Abstract
Background
The optimal surgical management of pancreatic neuroendocrine tumors in patients with
multiple endocrine neoplasia type 1 is controversial. This study sought to compare
clinicopathologic characteristics and outcomes of multiple endocrine neoplasia type
1–associated and sporadic pancreatic neuroendocrine tumors from a large multi-national
database.
Methods
A multi-institutional, international database of patients with surgically resected
pancreatic neuroendocrine tumors was analyzed. The cohort was divided into 2 groups:
those with multiple endocrine neoplasia type 1 versus those with sporadic disease.
Clinicopathologic comparisons were made. Overall and disease-free survival were analyzed.
Propensity score matching was used to reduce bias.
Results
Of 651 patients included, 45 (6.9%) had multiple endocrine neoplasia type 1 and 606
sporadic pancreatic neuroendocrine tumors. Multiple endocrine neoplasia type 1–associated
pancreatic neuroendocrine tumors were more common in younger patients and associated
with multifocal disease at the time of surgery and higher T-stage. Lymph node involvement
and the presence of metastasis were similar. Total pancreatectomy rate was 5-fold
higher in the multiple endocrine neoplasia type 1 cohort. Median survival did not
differ (disease-free survival 126 months multiple endocrine neoplasia type 1 vs 198
months sporadic, P > .5). After matching, survival remained similar (overall survival not reached in
either cohort, disease-free survival 126 months multiple endocrine neoplasia type
1 vs 198 months sporadic, P > .5). Equivalence in overall survival and disease-free survival persisted even when
patients who underwent subtotal and total pancreatectomy were excluded.
Conclusion
Multiple endocrine neoplasia type 1–associated pancreatic neuroendocrine tumors are
more common in younger patients and are associated with multifocality and higher T-stage.
Survival for patients with multiple endocrine neoplasia type 1–associated pancreatic
neuroendocrine tumors is comparable to those with sporadic pancreatic neuroendocrine
tumors, even in the absence of radical pancreatectomy. Consideration should be given
to parenchymal-sparing surgery to preserve pancreatic function.
Graphical abstract
Graphical Abstract
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to SurgeryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Recent topics around multiple endocrine neoplasia type 1.J Clin Endocrinol Metab. 2018; 103: 1296-1301
- Genotype-phenotype pancreatic neuroendocrine tumor relationship in multiple endocrine neoplasia type 1 patients: a 23-year experience at a single institution.Surgery. 2018; 163: 212-217
- Pancreatic neuroendocrine tumors in MEN1 disease: a mono-centric longitudinal and prognostic study.Endocrine. 2018; 60: 362-367
- Inherited pancreatic endocrine tumor syndromes: advances in molecular pathogenesis, diagnosis, management, and controversies.Cancer. 2008; 113: 1807-1843
- Timing and extent of surgery in symptomatic and asymptomatic neuroendocrine tumors of the pancreas in MEN 1.Langenbecks Arch Surg. 2002; 386: 558-569
- The surgical management of MEN-1 pancreatoduodenal neuroendocrine disease.Surgery. 2004; 136: 1205-1211
- Pancreatic neuroendocrine tumors: surgical resection.Arq Bras Cir Dig. 2019; 32
- Consensus: guidelines for diagnosis and therapy of MEN type 1 and type 2.J Clin Endocrinol Metab. 2001; 86: 5658-5671
- Pancreatic neuroendocrine tumors: biology, diagnosis, and treatment.Chin J Cancer. 2013; 32: 312-324
- Neuroendocrine tumors of the pancreas.Oncologist. 2009; 14: 456-467
- Pancreatic tumours as part of the MEN-1 syndrome.Best Pract Res Clin Gastroenterol. 2005; 19: 819-830
- Current concepts in the surgical management of multiple endocrine neoplasia type 1 pancreatic-duodenal disease: results in the treatment of 40 patients with Zollinger-Ellison syndrome, hypoglycaemia or both.J Int Med. 1998; 243: 495-500
