Introduction: Nonfunctioning pancreatic neuroendocrine tumor (NF-PanNET) ≤2 cm can be observed or resected. Surgery remains recommended for NF-PanNET >2 cm but its extent, enucleation (EN) versus formal resection, remains controversial. Methods: Multicentric retrospective cohort of sporadic NF-PanNET patients treated with EN. Short- and long-term outcomes were compared according to tumor size on imaging ≤2 cm versus >2 cm. Results: 131 patients underwent EN for NF-PanNET, including 103 (79.0%) ≤2 cm and 28 (21.0%) >2 cm (extremes, 4–55 mm). Patients’ characteristics were comparable, and tumor characteristics only differed in their diameter. Clavien III-IV complications were similar (18.4% vs. 17.9%, p = 1.00) with one death in NF-PanNET ≤2 cm. Grade B/C pancreatic fistula were comparable (16.5% vs. 10.7%, p = 0.850). In NF-PanNET >2 cm there were more pT2/3 stage tumors (85.7% vs. 21.4%, p < 0.001), similar rates of grade G2/3 tumors (25% vs. 16.5%, p = 0.408) with a median Ki67 of 2 (interquartile range: 1–3), and of lymphovascular and perineural invasions. Lymph node picking was done in 46 (35.1%) patients, with a higher median number of harvested lymph nodes in NF-PanNET >2 cm (4 vs. 3, p = 0.01). All were pN0. R0 resection rate (78.6% vs. 82.5%, respectively; p = 0.670) was equivalent. Five-year overall (100% vs. 99%, p = 0.602) and 10-year disease-free (96% vs. 92%, respectively; p = 0.532) survivals were comparable. Conclusions: EN for selected NF-PanNET >2 cm carries equivalent morbidity, overall and disease-free survivals compared to those observed with NF-PanNET ≤2 cm.

1.
Yao
JC
,
Hassan
M
,
Phan
A
,
Dagohoy
C
,
Leary
C
,
Mares
JE
, et al
.
One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States
.
J Clin Oncol
.
2008
;
26
(
18
):
3063
72
.
2.
Ehehalt
F
,
Saeger
HD
,
Schmidt
CM
,
Grützmann
R
.
Neuroendocrine tumors of the pancreas
.
Oncologist
.
2009
;
14
(
5
):
456
67
.
3.
Lawrence
B
,
Gustafsson
BI
,
Chan
A
,
Svejda
B
,
Kidd
M
,
Modlin
IM
.
The epidemiology of gastroenteropancreatic neuroendocrine tumors
.
Endocrinol Metab Clin North Am
.
2011
;
40
(
1
):
1
vii
.
4.
Vaghaiwalla
T
,
Keutgen
XM
.
Surgical management of pancreatic neuroendocrine tumors
.
Surg Oncol Clin N Am
.
2020
;
29
(
2
):
243
52
.
5.
Falconi
M
,
Eriksson
B
,
Kaltsas
G
,
Bartsch
DK
,
Capdevila
J
,
Caplin
M
, et al
.
ENETS consensus guidelines update for the management of patients with functional pancreatic neuroendocrine tumors and non-functional pancreatic neuroendocrine tumors
.
Neuroendocrinology
.
2016
;
103
(
2
):
153
71
.
6.
Vagefi
PA
,
Razo
O
,
Deshpande
V
,
McGrath
DJ
,
Lauwers
GY
,
Thayer
SP
, et al
.
Evolving patterns in the detection and outcomes of pancreatic neuroendocrine neoplasms: the Massachusetts General Hospital experience from 1977 to 2005
.
Arch Surg
.
2007
;
142
(
4
):
347
54
.
7.
Referenced with permission from the NCCN clinical practice guidelines in oncology (NCCN Guidelines®) for neuroendocrine tumors of the pancreas (Well-Differentiated grade 1/2) V1.2024© national comprehensive cancer Network
.
