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unresectable disease; must be meticulous and consider several prerequisites
including: (a) the presence of well‐differentiated lesions;
In “functioning tumors” the symptomatic control is a (b) the absence of extra‐abdominal disease; and (c) the
major therapeutic goal; absence of diffuse peritoneal carcinomatosis. [8]

In advanced end-stage disease, palliative symptomatic In the literature, clinical studies suggest that there is a
therapies are required to maintain patient’s quality of life. possible benefit in terms of survival when performing
surgical removal of primitive pNETs if metastases are
In the present paper, some controversial issues on the present. However, in the retrospective studies that
[9]
therapeutic approach for NET patients will be discussed. evaluated the role of surgery in pNETs with unresectable
liver metastases, there is a selection bias for patients
SURGICAL THERAPY related to the localization of primary tumors and the
type of surgical approach, the patient status in terms of
Small incidental non-functioning pancreatic comorbidity, age and performance status. In the Partelli et
[9]
NETs (pNETs): should they always be removed? al. paper, the 5-year overall survival (OS) after surgical
[10]
Surgical treatment of pNETs must always be planned and resection was 76% with an increase to 88% after curative
adapted to each individual patient considering several resection. Although palliative surgery was associated with
variables, including patient characteristics and disease an improved outcome, surgical management should be
stage. Some studies have recently suggested tumor diameter reserved in highly selected patients due to the high risk of
as the main criterion for surgery with radical intent. [2,3] For peri/postoperative complications.
pNETs ≤ 2 cm, and in the absence of symptoms and/or
suspected metastatic lesions, a conservative wait-and-see Small intestinal NETs (SI-NETs) with liver
approach may be adopted in selected cases, scheduling a metastases: should the primary tumor be
clinical and radiological follow-up. [4-7] Pancreatic NETs ≤ resected?
2 cm of diameter have a risk of “malignancy” of about Surgical treatment of SI-NETs is affected by disease clinical
6%, while 5-year disease mortality is 0%. In the small presentation. For SI-NETs diagnosed as stage I-III, the
[4]
and sporadic non-functioning pNETs, the mean overall choice of therapy is always surgical bowel resection with
tumor growth (difference between size at last follow- lymphadenectomy. [11-13] Curative resection of the primary
up and initial size) was 0.37 (+/-1.67) mm. Mean tumor and regional lymph node metastasis site improves
[7]
growth per month was 0.010 (+/-0.051) or 0.12 mm per long-term outcome, with a 100% 5-10 year survival for
year corresponding to a growth percentage of 1.5% (+/- patients with stage I and II tumors and more than 80% for
5.5) from the initial tumor size per year. The incidental patients with stage III jejuno-ileal NETs. In the presence
[14]
diagnosis and the absence of symptoms seem to correlate of synchronous liver lesions, surgical treatment is still
with a better prognosis in this subgroup of patients. highly debated. A recent systematic review analyzed
[2]
[15]
Histological confirmation of tumor neuroendocrine origin the studies in the literature on the surgical resection of
by endoscopic ultrasonography with tissue sampling is the primary tumor in patients with SI-NETs and distant
required before planning a patient’s management. The metastases. Although it was not possible to conduct a
primary tumor localization is an additional major factor meta-analysis of these works, the conclusions suggest
to determining the surgical approach. Finally, the patient’s improved survival after surgical removal of the primary
comorbidities and willing should always be considered in tumor in patients with metastatic unresectable disease and
the surgical management of pNETs. a reduction in local complications (bleeding, perforation,
and occlusion). In association with the intestinal resection,
Despite recent progress, morbidity remains significant, cholecystectomy should be performed in order to prevent
indeed, it is necessary to carefully evaluate the type gallstones due to long-term treatment with somatostatin
of surgery, the risks of surgery and the risks related to analogue. [16]
tumor growth in advance. Based on these considerations,
conservative non-surgical management may be proposed MEDICAL THERAPY
in selected patients with small, incidental non-functioning
pNETs. Being characterized by a relatively long OS, multiple
sequential therapies are adopted in digestive NETs although
Pancreatic NETs with liver metastases: should the best sequence for these patients is not well defined.
the primary tumor be resected?
The presence of metastases is the main factor associated Somatostatin analogs (SSAs): are they indicated
with mortality in pNET patients. Surgical options for for all NET patients?
patients, including those with metastatic disease, include SSAs clearly represent the first-line treatment for patients
different procedures such as curative liver and pancreatic with functioning NETs. As far as non-functioning tumors
resection, primary resection, local ablative techniques, are concerned, SSAs can control tumor proliferation, as
and liver transplantation. In these cases, patient selection shown by two randomized clinical trials. The PROMID
Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ August 17, 2016 ¦ 305