The Landmark Series: Pancreatic Neuroendocrine Tumors
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CONTINUING EDUCATION– PANCREATIC TUMORS
The Landmark Series: Pancreatic Neuroendocrine Tumors Jordan M. Cloyd, MD1
, and George A. Poultsides, MD, MS2
1
Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH; 2Department of Surgery, Stanford University, Stanford, CA
ABSTRACT Pancreatic neuroendocrine tumors (PNETs) comprise a heterogeneous group of neoplasms arising from pancreatic islet cells that remain relatively rare but are increasing in incidence worldwide. While significant advances have been made in recent years with regard to systemic therapies for patients with advanced disease, surgical resection remains the standard of care for most patients with localized tumors. Although formal pancreatectomy with regional lymphadenectomy is the standard approach for most PNETs, pancreas-preserving approaches without formal lymphadenectomy are acceptable for smaller tumors at low risk for lymph node metastases. Furthermore, observation of small, asymptomatic, lowgrade PNETs is a safe, initial strategy and is generally recommended for tumors \ 1 cm in size. In this Landmark Series review, we highlight the critical studies that have defined the surgical management of PNETs.
Pancreatic neuroendocrine tumors (PNETs) are a heterogeneous group of neoplasms arising from pancreatic islet cells.1 They are relatively rare, representing only 3% of pancreatic neoplasms and 7% of neuroendocrine tumors (NETs).2 However, the incidence of PNETs, like all NETs, is rising, likely due to a combination of more widespread use of cross-sectional imaging and endoscopic ultrasonography, as well as improved awareness among clinicians and pathologists.3 Although PNETs are commonly considered to be more indolent than their exocrine counterpart pancreatic ductal adenocarcinoma (PDAC),
Ó Society of Surgical Oncology 2020 First Received: 25 August 2020 Accepted: 29 August 2020 G. A. Poultsides, MD, MS e-mail: [email protected]
they do have the propensity to metastasize to regional lymph nodes and distant metastatic sites, in addition to their ability to exert locoregional effects due to their location and size. PNETs have traditionally been classified according to their grade and functionality. The 2017 World Health Organization updated their classification of PNETs into well-differentiated NETs and poorly differentiated neuroendocrine carcinomas (NECs) based on tumor morphology, with further stratification of well-differentiated NETs into grades 1–3 based on the Ki67 proliferation index and mitotic index per high power field. Even among well-differentiated tumors, PNETs exhibit a wide range of clinical behavior and prognosis. Furthermore, PNETs can be classified as nonfunctional (NF-PNETs) or functional (F-PNETs) based on their ability to secrete hormones characteristic of well-recognized clinical syndromes. Given their clinical heterogeneity, the optimal multidisciplinary and surgical management of PNETs has been challenging to clarify.4 Furthermore, research on PNETs has been hindered by the relative
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