection (or ablation), as this can efficiently palliate carcinoid syndrome-associated symptoms.
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Affiliation(s)
- Göran Åkerström
- Department of Surgical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden
| | - Olov Norlén
- Department of Surgical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden
| | - Katarina Edfeldt
- Department of Surgical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden
| | - Joakim Crona
- Department of Surgical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden
| | - Peyman Björklund
- Department of Surgical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden
| | - Gunnar Westin
- Department of Surgical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden
| | - Per Hellman
- Department of Surgical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden
| | - Peter Stålberg
- Department of Surgical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden
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40
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Partelli S, Inama M, Rinke A, Begum N, Valente R, Fendrich V, Tamburrino D, Keck T, Caplin ME, Bartsch D, Thirlwell C, Fusai G, Falconi M. Long-Term Outcomes of Surgical Management of Pancreatic Neuroendocrine Tumors with Synchronous Liver Metastases. Neuroendocrinology 2015; 102:68-76. [PMID: 26043944 DOI: 10.1159/000431379] [Citation(s) in RCA: 65] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2015] [Accepted: 05/14/2015] [Indexed: 12/21/2022]
Abstract
BACKGROUND The value of surgical resection in the management of pancreatic neuroendocrine tumors (PNET) with liver metastases (LM) is still debated. The aim of this study was to evaluate the outcomes of surgery of PNET with LM. METHODS Patients with PNET with synchronous LM between 2000 and 2011 from 4 high-volume institutions were included. The patients were divided into 3 groups: curative resection, palliative resection, and no resection. RESULTS Overall, 166 patients were included. Eighteen patients (11%) underwent curative resection, 73 patients (43%) underwent palliative resection, and 75 patients (46%) underwent conservative treatment. The median overall survival (OS) from the time of diagnosis was 73 months. Patients who underwent curative resection had a significantly better median OS from the initial diagnosis compared with those who underwent palliative resection and those who were conservatively treated (97 vs. 89 vs. 36 months, p = 0.0001). The median OS from the time of diagnosis in those patients who underwent radical or palliative resection was 97 months, with a 5-year survival rate of 76%. On multivariate analysis, factors associated with OS from the time of diagnosis were the presence of bilobar metastases, tumor grading, and curative resection in a first model. On a second model, curative or palliative surgery was an independent predictor of OS. Among 91 patients who underwent surgery, the presence of pancreatic neuroendocrine carcinoma G3 was the only factor independently associated with a poorer survival after surgery (median OS: 35 vs. 97 months, p < 0.0001). CONCLUSIONS Patients with LM from PNET benefit from surgical resection, although surgery should be reserved to well- or moderately differentiated forms.
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Affiliation(s)
- Stefano Partelli
- Pancreatic Surgery Unit, University Hospital of Ancona, Ancona, Italy
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Alagusundaramoorthy SS, Gedaly R. Role of surgery and transplantation in the treatment of hepatic metastases from neuroendocrine tumor. World J Gastroenterol 2014; 20:14348-14358. [PMID: 25339822 PMCID: PMC4202364 DOI: 10.3748/wjg.v20.i39.14348] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2014] [Revised: 04/24/2014] [Accepted: 06/13/2014] [Indexed: 02/06/2023] Open
Abstract
Neuroendocrine tumors (NET) are a heterogeneous group of cancers, with indolent behavior. The most common primary origin is the gastro-intestinal tract but can also appear in the lungs, kidneys, adrenals, ovaries and other organs. In general, NET is usually discovered in the metastatic phase (40%-80%). The liver is the most common organ involved when metastases occur (40%-93%), followed by bone (12%-20%) and lung (8%-10%).A number of different therapeutic options are available for the treatment of hepatic metastases including surgical resection, transplantation, ablation, trans-arterial chemoembolization, chemotherapy and somatostatin analogues. Recently, molecular targeted therapies have been used, usually in combination with other treatment options, to improve outcomes in patients with metastases. This article emphasizes on the role of surgery in the treatment of liver metastases from NET.
