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      Pneumatosis intestinalis after gefitinib therapy for pulmonary adenocarcinoma: a case report

      case-report

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          Abstract

          Background

          Pneumatosis intestinalis (PI) is defined as the presence of gas in the bowel wall and is a relatively rare finding. PI has been associated with various pathological conditions and medications. Although several chemotherapeutic agents and molecular targeted therapy agents are reported to be associated with PI, there have been few reports describing the association between the anti-epidermal growth factor receptor agent gefitinib, a tyrosine kinase inhibitor (TKI), and PI. The present report describes a case of PI secondary to gefitinib therapy.

          Case presentation

          An 80-year-old woman who had been diagnosed with recurrent lung adenocarcinoma presented with remarkable appetite loss, abdominal distension, and constipation after starting gefitinib therapy. A computed tomography (CT) scan of the abdomen revealed PI extending from the small intestine to the rectum. The patient was managed conservatively, and gefitinib therapy was discontinued. Subsequently, the symptoms improved and a follow-up abdominal X-ray showed a reduction in intramural air. After gefitinib was restarted, PI occurred three more times.

          Conclusions

          Although PI is extremely rare, physicians should be aware of the risk of PI in patients undergoing gefitinib therapy.

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          Most cited references15

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          Pneumatosis intestinalis in adults: management, surgical indications, and risk factors for mortality.

          Pneumatosis intestinalis (PI) is an unusual finding that can exist in a benign setting but can indicate ischemic bowel and the need for surgical intervention. We present a series of cases of PI in adults to illustrate factors associated with death and surgical intervention. We reviewed the radiology database of the Mount Sinai Medical Center for cases of PI between 1996-2006 in adult patients. Chi-square and multivariable logistic regression analyses were used to identify factors significant for surgery and death. Forty patients developed PI over a 10-year span. The overall in-hospital mortality rate was 20%, and the surgical rate was 35%. Factors independently associated with surgical management on multivariable analysis were age >or= 60 years (p = 0.03), the presence of emesis (p = 0.01), and a WBC > 12 c/mm3 (p = 0.03). Pre-existing sepsis was independently associated with mortality (p = 0.03) while controlling for surgery. Patients with the concomitant presence of PI, a WBC > 12 c/mm3, and/or emesis in the >60-year-old age group were most likely to have surgical intervention, whereas PI patients with sepsis had the highest risk for death. A management algorithm is proposed, but further research will be needed to determine which patients with PI may benefit most from surgery.
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            Pneumatosis intestinalis and bowel perforation associated with molecular targeted therapy: an emerging problem and the role of radiologists in its management.

            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.
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              Antiangiogenic tyrosine kinase inhibition related gastrointestinal perforations: a case report and literature review

              Anti-VEGF (vascular endothelial growth factor) therapy with the monoclonal antibody bevacizumab can cause gastrointestinal (GI) perforations. In recent years it became apparent that GI perforations also occur during treatment with antiangiogenic tyrosine kinase inhibitors (TKIs). It is of clinical importance to consider (vague) abdominal complaints during antiangiogenic treatment as a sign of a GI perforation. To illustrate this serious complication, we report four cases of antiangiogenic treatment related GI perforations. In three cases this was due to antiangiogenic TKI treatment. Reported risk factors of GI perforations due to bevacizumab include the presence of a primary tumor in situ and recent history of endoscopy or abdominal radiotherapy. Pathology assessments of surgical removal of the perforated intestinal part reveal that perforations are predominantly seen at the tumor or anastomotic site, in case of carcinomatosis or diverticulitis or when GI obstruction or an intra-abdominal abcess is present. Whether the same risk factors may be involved in antiangiogenic TKI related GI perforations is unknown. The underlying mechanisms responsible for GI perforation during antiangiogenic treatment is unknown, but disturbance of host cell homeostasis of immune cells as well as platelet-endothelial cell interactions may play an important role. In conclusion, while clinical awareness that antiangiogenic treatment can cause GI perforations is critical for current medical practice, it is also very important to get more insight in its underlying mechanisms so that this life-threatening complication may be prevented in the near future.
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                Author and article information

                Contributors
                +81-86-462-1124 , amaeda@med.kawasaki-m.ac.jp
                mnakata@med.kawasaki-m.ac.jp
                kshimizu@med.kawasaki-m.ac.jp
                tyukawa@med.kawasaki-m.ac.jp
                s.saisho@med.kawasaki-m.ac.jp
                riki0716okita@yahoo.co.jp
                Journal
                World J Surg Oncol
                World J Surg Oncol
                World Journal of Surgical Oncology
                BioMed Central (London )
                1477-7819
                29 June 2016
                29 June 2016
                2016
                : 14
                : 175
                Affiliations
                [1 ]Department of General Thoracic Surgery, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192 Japan
                [2 ]Department of General Surgery, Kawasaki Medical School, Okayama, Okayama 700-8505 Japan
                Article
                926
                10.1186/s12957-016-0926-1
                4974742
                27495256
                3d529e84-d589-4a9a-9217-ea073ef27b8e
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 18 August 2015
                : 15 June 2016
                Categories
                Case Report
                Custom metadata
                © The Author(s) 2016

                Surgery
                Surgery

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