Inc
.
2024
. All rights reserved. Accessed [Jul 1st, 2024]. To view the most recent and complete version of the guideline, go online to NCCN.org.
8.
Dong
DH
,
Zhang
XF
,
Lopez-Aguiar
AG
,
Poultsides
G
,
Makris
E
,
Rocha
F
, et al
.
Resection of pancreatic neuroendocrine tumors: defining patterns and time course of recurrence
.
HPB Oxf
.
2020
;
22
(
2
):
215
23
.
9.
Nießen
A
,
Bechtiger
FA
,
Hinz
U
,
Lewosinska
M
,
Billmann
F
,
Hackert
T
, et al
.
Enucleation is a feasible procedure for well-differentiated pNEN-A matched pair analysis
.
Cancers
.
2022
;
14
(
10
):
2570
.
10.
Pitt
SC
,
Pitt
HA
,
Baker
MS
,
Christians
K
,
Touzios
JG
,
Kiely
JM
, et al
.
Small pancreatic and periampullary neuroendocrine tumors: resect or enucleate
.
J Gastrointest Surg
.
2009
;
13
(
9
):
1692
8
.
11.
Bolm
L
,
Nebbia
M
,
Wei
AC
,
Zureikat
AH
,
Fernández-Del Castillo
C
,
Zheng
J
, et al
.
Long-term outcomes of parenchyma-sparing and oncologic resections in patients with nonfunctional pancreatic neuroendocrine tumors <3 cm in a large multicenter cohort
.
Ann Surg
.
2022
;
276
(
3
):
522
31
.
12.
Chen
J
,
Yang
Y
,
Liu
Y
,
Kan
H
.
Prognosis analysis of patients with pancreatic neuroendocrine tumors after surgical resection and the application of enucleation
.
World J Surg Oncol
.
2021
;
19
(
1
):
11
.
13.
Bassi
C
,
Marchegiani
G
,
Dervenis
C
,
Sarr
M
,
Abu Hilal
M
,
Adham
M
, et al
.
The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 Years after
.
Surgery
.
2017
;
161
(
3
):
584
91
.
14.
Dindo
D
,
Demartines
N
,
Clavien
PA
.
Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey
.
Ann Surg
.
2004
;
240
(
2
):
205
13
.
15.
Royal College of Pathologists
.
Standards and datasets for reporting cancers Dataset for histopathological reporting of neuroendocrine neoplasms of the gastroenteropancreatic tract
. Available from: https://www.acpgbi.org.uk/_userfiles/import/2019/05/Dataset-for-histopathological-reporting-of-neuroendocrine-neoplasms-of-the-gastroenteropancreatic-tract-For-Consultation-002.pdf (accessed May, 2019).
16.
Amin
MB
,
Greene
FL
,
Edge
SB
,
Compton
CC
,
Gershenwald
JE
,
Brookland
RK
, et al
.
The Eighth Edition AJCC Cancer Staging Manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging
.
CA Cancer J Clin
.
2017
;
67
(
2
):
93
9
.
17.
Kanda
Y
.
Investigation of the freely available easy-to-use software “EZR” for medical statistics
.
Bone Marrow Transplant
.
2013
;
48
(
3
):
452
8
.
18.
Hüttner
FJ
,
Koessler-Ebs
J
,
Hackert
T
,
Ulrich
A
,
Büchler
MW
,
Diener
MK
.
Meta-analysis of surgical outcome after enucleation versus standard resection for pancreatic neoplasms
.
Br J Surg
.
2015
;
102
(
9
):
1026
36
.
19.
Heidsma
CM
,
Tsilimigras
DI
,
van Dieren
S
,
Rocha
F
,
Abbott
DE
,
Fields
R
, et al
.
Indications and outcomes of enucleation versus formal pancreatectomy for pancreatic neuroendocrine tumors
.
HPB Oxf
.
