Abstract
Functional pancreatic neuroendocrine tumors (PNET) are uncommon neoplasms that often present with endocrine hypersecretory syndromes. Patients with underlying genetic disorders, especially multiple endocrine neoplasia type I and von Hippel-Lindau syndrome, are at an increased risk for developing PNETs. Surgical resection is the primary treatment for functional PNETs. However, the decision for surgery depends on multiple factors, including patient functional status and comorbidities, efficacy of medical management of the hypersecretory syndrome, malignant potential of the tumor, size and location of the tumor, presence of metastatic disease, and presence of a genetic tumor syndrome. The extent of surgical resection depends on the size, location, and malignant potential of a tumor and may include enucleation or anatomic resections, such as pancreaticoduodenectomy or distal pancreatectomy. In patients with metastatic disease, tumor debulking plays a key role in aiding the medical management of the hypersecretory syndrome. Interventional ablative and embolization procedures assist in the complex management of unresectable disease. Enhanced recovery after surgery pathways are employed by high-volume centers to help standardize postoperative care.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Vortmeyer AO, Huang S, Lubensky I, Zhuang Z. Non-islet origin of pancreatic islet cell tumors. J Clin Endocrinol Metab. 2004;89(4):1934–8.
Pictet RL, Rall LB, Phelps P, Rutter WJ. The neural crest and the origin of the insulin-producing and other gastrointestinal hormone-producing cells. Science. 1976;191(4223):191–2.
Andrew A, Kramer B, Rawdon BB. The origin of gut and pancreatic neuroendocrine (APUD) cells – the last word? J Pathol. 1998;186(2):117–8.
Dasari A, Shen C, Halperin D, Zhao B, Zhou S, Xu Y, et al. Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol. 2017;3(10):1335–42.
Singhi AD, Klimstra DS. Well-differentiated pancreatic neuroendocrine tumours (PanNETs) and poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs): concepts, issues and a practical diagnostic approach to high-grade (G3) cases. Histopathology. 2018;72(1):168–77.
Hodul PJ, Strosberg JR, Kvols LK. Aggressive surgical resection in the management of pancreatic neuroendocrine tumors: when is it indicated? Cancer Control. 2008;15(4):314–21.
Hill JS, McPhee JT, McDade TP, Zhou Z, Sullivan ME, Whalen GF, et al. Pancreatic neuroendocrine tumors: the impact of surgical resection on survival. Cancer. 2009;115(4):741–51.
Schurr PG, Strate T, Rese K, Kaifi JT, Reichelt U, Petri S, et al. Aggressive surgery improves long-term survival in neuroendocrine pancreatic tumors: an institutional experience. Ann Surg. 2007;245(2):273–81.
Lloyd RV, Osamura RY, Klöppel G, Rosai J, World Health O, International Agency for Research on C, et al. WHO classification of tumours of endocrine organs. Lyon: International Agency for Research on Cancer; 2017.
Choe J, Kim KW, Kim HJ, Kim DW, Kim KP, Hong SM, et al. What is new in the 2017 World Health Organization classification and 8th American joint committee on cancer staging system for pancreatic neuroendocrine neoplasms? Korean J Radiol. 2019;20(1):5–17.
Basturk O, Yang Z, Tang LH, Hruban RH, Adsay V, McCall CM, et al. The high-grade (WHO G3) pancreatic neuroendocrine tumor category is morphologically and biologically heterogenous and includes both well differentiated and poorly differentiated neoplasms. Am J Surg Pathol. 2015;39(5):683–90.
Basturk O, Tang L, Hruban RH, Adsay V, Yang Z, Krasinskas AM, et al. Poorly differentiated neuroendocrine carcinomas of the pancreas: a clinicopathologic analysis of 44 cases. Am J Surg Pathol. 2014;38(4):437–47.
Howe JR, Merchant NB, Conrad C, Keutgen XM, Hallet J, Drebin JA, et al. The North American Neuroendocrine Tumor Society consensus paper on the surgical management of pancreatic neuroendocrine tumors. Pancreas. 2020;49(1):1–33.
Nuñez-Valdovinos B, Carmona-Bayonas A, Jimenez-Fonseca P, Capdevila J, Castaño-Pascual Á, Benavent M, et al. Neuroendocrine tumor heterogeneity adds uncertainty to the World Health Organization 2010 classification: real-world data from the Spanish Tumor Registry (R-GETNE). Oncologist. 2018;23(4):422–32.
