malignant tracheoesophageal fistula ( tef ) is a serious complication of thoracic malignant diseases and is more common in esophageal cancer than in lung cancer .
tef sometimes results in aspiration pneumonia , sepsis , and malnutrition associated with trouble in eating . without proper and prompt treatment , life expectancy is estimated at about 6 weeks .
stent intubation into the trachea and/or esophagus is a reliable treatment leading to improved quality of life .
surgical bypass with gastrostomy is another option , though it might be too invasive in some patients with advanced cancer .
chemoradiotherapy ( crt ) is a controversial option , as it has the potential to induce or worsen tef as a side effect , especially in lung cancer . in esophageal cancer ,
meanwhile , some reports have described closure of tefs after crt [ 3 , 4 ] .
our group experienced a rare case of tef that closed after crt in a patient with poorly differentiated lung carcinoma .
crt seems to have good potential as a palliative treatment for tef in lung cancer , as well .
a 45-year - old man with complaints of cough , dyspnea , weight loss , and difficulty in swallowing was referred to our hospital .
the symptoms had emerged 3 months earlier and he had been completely unable to eat for several days before his admission . on physical examination , a solid mass at the right neck was palpable , the right palpebral fissure was narrowed , and inspiratory stridor was auscultated .
an enhanced chest ct scan revealed a small mass in the superior sulcus invading into the mediastinum ( fig .
1 ) . the sagittal view revealed a cavity within the mass and compression of the stenotic trachea by the mass , but there was no apparent communication between the esophagus and trachea .
laboratory data indicated mild normocytic anemia and elevated c - reactive protein . among tumor markers ,
an elevation of cytokeratin 19 fragment and neuron - specific enolase ( table 1 ) was noted .
the patient was diagnosed with poorly differentiated lung carcinoma by percutaneous needle biopsy ( fig .
the patient 's respiratory condition was too fragile to permit endoscopic examination at this point .
radiation therapy was commenced immediately , before confirmation of the pathological diagnosis , for fear of sudden asphyxiation by the occupying mass .
chemotherapy with cisplatin and docetaxel was added , but was discontinued when the patient developed febrile neutropenia requiring granulocyte - stimulating factor and antibiotics for several days .
when his respiratory condition improved enough to permit bronchoscopy and upper gastrointestinal endoscopy , these modalities revealed a hole with ulcerative edges in the trachea and upper esophagus ( fig .
we surmised that palliative treatment would prevent complications of tef , such as aspiration pneumonia .
as the fistula was located in the upper esophagus ( 20 cm below the incisive papilla ) , we anticipated that intubation of an expandable metallic stent to the esophagus would be deeply uncomfortable and intolerable . with airway stenting , an accidental insertion of the stent into the cavity inside the tumor was a concern .
as the initial effect of radiation had improved the compression of the tumor to the trachea , the therapy was continued up to a total dose of 61 gy .
about 2 weeks after the radiation therapy was completed , the patient 's severe cough subsided for several days .
encouraged by the improvement , he attempted to eat sweets and managed to do so without coughing .
a bronchoscopy a few days later revealed only one slit on the trachea , and upper gastrointestinal endoscopy showed a covering of normal epithelial tissue over the fistula ( fig .
3 ) . in the ensuing weeks he fully regained the ability to eat orally ,
traumas and malignancy , conditions that may be associated with side effects of crt , are common causes of acquired tef . as treatment , curative resection followed by repair of the trachea and/or esophagus
surgery is usually considered inappropriate in malignant tef , as the patients tend to be in a bad condition and near the end of their lives .
palliative therapy should be the primary choice in terms of quality of life , and the therapeutic goals should be to restore the patency of the trachea by reducing the extrinsic compression and to enable these patients to take nutrition and fluid .
intubation of a stent to the tracheobronchial tree and/or esophagus is somewhat safer than the other procedures and good for symptomatic relief .
some papers report high success rates in double stenting . when it is difficult to place a double stent at the same time , a tracheal stent has priority because an esophageal stent alone may compress the trachea and elicit respiratory distress .
we abandoned tracheal stenting in the current case for fear of a sudden impaction of the stent into the cavity . to avoid the risk of tracheal compression by the rapidly growing mediastinal tumor
, we decided to administer crt therapy in spite of the danger that the tef would worsen . with recent progress in the treatment of advanced and/or metastatic non - small - cell lung cancer , molecular targeted agents such as gefitinib , erlotinib , and bevacizumab play significant roles in improving patient survival .
but the standard therapy for locally advanced tumors not suited for surgery is radiotherapy combined with chemotherapy based on a platinum - containing drug .
it remains controversial whether such agents should be added to radiotherapy in locally advanced cases .
chemotherapy combined with the angiogenesis inhibitor bevacizumab , a monoclonal antibody to human vascular endothelial growth factor ( vegf ) , improves overall survival in colorectal cancer and non - small - cell lung cancer [ 8 , 9 ] .
although bevacizumab is recognized to be relatively safe , it is associated with the risk of hypertension , proteinuria , delayed wound healing , bowel perforation , and so on .
a recent report suggests that bevacizumab added to crt is associated with a higher incidence of tef formation in both small - cell and non - small - cell lung carcinomas .
most of the published papers on tef usually address the condition in patients with esophageal cancer .
reported that crt brought about fistula closure in 17 of 24 ( 70.8% ) patients with esophageal cancer and led to restored oral alimentation in 16 of those 17 ( 94.1% ) patients .
esophageal tissues around the fistula appear to epithelialize in response to crt , but the mechanisms behind this effect are unclear .
the major pathology of esophagus cancer is squamous cell carcinoma , a tumor with relatively high radiosensitivity .
, transforming growth factor- ( tgf- ) is a key cytokine that stimulates the production of surrounding extracellular matrix and heals the injured tissue . given that radiation often induces tgf- signaling , we also speculate that this type of wound healing mechanism might underlie the epithelialization .
tef formation in lung carcinoma is rarely reported . to our knowledge , this is the first report of primary lung cancer with tef successfully treated with crt .
the therapeutic agents for tef should be selected by carefully considering the patient 's particular condition and the risk of aggravating the tef .
though the usefulness and safety must be confirmed through further clinical research , crt may prove to be effective as a palliative treatment for malignant tef in lung cancer .
 a 45-year - old man complaining of cough , dyspnea , and difficulty in swallowing was referred to our hospital . 
 chest ct scan showed a mediastinal mass compressing the trachea . 
 he was diagnosed with poorly differentiated lung carcinoma by percutaneous needle biopsy . 
 bronchoscopy and upper gastrointestinal endoscopy revealed a tracheoesophageal fistula ( tef ) . 
 long - lasting febrile neutropenia made it impossible to continue chemotherapy , but a course of radiotherapy ( total 61 gy ) was completed . 
 the next endoscopy revealed closure of the tef . 
 chemoradiotherapy ( crt ) has been reported to close tef in esophageal cancer , but the risk of a crt - induced worsening of the fistula has dissuaded physicians from using crt to treat tef in lung cancer patients . 
 crt may serve as a palliative treatment for tef in lung cancer as well as esophageal cancer . 
Introduction
Case Report
Discussion