Neuroendocrine tumors (NETs) arise from enterochromaffin cells found in neuroendocrine tissues, with most occurring in the gastrointestinal tract. The global incidence of NETs has increased in the past 15 years, likely due to better diagnostic methods. Small-bowel NETs are frequently associated with carcinoid syndrome (CS). Carcinoid syndrome diarrhea occurs in 80% of CS patients and poses a substantial symptomatic and economic burden. Patients with CS diarrhea frequently suffer from diarrhea and flushing and report corresponding impairment in quality of life, requiring substantial changes in daily activities and lifestyle. Treatment paradigms range from surgical debulking to liver-directed therapies to treatment with somatostatin analogs, nonspecific anti-diarrheal agents, and a tryptophan hydroxylase inhibitor. Other causes of diarrhea, including steatorrhea, short bowel syndrome, and bile acid malabsorption, should be considered in NET patients with refractory diarrhea. More therapeutic options are needed for symptomatic management of patients with NETs, and better understanding of the pathophysiology can empower clinicians with improved patient care.
From the *Banner MD Anderson Cancer Center, Gilbert, AZ
†Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
‡Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
§University of Arizona Cancer Center (UACC), Phoenix, AZ
∥Neuroendocrine Cancer Program, University of Iowa Health Care, Iowa City, IA
¶Division of Medical Oncology, Mayo Clinic, Rochester, MN.
Received for publication December 13, 2018; accepted July 10, 2019.
Address correspondence to: Boris G. Naraev, MD, PhD, Banner MD Anderson Cancer Center, 2946 E Banner Gateway Drive, Gilbert, AZ 85234 (e-mail: Boris.Naraev@bannerhealth.com).
Medical writing and editorial assistance provided by Lalitha Priya Chandrashekhar and Kathryn Martin (Publication Practice Counsel™; Truposha, LLC), which was funded by Lexicon Pharmaceuticals, Inc. Authors retain control of publication content and decisions, including the choice of journal.
B.G.N. served as a consultant for Advanced Accelerator Applications, Lexicon Pharmaceuticals, Inc. and Novocure, Inc. D.M.H. served as a consultant for Lexicon Pharmaceuticals, Inc., Ipsen Biopharmaceuticals, Inc, and Novartis Pharmaceuticals, Inc. Received research grants from Ipsen Biopharmaceuticals, Inc, Novartis Pharmaceuticals, Inc., Tarveda Therapeutics, Genentech, and Thermo Fisher Scientific. A.J.P. served as an advisor for Lexicon Pharmaceuticals, Inc. T.R.H. served as a consultant for Advanced Accelerator Applications (paid to institution) and Lexicon Pharmaceuticals, Inc. Received research grants from Ipsen Biopharmaceuticals, Thermo Fisher Scientific, ArQule, Inc., and Agios Pharmaceuticals (all paid to institution). M.H. and T.M.OD. declare no conflicts of interest.