Da Silva Xavier G. The cells of the Islets of Langerhans. J Clin Med. 2018;7(3):54.
Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dungan K, et al. Endotext. South Dartmouth: MDText.com, Inc; 2000.
Sadot E, Reidy-Lagunes DL, Tang LH, Do RK, Gonen M, D’Angelica MI, et al. Observation versus resection for small asymptomatic pancreatic neuroendocrine tumors: a matched case-control study. Ann Surg Oncol. 2016;23(4):1361–70.
Lee LC, Grant CS, Salomao DR, Fletcher JG, Takahashi N, Fidler JL, et al. Small, nonfunctioning, asymptomatic pancreatic neuroendocrine tumors (PNETs): role for nonoperative management. Surgery. 2012;152(6):965–74.
Gaujoux S, Partelli S, Maire F, D’Onofrio M, Larroque B, Tamburrino D, et al. Observational study of natural history of small sporadic nonfunctioning pancreatic neuroendocrine tumors. J Clin Endocrinol Metab. 2013;98(12):4784–9.
Toste PA, Kadera BE, Tatishchev SF, Dawson DW, Clerkin BM, Muthusamy R, et al. Nonfunctional pancreatic neuroendocrine tumors <2 cm on preoperative imaging are associated with a low incidence of nodal metastasis and an excellent overall survival. J Gastrointest Surg. 2013;17(12):2105–13.
Finkelstein P, Sharma R, Picado O, Gadde R, Stuart H, Ripat C, et al. Pancreatic neuroendocrine tumors (panNETs): analysis of overall survival of nonsurgical management versus surgical resection. J Gastrointest Surg. 2017;21(5):855–66.
O’Toole D, Salazar R, Falconi M, Kaltsas G, Couvelard A, de Herder WW, et al. Rare functioning pancreatic endocrine tumors. Neuroendocrinology. 2006;84(3):189–95.
National Comprehensive Cancer Network. Neuroendocrine and adrenal tumors (Version 2.2020). 2020. Available from: https://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf.
Katabathina VS, Rikhtehgar OY, Dasyam AK, Manickam R, Prasad SR. Genetics of pancreatic neoplasms and role of screening. Magn Reson Imaging Clin N Am. 2018;26(3):375–89.
Ehrlich L, Hall C, Meng F, Lairmore T, Alpini G, Glaser S. A review of the scaffold protein Menin and its role in hepatobiliary pathology. Gene Expr. 2017;17(3):251–63.
Yates CJ, Newey PJ, Thakker RV. Challenges and controversies in management of pancreatic neuroendocrine tumours in patients with MEN1. Lancet Diabetes Endocrinol. 2015;3(11):895–905.
Frost M, Lines KE, Thakker RV. Current and emerging therapies for PNETs in patients with or without MEN1. Nat Rev Endocrinol. 2018;14(4):216–27.
Jensen RT, Norton JA. Treatment of pancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1: some clarity but continued controversy. Pancreas. 2017;46(5):589–94.
Varshney N, Kebede AA, Owusu-Dapaah H, Lather J, Kaushik M, Bhullar JS. A review of Von Hippel-Lindau syndrome. J Kidney Cancer VHL. 2017;4(3):20–9.
Keutgen XM, Hammel P, Choyke PL, Libutti SK, Jonasch E, Kebebew E. Evaluation and management of pancreatic lesions in patients with von Hippel-Lindau disease. Nat Rev Clin Oncol. 2016;13(9):537–49.
Tirosh A, Sadowski SM, Linehan WM, Libutti SK, Patel D, Nilubol N, et al. Association of VHL genotype with pancreatic neuroendocrine tumor phenotype in patients with von Hippel-Lindau disease. JAMA Oncol. 2018;4(1):124–6.
Morgat C, Vélayoudom-Céphise FL, Schwartz P, Guyot M, Gaye D, Vimont D, et al. Evaluation of (68)Ga-DOTA-TOC PET/CT for the detection of duodenopancreatic neuroendocrine tumors in patients with MEN1. Eur J Nucl Med Mol Imaging. 2016;43(7):1258–66.
van Asselt SJ, Brouwers AH, van Dullemen HM, van der Jagt EJ, Bongaerts AH, Kema IP, et al. EUS is superior for detection of pancreatic lesions compared with standard imaging in patients with multiple endocrine neoplasia type 1. Gastrointest Endosc. 2015;81(1):159–67.e2.