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Page AJ, Weiss MJ, Pawlik TM. Surgical management of noncolorectal cancer liver metastases. Cancer 2014; 120:3111-3121. [DOI: 10.1002/cncr.28743] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
Affiliation(s)
- Andrew J. Page
- Department of Surgery; Johns Hopkins Hospital; Baltimore Maryland
| | - Matthew J. Weiss
- Department of Surgery; Johns Hopkins Hospital; Baltimore Maryland
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Frilling A, Clift AK. Therapeutic strategies for neuroendocrine liver metastases. Cancer 2014; 121:1172-86. [PMID: 25274401 DOI: 10.1002/cncr.28760] [Citation(s) in RCA: 123] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2014] [Revised: 04/09/2014] [Accepted: 04/10/2014] [Indexed: 12/16/2022]
Abstract
Patients who have neuroendocrine tumors frequently present with liver metastases. A wide panel of treatment options exists for these patients. Liver resection with curative intent achieves the best long-term results. Highly selected patients may be considered for liver transplantation. Substantial recurrence rates reported after surgical approaches call for neoadjuvant and adjuvant concepts. Liver-directed, locally ablative procedures are recommended for patients with limited, nonresectable tumor burden. Angiographic liver-directed techniques, such as transarterial embolization, transarterial chemoembolization, and selective internal radiotherapy, offer excellent palliation for patients with liver-predominant disease. Peptide receptor radionuclide therapy is a promising palliative procedure for patients with hepatic and/or extrahepatic metastases. The efficacy of these treatment options needs to be evaluated in randomized trials. Somatostatin analogues have demonstrated effectiveness not only for symptomatic relief in patients with secreting tumors but also for the control of proliferation in small intestinal neuroendocrine tumors and most recently also in those originating from the pancreas. Chemotherapy is an option mainly for those with pancreatic neuroendocrine tumors and high-grade tumors irrespective of the origin. Novel drugs targeting specific pathways within the tumor cell have produced improved progression-free survival compared with placebo in patients with pancreatic neuroendocrine tumors. Despite such a diverse armamentarium, there is uncertainty with regard to the optimal treatment regimens. Newly introduced molecular-based markers, along with the conduction of clinical trials comparing the efficacy of treatment modalities, offer a chance to move the treatment of neuroendocrine tumor disease toward personalized patient care. In this report, the authors review the approaches for treatment of neuroendocrine liver metastases, identify shortcomings, and anticipate future perspectives. Furthermore, clinical practice recommendations are provided for currently available treatment options. Although multiple modalities are available for the treatment of neuroendocrine liver metastases, optimal management is unclear. The current knowledge pertaining to these treatment options is analyzed.
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Affiliation(s)
- Andrea Frilling
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
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Partelli S, Maurizi A, Tamburrino D, Baldoni A, Polenta V, Crippa S, Falconi M. GEP-NETS update: a review on surgery of gastro-entero-pancreatic neuroendocrine tumors. Eur J Endocrinol 2014; 171:R153-62. [PMID: 24920289 DOI: 10.1530/eje-14-0173] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The incidence of neuroendocrine tumors (NETs) has increased in the last decades. Surgical treatment encompasses a panel of approaches ranging from conservative procedures to extended surgical resection. Tumor size and localization usually represent the main drivers in the choice of the most appropriate surgical resection. In the presence of small (<2 cm) and asymptomatic nonfunctioning NETs, a conservative treatment is usually recommended. For localized NETs measuring above 2 cm, surgical resection represents the cornerstone in the management of these tumors. As they are relatively biologically indolent, an extended resection is often justified also in the presence of advanced NETs. Surgical options for NET liver metastases range from limited resection up to liver transplantation. Surgical choices for metastatic NETs need to consider the extent of disease, the grade of tumor, and the presence of extra-abdominal disease. Any surgical procedures should always be balanced with the benefit of survival or relieving symptoms and patients' comorbidities.
