Incident Gallstones During Somatostatin Analog Treatment are Associated with Acute Biliary Complications Especially After Discontinuation

Abstract

Introduction Gallstones are a known adverse effect of somatostatin analogs, but the exact incidence and clinical implications are unknown.Objectives The aim of this study was to investigate the incidence of gallstones on imaging and related complications in unbiased trial data. Methods Data from the DIPAK 1 trial, in which 305 polycystic kidney disease patients were randomized to standard of care (SoC) or lanreotide for 120 weeks, were used. Magnetic resonance imaging (MRI) was performed at baseline and end of treatment and was assessed for the presence, number, and size of gallstones. For all patients who had gallstones at the end of the trial, we obtained follow-up after the trial. Results Of 249 patients with data available, 11 patients randomized to lanreotide and four randomized to SoC had gallstones at baseline. During the study, new gallstones were formed in 19/124 patients using lanreotide (15%) and 1/125 patients receiving SoC (1%). The odds ratio for gallstone formation with lanreotide use was 25.9 (95% confidence interval 3.37-198.8; p < 0.001). Gallstones during lanreotide treatment were multiple (> 20 stones in 69% of patients) and small (≤ 3 mm in 63% of patients). Of the 19 patients with incident gallstones during lanreotide treatment, 9 experienced gallstone-associated complications, 8 of whom experienced gallstone-associated complications after discontinuation of treatment (median time after discontinuation 2.5 years). In patients with gallstones at baseline and in patients receiving SoC, no complications occurred. Conclusions Treatment with a somatostatin analog leads to the formation of multiple, small gallstones that are associated with severe complications, especially after discontinuation of therapy. Clinical Trial Registry Website and Trial Number ClinicalTrials.gov (https:// clini caltr ials. gov); NCT01616927.A list of DIPAK consortium members is given in the Acknowledgments section.

EASL Clinical Practice Guidelines on the management of cystic liver diseases

“…Other infrequent side effects of somatostatin analogues include cholelithiasis, hypo-and hyperglycaemia and alopecia. 190 Hyperglycaemia and diabetes are most frequently observed with pasireotide. 182 Pre-clinical data and observational studies in patients with ADPKD, who received a kidney transplantation and were treated with sirolimus, suggested that mammalian target of rapamycin inhibitors had a positive effect on liver volume.…”

Biliary Tract Disorders and Associated Acute Complications in Patients With Acromegaly: A Single-Center Study

“…In our series, acute biliary adverse effects occurred in 57% of cases with biliary lithiasis (4/7). As shown in a recent controlled randomized study, lanreotide treatment was associated with serious ABC [ 11 ]. This study reported one case of acute pancreatitis that occurred during lanreotide treatment complicated by gastro pancreatic fistula.…”

“…However, a higher prevalence of gallbladder lithiasis is also reported in patients with acromegaly compared to the general population [ 10 ]. This condition can lead to serious acute biliary complications (ABCs) such as pancreatitis, cholecystitis, or lithiasis angiocholitis, especially after medical treatment discontinuation by somatostatin receptor ligands (SRLs) [ 11 ].…”

Chinese Medical Association consensus for standardized diagnosis and treatment of pancreatic neuroendocrine neoplasms

“…Concomitant prophylactic cholecystectomy is recommended for patients expected to receive long-term SSAs postoperatively to reduce the risk of developing SSAinduced biliary symptoms and gallstones. [42,43] Systemic therapy…”