Barbe C, Murat A, Dupas B, Ruszniewski P, Tabarin A, Vullierme MP, et al. Magnetic resonance imaging versus endoscopic ultrasonography for the detection of pancreatic tumours in multiple endocrine neoplasia type 1. Dig Liver Dis. 2012;44(3):228–34.
Hashim YM, Trinkaus KM, Linehan DC, Strasberg SS, Fields RC, Cao D, et al. Regional lymphadenectomy is indicated in the surgical treatment of pancreatic neuroendocrine tumors (PNETs). Ann Surg. 2014;259(2):197–203.
Bilimoria KY, Talamonti MS, Tomlinson JS, Stewart AK, Winchester DP, Ko CY, et al. Prognostic score predicting survival after resection of pancreatic neuroendocrine tumors: analysis of 3851 patients. Ann Surg. 2008;247(3):490–500.
Roland CL, Bian A, Mansour JC, Yopp AC, Balch GC, Sharma R, et al. Survival impact of malignant pancreatic neuroendocrine and islet cell neoplasm phenotypes. J Surg Oncol. 2012;105(6):595–600.
Ekeblad S, Skogseid B, Dunder K, Oberg K, Eriksson B. Prognostic factors and survival in 324 patients with pancreatic endocrine tumor treated at a single institution. Clin Cancer Res. 2008;14(23):7798–803.
Postlewait LM, Ethun CG, Baptiste GG, Le N, McInnis MR, Cardona K, et al. Pancreatic neuroendocrine tumors: preoperative factors that predict lymph node metastases to guide operative strategy. J Surg Oncol. 2016;114(4):440–5.
Ballian N, Loeffler AG, Rajamanickam V, Norstedt PA, Weber SM, Cho CS. A simplified prognostic system for resected pancreatic neuroendocrine neoplasms. HPB (Oxford). 2009;11(5):422–8.
Conrad C, Kutlu OC, Dasari A, Chan JA, Vauthey JN, Adams DB, et al. Prognostic value of lymph node status and extent of lymphadenectomy in pancreatic neuroendocrine tumors confined to and extending beyond the pancreas. J Gastrointest Surg. 2016;20(12):1966–74.
Tomassetti P, Campana D, Piscitelli L, Casadei R, Santini D, Nori F, et al. Endocrine pancreatic tumors: factors correlated with survival. Ann Oncol. 2005;16(11):1806–10.
DeOliveira ML, Winter JM, Schafer M, Cunningham SC, Cameron JL, Yeo CJ, et al. Assessment of complications after pancreatic surgery: a novel grading system applied to 633 patients undergoing pancreaticoduodenectomy. Ann Surg. 2006;244(6):931–7; discussion 7–9.
Di Sabatino A, Carsetti R, Corazza GR. Post-splenectomy and hyposplenic states. Lancet. 2011;378(9785):86–97.
Hernandez MC, Khasawneh M, Contreras-Peraza N, Lohse C, Stephens D, Kim BD, et al. Vaccination and splenectomy in Olmsted County. Surgery. 2019;166(4):556–63.
Senthinathan P, Jankar SV, Sabnis SC, Kaje V, Srivatsan Gurumurthy S, Anand Vijai N, et al. Laparoscopic total pancreatectomy for multiple endocrine neoplasia type 1 syndrome-associated multifocal, non-functioning pancreatic neuroendocrine tumor: a case report. Asian J Endosc Surg. 2017;10(4):434–7.
Hüttner FJ, Koessler-Ebs J, Hackert T, Ulrich A, Büchler MW, Diener MK. Meta-analysis of surgical outcome after enucleation versus standard resection for pancreatic neoplasms. Br J Surg. 2015;102(9):1026–36.
Huang LC, Poultsides GA, Norton JA. Surgical management of neuroendocrine tumors of the gastrointestinal tract. Oncology (Williston Park). 2011;25(9):794–803.
Zogakis TG, Gibril F, Libutti SK, Norton JA, White DE, Jensen RT, et al. Management and outcome of patients with sporadic gastrinoma arising in the duodenum. Ann Surg. 2003;238(1):42–8.
Burghardt L, Meier JJ, Uhl W, Kahle-Stefan M, Schmidt WE, Nauck MA. Importance of localization of insulinomas: a systematic analysis. J Hepatobiliary Pancreat Sci. 2019;26(9):383–92.
