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The North American Neuroendocrine Tumor Society Consensus Paper on the Surgical Management of Pancreatic Neuroendocrine Tumors

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The North American Neuroendocrine Tumor Society Consensus Paper on the Surgical Management of Pancreatic Neuroendocrine Tumors NANETS GUIDELINES The North American Neuroendocrine Tumor Society Consensus Paper on the Surgical Management of Pancreatic Neuroendocrine Tumors James R. Howe, MD,* Nipun B. Merchant, MD,† Claudius Conrad, MD, PhD,‡ Xavier M. Keutgen, MD,§ 02/11/2020 on BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3y7wDLvMZ9kyrquKvxztSXoAOLXq9OrpAg0fi4JCpMSU= by https://journals.lww.com/pancreasjournal from Downloaded Julie Hallet, MD, MSc,|| Jeffrey A. Drebin, MD, PhD,¶ Rebecca M. Minter, MD,# Terry C. Lairmore, MD,** Jennifer F.Tseng, MD,†† Herbert J. Zeh, MD,‡‡ Steven K. Libutti, MD,§§ Gagandeep Singh, MD,|||| Downloaded Jeffrey E. Lee, MD,¶¶ Thomas A. Hope, MD,## Michelle K. Kim, MD,*** Yusuf Menda, MD,††† Thorvardur R. Halfdanarson, MD,‡‡‡ Jennifer A. Chan, MD,§§§ and Rodney F.Pommier, MD|||||| from https://journals.lww.com/pancreasjournal Abstract: Tumors making excess hormones can lead to clinical syn- This manuscript is the result of the North American Neuroen- dromes, and these tumors are termed functional tumors. These docrine Tumor Society consensus conference on the surgical management include insulinoma, gastrinoma, vasoactive intestinal polypeptide of pancreatic neuroendocrine tumors from July 19 to 20, 2018. The group (VIP)–secreting tumors, glucagonoma, somatostatinoma, NETs reviewed a series of questions of specific interest to surgeons taking care of resulting in carcinoid syndrome due to production of serotonin, patients with pancreatic neuroendocrine tumors, and for each, the available by as well as even less common tumors making hormones such BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3y7wDLvMZ9kyrquKvxztSXoAOLXq9OrpAg0fi4JCpMSU= literature was reviewed. What follows are these reviews for each question as adrenocorticotrophic hormone (ACTH), calcitonin, growth followed by recommendations of the panel. hormone–releasing factor, and parathyroid hormone–related Key Words: pancreas, neuroendocrine, pancreatic neuroendocrine tumor, peptide (PTHrP). The majority of PNETs (75%–90%) are not metastases, neuroendocrine tumor liver metastases, pancreatectomy associated with elevated hormone levels or do not cause a clin- 7,8 – ical syndrome, and these are termed nonfunctional (NF). (Pancreas 2020;49: 1 33) Some PNETs are associated with elevated levels of pancreatic polypeptide, neurotensin, or human chorionic gonadotropin, he pancreas is an important abdominal organ with multiple but without a clinical syndrome, these are still referred to as T functions and derives from the embryonic foregut. Its exo- NF.9 Functional tumors generally have a more favorable prognosis crine role is important for digestion, whereas its endocrine effects than their NF counterparts,7 possibly because of earlier detection. are carried out through hormones made within pancreatic islet The median survival of patients with grade 1 and 2 PNETs is cells, which are released into the bloodstream to affect distant tis- 42 months. In all patients with PNETs localized to the pancreas, sues. Hormones produced within the pancreas include insulin, the median survival is 136 months, which decreases to 77 months glucagon, somatostatin, ghrelin, and pancreatic polypeptide.1 Tu- when nodal metastases are present. However, 64% of patients mors that originate in the islet cells are also known as pancreatic present with distant metastases, and in this group, the median sur- neuroendocrine tumors (PNETs). These account for 1% to 2% vival is only 24 months.5 of all pancreatic tumors,2–4 and their incidence has been increasing, Approximately 5% of patients with PNETs have a family his- from 3.2 cases per million in 2003 to 8 per million in 2012.5,6 tory of PNET, whereas the other 95% are sporadic.3 Inherited con- ditions that are associated with PNETs include multiple endocrine – From the *Department of Surgery, University of Iowa Carver College of Med- neoplasia type 1 (MEN1), von Hippel Lindau syndrome (VHL), icine, Iowa City, IA; †Department of Surgery, University of Miami, Miami, FL; ‡Department of Surgery, St Elizabeth Medical Center, Tufts University School of Medicine, Boston, MA; §Department of Surgery, University of Chicago Conferences, NETRF, NCAN, and ENETS). X.M.K. received consulting Medicine, Chicago, IL; ||Department of Surgery, University of Toronto, honoraria from Advanced Accelerator Applications. J.H. has received Sunnybrook Health Sciences Centre, Toronto, Canada; ¶Department of speaking honoraria from Ipsen Biopharmaceuticals Canada and Novartis Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; #Depart- Oncology, and travel support from Baxter