2021
;
23
(
3
):
413
21
.
20.
Inchauste
SM
,
Lanier
BJ
,
Libutti
SK
,
Phan
GQ
,
Nilubol
N
,
Steinberg
SM
, et al
.
Rate of clinically significant postoperative pancreatic fistula in pancreatic neuroendocrine tumors
.
World J Surg
.
2012
;
36
(
7
):
1517
26
.
21.
Strobel
O
,
Cherrez
A
,
Hinz
U
,
Mayer
P
,
Kaiser
J
,
Fritz
S
, et al
.
Risk of pancreatic fistula after enucleation of pancreatic tumours
.
Br J Surg
.
2015
;
102
(
10
):
1258
66
.
22.
Brient
C
,
Regenet
N
,
Sulpice
L
,
Brunaud
L
,
Mucci-Hennekine
S
,
Carrère
N
, et al
.
Risk factors for postoperative pancreatic fistulization subsequent to enucleation
.
J Gastrointest Surg
.
2012
;
16
(
10
):
1883
7
.
23.
Sauvanet
A
,
Gaujoux
S
,
Blanc
B
,
Couvelard
A
,
Dokmak
S
,
Vullierme
MP
, et al
.
Parenchyma-sparing pancreatectomy for presumed noninvasive intraductal papillary mucinous neoplasms of the pancreas
.
Ann Surg
.
2014
;
260
(
2
):
364
71
.
24.
Hwang
HK
,
Song
KB
,
Park
M
,
Kwon
W
,
Jang
JY
,
Heo
JS
, et al
.
Minimally invasive versus open pancreatectomy for right-sided and left-sided G1/G2 nonfunctioning pancreatic neuroendocrine tumors: a multicenter matched analysis with an inverse probability of treatment-weighting method
.
Ann Surg Oncol
.
2021
;
28
(
12
):
7742
58
.
25.
Partelli
S
,
Gaujoux
S
,
Boninsegna
L
,
Cherif
R
,
Crippa
S
,
Couvelard
A
, et al
.
Pattern and clinical predictors of lymph node involvement in nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs)
.
JAMA Surg
.
2013
;
148
(
10
):
932
9
.
26.
Sallinen
VJ
,
Le Large
TYS
,
Tieftrunk
E
,
Galeev
S
,
Kovalenko
Z
,
Haugvik
SP
, et al
.
Prognosis of sporadic resected small (≤2 cm) nonfunctional pancreatic neuroendocrine tumors: a multi-institutional study
.
HPB Oxf
.
2018
;
20
(
3
):
251
9
.
27.
Sanli
Y
,
Garg
I
,
Kandathil
A
,
Kendi
T
,
Zanetti
MJB
,
Kuyumcu
S
, et al
.
Neuroendocrine tumor diagnosis and management: 68Ga-DOTATATE PET/CT
.
AJR Am J Roentgenol
.
2018
;
211
(
2
):
267
77
.
28.
Heidsma
CM
,
van Roessel
S
,
van Dieren
S
,
Engelsman
AF
,
Strobel
O
,
Buechler
MW
, et al
.
International validation of a nomogram to predict recurrence after resection of grade 1 and 2 nonfunctioning pancreatic neuroendocrine tumors
.
Neuroendocrinology
.
2022
;
112
(
6
):
571
9
.
29.
Rebours
V
,
Cordova
J
,
Couvelard
A
,
Fabre
M
,
Palazzo
L
,
Vullierme
MP
, et al
.
Can pancreatic neuroendocrine tumour biopsy accurately determine pathological characteristics
.
Dig Liver Dis
.
2015
;
47
(
11
):
973
7
.
30.
Zerbi
A
,
Falconi
M
,
Rindi
G
,
Delle Fave
G
,
Tomassetti
P
,
Pasquali
C
, et al
.
Clinicopathological features of pancreatic endocrine tumors: a prospective multicenter study in Italy of 297 sporadic cases
.