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Affiliation(s)
- Stefano Partelli
- Pancreatic Surgery UnitUniversità Politecnica delle Marche, Via Conca, 71, 60126 Ancona, ItalyDepartment of SurgeryUniversity of Verona, Verona, Italy
| | - Angela Maurizi
- Pancreatic Surgery UnitUniversità Politecnica delle Marche, Via Conca, 71, 60126 Ancona, ItalyDepartment of SurgeryUniversity of Verona, Verona, Italy
| | - Domenico Tamburrino
- Pancreatic Surgery UnitUniversità Politecnica delle Marche, Via Conca, 71, 60126 Ancona, ItalyDepartment of SurgeryUniversity of Verona, Verona, Italy
| | - Andrea Baldoni
- Pancreatic Surgery UnitUniversità Politecnica delle Marche, Via Conca, 71, 60126 Ancona, ItalyDepartment of SurgeryUniversity of Verona, Verona, Italy
| | - Vanessa Polenta
- Pancreatic Surgery UnitUniversità Politecnica delle Marche, Via Conca, 71, 60126 Ancona, ItalyDepartment of SurgeryUniversity of Verona, Verona, Italy
| | - Stefano Crippa
- Pancreatic Surgery UnitUniversità Politecnica delle Marche, Via Conca, 71, 60126 Ancona, ItalyDepartment of SurgeryUniversity of Verona, Verona, Italy
| | - Massimo Falconi
- Pancreatic Surgery UnitUniversità Politecnica delle Marche, Via Conca, 71, 60126 Ancona, ItalyDepartment of SurgeryUniversity of Verona, Verona, Italy
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Abstract
Neuroendocrine tumors have a disposition toward metastasis to the liver. A range of treatment modalities for neuroendocrine liver metastases is available in the clinical arena, the indications for which depend on tumor characteristics such as patterns of metastasis, tumor grade, and anatomical origin. The complete surgical resection of liver deposits represents the only option with the intent to cure and is the gold standard approach, whereas cytoreductive resection (debulking) presents another surgical option aiming to ameliorate the symptoms and prolong survival. Liver transplantation is generally an accepted option for highly selected patients. For patients ineligible for radical surgery, liver-directed therapies-transarterial embolization/chemoembolization, selective internal radiotherapy, and local tumor ablation-present alternative strategies. Systemic therapies include peptide receptor radiotherapy, somatostatin analogues, cytotoxic chemotherapeutics, and novel molecularly targeted drugs. However, despite the variety of treatments available, there exists little evidence to guide optimal clinical practice with currently available data predominantly retrospective in nature. In this review, we discuss the diagnostic procedures that influence the trajectory of treatment of patients with neuroendocrine liver metastases before critically appraising the evidence pertaining to these therapeutic strategies.
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Affiliation(s)
| | - Andrea Frilling
- Prof. Andrea Frilling, Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, DuCane Road, London W12 0NN, United Kingdom, T: 00442083833210, F: 00442083833963,
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Abstract
PURPOSE OF REVIEW Liver transplantation is a validated treatment of primary hepatobiliary tumours. Over the last decade, a renewed interest for liver transplantation as a curative treatment of colorectal liver metastasis (CR-LM) and neuro-endocrine metastasis (NET-LM) has developed. RECENT FINDINGS The ELTR and UNOS analyses showed that liver transplantation may offer excellent disease-free survival (ranging from 30 to 77%) in case of NET-LM, on the condition that stringent selection criteria are implemented. The interest for liver transplantation in the treatment of CR-LM has been fostered by the Norwegian SECA study. Five-year A 5-year survival rate of 60% could be reached. Despite the high recurrence rate (90%), one-third of patients were disease free following pulmonary surgery for metastases. SUMMARY Liver transplantation will take a more prominent place in the therapeutic algorithm of CR-LM and NET-LM. Larger experiences are necessary to improve knowledge about tumour biology and to refine selection criteria. A multimodal approach adding neo and adjuvant medical treatment to the transplant procedure will be key to bring this oncologic transplant project into the clinical arena. The preserved liver function in these patients will allow a more deliberate access to split liver and living donation for these indications.