Corporation. J.A.D. owns shares on 02/11/2020 ment of Surgery, University of Wisconsin School of Medicine and Public in biotech firms (ALNYand IONS) and his spouse is chief medical officer Health, Madison, WI; **Department of Surgery, LSU Health Sciences Center, for American Regent Pharmaceuticals. R.M.M. has received travel Shreveport, LA; ††Department of Surgery, Boston University Medical Center, expenses and/or honoraria for speaking at academic centers and meetings of Boston, MA; ‡‡Department of Surgery, University of Texas Southwestern Med- the American Board of Surgery, National Board of Medical Examiners, ical Center, Dallas, TX; §§Department of Surgery, Rutgers Cancer Institute of Society of University Surgeons, Americas Hepatopancreatobiliary New Jersey, New Brunswick, NJ; ||||Department of Surgery, City of Hope Com- Association, International Hepatopancreatobiliary Association Fellowship prehensive Cancer Center, Duarte, CA; ¶¶Department of Surgical Oncology, Council, and Royal Australasian College of Surgeons. J.F.T. has received a The University of Texas MD Anderson Cancer Center, Houston, TX; ##Depart- research grant from Mauna Kea Technologies, Inc. H.J.Z. has received a ment of Radiology and Biomedical Imaging, University of California San research funding from Intuitive Surgical Inc., and travel expenses for Francisco, San Francisco, CA; ***Department of Medicine, Mt Sinai Medical independent symposium on robotics and HPB surgery. T.A.H. was on the Center,NewYork,NY;†††Department of Radiology, University of Iowa advisory board and a consultant for Curium, Inc. M.K.K. received research Carver College of Medicine, Iowa City, IA; ‡‡‡Division of Medical Oncology, funds from Novartis. Y.M. has received research funding from Ipsen and Mayo Clinic Cancer Center, Rochester, MN; §§§Department of Medical Oncol- Advanced Accelerator Applications. T.R.H. has received research funding ogy, Dana-Farber Cancer Institute, Boston, MA; and ||||||Department of Surgery, from Ipsen and Thermo Fisher Scientific, and has served on the advisory Oregon Health & Science University, Portland, OR. boards of Ipsen, Curium, Novartis, and Lexicon. J.A.C. is a consultant and Received for publication August 24, 2019; accepted November 1, 2019. advisory board member of Crinetics, Ipsen, Novartis, and Lexicon; she Address correspondences to: James R. Howe, MD, Department of Surgery, receives royalties from UpToDate, and owns stock in Merck. R.F.P. is a University of Iowa Hospitals and Clinics, 4644 JCP,200 Hawkins Dr, Iowa consultant to Novartis, Lexicon, and Advanced Accelerator Applications. City, IA 52242 (e‐mail: [email protected]). The other authors declare no conflict of interest. J.R.H. has received travel expenses and/or honoraria for speaking at academic Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. centers and at some conferences (NANETS, NANETS Regional DOI: 10.1097/MPA.0000000000001454 Pancreas • Volume 49, Number 1, January 2020 www.pancreasjournal.com 1 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. Howe et al Pancreas • Volume 49, Number 1, January 2020 tuberous sclerosis complex (TSC1 and TSC2), and neurofibroma- relevant literature; as will be clear from the text, the majority of tosis (NF1). The management of familial disease is generally more the studies related to these topics are retrospective cohort studies complex, because tumors are more commonly multifocal, they (level 3 evidence), although a few have been addressed by ran- can develop throughout the patient's lifetime, and different tumors domized controlled trials (level 1 evidence). After each review may arise in other sites of the body. are summary statements with recommendations of the group Treatment options for patients with PNETs depend upon the based upon the best available evidence and expert opinion. anatomic location of the tumor within the gland, size, multifocality, the extent of disease (localized or metastatic), grade, involvement of adjacent structures, and patient comorbidities. Some management How do we Optimize the Use of Computed issues in patients with PNETs are clearer than others, such as the ap- Tomography and Magnetic Resonance Imaging in propriate surgical procedures for tumors in different parts of the the Diagnosis of PNETs (Sequences/Phases, gland. Many others are not clear at all, and evidence for the correct Intravenous Contrast)? approaches for specific patient situations is lacking. Furthermore, Imaging plays a central role in the initial staging of patients because of the rarity of these tumors, institutional experiences with PNETs. The best imaging modality for staging of the primary may be quite variable and clinicians must rely upon their judg- tumor is a pancreatic protocol computed tomography (CT), primar- ment and discussions in multidisciplinary tumor boards to best ily because of the characterization of vascular involvement
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