Original articleOutcome after pancreatectomy for neuroendocrine neoplams according to the WHO 2017 grading system: A retrospective multicentric analysis of 138 consecutive patients
Introduction
Neuroendocrine neoplams of the pancreas (panNET) are neoplasms that originate from the endocrine portion of the pancreas. These tumors, which newly affect 2–3 per 100,000 individuals per year, constitute only about 1% to 2% of all pancreatic neoplasms [1], [2]. PanNET can be classified as functioning and non-functioning [3]. At least 50% of panNET are non-functioning and hence asymptomatic. Prognosis of panNET depends on clinico-pathological factors including tumor size, differentiation and proliferative index that give an indication of the biological aggressiveness of the tumor and likelihood of lymph node involvement [4], [5], [6]. Complete surgical resection plays an important role in the curative treatment of patients with panNET. Several guidelines exist for the treatment of functioning and non-functioning panNET [7], [8]. It is generally accepted that tumors > 2 cm and functioning tumors should be resected but the management of non-functioning tumors < 2 cm remains controversial. Further controversy exists as to the surgical approach (open vs. laparoscopic) and the lymphadenectomy. PanNET are associated with synchronous liver metastasis in 30–80% of patients and require dedicated multidisciplinary staff discussion [9]. The prognostic classification of NET has been challenging due to their relative rarity. The WHO 2010 grading system adopted the Ki-67 index and/or mitotic index to divide digestive system NEN into 3 main types: NET G1, NET G2 NEC G3. Several studies leading to the new WHO 2017 grading system had reported that NEC G3 is a heterogeneous category that can be separated into two subcategories with significantly different prognosis and more importantly, therapeutic strategies seem to be distinct [10], [11], [12], [13]. The new WHO 2017 classification (dividing G3 tumors in well differentiated NET G3 or poorly differentiated NEC G3) validation is ongoing for its ability to predict disease-free survival (DFS) and overall survival (OS) for panNET [14].
Therefore, we aimed to explore the clinicopathological characteristics, short-term and survival outcome on the basis of 138 consecutive patients with panNET, as well as to evaluate the prognostic value of the proposed new WHO 2017 classification.
Section snippets
Patient selection and study design
This was a retrospective review of a prospectively maintained database including all consecutive patients requiring a pancreatic resection for panNET at 3 tertiary referral centers for pancreatic surgery in France, between January 1998 and December 2017. The 3 centers were Digestive Surgery Units of Montpellier, Nimes and Institute of Cancer of Montpellier. The University Institutional Review board approved the study (No.: 2019_IRB-MTP_01-02), which was registered on Clinicaltrials.gov registry
Patient characteristics
A total of 138 patients underwent pancreatic resection for panNET in our 3 centers. The age at surgery was 56 (13–77) years, and 48.5% (67/138) were female. ASA score at diagnosis was I/II in 86.5% of the patients. Diagnosis was incidental in 57 (41%) patients. panNET was sporadic in 132 patients (96%) and associated to Multiple Endocrine Neoplasia syndrome type 1 in 5 (3.5%) patients and Von Hippel-Lindau in 1 (0.5%) patients. Primary locations were equally distributed in the pancreas: head
Discussion
This study, which involved three centers with the same clinical RENATEN network, has many strengths: only panNET patients were included, standardization of work-up across our centers and systematic pathological review by 2 TENpath labeled experts. Pancreatic neuroendocrine neoplasms were majority non-functioning, sporadic, single lesion of 31 mm in median size, non-metastatic with homogenous stage distribution. Our findings confirm several specific issues related to the management of panNET and
Funding
The authors have no source of funding to disclose for this study.
Authors’ contributions
All authors declare that has participated sufficiently in the work to take public responsibility for appropriate portions of the content, as defined in to the guidelines of the International Committee of Medical Journal Editors (ICMJE).
R.S., A.C., M.D., J.R., B.R., M.P., E.A. and J.M.F. were responsible for study concept and design. R.S., A.C., M.D., M.B., I.R., B.G., A.H., S.O., F.P., B.R., F.B., J.R., F.Q., P.E.C., M.P., E.A. and J.M.F. contributed for acquisition and interpretation of data.
Disclosure of interest
The authors declare that they have no competing interest.
Acknowledgments
We thank RENATEN LR and the University of Montpellier for its support. We thank Lorenzo Ferre, Cyprien Toubert, John Chauvat and Françoise Guillon for data collection and their advice. We are grateful to Jacqueline Butterworth for editorial assistance. We thank the residents, fellows, and nurses of our division for the care they provided to these patients.
The data will not be made publicly available, but is available from the authors on request.
References (39)
- et al.
Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors
Gastroenterology
(2008) - et al.
Pancreatic endocrine tumors: improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients
Mod Pathol
(2010) - et al.
Scoggins CR: analysis of 6,747 pancreatic neuroendocrine tumors for a proposed staging system
J Gastrointest Surg
(2011) - 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) - et al.
The New World Health Organization Classification for Pancreatic Neuroendocrine Neoplasia
Endocrinol Metab Clin North Am
(2018) - et al.
Tumor size correlates with malignancy in nonfunctioning pancreatic endocrine tumor
Surgery
(2011) - et al.
Small, nonfunctioning, asymptomatic pancreatic neuroendocrine tumors (PNETs): role for nonoperative management
Surgery
(2012) - et al.
Postoperative pancreatic fistula: An International Study Group (ISGPF) Definition
Surgery
(2005) - et al.
Postpancreatectomy hemorrhage (PPH): an International Study Group of Pancreatic Surgery (ISGPS) definition
Surgery
(2007) - et al.
Medial pancreatectomy: a multi-institutional retrospective study of 53 patients by the French Pancreas Club
Surgery
(2002)
Parenchyma-sparing resections for pancreatic neuroendocrine tumors
J Gastrointest Surg
Pancreatic neuroendocrine tumors (PNETs): incidence, prognosis and recent trend toward improved survival
Ann Oncol
Prognosis of sporadic resected small (</ = 2 cm) nonfunctional pancreatic neuroendocrine tumors – A Multi-Institutional Study
HPB (Oxford)
Importance of lymph node involvement in pancreatic neuroendocrine tumors: impact on survival and implications for surgical resection
J Gastrointest Surg
Endocrine pancreatic tumors: factors correlated with survival
Ann Oncol
Multiple endocrine neoplasia type 1: clinical and genetic topics
Ann Intern Med
Neuroendocrine tumors of the pancreas
Curr Opin Oncol
ENETS Consensus Guidelines Update for the management of patients with functional pancreatic neuroendocrine tumors and non-functional pancreatic neuroendocrine tumors
Neuroendocrinology
Consensus guidelines for the management and treatment of neuroendocrine tumors
Pancreas
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