Biliary Stone Disease in Patients with Neuroendocrine Tumors Treated with Somatostatin Analogs: A Multicenter Study.
Adverse events
Gallstones
Neuroendocrine neoplasms
Prophylactic cholecystectomy
Ursodeoxycholic acid
Journal
The oncologist
ISSN: 1549-490X
Titre abrégé: Oncologist
Pays: England
ID NLM: 9607837
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
27
05
2019
accepted:
03
10
2019
entrez:
13
3
2020
pubmed:
13
3
2020
medline:
22
6
2021
Statut:
ppublish
Résumé
Somatostatin analogs (SSAs) are the mainstay of neuroendocrine tumor (NET) treatment. Biliary stone disease is reported as a common side effect of SSAs, with a frequency ranging from 10% to 63%. Studies on SSA-treated patients for acromegaly report an increased incidence of biliary stone disease compared with the general population, whereas data on patients with NETs are few. Guidelines are based on weak evidence, thus resulting in conflicting recommendations. The aim of the study is to evaluate biliary stone disease incidence, complications, and risk factors in a large population of SSA-treated patients with NETs. A retrospective analysis of a prospectively collected database was performed. Patients with a diagnosis of NET in seven dedicated centers from 1995 to 2017 were included at the time of SSA start. A total of 754 SSA-treated patients were evaluated. Patients with history of cholecystectomy or with known biliary stone disease were excluded; 478 patients were included. Among them, 118 patients (24.7%) received prophylactic ursodeoxycholic acid (UDCA). During the study period, 129 patients (27.0%) developed biliary stone disease; of them, 36 (27.9%) developed biliary complications. On multivariate analysis, primary gastrointestinal (GI)-NET (hazard ratio [HR] 1.76) and related surgery (HR 1.58) were independent risk factors for biliary stone disease. We report a high incidence of biliary stone disease particularly in GI-NET or GI surgery. UDCA prophylaxis does not seem to have a protective role. Our data suggest that all patients with primary GI-NET or undergoing abdominal surgery should be considered for prophylactic cholecystectomy; no conclusion could be drawn on the indication of prophylactic cholecystectomy in patients with primary pancreatic or thoracic NET for whom abdominal surgery is not planned. The results of this study confirm an increased rate of gallstones development and related complications in patients with neuroendocrine tumors (NETs) treated with somatostatin analogs (SSAs). NETs of the gastrointestinal (GI) tract and related surgery are independent risk factors for biliary stone disease development. Therefore, all patients with primary GI-NET or undergoing abdominal surgery should be considered for prophylactic cholecystectomy. Data on other subgroups are not exhaustive, and management also evaluating additional clinical features (life expectancy, surgical and anesthesiological risks) should be considered. Prophylactic treatment with ursodeoxycholic acid does not seem to be a protective factor for SSA-related biliary stone disease.
Sections du résumé
BACKGROUND
Somatostatin analogs (SSAs) are the mainstay of neuroendocrine tumor (NET) treatment. Biliary stone disease is reported as a common side effect of SSAs, with a frequency ranging from 10% to 63%. Studies on SSA-treated patients for acromegaly report an increased incidence of biliary stone disease compared with the general population, whereas data on patients with NETs are few. Guidelines are based on weak evidence, thus resulting in conflicting recommendations. The aim of the study is to evaluate biliary stone disease incidence, complications, and risk factors in a large population of SSA-treated patients with NETs.
MATERIALS AND METHODS
A retrospective analysis of a prospectively collected database was performed. Patients with a diagnosis of NET in seven dedicated centers from 1995 to 2017 were included at the time of SSA start.
RESULTS
A total of 754 SSA-treated patients were evaluated. Patients with history of cholecystectomy or with known biliary stone disease were excluded; 478 patients were included. Among them, 118 patients (24.7%) received prophylactic ursodeoxycholic acid (UDCA). During the study period, 129 patients (27.0%) developed biliary stone disease; of them, 36 (27.9%) developed biliary complications. On multivariate analysis, primary gastrointestinal (GI)-NET (hazard ratio [HR] 1.76) and related surgery (HR 1.58) were independent risk factors for biliary stone disease.
CONCLUSION
We report a high incidence of biliary stone disease particularly in GI-NET or GI surgery. UDCA prophylaxis does not seem to have a protective role. Our data suggest that all patients with primary GI-NET or undergoing abdominal surgery should be considered for prophylactic cholecystectomy; no conclusion could be drawn on the indication of prophylactic cholecystectomy in patients with primary pancreatic or thoracic NET for whom abdominal surgery is not planned.
IMPLICATIONS FOR PRACTICE
The results of this study confirm an increased rate of gallstones development and related complications in patients with neuroendocrine tumors (NETs) treated with somatostatin analogs (SSAs). NETs of the gastrointestinal (GI) tract and related surgery are independent risk factors for biliary stone disease development. Therefore, all patients with primary GI-NET or undergoing abdominal surgery should be considered for prophylactic cholecystectomy. Data on other subgroups are not exhaustive, and management also evaluating additional clinical features (life expectancy, surgical and anesthesiological risks) should be considered. Prophylactic treatment with ursodeoxycholic acid does not seem to be a protective factor for SSA-related biliary stone disease.
Identifiants
pubmed: 32162819
doi: 10.1634/theoncologist.2019-0403
pmc: PMC7066710
doi:
Substances chimiques
Somatostatin
51110-01-1
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
259-265Informations de copyright
© AlphaMed Press 2019.
Références
Pancreas. 2017 Jul;46(6):715-731
pubmed: 28609357
Dig Liver Dis. 2019 May;51(5):689-694
pubmed: 30314949
Expert Opin Drug Saf. 2015 Aug;14(8):1213-26
pubmed: 26184380
Neuroendocrinology. 2009;90(2):227-33
pubmed: 19713715
World J Surg. 2010 Jun;34(6):1361-7
pubmed: 20130865
Br Med J. 1969 Aug 30;3(5669):494-6
pubmed: 5805332
Gut Liver. 2012 Apr;6(2):172-87
pubmed: 22570746
Gut. 2005 May;54(5):575-8
pubmed: 15831896
J Clin Endocrinol Metab. 2009 May;94(5):1500-8
pubmed: 19208728
Surgery. 1988 Jul;104(1):18-25
pubmed: 3291168
Hepatology. 1995 Mar;21(3):655-60
pubmed: 7875663
J Clin Oncol. 2009 Oct 1;27(28):4656-63
pubmed: 19704057
Neuroendocrinology. 2017 Mar 29;105(3):266-280
pubmed: 28351033
Surgery. 1984 Aug;96(2):154-62
pubmed: 6463856
Clin Endocrinol (Oxf). 2007 May;66(5):723-6
pubmed: 17388793
Endocrine. 2003 Apr;20(3):299-305
pubmed: 12721511
J Hepatol. 2016 Jul;65(1):146-181
pubmed: 27085810
Gut. 1972 Jun;13(6):415-20
pubmed: 5040830
Neuroendocrinology. 2016;103(2):172-85
pubmed: 26731013
Cancer. 1997 Feb 15;79(4):830-4
pubmed: 9024721
Gastroenterology. 2009 Apr;136(4):1134-44
pubmed: 19245868
Endocrine. 2017 Sep;57(3):366-375
pubmed: 28726183
Lancet. 2006 Jul 15;368(9531):230-9
pubmed: 16844493
N Engl J Med. 2014 Jul 17;371(3):224-33
pubmed: 25014687
J Endocrinol Invest. 2008 Aug;31(8):704-10
pubmed: 18852531