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Giant hepatic carcinoid: a rare tumor with a favorable prognosis. Case Rep Surg 2014; 2014:456509. [PMID: 24653852 PMCID: PMC3932648 DOI: 10.1155/2014/456509] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2013] [Accepted: 12/31/2013] [Indexed: 01/27/2023] Open
Abstract
Primary hepatic carcinoids are rare tumors that are often diagnosed at a locally advanced stage. Their primary nature can only be ascertained after thorough investigations and long-term follow-up to exclude another primary origin. As with secondary neuroendocrine liver tumors, surgical resection remains the mainstay of therapy. Despite their large size and often central location liver resection is often feasible, offering long-term survival and cure to most patients. In selected patients liver transplantation appears to be a good indication for tumors not amenable to liver resection. An aggressive surgical attitude is therefore warranted. We report a large and unusually fast-growing liver carcinoid that appeared only marginally resectable in a patient who remains free of disease four years after surgery.
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Partelli S, Maurizi A, Tamburrino D, Crippa S, Pandolfi S, Falconi M. Surgical management of pancreatic neuroendocrine neoplasms. Ann Saudi Med 2014; 34:1-5. [PMID: 24658547 PMCID: PMC6074938 DOI: 10.5144/0256-4947.2014.1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
Pancreatic neuroendocrine neoplasms are relatively rare entities, representing approximately 1% to 2% of all pancreatic tumors. Owing to their rarity as well as their relatively indolent natural history, treatment approaches are not yet standardized. A formal pancreatic resection is usually mandatory for large and localized sporadic pancreatic tumors or in the presence of symptoms. However, in small and asymptomatic lesions, a conservative approach consisting in a careful wait-and-see policy is going to appear as more appropriate, particularly when, to remove the lesion, an aggressive surgical procedure is required, such as pancreaticoduodenectomy or distal splenopancreatectomy, depending on the localization of the tumor. Surgery has also a significant role in locally advanced and metastatic forms. In the setting of MEN 1 syndrome or Von-Hippel Lindau disease, the tumor size and the possible symptoms should be considered in the evaluation of a proper treatment.
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Affiliation(s)
| | | | | | | | | | - Massimo Falconi
- Prof. Massimo Falconi, Department of Surgery,, Clinical Chirurgia del Pancreas,, Ospedali Riuniti,, Via Conca 71,, Torrette-Ancona 60126, Italy, T: +39 0715965781, F: +39 0712206024,
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Resection of the primary pancreatic neuroendocrine tumor in patients with unresectable liver metastases: possible indications for a multimodal approach. Surgery 2013; 155:607-14. [PMID: 24582492 DOI: 10.1016/j.surg.2013.12.024] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2013] [Accepted: 12/19/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND Pancreatic neuroendocrine tumors (PNETs) present in more than 50% of cases with liver metastases as the only systemic localization. Liver metastases are unresectable in 80% of cases at diagnosis. In the context of a metastatic disease, the benefit of primary tumor removal in terms of survival is controversial. METHODS A single-center series of patients with PNETs presenting with synchronous unresectable hepatic metastases and treated within a framework of a multidisciplinary team was analyzed retrospectively to assess the prognostic factors and the potential benefit of primary tumor resection on long-term survival. RESULTS At the time of diagnosis, 12 of 43 patients (28%) underwent primary tumor resection. After a median follow-up of 5 years (range, 0.6-14 years), 22 disease-related deaths were observed. The corresponding 5-year survival and median disease-specific duration of survival were 58% and 77 months, respectively. In the operated and nonoperated patients the 5-year disease-specific survival was 82% and 50%, respectively (P = .027). At multivariate analysis, patients with primary tumor removed had an improved survival compared with patients who did not (hazard ratio 0.18; 95% CI 0.05-0.66; P = .010). Other important factors associated with improved survival at multivariate analysis were lesser age, lesser Ki-67 index, and 25% less liver tumor burden. CONCLUSION In the present series of patients with PNETs and unresectable liver metastases, resection of the primary tumor was associated with an improved survival. This observation suggests that resection of the primary tumor should be part of a global therapeutic strategy and its indication and timing should be discussed within a multidisciplinary team.
