[Successful treatment of secondary aortoesophageal fistula after thoracic endovascular aortic repair]. / Erfolgreiche Therapie einer sekundären aortoösophagealen Fistel nach Implantation eines endovaskulären Aortenstentgrafts.

HISTORY AND CLINICAL SYMPTOMS: A 58-year-old man was admitted to our hospital with acute chest pain and subfebrile temperatures. Two years ago, endovascular aortic stent-graft placement had been performed for acute type B aortic dissection complicated by malperfusion syndrome. DIAGNOSTIC ASSESSMENT: CT angiography showed a discrete soft-tissue attenuation mass between the aorta and esophagus. The patient developed progressive swallow disorder and esophago-gastro-duodenoscopy demonstrated deep esophageal ulcerations at the level of the implanted aortic stent-graft. Intravenous treatment with broad spectrum antibiotics was started. The FDG-PET/CT scan showed increased FDG uptake and air entrapment in the affected region establishing the diagnosis of aortoesophageal fistula formation. THERAPY AND OUTCOME: Given the generally poor condition of the patient and the high risk of any aggressive surgical intervention, a new limited surgical approach was chosen consisting of open transthoracic esophageal resection, blind closure of the stomach and cervical esophagostomy. A percutaneous endoscopic gastrostomy tube was placed. After three months, esophageal continuity was restored by retrosternal colon interposition. The presented therapeutic management resulted in a full recovery of the patient. CONCLUSION: Aortoesophageal fistula is a rare complication of thoracic aortic stent-graft placement. Patient may present with unspecific symptoms such as fever and rised inflammatory markers, but may also present with massive upper gastrointestinal bleeding. The herein presented limited therapy with esophageal resection represents a promising to the otherwise difficult therapy of aortoesophageal fistula.

Phase II trial of mapatumumab, a fully human agonistic monoclonal antibody that targets and activates the tumour necrosis factor apoptosis-inducing ligand receptor-1 (TRAIL-R1), in patients with refractory colorectal cancer.

BACKGROUND: Recombinant tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) induces tumour-selective apoptosis in various pre-clinical models by binding its specific receptors expressed on cancer cells. Mapatumumab is a fully human monoclonal antibody that is agonistic to the TRAIL Receptor 1 (TRAIL-R1). METHODS: This phase II multicentre study was designed to evaluate the efficacy and safety of mapatumumab in patients with colorectal cancer (CRC) who had failed to respond to, were intolerant to, or not candidates for fluoropyrimidine, oxaliplatin, and irinotecan-based regimens. All patients received two loading doses of mapatumumab (20 mg kg(-1) every 14 days), followed by maintenance therapy with 10 mg kg(-1) infused every 14 days. RESULTS: A total of 38 patients, who had progressive disease after a median of three earlier chemotherapy lines, were enrolled. No response according to the Response Evaluation Criteria in Solid Tumors was observed. A total of 12 patients (32%) achieved stable disease for a median of 2.6 months. The median progression-free survival was 1.2 months. The most common adverse events reported, regardless of relationship, were fatigue, nausea, anorexia, and abdominal pain. Plasma mapatumumab concentrations were within the range of exposures predicted by the results of phase I studies of mapatumumab. CONCLUSION: No clinical activity of single-agent mapatumumab was observed in patients with advanced refractory CRC. However, on the basis of its favourable safety profile and pre-clinical evidence of potential synergy in combination with agents commonly used in the treatment of colorectal cancer, further evaluation of mapatumumab in combination with chemotherapy is warranted.