Spinelli A, Del Fabbro D, Sacchi M, Zerbi A, Torzilli G, Lutman FR, et al. Intraoperative ultrasound with contrast medium in resective pancreatic surgery: a pilot study. World J Surg. 2011;35(11):2521–7.
Norton JA, Harris EJ, Chen Y, Visser BC, Poultsides GA, Kunz PC, et al. Pancreatic endocrine tumors with major vascular abutment, involvement, or encasement and indication for resection. Arch Surg. 2011;146(6):724–32.
Thiels CA, Bergquist JR, Laan DV, Croome KP, Smoot RL, Nagorney DM, et al. Outcomes of pancreaticoduodenectomy for pancreatic neuroendocrine tumors: are combined procedures justified? J Gastrointest Surg. 2016;20(5):891–8.
Prakash L, Lee JE, Yao J, Bhosale P, Balachandran A, Wang H, et al. Role and operative technique of portal venous tumor thrombectomy in patients with pancreatic neuroendocrine tumors. J Gastrointest Surg. 2015;19(11):2011–8.
Prakash L, Bhosale P, Cloyd J, Kim M, Parker N, Yao J, et al. Role of fluorouracil, doxorubicin, and streptozocin therapy in the preoperative treatment of localized pancreatic neuroendocrine tumors. J Gastrointest Surg. 2017;21(1):155–63.
Hüttner FJ, Schneider L, Tarantino I, Warschkow R, Schmied BM, Hackert T, et al. Palliative resection of the primary tumor in 442 metastasized neuroendocrine tumors of the pancreas: a population-based, propensity score-matched survival analysis. Langenbeck’s Arch Surg. 2015;400(6):715–23.
Bertani E, Fazio N, Radice D, Zardini C, Spinoglio G, Chiappa A, et al. Assessing the role of primary tumour resection in patients with synchronous unresectable liver metastases from pancreatic neuroendocrine tumour of the body and tail. A propensity score survival evaluation. Eur J Surg Oncol. 2017;43(2):372–9.
Starr JS, Sonbol MB, Hobday TJ, Sharma A, Kendi AT, Halfdanarson TR. Peptide receptor radionuclide therapy for the treatment of pancreatic neuroendocrine tumors: recent insights. Onco Targets Ther. 2020;13:3545–55.
Bertani E, Fazio N, Radice D, Zardini C, Grana C, Bodei L, et al. Resection of the primary tumor followed by peptide receptor radionuclide therapy as upfront strategy for the treatment of G1-G2 pancreatic neuroendocrine tumors with unresectable liver metastases. Ann Surg Oncol. 2016;23(Suppl 5):981–9.
Brighi N, Lamberti G, Maggio I, Manuzzi L, Ricci C, Casadei R, et al. Biliary stone disease in patients receiving somatostatin analogs for neuroendocrine neoplasms. A retrospective observational study. Dig Liver Dis. 2019;51(5):689–94.
Jayakrishnan TT, Groeschl RT, George B, Thomas JP, Clark Gamblin T, Turaga KK. Review of the impact of antineoplastic therapies on the risk for cholelithiasis and acute cholecystitis. Ann Surg Oncol. 2014;21(1):240–7.
Mirakhur B, Pavel ME, Pommier RF, Fisher GA, Phan AT, Massien C, et al. Biochemical responses in symptomatic and asymptomatic patients with neuroendocrine tumors: pooled analysis of 2 phase 3 trials. Endocr Pract. 2018;24(11):948–62.
Gerson JN, Witteles RM, Chang DT, Beygui RE, Iagaru AH, Kunz PL. Carcinoid syndrome complicating a pancreatic neuroendocrine tumor: a case report. Pancreas. 2017;46(10):1381–5.
Tsoukalas N, Chatzellis E, Rontogianni D, Alexandraki KI, Boutzios G, Angelousi A, et al. Pancreatic carcinoids (serotonin-producing pancreatic neuroendocrine neoplasms): report of 5 cases and review of the literature. Medicine (Baltimore). 2017;96(16):e6201.
Lillemoe HA, Aloia TA. Enhanced recovery after surgery: hepatobiliary. Surg Clin North Am. 2018;98(6):1251–64.
Lavu H, McCall NS, Winter JM, Burkhart RA, Pucci M, Leiby BE, et al. Enhancing patient outcomes while containing costs after complex abdominal operation: a randomized controlled trial of the Whipple accelerated recovery pathway. J Am Coll Surg. 2019;228(4):415–24.
