Biliary Stone Disease in Patients with Neuroendocrine Tumors Treated with Somatostatin Analogs: A Multicenter Study

Abstract

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.

EUS-guided gallbladder drainage in high-risk surgical patients with acute cholecystitis—procedure outcomes and evaluation of mortality predictors

“…Most reported complications are acute cholecystitis (AC), pancreatitis, jaundice, and cholangitis, with a cumulative incidence of 0.1–4% per year. Risk factors for biliary stone disease and its complications are female gender, age, pregnancy and puerperium, obesity, comorbidities (such as liver cirrhosis, Crohn's disease or hemolytic anemia) and concomitant medications (such as hormone therapy, parenteral nutrition or somatostatin analogs) [ 1 , 3 , 4 ] .…”

Octreotide long-acting release (LAR) in combination with other therapies for treatment of neuroendocrine neoplasia: a systematic review

“…Among these, gallstones formation is considered as the most serious one. In a recent multi-centre large study performed on 478 NEN patients receiving somatostatin analogues (octreotide in 70% of them), an incidence for developing gallstones of 27% was reported, and biliary complications (biliary colic, acute acute cholecystitis, cholangitis, biliary pancreatitis, or obstructive jaundice) occurred in 7.5% of patients (36). In that study, previous surgery for primary small-bowel NEN was a significant risk factor for developing gallstones, thus defining a specific subgroup of patients at high-risk who should monitor during therapy for this possible side effect, and supporting the recommendation to perform cholecystectomy in those NEN patients who are candidate to surgery for primary small bowel resection.…”

Prophylactic cholecystectomy is not mandatory in patients candidate to the resection for small intestine neuroendocrine neoplasms: a propensity score-matched and cost-minimization analysis

“…PaƟents excluded (N=50) N=34 no resecƟon of primary tumor N=16 previous cholecystectomy Fig. 1 Flow-diagram of the selection process (− 23 to 3). The re-hospitalization rate for BSD was lower PC arm (8.9% vs. 0%; P = 0.026).…”

“…Biliary stone disease (BSD) is common in patients treated with somatostatin analogues (SSA) for Small-intestine neuroendocrine neoplasms (Si-NENs) [1][2][3][4]. For this reason, a recent multicentric cohort study suggested the prophylactic cholecystectomy in all patients' candidates to the resection of the primary tumors.…”