Page 21 - Read Online

discovered during radiologic workup for other reasons, resection, compared with nonresectional treatment. They
to debilitating symptoms caused by acid hypersecretion, show a 74% 5-year survival for resection, compared
serotonin syndrome, or carcinoid syndrome. In any case, with 30% for angiographic techniques. The Cochrane
the vast majority of patients with hepatic involvement will systematic reviews [19,20] did not identify benefit of liver
die of liver failure. resection, either in terms of complete resection (R0 or R1)
or cytoreduction (R2). Despite poor data, surgery is the
The management of patients with LM from GEP-NETs main treatment of choice because it is the only approach
remains a matter of debate. It involves several specialties: with intent to cure. Whether cytoreductive surgery (90%
surgery, medical oncology, radiotherapy, interventional resection) should be done when alternative nonsurgical
radiology, and nuclear oncology. Despite the great number treatment options are available is unknown. [8]
of options, there is no general consensus on the optimal
treatment sequence in metastatic patients. In case of bilateral liver disease, different surgical
approaches can be performed, including a 2-staged liver
In this review, we focus on the most recent findings about resection. Another technical option is occlusion of the
management of LM from GEP-NETs. portal vein in the tumor-bearing liver lobe, either by
radiological portal vein embolization than with surgical
SURGERY portal vein ligation before surgery. [21,22]

Patients with pancreatic NETs frequently present with LIVER TRANSPLANTATION (LT)
LM. Treatment for LM includes a wide panel of
[6]
treatments with the aim of achieving the best long-term In patients affected by NETs with unresectable LM, LT
result in overall survival (OS). NETs LM have been can be proposed due to the relatively low biological
classified morphologically as type I (single metastasis), aggressiveness and slow growth of the majority of low-
type II (isolated bulk metastasis accompanied by smaller grade NETs. In the last 15 years, short-term outcomes have
deposits), or type III (disseminated metastatic spread). improved because of better selection of transplantation
[7]
Surgery can play a role for type I LM, whereas medical candidates, refinement of surgical techniques, and the
treatment is always the treatment of choice for type III introduction of novel immunosuppressive regimens.
LM. [7,8] The management of type II LM should be carefully Moving from their former experience with hepatocellular
evaluated, tailoring treatment to each individual patient. In cancer, the Milan group observed improved outcomes of
metastatic pancreatic NETs (pNETs), 5-year survival rate LT for NETs LM patients, prospectively applying strict
is around 40-60%. [9-11] inclusion criteria: (1) well-differentiated NETs (Ki67 <
5%); (2) portosystemic tumor drainage; (3) patient age
Radical surgery, including resection of primary tumor < 55 years; (4) stable disease for at least 6 months; (5)
and LM, improves survival rate up to 46-86% at 5 years pretransplant R0 primary tumor resection; (6) hepatic
and 35-79% at 10 years. [6,12,13] Nevertheless, only 15-20% tumor involvement < 50% of total liver volume; and
of patients with LM are suitable for radical resection (7) absence of extrahepatic disease. The two largest
[23]
due to the multifocality of the lesions or the inability to retrospective multicenter studies have shown that in
preserve an adequate amount of parenchyma following the absence of poor prognostic factors, LT is associated
[14]
resection. Nowadays in referral centers, resections with satisfactory outcomes. In particular, a European
of up to 70% of total liver volume may be carried out multicenter study included a large retrospective cohort of
with relatively low mortality rate (0-5%) and acceptable 213 patients who underwent LT for NET LM from 1982
morbidity (30%). For surgery with curative intent, to 2009. At a median follow-up of 56 months, 17% of
[15]
the European Neuroendocrine Tumor Society (ENETS) patients died from early or late complications of LT, and
have proposed the following criteria: (1) resectable G1- the 5-year OS rate was 52% with a disease-specific survival
G2 liver disease with acceptable morbidity and less than rate of 30%. A study from the United States included
[24]
5% mortality; (2) absence of right heart insufficiency; (3) 85 patients who underwent LT from 1988 to 2012. One,
absence of unresectable lymph node and extra-abdominal three, and five-year survival rates were 83%, 60%, and
metastases; (4) absence of diffuse or unresectable 52%, respectively, and half of deaths were due to recurrent
[16]
peritoneal carcinomatosis. Neuroendocrine carcinomas disease. Synchronous major primary tumor resections
(NECs) that are G3 are usually not amenable to resection (i.e. pancreatoduodenectomy, small bowel resection with
owing to their aggressive biology, high recurrence rates, distal pancreatectomy, multivisceral transplant) appeared
and the consequent need to establish disease control. to contribute to worse outcomes. In other single-center
[25]
[17]
In the presence of unresectable metastatic disease, the series, the 5-year OS rates ranged from 33% to 90%, and
role of debulking surgery (R2) is still controversial. In disease-free survival rates ranged from 11% to 77% at 5
selected cases surgery may improve the quality of life years. [26-29] Despite these experiences, firm evidence on
or relief from symptoms when medical treatment has this issue is still scarce because only 0.3% and 0.2% of
failed. Several nonrandomized series have documented transplants are performed for such indications (data from
[18]
the benefits of either complete or cytoreductive surgical the European Liver Transplant Registry and the United
Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ August 17, 2016 ¦ 295