Am J Gastroenterol
.
2010
;
105
(
6
):
1421
9
.
31.
Perinel
J
,
Nappo
G
,
Zerbi
A
,
Heidsma
CM
,
Nieveen van Dijkum
EJM
,
Han
HS
, et al
.
Sporadic nonfunctional pancreatic neuroendocrine tumors: risk of lymph node metastases and aggressiveness according to tumor size: a multicenter international study
.
Surgery
.
2022
;
172
(
3
):
975
81
.
32.
Partelli
S
,
Gaujoux
S
,
Boninsegna
L
,
Cherif
R
,
Crippa
S
,
Couvelard
A
, et al
.
Pattern and clinical predictors of lymph node involvement in nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs)
.
JAMA Surg
.
2013
;
148
(
10
):
932
9
.
33.
Jilesen
AP
,
van Eijck
CH
,
Busch
OR
,
van Gulik
TM
,
Gouma
DJ
,
van Dijkum
EJ
.
Postoperative outcomes of enucleation and standard resections in patients with a pancreatic neuroendocrine tumor
.
World J Surg
.
2016
;
40
(
3
):
715
28
.
34.
Genç
CG
,
Jilesen
AP
,
Partelli
S
,
Falconi
M
,
Muffatti
F
,
van Kemenade
FJ
, et al
.
A new scoring system to predict recurrent disease in grade 1 and 2 nonfunctional pancreatic neuroendocrine tumors
.
Ann Surg
.
2018
;
267
(
6
):
1148
54
.
35.
Pulvirenti
A
,
Javed
AA
,
Landoni
L
,
Jamieson
NB
,
Chou
JF
,
Miotto
M
, et al
.
Multi-institutional development and external validation of a nomogram to predict recurrence after curative resection of pancreatic neuroendocrine tumors
.
Ann Surg
.
2021
;
274
(
6
):
1051
7
.
36.
Zaidi
MY
,
Lopez-Aguiar
AG
,
Switchenko
JM
,
Lipscomb
J
,
Andreasi
V
,
Partelli
S
, et al
.
A novel validated recurrence risk score to guide a pragmatic surveillance strategy after resection of pancreatic neuroendocrine tumors: an international study of 1006 patients
.
Ann Surg
.
2019
;
270
(
3
):
422
33
.
37.
Giuliani
T
,
De Pastena
M
,
Paiella
S
,
Marchegiani
G
,
Landoni
L
,
Festini
M
, et al
.
Pancreatic enucleation patients share the same quality of life as the general population at long-term follow-up: a propensity score-matched analysis
.
Ann Surg
.
2023
;
277
(
3
):
e609
16
.
38.
De Bruijn
KM
,
van Eijck
CH
.
New-onset diabetes after distal pancreatectomy: a systematic review
.
Ann Surg
.
2015
;
261
(
5
):
854
61
.
39.
Dai
M
,
Xing
C
,
Shi
N
,
Wang
S
,
Wu
G
,
Liao
Q
, et al
.
Risk factors for new-onset diabetes mellitus after distal pancreatectomy
.
BMJ Open Diabetes Res Care
.
2020
;
8
(
2
):
e001778
.
40.
Crinò
SF
,
Napoleon
B
,
Facciorusso
A
,
Lakhtakia
S
,
Borbath
I
,
Caillol
F
, et al
.
Endoscopic ultrasound-guided radiofrequency ablation versus surgical resection for treatment of pancreatic insulinoma
.
Clin Gastroenterol Hepatol
.
2023
;
21
(
11
):
2834
43.e2
.
41.
Khoury
T
,
Sbeit
W
,
Napoléon
B
.
Endoscopic ultrasound guided radiofrequency ablation for pancreatic tumors: a critical review focusing on safety, efficacy and controversies
.
World J Gastroenterol
.
2023
;
29
(
1
):
157
70
.
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