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

Author:

Brighi Nicole12,Panzuto Francesco3,Modica Roberta4,Gelsomino Fabio5,Albertelli Manuela6,Pusceddu Sara7,Massironi Sara8,Lamberti Giuseppe19,Rinzivillo Maria3,Faggiano Antongiulio10,Spallanzani Andrea5,Ferone Diego6,Prinzi Natalie7,Rossi Roberta Elisa8,Annibale Bruno3,Colao Anna Maria4,Campana Davide111

Affiliation:

1. NET Team Bologna ENETS Center of Excellence, S. Orsola-Malpighi University Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy

2. Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

3. Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, Rome, Italy

4. Clinical Medicine and Surgery Department - Federico II University, Naples, Italy

5. Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy

6. Endocrinology Department (DiMi), San Martino University Hospital, Genova, Italy

7. Department of Medical Oncology, Fondazione IRCCS Istituto Tumori Milano, ENETS Center of Excellence, Milan, Italy

8. Gastroenterology and Endoscopy Department, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy

9. Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, Bologna, Italy

10. Department of Experimental Medicine, Sapienza University, Rome, Italy

11. Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, Bologna, Italy

Abstract

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.

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

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