ORIGINAL ARTICLE – ENDOCRINE TUMORS
Sporadic Small (£20 mm) Nonfunctioning Pancreatic
Neuroendocrine Neoplasm: is the Risk of Malignancy Negligible
When Adopting a More Conservative Strategy? A Systematic
Review and Meta-analysis
Claudio Ricci, MD
, Riccardo Casadei, MD
, Giovanni Taffurelli, MD
, Carlo Alberto Pacilio, MD
Davide Campana, MD
, Valentina Ambrosini, MD
, Santini Donatella, MD
, and Francesco Minni, MD
Department of Internal Medicine and Surgery (DIMEC), Chirurgia Generale-Minni, Alma Mater Studiorum-Universita
Bologna, Bologna, Italy;
Department of Specialized Diagnostic and Experimental Medicine (DIMES), Bologna, Italy
Background. The management of small (B20 mm), non-
functioning pancreatic neuroendocrine neoplasms (pNENs)
remains under debate. The European Neuroendocrine
Tumor Society guidelines advocate the possibility of a
Methods. A systematic literature search was conducted to
identify all studies comparing the risk of malignancy in
small pNENs with respect to large ones ([20 mm).
Malignancy was deﬁned based on the presence of nodal
metastases. Distant metastases, tumor grading (G2–3),
vascular microscopic invasion, stage III-IV, and overall
and disease-free survival also were evaluated. The data
were reported in two ways: using the risk difference (RD)
and the likelihood of being helped or harmed (LHH).
Results. The search identiﬁed only 6 eligible studies with
an overall population of 1697 resected pNENs: 382
(22.5%) small and 1315 (77.5%) large. The RD of lymph
nodal metastases was -0.26 (95% conﬁdence interval (CI):
-0.31 to -0.22; P \ 0.001). The LHH was 0.34, sug-
gesting that the risk of leaving a malignancy during follow-
up due to the adoption of a conservative strategy was three
times higher than the beneﬁts. The risk difference of distant
metastases, G3 lesions, G2–G3 lesions, stage III/IV,
microscopic vascular invasion, death, and recurrence of the
disease were lower in small NF-PNETs than large ones.
The related LHH values suggested that a watch-and-wait
policy never provided a beneﬁt.
Conclusions. Even if the malignancy rate in sporadic, small
pancreatic neuroendocrine neoplasms was lower than in large
ones, this difference did not justify a watch-and-wait policy.
The management of small, nonfunctioning pancreatic
neuroendocrine neoplasm (pNENs) remains under debate.
A recent update of the European Neuroendocrine Tumor
Society (ENETS) guidelines advocates, for the ﬁrst time,
the possibility of a conservative approach
tomatic small (B20 mm), sporadic pNENs without distant
metastases. However, the same 2016 guidelines clearly
stated that additional data were needed to guarantee the
safety of this policy, which was based on the inadequate
available literature at that time.
Conversely, some studies
have advocated that surgical management in patients with
pNENs \20 mm is the best curative option.
Partelli et al., using a systematic review, reported the safety
of active surveillance in small, sporadic pNENs.
from these different points of view, two questions remain:
(1) What is the real risk difference of malignancy in
patients having NF-PNETs B20 mm with respect to those
having a tumor [20 mm?; and (2) What are the beneﬁts
and the risks due to the adoption of the more conservative
strategy suggested by the 2016 ENETS guidelines? To
answer the two questions, a systematic review and meta-
analysis was performed.
Electronic supplementary material The online version of this
article (doi:10.1245/s10434-017-5946-8) contains supplementary
material, which is available to authorized users.
Ó Society of Surgical Oncology 2017
First Received: 7 March 2017;
Published Online: 5 July 2017
C. Ricci, MD
e-mail: firstname.lastname@example.org; email@example.com
Ann Surg Oncol (2017) 24:2603–2610