- What extent of pancreatic resection do patients with MEN-1 require?.J Pancreas. 2012; https://doi.org/10.6092/1590-8577/657
- Outcomes of pancreaticoduodenectomy for pancreatic neuroendocrine tumors: are combined procedures justified?.J Gastrointest Surg. 2016; 20: 891-898
- Pancreatic grade 3 neuroendocrine tumors behave similarly to neuroendocrine carcinomas following resection: a multi-center, international appraisal of the WHO 2010 and WHO 2017 staging schema for pancreatic neuroendocrine lesions.HPB. 2020; https://doi.org/10.1016/j.hpb.2019.12.014
- Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1).J Clin Endocrinol Metab. 2012; 97: 2990-3011
- Nonparametric estimation from incomplete observations.J Am Stat Assoc. 1958; https://doi.org/10.1080/01621459.1958.10501452
- The central role of the propensity score in observational studies for causal effects.Biometrika. 1983; 70: 41-55
- Constructing a control group using multivariate matched sampling methods that incorporate the propensity score.Am Stat. 1985; https://doi.org/10.1080/00031305.1985.10479383
- Matching using propensity scores: relating theory to practice.Biometrics. 1996; 5 (249-64)
- MatchIt: nonparametric preprocessing for parametric causal inference.J Stat Softw. 2011; 42: 1-28
- Multivariate matching methods that are monotonic imbalance bounding.J Am Stat Assoc. 2011; 106: 345-361
- Causal inference without balance checking: coarsened exact matching.Polit Anal. 2012; 20: 1-24
- R: A Language and Environment for Statistical Computing.2016
- Sporadic and MEN1-related primary hyperparathyroidism: differences in clinical expression and severity.J Bone Miner Res. 2009; 24: 1404-1410
- Differences between sporadic and MEN related primary hyperparathyroidism; clinical expression, preoperative workup, operative strategy and follow-up.Orphanet J Rare Dis. 2013; 8
- The treatment of sporadic versus MEN1-related pituitary adenomas.J Intern Med. 2003; 253: 599-605
- Surgery to cure the Zollinger-Ellison syndrome.N Engl J Med. 1999; 341: 635-644
- Impact of endocrine and exocrine insufficiency on quality of life after total pancreatectomy.Ann Surg Oncol. 2020; 27: 587-596
- Early and late complications after surgery for MEN1-related nonfunctioning pancreatic neuroendocrine tumors.Ann Surg. 2018; 267: 352-356
- Complications after pancreatectomy for neuroendocrine tumors: a national study.J Surg Res. 2010; 163: 63-68
- Results of duodenopancreatic reoperations in multiple endocrine neoplasia type 1.World J Surg. 2019; 43: 552-558
- First surgery for pancreatic neuroendocrine tumours in a patient with MEN1: enucleation versus disease-modifying surgery.Clin Endocrinol (Oxf). 2015; 83: 618-621
- Care for patients with multiple endocrine neoplasia type 1: the current evidence base.Fam Cancer. 2011; 10: 157-171
- Imaging in multiple endocrine neoplasia type 1: recent studies show enhanced sensitivities but increased controversies.Int J Endocr Oncol. 2016; 3: 53-66
- Recurrent loss of heterozygosity correlates with clinical outcome in pancreatic neuroendocrine cancer.NPJ Genom Med. 2018; 3: 18
- Pancreaticoduodenal endocrine tumors in multiple endocrine neoplasia type 1: surgery or surveillance?.Surgery. 2000; 128: 958-966
- Higher risk of death among Men1 patients with mutations in the Jund Interacting Domain: a Groupe d’Étude des Tumeurs Endocrines (GTE) Cohort Study.Hum Mol Genet. 2013; 22: 1940-1948
- Higher risk of aggressive pancreatic neuroendocrine tumors in MEN1 patients with Men1 mutations affecting the CHES1 interacting MENIN domain.J Clin Endocrinol Metab. 2014; 99: E2387-E2391
Article info
Publication history
Published online: May 13, 2022
Accepted:
April 6,
2022
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
