Multiple ulcers and perforation of small intestine with everolimus use in a patient with rectal neuroendocrine tumor: A case report

Abstract

Introduction: Everolimus is an orally administered inhibitor of the mammalian target of rapamycin, which is a serine/threonine protein kinase. It is used for the treatment of pancreatic and gastrointestinal neuroendocrine tumors (NETs). Gastrointestinal perforations in patients being treated with everolimus is extremely rare, with only five reported cases.

Case presentation: A 62-year-old woman, who had previously undergone surgery for rectal NET, presented to our hospital with fever and abdominal pain. Abdominal computed tomography revealed perforation of the lower gastrointestinal tract, and we performed emergency surgery. There were multiple ulcers 150 cm distal from the ligament of Treitz to the terminal ileum; an ulcer at the anastomosis of stoma closure, 35 cm from the terminal ileum, was transmural. We subsequently performed a partial intestinal resection.

Clinical discussion: The diagnosis of NETs is increasing worldwide, owing to recent improvements in diagnostic techniques. Although the use of everolimus has increased, gastrointestinal ulcer perforations caused by everolimus treatment have rarely been reported. The mechanism may be due to the inhibition of angiogenesis by mTOR inhibitors, as well as vascular endothelial growth factor inhibitors. In this case, It was considered that everolimus use most likely caused perforation.

Conclusion: It is necessary to recognize that drug-induced gastrointestinal ulcers and perforations may occur with the use of mTOR inhibitors, and careful follow-up should be performed during administration.

Keywords: Everolimus; Multiple ulcers; Perforation.

Fig. 1

Abdominal computed tomography (CT) revealing free air on the right side of the anastomosis of the ileostomy reversal in the pelvis (arrow).

Fig. 2

Intraoperative findings showing white and round ulcers on the serosal surface of the 130-cm small intestine section, starting 150 cm anorectal from the Treitz ligament to the end of the ileum (A, arrowhead). The largest ulceration was found at the anastomosis of the ileostomy reversal 35 cm from the Bauhin valve. The intestinal wall at the site appears to thin, and a 4 mm-sized perforation is observed (B, arrowhead). Abscesses are found around the perforation.

Fig. 3

Macroscopic evaluation of the resected specimen. Approximately 20 small ulcers with well-defined rounded borders are observed contralaterally to the mesentery in a 117-cm section of the resected intestine (A, arrowheads). The largest ulcer, 35 × 15 mm, is located at the anastomosis of the ileostomy closure (A, arrow), and a 4 mm perforation is found (B, arrow).

Fig. 4

Histopathological findings of the specimen. Multiple steep and deep ulcers were noted, some of which formed transmural necrosis. (A). Nonspecific acute inflammatory findings, such as intense neutrophilic infiltration (B) and edema are seen around the ulcer area. Scale bar = 2.5 mm (A) or 100 μm (B).