Linnemann RJA, Patijn GA, van Rijssen LB, Besselink MG, Mungroop TH, de Hingh IH, et al. The role of abdominal drainage in pancreatic resection - a multicenter validation study for early drain removal. Pancreatology. 2019;19(6):888–96.
Zaghal A, Tamim H, Habib S, Jaafar R, Mukherji D, Khalife M, et al. Drain or no drain following pancreaticoduodenectomy: the unsolved dilemma. Scand J Surg. 2020;109(3):228–37.
Narayanan S, Martin AN, Turrentine FE, Bauer TW, Adams RB, Zaydfudim VM. Mortality after pancreaticoduodenectomy: assessing early and late causes of patient death. J Surg Res. 2018;231:304–8.
Kagedan DJ, Ahmed M, Devitt KS, Wei AC. Enhanced recovery after pancreatic surgery: a systematic review of the evidence. HPB (Oxford). 2015;17(1):11–6.
Callery MP, Pratt WB, Kent TS, Chaikof EL, Vollmer CM Jr. A prospectively validated clinical risk score accurately predicts pancreatic fistula after pancreatoduodenectomy. J Am Coll Surg. 2013;216(1):1–14.
Trudeau MT, Casciani F, Ecker BL, Maggino L, Seykora TF, Puri P, et al. The fistula risk score catalog: toward precision medicine for pancreatic fistula after pancreatoduodenectomy. Ann Surg. 2020; https://doi.org/10.1097/SLA.0000000000004068.
Søreide K, Healey AJ, Mole DJ, Parks RW. Pre-, peri- and post-operative factors for the development of pancreatic fistula after pancreatic surgery. HPB (Oxford). 2019;21(12):1621–31.
Strobel O, Cherrez A, Hinz U, Mayer P, Kaiser J, Fritz S, et al. Risk of pancreatic fistula after enucleation of pancreatic tumours. Br J Surg. 2015;102(10):1258–66.
Chua TC, Yang TX, Gill AJ, Samra JS. Systematic review and meta-analysis of enucleation versus standardized resection for small pancreatic lesions. Ann Surg Oncol. 2016;23(2):592–9.
Bassi C, Marchegiani G, Dervenis C, Sarr M, Abu Hilal M, Adham M, et al. The 2016 update of the international study group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 years after. Surgery. 2017;161(3):584–91.
Malleo G, Pulvirenti A, Marchegiani G, Butturini G, Salvia R, Bassi C. Diagnosis and management of postoperative pancreatic fistula. Langenbeck’s Arch Surg. 2014;399(7):801–10.
Callery MP, Pratt WB, Vollmer CM Jr. Prevention and management of pancreatic fistula. J Gastrointest Surg. 2009;13(1):163–73.
McMillan MT, Fisher WE, Van Buren G 2nd, McElhany A, Bloomston M, Hughes SJ, et al. The value of drains as a fistula mitigation strategy for pancreatoduodenectomy: something for everyone? Results of a randomized prospective multi-institutional study. J Gastrointest Surg. 2015;19(1):21–30; discussion −1.
Tseng DS, Molenaar IQ, Besselink MG, van Eijck CH, Borel Rinkes IH, van Santvoort HC. Pancreatic exocrine insufficiency in patients with pancreatic or periampullary cancer: a systematic review. Pancreas. 2016;45(3):325–30.
Rickels MR, Bellin M, Toledo FG, Robertson RP, Andersen DK, Chari ST, et al. Detection, evaluation and treatment of diabetes mellitus in chronic pancreatitis: recommendations from PancreasFest 2012. Pancreatology. 2013;13(4):336–42.
Wu L, Nahm CB, Jamieson NB, Samra J, Clifton-Bligh R, Mittal A, et al. Risk factors for development of diabetes mellitus (Type 3c) after partial pancreatectomy: a systematic review. Clin Endocrinol. 2020;92(5):396–406.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this chapter
Cite this chapter
Kearney, J., Johnson, J., Kim, H.J. (2022). Surgical Treatment of Pancreatic Islet Cell Tumors. In: Yu, H., Burke, C.T., Commander, C.W. (eds) Diagnosis and Management of Endocrine Disorders in Interventional Radiology. Springer, Cham. https://doi.org/10.1007/978-3-030-87189-5_15
Download citation
DOI: https://doi.org/10.1007/978-3-030-87189-5_15
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-87188-8
Online ISBN: 978-3-030-87189-5
eBook Packages: MedicineMedicine (R0)