Lung Cancer: Global Case Report Poster - Lung Cancer |

Esophageal Ulcer and Fistula in a Patient With Advanced Adenocarcinoma of Lung Received Bevacizumab FREE TO VIEW

Ching-Min Tseng, MD; Mei-Yin Chen, MD; Tao Chi-Wei, MD
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Cheng Hsin General Hospital, Taipei, Taiwan

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;150(4_S):692A. doi:10.1016/j.chest.2016.08.787
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SESSION TITLE: Global Case Report Poster - Lung Cancer

SESSION TYPE: Global Case Report Poster

PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM

INTRODUCTION: We reported a lung cancer patient who reveived bevaizumab suffered from esophageal ulcer and progressed developing an esophageal fistula.

CASE PRESENTATION: A 48 year-old male, who had hypertension and hyperlipidemia, developed the adenocarcinoma of lung with mediastinal lymph adenopathy. Initially he received right upper lobe lobectomy on September, 2010. The pathological staging was pT1bN2M0, stage IIIA. Then he started on adjuvant chemotherapy consisting of docetaxel and cisplatin for 4 cycles. Chest computed tomography (CT) for restaging showed stable disease. However, he presented with productive cough, chest pain, dyspnea and left leg painful swelling 8 months later. Chest CT and limb sonography revealed extensive thrombosis in pulmonary artery, left femoral, bilateral popliteal, peroneal, posterior tibial and lower calf veins. We gave anti-coagulant agent with warfarin and chemotherapy consisted of pemetrexed, cisplatin and bevacizumab for deep vein thrombosis with pulmonary embolism, suspect malignancy related. After 4 cycles, he complained progressive painful swallowing and severe chest pain and tarry stool after the 5th cycle. The endoscope found a large, longitudinal ulcer with irregular margin and scattered bleeding spots in middle third of esophagus.(Figure 1) It supposed that these lesions were related to bevacizumab treatment, since there were no known factors associated with the esophageal ulcer. He was started with intravascular esomeprazole. The pathology report showed no evidence of malignancy. Unfortunately, his symptoms progressed and fever flared up. The result of esophagography showed a blind-ended fistula tract in the right posterior wall of middle third esophagus.(Figure 2) It showed no communication with the trachea or pericardium recess. He was fasted and started on empiric antibiotics piperacilline and tazobactem administration due to sepsis. Afterward he received feeding jejunostomy to bypass the esophageal fistula. He recovered and improved 4 weeks later after supportive treatment and jejunostomy

DISCUSSION: To our knowledge, an esophageal ulcer and following to become an esophageal fistula in lung cancer patient received bevacizumab had not been reported before. There are no known risk factors associated with esophageal ulcer, such as previous radiation therapy in esophageal area, tumor metastasis, gastric ulcer, alcohol consumption or so on in our case. Some reports reported the association between GI malignancy and esophageal ulcer, but not lung cancer. Judith et al. reported a 60 year-old woman with metastatic colon cancer, who received bevacizumab and chemotherapy, developed a deep esophageal ulcer. They suspected that it was an precursor lesion to GI perforation. They supposed that bevacizumab with chemotherapy causes esophageal mucosal inflammation resulting in mucosa breaks and ulceration. In our case, the progression of the esophageal ulcer was confirmed by endoscopy and chest CT. The association between bevacizumab and esophageal ulcer, in the presented case, is highly correlated. However, the underlying mechanism is still not clear. The process of GI ulcer healing and vascular remodeling and mucosa regeneration within ulcer scar is controlled by cytokines and growth factors, including VEGF. It demonstrated the impairment of wound healing due to anti-angiogenic agents in preclinical study. Moreover, inhibition of VEGF signaling for 2 - 3 weeks causes regression of capillaries of intestinal villi in normal adult mice. This vascular regression could contribute to poor ulcer healing in the presence of concurrent inflammation or other pathological conditions.

CONCLUSIONS: Our report shows the importance when gastrointestinal symptoms occur, such as heart burning sensation or anterior chest pain, in patients receiving bevacizumab and the necessity of performing endoscopy to find out an esophageal ulcer or impeding fistula or perforation. More importantly, bevacizumab needs to be discontinued in patients with any current gastrointestinal ulcer.

Reference #1: Meza-Junco J, Wong C, Fields A, et al. Esophageal ulcer in a patient who received bevacizumab. Invest New Drugs 2010; 28:98-101

Reference #2: Tarnawski AS. Cellular and molecular mechanisms of gastrointestinal ulcer healing. Dig Dis Sci 2005; 50 Suppl 1:S24-33

Reference #3: Kamba T, Tam BY, Hashizume H, et al. VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am J Physiol Heart Circ Physiol 2006; 290:H560-576

DISCLOSURE: The following authors have nothing to disclose: Ching-Min Tseng, Mei-Yin Chen, Tao Chi-Wei

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