title: Pneumatosis intestinalis and bowel perforation associated with molecular targeted therapy: an emerging problem and the role of radiologists in its management.
abstract: OBJECTIVE
  The purpose of this article is to study the imaging features, management, and outcome of pneumatosis intestinalis and bowel perforation associated with molecular targeted therapy.
  
  
  METHODS
  In this retrospective study, 48 patients with cancer who developed pneumatosis or intestinal perforation were found by searching a radiology database. Of these patients, 24 patients (13 women and 11 men; mean age, 61 years; range, 39-83 years) receiving molecular targeted therapy without any confounding factors for pneumatosis or perforation were selected. Initial and follow-up CT scans were evaluated by two radiologists; medical records were reviewed to note clinical features, management, and outcome.
  
  
  RESULTS
  Seventeen (70.8%) patients were asymptomatic. Colorectal cancer (n = 10) and renal cell carcinoma (n = 5) were the most common malignancies; bevacizumab (n = 14) and sunitinib (n = 6) were the most common associated drugs. Imaging findings included intestinal perforation (20 sites in 18 patients), pneumatosis (n = 10), ascites (n = 8), pneumoperitoneum (n = 7), fistula formation (n = 7), and fluid collections (six collections in five patients). Fifteen (62.5%) patients were treated conservatively, seven (29.2%) underwent surgery, and two (8.3%) underwent percutaneous drainage. Molecular targeted therapy was discontinued in 22 of 24 patients; findings resolved in 19 patients, remained stable in one, and worsened in one. One patient died after surgery. In both instances where the drug was continued, the abnormality worsened. Findings recurred in three of four patients in whom the drug was restarted after initial resolution.
  
  
  CONCLUSIONS
  Radiologists should be aware of intestinal complications associated with molecular targeted therapy, including pneumatosis, bowel perforation, and fistula formation. Most patients can be treated conservatively after discontinuation of molecular targeted therapy. Continuing or restarting molecular targeted therapy can cause worsening or recurrent pneumatosis or perforation.
authors.affiliation: Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA. ashinagare@partners.org
authors.forename: Atul B
authors.initials: AB
authors.lastname: Shinagare
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Howard
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Krajewski
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Zukotynski
authors.forename: Jyothi P
authors.initials: JP
authors.lastname: Jagannathan
authors.forename: Nikhil H
authors.initials: NH
authors.lastname: Ramaiya
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D003287:Contrast Media; D005260:Female; D006801:Humans; D007416:Intestinal Perforation / Q000139:chemically induced* / Q000000981:diagnostic imaging* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000009:adverse effects*; D009369:Neoplasms / Q000188:drug therapy*; D011006:Pneumatosis Cystoides Intestinalis / Q000139:chemically induced* / Q000000981:diagnostic imaging* / Q000628:therapy; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D003287:Contrast Media