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Stump R, Haueis S, Kalt N, Tschuor C, Limani P, Raptis DA, Puhan MA, Breitenstein S. Transplantation and surgical strategies in patients with neuroendocrine liver metastases: protocol of four systematic reviews. JMIR Res Protoc 2013; 2:e58. [PMID: 24366112 PMCID: PMC3875902 DOI: 10.2196/resprot.2891] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2013] [Accepted: 10/26/2013] [Indexed: 12/20/2022] Open
Abstract
Background Hepatic metastases of neuroendocrine tumors (NETs) are considered a major prognostic factor associated with significantly reduced survival compared to patients without liver metastases. Several surgical and nonsurgical strategies are present to treat resectable and nonresectable liver metastases, some of which have the potential to cure liver mestatases. Objective The aims of the four systematic reviews presented in the paper are to determine the effectiveness of liver resection versus nonsurgical treatment of patients with NET liver metastases, to investigate the impact of neoadjuvant and adjuvant treatment options on the tumor-free survival, to assess the role of liver transplantation in patients presenting with unresectable bilateral hepatic metastases, and to evaluate the role of primary tumor resection in presence of unresectable liver metastases. Methods Literature search was performed on Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, and the Cochrane Library (Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, and Cochrane Central Register of Controlled Trials). No language restrictions were applied. Randomized controlled trials, prospective and retrospective comparative cohort studies, and case-control studies will be used for the qualitative and quantitative synthesis of the systematic reviews. Case series will be only included in a separate database for descriptive purposes. Results This study is ongoing and presents a protocol system of four systematic reviews that will assist in determining the effectiveness of liver resection versus nonsurgical treatment of patients with NET liver metastases. This study is also assumed to investigate the impact of neoadjuvant and adjuvant treatment options on the tumor-free survival, the role of liver transplantation, and the relevance of primary tumor resection in presence of unresectable liver metastasis. Conclusions The systematic reviews will show the current evidence based on the effectiveness of surgical strategies in patients with NET liver metastases and serve as basis for clinical practice guidelines. Trial Registration The systematic reviews have been prospectively registered with the International Prospective Register of Systematic Reviews: liver resection (CRD42012002652); http://www.crd.york.ac.uk/prospero/display_record.asp?ID=CRD42012002652 (Archived by WebCite at http://www.webcitation.org/6LQUqMnqL,). neoadjuvant and adjuvant treatment strategies (CRD42012002656); http://www.crd.york.ac.uk/prospero/display_record.asp?ID=CRD42012002656 (Archived by WebCite at http://www.webcitation.org/6LQVvEHuf). liver transplantation (CRD42012002655); http://www.crd.york.ac.uk/prospero/display_record.asp?ID=CRD42012002655 (Archived by WebCite at http://www.webcitation.org/6LQW7WFo3,). resection of the locoregional primary NET (CRD42012002654); http://www.crd.york.ac.uk/prospero/display_record.asp?ID=CRD42012002654 (Archived by WebCite at http://www.webcitation.org/6LQWEIuGe).
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Affiliation(s)
- Reto Stump
- Division of Visceral and Transplantation Surgery, Department of Surgery, University Hospital Zurich, Zurich, Switzerland
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