GIST

An 82-year-old woman presented with acute abdominal pain, vomiting, and fever (38.8°C). One year earlier, she had an advanced gastrointestinal stromal tumor (GIST) with multiple intestinal and endoperitoneal localizations, not suitable for operation. Since then, she was treated with imatinib-mesylate, 400 mg once daily. On examination, her abdomen was diffusely tender with bulky elastic masses palpable in the middle and lower abdomen. Laboratory tests revealed moderate anemia (Hb 9.8 g/dL) with a white blood cell count of 16,200. Plain supine x-rays of the abdomen apparently showed some fluid levels with a marked dilatation of a bowel loop, simulating a closed-loop mechanical obstruction (A) CT scan showed neither bowel distention nor fluid levels, but there were contrast leaks from the small bowel communicating with large cavities (B, arrows).

Urgent surgery was warranted. Multiple large soft masses, covered by inflamed serosa and containing gas and fluid, were found adhering to the small-bowel wall at laparotomy (C, arrows). Small, solid, nodular lesions were diffusely disseminated over the bowel wall and onto the peritoneum. An extended small-bowel resection with en bloc excision of the lesions and entero-entero anastomosis were carried out. Macroscopic examination of the specimen showed large cavities, contained by the peritoneal serosa with a thin layer of necrotic solid tissue lining the inner surface, communicating with the gut lumen through multiple perforations of the small-bowel wall (D, arrow). Pus, colliquative necrotic tissue, and gas were found in each cavity. This suggested that small-bowel perforations had developed as the result of GIST necrosis induced by imatinib-mesylate. This diagnosis was supported by the histologic examination that, despite the extensive necrotic process, revealed the persistence of GIST (epithelioid cells variant) in the inner surface of the wall of the cavities. The course was uneventful and the patient was discharged 7 days after surgery.

Imatinib-mesylate, an inhibitor of the receptor tyrosine kinase (KIT), harbored in the GIST cells, has become the standard treatment for unresectable or recurrent GISTs not amenable to surgery. Exposure of GIST cells to imatinib blocks the kinase activity of KIT, arrests cell proliferation, and causes apoptotic cell death. Although treatment is generally well tolerated, adverse effects have been reported. These include periorbital or peripheral edema, fatigue, skin rash, vomiting, diarrhea, and occasionally myelosuppression.¹ Because of the massive cytolithic effect of the drug, when treatment is given for GISTs located in the wall of the gastrointestinal tract, gastrointestinal hemorrhage and, less commonly, perforation to the peritoneal cavity have been reported as the result of massive necrosis of the tumor.^{[1] and [2]}

References

1. G.D. Demetri, M. von Meheren and C.D. Blanke et al., Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors, N Engl J Med 347 (2002), pp. 472–480.

2. T. Van Oosterom, I. Judson and J. Verweij et al., Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study, Lancet 358 (2001), pp. 1421–1423.

Journal of the American College of Surgeons
Volume 206, Issue 2, February 2008, Pages 386-387
Multiple Bowel Perforations Complicating Imatinib Treatment for Advanced Gastrointestinal Stromal Tumor
Massimo Chiarugi MD, Christian Galatioto MD, Piero V. Lippolis MD and Massimo Seccia MD